This study aims to describe the COVID-19 risk mitigation strategies implemented in California prisons and the impact of these policies on the mental health of incarcerated women.The authors conducted semi-structured qualitative interviews with ten women who were over the age of 50 and/or had a chronic illness and had been incarcerated in California prisons during the COVID-19 pandemic. The authors also interviewed ten health-care providers working in California jails or prisons during the pandemic. Interviews were analyzed using a grounded theory coding framework and triangulated with fieldnotes from ethnographic observations of medical and legal advocacy efforts during the pandemic.Participants described being locked in their cells for 23 hours per day or more, often for days, weeks or even months at a time in an effort to reduce the spread of COVID-19. For many participants, these lockdowns and the resulting isolation from loved ones both inside and outside of the prison were detrimental to both their physical and mental health. Participants reported that access to mental health care for those in the general population was limited prior to the pandemic, and that COVID-19 risk mitigation strategies, including the cessation of group programs and shift to cell-front mental health services, created further barriers.There has been little qualitative research on the mental health effects of the COVID-19 pandemic on incarcerated populations. This paper provides insight into the mental health effects of both the COVID-19 pandemic and COVID-19 risk mitigation strategies for the structurally vulnerable older women incarcerated in California prisons. The COVID-19 pandemic has wreaked havoc on structurally vulnerable populations in the USA, with a disproportionate impact on Black, Indigenous and People of Color (BIPOC) . NowhereThere has been limited research to date on the mental health impact of COVID-19 on those who are incarcerated; yet, the implications of the pandemic for incarcerated populations are clear. Incarceration is a stressful experience even in normal times , and chrAccording to a 2017 Stanford Justice Advocacy Project analysis of CDCR data, within the past ten years, the California State Prison population has dropped, while the number of incarcerated individuals with mental health issues has risen; as of 2017, the number of incarcerated people with serious mental illnesses reached about 32% of the prison population in California (2017). For individuals incarcerated in CDCR prisons, mental health treatment is administered through a referral process categorized as Emergent, Urgent or Routine , our study highlights how carceral COVID-19 risk mitigation strategies intensified the chronic stressors associated with incarceration  and reinIt is worth noting that the social isolation that occurred as a result of the lockdown and quarantine procedures implemented by CDCR differed in substantial ways from solitary confinement, including being isolated with a roommate and, while at times limited, having access to forms of entertainment and communication . HoweverWhile access to COVID-19 vaccinations should ideally lessen the need for intense lockdown procedures, they have continued to be used in institutions with high rates of vaccination. It is important to emphasize that the vast majority of COVID-19 cases within CDCR occurred after lockdown procedures were routinely used; between September 2021 and February 2022, there were more than 20,000 new cases of COVID-19, despite 80% of incarcerated people being fully vaccinated . With thWithout intervention, COVID-19 mitigation strategies may result in more incarcerated people developing anxiety, depression and other mental health conditions, or the exacerbation of these conditions among those with prior mental health diagnoses. There may be unique consequences for older populations and people of color. While the California State Prison population decreased overall during the COVID-19 pandemic, the proportion of 50 to 69 year-olds increased by 2% and the proportion of individuals who are Black or Hispanic increased by 1% . California did engage in decarceration efforts in 2020, with the aim of easing overcrowding. However, the majority of individuals released through these efforts were those with determinant sentences who were due to be released within 180 days; older adults and/or those with longer sentences were a disproportionately low share of those released .CDCR has reported that demand for mental health services decreased during the COVID-19 pandemic (The most straightforward solution to address both the amount of time incarcerated individuals at risk for COVID-19 must spend in their cells and staffing shortages that have limited individual therapy in the general population is decarceration. Both providers we interviewed and medical and public health experts made fervent calls for decarceration early in the pandemic to prevent the large-scale outbreaks that took place over the past two years . Our resCOVID-19 has both laid bare and exacerbated the mental health challenges faced by people incarcerated in the USA. It is clear that prisons were designed for punishment, not public health. Our findings raise the question of how we go beyond returning to a pre-pandemic baseline to facilitate community healing on a deeper level. While we must act to address and improve mental health inside prisons, equally important is the need to acknowledge the collective grief that incarcerated people have experienced as a result of lost connections to their families on the outside and communities on the inside, delayed parole and court hearings and deaths of other incarcerated people to COVID-19, suicide and other causes. It is now well understood that COVID-19 inequities have been concentrated in structurally vulnerable environments (


Paraduodenal hernia (PDH) is the most frequent type of congenital hernia, especially on the left side. Although acute intestinal obstruction due to internal hernias is rare, it can be life-threatening if not detected and treated promptly. Here, we present the case of a 36-year-old man who presented to the emergency department with an acute intestinal obstruction that had been developing for three days. The patient had a history of recurrent abdominal pain but had never undergone any abdominal surgery. Surgical exploration revealed a left internal PDH with a collection of incarcerated jejunal loops retrocolically encased within the hernial sac. Resection of the gangrenous jejunal loops was performed, followed by hernia reduction and neck closure. This case highlights the importance of timely and accurate diagnosis of left PDHs, particularly in patients with a history of recurrent abdominal pain and no prior abdominal surgeries. Early detection and treatment can prevent life-threatening complications such as intestinal perforation and peritonitis. Paraduodenal hernias (PDHs) are rare but the most common type of congenital internal peritoneal recess hernia . Its incRadiologists and clinicians are challenged by internal hernias due to their rarity and the complexity of their diagnosis and treatment . The cliPreoperatively, timely diagnosis is often difficult, leading to grave consequences and a reported mortality rate of more than 20% . The ultA 36-year-old married man presented to the emergency room with a three-day history of colicky abdominal discomfort, vomiting, and constipation. The pain had started three days prior and gradually worsened over the past week, accompanied by non-projectile bilious vomiting and nausea. He had also experienced a decrease in urine output and was unable to pass stool or flatus. He had no comorbidities, and his drug history consisted of painkillers and laxatives taken for constipation. Moreover, he had no significant family history.9/L. Abdominal ultrasound showed gaseous distention of his abdomen and gallbladder sludge. An erect X-ray of the abdomen showed multiple air-fluid levels , paranormal , and abnormal . These defects may be congenital due to intestinal malrotation or the absence of retroperitoneal attachments or acquired due to past abdominal surgery, trauma, or any ischemic process .Schizas et al. stated that PDH typically develops between the ages of 40 and 60, while Muneer et al. reported that PDH typically develops at a mean age of 44.1 years .The diagnosis of PDHs is the most challenging aspect of management. This is because of the non-specific presentation of PDH. Presenting symptoms can range from diffuse abdominal pain that is frequently eased by positional modifications to acute intestinal obstruction, which is the most common presentation . A contrThe importance of CT in the early preoperative identification of PDH is justified by the significant death rate associated with these complications . The typThe ultimate modality of treatment is operative repair, either laparoscopic or open repair, depending on the operative facilities and level of competency available ,3,6. TheThis case report highlights the importance of early and accurate diagnosis of left PDHs, which can be life-threatening if not detected and treated promptly. The findings of this study demonstrate the necessity of a thorough physical examination and prompt imaging in patients with a history of recurrent abdominal pain and no prior abdominal surgeries. The successful treatment of this patient through laparotomy and resection of the gangrenous portion of the gut, followed by hernia reduction and neck closure, emphasizes the critical role of surgical intervention in such cases. This case report contributes to the existing literature on PDHs and provides valuable insights into the diagnosis and management of this rare condition.


BMC Psychology (2023) 11:35510.1186/s40359-023-01391-0Following publication of the original article [1], it was brought to the attention of the journal that the following competing interests declaration for the fourth author, Mark D. Griffiths, had been omitted:Norsk Tipping (the gambling operator owned by the Norwegian government). MDG has received funding for a number of research projects in the area of gambling education for young people, social responsibility in gambling and gambling treatment from Gamble Aware (formerly the Responsibility in Gambling Trust), a charitable body which funds its research program based on donations from the gambling industry. MDG undertakes consultancy for various gambling companies in the area of player protection and social responsibility in gambling.MDG has received research funding from The declaration has since been added to the published article. The authors thank you for reading and apologize for any inconvenience caused.


Nystagmus produced in response to air-conducted sound (ACS) stimulation—the Tullio phenomenon—is well known in patients with a semicircular canal (SCC) dehiscence (SCD). Here we consider the evidence that bone-conducted vibration (BCV) is also an effective stimulus for generating the Tullio phenomenon. We relate the clinical evidence based on clinical data extracted from literature to the recent evidence about the physical mechanism by which BCV may cause this nystagmus and the neural evidence confirming the likely mechanism. The hypothetical physical mechanism by which BCV activates SCC afferent neurons in SCD patients is that traveling waves are generated in the endolymph, initiated at the site of the dehiscence. We contend that the nystagmus and symptoms observed after cranial BCV in SCD patients is a variant of Skull Vibration Induced Nystagmus (SVIN) used to identify unilateral vestibular loss (uVL) with the major difference being that in uVL the nystagmus beats away from the affected ear whereas in Tullio to BCV the nystagmus beats usually toward the affected ear with the SCD. We suggest that the cause of this difference is a cycle-by-cycle activation of SCC afferents from the remaining ear, which are not canceled centrally by simultaneous afferent input from the opposite ear, because of its reduced or absent function in uVL. In the Tullio phenomenon, this cycle-by-cycle neural activation is complemented by fluid streaming and thus cupula deflection caused by the repeated compression of each cycle of the stimuli. In this way, the Tullio phenomenon to BCV is a version of skull vibration-induced nystagmus. Tullio found that following the fenestration of one semicircular canal (SCC) of a pigeon, ACS stimuli elicited pendular movement of the body in the plane of the opened SCC and, at higher intensity, ocular nystagmus. He showed that the sound stimuli produced fluid displacement of endolymph corresponding to these responses. Of the three SCCs in a labyrinth, it was the fenestrated SCC that had the largest displacement of endolymph and so caused the eye movement in the plane of that canal , 2. A coIn human patients, nystagmus due to ACS is found in a number of pathologies  and it hPubMed/Medline and Scopus were searched for the 2 last decades (2005–2022) and selection was performed according to the procedure and policy indicated by Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search criteria were “Vibration induced Nystagmus” , cranial vibrations , and Superior canal dehiscence . Only SCD patients corresponding to the definition given by Minor et al.  and withThe initial flow chart was 12 publications.Patients met the following conditions proposed as diagnostic criteria for superior canal dehiscence syndrome :High-resolution computed tomography images (≤0.625-mm slice thickness) reformatted in the plane of the superior SCC demonstrating dehiscence.S: A. Bone conduction hyperacusis  B. Sound-induced vertigo C. Pressure-induced vertigo  D. Pulsatile tinnitus.At least one of the following symptoms consistent with SCDAt least one of the following diagnostic tests indicating a third mobile window A. Negative bone conduction thresholds for low frequencies on pure tone audiometry B. Enhanced VEMP responses  C. Elevated ratio of the summating potential to action potential on electrocochleography in the absence of a sensorineural hearing loss.Three out of the 12 publications were not included because they did not meet the inclusion criteria and/or were an unacceptably small series of patients (<5).SVINT results in SCD patients described in the literature , 13–18 fAt present the possible mechanisms for BCV inducing a Tullio phenomenon are  , 20:Sound radiated into the ear canal.Inertial effect of middle ear ossicles.Inertial effect of the fluid in the inner ear.Space alteration of the inner ear due to vibrations of the bone surrounding the inner ear .It has been suggested that sound can reach the inner ear by vibrations applied to non-osseous factors . This last contribution particularly via the cerebrospinal fluid (CSF) through the cochlear aqueduct is very poor, and negligible in normal subjects but is likely substantial in uSCD patients depending on the location stimulated by vibration.The insight of SVIN in clinical practice is to contribute to SCD diagnosis as a useful and understandable tool when interpreted in the light of a bone-conducted Tullio phenomenon (BCTP).th Regular Meeting of the Barany Society   . A similGrieser et al.  reportedIversen et al.  developeIversen et al. then actually measured the fluid flow in a toadfish SCC and confirmed their model predictions: that sound energy causes fluid flow at the location of the defect, giving rise to traveling waves that subsequently excite mechano-electrical transduction in the vestibular sensory organs. They showed the direction of the fluid flow to BCV stimulation depended on the location of the stimulus, the size of the dehiscence, and the frequency of the stimulus. They also recorded single semicircular canal neurons (in toadfish) which confirmed the predictions from their measurements and modeling. They observed an excitatory endolymphatic ampullopetal flow in the horizontal SCC at frequencies from 100 Hz to around 500 Hz and a reversal of the flow and inhibition of neural regular discharges at frequencies from 500 to 850 Hz. In short, the “traveling wave” model of endolymph flow after artificially created SCD is an excellent account of the mechanism of semicircular canal response to BCV after SCD, both of the physical mechanisms and the neural results and thus the human patient nystagmus. In humans, such a reversal was observed at frequencies around 300 Hz or in rare cases at 30 Hz  shows a strong response (higher amplitudes and lower threshold) in SCD .The strong efficiency of vertex stimulation in SCD patients contrasts with the usual inefficiency of vertex stimulation in patients with unilateral vestibular loss (UVL) , 9. ThisBCV in SCD constitutes a more efficient test than AC Tullio phenomenon (ACTP) in clinical practice.Mehta et al.  Figure  observedSCD patients with a positive SVINT most often report dizziness or vertigo or discomfort during skull stimulation , 17, 23.This paper shows the new insight of SVIN in clinical practice among other vestibular explorations in SCD patients when it is interpreted as a bone-conducted Tullio phenomenon.The Tullio phenomenon initially described after air-conducted sound stimulation is currently most often observed in SCD patients but is not specific to this stimulus. The very similar symptoms of dizziness and nystagmus provoked by BCV stimulation are often observed in SCD and appear to constitute a more efficient stimulus compared to air-conducted sound stimulation to elicit a Tullio phenomenon.SVINT in SCD patients stimulated by BCV is comprised of a vertical and torsional component generated by the superior canal and by a horizontal component caused by spread to the horizontal SCC or by a utricular contribution. The direction of SVINT in SCD patients is most often beating ipsilaterally (when vertex is stimulated) but nystagmus direction cannot be always predicted in any simple fashion because of the instability of the created endolymphatic flow provoking a stimulation of inner ear hair cells of the cupula as shown by Iversen et al. This instability explains the variability following stimulus location and frequency observed in some patients but also discrepancies between investigators.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.GD and IC: original idea, general coordination, review, and co-writing the article. PP and SS: contributed to the MS editing and discussion. AC and LD: contributed to the table editing and figures. All authors contributed equally to the rewriting of the article and its conclusions.


Optimal design of a silicon nitride waveguide structure composed of resonant nanoantennas for efficient light coupling with interlayer exciton emitters in a MoSe Two-dimensional 2D) materials, ranging from semimetallic graphene to insulating hexagonal boron nitride, have attracted significant interest from the scientific community recently ,2,3. In D materiaoperties ,10,11,12operties .Owing to their fascinating properties, 2D TMD materials can be used for many practical applications such as optical modulators, classical and non-classical light sources, light-harvesting devices, photodetectors ,18,19,20Monolayers of different TMD materials also can be vertically stacked to form heterostructures with new peculiar properties, which are not observed in single layers of constituent materials . One of In order to fully utilize their functionality for existing devices, TMD layers can be optically coupled with photonic structures on a chip . It openResonant integrated photonics based on Mie-type nanoparticles has recently been introduced as a versatile tool to control light on a chip ,38. It cIn this paper, we propose a concept of a resonant waveguide system (RWS) based on a magnetic type high-Q photonic nanocavity for effective optical coupling with localized interlayer exciton emitters in vertically stacked monolayer MoSeh = 400 nm and the width of w = 850 nm on a silica substrate . FinallThe aspect ratio (height/width) of the nanoparticles is chosen in analogy with Ref.  to suppoructures . The finus works .In order to analyze the emission enhancement and radiation coupling efficiency associated with interlayer localized excitons in stacked MoSeP is radiated dipole power in the presence of the RWS and First, we trace the dependence of the Purcell effect and optical coupling efficiency on the position of the dipole emitter along the RWS. For Purcell effect enhancement definition, we introduce a factor The Purcell factor as well as optical coupling efficiency decrease with the dipole shifting along the nanoparticle chain. We also examine the dependence of the Purcell effect and the optical coupling efficiency on the dipole emitter transverse shift relative to the RWS. Two cases are considered: the dipole is in the center and on the edge of the RWS see . These aThe spectra of the radiation power transmitted along the RWS and the spectra of the AWe also perform simulations to estimate the optical coupling efficiency between intralayer exciton emitters (with in-plane orientation) and the conventional strip waveguide (configuration similar to the work ). Both lIt is worth mentioning that the Purcell effect increases the spontaneous emission rate of excitonic emitters due to a much higher photon density of states in the nanocavity. Typical lifetimes for interlayer excitons in TMD heterostructures are in the order of a few tens of ns . Taking Finally, for the experimental validation of the proposed system, one needs to take into consideration the variation of the RWS geometrical parameters during the sample fabrication. To this end, we have estimated the possible resonance shift and broadening for random geometrical parameter variations typical for electron-beam lithography and reactive ion etching processes. The results demonstrate that the resonance quality factor is not significantly affected, while the spectral shift in real devices can be compensated, for example, by electrical tuning of the TMD heterostructure .We propose the optimized resonant waveguide system composed of SiN nanoparticles forming magnetic type high-Q photonic nanocavity for efficient integration with interlayer exciton emitters in vertically stacked monolayer MoSe


Many children with Williams syndrome struggle with fears and phobias that significantly impact their daily lives. Yet, there is sparse literature about the impact of behavioral interventions to treat anxiety and phobias among children with Williams syndrome. Using observational coding of intervention videos, the current study examines patterns of the therapist's use of play and humor and relations to child behavioral responses for four children with Williams syndrome who were identified as treatment responders to humor- and play-infused exposure therapy for fears and anxieties. Sessions were coded for therapist behaviors  as well as positive, negative, and neutral child behaviors . Temporal patterns between therapist and child behaviors were analyzed using lag sequential analyses. The results showed that tolerance of feared stimuli improved for two of the four children following this play- and humor-infused exposure therapy approach, and the remaining two participants demonstrated progress beyond tolerating the feared stimulus and showed increased positive behaviors with the feared stimulus across sessions. Findings also showed patterns of therapist attunement to the child's anxiety level demonstrated through efforts to flexibly adjust the degrees of exposure. Therapist-initiated invited attention behaviors, indicative of the therapist's use of narration and priming, were associated with child tolerance and positive behaviors during exposure to the feared stimulus. Limitations of this study include a very small sample size, short duration of intervention, and a single-subject research design, which limit the generalizability of findings. Implications and future directions of this research are discussed. Williams syndrome is a rare neurodevelopmental disorder caused by a hemizygous microdeletion on chromosome 7q11.23 and characterized by physical, cognitive, and behavioral markers  found that 53.8% met diagnostic criteria for specific phobia and 11.8% met criteria for generalized anxiety disorder  populations  showed promise as a feasible and effective approach   and caregiver(s) to participate and/or observe throughout sessions. After the child acclimates to the therapy room and happily plays together with the therapist, the therapist begins introducing the feared stimulus using the least intimidating level of exposure, which may be talking about the item, showing video of the item, or incorporating some aspect or representation of the item into the adult–child play  and gauges the intensity of their reaction. As the child exhibits increased comfort in the presence of the feared stimulus, the therapist uses graduated exposure techniques to work up a fear ladder  toward direct contact with the feared stimulus. The therapist flexibly moves up and down levels of the fear hierarchy depending on the child's response following presentation or encouraged engagement with the feared stimulus. Throughout the sessions, socially engaging interactive play with the child is the consistent backdrop to help maintain contact and positive engagement with the feared stimulus. When anxiety becomes heightened as exposures incrementally move toward direct contact with a phobic stimulus, the therapist is likely to use socially attuned humor with the child  to help co-regulate, that is, to help the child sustain an emotionally regulated state, and to align themselves with the child, model emotional expression, and introduce a new emotional tone to interaction with the feared stimulus. In summary, the therapist spontaneously decreases the degree of exposure and/or increases playfulness and humor if the child shows signs of dysregulation and then increases the degree of exposure if the child appears regulated. Across sessions, the goal is for the child to sustain an emotionally regulated state, as manifested by exhibiting fewer fearful and anxious reactions to their feared stimulus to reduce functional impairment.Archival video-recorded intervention sessions of four participants  were coded and analyzed using Noldus Observer XT 15.0 software to determine how child fear and anxiety-related behaviors change within session and across sessions, and characterize therapist use of play and humor and exposure techniques in this therapy. Behavioral coding  was conducted based on the coding scheme described in Therapist behaviors were coded using duration and frequency recording. The duration of therapist use of play- and humor-infused exposure therapy and pure exposure was coded to identify patterns of therapist-led exposure by type, as well as spontaneous parent use of exposure by type. The use of different types of feared stimuli  was also coded during pure or play- and humor-infused exposure therapy. Therapist behaviors also included passive and invited attention to the feared stimulus. For example, the therapist may direct attention to a non-feared stimulus , thereby making the feared stimulus secondary to the stimulus where attention is invited . If the therapist used verbal and/or non-verbal cues to guide the child's gaze toward the feared stimulus , this was coded as invited attention to the stimulus. See Child behaviors were coded as frequency of positive, tolerating , and negative behaviors within intervals, to capture observable fear-related behaviors. Verbalizations  and physical behaviors  were also coded. See Interrater reliability was calculated using Noldus Observer XT 15.0, including Cohen's kappa and agreement percentage. Cohen's kappa ranges from −1 to +1, and kappa values should be interpreted using the following ranges: Values of ≤ 0 suggest no interrater agreement, values of 0.01–0.20 suggest no agreement to slight agreement, values of 0.21–0.40 suggest fair agreement, values of 0.41–0.60 suggest moderate agreement, values of 0.61–0.80 suggest substantial agreement, and values of 0.81–1.00 suggest almost perfect interrater agreement. For the current study, interrater reliability was considered met when k ≥0.70 and agreement percentage ≥80%.The first author and a graduate student trained in the coding scheme separately coded one intervention session video (of a participant that is not included in the current sample) to pilot the developed coding scheme. It was expected that the coding scheme would need revisions as the development of a behavior coding scheme is an iterative process, often requiring discussions about revisions and refinement of operational definitions  with one intervention session video of a participant that is not included in the current sample, one randomly selected intervention video for each participant was coded to ensure continued interrater reliability for all participants in this sample. Once interrater reliability was established with four intervention session videos (one for each participant), series data trends of frequency and duration of behaviors (per session and across) were coded, graphed, and visually inspected. Based on the interrater reliability findings, we elected to concentrate on frequency of child behavior and duration and frequency of therapist behavior. Specifically, the number of child behavior occurrences in each session of each participant (frequency) was calculated within 5-minute intervals and graphed and visually inspected to demonstrate patterns of change. Similarly, the duration and frequency of therapist behaviors  in each session were coded and calculated within 5-minute intervals and graphed and visually inspected. Lag sequential analyses (event state lag of 1) were also conducted to identify sequential patterns between therapist and child behaviors as well as sequential therapist behaviors .Each of the four participants' demographic information as well as verbal and non-verbal norm-referenced cognitive functioning are displayed in The duration of each therapist behavior code was analyzed using duration-within-interval recording. Intervals were also 5-minute each across the duration of each session.The frequency of each child behavior code was calculated, graphed, and visually inspected using frequency-within-interval recording. Intervals were defined as 5-minute each across the duration of each session. Each child participated in 3–4 therapy sessions. For two participants, one session video was excluded because the intervention focus was on a secondary feared stimuli . Each session video duration ranged from 30 to 65 min as indicated in Analyses of temporal patterns were conducted using lag sequential analyses in Noldus Observer XT 15.0. Lag sequential data are defined as identifying an event that immediately follows an event . Lag sequential data for therapist behavior codes following child behavior codes and child behavior codes following therapist behaviors were analyzed to identify high frequencies of sequential behavior patterns. First, lag sequential data for therapist behaviors following child behavior codes were analyzed to identify ways in which the therapist responded to the child, within and across sessions. Second, lag sequential data for child behaviors following therapist behaviors were analyzed to identify how each child responded to each therapist technique within the context of exposure therapy.Each participant's behavioral coding data analyses will be presented individually, using pseudonyms to protect privacy for each child, in a case series design format. Of note, passive exposure was only occasionally observed and is therefore not interpreted here. To illustrate the unique response to the intervention observed for the different participants in this sample, we have individually tailored presentations of the findings to best capture the nature of each participant's response. Common behavioral coding trends across participants will be presented in the discussion.Ashton's primary targeted fear was hand dryers found in public restrooms. Therapy sessions 1 and 3 were coded and analyzed as these sessions focused on this primary feared stimulus. Below child behavior (frequency coding) will be discussed first, followed by therapist behaviors (duration coding) and last, lag sequential findings (state event lag of 1).Across sessions, Ashton exhibited low frequencies of all negative behaviors , with a total frequency of 8 in session 1 and a total frequency of 7 in session 3. This highlights the flexible and attuned nature of the intervention, where the therapist works to minimize overly distressing the child during exposures. The observed frequency of tolerating the feared stimulus decreased from a total frequency of 47 in session 1, to a total session frequency of 21 in session 3. However, this decrease in tolerance of the feared stimulus can be explained by the maintained frequency of positive verbalizations (frequency of 34 during both sessions 1 and 3) and even an increase in positive physical behaviors  from session 1 (frequency of 33) to session 3 (frequency of 35) see .Furthermore, Ashton's observed positive behaviors maintained and increased in the face of increasingly challenging stimulus types used by the therapist across sessions. In session 1, the therapist used pure exposure with media stimulus types , followed by exposure with play and humor using a toy stimulus type  see . In the Table 7). Importantly, the results also show that following the therapist's use of invited attention, the most frequent child behavior code included positive physical behaviors  . When a child is observed to tolerate a feared stimulus, it can appear quite ambiguous to the therapist. For instance, the child's absence of negative or positive behaviors can suggest to the therapist that a redirection to the exposure activity may be warranted to prevent an occurrence of negative behavior  and to continue tolerance of the feared stimulus. The use of invited attention following the child's positive behaviors suggests that the therapist uses techniques to encourage continued positive engagement with the feared stimulus (see yer) see . This paBeth's primary targeted fear was identified as blenders. Therapy sessions 1, 2, and 3 were coded and analyzed as all sessions focused on this primary feared stimulus. Below child behavior (frequency coding) will be discussed first, followed by therapist behaviors (duration coding) and last, lag sequential findings (state event lag of 1).Beth exhibited lower frequencies of within-session negative behaviors  relative to within-session positive behaviors in the first session (negative behavior frequency of 28 and positive behavior frequency of 46) and in the final session (negative behavior frequency of 36 and positive behavior frequency of 50). Across session data show increasing frequencies of both negative and positive behaviors. It was observed that negative physical behaviors  often co-occurred with positive physical behaviors  within each of the three sessions. This behavior pattern has been highlighted in the literature as unique among children with Williams syndrome who experience fears and phobias  paired with specific stimulus type(s) across sessions. The therapist used play and humor to co-regulate, to help Beth sustain emotional regulation, and to prevent anxiety from becoming overwhelming. In session 1, the therapist infused play and humor into exposures with all stimulus types  and implemented pure exposure with media examples of blenders and brief durations of the actual stimulus. The actual blender was introduced near the end of session 1 and unplugged and turned off to begin exposure to the sight of the object before working up the fear hierarchy to auditory exposure of the blender turned on later in the course of treatment see .Next, temporal patterns between child and therapist behavior codes were analyzed using lag sequential data analyses. First, temporal patterns between therapist use of invited attention and all child behaviors were analyzed. Findings reveal that during sessions 1 and 2, when the actual stimulus was presented to Beth and elicited some avoidance  as well as interest in the blender , therapist invited attention often followed all child behaviors  see . DiffereColton's primary targeted fear was identified as blood pressure cuffs. Therapy sessions 1, 2, 3, and 4 were coded and analyzed as all sessions focused on this primary feared stimulus. Below child behavior (frequency coding) will be discussed first, followed by therapist behaviors (duration coding) and last, lag sequential findings (state event lag of 1).Colton exhibited lower frequencies of within-session negative behaviors  relative to within-session positive behaviors in sessions 1 and 2. In session 3, frequencies of negative behaviors were equal to his tolerating behaviors (frequency: 18), with twice the frequencies of positive behaviors (frequency: 36) in response to his feared stimulus. In session 4, although negative behaviors increased, Colton's observed tolerating of the feared stimulus increased as well  see . Colton The therapist attunement to Colton throughout treatment fostered the observed increase in his ability to tolerate his feared stimulus. Therapist use of pure exposure was brief and only used in session 1 with media examples of the feared stimulus. However, exposure with play and humor was used across all sessions with a toy version and the actual stimulus type see . Parent Next, temporal patterns between child and therapist behavior codes were analyzed using lag sequential data analyses. First, temporal patterns between therapist use of invited attention and all child behaviors were analyzed. The results show that in response to varied child behavior , the therapist frequently used invited attention techniques to either redirect the child to the activity (if negative child behavior was observed), use gesture or verbal prompts to gauge child's anxiety level (if child tolerating was observed), or narration in a playful and humorous way to continue child engagement in exposures (if positive child behavior was observed) see . FollowiDanny's primary targeted fear was identified as vacuum cleaners. Therapy sessions 1, 2, and 3 were coded and analyzed, but session 4 was not coded because the primary fear was not targeted during this session. Below, child behavior (frequency coding) will be discussed first, followed by therapist behaviors (duration coding) and last, lag sequential findings (state event lag of 1).Danny exhibited lower frequencies of within-session negative behaviors  relative to within-session tolerating and positive behaviors in session 1 , session 2 , and session 3 . Across session data show a slight increase in positive physical behaviors  from session 1 (frequency: 31) to session 3 (frequency: 39). Danny's profile of behavioral data trends shows his ability to tolerate and positively engage with vacuum cleaners within each session, even as the stimulus type became increasingly challenging . It is notable that the child spent several minutes independently vacuuming the carpet in session 3 see .Therapist use of pure exposure was primarily used with media versions of vacuum cleaners during sessions 1 and 2 and then used with a toy version and with an actual vacuum cleaner during session 3. Exposure with play and humor was used across all sessions primarily with a toy version and the actual stimulus type, and in shorter durations with media examples in session 1 see . NotablyNext, temporal patterns between child and therapist behavior codes were analyzed using lag sequential data analyses. First, temporal patterns between therapist use of invited attention and all child behaviors were analyzed. The results show that the most frequently used therapist technique following child behaviors was invited attention see . SpecifiIn our prior work demonstrating preliminary acceptability and utility of play- and humor-infused exposure therapy for children with Williams syndrome, parent and clinician ratings indicated improvements in fear for some children with Williams syndrome, even after a very brief course of treatment. The current study validated these clinician and parent ratings by demonstrating that this observed improvement was evident based on behavioral coding. Increased tolerance of the feared stimulus across sessions and/or movement from engagement with videos or toys to engagement with real feared objects was observed over the course of this brief intervention for all of the participants. These findings add to our preliminary evidence of the promise of this play- and humor-infused exposure therapy for children with Williams syndrome to address intense emotional dysregulation in response to specific stimuli . Additionally, the combination of therapist techniques, including use of invited attention, social play and humor, and relations of these techniques to child behavior, suggests that the therapist's attunement to the child's distress level encourages continued contact with the feared stimulus and results in adjustment of the intensity of the exposure through use of videos, toys, and real-world objects. Findings of the therapist techniques for co-regulation used within this play- and humor-infused approach show that attunement to the child, exaggerated emotion to join the child in their fear, and use of play and humor yield child behaviors suggestive of improved coping through co-regulation, ability to maintain contact with the feared stimulus without becoming overly distressed, ultimately leading to increase in the child's capacity to sustain emotional regulation, improved tolerance, and sometimes positive engagement with their feared stimulus.new association of fear inhibition that goes against the typical activation of the amygdala during fear conditioning, rather than simply extinguishing the previously established fear association  and type of exposure (pure exposure or exposure with play and humor). Media examples of the feared stimulus were most often used within pure exposures . Toy versions of the feared stimulus and the  feared stimulus were typically presented and incorporated within play- and humor-based exposures. This highlights the developmentally attuned nature of the therapeutic approach. By infusing more play and humor into the exposures as the child progresses up the fear hierarchy, the therapist is able to co-regulate with the child and thus the child is able to sustain emotional regulation, minimize distress and anxiety while simultaneously allowing for continued engagement and increasingly more direct contact with the feared stimulus. The feared stimulus is gradually incorporated into the sessions. As designed, this intervention is largely therapist-led, in the presence of the parent. Nevertheless, during this intervention, we observed some parent involvement in the exposures for one participant. It is likely that parental involvement would indeed facilitate generalization of the skills to the home environment. Therefore, future work developing this intervention approach may benefit from more explicit guidance of parents as play- and humor-infused exposure facilitators.The combination of both behavioral  and play-based  approaches may be especially well-suited for children with Williams syndrome. The gregarious nature of children with Williams syndrome may mask the underlying emotion dysregulation stemming from anxiety. The focus of this intervention for children with Williams syndrome was to improve emotion regulation relating to specific phobias by building coping skills through social play-based approaches  was used with all children in this study to encourage continued engagement and promote co-regulation by joining the child in their fear. This approach leverages the empathic and social nature of children with Williams syndrome, by allowing them to experience discomfort and co-regulate with the therapist in a safe and supportive setting. By joining each child in their fear during exposures, the therapist helped them work through these more difficult and uncomfortable emotions  while gently encouraging their progress through increasingly challenging levels of the fear hierarchy. In some instances, over the course of the intervention, a child even comforted the personified toy . Additionally, when a child's behavior was not clearly positive or negative , the therapist frequently used redirection to prevent escalated anxiety and to promote continued engagement in the exposure activity. The therapist-initiated techniques were often tailored to the individual needs of each child to facilitate progress through the fear hierarchies and ultimately reduce distress in the presence of the phobic stimulus.Although children with Williams syndrome tend to have auditory-based phobias, the underlying etiology of these sound sensitivities is still undefined. Noise sensitivities may be associated with biological or cognitive behavioral mechanisms. Hyperacusis  and phonophobia  are two concerns that are commonly expressed by people with Williams syndrome  and an A-B single-subject research design, which limit the generalizability of findings. This sample is made up of four participants who were White, hence lacked racial diversity. Recruitment strategies to diversify samples in future studies are needed. Furthermore, there were limitations to the behavior coding scheme. Specifically, the behavior coding scheme focused on coding the child's primary fear only  and did not capture the intensity of the stimulus sound or the intensity of the child's verbal responses . Therapist behavior patterns of exposure using sequenced feared stimuli across sessions that included secondary feared stimuli  were not coded . Furthermore, the behavior coding scheme did not explicitly capture child-initiated coping, which was on occasion observed. For example, Ashton was exhibiting increasing fearful behaviors while the hand dryer was turned on, and he then requested the use of a thunder tube to hold and shift attention toward; after holding and listening to the thunder tube while still in the presence of the hand dryer, his observable fear response reduced. Finally, we acknowledge that behavior coding introduces the possibility of rater bias , which we aimed to minimize through independent behavior coding by respective coders.Limitations include a very small sample size  and degree of general cognitive and language difficulties. Additionally, the role of parent psychoeducation within this play- and humor-infused exposure therapy may be investigated in future research. Specifically, examination of the effects of parent psychoeducation about mechanisms for fear and anxiety and parental instruction in the use of play- and humor-infused approaches on the sustained impact of the intervention within the naturalistic environment is warranted.This study adds to the sparse research on the utility and effectiveness of interventions for children with Williams syndrome and co-occurring fears and phobias. Specifically, the findings of the current study provide support for increased emotion regulation in the form of improved tolerance of the feared stimulus and/or the ability to progress through the fear hierarchy  following a brief social play- and humor-infused exposure therapy approach with four children with Williams syndrome and co-occurring fears and phobias based on observational behavior coding. For two of the four children, improvements were evident in a move beyond tolerating the feared stimulus toward increased positive behaviors with the feared stimulus across sessions. All four children in this sample progressed through their fear hierarchy and were able to tolerate or even positively engage with the real-world previously feared stimulus by the final therapy session. This line of research provides evidentiary support for developmentally attuned approaches to exposure-based interventions for children with Williams syndrome, adding to the paucity of treatment development literature addressing anxiety and phobias in children with rare neurogenic conditions.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by University of Wisconsin-Milwaukee Institutional Review Board. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin. Written informed consent was obtained from the individual(s), and minor(s)' legal guardian/next of kin, for the publication of any potentially identifiable images or data included in this article.BY contributed to the development of the coding scheme, served as the primary coder, analysis and interpretation of the data, drafting of the manuscript, and revising the manuscript based on co-author feedback. EM contributed to the refinement of the coding scheme, served as the secondary coder, contributed to data interpretation, and provided conceptual revision feedback on the manuscript. KL originated the humor- and play-infused exposure therapy approach, contributed to the development of the intervention manual, served as the study therapist, and provided conceptual feedback on the manuscript. BK-T collaborated with KL to operationalize the intervention approach into a treatment manual, recruited and enrolled participants, coordinated intervention appointments, assisted with intervention appointments, and supervised the development and implementation of the coding scheme, data interpretation, manuscript-writing, and including providing manuscript revisions. All authors contributed to the article and approved the submitted version.


Vertebral compression fractures are becoming increasingly common with aging of the population; minimally invasive materials play an essential role in treating these fractures. However, the unacceptable processing-performance relationships of materials and their poor osteoinductive performance have limited their clinical application. In this review, we describe the advances in materials used for minimally invasive treatment of vertebral compression fractures and enumerate the types of bone cement commonly used in current practice. We also discuss the limitations of the materials themselves, and summarize the approaches for improving the characteristics of bone cement. Finally, we review the types and clinical efficacy of new vertebral implants. This review may provide valuable insights into newer strategies and methods for future research; it may also improve understanding on the application of minimally invasive materials for the treatment of vertebral compression fractures. A vertebral compression fracture (VCF) is defined as a reduction in the height of a single vertebral body by 20% or 4 mm . It is cin situ (Percutaneous vertebroplasty (PVP) and kyphoplasty (PKP) are currently the most common modalities employed for the treatment of VCFs . The proin situ . Howeverin situ . In thisin situ . In recein situ . The proin situ . Four vein situ . NotablyMaterials used for minimally invasive treatment of VCFs have been widely studied in recent years. However, their clinical application is limited by limitations of the materials used. In this review, we describe the various types of bone cement used for minimally invasive treatment of VCFs, starting from the most commonly used material, namely, PMMA; we also discuss their limitations. In addition, we enumerate the materials that are commonly used to improve the properties of bone cement  in CPCs hinders angiogenesis and inward tissue growth; it can only be degraded layer-by-layer. This limits degradation at the bone-implant interface and thereby hinders the degradation process . In ordeThe poor injectability of CPC is one of the main factors that limit its use in PVP and PKP procedures. The higher liquid content in uncured CPC leads to lower viscosity, lower cohesion, increased setting times, and lower mechanical strength. This subsequently leads to extravasation of bone cement from the surgical site, leading to complications such as pulmonary embolism. This possible deviation of the actual composition of the extruded paste may be attributed to the filtration pressure, which affects the injectability of CPC pastes . During Cohesion represents the ability of CPC to harden and maintain the integrity of the cement paste in a static aqueous environment without disintegrating into small particles; it prevents attrition of the paste by the surrounding liquid . The cohThe study of magnesium phosphate for bone cement is a relatively recent development. The excellent osteogenic and vasculogenic properties of MPC are the key factors that contribute to its use in research; these factors are mainly attributed to magnesium ions, which exert an osteogenic effect via the activation of osteoblast activity. They promote the proliferation of osteoblasts via the mitogen-activated protein kinase/extracellular signal-regulated kinase signaling pathway by increasing phosphorylation of the latter (thereby enhancing the level of c-FOS) and inducing the phosphorylation of glycogen synthase kinase-β (thereby enhancing the level of β-conjugated proteins) . MagnesiCSC has also been used in orthopedic applications due to its superior biocompatibility and bone regeneration properties, which are similar to those of MPC. CSC generates less heat during the exothermic curing reaction and demonstrates superior bioactivity, excellent osteoconductive activity, and degradability. Huang et al. proposed a method to synthesize biodegradable calcium silicate cement by incorporating strontium into cement through solid-state sintering. The degradation rate of the cements increased with increasing content of strontium, consequentially raised the levels of released strontium and silicon ions. The elevated dissolving products may contribute to the enhancement of the cytocompatibility, alkaline phosphatase activity and osteocalcin secretion . FurtherBioactive materials are defined as those that stimulate a beneficial response in the body, especially in terms of binding to host tissues . BioactiHA has been used as an inorganic filler in bone cement to improve its biocompatibility, as it has a chemical composition and crystal structure similar to that of apatite found in human bone tissue. HA is highly osteoinductive; this promotes chemical interactions with osteoblasts and the local microenvironment and thereby promotes the formation of new bone . In term2MgSi2O7, AKT), and tremolite (CaO-MgO-2SiO2)  . The comO-2SiO2) . NotablyO-2SiO2) .Bioactive glass (BG) includes glass that can produce a specific biological response at the material-bone interface and promote efficient bonding between them . SilicatAlthough numerous experiments have demonstrated that the addition of BG sufficiently enhances the bioactivity of bone cement, it impacts the mechanical properties (including injectability) of the cement. In this context, borate-based BG demonstrates a controlled degradation rate; the bioactivity and degradation rate of borosilicate-based BG can be regulated by the introduction of variable quantities of boric oxide to match the growth rate of new bone tissue . In theiin vivo and decrease the possibility of heat-induced bone tissue necrosis induced by polymerization of PMMA cement. In their study, Ormsby et al. found that the addition of functionalized multi-walled CNTs led to a significant reduction in the quantity of heat generated by the exothermic polymerization reaction of PMMA bone cement; it also significantly reduced thermal necrosis index values from 3% to 99% (Carbon nanotubes (CNTs) can significantly improve the mechanical properties of bone cement. This may be mainly attributed to certain unique properties including nanoscale diameters, longer length, higher strength and stiffness, and considerably high aspect ratios. Multi-walled CNTs prevent cracks in the cement from expanding; they provide a bridging effect at the tails of the crack in a direction perpendicular to that of crack expansion. In their study, Sadati et al. found that the incorporation of 0.5% of multi-walled CNTs into PMMA significantly increased tensile strength, elastic modulus, and bending strengths by 37%. The finite element method was used to simulate the bridging mechanism of PMMA/multi-walled CNT nanocomposites . Combini% to 99% . Mabroum% to 99% .The possibility of nanotoxicity needs to be considered in the case of CNT-based biomaterials  Figure . PahlevaCOL1A1, BMP4, BMP2, RUNX2, and ALP demonstrate stimulatory effects, while catabolic genes (MMP2 and MMP9) exert inhibitory effects , and reduced GO, which is of particular interest. GO has a larger number of hydrophilic groups than simple CNT and graphene; these allow it to form chemical bonds  with molecules in the bone cement. This facilitates good dispersion, thereby enhancing mechanical strength and improving biological properties. In their study, Paz et al. loaded different proportions of graphene and GO onto PMMA; they found that the PMMA cement with a lower load of graphene or GO powder (≤0.25 percent by weight) showed significantly superior fracture toughness and fatigue properties . In addi effects . Another effects .3O4 in an ex vivo magnetic field; the increase in temperature of resected bovine liver was found to positively correlate with the iron content and time. This suggested that the intratumoral temperature is controllable  addresses the important issue of non-uniform heating of magnetic thermal materials; this allows for more rapid heating of the composite materials and achievement of thermal equilibrium. This shortens the time of thermal therapy and reduces heat-resistance caused by an excessively long heating time  for 20 min after the powders were thoroughly mixed. It demonstrates outstanding thermal insulating properties, which may inhibit thermal diffusion during the polymerization reaction of methylmethacrylate and help protect the surrounding osteoblast-associated cells. In addition, the magnesium ions released by LDH promote osteogenesis. The larger micro sheets of layered double hydroxide are able to produce a certain number of holes on the surface of PMMA; this is beneficial for osseointegration between cement and bone . Titaniuin vivo, its incorporation into PMMA bone cement creates appreciable porosity. The increase in porosity facilitates osseointegration between bone and cement and promotes more stable fixation; it also reduces the mechanical strength of PMMA-based bone cement, thereby reducing the difference with bone  due to their excellent high modulus of elasticity and tensile strength . The areUnlike minimally invasive injectable cement materials, vertebral implants are primarily composed of implantable metals  Figure . These iin vitro biomechanical study on the Osseofix system used human cadaveric vertebrae; it showed that the yield and ultimate loads of the vertebrae repaired by the system were similar to those of intact vertebrae. In addition, the Osseofix system was effective in restoring the original biomechanical strength of fractured vertebrae, unlike kyphoplasty  is widely used in the clinic. However, it lacks bioactivity and leads to a series of clinical complications. Therefore, newer bone cements including MPC and CSC have been developed; these have been favored by researchers owing to their superior osteoclastogenic and angiogenic effects. Biomaterials with various beneficial properties have been mixed with bone cement to improve its handling properties and bioactivity in a targeted manner. A review of the types and clinical efficacy of new vertebral implants used in third-generation vertebroplasty show that a wide variety of options are available for the treatment of different types of VCFs.Although the implant materials developed for minimally invasive treatment have various outstanding properties, their clinical effectiveness and safety remain unclear. In addition, clinical validation of processing properties such as injectability and setting time are lacking for new composite bone cement materials. Large-scale controlled clinical studies evaluating the efficacy of new vertebral implants are also lacking; the scope of their application warrants further investigation. Clinicians also need to address the issue of selection of appropriate materials for minimally invasive surgery. In conclusion, the ongoing improvements in technology and biomaterials are expected to make minimally invasive surgery for VCFs safer and more effective.


Glutamate and γ-aminobutyric acid (GABA) are the two main neurotransmitters in the human brain. The balance between their excitatory and inhibitory functions is crucial for maintaining the brain’s physiological functions. Disturbance of glutamatergic or GABAergic neurotransmission leads to serious health problems including neurodegeneration, affective and sleep disorders. Both GABA and glutamate are involved in the control of the sleep–wake cycle. The disturbances in their function may cause sleep and sleep-related disorders. Obstructive sleep apnea (OSA) is the most common sleep respiratory disorder and is characterized by repetitive collapse of the upper airway resulting in intermittent hypoxia and sleep fragmentation. The complex pathophysiology of OSA is the basis of the development of numerous comorbid diseases. There is emerging evidence that GABA and glutamate disturbances may be involved in the pathogenesis of OSA, as well as its comorbidities. Additionally, the GABA/glutamate targeted pharmacotherapy may also influence the course of OSA, which is important in the implementation of wildly used drugs including benzodiazepines, anesthetics, and gabapentinoids. In this review, we summarize current knowledge on the influence of disturbances in glutamatergic and GABAergic neurotransmission on obstructive sleep apnea. Glutamate is well known for its function as the major excitatory neurotransmitter and can be found in different areas of the human central nervous system (CNS). In a healthy brain, glutamate is responsible for maintaining synaptic plasticity and many physiological functions such as learning and memory consolidation. In pathological conditions, glutamate is described as a neurotoxin leading to neurodegeneration .de novo or it can be recycled in the glutamate/glutamine cycle and it is stored in synaptic vesicles (N-methyl D-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA), and kainic acid receptor. These receptors after the binding of a ligand, change their conformation allowing for an influx of sodium ions and efflux of potassium ions leading to fast depolarisation of postsynaptic neurons. The metabotropic receptors (mGluRs) can be divided into group I, II, and III, they are slower-acting receptors, that act indirectly on neurons through changes in gene expression and protein synthesis . There are 19 subunit genes that encode six α , three β (beta1-3), three γ (gamma1-3), three ρ (rho1-3), and one of the δ (delta), ε (epsilon), π (pi), and θ (theta) subunit  act indirectly on neurotransmission through G-protein and intracellular messengers, and it mediates the slow response of the neuron. The summary of GABAergic neurotransmission is illustrated in As mentioned above glutamate as the main excitatory neurotransmitter needs to be regulated and its extracellular concentration must be kept in the strict range, so as not to induce neurodegenerative effects. To maintain the homeostasis of a healthy brain it is important to achieve the delicate balance between glutamate and the main inhibitory neurotransmitter γ-aminobutyric acid (GABA). GABA is synthesized in presynaptic neurons from glutamate, stored in presynaptic vesicles, and released upon membrane depolarization. After releasing to the synaptic cleft, GABA binds to the postsynaptic ionotropic receptor GABAor GABAB . GABAA r subunit . The GAB neurons . This ty neurons  (see Tab neurons . GABAB rObstructive sleep apnea (OSA) is a common chronic disease associated with respiratory events during sleep . It is cDiscussing the correlation between sleep respiratory disorders and dysregulation in neurotransmitter systems, it is crucial to describe the difference between central and obstructive sleep apnea. In contrast to obstructive sleep apnea, in which the episodes of apnea/hypopnea are caused by collapsed upper airways, although the respiratory effort is present, central sleep apnea (CSA) is characterized by lack of respiratory drive during sleep resulting in repetitive periods of apnea. The pathogenesis of OSA as well as CSA may overlap, and therefore central respiratory events may frequently evoke obstruction in upper airways and obstructive events may result in central respiratory events. Symptoms and complications of both diseases may be also similar including excessive daytime sleepiness and increased risk of adverse cardiovascular outcomes. Nevertheless, there are several pathomechanisms involved in the development of CSA, including treatment related CSA, CSA due to other medical condition , high altitude related CSA and primary CSA. The most important mechanism underlying CSA is unstable ventilatory drive. The proper responsiveness to chemoreceptor stimuli is an important factor for homeostasis of ventilatory drive. Changed chemosensitivity to PaO2 or PaCO2 or H+ concentration could lead to destabilization of respiratory system feedback loop and therefore evoke central respiratory events. Transition from wakefulness to sleep is another factor contributing to the decreased chemosensitivity and can significantly disturb loop gain . These aBrain mechanisms involved in the control of sleep and wakefulness are very complex and still not fully known. The regulation of the sleep–wake balance is achieved by the complex interactions between several neurotransmitter systems in different parts of the brain. In recent years many pharmacological agents, that target specific neurotransmitters’ receptors have been designed to induce sleep. That fact highlights the role of neurochemistry in sleep/wake control. Both GABA and glutamate as two major inhibitory and excitatory neurotransmitters in the human brain are the main regulators of wakefulness and sleep.Wakefulness may be described as a characteristic pattern of behavioral and cognitive responses to the external world . It is cSleep is the state of mind and body characterized by reduced interactions with the surrounding world, subjectively perceived as a loss of consciousness. The changes in brain activity during the onset of sleep reflect in EEG as the replacement of low-amplitude high-frequency rhythms by high-amplitude slow rhythms. This represents the progressive inhibition of ARAS neurons activity during the transition from wake to sleep . Sleep cGlutamate, a major excitatory neurotransmitter, is involved in maintaining homeostasis of physiological sleep. As OSA is one of the most common sleep disorders, it has been suggested that dysfunction of the glutamatergic system may be involved in its pathophysiology and lead to the development of OSA comorbidities.Recent research on animal models has provided evidence concerning the role of glutamate in the development of OSA. The authors of the study observed that injection of L-glutamate into the rat insular cortex resulted in the decrease of genioglossus muscle electrical activity and therefore induced obstructive apnea . This phThe increased glutamate concentration and decreased N-acetylaspartate  have been observed in midbrain nuclei of OSA patients, which indicates neuronal injury. The results of another study show that chronic intermittent hypoxia characteristic of OSA patients decreases glutamate transporters expression in glial cells, which may lead to reduced tolerance to glutamate exposure . The excGlutamate is often used in research as a metabolite  of pathomechanism involved in the development of OSA. The recent research on the large cohort database of the Hispanic Community Health Study/Study of Latinos provided evidence that glutamate plasma concentration is positively associated with OSA . GlutamaDysregulation of GABA in OSA is often correlated with the upregulation of glutamate and could lead to similar effects as described previously. Even though, the function of these two neurotransmitters is co-dependent, distinct GABAergic dysfunction may be involved in the development of OSA and its comorbidities.In neuroimaging studies, the assessment of the balance of the inhibitory and excitatory neurotransmission in the dorsolateral prefrontal cortex (DLPFC) in patients with sleep-disordered breathing was performed. The proton magnetic resonance spectroscopy showed that the levels of GABA in DLPFC were negatively correlated with AHI, and positively correlated with minimal oxygen saturation during sleep. The fact of hypoxia-mediated decrease in inhibitory GABA neurotransmission in DLPFC of OSA patients may lead to potential excitotoxicity and cognitive dysfunction . AnotherA recent study evaluated the role of GABAergic neurons in the ventral medulla (VM) and its influence on hypoglossal motor activity. With the use of electrophysiological methods, authors observed the existence of a direct inhibitory neuronal monosynaptic pathway from GABA/glycine neurons in VM to brainstem hypoglossal motoneurons. After the activation of VM GABAergic neurons, the inhibitory effect on tongue electromyographic activity has been observed . These rB receptor 1 gene (GABABR1) polymorphisms and OSA has shown that the Phe658Phe polymorphism is associated with apnea-hypopnea index (AHI) and OSA occurrence  and act as a positive allosteric modulators. Their inhibitory effect on neurotransmission in respiratory regions in CNS is responsible for the reduction of central respiratory drive and depression of chemoreceptor responsiveness to the hypercapnia  may induce the central sleep apnea. Although hypnotic drugs may reduce sleep fragmentation, and improve sleep continuity, its depressant effect on the central nervous system may lead to the depressive effect on respiratory centre . On the Additionally what is worth mentioning is an influence of hypnotic drugs on sleep microstructure. Especially the agonistic GABA A receptor modulators  even tough different action on GABA A receptor, they produce their hypnotic effect through similar changes in the sleep microstructure. This group of drugs enhance the effect of GABA on GABA A receptors. The main effects of these hypnotic agents on sleep include the increased ability to fall asleep, increased sleep continuity, increase in NREM sleep time and stimulation of spindles appearance in NREM sleep. It has been also described that they may decrease the REM sleep time due to the suppression of REM sleep episodes . AccordiA receptor. The results of a study on the effects of eszopiclone on the apnea induced neurotoxicity in guinea pigs provided evidence that experimental recurrent apnea resulted in significant morphological apoptosis of the hippocampal region as well as an increase in synaptic responsiveness (The role of glutamate in OSA pathophysiology has been used to test possible therapeutic agents. Sabeluzole – a glutamate antagonist was implemented in the therapy of patients with OSA. It was found that sabeluzole was responsible for a significant reduction of the oxygen desaturation index in patients with OSA, although the affective effect of this treatment has not been found significant . With resiveness . In the siveness . These asiveness . It is esiveness . These oThis review summarized the current knowledge on the role of GABAergic and glutamatergic systems in OSA. Available data suggest that dysfunctional neurotransmitter systems might be involved in the pathogenesis of OSA as well as its comorbidities. As GABA and glutamate may have a different effects on the activation of targeted cells, they cooperate to maintain the homeostasis of physiological neurotransmission and structural unity of the brain. The excitatory effect of increased glutamate in different brain areas including the insular cortex and hippocampus may lead to its dysfunction and damage. Excitotoxicity is described as one of the most important mechanisms involved in brain structural changes. Additionally, the increased glutamate concentration in body fluids may serve as a molecular metabolite of OSA pathogenesis. The effects of GABAergic dysregulation in OSA are partially caused by the increase in the excitatory influences leading to similar damage to neurons. GABA is an important transmitter in the regulation of upper airways muscle tonus, which especially manifests during REM sleep and dysregulation of the GABAergic system may manifest as REM-predominant OSA. Overall, both GABA and glutamate may possibly contribute to the development of common OSA comorbidities including affective disorders, cognitive impairment, hypertension, autonomic dysregulation, and dysfunctional glucose metabolism. The functions of GABAergic pathways in OSA pathogenesis are important when assessing the adverse effects of GABA-modulating therapies including gabapentinoids, benzodiazepine, and non-benzodiazepine hypnotics, groups of drugs commonly used to treat OSA patients. The further research is needed for better recognition of complex neurological pathways involved in OSA-related changes in GABA/glutamate balance, as well as to establish possible therapeutic approaches for OSA comorbidities related to dysfunctional neurotransmission.AG and PK: creation of article concept. PK: conduction of preliminary literature search, writing original draft, and creation of figures. AG: supervision. AG, MS, DS, and PB: revision of manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Evolution in the chronic cold of the Southern Ocean has had a profound influence on the physiology of cryonotothenioid fishes. However, the suite of genetic changes underlying the physiological gains and losses in these fishes is still poorly surveyed. By identifying the genomic signatures of selection, this study aims to identify the functional classes of genes that have been changed following two major physiological transitions: the onset of freezing temperatures and the loss of hemoproteins. Looking at the changes that followed the onset of freezing temperatures, positive selective pressure was found among a set of broadly acting gene regulatory factors, suggesting a route through which cryonotothenioid gene expression has been retooled for life in the cold. Further, genes related to the cell cycle and cellular adhesion were found under positive selection suggesting that both present key challenges to life in freezing waters. By contrast, genes showing signatures of the relaxation of selective pressure showed a narrower biological impact, acting on genes related to mitochondrial function. Finally, although chronic cold-water temperatures appear correlated with substantial genetic change, the loss of hemoproteins resulted in little observable change in protein-coding genes relative to their red-blooded relatives. Combined, the influence of positive and relaxed selection shows that long-term exposure to cold has led to profound changes in cryonotothenioid genomes that may make it challenging for them to adapt to a rapidly changing climate. Evolution in the isolation of the cold Southern Ocean has led to widespread physiological change in the cryonotothenioid fishes, but how this is reflected in changes among their pool of protein-coding genes remains poorly described. Here, we comprehensively investigated changes in the suite of protein-coding genes to identify which genes and associated functional categories have been changed following evolution in the chronic cold.Today, the waters of the Antarctic shelf are dominated by the members of a single taxonomic group, the cryonotothenioid fishes, comprised of the five Antarctic families of the perciform suborder Notothenioidei . The oriThe most obvious shift in selective pressure experienced by the cryonotothenioids during the geological evolution of the Southern Ocean came from the region's cooling. In contrast to the cold-temperate waters inhabited by their closest non-Antarctic relatives, surface water temperatures around Antarctica remain below −1.5 °C, and freezing water temperatures define the most species-rich waters along the Antarctic coast, even to great depths . In addiAlthough the origin of the cryonotothenioid clade is estimated at 22.4 million years ago (Ma) , most ofIn addition to the influence of temperature, the isolation of the Southern Ocean has allowed the evolution of lineages characterized by substantial and, in some cases unique, physiological reorganization. This is exemplified by the members of the notothenioid family Channichthyidae (the icefishes) that are extraordinary for the absence of the respiratory pigment hemoglobin . Oxygen Several prior studies have aimed to develop a broad understanding of the changes to protein-coding genes in the cryonotothenioids associated with polar evolution. Looking first at global biases in amino-acid composition that may explain adaptation to polar conditions, Studies by Daane et al. , 2020 haAlthough results by Dissostichus mawsoni genome. Metrics on the filtered genomic and transcriptomic resources used to identify orthogroups are presented in To investigate how the shifts in selective pressure from evolution in chronic cold and loss of hemoproteins have affected the pool of protein-coding genes among the cryonotothenioids, we obtained and analyzed 3,453 orthogroups that contained all species in a 19-taxa data set . These tThis set of orthogroups was used for alignment construction then evaluated using HyPhy to identify genes showing signatures of either positive or relaxed selective pressures. The goal being to understand whether positive and relaxed selective pressures affected distinct functional categories of protein-coding genes.A). RELAX then identified 114 orthogroups as experiencing relaxed selective pressure (A). The set of genes showing signatures of positive selective pressure and relaxed purifying selective pressure was largely distinct, but nine genes were found to show signatures of both  and Branch-Site Unrestricted Statistical Test for Episodic Diversification (BUSTED) identified 113 and 89 orthogroups respectively under positive selection, with 160 orthogroups identified as experiencing positive selective pressure from either of the two analyses, and 42 orthogroups consistently identified as experiencing positive selective pressure by both analyses A. RELAX pressure A. The se of both  online.B). Similarly, relaxed selective pressure was detected for only 16 orthogroups using RELAX (B). There was no overlap among these sets of genes showing signatures of positive and relaxed selective pressures.Next, the icefishes were compared against a background set of the red-blooded cryonotothenioids, to identify genes under changed selective pressure following the loss of hemoproteins. This comparison showed a far smaller signature of impacts from both positive and relaxed selective pressures. The signature of significant positive selective pressure was identified on only 15 orthogroups using BUSTED, and 32 orthogroups with aBSREL, resulting in a total of 41 distinct orthogroups identified as experiencing positive selective pressure from either analysis, with six orthogroups identified under positive selective pressure by both analyses B. Similang RELAX B. There P-value threshold of 0.1 (A), identifying functional impacts on the regulation of gene expression, cell cycle progression, and cell adhesion. Looking at the more restricted set of 42 orthogroups where both BUSTED and aBSREL agreed they were under positive selection found 31 significantly enriched GO terms  enrichment analysis  online. d of 0.1  online. d of 0.1 A, identiGO terms  online. In contrast with the investigation of orthogroups showing signatures of positive selective pressure, enrichment analysis of the orthogroups under relaxed selective pressure in the red-blooded cryonotothenioids produced a much more restricted set of enriched GO terms after FDR correction  online. P value, these did not result in any enriched GO terms. Instead, the biological impact of changed protein-coding sequences among the icefishes was investigated by direct interrogation of the set of orthogroups, and to help characterize their disparate biological roles, they were grouped according to their Panther protein classification  and mRNA processing (THOC5). Prior studies have suggested that nascent protein synthesis , suggesting adaptative change has acted on this toolkit to enable a basic activity of life to continue at freezing temperature.Alongside changes related to the pattern and process of gene expression, the set of genes under positive selection suggests compensatory change to adapt to the rate-limiting effects of low temperature on biological systems. This change is first seen through impacts to genes with essential roles in the cell cycle. A critical constraint on an organism's viable temperature range is the temperature range over which cell division can occur , as thisHarpagifer antarcticus found this to progress at a faster rate at 0 °C than in its sub-Antarctic congener Harpagifer bispinis at 5 °C suggesting cold compensation in the Antarctic species . This could represent parts of the genetic change that allow the cell cycle to progress at a biologically relevant rate at the low temperatures of the Southern Ocean.In addition to challenges to the functioning of the cell cycle from the cold, the rate-limiting effects of low temperature present a further problem. However, past comparative studies have shown that adaptation can compensate for the rate-limiting effect of the cold on growth rates , and thi species . Here, sCADH1, DSC2L, and EPCAM) that link intercellular connections to the cytoskeleton (CTNA1) and that regulate cell junction organization (TMM47). The ability of cells to adhere to one another is strongly impacted by temperature, with a reduced capacity for adhesion as temperatures drop as cell–cell linkages lose the ability to organize and maintain cohesion , genes essential to mitochondrial function , and genes associated with biosynthesis within the mitochondria  or of essential mitochondrial proteins . Recent work analyzing the types of selection acting on the protein-coding genes in the notothenioid's mitochondrial genome by These genes span a range of roles within the mitochondria, including several components of the electron transport chain , change that is correlated with the highly modified cardiovascular system seen in the icefishes that allows the larger blood volume necessary to transport oxygen in blood plasma without the presence of red blood cells  correspond to increases in mitochondrial size and density within icefish cells, and perhaps the need to keep cellular metabolism fueled in these fishes as oxygen availability is more limited. Finally, selection was seen in genes related to cartilage biosynthesis (CHSTB) and neural patterning (IRX3) both of which would likely be tied to the continued modification of skeletal and skull shape than what is seen in the remaining cryonotothenioids.Although relatively few genes showed signatures of changed selective pressure in the icefishes when compared with the red-blooded cryonotothenioids, this set of icefish genes under changed selective pressure was diverse . The smaod cells . InteresBesides the more limited scope of the comparison compared with cold adaptation, are there other reasons why we might observe such muted signatures of genetic change among protein-coding genes following hemoprotein loss? One possibility is that the relatively recent divergence of the icefishes has not allowed sufficient time to see widespread changes in protein-coding genes even if selective pressures have shifted. Alternatively, The genomes of the cryonotothenioid fishes have been changed during their evolution in the isolation of the Southern Ocean as seen among their suite of protein-coding genes. The observed changes reflect not only the abiotic challenges of life in a cold and oxygen-rich environment but also the stability of the region's waters.The influence of positive selective pressure was most strongly felt on proteins with roles in gene expression, suggesting one route through which the cryonotothenioid transcriptomic profile was retooled for life in the cold. Further change observed in genes with roles in the machinery of transcription, cell cycle progression, and in cell adhesion, pointing to biological challenges for life in a freezing ocean. Contrasting with the influence of positive selection, the relaxation of selective pressure appears to have exerted a narrower influence. This seems to have driven change to a diverse group of genes related to mitochondrial function, perhaps due to the reduced challenges of carrying out aerobic metabolism given the cold-stable temperatures and high oxygen levels found in Southern Ocean waters. Finally, in icefishes, the loss of hemoglobin has resulted in far fewer detected signatures of change in the sequence of protein-coding genes, perhaps due to the smaller number of possible target genes compared with cold adaptation or due to the alternative genetic and physiological mechanisms that may have compensated for this unique loss.In evaluating these changes, one note of caution is that we are limited by the number of orthologous relationships that we could identify among the protein-coding sequences of the target species. It is likely that further biological systems under positive and relaxed selective pressures have yet been discovered in this group as a fuller view of protein-coding genes becomes available.Ultimately though, cryonotothenioid fishes have been exposed to long and intense selective pressure for survival in freezing waters and now show widespread change when compared with temperate fishes including long development and generation times, deferred maturity, and extended life spans . The genD. mawsoni Norman, 1937  were compiled for a background set of temperate and tropical fishes. These included two extant temperate notothenioid fishes that diverged prior to the adaptation to polar conditions in the cryonotothenioids, the Patagonian blenny e value.The transcriptomic reads were assembled for all of the cryonotothenioids. The reads were first cleaned with Fastp v0.20.1  and thenFinally, the relative completeness of species’ genome- or transcriptome-derived set of predicted peptides was evaluated using BUSCO v. 4 . BUSCO p16S and ND2) and 11 nuclear genes . Accession numbers for the genes used in this analysis are provided in To provide a phylogenetic frame of reference for later evolutionary hypothesis testing, we reconstructed the relationship among the 19 investigated species. This phylogeny was constructed using 2 mitochondrial . To evaluate our approach to paralog pruning, we generated an additional set of filtered orthogroups using the approach described in Orthogroups were inferred across species from their filtered set of predicted peptides using OrthoFinder v. 2.5.1 . The resMSAs were then generated for each retained orthogroup. The CDS for each orthogroup's predicted peptides were codon aligned with GUIDANCE2  using PrOrthogroups experiencing positive selective pressure were identified using the phylogeny-based strategy implemented in the BUSTED  and the P-value threshold of 0.1 was used in all tests to identify those orthogroups showing a significant change in selective pressure from the background set.The orthogroups were first used to compare protein-coding genes in the red-blooded cryonotothenioids as the foreground against the background set of temperate and tropical fishes to identify the set of orthologous genes that have come under changed selective pressure during the cryonotothenioid radiation in the frigid Southern Ocean. Similarly, the icefishes were tested as the foreground against a background of red-blooded cryonotothenioids to identify the set of orthogroups that have come under changed selective pressure specific to the loss of hemoproteins. A FDR-adjusted D. mawsoni predicted peptide set was annotated for GO terms using the Orthologous Matrix fast mapping utility (OMA browser; D. mawsoni using Blast2GO (D. mawsoni predicted peptide.GO enrichment analysis was used to place the impacts of positive and relaxed selective pressures into biological context. The Blast2GO . GO slimP-value threshold of 0.1, both on the results of the individual tests, on the intersected set of genes where both BUSTED and aBSREL agreed on signatures of positive selection, and on the combined set of genes identified under positive selection by either BUSTED or aBSREL. The identified set of significant GO terms was then visualized using the EnrichmentMap (TopGO v. 2.44  was usedhmentMap  plug-in hmentMap .evad049_Supplementary_DataClick here for additional data file.


Acute mesenteric ischemia (AMI) is a severe medical condition defined by insufficient vascular supply to the small bowel through mesenteric vessels, resulting in necrosis and eventual gangrene of bowel walls. We present the case of a 64-year-old man with recrudescence of prolonged epigastric pain at rest of few hours duration, cold sweating and episodes of vomiting. A computed tomography scan of his abdomen revealed multiple filling defects in the mid-distal part of the superior mesenteric artery (SMA) and the proximal part of jejunal branches, associated with small intestine walls thickening, suggesting SMA thromboembolism and initial intestinal ischemia. Considering the absence of signs of peritonitis at the abdominal examination and the presence of multiple arterial emboli was decided to perform an endovascular treatment with ultrasound assisted catheter-directed thrombolysis with EkoSonic Endovascular System—EKOS, which resulted in complete dissolution of the multiple emboli and improved blood flow into the intestine wall. The day after the procedure the patient's pain improved significantly and 5 days after he was discharged home asymptomatic on warfarin anticoagulation. After 1 year of follow-up the patient is fine with no further episodes of mesenteric ischemia or other embolisms. EtiologThe landmark symptom for the vast majority of patients is abdominal pain which is usually sudden in patients with AMI caused by emboli, and instead has insidious onset in patients with thrombotic etiology where the atypical clinical presentation of pain often postpones the diagnosis, worsening the prognosis . MortaliTreatment options depends on the etiology, hemodynamic stability of the patient and the experience and expertise of the treating team . Surgica2.A 64-year-old man, with a history of transient ischemic attack and hypertrophic cardiomyopathy with an implantable cardioverter-defibrillator (ICD) and in therapy with atenolol 50 mg/day, presented to our Emergency Department for recrudescence of prolonged epigastric pain at rest of few hours duration, cold sweating and episodes of vomiting. The reported pain has been present for about 1 year under effort  with remission at rest. The patient wasn't on any anticoagulation therapy at the time of admission. The patient was hemodynamically stable with a heart rate of 118 bpm controlled by the pacemaker and a blood pressure of 160/80 mmHg. Cardiologic evaluation revealed symmetrical pulses, no murmurs at the auscultation and no abnormal findings were found on echocardiography. An abdominal examination revealed minimal epigastrium tenderness with no signs of peritonitis. A laboratory examination revealed a white blood cell (WBC) count of 12.3 K/μl, a serum C-reactive protein of 4.2 mg/L, a serum lactate on venous blood gas of 3.1 mmol/L, a serum troponin I of 1,143.4 pg/ml and on second control a serum troponin I of 1,117.2 pg/ml.The patient was hospitalized in coronary care unit where he showed poor response to gastroprotective and antacid drugs. The movement of troponin curve wasn't compatible with a pattern of myocardial infarction but referable to chronic myocardial damage related to the known hypertrophic cardiomyopathy.Due to the persistence of symptomatology 36 h after the admission in emergency room a contrast-enhanced computed tomography scan of the abdomen was performed, and the arterial phase revealed multiple filling defects in the mid-distal part of the superior mesenteric artery (SMA) and in the proximal part of jejunal branches with no evidence of atherosclerosis, associated in portal phase with small intestine walls thickening without intramural or extramural air, suggestive for SMA thromboembolism and initial intestinal ischemia . AdditioA multidisciplinary evaluation with general surgeon, vascular surgeon and interventional radiologist was done and considering the absence of signs of peritonitis at the abdominal examination, the patient was sent to the angio suite. The option of open surgery was also considered but the lack of physical findings and the presence of multiple arterial emboli prompted us to attempt endovascular treatment. In case of any clinical deterioration the patient would have undergone an open intervention.The patient underwent ultrasound-guided right femoral artery puncture after local groin anesthesia with 10 ml of lidocaine and a 6-Fr introducer sheath was inserted over a J-wire. Subsequently, a Cobra-C2 catheter  was inserted into the superior mesenteric artery. An angiographic study was done which showed the presence of subtotal thrombotic occlusion of the SMA with multiple emboli in jejunal branches and still a hemodynamic compensation by collateralization . Due to After the therapeutic treatment period the patient's pain improved significantly and the EKOS catheter was removed. The patient returned into the angio suite the following morning to repeat an angiogram. The SMA angiographic study confirmed the absence of vessel stenosis and revealed a complete dissolution of the multiple emboli with an improvement of the blood flow into the intestine wall .Four days after the procedure the patient underwent an abdominal CT scan that confirmed the previous angiogram images without any filling defects of thrombotic nature of the upper mesenteric artery, thoracic aorta, and large splanchnic vessels . CompareThe patient was discharged home the day after asymptomatic on warfarin anticoagulation, beta-blockers, and large spectrum antibiotic therapy.After 1 year of follow-up the patient is fine with no further episodes of mesenteric ischemia or other embolisms.3.The optimal management of AMI remains controversial, while many authors suggest the surgical approach with concurrent assessment of bowel viability as the first line treatment, others consider endovascular approach a superior alternative. Usually, the choice of the first therapeutic option appeared mostly dependent on surgeon or interventional radiologist expertise and institutional preference, confirming lack of a standardized protocol . FurtherThe surgical treatment consists in exploratory laparotomy with the assessment of bowel viability, removal of the non-viable bowel tract and in case of embolism in SMA the restoration of blood flow by mechanical embolectomy with a Fogarty catheter. The endovascular treatment consists in a mechanical embolectomy by thromboaspiration or stent-retriever or by the combination of these two techniques. While surgery is required in cases of non-viable bowel, minimally invasive interventional approaches have several advantages, such as the avoidance of general anesthesia and the use of laparotomy in high-risk patients. However, the disadvantage is that some useful time could be lost, a delayed surgical intervention place additional bowel at risk due to only partial resolution of the obstruction to blood flow .In this reported case the patient had a recent onset of abdominal pain with no peritoneal signs and a suspected cardiac embolism origin. The abdomen CT scan showed wall thickening and hyperemia in multiple small bowel loops without intramural or extramural air, the SMA presented multiple filling defects in the mid part and in proximal side branches with no evidence of atherosclerosis. According to the recently published update of the ACR criteria of the radiologic management of mesenteric ischemia, in our case is considered appropriate an endovascular approach. The ACR criteria also suggest that a transcatheter thrombolysis may be considered if aspiration embolectomy fails .In this case, in presence of a partial occlusion of the SMA and the presence of multiple distal emboli with still a blood flow to the intestinal loops, has been decided to proceed directly with catheter thrombolysis using EKOS.The EkoSonic Endovascular System is designed for ultrasound assisted catheter-directed thrombolysis. The 0.035-inch guidewire compatible catheter allows selective and controlled delivery through its multiside hole ports directly to the affected vascular segments of high concentration of thrombolytic agent (Alteplase 1 mg/h), high frequency ultrasound increase the permeability of the thrombolytic agent into the thrombus disassociating the fibrin strands, increasing thrombus surface area and making more plasminogen activator receptor sites available for facilitating thrombolysis , 10. ThiIn conclusion this case illustrates the successful applications of ultrasound assisted thrombolysis to dissolve a SMA embolic thrombus in patient with acute mesenteric ischemia. While, this procedure can't be used to perform a rapid restoration of the intestinal blood flow, in some specific case with a partial occlusion of the SMA and a residual blood flow to the intestine loops can be employed successfully. Thus, the limitations of this procedure are prolonged treatment duration, risk of bleeding and need to return to the angio suite for the evaluation of the therapy. The advantages include being a minimally invasive procedure without the need of a general anesthesia of a long operation in these high-risk patients.This device can represent a new therapeutic option also in these characteristic cases of acute mesenteric ischemia with widespread thrombosis but presence of residual flow and no signs of peritonitis. Larger case series are needed to confirm this result, to establish proper patient selection and treatment timing.