Leber’s hereditary optic neuropathy (LHON) is thought to be a neurovascular disease due to presence of vascular changes in asymptomatic patients. Here we present 2 patients in whom optical coherence tomography angiography (OCTA) imaging demonstrated capillary drop-out areas and decreased radial peripapillary capillary (RPC) density in the quadrants that had thinner retinal nerve fiber layer (RNFL) in OCT images. Progressive decrease in RNFL and RPC density were shown in each patient at month 12 and 30 of follow-up. Following up patients with OCTA imaging in the future will provide insight into the pathogenesis and prognosis of LHON. Increased vessel tortuosity and capillary size at the optic disc suggest that the disease is a neurovascular disorder.2 Recently, the development of optical coherence tomography angiography (OCTA) has enabled noninvasive evaluation of the ocular microvasculature. With this method, the peripapillary retinal and vascular circulation can be evaluated three-dimensionally. Evaluation of vascular changes in LHON using OCTA may help us to understand the pathophysiology of the disease, assess disease progression, and monitor the efficacy of treatment. Here we presented the optical coherence tomography (OCT) and OCTA findings of 2 patients with LHON.Leber’s hereditary optic neuropathy (LHON) is a maternally inherited mitochondrial DNA-related disease.A 28-year-old man with no relevant history was referred to our clinic with loss of vision in both eyes, starting first in his right eye and 1 week later in the left eye. His best corrected visual acuity (BCVA) was counting fingers at 25 cm in the right eye and 1/20 in the left eye. Optic discs were pale in both eyes. OCT showed thinner retinal nerve fiber layer (RNFL) in all quadrants in the right eye and consistent with the OCT findings, there were areas of capillary drop-out and decreased radial peripapillary capillary (RPC) density in all quadrants on OCTA . The RNFL was thinner in the inferior and temporal quadrants and, similar to OCT findings, capillary drop-out areas and decreased RPC density were detected in the inferior and temporal quadrants in the left eye . GeneticAn 8-year-old boy with family history of LHON in his maternal uncle was examined. Ophthalmologic examination revealed normal findings. Although the family was informed, they did not consent to genetic evaluation. Two years later, the patient presented with loss of vision in his left eye. BCVA was 20/20 in the right eye and counting fingers at 1 meter in the left eye. Optic discs were normal in the right eye and pale temporally in the left eye. He was diagnosed as having LHON with G11778A mutation and idebenone (450 mg/day) treatment was given orally. At 6-month follow-up, the right eye was also affected. Visual acuities were 2/20 in the right eye and counting fingers at 1 m in the left eye, and both optic discs were pale temporally. The patient was followed up with idebenone therapy OCT and OCTA imaging for 30 months. Visual acuity was counting fingers at 1 m and there was optic disc pallor in the both eyes at the last visit. Although his right eye was not affected in the first visit, drop-out areas were determined by OCTA imaging. Decreased RNFL thickness and RPC density and increased capillary drop-out were shown by OCT and OCTA in the follow-up period .4 Balducci et al.4 reported decreases in RPC mostly in the temporal region in patients at different stages.Since OCTA imaging is a noninvasive and easy method to evaluate vascular structures, different studies evaluated vascular changes in LHON patients and demonstrated RPC defects.Our case reports have importance for evaluating RPC density and capillary drop-out areas in LHON over long-term follow-up and we were also able to compare OCTA findings in patient 2 before and after involvement. In both cases, in parallel to the decrease in RNFL, RPC density decreased and peripapillary capillary drop-out areas increased.6 In accordance with this knowledge, loss of RNFL and RPC density were detected in the inferior and temporal quadrant in the left eye in the early stage of disease. In the follow-up period, both RNFL and RPC density decreased progressively in all quadrants.In our first case, both eyes were affected when the patient presented to our clinic. A decrease in RNFL was observed in all quadrants in the right eye, which was involved first, while the left eye was affected later and the decrease in RNFL was shown only in the temporal and inferior quadrants. Decrease in RPC density was correlated with loss of RNFL. RPC density was decreased in all quadrants in the right eye and in the temporal and inferior quadrant in the left eye in the first evaluation. In the early stage of LHON, it is known that the smaller caliber fibers of papillomacular bundle are lost, and then loss of fibers progresses and all fibers of the optic nerve can be affected.7 The increase in thickness can be explained by impaired axoplasmic transport and a compensatory increase of mitochondrial biogenesis. It is followed by progressive thinning as atrophy develops in the later stages. Decrease in RPC density can be associated with the thinning of RNFL. When the RNFL get thinner, the required metabolic activity is reduced and this can explain the progressive decrease of RPC density in LHON as the disease progresses and RNFL get thinner.In the second case, we were able to evaluate the OCT and OCTA findings of the right eye before involvement and we detected drop-out areas. Before visual acuity decreased in the right eye, we showed that there were drop-out areas. This finding is important in terms of demonstrating OCTA changes in asymptomatic carriers. In the acute phase of the right eye, RNFL thickness increased and visual acuity decreased without any change in RPC density. Decrease in RPC density followed the decrease of RNFL. In LHON, it has been shown that RNFL thickness increases in the early acute phase (within 12 weeks of symptom onset) and decreases gradually in the late acute (12 to 24 weeks after symptom onset) and chronic (24 weeks or more after symptom onset) phases.8 determined that the severity of visual loss was associated with the density of macular superficial capillary plexus. A shortcoming of these case reports is that macular microvascular changes were not evaluated.In the follow-up period of our patients, although the decrease in RPC density progressed, visual acuity was stable. This may be explained by macular microvascular changes. In LHON patients, not only the optic disc but also macular microvascular structures are affected. Borrelli et al.In conclusion, OCTA imaging is thought to be an important test for evaluating changes in LHON patients and asymptomatic carriers. In the future, following patients with treatment will help us to gain insight into the pathogenesis and prognosis of LHON.


Psoriasis only affecting the genital area occurs in 2-5% of subjects with psoriasis. This condition is a frequent reason for consultation with a specialist in men’s genital mucosa, since it accounts for 24% of the reasons for consultation. The gland of circumcised subjects is usually finely squamous and non-squamous in non-circumcised subjects, based on preputial moisture. Gland involvement can be diffuse and associated with an involvement of the internal face of the prepuce. We here report the case of a 30-year old patient with a family history (grandfather) of psoriasis. The patient involved in the study had a 2-month history of squamous circumferential erythematous lesions on the glans penis without pruritus or associated urinary signs and without cutaneous manifestations. Biopsy of the mucosa of the glans penis was performed which confirmed the diagnosis of psoriasis. A 50-year-old man came to our private practice, for palate pain and difficulty swallowing. The medical history reported gastro esophageal reflux, otherwise the patient was in good health. He reported having recently suffered from a flu syndrome treated with antibiotics (amoxicillin and clavulanic acid) cortisone and anti-inflammatory drugs. At the second day of drug therapy, the patient started to have severe oropharyngeal pain with inability to eat, reflex sialorrhea and dysphagia. From an objective examination of the oral cavity, we could see vesicular lesions along the right arch of the hard palate with partial extension to the left. A diagnosis of herpetic infection was made. The erythematous and oedematous mucosa was in the ulcerative phase. Paracetamol and systemic acyclovir have been recommended to alleviate general symptoms, fever and pain. The patient was advised to not touch the palate with his hands to avoid the expansion of the virus in other facial areas. The prescribed therapy was not performed due to the increase in esophageal gastrointestinal reflux, so after 3 weeks the lesion was still present if reduced. The differential diagnosis could be thermal burn, chemical trauma, herpes zoster lesion (VZV).


Objective: To provide information on the clinical characteristics and management of an uncommon acquired nasolacrimal drainage system obstruction (NLDSO).Methods: A patient was treated with microdebrider-assisted endoscopic marsupialization for a cystic lesion located in the synechiae between the inferior turbinate and the lateral wall of the inferior meatus.Results: A 21-year-old woman suffered from epiphora and purulent discharge 1 week after inferior turbinate surgery. Endoscopy reveled synechiae between the inferior turbinate and the lateral wall of the inferior meatus. Computed tomography-dacrocystography (CT-DCG) showed enlargement of the nasolacrimal duct and cystic accumulation of contrast medium from the lacrimal orifice posteriorly. The patient was treated with nasal endoscopic marsupialization of the cyst and then powered inferior turbinoplasty. Six months after the operation, both endoscopy and CT scan showed a widely patent left inferior meatus and nasolacrimal orifice.Conclusions: We report the first case of post-operative NLDSO following inferior turbinate surgery. Nasal endoscopy and CT-DCG are useful to diagnose the location of a NLDSO. Otorhinolaryngologists should be aware that surgery may lead to the formation of a NLDSO and that endoscopic marsupialization is a curative treatment for these distal-end NLDSO. NLDSOs are caused by synechiae, which are a complication of inferior turbinate surgery. Inferior turbinate hypertrophy is one of the main causes of chronic nasal obstruction and can have an allergic, infectious or vasomotoric etiology. Inferior turbinate surgery is widely performed to treat this disease. Complications of inferior turbinate surgery are rare , but bleThe patient was a 21-year-old female university student who had undergone bilateral submucosal resection of the inferior turbinate at another hospital to treat her nasal obstruction. She had never complained of epiphora before her first surgery. One week after discharge, she began to experience both epiphora from her left eye and swelling of her left eyelid, but her symptoms were tolerable. So, she left her symptoms untreated for 6 months until she began to suffer from purulent discharge from the left eye. She visited the same hospital again, where the doctor in charge suspected dacrycystitis and subsequently referred her to our hospital where her university was located.Flexible endonasal fiberscopic examination showed bilateral inferior turbinate hypertrophy. In addition, the anterior part of the left inferior nasal meatus had disappeared because the lateral portion of the inferior turbinate was adhering to the lateral wall of the inferior meatus . CoronalWe reported the first case of post-operative NLDSO following submucosal resection of the inferior turbinate. Because of its anatomical characteristics , the lacAt least 13 surgical techniques have been used over the past 130 years to treat hypertrophy of the inferior turbinate . SynechiEpiphora secondary to NLDSO is usually treated with a dacryocystorhinostomy (DCR) performed via an open or endonasal approach . RecentlWe report the first case of post-operative NLDSO following inferior turbinate surgery. CT-DCG showed patency of the lacrimal duct from the sac to the orifice, and significant cystic accumulation of contrast medium extended from the orifice, suggesting that the synechia occurring post-operatively following the previous inferior turbinate surgery had created a cystic lesion that stored lacrimal fluid between the inferior turbinate and the lateral wall of the internal meatus. We performed endoscopic marsupialization of the cystic lesion and repeated the inferior turbinoplasty. Nasal endoscopy and CT-DCG are useful to diagnose the location of a NLDSO. Otorhinolaryngologists should be aware that surgery may lead to the formation of a NLDSO and that endoscopic marsupialization is a curative treatment for these distal-end NLDSOs. Based on the findings in our patient, NLDSO might be caused by synechiae, which are a complication of inferior turbinate surgery.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.HTac, HS, MF, and HTak: conception and design. HTac and HS: literature search and obtaining of images. HS and HTak: wrote the article. All authors: critical revision and final approval of the article.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.


The REGARDS-MI ancillary study provided new outcomes of heart disease events and adjudicated cause of death. A primary focus has been disparities in and risk factors for coronary artery disease. We demonstrated that compared to White men, Black men have a higher risk of fatal coronary heart disease (CHD) but a lower risk of non-fatal CHD. Ongoing work is investigating potential reasons for this. We have investigated the role of CHD in aging including the relationship between heart failure and cognitive function and the association of MI with functional status. The REGARDS-MI study has served as a platform for mentoring trainees and early stage investigators, many from underrepresented groups, and provided data to a large number of investigators to purse research in CHD. To date, REGARDS-MI has contributed to nearly 200 publications and spawned additional ancillary studies. This presentation will highlight some of these publications and other research in progress.


Dual mobility hip implants have been widely introduced to overcome dislocation in recent years. However, the potential influence of different gaits on kinematics and contact mechanics for dual mobility hip implants is still unclear. Furthermore, a large range of motion coupling with the implant position, especially high inclination or anteversion angle, may result in poor kinematics and contact mechanics. A previously developed dynamic finite element method was adopted in this study to examine the kinematics and corresponding stability of dual mobility hip implants under different gaits coupling with different inclinations or anteversion angles. The results showed only inner relative sliding under knee-bending for dual mobility hip implants under moderate inclination and anteversion angles, whereas an anteversion angle of 25° induced both impingement and consequent relative sliding of the outer articulation. However, the impingement (between the stem neck and the liner inner rim) indeed happened under stair-climbing and sitting-down/stand-up as well as combined movements when inclination and anteversion angles were set as 45° and 0°, respectively, and this finally led to relative sliding at the outer articulation. A high inclination angle did not worsen both the impingement and related outer sliding compared to modest inclination and anteversion angles of the liner, but a high anteversion angle prolonged the period of both the impingement and the outer relative sliding. The extreme motions and high anteversion angles are hardly inevitable, and they indeed lead to motions at both articulations for dual mobility hip implants. Dual mobility hip implants have been introduced extensively to prevent long-term dislocation of artificial hip joints , 2. AfteThe dual mobility hip implant is mainly composed of a back shell, an intermediate liner, and a modular femoral head (a stem is coupled). Because the liner is not constrained onto the back shell anymore as the conventional hip joint done, it is intended to be mobile and thus two articulations are introduced  for this kind of implant. The liner will remain static when the stem rotates during walking movement, and thus, only inner articulation relative motion occurs if both articulations are of similar lubrication. However, it is possible that the stem neck impinges the inner rim of the liner when high anteversion angle is initially set for the liner and finally leads to rotation of the liner together with the stem (relative motion at the outer articulation) under the same walking activity. Both of these two different relative motions during walking gait cycle were observed in the studies by Gao et al. , 8. BesiX-axis was pointed medial, the Z-axis was along superior, and the Y-axis was perpendicular to both the X-axis and the Z-axis and towards to posterior.A dual mobility hip implant, including the back shell, the liner, the femoral head, and stem, was modeled as in The dual mobility hip implant would experience different range of motions under different daily activities such as walking and knee-bending. In this study, knee-bending, stair-climbing, sitting-down/up, and combination of them were considered. The original data of these movements were from Bergmann et al. , and theAlthough the dual mobility hip implant is generally implanted with appropriate inclination and anteversion angles as the conventional artificial hip joint, the liner is hard to be fixed and keep the position unchanged. The ideal position of the liner in THR surgery is of 0° and 45° for inclination and anteversion angles, respectively. For other positions, the liner may be of high inclination or/and anteversion angles. These possible positions of the liner were designed to three different cases in this study. Case 1 specified the inclination angle and anteversion angle of the liner of 45° and 0° for all gaits, respectively. In Case 2, the inclination angle of 70° and anteversion angle of 0° were used for the liner, with a reference to a previous study . For CasAn explicit dynamic finite element method, which was developed in a previous study , was useAll three surface-to-surface contact pairs were modeled, including the back shell and liner, the liner and the femoral head, and the liner inner rim and the stem neck as shown in The contours of the maximum accumulated sliding distances of the inner and outer surfaces of the liner at three different inclination and anteversion angles for an entire knee-bending gait cycle are shown in The contours of the maximum accumulated sliding distance at the inner and outer articulations of the liner are shown in The liner inner rim also experienced impingements during both stair-climbing and combined gait cycles. These impingements showed similar influence on the liner inner and outer surface maximum accumulated sliding as the sitting-downing/standing-up gait cycle; the detailed results are listed in The dual mobility hip implant may experience impingement and consequent relative sliding at both inner and outer articulations under extreme movements such as stair-climbing. However, the kinematics and the contact mechanics of dual mobility hip implants under the condition of impingement are still unclear. If the liner is at a high anteversion angle which has been proven to result in impingement between its inner rim and the stem neck in a previous study , this imBoth contact pressure and the accumulated sliding distance and ROM of dual mobility hip implant under different daily activities were predicted. The main findings of this study can be concluded as three points. First, the impingement between the stem neck and the inner rim of the line occurred during sitting-down/standing-up, stairs-climbing, and combined movements. Just the impingement led to the liner rotated together with the stem and finally resulted in relative motion at the outer articulation for the dual mobility hip implant. However, the impingement did not increase the contact pressure of both inner and outer surfaces of the UHMWPE liner. Secondly, if the liner was initially set high anteversion angle, it would prolong the period of both impingement and increased consequent relative sliding distance of the outer articulation for the dual mobility hip implant. Similarly, this still did not obviously worsen the contact mechanics of the liner. Third, the dual mobility hip indeed experienced large ROM under knee-bending, sitting-down/standing-up, stairs-climbing, and combined movements. The lasting period of impingement did not obviously influence the ROM for dual mobility hip implant under these different activities.The study of Fabry et al.  showed tThe dual mobility hip implant would also experience impingement of the liner under extreme anteversion angle during walking movement according to previous study . The curWhen it refers to contact pressure at all contact pairs during different inclinations and anteversion angles for daily activities, the impingement between the stem neck and the liner inner rim resulted in very high contact pressure at liner inner rim during the impinging period which could be harmful for the liner. However, this impingement did not apparently influence the contact pressure of both the liner inner and outer surfaces. For all daily activities, the relative motion of the inner articulation dominated for the dual mobility hip implant even under the worst position that the liner was of high anteversion angle. This probably finally led to the inner wear dominating for the dual mobility hip under extreme range of motions such as sitting-down/up and stair-climbing. This was in agreement with the result of the study by Imbert et al.  that theThe current study predicted the kinematics and the contact mechanics of the dual mobility hip implant under daily activities of patients and high inclination or anteversion angle. However, several limitations should be pointed out. First, the relative experiments were still unavailable to be performed in this study. Second, the impingement and consequent relative sliding of the outer articulation for the dual mobility hip are dependent with the geometry and the size of the liner; however, only one kind of liner and constant size of liner were investigated in this study, and other geometry and sizes of the liner should be considered in the future. Third, average gaits data was used in this study; it is still needed to investigate kinematics and contact mechanics of dual mobility hip implant for a specified-patient according to his or her gait data. Besides, the soft tissue still has not been included in the FE model of the dual mobility hip implant; however, this may result in insert blocking and introprosthetic dislocation, and this should also be considered in future study.Different daily activities and implant positions were considered to investigate their effects on the kinematics and the contact mechanics of a dual mobility hip implant using previous developed dynamic explicit finite element method. The impingement of the liner and consequent dual relative rotations were obtained during the movements of sitting-downing/standing-up, stairs-climbing, and their combinations even at appropriate inclination and anteversion angles of the liner . When a higher inclination or anteversion angle was set for the liner, both the impingement and the outer articulation relative sliding would increase for the dual mobility hip implant. However, both the impingement and the outer articulation relative sliding did not occur during a knee-bending gait cycle even at high inclination or anteversion angles. The dual mobility hip implant indeed experienced impingement and related rotation of the liner during an increased range of motions, particularly combined with high anteversion angles. The impingement and consequent relative sliding of outer articulation for dual mobility hip implant could be inevitable because of patients' daily activities and uncertainly of the liner orientation in vivo for the dual mobility hip implant, but the inner articulation would probably dominate in both the relative motion and wear for the dual mobility hip implant under these extreme conditions.


The entorhinal cortex (EC) is a vital component of the medial temporal lobe, and its contributions to cognitive processes and memory formation are supported through its extensive interconnections with the hippocampal formation. During the pathogenesis of Alzheimer's disease (AD), many of the earliest degenerative changes are seen within the EC. Neurodegeneration in the EC and hippocampus during AD has been clearly linked to impairments in memory and cognitive function, and a growing body of evidence indicates that molecular and functional neurodegeneration within the EC may play a primary role in cognitive decline in the early phases of AD. Defining the mechanisms underlying molecular neurodegeneration in the EC is crucial to determining its contributions to the pathogenesis of AD. Surprisingly few studies have focused on understanding the mechanisms of molecular neurodegeneration and selective vulnerability within the EC. However, there have been advancements indicating that early dysregulation of cellular and molecular signaling pathways in the EC involve neurodegenerative cascades including oxidative stress, neuroinflammation, glia activation, stress kinases activation, and neuronal loss. Dysfunction within the EC can impact the function of the hippocampus, which relies on entorhinal inputs, and further degeneration within the hippocampus can compound this effect, leading to severe cognitive disruption. This review assesses the molecular and cellular mechanisms underlying early degeneration in the EC during AD. These mechanisms may underlie the selective vulnerability of neuronal subpopulations in this brain region to the disease development and contribute both directly and indirectly to cognitive loss.This paper has an associated Future Leader to Watch interview with the first author of the article. Summary: This review evaluated the molecular mechanisms that may explain the vulnerability and susceptibility of the entorhinal cortex to early neurodegeneration during the pathogenesis of Alzheimer's disease. Alzheimer's disease (AD) is a progressive neurodegenerative disorder that results in widespread neuropathology throughout the brain, and severe disruption of cognitive and mnemonic function . AD invoA substantial body of research has linked dysfunction of the EC to cognitive impairments experienced early in the progression of AD, and there is also a growing understanding of the factors that may make the EC particularly susceptible to molecular degeneration . One facThe development and advancement of neuropathogenesis in most neurodegenerative diseases is governed both by the selective initial vulnerability of particular neuronal subpopulations to the disease pathology, and a generally predictable pattern of gradual spread of pathology across multiple brain regions . MultiplEarly declines in memory function are associated with the onset of neuronal and synaptic degeneration in the EC, hippocampus and posterior cingulate cortex . The EC In vivo quantification of atrophy and molecular changes in the EC could also improve monitoring and evaluation of the effectiveness of therapeutic strategies. A crucial objective in Alzheimer's research is the identification of biomarkers that can promote early diagnosis and treatment of the disease. The belief is that pre-symptomatic intervention will be far more potent than applying therapy after the onset of disease. The progressive pathological changes that occur in the EC during early AD can serve as effective biomarkers that may aid prediction and diagnosis of AD long before its clinical manifestation . In vivoThe EC provides the hippocampus with most of its cortical sensory and associational input, and degradation within the EC can therefore disrupt entorhinal function, as well as hippocampal processing that is dependent on entorhinal inputs . The supDeterioration within the medial EC (MEC) versus lateral EC (LEC) may contribute in different ways to the symptomatology of AD . The MECAlthough the origin of AD-related degenerative changes has been extensively linked to regions of the EC, subcortical structures are also early targets of AD, and degeneration in subcortical regions may contribute to cortical degeneration during AD. For example, selective vulnerability to early AD has been observed in neurons of the nucleus basalis of Meynert (NbM), the largest of the cholinergic cell clusters constituting the basal forebrain that widely innervate the neocortex . Extensi1-42 rapidly enhances excitatory postsynaptic potentials in layer II through activation of NMDARs . Exaggerated synaptic strengthening contributes to increased activation of the hippocampus early in the progression of AD during mild cognitive impairment , excitotoxicity, and cell death . NMDARs pairment , and thepairment . The rap2+)-dependent glutamate release . These findings are similar to those in the hippocampus which also show downregulation of NR2A and NR2B mRNA expression in AD , which have been associated with early onset AD . For exaon in AD . In addion in AD . This fu2+-mediated excitotoxicity and neuron death  glutamate receptors, their recruitment to the postsynaptic membrane, and growth of dendritic spines  to generate large-scale transcriptomic profiles of individual EC cells from control and post-mortem AD brains, in order to assess cell-type-specific differences in gene expression patterns that may influence AD susceptibility; subpopulations of cells with unique networks of co-regulated genes and functions were identified across different cell types in the EC of AD brains . ImportaA substantial contributor to cognitive decline in AD is thought to be the deterioration of neuromodulatory transmitters including noradrenergic, serotonergic, and cholinergic neurons . NeuronaIn addition to increases in excitatory synaptic transmission, disruption of inhibitory synaptic transmission in the LEC is thought to contribute to excitotoxicity . In a knThe production of reactive oxygen species (ROS) at physiological levels in mitochondria during aerobic respiration has a positive role in cellular signaling, but if ROS exceed the cellular antioxidant capacity, ROS can disrupt the redox balance and result in oxidative stress. Oxidative stress alters the structure of macromolecules through the formation of cross-linkages, and leads to the functional alteration of proteins, lipids, and nucleic acids. Effects on DNA and RNA are a major trigger for neuronal degeneration, and several lines of evidence including our previous studies suggest that oxidative stress resulting from mitochondrial dysfunction are at the forefront of neuronal death during AD pathogenesis . In AD, Oxidative stress and mitochondria dysregulation appears to be an important early molecular driver of AD-type neuropathology within the EC. Oxidative stress manifests very early during AD, leading to the hypothesis that it then drives further pathogenesis mediated by Aβ . NeuronaOxidative damage to RNA in subjects with AD has been assessed using immunoreactivity for the oxidised nucleoside 8-hydroxyguanosine (8OHG), and it is elevated in neuronal cytoplasm of brain regions that are vulnerable to AD pathology including the EC, hippocampus, subiculum and temporal neocortex . Levels 1-42-rich areas like the hippocampus as compared to Aβ1-42-poor brain regions -alpha and monocyte chemoattractant protein (MCP-1), and these changes are correlated with increases in F4/80-positive microglia and macrophages . F4/80 pNeuronal death during AD has been attributed to both Aβ and tau dysregulation as shown in The loss of neurons in AD occurs very early in the EC , and sevAlthough the field is still nascent, evidences of the molecular mechanisms driving selective activation of cell-death pathways in the EC during AD are beginning to emerge. The selective activation of stress and cell-death kinases by Aβ or/and tau may contribute to the vulnerability of the EC to neuron loss . There iThough the full mechanistic spectrum accounting for the unique response of the EC to intrinsic and extrinsic neurotoxic stimuli leading to AD has not been fully determined, we have discussed the emerging understanding of the biochemical and anatomical variabilities that are specific to this brain region which may underlie molecular and functional neurodegeneration in AD. Studies reviewed here indicate that the EC may show selective vulnerability during the early pathogenesis of AD due to interacting factors including genetic and physiological differences in neuronal subpopulations, the expression level of neurochemicals modulating neural functions, and the sensitivity of multiple intracellular signalling cascades to triggers of AD pathology including Aβ protein.


Over the last two decades, Gambia has made noticeable progress in the reducing the high maternal mortality rates and improving child survival rates. Nonetheless, numerous infrastructural and financial constraints continue to restrict access to institutional delivery care, a key component of achieving the maternal and child health related Sustainable Development Goals (SDG 3.1). This study assesses factors that predict women’s choice of mode and place of delivery in urban and rural Gambia.n = 5351) were analyzed. The outcome measures were place  and mode of delivery  in urban and rural Gambia. Data were analyzed using descriptive and multivariate regression methods.Cross-sectional data from the latest round of Gambia Demographic and Health Survey (2013) on women aged 15–49 years (About three-fifth (60.8%) of the participants had their last childbirth at a health facility and 39.2% at their home. There was a significant urban-rural difference in the prevalence of facility delivery with 86.9% of the urban women choosing health facility over home compared with 45.8% among the rural women. In the regression analysis, place of residence, education of participants and the husband, employment, parity and use of antenatal care were significantly associated with the use of health facility delivery services. For instance, having secondary  and higher education  showed higher odds for using facility delivery services; and women from the richest wealth quintile had significantly higher  odds of using facility delivery compared with those in the lowest quintile.Our findings suggest a sub-optimal use of professional childbirth services among Gambian women which appears to be driven by various geographical, educational, wealth inequality, parity and low use of ANC services. Addressing the socioeconomic and demographic inequalities may lead to a more widespread usage of maternity services in Gambia. Women in the rural areas with a professional/managerial job had 3.839 times  higher odds of using C-section. Being in the richest wealth quintile also showed a positive association , especially among rural  women. Rest of the sociodemographic  and healthcare (ANC use) factors did not show any significant association.Even though The Republic of The Gambia has made it a national priority to promote reproductive health the country still has one of the highest maternal mortality rates  in Sub-Saharan Africa. That being said, since the launch of the global Safe Motherhood Initiative in 1987, MMR has decreased mainly because the government has implemented a number of interventions  to combat the dual scourge of neonatal and morbidity and mortality.The present study is concerned about the pattern of using professional childbirth services, namely health and C-section. The results show that about two-fifth of the women in Gambia are deprived from facility delivery services. After taking into consideration the geographical factors, the situation looks even more challenging, with the prevalence being 45.8% among rural residents compared with 86.9% among the urbans. This striking disparity echoes the growing urban-rural inequality in health status and healthcare utilization across the continent. Women in the urban areas generally enjoy higher access to resources and better quality of services , 17. SimThe beneficial aspects of C-sections have been highlighted in previous studies; however, it was reported the benefits generally plateau beyond the range of 19%. Results indicate that national prevalence of using C-sections in Gambia is far below the optimum range, and the African average as well. A global analysis on the trend in C-section between 1990 and 2014 reported that South America and the Caribbean region had the highest C-Section rates (40.5%) followed by Northern America (32.3%), Oceania (31.1%), Europe (25%), Asia (19.2%) with the African region having lowest rate (7.3%) of all . The natIn the multivariable analysis, significant sociodemographic differences were observed in the likelihood of the utilization of facility delivery services. Interestingly, higher age was associated negatively with facility delivery use, although increasing age is a good predictor of health literacy, education, decision-making power which are regarded as enabling factors of healthcare use , 19. As The use of C-section is comparatively less common in low-income settings, especially in countries like Gambia where maternal healthcare centers, especially those in the rural areas may not be equipped to the provide the service –23. The The results further indicate that women in agrarian communities are more deprived of facility delivery services compared even with non-working women. The financial and livelihood hardship endured by women employed in agriculture is well-known. It is therefore recommended that maternal healthcare promotion programs pay special attention to farming communities. Several other factors were found to be significantly associated with facility delivery service utilization that merit special attention including media access, higher parity and adequate use of ANC services. Mass media communication plays a key role in promoting health knowledge and awareness among general population, and can help promote the use of maternity services in low-income settings. The positive association between media access and facility delivery service utilization in the present study suggests that investing on media exposure and quality healthcare communication can improve the uptake of the services. Media exposure can equally raise awareness regarding family planning services and help women gaining control over their reproductive preferences. As shown by the results, women with higher parity are less likely to use facility delivery services. Lastly, using ANC also showed significantly positive association with facility delivery service utilization. Women who visit healthcare professionals during pregnancy are generally more likely to gain knowledge about the dangers of unattended childbirth, consequences of complicated pregnancy, and understand the importance of choosing skilled birth services. In light of this finding, it is recommended to improve the coverage of ANC services which may increase the use of professional childbirth services.This study is the first to report the prevalence of using facility delivery and C-section use in nationally-representative sample in Gambia. Important sociodemographic disparities were observed in the odds of using the services, among which the most notable were women’s education, ethnic background, wealth status of the household, parity, and family planning communication through mass media. These findings of the present study fill an important gap in the literature. Main strengths were the use of nationally representative data from four rounds of survey that allows making a generalizable conclusion about the prevalence and associations. Nonetheless, this study has several limitations to report. First of all, the data were cross-sectional and hence no causality can be inferred from the associations. The data were secondary and authors have to influence over the selection and measurement of the variables. As the data were self-reported, the chances of recall and reporting bias cannot be ignored. The factors that influence healthcare service utilization are diverse and multifaceted, but the choice of the explanatory factors was limited as the survey was not conducted by the authors. Factors such as geographical distance, transportation facilities, quality of services in local healthcare settings, availability of female care provider have been found to be important in primary studies, that we were not able to adjust for in the current analysis. The use of C-sections is also a complex outcome that can be driven by various personal and medical factors. However, no such data were collected in this survey. For large-scale surveys like the GDHS, collecting in-depth data may not always be feasible due to time and resource constraints. Future studies should aim to address these limitations by considering more sociocultural and environmental variables. Lastly, due to the nature of the survey and analyses, causality cannot be inferred for the relationship between the outcome and explanatory factors.Finding of the present study reflect sub-optimal use of professional childbirth services in Gambia. The factors behind this scenario can be multifactorial and require in-depth investigations. As implied by the findings, the differences might be rooted in geographical, educational, wealth inequality, parity and low use of ANC services. The role of socioeconomic and demographic factors in accessing childbirth services are well-supported by the present study. Based on these insights, it is recommended that health policy makers establish special intervention programs focusing on socially disadvantaged communities with the aim of reducing maternal health related inequalities, which can also pay off for the actions towards attaining Sustainable Development Goals (SDGs).


Adaptive design methods are a potential solution to improve efficiency of clinical trials but their uptake in dialysis is unknown. We aim to investigate the use of adaptive design methods in dialysis clinical trials and to cultivate further adoption of adaptive design methods by the nephrology community.We will adhere to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines and the Cochrane Collaboration Handbook. We will perform a literature search through MEDLINE (PubMed), EMBASE and CENTRAL, a detailed data extraction of trial characteristics and a narrative synthesis of the data. There will be no language restrictions. We will estimate the percentage of adaptive clinical trials per year in dialysis. Subgroup analysis will be performed by dialysis modality, funder and geographical location.Ethical approval will not be required for this study as data will be obtained from publicly available clinical trials. We will disseminate our results in a peer-reviewed publication. This study presents a comprehensive methodology for a systematic review of the current state of adaptive designs (ADs) clinical trials in dialysis.Two researchers will independently perform the study selection, data extraction and risk of bias assessment.Detailed characteristics of trials will be collected and analysed including nature of intervention, funding source, dialysis modality and the nature of the AD.Subgroup analysis will be performed to highlight differences in design characteristics between dialysis modality, temporal trends, types of intervention, funding and geographical location.Randomised controlled trials (RCTs) are the gold standard for confirming efficacy or futility of new therapies.5There are an estimated 726 331 prevalent cases of ESRD in the USA11Adaptive clinical trials use the results from interim data analysis of ongoing trials to modify the study design in a predefined way.20The systematic review will aim to: (1) summarise the use of AD methods in dialysis clinical trials per year, (2) describe the characteristics of the ADs including dialysis modality, funding and geographical location, (3) describe the AD characteristics of the trial, (4) estimate the percentage of adaptive clinical trials in dialysis and (5) outline trends in all the above.This systematic review has been registered with PROSPERO (registration number: 163 946 (Temporary ID)). We will conduct this systematic review according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) and have completed the PRISMA-P checklist .10.1136/bmjopen-2019-036755.supp1Supplementary dataRCTs of interventions in patients with ESRD or acute kidney injury (AKI) undergoing renal replacement therapy (RRT) including haemodialysis, peritoneal dialysis, haemodiafiltration and haemofiltration. We will not limit our population or any specific disease.We will not place a restriction on the intervention type and will include trials that study medications during dialysis, medical devices, dialysis parameters, and so on.We will include all outcomes including surrogate markers, patient-centred outcomes and hard clinical outcomes.et alWe will perform electronic searches on MEDLINE (PubMed), EMBASE and CENTRAL from database inception until 1 January 2020. Zotero will be used as our reference manager and the Revtools package on R will be used to eliminate duplicate records. The search will be conducted in English. The dialysis search terms were adapted fromBeaubien-Souligny et alThe AD search terms were adapted from Bothwell ‘sample size adjustment’(tiab). We will perform two searches, first, we will combine the dialysis and adaptive search terms using a Boolean AND. The specific search will be carried out as described in We will use the high sensitivity machine learning classifier (RobotSearch) to identify RCTs from the combined search  and from the dialysis search.et al 2016)CJ and RPPM will extract the following information .Year of completion of study.Trial population.Duration of time participants was receiving RRT (AKI or ESKD).Intervention.Domain of the intervention .Primary outcome measure.Type of primary outcome variable (continuous or dichotomous).Nature of primary outcome .Dialysis modality .Sample size.The country of the lead investigator.The funder of the study (public or private).Published in journal with impact factor >10.We will use the Cochrane Risk of Bias Tool26A descriptive synthesis of the data will be performed. We will estimate the percentage of adaptive clinical trials in dialysis per year by dividing the adaptive clinical trials per year by the total number of RCTs per year.We will report overall outcomes and outcomes by dialysis modality .This systematic review will start in April 2020.There was no formal patient and public involvement in the design of this study.Ethical approval was not required for this study. We will publish the results of this systematic review in a peer-reviewed journal.The number of clinical trials performed in ESRD is low compared with other medical subspecialties.We expect to provide the following results: first, we will report on the proportion of RCTs in dialysis that include an AD; second, we will outline the most popular type of AD in ESRD trials; third, we will report the main dialysis modalities where ADs are used and possibly highlight underutilisation in additional modalities; and fourth, we will report the geographical locations and funding pattern for trials using AD in dialysis.Furthermore, the main impact from this systematic review will be increased awareness in the nephrology community of the potential benefit of using ADs in clinical trials. Having clear examples and use cases of successful AD will stimulate further use of these designs. Patients with ESKD are often excluded from RCTs, we urgently need novel design methods for investigating treatments in this underserved population. This systematic review will highlight ADs as one part of the solution to this problem. A secondary impact from this systematic review will be an up-to-date census of all RCTs in dialysis with a yearly count of trials. This information can be used to influence funders and policymakers about the importance of funding nephrology and especially ESKD research.This review will have potential limitations including publication and reporting bias. We will not be able to include studies with unpublished data and we will misclassify studies that do not have clear reporting of ADs in their methodology.


This research paper investigates entropy generation analysis on two-dimensional nanofluid film flow of Eyring–Powell fluid with heat amd mass transmission over an unsteady porous stretching sheet in the existence of uniform magnetic field (MHD). The flow of liquid films are taken under the impact of thermal radiation. The basic time dependent equations of heat transfer, momentum and mass transfer are modeled and converted to a system of differential equations by employing appropriate similarity transformation with unsteady dimensionless parameters. Entropy analysis is the main focus in this work and the impact of physical parameters on the entropy profile are discussed in detail. The influence of thermophoresis and Brownian motion has been taken in the nanofluids model. An optima approach has been applied to acquire the solution of modeled problem. The convergence of the HAM  has been presented numerically. The disparity of the Nusslet number, Skin friction, Sherwood number and their influence on the velocity, heat and concentration fields has been scrutinized. Moreover, for comprehension, the physical presentation of the embedded parameters are explored analytically for entropy generation and discussed. In the past few years, it has been observed that the entropy generation on nanofluid flow analysis has significantly contributed in the area of industries, engineering and technology as well as in other emerging fields of science. Actually, entropy is a thermodynamic quantity representing the unavailability of a system’s thermal energy for conversion into mechanical work, often interpreted as the degree of disorder or randomness in the system. In other words, entropy is a measure of the energy dispersal in the system. We see evidence that the universe tends towards highest entropy many places in our lives. A campfire is an example of entropy. The solid wood burns and becomes ash, smoke and gases, all of which spread energy outwards more easily than the solid fuel. Thin film flow problems have diverse applications in many fields, fluctuating from specific situations in the flow in human lungs to lubrication problems in engineering, which is probably one of the largest subfields of thin film flow problems. The practical applications of thin film flow is a challenging interplay between fluid mechanics and structural mechanics. A nanofluid is comprised of a base fluid with tiny (nanometer) sized nanoparticles, such as carbides or carbon nanotubes, oxides, and metals, whereas traditional base liquids involve ethylene glycol, oil, and water. A nanofluid is very helpful in enhancing thermal conductivity and convection of heat transfer coefficient when it is analyzed with the base fluid. In modern technology, nanomaterials are becoming increasingly important in the performance of various heat exchangers, such as microelectronics, optical modulators, and chemical production. Magneto-nanofluids are also remarkable for their use in various applications, such as tunable optical fiber filters, magneto-optical wavelength filters, optical modulators, and optical switches. In biomedical engineering, magneto-nanoparticles are also very helpful in cancer therapy, sink-float separation, hyperthermia, magnetic resonance imaging (MRI), magnetic cell separation, drug delivery, and magnetic drug targeting. In particular, heat transfer and convective flow are influenced by the features of nanofluids, such as thermal conductivity and viscosity. Conventional heat transfer in various Newtonian and non-Newtonian fluids, such as ethylene glycol, oil, water, etc. holds a poor rate of heat transfer. However, the thermal conductivity of these kinds of fluids plays a significant role in the heat transfer coefficient between a heat transfer surface and heat transfer medium. During the last few decades, an innovative methodology has been used to enhance heat transfer with the help of ultra-fine solid particles in fluids. Non-Newtonian fluids are of various kinds; thus, all non-Newtonian fluids cannot be addressed by using single constitutive expression between stress and shear rate. Much attention has been devoted to study different models of non-Newtonian fluids. Among them is an Eyring–Powell fluid model, which is very complex, but it has certain advantages over other fluid models. Firstly, it was derived from a kinetic theory of liquids rather than the empirical relation as in the case of the Power-law model. Secondly, it appropriately reduces to Newtonian behavior for low and high shear rates. The Eyring–Powell fluid model describes properties of shear thinning fluids. Examples of such fluids are human blood, ketchup, toothpaste, etc. Thus, researchers are attracted to investigate its thermo physical properties. In view of all these applications, it becomes an important issue for researchers to develop the study of liquid film flow on the stretching sheet. The flow of liquid film was first studied for viscous flow and further it is extended to non-Newtonian fluids. Crane  was the The equation of continuity isThe equation of momentum isThe equation of heat transfer isThe equation of mass transfer isThe constitutive equation for a Cauchy stress in an Eyring–Powell model fluid  is givenx-axis and surface is perpendicular to y-axis. Linear velocity of the plate is along positive x-axis and assumed asx-axis direction at the rate Assume two-dimensional incompressible nanofluid liquid film flow of Eyring–Powell fluid having thermal radiation on the unsteady porous stretching surface with simultaneous transfer of mass and heat. The coordinate axes are selected such that the slit is along the direction of The basic governing equations are as follows :K represents porosity, Considering the above assumptions, the leading equations of continuity, momentum, energy and concentration of two-dimensional thin film flow are as under (10)∂u^∂Here, For our physical interest, the Skin Friction is defined as The dimensionless form of Liao in 1992 was the first one who proposed the Homotopy analysis method. He deduced HAM from one of the fundamental ideas of the topology called Homotopy. He used two Homotopic functions in the derivation of this technique. The functions are called to be Homotopic when one function can be continuously distorted into another. HAM is a substitute method and its main importance is that it is applied to the nonlinear differential equations without discretization and linearization. This technique has several advantages, some of them are (a) It is free from the values of the parameters which may be small or large. (b) Its declarations about the convergence of the solution. (c) It is independent from collection of base function and linear operator. The solution of Equations (22)–(24), with the reliable boundary conditions (25) and (26), are gained by use of analytic method. Solution results obtained by HAM contained the assisting parameters which regulate and control to converge the solutions and bases functions. The initial guesses areth Order system form Equations (34)–(36)The 0The Diffusive irreversibility (DI) .Fluid friction irreversibility (FFI).Heat transfer irreversibility(HTI) .The characteristics of entropy generation isEntropy generation(volumetric) for the Eyring–Powell fluid is as follows:When we computed the series solutions of concentration, velocity and temperature functions using HAM, the assisting parameters A on the A. The effect of film thickness k over the k increases, then it raises the nanofluid film motion, and this effect is clear at the stretching surface. The characteristics of magnetic factor M on fluid velocity profile is shown in M is inversely varied with velocity distribution M decreases the velocity field. This influence of magnetic field is caused by the production of friction force to the movement known as the Lorentz force, which brings retardation to the flow of the fluid and hence reduces fluid velocity at the edge.The characteristics of porosity parameter A has an opposite effect on temperature profile. A. Each and every fluid has the similar effect on temperature for the unsteady parameter A. The fluid produces confrontation to the flow of film and shows a tendency to reduce the velocity of fluid flow having larger values of M on temperature profile is shown in x-direction. The logic behind is that the Schmidt parameter is the ratio of momentum and concentration diffusivities. The rise in the values of x-direction, which is reflected in the graph. The influence of x-direction. The logic behind is that the Schmidt parameter is the ratio of momentum and concentration diffusivities. The viscidness dissipation effect on the nanoparticle volume fraction is insignificant for higher quantities of Schmidt numbers. k, Magnetic parameter M, Radiation parameter M, and k and This section deals with the theoretical and graphical behavior of different physical quantities that are obtained in the present flow problem. The computational software Mathematica has been utilized to investigate the novelties of all the physical parameters. Table quantities such as film thickness ith Wang , Narayanith Wang , and Qasith Wang . Completith Wang , Narayanith Wang , and Qasith Wang  for incre tables , respectThe present research work investigates entropy generation in two-dimensional nanofluid film flow of Eyring–Powell Fluid along with variable heat transmission through a porous stretching surface in the existence of constant magnetic field (MHD). The flow of liquid films are taken under the consideration of thermal radiation. The observation of this work depends upon the impact of variable temperature, thermal radiation and magnetic field on nanoliquid film flows. The modeled equations are solved analytically using HAM. The convergence has been shown numerically and the effect of the embedded parameters are observed and studied graphically. The influence of the skin fraction and nusslet number and sherwood number is shown numerically.M drop the velocity distribution of the nanofluid films.It is perceived that the large values of Magnetic parameter M, and Reynolds number Entropy profile increases with the increasing values of Brinkmann k and Radiation parameter Entropy profile decreases with the increasing values of Eyring–Powell parameter The larger values of Brownian motion The thermal boundary layer thickness reduces with rise of A, that is, the large values of A reduce the surface temperature.The growing behavior of Porosity parameter decreases the motion of the liquid films.It is perceived that the Thermal Radiation parameter It is observed that the heat profile falls with the large values of thermophoresis parameter The increasing values of The convergence of the HAM method with the variation of the physical parameters observed numerically.Non-dimensional velocity reduces with variable viscosity and magnetic constraints.The temperature gradient and concentration fields are both directly related with magnetic field.Rise in the nanoparticle concentration efficiently increases the friction feature of Eyring–Powell nanofluid.The central concluded points are as:


The objective of this review was to analyze the process of wear of implants leading to the shedding of titanium particles into the peri-implant hard and soft tissues. Titanium is considered highly biocompatible with low corrosion and toxicity, but recent studies indicate that this understanding may be misleading as the properties of the material change drastically when titanium nanoparticles (NPs) are shed from implant surfaces. These NPs are immunogenic and are associated with a macrophage-mediated inflammatory response by the host. The literature discussed in this review indicates that titanium NPs may be shed from implant surfaces at the time of implant placement, under loading conditions, and during implant maintenance procedures. We also discuss the significance of the micro-gap at the implant-abutment interface and the effect of size of the titanium particles on their toxicology. These findings are significant as the titanium particles can have adverse effects on local soft and hard tissues surrounding implants, implant health and prognosis, and even the health of systemic tissues and organs. Dental implants have become a popular option for the replacement of one or more missing teeth in the oral cavity due to their long-term success rate . Almost Recently, studies on biomaterials have become an important part of dental implant research as investigators attempt to better understand the etiology of implant failures. Manufacturers have developed numerous different implant designs differing in proportions of metals and other materials as well as surface roughening treatments all in an effort to improve osseointegration and biocompatibility while decreasing the rate of implant failure . Some ofManufacturers have also modified the surface roughness of implants to improve the osseointegration by acid etching, sandblasting, and oxidation techniques . ExtensiThe aim of this review was to summarize the current knowledge related to titanium wear produced during implant placement, loading, and maintenance with special focus in the biophysiological interactions at the implant abutment interface. Additionally, the mechanisms by which titanium particles are taken up by cells and induce inflammation will be discussed. Finally, the significance of the size of the particles, and the possible systemic effects the titanium particles can cause following ingestion from the oral cavity will also be evaluated.The study of titanium particles liberated from dental implant surfaces has become an important area of research in dental implantology. A 1993 study conducted by Schliephake et al. revealed the presence of titanium in the adjacent soft tissue surrounding titanium screws used to treat jaw fracture. The titanium was viewed 5–8 months post-operatively in transmission electron microscope images. The study suggested that the titanium particles localized extracellularly may be taken up by cells for lysosomal degradation, and the remnants may be left in place after the macrophages eventually clear out . SubsequThese results are further supported by a study done by Palazzo et al. . Their hSimilar findings are seen in recent microscopical EDX analyses of the peri-implant tissues of immediately loaded implants placed in the maxilla and mandible. In an autopsy report conducted 7.5 months after implant placement and loading, analyses showed titanium particles in direct contact to the implant and in distant areas from the implant-bone interface .One of the most important factors affecting the longevity of a dental implant restoration, is the fit of the implant with the abutment . A less A poor fit with a large micro gap will leave the implant vulnerable to structural damage in the form of fretting and micromovements at the connection when subjected to forces of mastication . In thisTo understand the significance of the interactions at the implant-abutment interface, it is important to understand the phenomena of corrosion and fretting. Corrosion is a process by which a refined metal becomes a more stable oxide, hydroxide, or sulfide. Pure titanium becoming titanium dioxide NP in the peri-implant environment is an example of this conversion. Fretting is the process of wear at the contact points of uneven surfaces. This process occurs under loading forces and may also occur in the presence of corrosion . FrettinThere has recently been an observation of increased titanium dissolution products in biofilms isolated from peri-implantitis cases. These results suggest a possible modification in the structure and diversity of the microbiome due to the titanium dissolution . These f2O2 and albumin [2, so called reactive oxygen species (ROS), such as H2O2 and superoxide ions, which further increase the corrosion of titanium metal. The inflammatory state is associated with increased neutrophils and macrophages which generate ROS via the respiratory burst pathway [The corrosion of titanium is enhanced by the presence of H albumin ,50,51. I pathway . This ph pathway . Metal d pathway .Surface analysis of retrieved titanium alloy hip implants from humans were investigated for evidence of localized or general corrosion in modular interfaces when mechanical abrasion of the oxide film (fretting) occurs. The study showed cracking, etching, pitting and delamination of the surface, as well as degradation in the crevice environment during fretting-crevice corrosion and hydrogen embrittlement . Two surTitanium accumulation of 13 ppm and above has been shown to induce epithelial cell necrosis and increase the sensitivity of epithelial cells of the peri-implant mucosa in microorganisms. This observation is due to ROS production and increased cytokine levels, leading to a reduction of cell viability and proliferation. Additionally, the induction of apoptosis and genotoxicity have been documented . The bioThere is no doubt that implant maintenance is required after implant therapy as a standard of care. Many clinicians practice instrumentation of dental implants routinely in order to control and manage peri-implant diseases ,65,66. LRecent studies have shown that mechanical alteration of implant surfaces may lead to negative consequences . The insPeri-implantitis is a feared complication of dental implants as the inflammation and osteolysis surrounding the implant is nearly impossible to reverse ,68. UltrPettersson et al. supported the above conclusions with their study . In thisImplant manufacturers practice various surface modification strategies in an attempt to increase surface roughness of the implants to increase osseointegration ,77,78,79Titanium particles shed from the implant surface are immunogenic. Along with dental cement, studies have identified titanium as a predominant foreign body in peri-implantitis biopsies, and these metals are surrounded by inflammatory cells in the tissues . TitaniuMetal debris was first identified as a potential etiologic factor for implant complications in orthopedics and has since then become a growing area of interest in implant dentistry . SpecifiTitanium particles shed from implant surfaces range in size from microparticles to NPs. The toxicology of titanium dioxide NPs has been extensively studied. These particles are small enough to be transported systemically throughout the body, and due to their size, they are capable of being internalized by cells, allowing them to interact with organelles and cause intracellular lesions ,89,90. R2 NPs in case of “overload” in the body [Generally, three crystalline phases of titanium dioxide (titania) NPs exist. Anatase  and rutile are tetragonal, brookite is orthorhombic. The potential toxicity depends on the size and crystalline form. It is important to consider the potential risk from the TiOthe body .2) NPs become bio-camouflaged prior to being internalized by cells. It is important to understand the concept of biocompatibility and the issues surrounding the nature of this term. While an implant or medical device may be considered biocompatible as a whole unit, the NPs which are shed from the devices may have different properties which allow them to enter cells in numbers exceeding toxic threshold [In 2017, the same research group utilized transmission electron microscopy and graphene liquid cells to further investigate the mechanism by which anatase  comprising 40–65% TiO2 and leucoxene (Fe2O3 nTiO3) containing more than 65% TiO2 [The body normally contains 10–20 mg of Ti, and research has shown this level to increase following treatment with medical implant devices . Additio65% TiO2 . These m2), cobalt NPs or zirconia (ZiO2) [Titanium dioxide NP absorption is a complex phenomenon as seen in NPs used in sunscreen for skin protection, which have different scattering and absorption factors within the skin in the different wavelengths of light . Howevera (ZiO2) . NPs cana (ZiO2) ,111.2 NPs accumulating in systemic tissues. Weingart et al. found these particles deposited in regional lymph nodes via spectroscopic and energy dispersive x-ray analysis [Titanium is transported systemically following uptake by the GI tract as the binding affinity of titanium for transferrin is greater than that of iron ,112. Oncanalysis . This meanalysis ,115. Howanalysis . The noranalysis ,118.Corrosion of varying degree was identified close to the metal surface forming a pseudo-membrane with varying thicknesses. The thickness was the lowest around titanium, tungsten and zirconium compared to the increased thickness around iron, manganese, cobalt, molybdenum, chromium, and vanadium. Interestingly, the pseudo membrane around titanium or titanium alloys was consistently thin and around zirconia implants the results were not satisfactory since the thickness was related to the consistency of the zirconia alloys.Additional studies in baboons using titanium-based prosthetic segmental replacements in long bones showed a six-fold increase of titanium in the implanted group, but no difference in the serum of the animals. The authors also found an increase in the titanium concentration in the lungs, spleen, and regional lymph nodes up to 12 months after implantation. Serum chemistry and hematological analysis did not show any statistical differences in any of the tested electrolytes or complete blood counts and the data were similar to the normal baboons without surgery .Palazzo et al. utilized histological analysis to show the release of metals from osteosynthesis implants even in bone after the removal of the plates where radiological findings were no longer found . The autThere is a growing concern regarding the potential of titanium NP to enter the central nervous system (CNS). Their small size and biocompatibility enable them to cross the blood-brain barrier . These p2 NPs have previously been thought to be poorly soluble and possess low toxicity, but recent studies have explored other properties of these NP, which play a role in their toxicity to various systems. The key structural features of TiO2 NP in this regard are size, shape, coating, and crystal phase [2 NP facilitate the accumulation of the particles in the interstitium of lung tissue if they are inhaled [2 NP. Specifically, the titanium citrate soluble metal can be quickly eliminated by the kidneys, but titanium metal can gradually accumulate in the liver [TiOal phase . It has  inhaled . Additiohe liver .Actinomyces naeslundii with pure titanium within seven days has been shown. This bacterial growth depends on the surface energy and TiO2 crystalline phase, which influence the release of bone morphogenetic proteins-2 (BMP-2) when nanotubes have a diameter up to 120 nm or when the diameters are smaller (80 nm) control the expression of pre-inflammatory mediators, such as cytokines and chemokines [2 nanocrystals with high stability, especially since TiO2 NPs release from the implant surfaces induce pro-inflammatory responses, cell surface damage and cytotoxicity.The current crystalline phases of titanium on the implant surface play a significant role in the biomaterial sciences for improvement of the osseointegration and clinical applications. The modern nanotechnology plays a key role in the identification and elimination of side effects from the scientific metallurgic reactions of the titanium in order to control hypersensitivity of patients to the titanium as material. Plaque accumulation in the oral cavity reduces the corrosion resistance of the titanium surface . Growth emokines ,128,129.2 nanoparticles) can cause local inflammation. Additionally, these particles may be ingested from the oral cavity and eventually cause systemic inflammatory reactions since animal studies show translocation of NPs in different organs. Future research in this field is critical to better understand the full extent of the toxicity of titanium dioxide NP, as well as how great of a role these particles play in inducing inflammation associated with peri-implantitis and implant failure.The present literature review highlights the significance of titanium wear from implant surfaces. It is concluded that titanium wear likely begins at the time of implant placement and continues under forces of mastication. Maintenance and reparative procedures aimed towards preventing the progression of peri-implant mucositis to peri-implantitis may also increase the amount of titanium particles released from the implant surfaces. The size of the titanium particles is critical to their ability to be immunogenic, and there is strong evidence that anatase (TiO


Identification of denatured biological tissue is crucial to high-intensity focused ultrasound (HIFU) treatment, which can monitor HIFU treatment and improve treatment efficiency. In this paper, a novel method based on compressed sensing (CS) and improved multiscale dispersion entropy (IMDE) is proposed to evaluate the complexity of ultrasonic scattered echo signals during HIFU treatment. In the analysis of CS, the method of orthogonal matching pursuit (OMP) is employed to reconstruct the denoised signal. CS-OMP can denoise the ultrasonic scattered echo signal effectively. Comparing with traditional multiscale dispersion entropy (MDE), IMDE improves the coarse-grained process in the multiscale analysis, which improves the stability of MDE. In the analysis of simulated signals, the entropy value of the IMDE method has less fluctuation compared with MDE, indicating that the IMDE method has better stability. In addition, MDE and IMDE are applied to the 300 cases of ultrasonic scattered echo signals after denoising . The experimental results show that the MDE and IMDE values of denatured tissues are higher than normal tissues. Both the MDE and IMDE method can be used to identify whether biological tissue is denatured. However, the multiscale entropy curve of IMDE is smoother and more stable than MDE. The interclass distance of IMDE is greater than MDE, and the intraclass distance of IMDE is less than MDE at different scale factors. This indicates that IMDE can better distinguish normal tissues and denatured tissues to obtain more accurate clinical diagnosis during HIFU treatment. High-intensity focused ultrasound (HIFU) has strong penetrability and focusing capability. As a noninvasive modality for conducting high-temperature thermal therapy, HIFU can focus ultrasonic energy on a target region of the body to kill the cells in the treatment region . In modeUltrasonic signals contain a lot of noise during HIFU treatment, so we need to denoise the signals. However, traditional wavelet and empirical mode decomposition (EMD) ultrasonic denoising methods have some disadvantages. For example, the wavelet denoising method requires a preset wavelet basis function, and the EMD method is prone to modal aliasing problems during decomposition ,18. ThusThe ultrasonic echo signal is a nonlinear signal during HIFU treatment. Some properties of the ultrasonic echo signal change when the biological tissues have been denatured. Researchers in the field of ultrasound have studied the characteristics of ultrasonic attenuation, sound velocity, and entropy of ultrasonic echo signals, and hope to find characteristics that can accurately reflect the characteristics of biological tissues. In ,22, the In this paper, CS was used to denoise the ultrasonic scattered echo signal. The IMDE method was proposed based on traditional MDE. Considering the stability and reliability of IMDE, the IMDE method is employed to analyze the difference between normal biological tissues and denatured biological tissues. Comparing with wavelet-IMDE and EMD-IMDE methods, CS-OMP-IMDE can better identify whether biological tissues have been denatured and guide doctors to obtain a more accurate assessment of treatment effect during HIFU treatment. The outline of this paper is as follows: Donoho proposed the compressed sensing (CS) theory, which suggests that if signals are sparse or nearly sparse, it can be reconstructed and restored to obtain denoised signals . CS theoXN*1 should be converted into a sparse domain Ψ, which is “K-sparse” in the sparse domain Ψ (K << N). The process isf is the sparse representation of X in the sparse domain; Ψ is the sparse basis; X is the signal to be denoised. (1) Sparse expression of the signal: when most signals are not sparse in the time domain, the one-dimensional signal y. The process is(2) Compression observation of signal: An appropriate observation matrix Φ is selected for observation and obtains the observation value y value in Equation (2), the denoised signal is obtained by the reconstruction method, where the reconstruction methods of L1 norm and orthogonal matching pursuit (OMP) are used for signal reconstruction, respectively. The L1 norm reconstruction method is a convex optimization algorithm, which uses the L1 norm for linear programming to achieve signal reconstruction. The OMP reconstruction method selects the atom that best matches the original signal from the observation matrix to reconstruct the sparse approximation, then, subtracts the relevant part from the observation matrix, and obtains the reconstructed signal that satisfies the sparsity after loop iteration.(3) Reconstruction of the signal: According to the c through Equation (4).c represents the number of categories. For embedding dimension For time series c values, the number of potential dispersion patterns is Through The coarse-grained time series can be expressed asThe multiscale dispersion entropy (MDE) can be defined asThe traditional coarse-grained process is shown in For the one-dimensional time series, For each scale factor In feature selection, the intraclass distance and interclass distance are widely used as indicators of separability and compactness. The smaller intraclass distance and larger interclass distance mean that the features have better compactness and separability. For sample sets for each pattern in The definition of interclass distance is as follows.The simulated signal was analyzed by compressed sensing (CS). The simulated signal was as follows.The time-domain waveform and frequency spectrum of the simulated signal are shown in Meanwhile, we compared with the traditional wavelet and empirical mode decomposition (EMD) denoising methods. The CS-OMP method was used to denoise the actual ultrasonic scattered echo signal. The waveform of the ultrasonic scattered echo signal before and after denoising is shown in To illustrate the advantages of the IMDE method, white Gaussian noise of 5000 data points was generated as the simulated signal. According to the published reports ,33, we cAt the same time, we also analyzed the standard deviation of MDE and IMDE of simulated signals at different data points. The standard deviations of MDE and IMDE of simulated signals at 500, 1000, 3000, and 5000 data points are shown in The MDE and IMDE methods were used to calculate the entropy value of the ultrasonic scattered echo signals after CS-OMP denoising. The results are shown in In order to further prove the advantage of IMDE, the two indicators of interclass distance and intraclass distance were used to measure the separability and compactness of the MDE and IMDE of the normal and denatured tissues in vitro. In HIFU treatment, the ultrasonic scattered echo signal is often used to identify whether the biological tissues have been denatured. In this process, the ultrasonic echo signal contains a large number of noises that affect the identification results, and it is necessary to find a method that can accurately reflect the characteristics of denatured tissue.In this paper, the CS-OMP method is applied to signal denoising. Compared with the traditional wavelet and EMD methods, the CS-OMP method can obtain a better denoising effect , Table 1This paper realizes the identification of denatured tissues based on CS and IMDE of the ultrasonic scattered echo signal. In the analysis of CS, the CS-OMP method can denoise the ultrasonic scattered echo signal effectively. In view of the shortcomings of the traditional MDE method, the IMDE method is proposed by improving the coarse-grained process of MDE. The proposed IMDE has better stability compared with MDE. MDE and IMDE are applied to ultrasonic scattered echo signals of normal and denatured tissues. The results show that the interclass distance of IMDE is greater than MDE, and the intraclass distance of IMDE is less than MDE. IMDE has better compactness and separability to identify whether biological tissues have been denatured. Furthermore, when the scale factor is 14, IMDE can obtain the optimal identification effect for normal tissues and denatured tissues during HIFU treatment. Comparing with the wavelet-IMDE and EMD-IMDE methods, CS-OMP-IMDE has better effect in the identification of denatured biological tissue.


Intracranial pial arteriovenous fistula (PAVF) is a rare cerebrovascular pathology characterized by abnormal direct high-flow connection between the pial or cortical feeding artery and draining vein. Dural arteriovenous fistula (DAVF) is a pathological shunt between the meningeal arteries and dural sinuses or meningeal veins. In case of association between PAVF and DAVF, diagnosis and treatment are more challenging. The high-flow arteriovenous shunt and deep venous drainage make PAVF more preferable for endovascular treatment; however, their embolization during single-session procedures can lead to extensive thrombosis of the draining veins and unfavorable outcomes. We present a case report of endovascular embolization of an intracranial PAVF–DAVF in a 2.5-year-old child. At the time of admission, the patient had hydrocephalus, mental retardation, pyramidal insufficiency, and seizures. Occlusion of the fistula was performed during two stages of embolization to reduce the risk of severe venous stasis and venous thrombosis. Guglielmi detachable coils (GDCs) and a liquid embolic agent (Histoacryl with Lipiodol) were used for embolization. The patient recovered well after the procedure, with significant mental improvement. This suggests that the deployment of GDCs in the afferent artery near a fistula before embolization with a liquid embolic agent can minimize the risk of uncontrolled penetration of the embolization into the draining veins and dural sinus. A multisession procedure can be an effective and reasonable method of PAVF and DAVF occlusion among existing treatment options. Intracranial pial arteriovenous fistula (PAVF) is a rare cerebrovascular pathology, which comprises a specific subgroup of arteriovenous shunts and accounts for 1.6 to 4.7% of all intracranial arteriovenous malformations.However, unlike other arteriovenous malformations, PAVF does not demonstrate a nidus, is supplied from the pial or cortical arteries, and is characterized by abnormal direct high-flow connection between an arterial feeding vessel and draining vein, which has a significant impact on the cerebral blood flow.A dural arteriovenous fistula (DAVF) is a pathological shunt between the meningeal arteries and dural sinuses or meningeal veins.In our present report, we describe a case of PAVF–DAVF in a 2.5-year-old child treated by endovascular method with good clinical outcomes.A 2.5-year-old male child was admitted to the State Organization “Scientific-Practical Center of Endovascular Neuroradiology, NAMS of Ukraine” in February 2014. Intracranial arteriovenous fistula was diagnosed in utero. The patient was born at term, and up to 1 year of age, showed no mental retardation, and began to walk and speak certain words at 1 year of age. However, after 1 year, a gradual decrease in mental development with progressive vision loss was noted, and 2 months later, first ictus of generalized seizures occurred. Subsequently, the patient stopped walking and talking. At admission, the patient demonstrated hydrocephalus, severe mental retardation, right pyramidal insufficiency, seizures, without any evidence of heart failure. Using magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA), an intracranial arteriovenous fistula was diagnosed . FurtheEndovascular occlusion of the arteriovenous fistula was performed in two stages, that is, in February and August 2014. The aim of the procedure was disconnection of direct AV shunts. During the first session of PAVF occlusion, the purpose was to slow the blood flow in the fistula; to achieve this, at the level of the fistula entrance in a parent artery, Guglielmi detachable coils (GDCs)  were deployed. Then, between the loops of the coils, a liquid embolic agent  with lipiodol  was injected. After the first stage, total occlusion of the PAVF from the left posterior cerebral artery and incomplete occlusion from the left middle cerebral artery were achieved . One fiThe patient was admitted to our hospital after 6 months in August 2014 with a significant improvement in neurological state; his vision was also completely restored, and the right-sided pyramidal insufficiency had regressed to mild hemiparesis. The patient began to independently walk and speak. However, control cerebral angiography revealed the persistence of a left middle meningeal artery DAVF and a partially thrombosed left middle cerebral artery PAVF after the first procedure, with a significant decrease in the drainage vein .During the second session, the shunts of PAVF and DAVF between the left middle meningeal artery and left middle cerebral artery were totally occluded with the aforementioned liquid embolic agent .After the second stage of PAVF–DAVF embolization, the patient was discharged with satisfactory results. MRI after 4 months revealed a significant decrease of the previously dilated draining vein and signs of its thrombosis, with a reduction in the mass-related effect on the brain structures and the severity of hydrocephalus .Four years after embolization, the patient's neurological status remained unremarkable, and his psychosocial and motor development was age-appropriate.Brain MRI and MRA revealed a decrease in the hydrocephalus, total occlusion of the arteriovenous fistula, and almost complete resolution of the previously dilated drainage vein with MRI signs of its thrombosis .The manifestation of an intracranial PAVF usually occurs in early childhood and can be present with intracranial venous hypertension with the development in hydrocephalus, epileptic seizures, delayed mental retardation, and focal neurological signs, as observed in this patient at the time of admission to the hospital.The treatment of PAVF should include multidisciplinary approach and be based on the experience of the medical team. It is important to evaluate the PAVFs location and degree of lesion complexity.The treatment strategy in each case has to be made by the team of neurosurgeons and neurointerventionists to identify the best effective method based on patient-specific presentation and angioarchitecture.In our case, a two-staged surgical procedure using a simple and widely available technique (a combination of a liquid embolic agent [Histoacryl with Lipiodol] and GDCs) resulted in the total occlusion of PAVF–DAVF. Cerebral venous thrombosis is a terrible complication after the endovascular embolization of PAVF. Complete occlusion can lead to the extensive thrombosis of the draining veins, causing venous infarction or intracranial hemorrhage.Understanding the angiographic peculiarities of arteriovenous fistulas angioarchitecture is important for optimal treatment planning. Endovascular embolization in high volume center that is performed by experienced neurointerventionists is a safe and effective technique for treating this pathology. The introduction of GDC at the level of the fistula entrance in a parent artery before the application of the liquid embolic agent can minimize the risk of uncontrolled penetration of the embolization into the draining veins and dural sinuses. A multisession procedure can be an effective and reasonable approach to PAVF and DAVF occlusion among existing treatment options. Ultimately, the elimination of abnormal arteriovenous shunting in children allows the normal development of the central nervous system.