The digital pathology images obtain the essential information about the patient’s disease, and the automated nuclei segmentation results can help doctors make better decisions about diagnosing the disease. With the speedy advancement of convolutional neural networks in image processing, deep learning has been shown to play a significant role in the various analysis of medical images, such as nuclei segmentation, mitosis detection and segmentation etc. Recently, several U-net based methods have been developed to solve the automated nuclei segmentation problems. However, these methods fail to deal with the weak features representation from the initial layers and introduce the noise into the decoder path. In this paper, we propose a multiscale attention learning network (MSAL-Net), where the dense dilated convolutions block captures more comprehensive nuclei context information, and a newly modified decoder part is introduced, which integrates with efficient channel attention and boundary refinement modules to effectively learn spatial information for better prediction and further refine the nuclei cell of boundaries.Both qualitative and quantitative results are obtained on the publicly available MoNuseg dataset. Extensive experiment results verify that our proposed method significantly outperforms state-of-the-art methods as well as the vanilla Unet method in the segmentation task. Furthermore, we visually demonstrate the effect of our modified decoder part.The MSAL-Net shows superiority with a novel decoder to segment the touching and blurred background nuclei cells obtained from histopathology images with better performance for accurate decoding. Cancer grading has an essential importance in clinics because it allows doctors to treat patients more effectively and analyze the effectiveness of treatments. The microscopic images are broadly utilized to diagnose tumors in clinical medicine, consists of vital information about encompassing the tissue structure and tumors. The particular structures of tissue such as glands, collagen and nuclei are stained to highlight. The hematoxylin and eosin (H&E) staining is the most common method for separating nuclei and cytoplasm in slices. The characteristics of nuclei are used by clinicians to grade tumor, and in the slices, morphology and nucleus polymorphism are observed.Digital pathology has gained significant research focus in the medical field due to the constant advancement of software and hardware proficiencies. Whole slide images (WSIs) can be obtained using high-intelligence and automation scanning devices to create an advanced database of digital pathology. Computerized strategies have proven effective in explaining a wide range of pathology issues for analyzing histopathological images , 2. NuclRecently, deep learning algorithms such as convolutional neural networks (CNN)  and autoIn recent years, transfer learning has been a beneficial method and widely applied in medical image tasks when the training samples are in shortage. However, deep learning algorithms prone to overfitting on the small training samples and the time-consuming image labelling task solve this problem –34. In cThe contribution of this research study are: (1) We employ the residual blocks in the encoder to improve the feature extraction capability of the network. (2) In order to generate more high-level features maps and reduce the semantic gap between the encoder and decoder, we add a dense dilated convolution (DDC) block in the middle of the network. (3) We present an idea of a novel decoder path that combines with the ECA and BR modules to learn the essential feature map, refine the information of nuclei boundaries, and significantly enhance the network performance for accurate decoding. (4) we combine the encoder-decoder architecture with the DDC and ECA + BR modules for nuclei segmentation in histopathology images is present. (5) The experiments have been carried out on the public nuclei histopathology dataset. Additionally, some selected advanced semantic segmentation approaches compared with the proposed model and the outcomes of all experiments are thoroughly examined. The experimental results reveal that our method learns robust features and produces an outstanding effect in the segmentation. Besides, our proposed model also compared with the current state-of-the-art approaches.Motivated by the ResNet , InceptiIn our proposed method, the structure of the encoder was modified from the Unet design and replaced it with the In-Block, 4 Residual-Blocks of Resnet 34  pretrainIn semantic segmentation tasks, the pooling layers caused the loss of semantic information in images . InspireThe decoder was used to retrieve the combined spatial information from the encoder and dense dilated convolutions block. However, skip connection brought the poor feature representation from the initial layers and introduced the noise into the decoder. Similar to , each blThe MoNuseg dataset consists of 44 pathological tissue slices and is stained with H&E captured at 40x magnification. Paches sampled from whole slide images with a fixed size of 1000 mentclasspt{minimach image  and fed The proposed MSAL-Net was built by PyTorch  deep leaentclass1pt{minimaThe four metrics used to evaluate the effectiveness of our proposed method in the nuclei segmentation tasks such as Dice coefficient (DC), Intersection over Union (IoU) Precision (PR), and Recall (RC). These matrices formulas can be computed as:First, let say Now, we haveThis section explained the ablation study to demonstrate the efficacy of each component in the MSAL-net on the test set, as indicated in Table The proposed method demonstrated both qualitative and quantitative results to evaluate the effect of the ECA and BR modules with the decoder part, as illustrated in Fig. We evaluated the computational cost of segmentation on a machine with an NVIDIA GeForce GTX 1080 Ti GPU. The nuclei histopathology images with a size of 512 We obtained results using other methods compared qualitatively and quantitatively. Figure Apart from the visual comparison, the performance of our proposed method compared to the first four selected state-of-the-art segmentation methods displayed in Table Our research study proposed a model to tackle the accurate segmentation of nuclei in histopathology images. Our model introduced an idea of a novel decoder that was integrated with the attention and refinement modules. We tested our model through four performance metrics on the MoNuseg test set and compared it with the current deep learning mainstream approaches. The extensive experiment results visually and quantitatively demonstrated the feasibility and superiority of the proposed MSAL-Net in nuclei segmentation. We also carried out an ablation test on each component of our proposed technique and analyzed the effectiveness of the ECA and BR modules with the decoder. The above study claimed that the proposed method could effectively segment the nuclei, while still there was potential for improvement. Besides, we believe that the proposed MSAL-Net can be helpful for other segmentation problems.This study aimed to introduce a method to improve the accurate segmentation of nuclei in histopathology images. In this paper, we presented a method called MSAL-Net for the nuclei segmentation task, which employed residual blocks in the encoder structure to improve the feature extraction capability and used the DDC block to capture broader nuclei context information. The ECA and BR modules were integrated with decoder structure to learn spatial information for better prediction and refine the information of nuclei boundaries. Extensive experiments demonstrated that the proposed MSAL-Net outperformed other state-of-the-art methods in visual perception and quantitative metrics using the publicly available MoNuseg dataset. Furthermore, though the proposed MSAL-Net was designed to solve the nuclei segmentation problem, we believe it may also be effective for other segmentation challenges as well, which we want to investigate further in the future study.


Lisfranc injury is increasingly being recognised in the high-performance athletic cohort, particularly in contact sports. In this cohort, there is a pattern of low-energy Lisfranc injury which combines magnetic resonance findings of both ligamentous sprain and adaptive bone stress response that infers a longer timeframe of stress than the duration of symptoms would suggest. This has not been previously described, and the authors believe that this is an unrecognized subset of midfoot sprain in the context of sustained stress to the midfoot. This retrospective case report describes MRI findings of three index cases of this entity in professional athletes presenting with acute foot pain. Two responded with conservative management whilst the third ultimately required surgery. All athletes were eventually able to return to play. Foot injury accounts for 16% of all sports-related injuries of which low-energy Lisfranc injury is uncommon but increasingly being diagnosed, presumably from the increased awareness of this condition and the increased use of magnetic resonance imaging (MRI) in imaging of foot pain . In contIn elite international athletes that we have imaged in the acute setting, we have noticed a pattern of Lisfranc injury that has not been previously described, which includes a mixed picture of acute Lisfranc sprain and chronic adaptive response of the Lisfranc bone unit. It has also come to the authors' attention that there is a relative paucity in radiology literature on Lisfranc ligamentous injury in athletes with low-energy Lisfranc injuries.This manuscript showcases three high-level athletes with Lisfranc ligament injury demonstrating chronic stress response in the metatarsal bases. It provides a hypothesis for the imaging findings.This is a retrospective study from January 2019 to June 2020. Three international athletes who presented to the radiology clinic for investigation of acute-onset foot pain were identified. All the studies were reported by dedicated musculoskeletal radiologists with combined experience of 45 years.A 19-year-old international-level male soccer player presents with a two-week history of midfoot pain, worse with running. This occurred during an overseas match. There was no single traumatic event recalled. There was no other medical comorbidity. Routine panel of metabolic and blood screen including calcium and vitamin-D level was normal at the start of the season.The MRI showed localized marrow oedema signal centered at the base of the second metatarsal with suspicion of an avulsion fracture at the footprint of the plantar Lisfranc ligament . The corThe undisplaced avulsion fracture was confirmed on computed tomography (CT) Figures .He was treated conservatively with protected weight-bearing for 6 weeks with good outcome and was able to return to baseline shortly after.An 18-year-old male Australian footballer presents with sudden-onset midfoot pain, exacerbated by running and jumping.The MRI demonstrated localized marrow oedema signal at the plantar margin of the second metatarsal base . This inThere was second metatarsal cortical thickening centered around the ligamentous attachments . This waA 29-year-old female elite soccer player presents with nonspecific, 1-day history of foot pain during an international soccer tournament. She was unable to complete warmup. There was no history of trauma recalled. There is no significant past medical history apart from mild asthma.On assessment, she had an antalgic gait.On imaging, there was periligamentous oedema surrounding the otherwise-intact plantar Lisfranc ligament . PlantarPatient had to be taken out of the soccer tournament. Following a 3-month period of failed conservative management, this was surgically managed as a nonhealing stress fracture with drilling and plate fixation of the second metatarsal base. She responded well to treatment and was able to return to game at prior baseline level.The Lisfranc ligamentous complex confers stability to the tarsometatarsal (TMT) articulation by providing structural support to the transverse arch of the mid- and forefoot. The first intermetatarsal space is held by the dorsal, interosseous, and plantar ligaments extending from the medial cuneiform to the base of the second metatarsal. These three ligaments constitute the Lisfranc proper , 8. The Injuries to this Lisfranc complex can be differentiated into high-impact or low-impact trauma. The low-impact trauma, also coined midfoot sprain, constitutes up to a third of Lisfranc injuries and will be the main focus of this manuscript . These aThere is a three-stage classification system for low-energy Lisfranc injury or midfoot sprains coined by Nunley and Vertullo . This clWhen normal bone is subjected to abnormal or repetitive stress, it undergoes physiologic, adaptive changes with new bone deposition at the sites of the stress . If the We also note that stress fractures reported in ballet dancers characteristically occur at the base of the second metatarsals . Whilst There is one case report in the English literature describing Lisfranc ligamentous injury in a low-energy context in the presence of bone stress reaction, as indicated by cortical reaction and thickening. However, this occurred spontaneously and did not occur in the context of a sports injury. The patient had a background of autoimmune condition (systemic lupus erythematosus and antiphospholipid syndrome) and osteoporosis. The presentation was also delayed, potentially confounding the imaging findings. Also, an MRI was not performed and Lisfranc ligamentous injury was only inferred based on the fracture which delineated the footprint of the Lisfranc ligament .In our cases, the initial imaging was performed in a relatively short timeframe since the onset of symptoms, showing changes of bone stress response with Lisfranc ligamentous sprain. Extrapolating the available data on athletes and ballet dancers, it is expected that the Lisfranc ligament in this subset of high-performing athletes has to withstand a substantial amount of stress over a prolonged period of time, enough for bony adaptive response at the footprint of the Lisfranc ligaments with cortical remodeling and thickening. The symptoms may only manifest when this adaptive response fails, such as in the context of impending stress fracture. The authors would like to raise chronic stress response as a subset of low-energy injury to the Lisfranc ligament. This hypothesis will have to be further explored with prospective studies, potentially with longitudinal surveillance of these athletes.Complications of untreated Lisfranc injuries include persistent pain, flattening of the longitudinal arch, and accelerated osteoarthritis in the midfoot. This injury is associated with significant morbidity with up to 18% of affected athletes being unable to return to baseline sports after injury . The treIn conclusion, low-energy injuries of the Lisfranc articulation, or midfoot sprain, are increasingly being recognised as a common sports injury, particularly in high-level athletes, with potential long-term morbidity. We present three cases in which the presentation and duration of symptoms of the high-level athletes do not fit with the degree of bone remodeling observed on MRI, suggesting sustained period of stress to the Lisfranc ligament in sporting activities. We speculate that there is a subset of chronic, repetitive, low-energy Lisfranc stress which can manifest as bone adaptive response and ligamentous sprain.


Children and adolescents living under the supervision of child protective services have complex mental health care needs. The scarcity and uneven distribution of specialized mental health teams in Chile may limit the provision and quality of care for this vulnerable population. Telepsychiatry can address such health inequities.The objective of this study was to evaluate the feasibility of a telepsychiatry consultation program for primary health care (PHC) treatment of children and adolescents living under the supervision of child protective services.We developed a telepsychiatry consultation program for two rural PHC clinics located in central Chile  and evaluated its implementation using a mixed methods study design. The program consisted of videoconferencing mental health consultation sessions scheduled twice per month (each 90 minutes long), over a 6-month period, delivered by child and adolescent psychiatrists based in Santiago, Chile. We described the number of mental health consultation sessions, participant characteristics, perceived usefulness and acceptability, and experiences with the telepsychiatry consultation program.During the 6-month study period, 15 videoconferencing mental health consultation sessions were held. The telepsychiatry consultation program assisted PHC clinicians in assigning the most adequate diagnoses and making treatment decisions on pharmacotherapy and/or psychotherapy of 11 minors with complex care needs. The intervention was perceived to be useful by PHC clinicians for improving the resolution capacity in the treatments of this patient population. Limitations such as connectivity issues were resolved in most sessions.The telepsychiatry consultation program was feasible and potentially useful to support PHC clinicians in the management of institutionalized children and adolescents with complex psychosocial care needs living in a poorly resourced setting. A larger scale trial should assess clinical outcomes in the patient population. Regulations and resources for this service model are needed to facilitate sustainability and large-scale implementation. About half of the children and adolescents living under the supervision of child protective services (CPS) in high-income countries have mental disorders . In ChilTelepsychiatry, that is, videoconferencing to deliver mental health care, might address the shortage of SMHC by facilitating remote and timely access to quality care for underserved populations  -8. TechnTo our knowledge, no previous study has examined the collaboration between SMHC and PHC to specifically treat CPS populations. The objective of this study was to evaluate the feasibility of a telepsychiatry consultation program (TCP) for the PHC treatment of children and adolescents living under the supervision of CPS.A feasibility study combining descriptive quantitative and qualitative methods was conducted in two rural PHC clinics located in the Valparaíso Region of Chile. PHC clinics were conveniently selected as local health services, and staff were open to engage with this pilot project. Four psychologists and one physician working in PHC clinics were recruited. These clinicians treated children and adolescents living under the supervision of CPS as part of their usual case load. We provided the technical infrastructure, security, and protocols needed to connect the rural PHC clinicians with the SMHC team comprising 3 child and adolescent psychiatrists who were working at the Department of Psychiatry and Mental Health of Hospital Clínico Universidad de Chile, Faculty of Medicine of Universidad de Chile, and Department of Psychiatry of Hospital El Pino, Santiago. The following measures were taken to implement the intervention: (1) securing institutional permissions to move and install technological equipment, (2) installing computers and teleconferencing devices in the intervention sites, (3) ensuring that the PHC clinicians and the SMHC teams had compatible schedules, (4) training the PHC clinicians and the SMHC teams in the technical aspects of the interventions, and (5) running connectivity tests between the study sites to pilot the intervention. This study was approved by the institutional review board at Hospital Clínico Universidad de Chile. PHC clinicians provided written informed consent and participated voluntarily at any time. Patients  were not directly involved in the feasibility testing due to complicated consent procedures required for their participation.The TCP used a computer-based teleconferencing service that met communication and security standards for voice over transmission control protocol/IP. Videoconferencing mental health consultation (MHC) sessions were held between PHC clinicians and the SMHC team through a secure web-based treatment platform, that is, closed network, personalized access passwords, and disabled recording function, by using the desktop video-conferencing program Vidyo .Videoconferencing MHC sessions were scheduled twice per month over a 6-month period, reserving time slots of 90 minutes each. Electronic health records (EHRs) were implemented to share patient information  between PHC clinicians and the SMHC team. EHRs were updated after each videoconferencing MHC session. Neither in-person visits nor emergency treatments were included in the study, as PHC clinicians referred such cases to local SMHC consultants. The TCP was not provided to other populations.The TCP followed the protocol of the Chilean Ministry of Health for MHC , providiThe number of videoconferencing MHC sessions held during the 6-month study period was registered and compared to in-person standard MHC sessions that were provided by local SMHC consultants in the 6 months prior to TCP implementation. The following data were collected for each videoconferencing MHC session: (1) number and types of health care providers participating, duration (in minutes) of the session, and network connection technology used; (2) clinician-rated usefulness and acceptability ; and (3) clinical patient information and actions taken or agreed for patient management (retrieved through inspection of the shared EHRs). The aforementioned information was analyzed using descriptive statistics.After the 6-month study period, an open-ended, email questionnaire was used to explore the experiences of PHC clinicians and SMHC teams with the TCP . Following a grounded theory approach , two resHalf of the MHC sessions planned  were held in the 6 months prior to the implementation of TCP. In contrast, 15 of the 24 (63%) videoconferencing MHC sessions planned were held during the 6-month study period. Nine videoconferencing MHC sessions were cancelled due to a strike of the health care workers, incompatible schedules, and low clinical demand.On average, videoconferencing MHC sessions were conducted every 3.7 weeks, lasted 66 minutes (range 30-100 minutes), covered 1.1 cases, and involved the participation of 2.1 PHC clinicians. The SMHC team mostly used wireless connections in about 73% (11/15) of the sessions, whereas the PHC clinicians used wired connections in 73% (11/15) of the sessions. On two occasions, participants communicated over telephone due to important and unresolved internet connectivity problems. Connectivity issues caused shortening and/or interruption of 12 videoconferencing MHC sessions.Most cases of minors included in the TCP were girls who lived under CPS  due to parental neglect . The mosData collected during each videoconferencing MHC session showed that these were clinically useful to PHC clinicians ; its durThe implementation of TCP was feasible and supported PHC clinicians in diagnosing and/or treating children and adolescents with complex psychosocial care needs living under the supervision of CPS. The intervention was perceived to be clinically useful for the patient population, and it increased the resolution capacity of PHC clinicians and their willingness to receive a future TCP.To our knowledge, this is the first study to report a TCP connecting SMHC teams with PHC clinicians to improve mental health care among minors living under the supervision of CPS. A protocol for future implementations was developed. To improve the generalizability of the study results, larger and geographically more varied samples are needed to reflect the heterogeneous scenario of PHC and CPS in resource-poor Latin American contexts. A limitation of the study was that it did not directly assess mental health outcomes in the minors living under the supervision CPS. The common connectivity issues experienced during the study period were a further limitation, although they were fixed in a timely manner and usually did not affect the workflow of the MHC. Nevertheless, they may be important barriers to the adoption of TCPs in resource-constrained rural areas. Other important limitations of the implementation process included the lack of patient information and history in the EHRs, reflecting problems of sharing essential information among CPS, PHC, and SMHC.In Chile, the use of technology-based solutions for mental health care of remote and underserved populations has been important due to the geography, and it has become increasingly relevant during the COVID-19 pandemic—with a rapid shift to this mode of mental health service delivery to ensure access and continuity of care . For insEvidence from the United States has provided strong foundations for the feasibility and potential efficacy of community-based child and adolescent telepsychiatry -15. DigiExperiences reported from the United States resemble those reported in the present study in that they have applied technology-based solutions to build partnerships between SMHC and community or PHC providers, having included data from CPS population in their analyses ,17. ThesAlthough our findings are consistent with these experiences ,17, thisImplementing a TCP was feasible and potentially useful for addressing mental health challenges in PHC of children and adolescents living under the supervision of CPS. Future programs may consider incorporating a child and adolescent psychologist to the SMHC team. To demonstrate the effectiveness of these interventions, a future clinical trial should assess the clinical outcomes in the children and adolescents living under the supervision of CPS. Furthermore, future research should consider scaling the TCP to more PHC clinics, including a larger patient population. Health care policies should be developed to provide regulation and resources for this model of mental health care, to be sustainable over time.


The remediation of petroleum-contaminated soil and groundwater is a challenging task. The petroleum hydrocarbons have a long persistence in both the vadose zone and in the aquifer and potentially represent secondary and residual sources of contamination. This is particularly evident in the presence of residual free-phase. Pump-and-treat is the most common hydrocarbon decontamination strategy. Besides, it acts primarily on the water dissolved phase and reduces concentrations of contaminants to an asymptotic trend. This study presents a case of enhanced light non-aqueous phase liquid (LNAPL) remediation monitored using noninvasive techniques. A pilot-scale field experiment was conducted through the injection of reagents into the subsoil to stimulate the desorption and the oxidation of residual hydrocarbons. Geophysical and groundwater monitoring during pilot testing controlled the effectiveness of the intervention, both in terms of product diffusion capacity and in terms of effective reduction of pollutant concentrations. In particular, non-invasive monitoring of the reagent migration and its capability to reach the target areas is a major add-on to the remediation technique. Most of the organic contaminants were decomposed, mobilized, and subsequently removed using physical recovery techniques. A considerable mass of contaminant was recovered resulting in the reduction of concentrations in the intervention areas. The remediation of the areas contaminated by petroleum hydrocarbons and the selection of the best decontamination methods represent a growing global concern  located in Sardinia , where about ten years ago a jet fuel spill occurred due to leakage of a transfer pipeline around the fuel tanks. The detected contamination, despite being mainly caused by a single spill, is quite extensive and has been the subject of years of pump-and-treat intervention . The water samples were subjected to gas chromatography and mass spectrometry (GC-MS) analysis to obtain the chemical speciation of the hydrocarbons  the effects of pump-and-treat intervention over time, (2) the reduction of the total contaminant mass, and 3) a narrowing of the contaminant plume that progressively reaches an asymptotic trend  (Ciampi et al. Simultaneous data integration and the multi-source model enabled accurate pilot site selection and the implementation of innovative remediation approaches. Geophysical surveys and groundwater sampling during pilot testing evaluated the effectiveness of the intervention, both in terms of product diffusion capacity and effective reduction of pollutant concentrations. Time-lapse geophysical imagery throughout field experimentation yielded crucial insights, especially about where and how in situ remediation activities impacted distinct parts of the subsoil as a consequence of underground hydraulic inhomogeneity. Chemical analysis showed a significant recovery and a reduction of hydrocarbons, increasing the pumping system efficiency. The physicochemical model, which links geophysical signals to contaminant characteristics within contaminated porous media, was explained through the observation of contaminant-geophysical behavior. The mobilization of the immobile and residual material which constitutes the residual phase of hydrocarbons reveals the limitations of hydraulic barriers. Analysis of all data clearly shows that traditional extraction techniques are ineffective in removing secondary sources of fuel contamination. Our findings suggest that the desorption process using PetroClenze™ and Regenox™ can contribute significantly to the enhancement of hydrophobic pollutantsʼ vacancy. When applied, this two-part reagent generates detergent-like properties, significantly increasing the desorption rates of hydrocarbons bound in saturated soils. Once the hydrocarbons are liberated into the dissolved phase, they are more readily available for removal using physical recovery techniques. The injections of PetroCleanze™ followed by contaminant extraction revealed a significant removal of residual LNAPL, acting as a chemical enhancer for pump and treat.


Colorectal cancer (CRC) is the second most deadly cancer affecting US adults and is also one of the most treatable cancers when detected at an earlier clinical stage of disease through screening. CRC health disparities experienced by African Americans are due in part to the later stage of diagnosis, suggesting the importance of improving African Americans’ CRC screening participation. The national Screen to Save (S2S) initiative employs a community health educator to deliver CRC screening education which can be tailored for specific populations, and such approaches have increased CRC screening rates in disadvantaged and racial/ethnic minority populations.In this trial emphasizing stool-based CRC screening, focus groups informed the development of an adapted S2S video and brochure tailored for African Americans and identified preferred motivational text messages for a multicomponent community health advisor (CHA) intervention. A CHA hired from the community was trained to deliver a 6-week CRC educational intervention consisting of an initial face-to-face meeting followed by 5 weeks of calls and texts. Interested eligible persons are enrolled primarily through recruitment by two partnering community health centers (CHCs) and secondarily through various outreach channels and, after consenting and completing a baseline survey, are randomly assigned to one of two study arms. The CHCs are blinded to study arm assignment. Intervention arm participants receive the brochure and CHA intervention while participants assigned to the control group receive only the brochure. All participants receive a stool-based CRC screening test from their health center, and the primary outcome is the completion of the screening test at 12 months. Secondary objectives are to estimate the effect of the intervention on mediating factors, explore the effect of moderating factors, and perform a cost-effectiveness analysis of the CHA intervention.The TUNE-UP study will enhance understanding about CRC screening in African Americans obtaining primary health care through CHCs and is one of the very few studies to examine a CHA intervention in this context. A better understanding of the mechanisms by which the intervention affects patient beliefs and behaviors will help focus future research while the exploratory cost-effectiveness analysis will inform CHCs’ decision-making about implementing a CHA program to increase screening and reduce cancer health disparities.ClinicalTrials.govNCT04304001. Registered on March 11, 2020. Trial Sponsor: Florida A&M University, Charles Weatherford, PhD, Vice President for Research, Office of the Vice President, Division of Research, 410 Foote-Hilyer Administration Center, Tallahassee, FL 32307-3200.The sponsor principal investigator (JL) has authority over research activities, writing of reports, and submission of written reports.Principal investigator: Design and conduct of TUNE-UP, Preparation of protocol and revisions, publication of study reports. All lead investigators are steering committee members involved with overseeing the trial and meet weekly. Data verification, randomization, data management is led by the study biostatistician (GK). The study coordinator (MV) is responsible for identifying potential research participants in partnership with the Community Health Centers, who send out recruitment messages to contact the study coordinator.Colorectal cancer (CRC) is the second most common type of cancer and second leading cause of cancer-related deaths in the USA affecting both men and women, after lung cancer. It is projected that close to 53,000 people in the USA will die of CRC in 2021 [African Americans have the highest rates of CRC compared to any other racial or ethnic group in the USA . The disAccording to the CDC, approximately 69% of the US population 50–75 years were reported to be up to date with CRC screening in 2018, with the largest variations in screening observed for segments of the population without health insurance, from racial/ethnic minority groups, those living in rural areas, and those living in areas with low availability of gastroenterologists who can perform colonoscopies . The cauBeginning over two decades ago, overall CRC incidence rates started declining steadily because of increased uptake of colonoscopy screening; however, rates have continued to increase in the <65-year-old population . BecauseAccess and timely use of appropriate screening procedures are of utmost importance in bridging the disparities in CRC incidence, mortality, and 5-year survival rates for African Americans. Recommended CRC screening methods range from clinic-based to home-based tests. The gold standard CRC screening test is colonoscopy where the entire large bowel is visualized but requires colonic preparation and sedation and is often, but not always readily accessible in some locations, especially in rural communities. Although colonoscopy screening has the advantage of removing preinvasive lesions before they become cancer, and a longer screening interval if no pathology is identified up to 10 years), average-risk patients may prefer a less invasive option. The stool-based tests are less costly and easier to access and complete. To boost acceptance and screening rates among medically underserved populations, several studies have stressed the positive impact of annual stool-based tests , 9. One  years, aThere are three common recommended stool-based screening methods , 11. Thepromotoras, lay health advisors, and patient navigators. These individuals are trusted community members operating in a culturally competent manner who are either paid employees or work as volunteers to connect members of the community with health services. The use of a patient navigator or similar advocate not only helps to increase cancer screenings in hard-to-reach populations but is also cost-effective [A community health advisor (CHA) is a member of the community who has been trained to deliver health education and other services to assist community members to engage in healthy behaviors such as cancer screening, diabetes management, or nutrition counseling. Other positions who fill similar roles as the CHA include community health workers, ffective . The useffective , 15.Screen to Save (S2S) is an initiative of the National Cancer Institute (NCI) to increase CRC screening in the USA . One comThis study examines decision-making factors that lead African Americans to participate in CRC screening. Such factors include perceived susceptibility, perceived benefits, perceived barriers, fear and fatalistic beliefs, social norms, self-efficacy, cultural factors, and knowledge. Hypothesized moderating variables which may influence the strength of the relationship between receiving the intervention and CRC screening adherence include a family history of cancer and health literacy. These variables included in our conceptual framework are drawn from health behavior theories including Social Cognitive Theory, the Health Belief Model, and the Theory of Planned Behavior/Theory of Reasoned Action –21. The To determine the effectiveness of a CHA intervention, which includes patient education videos and a tailored brochure, relative to a control group receiving only a tailored brochure, on completion of stool-based CRC screening (completing the FIT by 12 months post-randomization) in African Americans who are patients of participating CHCs and not up to date with screeningTo estimate the effect of a CHA intervention on mediators  associated with completion of stool-based CRC screeningTo explore moderators  between the CHA intervention and completion of stool-based CRC screeningTo conduct a cost-effectiveness analysis of the CHA interventionThe primary hypothesis is that participants receiving the CHA intervention will exhibit higher rates of stool-based CRC screening completion than participants in the control group, because participants in the intervention group will have higher levels of knowledge, perceived susceptibility, and self-efficacy and lower levels of fear and fatalism after receiving the CHA intervention.The TUNE-UP study is designed as a two-group pretest/posttest pragmatic randomized controlled trial. The study uses the parallel group, two-arm superiority trial design with a 1:1 allocation ratio. The pragmatic trial aims to test the effectiveness of the intervention in a generalizable setting. To conduct the intervention trial, 244 participants will be randomized at the time of enrollment following completion of the baseline survey  CRC screening rates increased from 58 to 68% in the 65-year and older cohort, possibly due to Medicare coverage; (2) an increasing number of CRC cases are diagnosed in people under 50 years and ACS and USPSTF recently updated their recommendations to include adults 45 years and older as persons with “average risk” and recommended for screening; and (3) the use of technologies such as text messaging is more likely to be familiar to participants under 65 years . ParticiThe study uses the block randomization method. This method is commonly used in clinical trial designs to lower bias and attain balance in the assignment of study participants to treatment and control groups. The trial randomizes participants at the individual level, stratified by the two CHC sites, using a 1:1 ratio between intervention and control arms. The randomization algorithm uses randomly permuted blocks with random block sizes for the purpose of assigning participants. The random selection of block sizes has the advantage of reducing selection bias. The randomization file was produced in SAS v. 9.4 by the biostatistician. The principal investigator informs the study coordinator of the study arm assignment using ID numbers after the patient gives consent to participate in the study and completes the baseline survey. If a participant is assigned to the intervention arm, the study coordinator informs the CHA so the participant can be contacted to complete the intervention arm protocol.All participants receive the tailored educational brochure at the initial visit when they complete the baseline survey with the project coordinator. The participants who are randomized to the intervention group view the S2S video, and the CHA explains the contents if there are questions. This is followed by 2 weeks of short CHA follow-up calls, concluding with 3 weeks of motivational text messages on CRC screening. Participants who are randomized to the control group receive the educational brochure only. Both intervention and control groups receive the FIT from their CHC either in the mail, in person, or during a scheduled patient visit. The CHCs are blinded to the study arm. There are no circumstances where unblinding participants for the CHCs would be necessary given all participants receive the FIT from their CHC.In the context of the behavioral clinical trial, a CHA was trained by the research team to deliver the 6-week intervention consisting of an initial face-to-face CRC educational presentation using the S2S video, 2 weeks of phone-call follow-up, and 3 weeks of text message follow-up. The intervention’s one-on-one education, small media, follow-up reminders, and reduction of structural barriers to screening align with client-oriented recommendations of the Community Guide to Preventive Services . In aligThe adapted S2S PowerPoint developed by the research team was professionally produced into an approximately 11-min video narrated by an African American woman. As with the educational brochure, the adapted S2S video featured culturally tailored content including anatomical figures with brown skin tone and a photo of a local African American couple, a pastor and his wife, who are well-known in the community. After the participant views the adapted S2S video on the CHA’s tablet, the CHA asks if the participant wishes to discuss the video or ask any questions. After allowing 2–3 min for discussion, the CHA shows the participant a 5-min FIT patient education video. This video walks the viewer through the steps of completing their at-home screening test. The video was obtained from the manufacturer of the FIT after the research team was informed by CHCs that it was the primary FIT they use. Once the participant has finished viewing the second video, the CHA again engages the participant to discuss any topics or questions the participant may have. The CHA uses a fidelity checklist to document the completion of the week 1 educational presentation and make appropriate notes. In weeks 2 and 3 of the intervention, the CHA calls the participant to ascertain receipt of the FIT from their CHC and the participant’s completion of their FIT. Fidelity checklist phone scripts allow the CHA to document the delivery of the calls and facilitate their use of motivational interviewing to address any barriers to completing the screening that may be verbalized by the participant. In weeks 4–6 of the intervention, participants receive one motivational text message per week to encourage them to complete their screening. The three text messages were among those most preferred by focus groups during the project’s learner verification phase. The intervention is completed in 6 weeks or potentially earlier if the participant reports completion of their FIT.What Black Men and Women need to know about Colorectal Cancer Screening, and features a photo of a middle-age African American couple. The brochure’s inner panels include information on the different CRC screening tests, emphasizing the stool-based test; an anatomical picture of the human colon with polyps; lists of modifiable and nonmodifiable CRC risk factors; questions/answers about CRC screening and the colonoscopy procedure; and a short testimonial about overcoming the fear of completing CRC screening. The back cover provides information about covering the cost of CRC screening, sources of additional information including the NCI and the American Cancer Society, and TUNE-UP contact information.The educational tri-fold brochure provided to all participants was professionally designed and incorporated focus group input through learner verification. The brochure cover has the TUNE-UP header and is subtitled, The data collection occurs over three time periods: baseline, 3 months after baseline, and 9–12 months after baseline .Study sample size and power considerations are based on the primary outcome of receiving stool-based CRC screening. Based on a systematic review, we estimate a 20% increase in CRC screening among intervention arm participants and a 5% increase among control arm participants . The larThe novel coronavirus pandemic and attendant prioritization of COVID-19 testing and vaccination by partnering CHCs exacerbated CHC staffing challenges and made it more difficult for CHCs to fulfill essential recruitment tasks, in particular, monthly dissemination of recruitment messaging through CHCs’ electronic health record systems. Once virtual and in-person meetings with CHC leadership teams were scheduled however, workable solutions were identified with each CHC regarding identifying the project coordinator’s CHC contacts and establishing mutual understanding about CHCs’ dissemination of email/text/phone messaging to potentially eligible patients to contact the study coordinator for study eligibility determination. Phone contacts are repeated as necessary to enroll participants. The eligibility criteria exclude those who are up to date with USPSTF CRC screening guidelines, so there are challenges to identify those patients due for screening. Also, participants from the same household were excluded to avoid possible study contamination. The research team developed two versions of a recruitment flyer, one for posting within partnering CHCs and the other for community posting/dissemination. It was important to ensure that both CHCs had an adequate supply of flyers for posting in waiting rooms and patient exam rooms and to encourage CHC medical staff to discuss study participation with clients during in-person visits. Additional participant recruitment methods included participant monetary incentives for baseline and follow-up survey completion, promotion by collaborating African American churches, regular broadcasting of a radio advertisement during programming with significant study population listenership, engaging potential participants at community events , and flyers posted at local businesses . There are no special criteria for discontinuing or modifying allocated interventions; however, participants may withdraw from the study at any time.To achieve fidelity of the CHA-delivered educational intervention, the CHA training provided by the research team informed the CHA about the essential concepts and significance of—and ways to maintain—fidelity. Maintaining intervention fidelity was presented in the context of essential skills and responsibilities of the CHA. Fidelity checklists were created to guide the CHA through each participant encounter and facilitate the CHA’s documentation of pertinent information from the encounter. These included a checklist for the in-person educational presentation and for each of two follow-up phone calls made by the CHA. The fidelity checklists, especially those for the follow-up phone calls, also served as conversation scripts for the CHA and were designed to facilitate the use of motivational interviewing. Training of the CHA culminated with the CHA practicing delivery of the scripts with research team members to simulate CHA-client interactions. Implementing an educational intervention with CHA counseling support or phone contact or usual educational materials about CRC screening plus a resource list will not affect any other concomitant care during the trial.Baseline and 12-month follow-up surveys are completed face-to-face and 3-month follow-up surveys are administered over the phone using paper surveys. Participants are identified by an ID number. A separate file is maintained with matched ID numbers and contact information to facilitate follow-up assessment administration. Date management is facilitated using the REDCap research management software platform . REDCap t-tests. The multivariate analyses will be conducted using the GEE procedure in SAS that implements the generalized estimating equations regression. Analyses will be performed using an intent-to-treat approach that includes all participants randomized. Significance tests will be two-sided and employ an overall significance level of α = 0.05. Sensitivity analyses will be employed to assess the impact of any missing data. For each arm, the proportion of participants who receive CRC screening by 12 months will be computed. The chi-square test will be used to compare the two treatment arms for screening receipt. If the proportion of participants receiving CRC screening in the intervention arm is at least 15% higher than that in the control arm, the intervention will be determined to be effective. To assess the influence of key covariates  on the primary outcome, regression analysis will be employed. In addition, to investigate treatment effects over time , we will estimate hazard ratios by fitting Cox proportional models using time-varying covariates. In these models, the receipt of CRC screening will be regressed at each actual time point on time elapsed since baseline to test for an interaction between time and treatment group. The basic model will be repeated, adjusting for age, income, marital status, education, and any other significant covariates at baseline. To test the proportional hazard assumption, the Kaplan-Meier curve and the Schoenfeld residuals will be used for fixed and time-varying covariates, respectively.All statistical analyses will be performed using SAS v. 9.4. First, summary statistics will be generated for all variables. Then, bivariate analyses will be conducted for key variables to compare differences between the intervention and control arms. Categorical variables will be compared using chi-square tests; continuous variables will be compared using two-sample Mediation and moderation analyses will be conducted to determine why and when variables are related, respectively. We will focus on specific mediators to include CRC perceived susceptibility, CRC fear and fatalism, CRC self-efficacy, and CRC knowledge in the conceptual model Fig. .Fig. 3CX) and the endogenous variables (Y) as a function of the mediators (Mn = 1–4) will be examined using four separate regression models. We will ensure that the assumptions of continuous measurements , normality , independence , and linearity  are met. We will assess direct causality and indirect causality using standardized regression coefficients  to determine the direction and magnitude of the effect of one variable upon the other variable ) and endogenous variables ), the exogenous and mediator variable, and the mediator and the endogenous variables in the presence of the IV , and lastly, we will confirm the lack of significance (or the meaningful reduction in effect) of the relationship between X and Y in the presence of the mediators.We will confirm that the mediators  are caused by the exogenous variables X/independent variable (IV) is related to an outcome Y/dependent variable (DV). We will assess whether the moderation effect is enhancing , buffering , or antagonistic . We will apply hierarchical multiple regression to examine the effects of the moderating variable. We will assess the interaction effect between X and M and whether or not such an effect significantly predicts the occurrence of Y. All variables will be standardized to facilitate data interpretation and avoid multicollinearity. We will fit a regression model predicting the outcome from both the predictor and moderator variables. We will check that both the effect of the predictor and the effect of the moderator, as well as the model (R2), are statistically significant. Then, we will fit another regression model that includes the interaction effect of the first model and check for a statistically significant R2 change and a statistically significant effect of the interaction term to determine if moderation is occurring .Additionally, we will assess the moderator variables  to determine under what condition  a given predictor Mediation analysis allows assessment of each covariate’s impact on the primary outcome independent of whether the intervention’s effect is significant, thus adding to the scientific understanding of the relevance of each. To examine the mediating effects on the primary outcome of each of the short items scored on a Likert-type scale, we will follow the strategy of Baron and Kenny . We willTo assess the impact of candidate moderators, we will use the Cox proportional hazard model and other appropriate survival analysis models to investigate the primary outcome on the treatment group, each candidate moderator, and the interaction of treatment and each candidate moderator at each measurement time point.To accomplish the cost-effectiveness study objective, we will conduct a randomized controlled community trial-based cost-effectiveness analysis to determine whether CHA intervention is worth implementing compared to the standard of care from a payer perspective. The effectiveness of CHA intervention will be measured in terms of CRC screening rate, while costs will be measured using the micro-costing approach to capture resource utilization , 28. TheThe TUNE-UP trial will aid in understanding how to improve stool-based CRC screening in an uninsured and underinsured African American patient population whose source of primary health care is through CHCs. While there have been several previous trials to test the effectiveness of clinic-based interventions to increase stool-based CRC screening in large public hospital or primary care settings, there have been very few studies conducted with CHCs focusing exclusively on an African American patient population, where CRC disparities are ongoing , 29. TheThere are several ethical considerations involved in monitoring, consent, and dissemination provisions. The trial steering group meets weekly, and the IRB Ethics Committee meets annually to review conduct throughout the trial period for auditing trial conduct. The TUNE-UP study is IRB approved and subject to continuing IRB approval by the Florida A&M University IRB (IRB#1439452-2). Any important changes to the protocol will be communicated to the IRB and the funder. Next, a copy of the revised protocol would be documented and updated in the clinical trial registry. Because of the educational nature of the study, there is no anticipated harm and compensation for trial participation. The trial results will be reported to the clinical trial registry at the end of the study period and published in a peer-reviewed publication. The datasets analyzed during the current study and statistical code are available from the corresponding author on reasonable request, as is the full protocol.Through the conceptual framework, the trial will test the relationships between several health behavior constructs to better understand the mechanisms by which the intervention affects beliefs and behaviors of patients to make the decision to participate in stool-based CRC screening. By identifying specific health behavior constructs of import to CRC screening, the research will identify areas of focus for future intervention studies to improve intervention components and increase CRC screening participation. There also may be a subset of patients who are uninformed about the opportunity to participate in CRC screening, and this trial may potentially reach these patients with low CRC knowledge and increase their knowledge, which may increase screening in this subgroup.promotora intervention was $104 when compared to the comparison group [The addition of an exploratory aim on cost-effectiveness will add to the literature to approximate costs for the intervention to assist financially constrained CHCs to decide if hiring an additional staff member might improve stool-based test return rates and thus improve their cancer screening programs. In a CRC screening study conducted in El Paso, TX, the cost per additional person screened for their on group . By provThe trial is in progress and enrolling participants. Trial enrollment began in April 2021 and will continue until March 2023.


Colonization of breast carcinoma by non-neoplastic melanocytes of epidermal origin was first described by Azzopardi and Eusebi in 1977. We herein report two cases on the exceptional clinical and pathological features of this phenomenon in a 66-year-old and a 51-year-old patients. The pathogenesis is not fully understood, but a disrupted basement membrane and the role of tumoral growth factors are considered essential. Melanocyte colonization and pigmentation of breast carcinoma was first described by Azzopardi and Eusebi in 1977 on a series comprising 14 cases . Im. Im38]. Our cases were histologically composed by dendritic melanocytes carrying abundant melanin pigment colonizing the surrounding neoplastic epithelial cells that had infiltrated the superficial dermis and penetrated the dermo-epidermal junction. Interestingly, similarly to the report of Mele M. et al. , one of The presence of melanocytes colonization and melanin pigmentation is described in various epithelial tumors like carcinomas of oral mucosa, larynx, salivary gland, prostate gland, and the rectal mucosa. On the other hand, the breast gland is an unusual ‘host’ for this phenomenon, maybe due to the improvement in early diagnosis of breast cancer, with only rare cases detected in T4 stage . The exact pathogenesis of melanocyte migration is not fully understood . Clinical and histological examination, but also additional immunohistochemical staining are essential to differentiate breast cancer with melanocyte colonization and pigmentation from other pathological entities that can affect breast gland . Further studies are required to exactly understand the molecular basis of this phenomenon and the possible association to clinical and pathological data.


Unfortunately, the vaccine development has been hindered by major antigenic diversity in protozoan parasite and they have also a digenetic or multigenic life-cycle in two hosts (human and vector) at least. Contribution of the target host population genetics and their susceptibility to infection/disease is an equally important concern for the design and accomplishment of anti-parasitic vaccines.Current control measures of protozoan infection rely only on chemotherapy to improve the disease. Vector control is also doing to reduce the transmission of protozoan infections. To date, there are no reliable vaccines are available against these infections and there is also an alarming rise of drug resistance.Plasmodium). The contents/function of these rhoptries have been the focus of substantial attention to comprehend the ability to invade a host cell which is most important of all apicomplexan characteristics.2 The obligate intracellular parasites Trypanosoma can parasitize a wide variety of cells during which these specialized secretory organelles play a central role.3 Parasitophorous vacuole facilitates the survival of the Leishmania parasite in humans.4 Genome sequence availability to support a proteomic database represents an extraordinary opportunity to characterize the composition and function of the protein in protozoan parasites. The rapid expansion of our understanding in proteomics has directed to new understandings into their function and set the foundation for a more complete insight of how these parasites contribute to invasion and intracellular survival process in the host.5 Immune responses to protozoan infection are highly multifaceted and it involves both humoral and cell-mediated responses to parasitic antigens array. In these protozoan parasites, infection often involves multiple lifecycle stages, which enhances antigenic diversity. Recent efforts have intensive to evaluate the response of defined parasite T-cell epitopes to examine the molecular basis of the immune reaction prompted during the infection with protozoan parasites. The severity of infection is a function of the infecting species together with consequent inflammatory/immune responses and host genetics. It has shown by the genetic and immunologic studies using the animal model and now becomes evident. They seem to singularly involve in immune subversion and require the participation of both B-cells and CD4+ T-cells during pathogenesis. A low level of IFN-γ production in host appears to be an important feature of disease progression. The monocyte recruitment and antigen presentation at the site of infection appear to be perilous for the pathogenesis development of the protozoan parasite. The roles of immune B-cells and T-cells in pathology could affect the efficiency of vaccines against protozoan parasite-mediated infectious diseases.Rhoptry organelles are part of the defining features of the phylum Apicomplexa  for sale in the market against infections and infectious diseases is listed in 7 Despite some challenges, proteomics has rapidly extended to comprise the finding of novel targets and biomarkers for a vast clinical application like early detection, diagnosis, and prognosis. The pharmaceutical application of proteomics could be explored in-depth for the documentation of novel drug targets. Several innovative proteomics technologies , protein array techniques, isotope-coded affinity tag, NMR spectroscopy, X-ray crystallography, and computational methods such as de novo/comparative prediction of protein structure, molecular dynamics simulation, etc) have progressed to achieve these goals. These proteomics technologies have been being used in different combinations. Proteomics has been extensively used to develop protein databases for protozoan parasite and evaluate the expression profile of genes under different environmental conditions. Such kind of proteomic investigation provides access to global changes related to specific mutations and explain drug targets of disease-causing protozoic pathogens. Above mentioned proteomics techniques may also be used to identify B-cell and T-cell antigens response of host after parasitic infection within complex protein mixtures when they coupled to immunological assays. This article provides a glimpse of the proteomics field and confers the extensive use of proteomic technologies to researchers. Article accentuates the proteomic approaches application in the development of a strong understanding of host-protozoan parasite interactions and promising drug targets and vaccines against infection of protozoa parasite.Many laboratories across the globe are utilizing proteomics as rapidly emerging technology to elucidate the fundamental mechanism associated with the severity detection of disease, cancer development, drug development, and identification of disease conditions in patients.Not applicable.The author declares no conflict of interest.Author thanks the National Institute of Technology, Raipur (CG), India for continuous support and assistance during research work and scientific writing.


The gold-standard therapy for the treatment of aortic arch pathologies is conventional open surgery. Recently, total endovascular aortic arch replacement with branched stent-grafts has been introduced into clinical practice with the aim of reducing invasiveness especially in selected high-risk patients. The aim of this review is to describe the two most commonly used branched devices for endovascular arch stent-grafting: Nexus  and RelayBranch . Nexus is a CE-certified off-the-shelf, single branch, double stent graft system. It consists of two different components: a main module for the aortic arch and the descending aorta with a side-branch for the brachiocephalic artery (BCA), and a curved module for the ascending aorta that lands into the sino-tubular junction and connects to the main module through a side-facing self-protecting sleeve. Nexus may be used in urgent-emergency cases and also in patients with only one suitable supra-aortic target vessel but, on the other hand, it makes cerebral blood flow dependent on one source vessel only. The RelayBranch Thoracic Stent-Graft System is a custom made, double branched endograft with a wide window on its superior portion to accommodate two inner tunnels for BCA and left common carotid artery connection; bilateral cervical accesses are generally used to advance guidewires for catheterization of the inner tunnels in a retrograde fashion. RelayBranch can be customized on every patient’s specific anatomy and provides a double blood source for the brain, but it cannot be used in urgent-emergency conditions. Therefore, in order to optimize outcomes, the choice of the most appropriate device should be made considering pros and cons of each system and patient’s anatomy by an experienced aortic team. In conclusion, total endovascular aortic arch exclusion is a promising reality in selected high-risk patients. Nowadays, aortic arch surgery is one of the most complex procedures in cardiac surgery. The gold-standard therapy for the treatment of aortic arch pathologies  remains open surgery performed under Cardiopulmonary Bypass (CPB) with hypothermic circulatory arrest and selective cerebral perfusion .Starting in the 1990s, hybrid procedures (combination of both open and endovascular procedures) have become an alternative to standard open surgery in order to treat, during the same procedure, both pathologies of the aortic arch and of the descending aorta. The core principle behind this treatment relies on the endovascular exclusion of the pathologic aorta after the creation of an adequate proximal landing zone by means of supra-aortic transposition (debranching) of one, two or three arch vessels. Therefore, the frozen elephant trunk (FET) is considered as the first-choice therapy: this procedure allows the replacement of the aortic arch using a non-stented vascular prosthesis and prepares the thoraco-abdominal aorta for other possible interventions thanks to a distal part composed of a covered stent graft ,3. This The aim of this review is to describe these different endovascular approaches with particular interest towards branched aortic arch stent grafts.The NEXUS Aortic Arch Stent Graft System is a CE-certified off-the-shelf, single branch, double stent graft system, specifically designed to address aortic pathologies involving or extending in the aortic arch.It consists of two different components: a main module for the aortic arch and the descending aorta with a side-branch for the brachiocephalic artery (BCA), and a curved module for the ascending aorta that lands into the sino-tubular junction and connects to the main module through a side-facing self-protecting sleeve .Although BCA is the suggested approach for main module deployment, landing is possible in any suitable supra-aortic vessel after careful evaluation of its anatomy. Generally, the left subclavian artery represents a good alternative landing site .Tantalum radiopaque markers and an active locking mechanism facilitate the correct rotational and longitudinal deployment in order to achieve good sealing and to avoid coverage of the BCA branch. Like other off-the-shelf devices, different sizes of the components are available to fit the great majority of aortic anatomies.Before device implantation, an extra anatomical surgical debranching of supra-aortic vessels is mandatory to redirect blood to the brain and to upper arms vessel from the BCA. To minimize handling and arch friction, the delivery systems are hydrophilic and pre-shaped. The delivery system is compatible with a 20 Fr introducer. The procedure is performed under general anesthesia and fluoroscopy guidance with bilateral percutaneous femoral and right axillary artery access (or left if the target vessel is the left subclavian artery). Near-infrared spectroscopy (NIRS) may be used as a cerebral monitoring system to rule out significant perfusion deficit during the procedure. A through-and-through axillary-femoral artery guideline is placed. A temporary trans-venous pacemaker lead is placed in the right ventricle for rapid pacing during the stent deployment. After systemic heparinization (ACT > 350 s), the main module is advanced over the guidewire to its final position and deployed from the BCA to the descending aorta. Subsequently, via the stiff guidewire placed in the left ventricle and during rapid pacing the ascending aorta module is implanted and connected to the main module through the self-docking sleeve and the delivery system is then withdrawn. Care has to be taken in positioning the ascending module at the level of the tantalum ring of the main module to achieve adequate fixation and sealing. Under rapid pacing, a simultaneous inflation of two molding balloons one at the locking section and the second at the BCA branch, is performed .A multicenter study involving five centers in Europe, Canada and New Zealand investigated safety and performance of NEXUS. Twenty-eight patients (mean age 72 ± 6 years) with aortic arch pathology considered to be at high or prohibitive risk for surgery and with anatomical fit criteria for endoprosthesis implantation were enrolled [The RelayBranch Thoracic Stent-Graft System is a custom made, double branched endograft with a wide window on its superior portion to accommodate two inner tunnels for BCA and left common carotid artery (LCCA) connection .These extensions are custom-made or off-the-shelf bridging limbs. Stent grafts are manufactured according to preoperative CT scan measurement and the customization process generally takes about 4 to 8 weeks. A pre-curved delivery system allows a window for supra-aortic branches to be automatically aligned with the outer curvature of the aorta. Radiopaque markers are placed in the window and in the ends of the stent grafts to facilitate the positioning and the reorientation. Specific lock stent systems are present in the tunnels to prevent potential disconnection and migration of the extensions. A left subclavian artery (LSA) revascularization is needed prior to the procedure.The procedure is carried out under general anesthesia, angiography guidance, NIRS monitoring and systemic heparinization (ACT > 350 s) as described above for a single-branch stent graft system. Usually, a common femoral artery access is used to place a stiff guidewire into the left ventricle and to advance the main stent graft in the aortic arch. Rapid pacing through a temporary trans-venous pacemaker is established while the endoprosthesis is deployed. Bilateral cervical accesses are generally used to advance soft guidewires for catheterization of the inner tunnels in a retrograde fashion. Once the target tunnel is engaged, a stiffer wire is introduced, and the correct positioning is monitored under fluoroscopy. Then the extension graft is deployed with maximum overlapping within the tunnel and inflation of a molding balloon is performed to ensure a correct sealing of the components. The same procedure is done for the other tunnel in a sequential fashion .The Italian registry of double inner branch stent graft for arch pathology (TRIUMPH Registry) evaluates early and mid-term results in 24 patients, from nine Italian cardiovascular centers, considered unfit for open arch surgery and treated with the RelayBranch Thoracic Stent-Graft System . All patA Japanese cohort of 28 patients  treated with a double branched endograft reported a complete procedural success without any in hospital death [Alternatives to branched endoprostheses in the endovascular treatment of aortic arch pathologies are mainly represented by fenestrated endoprosthesis and by the chimney technique.Fenestrated endoprosthesis are designed to reduce manipulation of the supra-aortic trunks and the subsequent risk of embolic events. These endografts have single or multiple fenestrations created along their greater curvature to secure blood supply via the arch vessels. They can be both custom made and off-the-shelf, with different sizes available. Aneurysms involving supra-aortic branches or located at the greater curvature and proximal fusiform aneurysms are not optimal candidates for this type of endoprosthesis due to the related high risk of endoleak. On the other hand, saccular aneurysms of the lesser curvature of the arch should be considered eligible for treatment. Fenestrated procedures are indicated in arch pathologies that do not necessarily require a landing zone in the ascending aorta but rather in the middle arch. In general, the most challenging aspects to address are related to the curved configuration of the aortic arch and to the anatomical variability of the supra-aortic branches. Suitable candidates are also represented by patients with previous type A dissection who underwent replacement of the ascending aorta because the presence of a prosthetic graft ensures an optimal proximal landing zone. Some authors  have raiThe Najuta stent endograft  is a semi-custom-made pre-curved and fenestrated stent graft with 64 structure patterns and three fenestrations that can be customized in 21 patterns, depending on the patient’s anatomy of the aorta. Pre-shaped structuring prevents malsealing adhesion on the inner curvature and a “bird-beak” effect. The simplicity of the delivery procedure is represented by the pre-curved shape and the easy orientation of the device, with the use of the “through-and-through” guidewire technique that minimizes contact with the atherosclerotic wall of the aorta and possibly reduces neurological risk. The endoprosthesis configuration is selected on the basis of preoperative CT 3D reconstruction. The device has a stabilization system with a rigid fixation at the proximal tip and a traction suture to narrow the proximal end of the graft for exact placement of the endograft in the aortic arch. The tip of the system is soft to avoid friction on the aortic wall. During deployment, the second and third graft units are opened first. At this stage, the endograft is still susceptible to adjustment. The endograft can be pushed up to greater curvature to achieve good conformability to the aortic arch configuration and the graft material is expanded to the proximal landing zone without ballooning.Iwakoshi et al. reported a 6-year experience with 32 patients treated with the Najuta fenestrated stent endografts  at three Japanese centers . The meaA multicenter investigation with Najuta fenestrated stent endografts  for the treatment of aortic arch pathologies enrolled 35 centers in Japan and 383 patients . All patTsilimparis and the Hamburg group compared the outcomes of Cook Medical  custom made branched versus fenestrated endoprostheses for endovascular treatment of aortic arch pathologies . This siConcerning the fenestrated endoprosthesis, another technical solution is represented by the “in situ” fenestration of the stent grafts. It offers a bailout option in the treatment of emergent endovascular acute aortic syndromes when debranching, use of custom-made prostheses and the chimney technique may be options that are not always available. Coverage of the left subclavian artery has been seen to lead to a significantly increased risk of subclavian steal syndrome and stroke in the vertebral and medullary territory. In situ fenestration provides a rapid and reproducible method to create a fenestration in the endograft and revascularize aortic branches. Several techniques have been described such as the use of retrograde lasers, the graft puncture with the use of a PTC needle and a flexible bronchoscopy aspiration needle or the “cutting balloons” technique for transluminal fenestration ,13. AnatThe chimney technique represents another alternative for the endovascular treatment of aortic arch pathologies and is widely used in the abdominal aorta and visceral vessels. It involves the placement of parallel stent grafts from each of the supra-aortic branches, with the proximal portions placed parallel to the main thoracic endoprosthesis. This technique requires advanced endovascular expertise. Although endovascular repair of the aortic arch with chimney grafts is associated with a lower mortality rate than open reconstruction, some concerns regarding the stroke rate have been raised. Compared with fenestrated or branched prostheses, it has the advantage of avoiding customization process delay and high cost, as they are off-the-shelf devices. The main weakness of the chimney technique is the risk of type Ia endoleaks through the gutters between the main aortic grafts and the parallel grafts. Appropriate sizing of the thoracic graft and the use of the kissing balloon technique can minimize gutter formation. The presence of a healthy proximal landing zone to ensure an adequate seal is crucial. Sizing should take into account the number and diameter of planned chimney grafts and aortic pathology. A major advantage of the chimney technique is the creation of an additional landing zone for proximal fixation of the stent-graft while maintaining aortic branch perfusion.A literature review by Moulakakis investigates the outcomes of the chimney technique in high-risk patients unfit for conventional aortic arch repair . A totalTotal endovascular aortic arch exclusion with branched devices is a reasonable option for selected patients with increased risk for open surgery and, in particular, for those who already underwent open repair of type A acute aortic dissection.Looking at the 2018 guidelines of the American Heart Association and the European Society of Cardiology, endovascular aortic arch repair in zone 0 should be considered in patients unfit for open surgery and with a suitable anatomy . FurtherHybrid aortic arch repair with the frozen elephant trunk technique is associated with a 30-day mortality of up to 12% and a postoperative risk of stroke ranging from 5% to 13%. Despite the fact that no randomized data are available, the experience is still limited, follow-up is short and only highly selected patients have been treated so far; current results of endovascular aortic arch repair are definitely encouraging considering that mortality and stroke rate, in patients deemed unfit for open surgery due to high or prohibitive risk, are similar to those reported with open surgery. To date, the risk of major stroke still appears to be the Achille’s heel of endovascular procedures due to guidewire navigation in the arch and in supra-aortic arteries, which are frequently burdened by atherosclerosis with consequent potential emboli production. Therefore, the use of cerebral embolic protection devices (EPD) may be of help to reduce the risk of periprocedural cerebrovascular events.The majority of currently available EPD pose a technical challenge especially during the implantation of branched devices as they may interfere with the components of the endovascular device also carrying the risk of resulting entrapped after stent-graft positioning. The most commonly used EPD in this field are distal filters like those used during carotid artery stenting  but the Another specific population is represented by patients with urgent or emergent indications to aortic arch treatment like pseudo-aneurysms of the anastomotic site  or confiIn conclusion, total endovascular aortic arch exclusion is a promising reality that can be performed with several different technologies: branched devices, fenestrated grafts, chimney technique. Branched stent-grafts for the aortic arch come in two different configurations: off-the-shelf single branch and custom-made double branch. The first may be used in urgent-emergency cases and also in patients with only one suitable supra-aortic target vessel but, on the other hand, makes cerebral blood flow dependent on one source vessel only. The latter can be customized on every patient’s specific anatomy and provides a double blood source for the brain, but it cannot be used in urgent-emergency conditions. Therefore, in order to optimize outcomes, the choice of the most appropriate device should be made considering the pros and cons of each system and patient’s anatomy by a high-volume aortic center where all options are available.A comprehensive aortic team, able to provide open surgery, hybrid procedures and total endovascular solutions is the most experienced and unbiased decision maker for these complex patients. Due to the lack of long-term follow-up and to the limited experience, especially with branched devices, these procedures should still be considered in selected patients deemed inoperable or high risk for conventional open surgery.Further randomized studies will address whether these new technologies can be compared to open surgery that, at the moment, should still be considered the first choice for the treatment of aortic arch pathologies.


Little has been published regarding postgraduate assessments during the COVID-19 pandemic. There is an urgent need to graduate well-trained specialists including family physicians who play a key role in patient care. The successes and challenges encountered in mounting qualifying 2020 Family Medicine examinations during the COVID-19 pandemic at the University of the West Indies are described in this paper. Human resource, planning, use of technology and virtual environments are discussed, which enabled successful examinations at this multicampus regional site. All facets of medical education have been challenged with the declaration of the novel SARS-COV-2 virus COVID-19) pandemic in March 2020.9 pandemi7In this context, we describe the successes and challenges encountered in mounting qualifying Family Medicine examinations during the COVID-19 pandemic at the authors’ institution. The University of the West Indies (The UWI). The Family Medicine programmes at The UWI have been in existence for 40 years. Uniquely, we are a multicampus university with teaching centres across four Caribbean islands, with common exit examinations for a Diploma and Doctor of Medicine, in Family Medicine.The examinations are typically held in May–June each year, but in 2020, The UWI administration decided to postpone examinations due to the pandemic. During the new examination period (24 November to 2 December 2020), there were on average 18, 500, 4387 and 795 active COVID-19 cases on The UWI islands of Barbados, Bahamas, Jamaica and Trinidad and Tobago, respectively.The written examinations comprised multiple-choice questions (MCQs) and extended matching questions (EMQs) that were proctored in person by invigilators and staff following strict regulations both at the university and national levels. Selected venues allowed for at least 2 m between candidates. Students completed screenings for elevated temperature and symptoms of COVID-19 infection and prevention measures were enforced at examination sites.The emphasis of the Family Medicine Objective Structured Clinical Examinations (OSCE) has traditionally tested students’ ability to conduct patient-centred consultations across the spectrum of clinical scenarios typical of first-contact, community-based care. Maintaining such standards while adhering to COVID-19 public health regulations meant transforming this examination into a completely virtual exercise that was challenging. This new concept required significant planning on the practicalities of the examination process while maintaining traditional assessment goals and integrity.Written papers were redesigned using MCQs and EMQs in anticipation of mounting online synchronous examinations. The mandate of The UWI, however, shifted to in-person proctored examinations adhering to all national pandemic protocols. All written papers were blueprinted, as before, for validity based on learning outcomes. Questions on COVID-19 were included. As with past examinations, review and feedback on all written examinations by an external examiner were accomplished using secure password-protected online platforms. OSCE examinations were developed such that all participating sites had a unique examination with different clinical cases. Training of simulated patients was done virtually to ensure reliability in performance. Oral presentations and examination of research projects also occurred via videoconferencing in a secure environment with social distancing restrictions in place. Written and OSCE examinations were all standard set to provide minimal competencies as determined by academics from all sites using modified dichotomous Angoff methods.The use of Zoom video conferencing online software for OSCE examination has been well described.Oral examinations were also part of the postgraduate Family Medicine examinations. These were conducted virtually using Zoom. In addition to the functionalities described above, grading was also done electronically using Google forms. The use of such customisable online forms in creating online marksheets has also been used in the OSCE setting.First, distance education technology had been frequently used by Family Medicine academics prior to the pandemic  and staff were comfortable and experienced in using it. This situation had been fueled previously by the physical distance between islands.Second, both Jamaica and Barbados currently conduct a portion of their academic work for rural Jamaica and the Eastern Caribbean by distance education modalities. The physical separation and distance of the archipelago meant that the administration of The UWI had been investing significantly in distance education technology for several years.Furthermore, there was institutional support embodied by The UWI’s triple-A strategic plan 2017–2022: Access to quality tertiary education, alignment with the needs of the region and agility in response to the ever-changing environment.The mounting of such an examination was no easy feat and was only accomplished because of immense preparation and collaboration. A core group of about 14 persons from all four sites held regular meetings using Zoom. All academics, most of whom were familiar with online technologies, were forced to rely more on this modality for teaching and meetings from the onset of the pandemic. The UWI’s plan for digital transformation was agile in staff training and IT support to ensure smooth and timely pivoting to online teaching for those who needed it.IT support persons were critical in the smooth conduct of these examinations. They were pooled from all campuses to discuss the feasibility of virtual examinations, and a joint needs analysis was conducted across campuses to determine the specific requirements for all virtual examinations. Key responsibilities of IT specialists included the creation of hosting links, configuring devices, troubleshooting and breakout room management. Virtual simulation exercises with IT specialists allowed for troubleshooting. Students were kept abreast of the proposed changes and participated in virtual practice runs to familiarise them with the technology. Virtual training of the simulated patients also minimised physical contact.In addition to the maintenance of assessment validity and reliability, there were also several noteworthy achievements. A total of 53 candidates were examined with 48 successfully completing their examinations, a pass rate (91%) comparable to that of pre-COVID-19 years. All virtual clinical examinations ran on time with few technical glitches and without any breaches in local COVID-19 regulations. Virtual breakout rooms allowed for the shuffling of students without them leaving their assigned individual physical space as obtained in face-to-face examinations. It also meant that students, patients and examiners could communicate unhindered without a mask inside their enclosed spaces. Virtual rooms allowed examiners from one campus to examine candidates from another, off-site examination of candidates as well as examiner meetings.The absence of all examiner-related travels in 2020 would have translated into reduced costs of air travel and accommodation. It also meant more efficient use of examination time. An independent external examiner would usually visit to observe the entire examination process as a quality control measure to maintain examination integrity. The virtual environment allowed the external examiner to fulfil this role having observed all candidates and all OSCE scenarios at all four sites. Usual examination rules of no personal electronic devices and communication were also enforced at all physical sites by invigilators.Candidates, simulated patients and, in some cases, examiners were brought to a central location at each site. They were each housed in a separate room/space in accordance with COVID-19 protocols. This allowed invigilator oversight of candidates and IT presence for troubleshooting and on-hand support for all. IT personnel had the opportunity to work collaboratively in the planning process, affirming our concept of operating as The One UWI.20The main challenge faced in mounting these examinations was the heavy dependence on technology and IT support. The initial investment in purchasing additional devices and equipment may, however, prove to be cost-effective as this mode of examination may be required in the medium term. Power losses and loss of connectivity were also possible threats. Examination venues with power backup and redundant internet hotspots were some of the contingencies in place to cater for these eventualities. Fortunately, major internet disruptions were not common during the examinations, and the minor lapses in audio and video quality that occurred did not detract significantly from the point of view of the participants. Training of backup patients, having extra examiners on standby and having backup physical spaces with ready devices, were some of the contingencies in place to avoid unplanned mishaps.The inability to reliably test physician skills at physical examinations on real patients was a limitation. Structuring OSCE scenarios where examination findings are elicited by questioning, while not a replacement for a physical examination, may test integration of clinical findings. Observing candidates perform examinations during their training until a defined competency level is attained, and formative in-house clinical skills assessments may also negate the need to test such a skill in an exit examination.Future research involving the students, simulated patients and examiners from all sites may prove useful. The perspective of all parties who participated in the Family Medicine examinations may produce useful insights into how the above examination experience described can be improved. Due to worldwide changes in modes of learning, training programmes should incorporate development of basic IT competencies as an ongoing requirement for their faculty. This will help mitigate future disruptions to face-to-face training and assessments and can take the form of online modules, Continuing Medical Education or onsite instructions. These IT competencies will serve to build capacity not only for assessment and examinations but also for the development of Telehealth capabilities which will surely play a crucial role in the delivery of clinical services and training.et al, COVID-19 may have led some to experience ‘there is no alternative’ moment in assessment, but through collegiality, communication, flexibility and compassion, we turned this challenge into an opportunity.The mandate of UWI to mount clinical postgraduate examinations in the face of a pandemic with so many uncertainties seemed a daunting task initially. In the words of Fuller Family Medicine certification examinations can be successfully conducted virtually during a pandemic.Information technology support and redundancies and use of videoconferencing software are necessary for delivering virtual clinical examinations.Careful planning, collaboration, human resource and institutional investment are key to ensure smooth running of examinations across distant multicampus sites.