Structural basis of closed groove scrambling by a TMEM16 protein.

Activation of Ca2+-dependent TMEM16 scramblases induces phosphatidylserine externalization, a key step in multiple signaling processes. Current models suggest that the TMEM16s scramble lipids by deforming the membrane near a hydrophilic groove and that Ca2+ dependence arises from the different association of lipids with an open or closed groove. However, the molecular rearrangements underlying groove opening and how lipids reorganize outside the closed groove remain unknown. Here we directly visualize how lipids associate at the closed groove of Ca2+-bound fungal nhTMEM16 in nanodiscs using cryo-EM. Functional experiments pinpoint lipid-protein interaction sites critical for closed groove scrambling. Structural and functional analyses suggest groove opening entails the sequential appearance of two π-helical turns in the groove-lining TM6 helix and identify critical rearrangements. Finally, we show that the choice of scaffold protein and lipids affects the conformations of nhTMEM16 and their distribution, highlighting a key role of these factors in cryo-EM structure determination.

The Efficacy, Tolerance, and Adverse Events of Endoscopic Intragastric Balloon in Obese and Overweight Patients: A Retrospective Cross-Sectional Study.

Introduction Obesity is a pandemic causing a significant burden on healthcare systems and carries increased morbidity and mortality. One of the options for managing obesity is endoscopic intragastric balloon (IGB) insertion. The aim of the study is to assess the efficacy, tolerance, and side effects of IGB insertion in overweight and obese patients. Methods This is a cross-sectional retrospective study that includes 71 patients who underwent IGB insertion from 2015 to 2019 at King Hamad University Hospital (KHUH), Kingdom of Bahrain. Records of these patients were accessed to assess the percentage of weight loss at the time of balloon removal, complications, and tolerance of the procedure. Furthermore, telephonic interviews were conducted to enquire about side effects and the satisfaction of the procedure. Results A total of 57 patients were included in the weight loss analysis. Thirteen patients did not tolerate the balloon, and one patient had a balloon rupture. The patients experienced a significant reduction in weight upon balloon removal with a mean of 9.74 ± 8.71 kg (p-value of <0.001) and percentage total body weight loss of 10.48 ± 8.07 (p-value of <0.001). A significant reduction was also seen in the body mass index of 3.67 ± 3.57 (p-value of <0.001). The most frequent side effects were nausea, vomiting, and abdominal pain. No major complications or mortalities occurred. Conclusion Intragastric balloons are effective in establishing weight loss. Among patients who tolerated the procedure, the most frequently reported side effects were nausea, vomiting, and abdominal pain.

Diagnostic accuracy of ePOS score in predicting DNR labeling after ICU admission: A prospective observational study (ePOS-DNR).

Background: Resuscitation can sometimes be futile and making a do-not-resuscitate (DNR) decision is in the best interest of the patient. The electronic poor outcome screening (ePOS) score was developed to predict 6-month poor outcomes of critically ill patients. We explored the diagnostic accuracy of the ePOS score in predicting DNR decisions in the intensive care unit (ICU). Methods: This study was conducted at the ICU of a tertiary referral hospital in Saudi Arabia between March and May 2023. Prospectively, we calculated ePOS scores for all eligible consecutive admissions after 48 h in the ICU and recorded the DNR orders. The ability of the score to predict DNR was explored using logistic regression. Youden's ideal cut-off value was calculated using the DeLong method, and different diagnostic accuracy measures were generated with corresponding 95 % confidence intervals (CIs). Results: We enrolled 857 patients, 125 received a DNR order and 732 did not. The average ePOS score of DNR and non-DNR patients was 28.2±10.7 and 15.2±9.7, respectively. ePOS score, as a predictor of DNR order, had an area under receiver operator characteristic (AUROC) curve of 81.8 % (95% CI: 79.0 to 84.3, P <0.001). Youden's ideal cut-off value >17 was associated with a sensitivity of 87.2 (95% CI: 80.0 to 92.5, P <0.001), specificity of 63.9 (95% CI: 60.3 to 67.4, P <0.001), positive predictive value of 29.2 (95% CI: 24.6 to 33.8, P <0.001), negative predictive value of 96.7 (95% CI: 95.1 to 98.3, P <0.001), and diagnostic odds ratio 12.1 (95% CI: 7.0 to 20.8, P <0.001). Conclusions: In this study, the ePOS score performed well as a diagnostic test for patients who will be labeled as DNR during their ICU stay. A cut-off score >17 may help guide clinical decisions to withhold or commence resuscitative measures.

Acinetobacter baumannii, a Multidrug-Resistant Opportunistic Pathogen in New Habitats: A Systematic Review.

In recent years, humanity has begun to face a growing challenge posed by a rise in the prevalence of antibiotic-resistant bacteria. This has resulted in an alarming surge in fatalities and the emergence of increasingly hard-to-manage diseases. Acinetobacter baumannii can be seen as one of these resilient pathogens due to its increasing prevalence in hospitals, its resistance to treatment, and its association with elevated mortality rates. Despite its clinical significance, the scientific understanding of this pathogen in non-hospital settings remains limited. Knowledge of its virulence factors is also lacking. Therefore, in this review, we seek to shed light on the latest research regarding the ecological niches, microbiological traits, and antibiotic resistance profiles of Acinetobacter baumannii. Recent studies have revealed the presence of this bacterium in a growing range of environmental niches, including rivers, treatment plants, and soils. It has also been discovered in diverse food sources such as meat and vegetables, as well as in farm animals and household pets such as dogs and cats. This broader presence of Acinetobacter baumannii, i.e., outside of hospital environments, indicates a significant risk of environmental contamination. As a result, greater levels of awareness and new preventive measures should be promoted to address this potential threat to public health.

Factors influencing implementation of point-of-care testing for acute respiratory infectious diseases in community pharmacies: A scoping review using the Consolidated framework for implementation research.

BACKGROUND: Emerging evidence suggests pharmacy-based point-of-care (POC) testing for acute respiratory infections diseases is beneficial, but not widely implemented. A theory-informed review to understand the factors influencing service implementation is lacking. OBJECTIVE: To examine the extent, range, and nature of research available on enablers and barriers to POC testing implementation for infectious respiratory diseases in community pharmacies and identify their underpinning theoretical constructs using the Consolidated Framework for Implementation Research (CFIR). METHODS: Scoping review guided by the JBI Manual for Evidence Synthesis. A comprehensive search from inception to June 28th, 2022 was conducted using Medline, Embase, CINAHL, Cochrane Library, and ProQuest dissertations without date or language restriction. Eligible articles investigated barriers and/or facilitators to strep throat, influenza, C-reactive protein, and COVID-19 POC testing in community pharmacies. Two reviewers independently performed title & abstract screening, full-text screening, and data extraction. Content analysis was conducted according to a pre-established framework and concepts were mapped to the CFIR. RESULTS: Forty-three studies were included. Most originated from the USA (n = 24; 56%) and investigated strep throat. The majority were testing/initial implementation projects (n = 23; 54%) conducted in urban centers (n = 17; 40%). Thirty-six (84%) studies used quantitative methodology, while 6 (14%) were qualitative. Only four studies (9%) used theory to guide their inquiry. The 124 identified implementation factors mapped onto 21 CFIR constructs, covering all 5 domains. The domain "Outer setting" (n = 35/43; 81%) was most prevalent as were the constructs "Patient needs and resources," (n = 21/43; 49%) "External policy & incentives," (n = 17/43; 40%) and "Relative advantage" (n = 17/43; 40%). CONCLUSION: A large volume of research explores factors influencing the implementation of pharmacy-based respiratory infectious disease POC testing services, but few studies use qualitative or theory-informed methods. Knowledge of the wide range of facilitators and barriers identified can help pharmacy managers and researchers design strategies to support successful service implementation.

The underappreciated diversity of bile acid modifications.

The repertoire of modifications to bile acids and related steroidal lipids by host and microbial metabolism remains incompletely characterized. To address this knowledge gap, we created a reusable resource of tandem mass spectrometry (MS/MS) spectra by filtering 1.2 billion publicly available MS/MS spectra for bile-acid-selective ion patterns. Thousands of modifications are distributed throughout animal and human bodies as well as microbial cultures. We employed this MS/MS library to identify polyamine bile amidates, prevalent in carnivores. They are present in humans, and their levels alter with a diet change from a Mediterranean to a typical American diet. This work highlights the existence of many more bile acid modifications than previously recognized and the value of leveraging public large-scale untargeted metabolomics data to discover metabolites. The availability of a modification-centric bile acid MS/MS library will inform future studies investigating bile acid roles in health and disease.

Exploring Promising Therapies for Non-Alcoholic Fatty Liver Disease: A ClinicalTrials.gov Analysis.

Background: Non-alcoholic fatty liver disease (NAFLD) is a common disease and has been increasing in recent years. To date, no FDA-approved drug specifically targets NAFLD. Methods: The terms "Non-alcoholic Fatty Liver Disease" and "NAFLD" were used in a search of ClinicalTrials.gov on August 24, 2023. Two evaluators independently examined the trials using predetermined eligibility criteria. Studies had to be interventional, NAFLD focused, in Phase IV, and completed to be eligible for this review. Results: The ClinicalTrials.gov database was searched for trials examining pharmacotherapeutics in NAFLD. The search revealed 1364 trials, with 31 meeting the inclusion criteria. Out of these, 19 were finalized for evaluation. The dominant intervention model was Parallel. The most prevalent studies were in Korea (26.3%) and China (21.1%). The most common intervention was metformin (12.1%), with others like Exenatide and Pioglitazone accounting for 9.1%. Conclusion: Therapeutics used to manage NAFLD are limited. However, various medications offer potential benefits. Further investigations are definitely warranted.

Assessing mental health among students in the UAE: A cross-sectional study utilizing the DASS-21 scale.

Background: The escalating worldwide concerns for mental health, significantly amplified by the COVID-19 pandemic, necessitates understanding the impact on vulnerable populations, such as university students. This study aims to investigate the prevalence and implications of depression, anxiety, and stress among university students in the United Arab Emirates (UAE) using the Depression, Anxiety, and Stress Scale-21 Items (DASS-21). Methods: This study utilized convenience sampling to investigate the mental health of undergraduates in UAE universities using a bilingual DASS-21 questionnaire via Google Forms. Analysis was conducted using SPSS version 29.0, employing descriptive statistics, Chi-squared tests, Mann-Whitney tests, Kruskal-Wallis tests, and Multinomial Logistic Regression to analyze relationships between sociodemographic variables and mental health scores. Results: The study examined 332 students, with most female participants (81 %, n = 269) and individuals aged 18-20 (89.8 %, n = 298). It revealed higher mean DASS scores among females: Depression (M = 15.80, p = 0.030), Anxiety (M = 17.63, p < 0.001), and Stress (M = 22.61, p < 0.001). Fourth-year students exhibited the highest DASS scores for depression (M = 30.33, p = 0.002), anxiety (M = 21.33, p = 0.002), and stress (M = 27.00, p = 0.005). Younger participants aged 18-20 had an odds ratio (OR) of 4.925 for depression, indicating they were approximately five times more likely to experience depression. Conclusions: This study reveals gender, age, and academic-year variations in depression, anxiety, and stress among UAE university students. Specifically, our findings indicate higher levels of anxiety and stress among females and reveal academic-year and age-related patterns in mental health conditions. University support services in the UAE should better address student needs, including counseling focused on high school to university transition challenges.

Wide-angle non-uniform optical phased array using compact and efficient antenna design.

In the need for a more compact and efficient optical phased array with a wide steering beam for LIDAR applications, a wide steering array with high resolution is desirable. However, in the published work, a trade-off is often made for one over another. Apodized grating antennas have shown good efficiency with a compact size and wide beam profile, which improve optical phased array beam steering capability and are also compatible with the CMOS silicon photonics process. A promising studies shows enhancement in steering range with good resolution utilizing a non-uniform optical phased array. In this work, we present two highly efficient optical antennas with 94% and 93.5% upward power at the center frequency for the first and second antenna respectively, exceeding state-of-the-artwork to the best of our knowledge, and wide full-width half maximum of 8.88° x 78.05° and 7.53° x 69.85° in elevation and azimuthal planes, respectively. Both antennas provide a broad bandwidth across the 1400-1700 nm wavelength range with more than 80% efficiency in the S, C, and L bands. To overcome the limited scan ranges and small aperture size, a two-dimensional non-uniform array of 10 × 10 elements is utilized to increase the beam steering capability. A genetic algorithm is used to optimize the position of array elements, resulting in an aliasing-free array with a wide steering range of 160° with beam width 0.5° and consistent -11 dB maximum side lobe level across the steering range.

Phylogenetic congruence of Plasmodium spp. and wild ungulate hosts in the Peruvian Amazon.

Malaria parasites are known to infect a variety of vertebrate hosts, including ungulates. However, ungulates of Amazonia have not been investigated. We report for the first time, the presence of parasite lineages closely related to Plasmodium odocoilei clade 1 and clade 2 in free-ranging South American red-brocket deer (Mazama americana; 44.4%, 4/9) and gray-brocket deer (Mazama nemorivaga; 50.0%, 1/2). We performed PCR-based analysis of blood samples from 47 ungulates of five different species collected during subsistence hunting by an indigenous community in the Peruvian Amazon. We detected Plasmodium malariae/brasilianum lineage in a sample from red-brocket deer. However, no parasite DNA was detected in collared peccary (Pecari tajacu; 0.0%, 0/10), white-lipped peccary (Tayassu pecari; 0.0%, 0/15), and tapir (Tapirus terrestris; 0.0%, 0/11). Concordant phylogenetic analyses suggested a possible co-evolutionary relationship between the Plasmodium lineages found in American deer and their hosts.

Static and dynamic magnetic properties of circular and square cobalt nanodots in hexagonal cells.

In this work we performed a detailed numerical analysis to investigate the static and dynamic magnetic properties of hexagonal cells of square and circular cobalt nanodots as a function of the distance between them and the external magnetic field to which they are subjected. By simulating hysteresis curves with the external magnetic field applied parallel and perpendicular to the plane of these nanostructures, we can conclude that the cobalt nanodots presented a significant perpendicular magnetic anisotropy. We also obtained that the coercivity increases with decreasing volume, which implies that the circular dots have a higher coercivity than the square dots. Furthermore, we studied the dynamic susceptibility of these systems and found that it is possible to control both the position and the number of resonance peaks by controlling the geometry and the distance between the magnetic nanodots. This work provides useful information on the behaviour of cobalt nanodot arrays, opening paths for the design and improvement of two-dimensional technological devices.

Structural basis of closed groove scrambling by a TMEM16 protein.

Activation of Ca2+-dependent TMEM16 scramblases induces the externalization of phosphatidylserine, a key molecule in multiple signaling processes. Current models suggest that the TMEM16s scramble lipids by deforming the membrane near a hydrophilic groove, and that Ca2+ dependence arises from the different association of lipids with an open or closed groove. However, the molecular rearrangements involved in groove opening and of how lipids reorganize outside the closed groove remain unknown. Using cryogenic electron microscopy, we directly visualize how lipids associate at the closed groove of Ca2+-bound nhTMEM16 in nanodiscs. Functional experiments pinpoint the lipid-protein interaction sites critical for closed groove scrambling. Structural and functional analyses suggest groove opening entails the sequential appearance of two π-helical turns in the groove-lining TM6 helix and identify critical rearrangements. Finally, we show that the choice of scaffold protein and lipids affects the conformations of nhTMEM16 and their distribution, highlighting a key role of these factors in cryoEM structure determination.

Relative contributions of the supraspinatus cord and strap tendons to shoulder abduction and translation.

BACKGROUND: The supraspinatus (SS) is formed by a larger anterior bipennate muscle with a cord-like tendon and a posterior unipennate muscle with a strap-like tendon. There is a tendinous connection between the 2 SS subunits. Yet, the relative mechanical contribution of the SS cord and SS strap musculotendinous units to load transmission and subsequent shoulder abduction force is unknown. We hypothesized that a simulated SS cord vs. an SS strap tear would generate less shoulder abduction force and, further, an intact SS cord would offset the expected abduction loss from an SS strap tear, but the inverse would not be true. MATERIALS AND METHODS: Twenty fresh-frozen cadaveric specimens were tested in a shoulder simulator with physiological load vectors applied to the upper and lower subscapularis, SS cord, SS strap, infraspinatus, and teres minor. The roles of the SS cord and SS strap muscles were delineated by varying their loads, while keeping constant loads on other muscles. The randomized testing trials included a native condition and 4 test cases that simulated tears by dropping the load and force transfer via the SS cord-to-SS strap connection by adding the load. Testing was completed at both 0° and 30° of abduction. During each test, shoulder abduction force, rotator cuff strains, and humeral translation were measured. RESULTS: Simulated isolated SS cord and SS strap tears led to a significantly lower shoulder abduction force (P < .001). A simulated cord tear at 0° and 30° reduced the abduction force by 53% and 38%, respectively. A simulated strap tear at 0° and 30° dropped the abduction force by 27% and 23%, respectively. The decline in the abduction force was larger for the SS cord tear vs. SS strap tear (P ≤ .001). An SS cord tear with full-load transfer to the strap was able to recover to native values at both 0° and 30° (P ≥ .288). Likewise, an SS strap tear with full-load transfer to the SS cord showed a similar recovery to native values at both 0° and 30° (P ≥ .155). During full-load transfer, the tendon strain followed the loading pattern. An SS cord tear or SS strap tear did not cause a change in humeral translation (P ≥ .303). DISCUSSION: The mechanical findings support the efficacy of nonoperative treatment of small (<10 mm) SS tears,11 because an intact SS strap tendon can effectively offset the abduction loss of a torn SS cord tear and vice versa.

Systemic lupus erythematosus in pediatric patients: Pulmonary manifestations.

The pulmonary manifestations of Systemic Lupus Erythematosus (SLE) in pediatric patients are poorly understood and the pulmonary manifestations reported from the adult population are generally extrapolated to the pediatric population. In the present work, the review of 228 files was carried out, in which the pulmonary manifestations, symptoms and antibody levels of the patients treated at the Hospital Regional de Alta Especialidad de Ixtapaluca (HRAEI), State of Mexico, Mexico, were identified. Statistical significance between groups was estimated using the Chi-square and Mann-Whitney U test. The main pulmonary manifestations identified were pleurisy (14 %), pulmonary hemorrhage (3.9 %), pulmonary thromboembolism (0.9 %), acute lupus pneumonitis (0.4 %), pulmonary arterial hypertension (0.4 %), and small lung syndrome (0.4 %). While the initial symptomatology was dyspnea with an incidence of 9.6 %, the mean oxygen saturation in the population was 96.87 %. Pleural effusion was identified as the most frequent pulmonary manifestation in radiographic changes. No statistically significant difference was found in antibody levels when comparing the groups. The most common pulmonary manifestation associated with SLE is pleurisy, however, the range of pulmonary manifestations in this type of patient can be very varied, as well as the presentation of each of them.

Amphetamines in child medicine: a review of ClinicalTrials.gov.

Background: Globally, the use of amphetamines as therapeutic agents in pediatric medicine is a crucial area of concern, especially given the population's vulnerability. Methods: On 6 August 2023, a search was conducted on ClinicalTrials.gov using "amphetamine" as the keyword. Two independent examiners screened trials against set criteria, including a focus on amphetamine, completion status, an interventional approach, and included children. Ongoing or observational studies were excluded. Data extracted from the qualified trials encompassed primary objectives, participant counts, study duration, and outcomes, with the aim of analyzing children disorders treated by amphetamine. Results: On 6 August 2023, a search of the ClinicalTrials.gov database with the term "amphetamines" identified 179 clinical trials. After extensive exclusion criteria, 19 trials were ultimately selected for analysis. The predominant condition under investigation was attention deficit hyperactivity disorder (ADHD), present in 84.2% of studies. Key study characteristics included: phase 4 trials (36.8%), randomized allocation (63.2%), and the parallel intervention model (42.1%). Masking techniques varied, with no masking in 42.1% of studies, and double and quadruple masking both accounting for 21.1%. Geographically, 78.9% of the studies' participants were from the United States. Conclusion: This study highlights the notable therapeutic potential of amphetamines in pediatric ADHD populations and emphasizes the importance of recognizing potential side effects and addiction risks. As pharmacogenomics offers the prospect of personalized treatments, there is potential to increase therapeutic efficacy and decrease adverse reactions. It is vital to balance these benefits against the inherent risks, understanding the need for continued research to optimize the use of amphetamines in medicine.

NAFLD and nutraceuticals: a review of completed phase III and IV clinical trials.

Background: Nonalcoholic Fatty Liver Disease (NAFLD) has become a significant public health concern, affecting approximately one-fourth of the population. Despite its prevalence, no FDA-approved drug treatments specifically target NAFLD. Aim: To provide a review of clinical trials investigating the use of herbal remedies and dietary supplements in NAFLD management, utilizing the ClinicalTrials.gov database. Methods: This review evaluates the current evidence by examining completed phase III and IV clinical trials registered on ClinicalTrials.gov. An exhaustive search was performed on April 17, 2023, using the terms "Nonalcoholic Fatty Liver Disease" and "NAFLD." Two independent reviewers appraised eligible trials based on pre-defined inclusion and exclusion criteria. Results: An initial search yielded 1,226 clinical trials, with 12 meeting the inclusion criteria after filtration. The majority of trials focused on Omega-3 fatty acids (20.0%) and vitamin D (26.7%), followed by caffeine, chlorogenic acid, ginger, phosphatidylcholine, Trigonella Foenum-graecum seed extract, vitamin C, and vitamin E (each 6.7%). Most studies were Phase 3 (75.0%) and used a parallel assignment model (91.7%). Quadruple masking was the most prevalent technique (58.3%), and Iran was the leading country in terms of trial locations (25.0%). These interventions constitute two herbal interventions and nine supplement interventions. Conclusion: This reveals a diverse range of nutraceuticals, with Omega-3 fatty acids and vitamin D being predominant in the management of NAFLD. The global distribution of trials highlights the widespread interest in these therapeutics. However, more rigorous, large-scale trials are needed to establish safety, efficacy, and optimal dosages.

Association Between COVID-19 Infection and Cardiac Biomarkers in Hospitalized Patients at a Tertiary Care Center.

Background The effects of coronavirus disease 2019 (COVID-19) on the cardiovascular system are well established. However, knowledge gaps in the clinical implications of cardiac involvement in COVID-19 patients are yet to be addressed. This study aimed to investigate acute cardiac injury (ACI) risk factors and outcomes associated with COVID-19 infection with cardiac involvement. Methodology In this retrospective study, we included hospitalized patients between March 2020 and May 2022 with confirmed COVID-19 infection and evidence of cardiac involvement. Results In total, 501 patients were included, of whom 396 (79%) had evidence of ACI. The median troponin level was 25.8 (interquartile range (IQR) = 10.8-71). Patients with evidence of ACI were significantly more likely to have diabetes mellitus (75% vs. 60%), cardiovascular disease (48% vs. 37%), chronic lung disease (22.2% vs. 12.4%), and chronic kidney disease (32.3% vs. 16.2%). Additionally, patients with ACI were significantly more likely to have cardiomegaly (60.6% vs. 44.8%) and bilateral lobe infiltrates (77.8% vs. 60%) on X-ray. Patients with ACI were significantly more likely to suffer from complications such as cardiogenic shock (5.3% vs. 0%), pneumonia (80.1% vs. 65.7%), sepsis (24.2% vs. 9.5%), and acute respiratory distress syndrome (33.1% vs. 8.6%). Patients with ACI were also significantly more likely to be admitted to the intensive care unit (ICU) (57% vs. 26.7%) and significantly more likely to die (38.1% vs. 11.4%). The results of the multivariate regression analysis indicated that mortality was significantly higher in patients with elevated troponin levels (adjusted odds ratio = 4.73; 95% confidence interval = 2.49-8.98). Conclusions In COVID-19-infected patients, old age, diabetes mellitus, cardiovascular disease, chronic lung disease, and chronic kidney disease were associated with an increased risk of ACI. The presence of ACI in the context of COVID-19 infection was noted to increase the risk for severe complications, such as cardiogenic shock, ICU admission, sepsis, and death.

Structural basis of closed groove scrambling by a TMEM16 protein.

Activation of Ca2+-dependent TMEM16 scramblases induces the externalization of phosphatidylserine, a key molecule in multiple signaling processes. Current models suggest that the TMEM16s scramble lipids by deforming the membrane near a hydrophilic groove, and that Ca2+ dependence arises from the different association of lipids with an open or closed groove. However, the molecular rearrangements involved in groove opening and of how lipids reorganize outside the closed groove remain unknown. Using cryogenic electron microscopy, we directly visualize how lipids associate at the closed groove of Ca2+-bound nhTMEM16 in nanodiscs. Functional experiments pinpoint the lipid-protein interaction sites critical for closed groove scrambling. Structural and functional analyses suggest groove opening entails the sequential appearance of two π-helical turns in the groove-lining TM6 helix and identify critical rearrangements. Finally, we show that the choice of scaffold protein and lipids affects the conformations of nhTMEM16 and their distribution, highlighting a key role of these factors in cryoEM structure determination.

Stereotactic Body Radiation Therapy Salvage for Lymph Node Recurrent Prostate Cancer in the Era of PSMA PET Imaging.

PURPOSE OF REVIEW: Our understanding of patterns of prostate cancer recurrence after primary treatment of localized disease has significantly evolved since the development of positron emission tomography (PET) agents targeting prostate cancer. Previously, most biochemical recurrences were not associated with imaging correlates when restaging with computed tomography (CT), magnetic resonance imaging (MRI), or bone scintigraphy and, hence, were typically assumed to represent occult metastases. A rising prostate specific antigen (PSA) after previous local therapy prompting a PET scan showing uptake limited to regional lymph nodes is an increasingly common clinical scenario as advanced prostate cancer imaging becomes more widely utilized. The optimal management strategy for patients who have lymph node recurrent prostate cancer is both unclear and evolving, particularly in terms of local and regionally directed therapies. Stereotactic body radiation therapy (SBRT) utilizes ablative radiation doses with steep gradients to achieve local tumor control while sparing nearby normal tissues. SBRT is an attractive therapeutic modality due to its efficacy, favorable toxicity profile, and flexibility to administer elective doses to areas of potential occult involvement. The purpose of this review is to briefly describe how SBRT is being implemented in the era of PSMA PET for the management of solely lymph node recurrent prostate cancer. RECENT FINDINGS: SBRT has been shown to effectively control individual lymph node tumor deposits within the pelvis and retroperitoneum for prostate cancer and is well-tolerated with a favorable toxicity profile. However, a major limitation thus far has been the lack of prospective trials supporting the use of SBRT for oligometastatic nodal recurrent prostate cancer. As further trials are conducted, its exact role in the treatment paradigm of recurrent prostate cancer will be better established. Although PET-guided SBRT appears feasible and potentially beneficial, there is still considerable uncertainty about the use of elective nodal radiotherapy (ENRT) in patients with nodal recurrent oligometastatic prostate cancer. PSMA PET has undoubtedly advanced imaging of recurrent prostate cancer, revealing anatomic correlates for disease recurrence that previously went undetected. At the same time, SBRT continues to be explored in prostate cancer with feasibility, a favorable risk profile, and satisfactory oncologic outcomes. However, much of the existing literature comes from the pre-PSMA PET era and integration of this novel imaging approach has led to greater focus on new and ongoing clinical trials to rigorously evaluate this approach and compare to other established treatment modalities utilized for oligometastatic, nodal recurrence of prostate cancer.

Knowledge, Attitude and Practice of Undergraduate Medical Students of Bangladesh Regarding COVID-19 and its Vaccination.

Medical students are one of the socially active, reliable, and persuading population of information, prevention and control, and incentive of vaccination to stop the current pandemic situation. Consequently, knowing the status of medical students' knowledge, about symptoms, and transmission of disease, prevention of COVID-19 and their attitudes towards a vaccine is important. This multi-center cross-sectional descriptive study was one of the first ones in Bangladesh among the undergraduate medical students who completed pathology, microbiology, and pharmacology. The study was conducted from March to April 2021, using a convenience sampling method in twelve government and non-government medical colleges. Among 1132 who completed the questionnaire, and 15 students from different centers were excluded from the pre-testing and face validation. The age of the 1117 respondents were 22 to 23 years, of which the majority of the respondents were female 749 (67.0%), and 368 (33.0%) were male. Almost all participants had correct knowledge (84.1%) about the symptoms of COVID-19. But 59.2% had wrong knowledge about transmission of disease by an afebrile person. Above 60.0 % of the participants have worn a facial mask when contacting people, refrained from shaking hands, washed hands, avoided people with signs and symptoms suggestive of COVID-19, and avoided crowded places as a practice of prevention. 37.6% of medical students showed positive attitudes about the participation of management of a COVID-19 patient. Most of the participants' decided to have a vaccine depending on its availability. But 31.5% had trust in natural immunity rather than vaccination. Most undergraduate Medical college students understood the basic information, possessed a positive attitude, and presented good practice towards the COVID-19 and vaccination. They play a crucial role in motivation and acceptance of vaccines among the general citizen to fight back against the pandemic in the country with limited resources.