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Abstract Background CD55 deficiency with hyper-activation of complement, angiopathic thrombosis, and protein-losing enteropathy (CHAPLE) disease is ultra-rare (

Background: Although studies often report the prevalence of obesity, community-based studies reporting the incidence of overweight or obesity in India are scarce. Such incidence data are crucial for improving projections about the future burden of obesity. Methods: A non-concurrent follow-up study was done in 2015 in urban Vellore, Tamil Nadu, among two groups of women aged 30-40 years, with body mass index (BMI) 25 kg/m2. The incidence of overweight (BMI ≥25 kg/m2) in three years, was 29.2% (24/82), among women with a normal BMI (

Introduction The use and value of artificial intelligence (AI)-driven tools and techniques are under investigation in detecting coronary artery disease (CAD). EchoGo Pro is a patented AI-driven stress echocardiography analysis system produced by Ultromics Ltd. (henceforth Ultromics) to support clinicians in detecting cardiac ischaemia and potential CAD. This manuscript presents the research protocol for a field study to independently evaluate the accuracy, acceptability, implementation barriers, users’ experience and willingness to pay, cost-effectiveness and value of EchoGo Pro.Methods and analysis The ‘Evaluating AI-driven stress echocardiography analysis system’ (EASE) study is a mixed-method evaluation, which will be conducted in five work packages (WPs). In WP1, we will examine the diagnostic accuracy by comparing test reports generated by EchoGo Pro and three manual raters. In WP2, we will focus on interviewing clinicians, innovation/transformation staff, and patients within the National Health Service (NHS), and staff within Ultromics, to assess the acceptability of this technology. In this WP, we will determine convergence and divergence between EchoGo Pro recommendations and cardiologists’ interpretations and will assess what profile of cases is linked with convergence and divergence between EchoGo Pro recommendations and cardiologists’ interpretations and how these link to outcomes. In WP4, we will conduct a quantitative cross-sectional survey of trust in AI tools applied to cardiac care settings among clinicians, healthcare commissioners and the general public. Lastly, in WP5, we will estimate the cost of deploying the EchoGo Pro technology, cost-effectiveness and willingness to pay cardiologists, healthcare commissioners and the general public. The results of this evaluation will support evidence-informed decision-making around the widespread adoption of EchoGo Pro and similar technologies in the NHS and other health systems.Ethics approval and dissemination This research has been approved by the NHS Health Research Authority (IRAS No: 315284) and the London South Bank University Ethics Panel (ETH2223-0164). Alongside journal publications, we will disseminate study methods and findings in conferences, seminars and social media. We will produce additional outputs in appropriate forms, for example, research summaries and policy briefs, for diverse audiences in NHS.

The electrocardiogram (ECG) is a fundamental tool in cardiology, providing invaluable insights into cardiac physiology and detecting various abnormalities. This review article presents a comprehensive overview of ECG interpretation, focusing on the procedure, application, and methodology. The placement of electrodes, ECG paper speed, and measurements of intervals and blocks are discussed in detail. The article emphasizes the importance of a systematic approach to ECG interpretation, highlighting six main sections: determination of heart rhythm, calculation of heart rate, assessment of intervals and blocks, analysis of atrial depolarization patterns, assessment of ventricular depolarization complexes, and delving into the intricate characteristics of ST segments and exploration of the electrocardiographic T-wave manifestations. Specific criteria for identifying abnormalities in each section are provided, along with their associated etiologies and clinical implications. Furthermore, the limitations of ECG as a diagnostic tool are acknowledged, emphasizing the need for clinical correlation and consideration of additional tests. The abstract encapsulates the breadth and depth of the review, conveying the relevance and the profound significance of ECG interpretation in the realm of clinical practice and scientific inquiry.

Background Anxiety has been reported to be one of the most common epidemics in recent years. The present study focused on understanding the association between early menarche and the prevalence of anxiety and anxiety symptoms among adult undergraduate students. Methods This was an observational, case-control study. The sample included 146 young female adults aged more than or equal to 18 years pursuing the Bachelor of Medicine and Bachelor of Surgery (MBBS) and Bachelor of Dental Sciences (BDS). Using an online questionnaire, participants were asked to recall and enter the age at which they attained menarche. We used the Generalized Anxiety Disorder 7- Item Questionnaire (GAD-7) to measure the severity of their present anxiety symptoms. Results The results showed a significant increase in anxiety symptoms in participants who had early menarche compared to those who did not have early menarche. The mean score on the GAD-7 Questionnaire for the cases was 9.93 and the control group was 6.89. The GAD-7 scores among the cases group were significantly higher in the GAD-7 scores than in the control group. Conclusions This study concluded that early menarche is associated with higher anxiety levels in young adults.

Background There has been increasing emphasis towards adopting strengths-based practice (SBP) within adult social care in England. Whilst there is agreement that SBP is the right approach to discharge adult social care duties, there is limited evidence regarding the implementation of SBP. This paper presents findings from the evaluation of the implementation of SBP in fourteen local authorities in one region in England. Methods We employed a mixed methods research design, drawing on data from a scoping review, 36 interviews with practice leaders and two surveys, one with wider adult social care staff and the other, with external organisations like independent care providers and community and voluntary organisations. Our data collection and analysis were guided by two well established implementation theories: the Consolidated Framework for Implementation Research (CFIR) and Normalisation Process Theory (NPT). Interviews were analysed deductively, and surveys were analysed descriptively. Results Local authorities are at different stages in their implementation journey. The Care Act 2014 and support for SBP demonstrated by key professional groups were seen as major drivers for implementing SBP. Whilst SBP resonated with the professional principles of social workers and occupational therapists, staff did not always have the confidence and skills to adapt to SBP. Changing paperwork and recording systems, providing training opportunities to develop staff competencies, establishing new care pathways, genuine co-production, and senior management buy-in were key enablers supporting implementation. Conclusions To successfully implement SBP, a whole system approach that meaningfully collaborates with key professionals across sectors is essential. When implemented well, SBP has the potential to empower individuals by focusing on what matters to them.

In the 21st century, impact of social media, particularly Social Networking Sites (SNSs) has been linked to a wide range of human beliefs and expectations. Growing body of research has indicated that body image concerns along with exercise motivation and social comparison are on the rise among young adults. The present study aimed to examine the sex difference in body image, exercise motivation and social comparison among people who use Instagram in the age group 20-30. A total of 212 participants (men=106, women=106) aged 20-30 years, who are users of Instagram completed Body Self Image Questionnaire Short Form as a measure of Body image, Exercise Motivation Inventory – 2 as a measure of Exercise Motivation and Instagram as a Tool for Social Comparison as a measure of Social Comparison. Results showed that a significant difference in body image exist across gender with body image issues higher among females and significant difference in exercise motivation across gender with exercise motivation higher among males. No sex differences were seen in social comparison. It was concluded that body image concerns are higher among females and the drive for exercise is higher among males who used Instagram. It was found that body image concerns were higher among people who exercised regularly as well as among those who followed fitness related pages on Instagram as compared to those who did not. These results provide an insight into the sex differences between the variables and future directions can be aimed at conducting an in-depth analysis using body image, exercise motivation and social comparison.

Introduction: Cannabis is one of the most widely used psychoactive substances globally, with an increasing trend in its legalization for both medical and recreational purposes in various countries. While cannabis offers potential therapeutic benefits, its regular use can lead to the development of Cannabis Use Disorders (CUDs). Understanding the epidemiology of CUDs is crucial in assessing the public health burden associated with cannabis use. Methods: Epidemiological parameters of CUDs were assessed using the Global Burden of Disease (GBD) methodology across different age-groups, years, sexes, and locations worldwide from 1990-2019. Results: Globally, for both sexes combined, prevalent cases of CUDs increased steadily from 17.1 million(95%UI=12.7-22.8million) in 1990 to 23.8-million(95%UI=17.8-30.9 million) in 2019. All age-adjusted highest number of incidence observed in High-Income-North-America(HINA)(121/100,000), followed by Australasia(100/100,000), Oceania(83.97/100,000), Tropical Latin America(69.59/100,000). Globally, age-standardized disability-adjusted life years rate(ASDR) observed higher in HINA, followed by Australasia, and Western-Europe. In male, all-age incidence counts increased from 1.7 million(95%UI=1.3-2.4million) in 1990 to 2.4 million(95%UI=1.8-3.2 million) in 2019. The highest annual percentage of change in age-standardized incidence rate(ASIR) was found in East-Asia (22%) followed by Middle-East and North-Africa(MENA)(15%). The age group of 15-24 years exhibited the highest burden of CUDs. Conclusion: The widespread occurrence of CUDs on a global scale poses a substantial challenge to public health. Understanding the impact of CUDs and implementing evidence-based interventions is crucial in mitigating the associated individual, societal, and economic burdens. Continued research, collaboration, and knowledge dissemination are essential to inform policies, prevention efforts, and treatment strategies aimed at addressing CUDs on a global-scale.

The human gut microbiota forms a biome and acts as a neglected organ, playing vital roles in organ integrity, metabolism, immunity, and homeostasis. Variations in the microbiome can lead to disease initiation. Research using bacterial sequencing of faeces and digestive tissues has focused on understanding the role of gut microbiota in cancer development, particularly Colorectal Cancer (CRC), Dysbiosis and modifications in the intestinal microbiota have been observed in CRC cases. Hypotheses like the alpha bug hypothesis and the driver-passenger model aim to explain the correlation between gut microbiota and CRC pathogenesis. The present article summarise the functions of gut microbiota, mechanisms involved in colorectal carcinogenesis, and discusses the clinical significance of gut microbiota in CRC screening and therapy.

Background Rational prescription writing is an important skill to master during internship. This Quality Improvement (QI) project aimed to understand the state of prescription writing among interns posted in the Department of Psychiatry, analyze the causes responsible for errors in prescription writing and bring about a change in the current practice. Methods The MBBS interns are posted in the Department of Psychiatry for 15 days. During day 1 to day 5 of their posting, a pre intervention phase was conducted wherein prescriptions written by interns in the Department of Psychiatry were collected. The prescriptions were scored based on 14 criteria which were selected based on World Health Organization (WHO) guidelines and Medical Council of India (MCI) ideal prescription format. During PDSA (Plan Do Study Act) Cycle 1, an educational handout was distributed to the interns containing the MCI ideal prescription format and WHO guidelines regarding prescription writing. The brochure was also verbally explained to the interns. From day 7 to day 15 of their posting, prescriptions written by the interns were collected. The prescriptions were scored using the same criteria. Results During the pre intervention phase the mean total score of prescriptions was 9.54 ± 1.003. There was a significant improvement in the mean total score to 10.26 ± 0.746. There was a 7.54% improvement. There was also a significant improvement in several individual criteria. Conclusions The first PDSA cycle was successful in improving the quality of prescription writing among interns posted in the Department of Psychiatry. There is a need to implement more PDSA cycles to improve the quality still further.

Bromocriptine (BCR) presents poor bioavailability when administered orally because of its low solubility and prolonged first-pass metabolism. This poses a significant challenge in its utilization as an effective treatment for managing Parkinson’s disease (PD). The utilization of lipid nanoparticles can be a promising approach to overcome the limitations of BCR bioavailability. The aim of the research work was to develop and evaluate bromocriptine-loaded solid lipid nanoparticles (BCR-SLN) and bromocriptine-loaded nanostructured lipid carriers (BCR-NLC) employing the Box-Behnken design (BBD). BCR-SLNs and BCR-NLCs were developed using the high-pressure homogenization method. The prepared nanoparticles were characterized for particle size (PS), polydispersity index (PDI), and entrapment efficiency (EE). In vitro drug release, cytotoxicity studies, in vivo plasma pharmacokinetic, and brain distribution studies evaluated the optimized lipid nanoparticles. The optimized BCR-SLN had a PS of 219.21 ± 1.3 nm, PDI of 0.22 ± 0.02, and EE of 72.2 ± 0.5. The PS, PDI, and EE of optimized BCR-NLC formulation were found to be 182.87 ± 2.2, 0.16 ± 0.004, and 83.57 ± 1.8, respectively. The in vitro release profile of BCR-SLN and BCR-NLC showed a biphasic pattern, immediate release, and then trailed due to the sustained release. Furthermore, a pharmacokinetic study indicated that both the optimized BCR-SLN and BCR-NLC formulations improve the plasma and brain bioavailability of the drug compared to the BCR solution. Based on the research findings, it can be concluded that the BCR-loaded lipid nanoparticles could be a promising carrier by enhancing the BBB penetration of the drug and helping in the improvement of the bioavailability and therapeutic efficacy of BCR in the management of PD.

Background The pyramidalis muscle is a tiny triangular-shaped muscle that is located in the anterior abdominal wall, which originates from the body of the pubis and pubic symphysis and is inserted into linea alba. This study aimed to measure the different parameters of the pyramidalis muscle in adult cadavers. Methods This study was carried out on 31 adults (26 males and five females) 10% formalin embalmed cadavers of both sexes from the Department of Anatomy at Kasturba Medical College, Manipal. Results The mean length of the right pyramidalis muscle was 64.44 ± 12.52 mm and the left pyramidalis muscle was 64.73 ± 12.81 mm. The mean width of the muscle was 15 ± 4.18 mm and 15.03 ± 3.52 mm on the right and left sides, respectively. The mean thickness of the muscle was 1.32 ± 0.55 mm and 1.4 ± 0.80 mm on the right and left sides, respectively. The distance between the umbilicus to pubic symphysis ranged from 130–192 mm and their mean was calculated to be 159.77 ± 15.36. The distance between the umbilicus and the apex of the muscle ranged from 72–123 mm. Conclusions The measured parameters like length, width and thickness may help the surgeons to locate the muscle during infra umbilical surgeries.

Background: The pyramidalis muscle is a tiny triangular-shaped muscle that is located in the anterior abdominal wall, which originates from the body of the pubis and pubic symphysis and is inserted into linea alba. This study aimed to measure the different parameters of the pyramidalis muscle in adult cadavers. Methods: This study was carried out on 31 adults (26 males and five females) 10% formalin embalmed cadavers of both sexes from the Department of Anatomy at Kasturba Medical College, Manipal. Results: The mean length of the right pyramidalis muscle was 64.44 ± 12.52 mm and the left pyramidalis muscle was 64.73 ± 12.81 mm. The mean width of the muscle was 15 ± 4.18 mm and 15.03 ± 3.52 mm on the right and left sides, respectively. The mean thickness of the muscle was 1.32 ± 0.55 mm and 1.4 ± 0.80 mm on the right and left sides, respectively. The distance between the umbilicus to pubic symphysis ranged from 130–192 mm and their mean was calculated to be 159.77 ± 15.36. The distance between the umbilicus and the apex of the muscle ranged from 72–123 mm. Conclusions: The measured parameters like length, width and thickness may help the surgeons to locate the muscle during infra umbilical surgeries.

Context: The foramen ovale is an obliquely placed, oval-shaped opening at the base of the skull in the greater wing of sphenoid. As the foramen transmits mandibular nerve, accessory meningeal artery, lesser petrosal nerve, and emissary veins, it knowledge of its variations is of supreme interest for surgeons. Aims: The aim of this study is to study the metric and nonmetric variations, of the foramen ovale of 40 dry adult human dried skulls. Settings and Design: The study was conducted in the dissection hall of Chettinad Academy of Research and Education. The study undertaken here is an observational study. Subjects and Methods: Human skulls were studied for location, patency, and various morphometric parameters bilaterally. The materials used were thin copper wire and a digital Vernier caliper of precision 0.01 mm. Statistical Analysis Used: Metric and nonmetric data were analyzed using the SPSS software. Results: The shape of foramen ovale was D shaped in most of the skulls (35%) followed by almond (21%), elongated oval (15%), and oval shape (11%). The presence of bony variations like spur was seen in 27.5% foramina, bony septa in 3.75%, and duplication in 21.25% foramina. The mean length and width of foramen ovale were 6.51 ± 1.24 mm and 3.66 ± 0.82 mm on right and 6.59 ± 1.33 mm and 3.75 ± 0.68 mm on the left, respectively. The mean area of foramen ovale was 19.08 ± 5.71 mm2 and 17.88 ± 5.85 mm2 on the right and the left, respectively. Conclusions: A sound knowledge on the morphometric variations of the foramen ovale helps the operating surgeon to avoid damage to the adjacent structures.

Traumatic acute cervical spinal cord injury (ACSCI) often presents with non-emergent coexisting injuries, which might need surgical intervention. The ACSCI affects multiple systems including respiratory, cardiovascular, and neurological systems, which pose a great challenge to the treating anesthesiologist. The ideal time and anesthetic technique for non-emergent surgeries following ACSCI is not clear. Maintenance of mean arterial blood pressure between 85 and 90 mmHg for 7 days following spinal cord injury would improve the outcome. The secondary injury peaks at 4–6 days following the primary cord injury. Considering the above-mentioned factors, the non-emergent procedures could be performed after the seventh day following an injury of the spinal cord. Regional anesthesia (RA) (diaphragm sparing supraclavicular block (SCB)) edges over general anesthesia (GA), as the manipulation of the cervical spine could be avoided and it also provides stable cardiac and respiratory dynamics. In this case report, we are discussing about a case of conservatively managed ACSCI posted for left humerus plating. We conclude that ultrasound-guided diaphragm sparing SCB is a safe alternative to GA for ACSCI patients posted for upper limb surgeries in neurogenic shock.

Since 2013, the US Centers for Disease Control and Prevention has offered the Public Health Emergency Management Fellowship to health professionals from around the world. The goal of this program is to build an international workforce to establish public health emergency management programs and operations centers in participating countries. In March 2021, all 141 graduates of the fellowship program were invited to complete a web survey designed to examine their job roles and functions, assess their contributions to their country’s COVID-19 response, and identify needs for technical assistance to strengthen national preparedness and response systems. Of 141 fellows, 89 successfully completed the survey. Findings showed that fellowship graduates served key roles in COVID-19 response in many countries, used skills they gained from the fellowship, and desired continuing engagement between the Centers for Disease Control and Prevention and fellowship alumni to strengthen the community of practice for international public health emergency management.

Tissue-resident stem and progenitor cells are present in many adult organs, where they are important for organ homeostasis and repair in response to injury. However, the signals that activate these cells and the mechanisms governing how these cells renew or differentiate are highly context-dependent and incompletely understood, particularly in non-hematopoietic tissues. In the skin, melanocyte stem and progenitor cells are responsible for replenishing mature pigmented melanocytes. In mammals, these cells reside in the hair follicle bulge and bulb niches where they are activated during homeostatic hair follicle turnover and following melanocyte destruction, as occurs in vitiligo and other skin hypopigmentation disorders. Recently, we identified melanocyte progenitors in adult zebrafish skin. To elucidate mechanisms governing melanocyte progenitor renewal and differentiation we analyzed individual transcriptomes from thousands of melanocyte lineage cells during the regeneration process. We identified transcriptional signatures for progenitors, deciphered transcriptional changes and intermediate cell states during regeneration, and analyzed cell–cell signaling changes to discover mechanisms governing melanocyte regeneration. We identified KIT signaling via the RAS/MAPK pathway as a regulator of melanocyte progenitor direct differentiation and asymmetric division. Our findings show how activation of different subpopulations of mitfa-positive cells underlies cellular transitions required to properly reconstitute the melanocyte pigmentary system following injury.

Disparities in HIV incidence and PrEP uptake suggest a need to prioritize Black sexual minority men (SMM) in PrEP social marketing initiatives. However, images linking Black SMM to HIV and PrEP may inadvertently reinforce stigma. We examined HIV-negative/status-unknown Black SMM's responses to targeted PrEP advertisements using mixed methods, including an experiment embedded in a longitudinal online survey (Time 1: n = 96; Time 2 [eight weeks]: n = 73) and four focus groups (n = 18). The full factorial experiment included between-groups and within-subjects comparisons. For between-groups comparisons, each participant was randomly assigned to view one of 12 advertisements, which varied by couple composition (Black SMM couple/Black heterosexual couple/multiple diverse couples/no couples) and campaign (PrEPare for the Possibilities/PlaySure/PrEP4Love). We examined couple composition, campaign, and interaction effects on: advertisement judgments (Time 1), PrEP stigma (Time 1), PrEP motivation (Times 1 and 2), and PrEP behavior (Time 2). For within-subjects comparisons, each participant viewed all 12 advertisements, and we examined couple composition, campaign, and interaction effects on advertisement judgments (Time 2). Focus group participants discussed advertising preferences and responded to the same set of advertisements. For between-groups and within-subjects comparisons, we found significant couple composition effects but no or limited campaign and interaction effects on advertisement judgments. Advertisements featuring Black SMM exclusively were judged as more stigmatizing than advertisements without couples. Advertisements with diverse (vs. no) couples were considered more eye-catching and motivating. There were minimal effects of couple composition and campaign on PrEP stigma, motivation, and behavior. Focus group participants corroborated concerns about the potential for PrEP advertisements to be stigmatizing, suggesting advertisements featuring Black SMM exclusively could be alienating and fuel conspiracy theories. Focus group participants generally favored diverse and less sexualized advertisements, particularly for public spaces. Findings collectively highlight the potential for targeted PrEP advertisements to stigmatize Black SMM and support diverse representation.

Introduction: In adult patients seeking orthodontic treatment, some common reasons include unesthetic appearance and functional impairment such as difficulty in speaking or breathing. Thus, malocclusion and orthodontic care have become a Quality of Life (QoL) issue. Aim: To investigate the oral health-related quality of life in adults before and after orthodontic treatment. Materials and Methods: This quasi-experimental study was conducted in Faculty of Dental Sciences, M.S. Ramaiah University of Applied Sciences, Bangalore, India over a two year period from December 2014 to October 2016. Finally, 34 patients were included in the study. Longitudinal data which included OHRQoL (Oral Health-Related Quality of Life) and study casts for assessing the outcome by the Peer Assessment Rating (PAR) index was collected from two periods: (i) pretreatment data (T1), and (ii) post-treatment data (T2) collected one month after fixed orthodontic appliance debonding. Pretreatment and post-treatment Oral Health Impact Profile (OHIP-14) and PAR scores were compared using Paired t-test. Correlations between occlusal indices (PAR) and OHRQoL (OHIP-14) were determined by Spearman’s rank correlation coefficient. Results: Total of 42 patients were included in the study, out of which 34 patients responded to the questionnaire in which 11 were males and 23 females in the age range 18-30 years. From pre to postorthodontic treatment mean OHIP-14 summary score had significantly improved (score reduced) from 30.3 to 16.0. Similarly, mean PAR scores had reduced from 17.62 to 3.44. Significant correlation (p-value

Introduction: Micro-osteoperforation (MOP) and Low Level Laser Therapy (LLLT) are rapidly gaining popularity in clinical practice due to their proven success in accelerating tooth movement and acceptable patient compliance. However, literature shows an inconsistent and variable evidence of their iatrogenic effects on the root and pulp due to biological variations of the samples chosen by the previous studies. Aim: To evaluate and compare the rate of tooth movement, changes in amount of external root resorption and pulp vitality in teeth during en masse anterior retraction associated with MOP and LLLT using split mouth technique. Materials and Methods: This was a double blinded, single centre split mouth randomised clinical trial conducted at Faculty of Dental Sciences, MS Ramaiah University of Applied Sciences, Bangalore, Karnataka, India from March 2019 to October 2019. Total of 11 patients with bimaxillary dentoalveolar protrusion which required all four first premolar extractions were included in the study. Nickel Titanium (NiTi) closed coil springs were used for en masse retraction in upper and lower arches with force of 150 g per side. Root resorption of all anterior teeth was evaluated using Cone Beam Computed Tomography systems (CBCT) and pulp vitality was checked using cold test after four months. The data was entered in Microsoft excel and the Statistical Package for Social Sciences software (SPSS) version 18.5 (SPSS Inc, Chicago) software was used for data entry and statistical analysis. A p-value of less than 0.05 was considered as statistically significant. Results: Total of 11 patients in which 9 were females and 2 males aged between 18-30 years with mean age 19±4.21 year, participated in this trial. LLLT (4 mm) and MOP (4.05 mm) showed similar performance in acceleration of tooth compared to each other. The overall root resorption was more in the experimental groups (LLLT- 2.60 mm, MOP- 2.84 mm) compared to the allotted controls. However, the canine showed less root resorption in both the experimental groups compared to the control. The overall root resorption was similar in both the experimental groups. The canine in LLLT group (0.30 mm) showed less root resorption compared to canine in MOP group (0.59 mm). There was no change in the pulp vitality status in both the experimental groups and the control groups. Conclusion: The overall root resorption in a given quadrant increases with increased rate of tooth movement. The tooth which was subjected to acceleratory orthodontic technique showed less root resorption compared to control. The tooth subjected to LLLT showed less root resorption as compared to the tooth subjected to MOP.

Introduction: Knowledge of transverse dentofacial dimensions is crucial for accurate diagnosis and treatment planning. Periodontitis can alter the widths of the arches by causing pathological migration of teeth and the concurrent bone loss can affect the transverse width of the arches. Aim: To compare the transverse dentofacial widths in adults with skeletal class I and class II malocclusions with horizontal growth pattern and with mild to moderate periodontitis using Cone Beam Computed Tomography (CBCT). Materials and Methods: This retrospective observational study was conducted in Department of Orthodontics, Faculty of Dental Sciences, Ramaiah University of Applied Sciences, Bengaluru, Karnataka, India, from January 2019 to January 2021. Total 96 CBCT samples (48 skeletal Class I, 48 skeletal Class II) of patients between age group of 25-35 years, patients having mild to moderate periodontitis based on bone loss seen on CBCT and patients having a horizontal growth pattern with the angle between sella-nasion and mandibular plane less than 32° were included in the study. Transverse dentofacial measurements were made on the coronal plane of the CBCT scans. Data were analysed using Statistical Package for Social Sciences (SPSS) version 20. Chi-square test and Student’s t-test were used to compare age, linear measurements and angular measurements between the skeletal class I and skeletal Class II groups. A p-value of

SARS-CoV-2 vaccinations were initially shown to substantially reduce risk of severe disease and death. However, pharmacokinetic (PK) waning and rapid viral evolution degrade neutralizing antibody (nAb) binding titers, causing loss of vaccinal protection. Additionally, there is inter-individual heterogeneity in the strength and durability of the vaccinal nAb response. Here, we propose a personalized booster strategy as a potential solution to this problem. Our model-based approach incorporates inter-individual heterogeneity in nAb response to primary SARS-CoV-2 vaccination into a pharmacokinetic/pharmacodynamic (PK/PD) model to project population-level heterogeneity in vaccinal protection. We further examine the impact of evolutionary immune evasion on vaccinal protection over time based on variant fold reduction in nAb potency. Our findings suggest viral evolution will decrease the effectiveness of vaccinal protection against severe disease, especially for individuals with a less durable immune response. More frequent boosting may restore vaccinal protection for individuals with a weaker immune response. Our analysis shows that the ECLIA RBD binding assay strongly predicts neutralization of sequence-matched pseudoviruses. This may be a useful tool for rapidly assessing individual immune protection. Our work suggests vaccinal protection against severe disease is not assured and identifies a potential path forward for reducing risk to immunologically vulnerable individuals.

OBJECTIVES/GOALS: Sex differences in aortic stenosis (AS) are vastly underestimated, contribute to disparities in treatment and worse outcomes for women including disproportionately higher mortality rates. This study aims to investigate sex differences in extent of cardiac damage (CD) from pressure overload in AS that may help account for the observed disparities. METHODS/STUDY POPULATION: CD in AS refers to a series of pathologic changes in the myocardium that occur due to chronic pressure overload imposed on the left ventricle by a progressively stenotic aortic valve (AV). These changes are associated with poor outcomes and lower survival in patients with AS. To acquire a deeper understanding of the factors and mechanisms affecting differences in the long-term survival and management of patients with AS, we are proposing to assess baseline stage of CD on echocardiography, and changes in transvalvular hemodynamics and CD stage (Δ CD) over time, in patients with moderate and severe AS at one of 2 large tertiary-care hospitals in MA. We also plan to assess time to and performance of aortic valve replacement (AVR), stratified by hemodynamic severity of stenosis and CD stage, and their interaction with sex. RESULTS/ANTICIPATED RESULTS: We hypothesize that women will have a higher stage of CD on their initial echocardiogram (TTE), demonstrating moderate or greater severity of AS, than men with the same hemodynamic severity of valvular stenosis. We additionally hypothesize that those with more advanced cardiac damage stage will likely have masking of transvalvular progression on echocardiogram. Finally, we anticipate that women will have AVR performed less frequently than men and will have minimal improvement in their Kansas City Cardiomyopathy Questionnaire (KCCQ) scores post-AVR indicative of more heart failure symptoms and a lower quality of life. DISCUSSION/SIGNIFICANCE: This study will seek to better understand sex-based differences in extent of cardiac damage to pressure overload in aortic stenosis (AS) to minimize treatment and outcome disparities for women and allow for more individualized and patient-centered care.

Abstract Articular cartilage is built by chondrocytes which become less active with age. This declining function of the chondrocytes, together with the avascular nature of the cartilage, impedes the spontaneous healing of chondral injuries. These lesions can progress to more serious degenerative articular conditions as in the case of osteoarthritis. As no efficient cure for cartilage lesions exist yet, cartilage tissue engineering has emerged as a promising method aiming at repairing joint defects and restoring articular function. In the present work, we investigated if a new self-assembling peptide (referred as IEIK13), combined with articular chondrocytes treated with a chondrogenic cocktail (BMP-2, insulin and T3, designated BIT) could be efficient to restore full-thickness cartilage defects induced in the femoral condyles of a non-human primate model, the cynomolgus monkey. First, in vitro molecular studies indicated that IEIK13 was efficient to support production of cartilage by monkey articular chondrocytes treated with BIT. In vivo, cartilage implant integration was monitored non-invasively by contrast-enhanced micro-computed tomography, and then by post-mortem histological analysis and immunohistochemical staining of the condyles collected 3 months post-implantation. Our results revealed that the full-thickness cartilage injuries treated with either IEIK13 implants loaded with or devoid of chondrocytes showed similar cartilage-characteristic regeneration. This pilot study demonstrates that IEIK13 can be used as a valuable scaffold to support the in vitro activity of articular chondrocytes and the repair of articular cartilage defects, when implanted alone or with chondrocytes.

Introduction: Ultrasonography has revived the infraclavicular approach to brachial plexus block resulting in many studies available in the literature. However, very few studies have assessed the sensory block characteristics of individual nerve territories by this approach. Aim: To compare the supraclavicular with the infraclavicular approach with special emphasis on the assessment of block characteristics of each nerve domain. Materials and Methods: This randomised clinical trial was conducted on 40 patients of American Society of Anaesthesiologist (ASA) physical status I and II, aged between 20-60 years of age undergoing elective surgical procedures of the upper limb. They were randomly allocated into either group Supraclavicular (SC group) or Infraclavicular (IC group). Ultrasound-guided block was performed using 30 mL of 0.25% bupivacaine. The primary outcome measure was the efficacy of block, and the secondary outcome was the time taken for performance of block. Categorical variables were compared with the Chi-square test or Fisher’s-exact test. Continuous variables were analysed using the unpaired t-test. The p-value

Cervicofacial botryomycosis is a chronic, granulomatous suppurative infection with varied presentations in the head and neck region. Since the discovery of this entity, treatment has been elusive without evidence of complete resolution of the lesion with a long period of follow-up. Here the authors report a case of cervicofacial botryomycosis with oral manifestations in a 37-year-old male patient with a history of trauma, for whom the authors devised a treatment plan tailored to the patient’s microbiological profile after culture and sensitivity testing in addition to systemic and local antibiotic therapy and heat therapy which showed drastic regression of the lesion and an improved mouth opening. The patient has been under follow-up for the past four years without signs of recurrence. Botryomycosis is an aggressive lesion where a surgery-only approach is usually futile and requires further intervention due to recurrences. The present experience suggests surgical debridement along with antibiotic and local heat therapy to be effective in managing this usually recurring lesion.

As the COVID-19 pandemic drags into its second year, there is hope on the horizon, in the form of SARS-CoV-2 vaccines which promise disease suppression and a return to pre-pandemic normalcy. In this study we critically examine the basis for that hope, using an epidemiological modeling framework to establish the link between vaccine characteristics and effectiveness in bringing an end to this unprecedented public health crisis. Our findings suggest that a return to pre-pandemic social and economic conditions without fully suppressing SARS-CoV-2 will lead to extensive viral spread, resulting in a high disease burden even in the presence of vaccines that reduce risk of infection and mortality. Our modeling points to the feasibility of complete SARS-CoV-2 suppression with high population-level compliance and vaccines that are highly effective at reducing SARS-CoV-2 infection. Notably, vaccine-mediated reduction of transmission is critical for viral suppression, and in order for partially-effective vaccines to play a positive role in SARS-CoV-2 suppression, complementary biomedical interventions and public health measures must be deployed simultaneously.

16S rRNA gene sequencing of DNA extracted from clinically uninfected hip and knee implant samples has revealed polymicrobial populations. However, previous studies assessed 16S rRNA gene sequencing as a technique for the diagnosis of periprosthetic joint infections, leaving the microbiota of presumed aseptic hip and knee implants largely unstudied. These communities of microorganisms might play important roles in aspects of host health, such as aseptic loosening. Therefore, this study sought to characterize the bacterial composition of presumed aseptic joint implant microbiota using next generation 16S rRNA gene sequencing, and it evaluated this method for future investigations. 248 samples were collected from implants of 41 patients undergoing total hip or knee arthroplasty revision for presumed aseptic failure. DNA was extracted using two methodologies-one optimized for high throughput and the other for human samples-and amplicons of the V4 region of the 16S rRNA gene were sequenced. Sequencing data were analyzed and compared with ancillary specific PCR and microbiological culture. Computational tools (SourceTracker and decontam) were used to detect and compensate for environmental and processing contaminants. Microbial diversity of patient samples was higher than that of open-air controls and differentially abundant taxa were detected between these conditions, possibly reflecting a true microbiota that is present in clinically uninfected joint implants. However, positive control-associated artifacts and DNA extraction methodology significantly affected sequencing results. As well, sequencing failed to identify Cutibacterium acnes in most culture- and PCR-positive samples. These challenges limited characterization of bacteria in presumed aseptic implants, but genera were identified for further investigation. In all, we provide further support for the hypothesis that there is likely a microbiota present in clinically uninfected joint implants, and we show that methods other than 16S rRNA gene sequencing may be ideal for its characterization. This work has illuminated the importance of further study of microbiota of clinically uninfected joint implants with novel molecular and computational tools to further eliminate contaminants and artifacts that arise in low bacterial abundance samples.

A60-year-old man came to the orthopedics department with swelling of the entire right foot with multiple painful nodules, which oozed pus and blood intermittently for 25 years [Figure 1]. This caused disability and daily limitations to his lifestyle. He had presented with this complaint several times and was referred to a tertiary care center. Examination of the foot showed a swollen foot and ankle with multiple subcutaneous nodules and draining sinuses.

Tumors are composed of many different cell types including cancer cells, fibroblasts, and immune cells. Dissecting functional metabolic differences between cell types within a mixed population can be challenging due to the rapid turnover of metabolites relative to the time needed to isolate cells. To overcome this challenge, we traced isotope-labeled nutrients into macromolecules that turn over more slowly than metabolites. This approach was used to assess differences between cancer cell and fibroblast metabolism in murine pancreatic cancer organoid-fibroblast co-cultures and tumors. Pancreatic cancer cells exhibited increased pyruvate carboxylation relative to fibroblasts, and this flux depended on both pyruvate carboxylase and malic enzyme 1 activity. Consequently, expression of both enzymes in cancer cells was necessary for organoid and tumor growth, demonstrating that dissecting the metabolism of specific cell populations within heterogeneous systems can identify dependencies that may not be evident from studying isolated cells in culture or bulk tissue.

Abstract Background The prevalence of menopause in women with or at risk of chronic kidney disease is increasing globally. Although international guidelines on menopause recommend the use of postmenopausal hormone therapy with or without selective estrogen receptor modulators for control of vasomotor symptoms, the effects of these treatments on kidney function and albuminuria are unclear. Furthermore, women with chronic kidney disease are at significantly increased risk of venous thromboembolism and malignancy, well-documented adverse effects of postmenopausal hormone therapy. Our study aims to establish the effect of these treatments on kidney function and albuminuria in women, as well as determine the safety of these treatments in the chronic kidney disease population. Methods We will conduct a systematic review and meta-analysis addressing the effect and safety of postmenopausal hormone therapy and selective estrogen receptor modulators on kidney outcomes in women. We plan to search for published (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), tables of contents of relevant journals) and unpublished (ongoing studies, conference proceedings) studies in all languages examining the effect of postmenopausal hormone therapy, including selective estrogen receptor modulators, on kidney function and albuminuria, as well as the risk of adverse outcomes of these treatments in women with chronic kidney disease. Two independent investigators will screen identified abstracts and select studies that examine the effect of postmenopausal hormone therapy and selective estrogen receptor modulators on kidney outcomes in the general population or adverse outcomes in the chronic kidney disease population. Data on study population, intervention, outcomes, as well as study quality and risk of bias will be independently extracted from each eligible study. Along with descriptive presentation of data, outcome measures will be presented as meta-analyses using a random effects model. Planned subgroup analyses will be completed, and meta-regression will be performed if significant heterogeneity is noted. Discussion By examining the effects of postmenopausal hormone therapy and selective estrogen receptor modulators on kidney function and albuminuria, the results of this systematic review and meta-analysis will inform management of postmenopausal women in the general population. Furthermore, it will evaluate the safety, including the risks of known adverse outcomes of postmenopausal hormone therapy and selective estrogen receptor modulators, in the already vulnerable chronic kidney disease population. Systematic review registration PROSPERO CRD42016050651

Background: Herein we report a rare case of acute liver failure due to levetiracetam, which has been considered to have an excellent safety profile with minimal hepatic side effects. Case presentation: A 55-year-old male patient presenting with sudden onset dizziness, slurring of speech and headache was operated for posterior fossa cerebellar hematoma. His post-surgical period was complicated by development of icterus with elevation of liver enzymes. After ruling out common inciting factors, it was decided to stop levetiracetam which was given prophylactically for preventing seizures owing to presence of external ventricular drain. From the next day patient had dramatic improvement in liver functions and sensorium. Conclusions: We would like to highlight this side effect that is potentially life threatening, though rare, of levetiracetam, which is very commonly used in today’s practice and fast superseding all other time-tested antiepileptics.

A24-year-old married woman presented to the outpatient clinic with abdominal pain and weight and appetite loss lasting a few months. The abdomen appeared soft on clinical examination, with a palpable midline mass eliciting fluid thrill, corresponding to 32 weeks gestation.

Invasive Candidal infections have emerged as one of the major threats to the world. Although, many new antifungal drugs have been developed in the recent years, the emergence of drug resistance has become a major deterrent in the antifungal therapy. Candida develops several molecular mechanisms to resist the exposure to antifungal drugs. Prolonged treatment in patients may trigger development of resistance to the prescribed drugs. Most of the antifungal therapeutic agents being fungistatic rather than fungicidal are the key reason for selection of resistant Candida strains. Overexpression or mutation of the target enzymes as well as transcriptional activation of genes encoding the drug efflux pumps of ATP Binding Cassette (ABC) and Major Facilitator Superfamilies (MFS) are some of the factors implicated in the development of drug resistance. Basic understanding of the underlying molecular mechanisms of antifungal drug resistance and their clinical impact is vital in planning of the effective management of Candidal infections. There is an interesting possibility of antifungal resistance in Candida becoming a marker in the assessment of the outcome of antifungal therapy in the future. This review describe and summarises the molecular mechanisms of drug resistance in candida species.

Introduction: Application of orthodontic forces to a tooth is characterised by extensive macroscopic and microscopic changes during remodelling which occurs in the Periodontal Ligament (PDL), alveolar bone and gingiva. This occurs mainly due to the local stresses and strains subjected on the supporting tissues. As direct measurement of these parameters is almost impossible, Finite Element Method (FEM) is an effective method for calculating stress and strain distribution on the alveolar bone. Aim: To assess the stress and strain distribution in the cortical and cancellous bone around maxillary central incisors during the process of diastema closure with a constant force using FEM. Materials and Methods: A three-dimensional computer model of anterior segment of the maxilla simulated from a CBCT scan was reproduced using MIMICS software and they had varying width of midline diastema of 4 mm, 3 mm and 2 mm. Each tooth was designed with a bracket on the labial surface and a 0.019×0.025 orthodontic stainless steel wire. A 1.5 N of force was applied on the labial surface of the brackets. Stresses and strains around the two central incisors on the alveolar bone were calculated. Results: In the cortical bone, maximum compressive stress (Von-Mises stress) was concentrated at the mesial side and tensile stress (principle stress) on the distal side near the cervical region of the central incisors in all the 3 models. Maximum stress was seen in the 2mm midline diastema model. In the cancellous bone, both these stresses were concentrated along the roots of central incisor cavity more towards the middle of the tooth in all the 3 models. In the longitudinal section, stress and strain was more concentrated at the cervical region gradually decreasing as they reached apex of the tooth in cortical bone and in the cancellous bone maximum stress was observed in the middle third. Conclusion: Stresses in the cortical bone increases when the diastema gap is small while strain in cancellous bone increases when the midline diastema width is large. The stresses in cancellous bone remain constant in all the 3 models. Graphically the strains were more concentrated near cervical region of the teeth in both the cortical and in cancellous bone maximum stress was observed in the middle third.

Using a nuclease-dead Cas9 mutant, we show that Cas9 reproducibly induces chromatin accessibility at previously inaccessible genomic loci. Cas9 chromatin opening is sufficient to enable adjacent binding and transcriptional activation by the settler transcription factor retinoic acid receptor at previously unbound motifs. Thus, we demonstrate a new use for Cas9 in increasing surrounding chromatin accessibility to alter local transcription factor binding.

Introduction: The emergence of artificial intelligence (AI) chat programs has opened two distinct paths, one enhancing interaction and another potentially replacing personal understanding. Ethical and legal concerns arise due to the rapid development of these programs. This paper investigates academic discussions on AI in medicine, analyzing the context, frequency, and reasons behind these conversations. Methods: The study collected data from the Web of Science database on articles containing the keyword "ChatGPT" published from January to September 2023, resulting in 786 medically related journal articles. The inclusion criteria were peer-reviewed articles in English related to medicine. Results: The United States led in publications (38.1%), followed by India (15.5%) and China (7.0%). Keywords such as "patient" (16.7%), "research" (12%), and "performance" (10.6%) were prevalent. The Cureus Journal of Medical Science (11.8%) had the most publications, followed by the Annals of Biomedical Engineering (8.3%). August 2023 had the highest number of publications (29.3%), with significant growth between February to March and April to May. Medical General Internal (21.0%) was the most common category, followed by Surgery (15.4%) and Radiology (7.9%). Discussion: The prominence of India in ChatGPT research, despite lower research funding, indicates the platform's popularity and highlights the importance of monitoring its use for potential medical misinformation. China's interest in ChatGPT research suggests a focus on Natural Language Processing (NLP) AI applications, despite public bans on the platform. Cureus' success in publishing ChatGPT articles can be attributed to its open-access, rapid publication model. The study identifies research trends in plastic surgery, radiology, and obstetric gynecology, emphasizing the need for ethical considerations and reliability assessments in the application of ChatGPT in medical practice. Conclusion: ChatGPT's presence in medical literature is growing rapidly across various specialties, but concerns related to safety, privacy, and accuracy persist. More research is needed to assess its suitability for patient care and implications for non-medical use. Skepticism and thorough review of research are essential, as current studies may face retraction as more information emerges. [ABSTRACT FROM AUTHOR]