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Abstract Three-dimensional (3D) printed surgical models provide an excellent surgical training option to closely mimic real operations to teach medical students who currently rely largely on visual learning aided with simple suturing pads. There is an unmet need to create simple to complex surgical training programs suitable for medical students. A prospective cohort study was conducted on a group of 16 6th year students. They were randomly divided into two groups for suture training on a basic training pad or on unique 3D-printed intestinal anastomosis models. After 4 weeks of open and laparoscopic surgical training, exams were performed on the standardized 3D-printed model at the end of each stage to assess surgical performance including surgical time and scores. Both groups had similar skills before the start of each stage. In stage 1, both groups showed comparable learning performance, but the 3D model group performed better in Exam 1. In stage 2, the 3D model group took more time but showed significant improvements and outperformed the pad group in Exam 2 in both performance scores and time. Post-training questionnaires indicated increased interest in surgery and technical training among students using 3D models. Realistic 3D-printed models benefit surgical training, expected to become integral in teaching operative skills and techniques to medical students.

Abstract Background As previously published, the MMPOWER-3 clinical trial did not demonstrate a significant benefit of elamipretide treatment in a genotypically diverse population of adults with primary mitochondrial myopathy (PMM). However, the prespecified subgroup of subjects with disease-causing nuclear DNA (nDNA) pathogenic variants receiving elamipretide experienced an improvement in the six-minute walk test (6MWT), while the cohort of subjects with mitochondrial DNA (mtDNA) pathogenic variants showed no difference versus placebo. These published findings prompted additional genotype-specific post hoc analyses of the MMPOWER-3 trial. Here, we present these analyses to further investigate the findings and to seek trends and commonalities among those subjects who responded to treatment, to build a more precise Phase 3 trial design for further investigation in likely responders. Results Subjects with mtDNA pathogenic variants or single large-scale mtDNA deletions represented 74% of the MMPOWER-3 population, with 70% in the mtDNA cohort having either single large-scale mtDNA deletions or MT-TL1 pathogenic variants. Most subjects in the nDNA cohort had pathogenic variants in genes required for mtDNA maintenance (mtDNA replisome), the majority of which were in POLG and TWNK. The mtDNA replisome post-hoc cohort displayed an improvement on the 6MWT, trending towards significant, in the elamipretide group when compared with placebo (25.2 ± 8.7 m versus 2.0 ± 8.6 m for placebo group; p = 0.06). The 6MWT results at week 24 in subjects with replisome variants showed a significant change in the elamipretide group subjects who had chronic progressive external ophthalmoplegia (CPEO) (37.3 ± 9.5 m versus − 8.0 ± 10.7 m for the placebo group; p = 0.0024). Pharmacokinetic (exposure–response) analyses in the nDNA cohort showed a weak positive correlation between plasma elamipretide concentration and 6MWT improvement. Conclusions Post hoc analyses indicated that elamipretide had a beneficial effect in PMM patients with mtDNA replisome disorders, underscoring the importance of considering specific genetic subtypes in PMM clinical trials. These data serve as the foundation for a follow-up Phase 3 clinical trial (NuPOWER) which has been designed as described in this paper to determine the efficacy of elamipretide in patients with mtDNA maintenance-related disorders. Classification of evidence Class I ClinicalTrials.gov identifier NCT03323749

Abstract Season of birth, viral infections, HLA haplogenotypes and non-HLA variants are implicated in the development of celiac disease and celiac disease autoimmunity, suggesting a combined role of genes and environmental exposures. The aim of the study was to further decipher the biological pathways conveying the season of birth effect in celiac disease autoimmunity to gain novel insights into the early pathogenesis of celiac disease. Interactions between season of birth, genetics, and early-life environmental factors on the risk of celiac autoimmunity were investigated in the multicenter TEDDY birth cohort study. Altogether 6523 genetically predisposed children were enrolled to long-term follow-up with prospective sampling and data collection at six research centers in the USA, Germany, Sweden and Finland. Celiac disease autoimmunity was defined as positive tissue transglutaminase antibodies in two consecutive serum samples. There was a significant season of birth effect on the risk of celiac autoimmunity. The effect was dependent on polymorphisms in CD247 gene encoding for CD3ζ chain of TCR-CD3 complex. In particular, children with major alleles for SNP rs864537A > G, in CD247 (AA genotype) had an excess risk of celiac autoimmunity when born March–August as compared to other months. The interaction of CD247 with season of birth on autoimmunity risk was accompanied by interactions with febrile infections between the ages of 3–6 months. Considering the important role of TCR-CD3 complex in the adaptive immune response and our findings here, CD247 variants and their possible effect of subgroups in autoimmunity development could be of interest in the design of future gene-environment studies of celiac disease. ClinicalTrials.gov Identifier: NCT00279318.

BackgroundSpinal pain is prevalent and burdensome worldwide. A large proportion of patients with neck and thoracic pain experience chronic symptoms, which can significantly impact their physical functioning. Therefore, it is important to understand factors predicting outcome to inform effective examination and treatment. Knowledge of physical measures of physical functioning as prognostic factors can enhance patient-centered care and aid decision-making. The evidence regarding physical outcome measures as prognostic factors for neck and thoracic pain is unclear. The objective of this study is to summarize the evidence for physical outcome measures of physical functioning as prognostic factors in predicting outcomes in people with neck and thoracic pain.Methods and analysisThis systematic review follows Cochrane guidelines and aligns with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). Included studies will be prospective longitudinal cohort studies in which physical measures of physical functioning are explored as prognostic factors for adults with neck and thoracic pain. A comprehensive search will be performed in key databases (MEDLINE, EMBASE, CINAHL, Scopus, and Web of Science) and the grey literature, with hand searches of key journals, and the reference lists of included studies. Two reviewers will independently perform study selection, data extraction, risk of bias assessment (QUIPS, Quality in Prognostic Studies tool), and quality assessment (Grading of Recommendations Assessment, Development, and Evaluation).ImplicationsThis systematic review will identify physical measures of physical functioning prognostic factors for neck and thoracic pain populations. Findings will inform researchers about gaps in existing evidence, and clinicians about factors to aid their clinical decisions and to enhance the overall quality of care for individuals with neck and thoracic pain.

Objective: Compare the differences in cost, complications, new intra-articular diagnoses, and reoperations among patients with ankle instability submitted to lateral ankle ligament repair/reconstruction with or without arthroscopic procedures. Methods: A retrospective analysis of 2,428 patients from the PearlDiver Humana dataset with ankle sprain or instability codes and compared outcomes between those submitted to lateral ankle ligament repair/reconstruction with or without arthroscopy. Results: Patients without arthroscopy had higher complication rates (9.87% vs. 5.41%; χ2[1, n = 1,236] = 5.83, p = 0.01), while the difference in reconstruction groups was insignificant (p = 0.09). Arthroscopy groups had higher rates of newly diagnosed intra-articular pathology: repair with arthroscopy (57.0%) vs. without (35.6%; χ2[1, n = 1,236] = 44.47, p < 0.001); reconstruction with arthroscopy (63.0%) vs. without (39.8%; χ2[1, n = 1,211] = 61.90, p < 0.001). Reoperation rates for intra-articular pathology were higher in the arthroscopy group (6.89% vs. 4.18%; χ2[1, n = 2,433] = 8.09, p = 0.006), with significantly shorter time to reoperation (303 vs. 474 days, p = 0.045). Conclusions: Arthroscopy does not increase complication rates and allows for earlier diagnosis and treatment of intra-articular pathology, potentially leading to earlier reoperation. Level of evidence III; Retrospective Comparative Study.

Background: Gastrointestinal (GI) disorders are one of the most commonly encountered health problems in routine clinical practice. Dietary, environmental, geographic, and genetic factors are some of the key reasons contributing to the prevalence of these diseases. A wide spectrum of lesions is observed on histopathological examination of the upper GI tract (GIT). Aims and Objective: The study was carried out to determine the histopathological spectrum of upper GIT lesions and to compare the lesions with demographic and clinical data. Materials and Methods: The study was conducted on all consecutive upper GI endoscopic biopsies received in the Department of Pathology, Narendra Modi Medical College, Ahmedabad during the period from August 2020 to October 2022. Results: Non-neoplastic lesions were observed in 91.3% of all upper GI biopsies. Among these, gastric lesions (63.3%) were the most common followed by duodenal lesions (21.3%) and esophageal lesions (6.6%). The most commonly observed non-neoplastic lesions from the esophagus, stomach, and duodenum were reflux esophagitis with its consequence Barrett’s esophagus, chronic gastritis, and chronic duodenitis, respectively. Neoplastic lesions were observed in 8.7% of all upper GI biopsies; out of which 4% were esophageal, 3.3% were gastric and 1.3% were duodenal. The most commonly observed neoplastic lesions from the esophagus, stomach, and duodenum were squamous cell carcinoma of the esophagus, adenocarcinoma of the stomach, and adenocarcinoma of duodenum, respectively. Conclusion: Endoscopic biopsy examination followed by histopathologic assessment is a convenient procedure and current gold standard for the accurate diagnosis of patients with upper GIT lesions.

Haemorrhagic ascites is primarily associated with perforated abdominal viscera, malignancies and tuberculosis or hepatic pathologies. However, its presentation due to ovarian endometriosis is a rare finding. We report the rare occurrence of haemorrhagic ascites due to ovarian endometriosis in a 26-year-old multiparous female presentingwith severe abdominal pain. The other probable causes of ascites were excluded and computed tomography of abdomen and pelvis revealed moderate ascites with bulky left ovarian cyst. Abdominal paracentesis revealed haemorrhagic ascitic fluid which on cytopathology did not reveal evidence of malignancy. Diagnostic work-up including magnetic resonance imaging and diagnostic laparoscopy confirmed the diagnosis. She was treated with oral dienogest which caused regression of the mass and pain. This case highlights that endometriosis may be included in the differential diagnosis while treating haemorrhagic ascites in women in reproductive age.

Abstract Background Vascular pathologies of the head and neck are rare but can present as musculoskeletal problems. The International Federation of Orthopedic Manipulative Physical Therapists (IFOMPT) Cervical Framework (Framework) aims to assist evidence-based clinical reasoning for safe assessment and management of the cervical spine considering potential for vascular pathology. Clinical reasoning is critical to physiotherapy, and developing high-level clinical reasoning is a priority for postgraduate (post-licensure) educational programs. Objective To explore the influence of the Framework on clinical reasoning processes in postgraduate physiotherapy students. Methods Qualitative case study design using think aloud methodology and interpretive description, informed by COnsolidated criteria for REporting Qualitative research. Participants were postgraduate musculoskeletal physiotherapy students who learned about the Framework through standardized delivery. Two cervical spine cases explored clinical reasoning processes. Coding and analysis of transcripts were guided by Elstein’s diagnostic reasoning components and the Postgraduate Musculoskeletal Physiotherapy Practice model. Data were analyzed using thematic analysis (inductive and deductive) for individuals and then across participants, enabling analysis of key steps in clinical reasoning processes and use of the Framework. Trustworthiness was enhanced with multiple strategies (e.g., second researcher challenged codes). Results For all participants (n = 8), the Framework supported clinical reasoning using primarily hypothetico-deductive processes. It informed vascular hypothesis generation in the patient history and testing the vascular hypothesis through patient history questions and selection of physical examination tests, to inform clarity and support for diagnosis and management. Most participant’s clinical reasoning processes were characterized by high-level features (e.g., prioritization), however there was a continuum of proficiency. Clinical reasoning processes were informed by deep knowledge of the Framework integrated with a breadth of wider knowledge and supported by a range of personal characteristics (e.g., reflection). Conclusions Findings support use of the Framework as an educational resource in postgraduate physiotherapy programs to inform clinical reasoning processes for safe and effective assessment and management of cervical spine presentations considering potential for vascular pathology. Individualized approaches may be required to support students, owing to a continuum of clinical reasoning proficiency. Future research is required to explore use of the Framework to inform clinical reasoning processes in learners at different levels.

Abstract Episodic counterfactual thinking (eCFT) is the process of mentally simulating alternate versions of experiences, which confers new phenomenological properties to the original memory and may be a useful therapeutic target for trait anxiety. However, it remains unclear how the neural representations of a memory change during eCFT. We hypothesized that eCFT-induced memory modification is associated with changes to the neural pattern of a memory primarily within the default mode network, moderated by dispositional anxiety levels. We tested this proposal by examining the representational dynamics of eCFT for 39 participants varying in trait anxiety. During eCFT, lateral parietal regions showed progressively more distinct activity patterns, whereas medial frontal neural activity patterns became more similar to those of the original memory. Neural pattern similarity in many default mode network regions was moderated by trait anxiety, where highly anxious individuals exhibited more generalized representations for upward eCFT (better counterfactual outcomes), but more distinct representations for downward eCFT (worse counterfactual outcomes). Our findings illustrate the efficacy of examining eCFT-based memory modification via neural pattern similarity, as well as the intricate interplay between trait anxiety and eCFT generation.

Primary gastric lymphoma is considered most common primary type of extra-nodal non-Hodgkin’s lymphoma and constitutes approx. 5% of total gastric malignancy. As the clinical symptoms of gastric lymphomas are nonspecific, diagnosis of gastric lymphoma is often difficult clinically. This case report presents a case of non-Hodgkin lymphoma which presents clinically and on blood investigations as acute necrotizing pancreatitis. This case is being prepared in view of its rarity and also to alert the treating physicians to consider underlying gastric lymphoma as an uncommon cause in some unexplained cases of pancreatitis.

Abstract Safety incidents have always been a crucial risk in work spaces, especially industrial sites. In the last few decades, significant efforts have been dedicated to incident control measures to reduce the rate of safety incidents. Despite all these efforts, the rate of decline in serious injuries and fatalities (SIFs) has been considerably lower than the rate of decline for non-critical incidents. This observation has led to a change of risk reduction paradigm for safety incidents. Under the new paradigm, more focus has been allocated to reducing the rate of critical/SIF incidents, as opposed to reducing the count of all incidents. One of the challenges in reducing the number of SIF incidents is the proper identification of the risk prior to materialization. One of the reasons for risk identification being a challenge is that companies usually only focus on incidents where SIF did occur reactively, and incidents that did not cause SIF but had the potential to do so go unnoticed. Identifying these potentially significant incidents, referred to as potential serious injuries and fatalities (PSIF), would enable companies to work on identifying critical risk and taking steps to prevent them preemptively. However, flagging PSIF incidents requires all incident reports to be analyzed individually by experts and hence significant investment, which is often not affordable, especially for small and medium sized companies. This study is aimed at addressing this problem through machine learning powered automation. We propose a novel approach based on binary classification for the identification of such incidents involving PSIF (potential serious injuries and fatalities). This is the first work towards automatic risk identification from incident reports. Our approach combines a pre-trained transformer model with XGBoost. We utilize advanced natural language processing techniques to encode an incident record comprising heterogeneous fields into a vector representation fed to XGBoost for classification. Moreover, given the scarcity of manually labeled incident records available for training, we leverage weak labeling to augment the label coverage of the training data. We utilize the F2 metric for hyperparameter tuning using Tree-structured Parzen Estimator to prioritize the detection of PSIF records over the avoidance of non-PSIF records being mis-classified as PSIF. The proposed methods outperform several baselines from other studies on a significantly large test dataset.

Abstract Serum creatinine levels are insensitive to real-time changes in kidney function or injury. There is a growing interest in assessing kidney injury by measuring biomarkers in body fluid. From our previous studies, we identified and reported three urinary biomarkers namely Uromodulin (UMOD), Osteopontin (OPN), and Interleukin-9 (IL-9) to be associated with kidney health. The availability of a rapid point-of-care test for these urinary biomarkers will potentially accelerate its applicability and accessibility. In this study, we aimed to develop novel lateral flow device (LFD) for UMOD, OPN and IL-9. We tested paired antibodies using Enzyme Linked Immunosorbent Assay wherein we observed functionality only for UMOD and OPN and not for IL-9. A conjugation buffer pH of 7.8 and 8.5 was found suitable at a detection antibody concentration of 15 µg/mL for LFD development. The developed LFDs were found to quantitatively measure UMOD standard (LLOD of 80,000 pg/mL) and OPN standard (LLOD of 8600 pg/mL) respectively. The LFD was also able to measure human urinary UMOD and OPN with a percent CV of 12.12 and 5.23 respectively.

Isolated polycystic disease of the pancreas is an extremely uncommon condition, with very few examples documented in the literature. Pancreatic cystic lesions are usually associated with other genetic disorders that involve other organs as well. However, isolated pancreatic polycystic disease is rare. We reported a symptomatic case of polycystic disease of the pancreas without evidence of cystic lesions in other organs.

Abstract Determination of prognosis in the triage process after traumatic brain injury (TBI) is difficult to achieve. Current severity measures like the Trauma and injury severity score (TRISS) and revised trauma score (RTS) rely on additional information from the Glasgow Coma Scale (GCS) and the Injury Severity Score (ISS) which may be inaccurate or delayed, limiting their usefulness in the rapid triage setting. We hypothesized that machine learning based estimations of GCS and ISS obtained through modeling of continuous vital sign features could be used to rapidly derive an automated RTS and TRISS. We derived variables from electrocardiograms (ECG), photoplethysmography (PPG), and blood pressure using continuous data obtained in the first 15 min of admission to build machine learning models of GCS and ISS (ML-GCS and ML-ISS). We compared the TRISS and RTS using ML-ISS and ML-GCS and its value using the actual ISS and GCS in predicting in-hospital mortality. Models were tested in TBI with systemic injury (head abbreviated injury scale (AIS) ≥ 1), and isolated TBI (head AIS ≥ 1 and other AIS ≤ 1). The area under the receiver operating characteristic curve (AUROC) was used to evaluate model performance. A total of 21,077 cases (2009–2015) were in the training set. 6057 cases from 2016 to 2017 were used for testing, with 472 (7.8%) severe TBI (GCS 3–8), 223 (3.7%) moderate TBI (GCS 9–12), and 5913 (88.5%) mild TBI (GCS 13–15). In the TBI with systemic injury group, ML-TRISS had similar AUROC (0.963) to TRISS (0.965) in predicting mortality. ML-RTS had AUROC (0.823) and RTS had AUROC 0.928. In the isolated TBI group, ML-TRISS had AUROC 0.977, and TRISS had AUROC 0.983. ML-RTS had AUROC 0.790 and RTS had AUROC 0.957. Estimation of ISS and GCS from machine learning based modeling of vital sign features can be utilized to provide accurate assessments of the RTS and TRISS in a population of TBI patients. Automation of these scores could be utilized to enhance triage and resource allocation during the ultra-early phase of resuscitation.

BackgroundSelf-injurious thoughts and behaviors (SITBs) are increasing dramatically among children and adolescents. Crisis support is intended to provide immediate mental health care, risk mitigation, and intervention for those experiencing SITBs and acute mental health distress. Digital mental health interventions (DMHIs) have emerged as accessible and effective alternatives to in-person care; however, most do not provide crisis support or ongoing care for children and adolescents with SITBs. ObjectiveTo inform the development of digital crisis support and mental health care for children and adolescents presenting with SITBs, this study aims to (1) characterize children and adolescents with SITBs who participate in a digital crisis response service, (2) compare anxiety and depressive symptoms of children and adolescents presenting with SITBs versus those without SITBs throughout care, and (3) suggest future steps for the implementation of digital crisis support and mental health care for children and adolescents presenting with SITBs. MethodsThis retrospective study was conducted using data from children and adolescents (aged 1-17 y; N=2161) involved in a pediatric collaborative care DMHI. SITB prevalence was assessed during each live session. For children and adolescents who exhibited SITBs during live sessions, a rapid crisis support team provided evidence-based crisis support services. Assessments were completed approximately once a month to measure anxiety and depressive symptom severity. Demographics, mental health symptoms, and change in the mental health symptoms of children and adolescents presenting with SITBs (group with SITBs) were compared to those of children and adolescents with no SITBs (group without SITBs). ResultsCompared to the group without SITBs (1977/2161, 91.49%), the group with SITBs (184/2161, 8.51%) was mostly made up of adolescents (107/184, 58.2%) and female children and adolescents (118/184, 64.1%). At baseline, compared to the group without SITBs, the group with SITBs had more severe anxiety and depressive symptoms. From before to after mental health care with the DMHI, the 2 groups did not differ in the rate of children and adolescents with anxiety symptom improvement (group with SITBs: 54/70, 77% vs group without SITBs: 367/440, 83.4%; χ21=1.2; P=.32) as well as depressive symptom improvement (group with SITBs: 58/72, 81% vs group without SITBs: 255/313, 81.5%; χ21=0; P=.99). The 2 groups also did not differ in the amount of change in symptom severity during care with the DMHI for anxiety (t80.20=1.37; P=.28) and depressive (t83.75=–0.08; P=.99) symptoms. ConclusionsThis study demonstrates that participation in a collaborative care DMHI is associated with improved mental health outcomes in children and adolescents experiencing SITBs. These results provide preliminary insights for the use of pediatric DMHIs in crisis support and mental health care for children and adolescents presenting with SITBs, thereby addressing the public health issue of acute mental health crisis in children and adolescents.

Purpose We developed a comprehensive sleeve gastrectomy (SG) weight loss study cohort and biorepository to uncover mechanisms, biomarkers and predictive factors of weight loss, weight maintenance and amelioration of obesity-related comorbidities. For this purpose, we collected psychosocial, anthropometric, clinical data and a variety of samples pre-surgery, intraoperatively and 1.5, 3, 12 and 24 months post-surgery. For longer-term assessment, the collection of psychosocial and anthropometric data was extended to 10 years. Here, we present in-depth characterisation of the cohort and detailed overview of study procedures as a foundation for future analyses.Participants We consented 647 participants between June 2017 and March 2020 from two bariatric surgery clinics in New York City—one major urban hospital and one private hospital. Of 355 participants who provided baseline data, 300 underwent SG. Of these, 79% are females with an average age of 38 years, 68% are Hispanic, 20% are non-Hispanic Black and 11% are non-Hispanic White.Findings to date We collected intraoperative adipose and stomach tissues from 282 patients and biosamples (blood, urine, saliva, stool) from 245 patients at 1.5 months, 238 at 3 month, 218 at 12 months and 180 at 24 months post-surgery. We are currently collecting anthropometric and psychosocial data annually until 10 years post-surgery. Data analysis is currently underway.Future plans Our future research will explore the variability in weight loss outcomes observed in our cohort, particularly among Black and Hispanic patients in comparison to their White counterparts. We will identify social determinants of health, metabolic factors and other variables that may predict weight loss success, weight maintenance and remission of obesity-related comorbidities. Additionally, we plan to leverage our biorepository for collaborative research studies. We will complete long-term follow-up data by December 2031. We plan to apply for funding to expand biosample collection through year 10 to provide insights into the mechanisms of long-term weight maintenance.

Brucellosis is the most common bacterial zoonosis and it causes approx half million human infections per year worldwide. Neurobrucelosis should be considered as possible differential diagnosis when a patient presents with symptomps of neruropasychiatric spectrum and fever. We report a case of neurobrucellosis in a patient who presented with headache, vomiting and an episode of generalized tonic clonic seizure.

Purpose: The purpose of this meta-analysis is to study the impact of varicocele repair in the largest cohort of infertile males with clinical varicocele by including all available studies, with no language restrictions, comparing intra-person conventional semen parameters before and after the repair of varicoceles. Materials and Methods: The meta-analysis was performed according to PRISMA-P and MOOSE guidelines. A systematic search was performed in Scopus, PubMed, Cochrane, and Embase databases. Eligible studies were selected according to the PICOS model (Population: infertile male patients with clinical varicocele; Intervention: varicocele repair; Comparison: intraperson before-after varicocele repair; Outcome: conventional semen parameters; Study type: randomized controlled trials [RCTs], observational and case-control studies). Results: Out of 1,632 screened abstracts, 351 articles (23 RCTs, 292 observational, and 36 case-control studies) were included in the quantitative analysis. The before-and-after analysis showed significant improvements in all semen parameters after varicocele repair (except sperm vitality); semen volume: standardized mean difference (SMD) 0.203, 95% CI: 0.129–0.278; p

Abstract Prenatal tobacco smoke exposure (TSE) and prematurity are independent risk factors for abnormal neurodevelopment. The objectives were to compare differences in Bayley-III cognitive, language, and motor scores at 2 years corrected age (CA) in 395 infants born very preterm (≤ 32 weeks gestation) with and without prenatal TSE. We performed multivariable linear regression analyses to examine associations between prenatal TSE and neurodevelopmental outcomes and a mediation analysis to estimate direct effects of prenatal TSE on outcomes and indirect effects through preterm birth. In total, 50 (12.6%) infants had prenatal TSE. Infants with prenatal TSE had lower mean [95% CI] Cognitive score (82.8 [78.6, 87.1]) vs. nonexposed infants (91.7 [90.1, 93.4]). In children with and without prenatal TSE, there were significant differences in mean [95% CI] Language scores (81.7 [76.0, 87.4] vs. 92.4 [90.2, 94.6], respectively) and mean [95% CI] Motor scores (86.5 [82.2, 90.7] vs. 93.4 [91.8, 95.0], respectively); scores remained significant after controlling for confounders. Preterm birth indirectly mediated 9.0% of the total effect of prenatal TSE on Cognitive score (P = NS). However, 91% of the remaining total effect was significant and attributable to TSE’s direct harmful effects on cognitive development (β = − 5.17 [95% CI − 9.97, − 0.38]). The significant association is largely due to TSE’s direct effect on cognitive development and not primarily due to TSE’s indirect effect on preterm birth.

Abstract Feeding on plant-derived sugars is an essential component of mosquito biology, affecting key aspects of their lives such as survival, metabolism, and reproduction. Among mosquitoes, Aedes aegypti and Aedes albopictus are two invasive mosquito species in the US, and are vectors of diseases such as dengue fever, chikungunya, and Zika. These species live in heavily populated, urban areas, where they have high accessibility to human hosts as well as to plants in backyards and public landscapes. However, the range of plants that are suitable sugar hosts for these species remains to be described, despite the importance of understanding what plants may attract or repel mosquitoes to inform citizens and municipal authorities accordingly. Here, we tested whether Ae. aegypti and Ae. albopictus would sugar-feed on eleven commonly planted ornamental plant species. We confirmed feeding activity using the anthrone method and identified the volatile composition of plant headspace using gas-chromatography mass-spectroscopy. These chemical analyses revealed that a broad range of olfactory cues are associated with plants that mosquitoes feed on. This prompted us to use plant DNA barcoding to identify plants that field-caught mosquitoes feed on. Altogether, results show that native and invasive mosquito species can exploit a broader range of plants than originally suspected, including wild and ornamental plants from different phyla throughout the Spring, Summer and Fall seasons.

Ecuador has gone through a significant reduction in new cases from 2000 (106) to 2023 (12), suggesting a trend towards zero leprosy. An ecological spatiotemporal study design was used to describe the epidemiological distribution of the disease in the country during 2000–2023. Leprosy cases registered by the surveillance system of the Ecuadorian Ministry of Public Health were the data utilized for the study. From January 2000 to December 2023, 1539, incidence cases were diagnosed with leprosy in Ecuador. At the time of diagnosis, the median age was 54 years. Most of the cases were males (71.5%). The proportion of incidence cases in subjects over 50 years was 63% and 1.5% in children ≤ 15 years old. The yearly incidence rate ranged from 8.5/1,000,000 population in 2000 to 0.68/1,000,000 population in 2023, remaining within the low-endemic parameter. In total, 35 cantons reported newly detected leprosy cases in the year 2000. By the end of 2023, only eight cantons actively reported cases of leprosy. High-risk clusters for leprosy were detected in the tropical coastal region of Ecuador. The provinces with the highest number of cases during the study period were Guayas (44.8%) and Los Rios (15.7%), with zero cases being found in the Galapagos Islands. Our study is unique in that it documents a retrospective dataset over a two-decade timespan from a South American country that has effectively applied global guidelines for the control and elimination of leprosy.

Background: One of the key factors in the prevention of the disease is the identification of the risk factors early in life. Based on multifactorial causation of oral submucous fibrosis (OSMF), apart from habit history, the genetical predisposition may be considered as an important risk factor in the occurrence of OSMF disease. The dermatoglyphic pattern may prove a salient genetic marker for the determination of OSMF as both are having similar intrauterine development period. Objectives: To find out and compare the association between dermatoglyphics and OSMF. Materials and Methods: The present study was conducted on total 108 subjects divided in three groups where Group A was subjects with OSMF, Group B was subjects with tobacco related habits but without OSMF, and Group C was healthy controls. Fingerprint patterns of both hands were recorded and classified into whorls, loops and arches. Results: The loop pattern was significantly higher in subjects having OSMF (Group A) as compared Group B and Group C in general as well as for left and right hands. The maximum prominence of loop patterns was noted in the little finger among the subjects with OSMF. Results for subjects with OSMF and without OSMF under five years of having tobacco chewing habits had also clearly demonstrated prominence of loop patterns in the subjects with OSMF. Conclusion: The results of our study show that there is a staunch possibility of genetically determined factors in the form of loop finger prints can be responsible for the occurrence of OSMF.

Abstract Monitoring sleep and activity through wearable devices such as wrist-worn actigraphs has the potential for long-term measurement in the individual’s own environment. Long periods of data collection require a complex approach, including standardized pre-processing and data trimming, and robust algorithms to address non-wear and missing data. In this study, we used a data-driven approach to quality control, pre-processing and analysis of longitudinal actigraphy data collected over the course of 1 year in a sample of 95 participants. We implemented a data processing pipeline using open-source packages for longitudinal data thereby providing a framework for treating missing data patterns, non-wear scoring, sleep/wake scoring, and conducted a sensitivity analysis to demonstrate the impact of non-wear and missing data on the relationship between sleep variables and depressive symptoms. Compliance with actigraph wear decreased over time, with missing data proportion increasing from a mean of 4.8% in the first week to 23.6% at the end of the 12 months of data collection. Sensitivity analyses demonstrated the importance of defining a pre-processing threshold, as it substantially impacts the predictive value of variables on sleep-related outcomes. We developed a novel non-wear algorithm which outperformed several other algorithms and a capacitive wear sensor in quality control. These findings provide essential insight informing study design in digital health research.

Abstract Growth in preterm infants in the neonatal intensive care unit (NICU) is associated with increased global and regional brain volumes at term, and increased postnatal linear growth is associated with higher language scores at age 2. It is unknown whether these relationships persist to school age or if an association between growth and cortical metrics exists. Using regression analyses, we investigated relationships between the growth of 42 children born extremely preterm (

Background: The predictive normal value of peak expiratory flow rate (PEFR), in children, is correlated with height and other anthropometric measurements, however, it shows ethnic Differences. The present study was conducted to establish the normal value of PEFR in healthy school children and to know the effect of various anthropometric factors on PEFR. Methodology: This study was conducted among 2200 students to assess their Peak Expiratory Flow Rate (PEFR) using Mini-Wright peak flow meter. PEFR values correlated with age, gender and various anthropometric measurements. Results: Out of total 2200 students, 1122 were boys which accounted for 51%. Mean PEFR for boys was 282.53 L/min and for girls was 270/.79 L/min. In boys and girls PEFR value increase as the age advances. Multiple regression modeling with PEFR as dependent variable and MUAC, BMI, Age, CC, Height, Weight and BSA as independent variables shows that Height, Weight, BMI, BSA, Age and chest circumference are independently associated with PEFR value. However, MUAC is not independently associated with PEFR values. Conclusion: From this study we conclude that in children between 6 to 17 year of age group the PEFR value in higher in boys compared to girls at any age. Height has strongest association with PEFR then the other variables.

Abstract Background Data are limited regarding the combined impact of headache frequency and failure of preventive medication (efficacy and/or tolerability) on the humanistic/economic burden of migraine. Methods A retrospective, cross-sectional analysis of 2020 National Health and Wellness Survey (NHWS) data was conducted. An opt-in online survey identified adults in France, Germany, Italy, Spain, and United Kingdom with self-reported physician-diagnosed migraine. Participants with ≥ 4 monthly headache days (MHDs) were stratified by prior preventive medication use/failure (preventive naive; 0–1 failure; ≥ 2 failures). Quality-of-life and economic outcomes were compared among groups using generalized linear modeling. Results Among individuals with ≥ 4 MHDs (n = 1106), the NHWS identified 298 (27%) with ≥ 2 failures, 308 (28%) with 0–1 failure, and 500 (45%) as preventive naive. Individuals with ≥ 2 failures versus preventive-naive individuals had significantly lower scores on the 12-Item Short Form Survey Physical Component Summary (42.2 vs 44.1; P

Abstract Cisplatin-based combination chemotherapy is the foundation for treatment of advanced bladder cancer (BlCa), but many patients develop chemoresistance mediated by increased Akt and ERK phosphorylation. However, the mechanism by which cisplatin induces this increase has not been elucidated. Among six patient-derived xenograft (PDX) models of BlCa, we observed that the cisplatin-resistant BL0269 express high epidermal growth factor receptor, ErbB2/HER2 and ErbB3/HER3. Cisplatin treatment transiently increased phospho-ErbB3 (Y1328), phospho-ERK (T202/Y204) and phospho-Akt (S473), and analysis of radical cystectomy tissues from patients with BlCa showed correlation between ErbB3 and ERK phosphorylation, likely due to the activation of ERK via the ErbB3 pathway. In vitro analysis revealed a role for the ErbB3 ligand heregulin1-β1 (HRG1/NRG1), which is higher in chemoresistant lines compared to cisplatin-sensitive cells. Additionally, cisplatin treatment, both in PDX and cell models, increased HRG1 levels. The monoclonal antibody seribantumab, that obstructs ErbB3 ligand-binding, suppressed HRG1-induced ErbB3, Akt and ERK phosphorylation. Seribantumab also prevented tumor growth in both the chemosensitive BL0440 and chemoresistant BL0269 models. Our data demonstrate that cisplatin-associated increases in Akt and ERK phosphorylation is mediated by an elevation in HRG1, suggesting that inhibition of ErbB3 phosphorylation may be a useful therapeutic strategy in BlCa with high phospho-ErbB3 and HRG1 levels.

Introduction: Epilepsy is a serious psychological condition associated with social stigma, psychiatric co-morbidity, and a high economic burden. It is pertinent to develop novel treatment methods given the ever-evolving nature of the disease. Recently, various newer Antiepileptic Drugs (AEDs) have been under study, among which a newer targeted modality consists of SV2A receptors. Aim: To compare the antioxidant properties or free radical scavenging activity of the newer heterogeneous AEDs acting on the SV2A receptors, namely Levetiracetam (LEV) and Brivaracetam (BRV). Materials and Methods: This in-vitro study was conducted at Department of Pharmacology, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu, India from July 2021 to August 2021. The study evaluated the antioxidant properties of LEV and BRV using various assays such as the Ferric Reducing Antioxidant Power (FRAP) test, DPPH (1,1-diphenyl-2-picrylhydrazyl) assay, Nitric Oxide (NO) radical scavenging assay, Superoxide Dismutase activity (SOD), and catalase activity. The obtained results were expressed using specific formulas related to the absorbance of the respective chemicals, along with the percentage of inhibition, and have been tabulated in Microsoft excel Sheet Version 16.16.27. Half-maximal Inhibitory Concentration (IC50) values were calculated using scatter plot graphs. Results: The FRAP values for LEV were reported to be significantly higher compared to BRV at concentrations of 20, 40, 60, 80 μg/mL, while at 100 μg/mL, BRV showed better ferric reducing activity. Although both drugs exhibited antioxidant activity, the results clearly identified LEV as a better NO radical scavenger, with a percentage of inhibition reaching up to 80.52%. During the SOD assay, the percentage inhibition of superoxide generation by LEV was found to be 99.02%, while that of BRV was 97.07% at a concentration of 100 μg/mL. LEV (0.573) also showed a higher degradation of H2O2 per minute than BRV (0.065) at a concentration of 100 μg/mL. Conclusion: The results showed that both drugs, BRV and LEV, exhibited significant antioxidant capacity. However, LEV demonstrated increased antioxidant potency and efficacy compared to BRV.

Abstract Background and Aims Cannabis and its various derivatives are commonly used for both recreational and medicinal purposes. Cannabinoids have been shown to have anti‐inflammatory properties. Inflammation is an important component of wound healing and the effect of cannabinoids on wound healing has become a recent topic of investigation. The objective of this article is to perform a comprehensive review of the literature to summarize the effects of cannabinoids on wound healing of the skin and to guide future avenues of research. Methods A comprehensive literature review was performed to evaluate the effects of cannabinoids on cutaneous wound healing. Results Cannabinoids appear to improve skin wound healing through a variety of mechanisms. This is supported through a variety of in vitro and animal studies. Animal studies suggest application of cannabinoids may improve the healing of postsurgical and chronic wounds. There are few human studies which evaluate the effects of cannabinoids on wound healing and many of these are case series and observational studies. They do suggest cannabinoids may have some benefit. However, definitive conclusions cannot be drawn from them. Conclusion While further human studies are needed, topical application of cannabinoids may be a potential therapeutic option for postsurgical and chronic wounds.

BackgroundYoung people today are exhibiting increasing rates of disordered eating behaviors, as well as eating disorders (EDs), alongside other mental and behavioral problems such as anxiety and depression. However, limited access to mental health care means that EDs, disordered eating behaviors, and comorbid mental health problems are often underdiagnosed and undertreated. Digital mental health interventions (DMHIs) offer accessible and scalable alternatives to traditional treatment modalities, but their effectiveness has not been well established among adolescents with EDs and disordered eating behaviors. ObjectiveThis study uses data from a collaborative care pediatric DMHI to determine whether participation in a DMHI is associated with a reduction in adolescents’ disordered eating behaviors. MethodsAdolescent members in care with Bend Health Inc completed the SCOFF questionnaire at baseline (before the start of care) and approximately every month during care to assess disordered eating behaviors. They also completed assessments of mental health symptoms at baseline. Member characteristics, mental health symptoms, and disordered eating behaviors of adolescents with elevated SCOFF scores at baseline (before the start of care) were compared to those of adolescents with nonelevated SCOFF scores at baseline. Members participated in web-based coaching or therapy sessions throughout the duration of mental health care. ResultsCompared to adolescents with nonelevated SCOFF scores (n=520), adolescents with elevated SCOFF scores (n=169) were predominantly female and exhibited higher rates of elevated anxiety and depressive symptoms. SCOFF scores decreased over time in care with the DMHI for 61.4% (n=70) of adolescents with elevated SCOFF scores, and each additional month of participation was associated with greater improvements in disordered eating behaviors (F1,233=72.82; P

Background Pulmonary hypertension (PH) leads to increased morbidity and mortality in interstitial lung disease (ILD). While the INCREASE trial highlighted the use of inhaled prostacyclin in PH-ILD patients, such therapy may be inadequate when right ventricular failure (RVF) is also present. In this study, we report the use of intravenous prostacyclin in three PH-ILD patients to stabilise right ventricular (RV) function, with a subsequent transition to maintenance therapy with inhaled prostacyclin. Methods We evaluated three consecutive PH-ILD patients with RVF. RV afterload and pulmonary vascular resistance (PVR) were treated with intravenous prostacyclin during the induction phase of the therapy. Patients transitioned from intravenous prostacyclin to the maintenance phase of the treatment with inhaled prostacyclin once three transition criteria were met: cardiac index (CI) >2 L·min−1·m−2, PVR 1 mm or TAPSE >1.6 cm. Results Pre-treatment parameters for the three patients were a mean PVR of 14.3 WU, a mean Fick CI of 1.8 L·min−1·m−2 and a mean TAPSE of 1.4 cm. The average intravenous prostacyclin dose at the time of transition to maintenance therapy was 20.7 ng·kg−1·m−2 of treprostinil. At 3-months follow-up, the mean PVR was 6.3 WU, Fick CI 2.2 L·min−1·m−2 and TAPSE 1.7 cm. Conclusion This case series of three PH-ILD patients with RVF introduces the concept of an initial intravenous prostacyclin induction phase, followed by a transition to maintenance therapy with inhaled prostacyclin. Further development of this treatment algorithm with a refinement of the transition criteria, potential testing in a clinical trial and a longer-term follow-up period is warranted to improve the outcomes of advanced PH-ILD patients with concomitant RVF.

IntroductionInterruptions during dental treatment are frequent, and often impact provider satisfaction and processing times We investigate the source and duration of such interruptions at a German dental clinic.MethodsA pre-post approach was adopted at this dental clinic. This included direct observations of 3 dentists and 3 dental hygienists, and a survey of providers. Following that, an intervention (switchable 'Do Not Enter' sign) was chosen, and a pilot study was conducted to evaluate if the chosen intervention can reduce processing time and improve provider satisfaction. Additional observations and surveys were performed afterwards.ResultsPre-intervention data indicated that interruptions have the highest negative impact on provider satisfaction at this clinic as well as on processing time during longer and more complex treatments, where a minor error due to an interruption could lead to rework of 30 minutes and more. The total number of interruptions dropped by 72.5% after the intervention, short interruptions (< 1min) by 86%. Provider survey indicated improvement due to the intervention in perceived workload, provider work satisfaction, patient safety and stress.ConclusionsThis study demonstrates that a switchable sign can substantially reduce the number of interruptions in this dental clinic. It also shows the potential of improving the work environment by reducing interruptions to the dental providers.

BackgroundOpen science practices are implemented across many scientific fields to improve transparency and reproducibility in research. Complementary, alternative, and integrative medicine (CAIM) is a growing field that may benefit from adoption of open science practices. The efficacy and safety of CAIM practices, a popular concern with the field, can be validated or refuted through transparent and reliable research. Investigating open science practices across CAIM journals by using the Transparency and Openness Promotion (TOP) guidelines can potentially promote open science practices across CAIM journals. The purpose of this study is to conduct an audit that compares and ranks open science practices adopted by CAIM journals against TOP guidelines laid out by the Center for Open Science (COS).MethodsCAIM-specific journals with titles containing the words "complementary", "alternative" and/or "integrative" were included in this audit. Each of the eight TOP criteria were used to extract open science practices from each of the CAIM journals. Data was summarized by the TOP guideline and ranked using the TOP Factor to identify commonalities and differences in practices across the included journals.ResultsA total of 19 CAIM journals were included in this audit. Across all journals, the mean TOP Factor was 2.95 with a median score of 2. The findings of this study reveal high variability among the open science practices required by journals in this field. Four journals (21%) had a final TOP score of 0, while the total scores of the remaining 15 (79%) ranged from 1 to 8.ConclusionWhile several studies have audited open science practices across discipline-specific journals, none have focused on CAIM journals. The results of this study indicate that CAIM journals provide minimal guidelines to encourage or require authors to adhere to open science practices and there is an opportunity to improve the use of open science practices in the field.

Introduction Atrial fibrillation (AF) is the most common arrhythmia and confers an increased risk of mortality, stroke, heart failure and cognitive decline. There is growing interest in AF screening; however, the most suitable population and device for AF detection remains to be elucidated. Here, we present the design of the CONSIDERING-AF (deteCtiON and Stroke preventIon by moDEl scRreenING for Atrial Fibrillation) study.Methods and analysis CONSIDERING-AF is a randomised, controlled, siteless, non-blinded diagnostic superiority trial with four parallel groups and a primary endpoint of identifying AF during a 6-month study period set in Region Halland, Sweden. In each group, 740 individuals aged≥65 years will be included. The primary objective is to compare the intervention of AF screening enrichment using a risk prediction model (RPM), followed by 14 days of a continuous ECG patch, with no intervention (standard care). Primary outcome is defined as the incident AF recorded in the Region Halland Information Database after 6 months as compared with standard care. Secondary endpoints include the difference in incident AF between groups enriched or not by the RPM, with and without an invitation to 14 days of continuous ECG recording, and the proportions of oral anticoagulation treatment in the four groups.Ethics and dissemination This study has ethical approval from the Swedish Ethical Review Authority. Results will be published in peer-reviewed international journals.Trial registration number NCT05838781.

Objectives Homelessness among families with children under 5 residing in temporary accommodation is a growing global concern, especially in high-income countries (HICs). Despite significant impacts on health and development, these ‘invisible’ children often fall through the gaps in policy and services. The study’s primary objective is to map the content and delivery methods of culturally sensitive interventions for children under 5 experiencing homelessness in HICs.Design A scoping review guided by the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews checklist.Data sources Databases include PubMed, Medline, SCOPUS, The Cochrane Library and Google Scholar were searched up to 24 March 2022.Eligibility criteria This scoping review includes studies that describe, measure or evaluate intervention strategies aimed at improving child health programmes, specifically those yielding positive outcomes in key areas like feeding, nutrition, care practices and parenting.Data extraction and synthesis Articles were selected and evaluated by two independent reviewers, with a dispute resolution system involving a third reviewer for contested selections. The methodological quality of the studies was assessed using various tools including the Risk of Bias (RoB) tool, Cochrane RoB V.2.0, the Risk of Bias Assessment Tool for Non-randomized Studies (RoBANS) and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE), each selected according to the type of article.Results The database search yielded 951 results. After deduplication, abstract screening and full review, 13 articles met the inclusion criteria. Two predominant categories of intervention delivery methods were identified in this research: group-based interventions (educational sessions) and individual-based interventions (home visits).Conclusion This review highlights effective interventions for promoting the health and well-being of children under 5 experiencing homelessness, including educational sessions and home visits. Research has supported the importance of home visiting to be instrumental in breaking down language, cultural and health literacy barriers.

BackgroundMusculoskeletal (MSK) spinal pain encapsulates various conditions including lumbar (low back), cervical (neck), and thoracic pain that significantly impact individual and global health. While clinical aspects of spinal pain have been well-studied, understanding patients' personal narratives and lived experiences remains essential for enhancing patient-centered care, improving treatment adherence, and informing healthcare policies. It provides deep insights into the impacts of spinal pain, guiding more effective and empathetic treatment approaches. This systematic review aims to synthesize qualitative evidence on patients' experiences with MSK spinal pain, providing insight into the challenges faced, coping strategies, daily life impacts, and healthcare interactions. The objective of this review is to synthesize the qualitative evidence regarding the lived experiences of patients with MSK spinal pain.MethodsThis systematic review will use a meta-aggregation approach to synthesize data from qualitative studies, that will be identified through a comprehensive search of electronic databases and supplemented by grey literature searches. Two independent reviewers will screen, identify, and extract data from eligible studies. In cases of disagreement, conflicts will be resolved by consulting a third reviewer. These same reviewers will then use the Joanna Briggs Institute (JBI) qualitative quality assessment tool to evaluate the methodological quality of the identified studies, with the derived scores informing the synthesis process, that will involve extracting each study's findings along with their supporting illustrations, then grouped into categories based on similarity in meaning. These categories will then be aggregated to form synthesized findings.ImplicationsSynthesized findings on patients' lived experiences with MSK spinal pain including key themes, patterns, and insights will be presented. By emphasizing patient narratives, the results of the review can contribute to the optimization of outcomes, and to enhance patient-provider relations and improve quality of care in MSK spinal health.

Traditional approaches for evaluating the impact of scientific research – mainly scholarship (i.e., publications, presentations) and grant funding – fail to capture the full extent of contributions that come from larger scientific initiatives. The Translational Science Benefits Model (TSBM) was developed to support more comprehensive evaluations of scientific endeavors, especially research designed to translate scientific discoveries into innovations in clinical or public health practice and policy-level changes. Here, we present the domains of the TSBM, including how it was expanded by researchers within the Implementation Science Centers in Cancer Control (ISC3) program supported by the National Cancer Institute. Next, we describe five studies supported by the Penn ISC3, each focused on testing implementation strategies informed by behavioral economics to reduce key practice gaps in the context of cancer care and identify how each study yields broader impacts consistent with TSBM domains. These indicators include Capacity Building, Methods Development (within the Implementation Field) and Rapid Cycle Approaches, implementing Software Technologies, and improving Health Care Delivery and Health Care Accessibility. The examples highlighted here can help guide other similar scientific initiatives to conceive and measure broader scientific impact to fully articulate the translation and effects of their work at the population level.

BackgroundRates of anxiety and depression have been increasing among children and adolescents for the past decade; however, many young people do not receive adequate mental health care. Digital mental health interventions (DMHIs) that include web-based behavioral health coaching are widely accessible and can confer significant improvements in youth anxiety and depressive symptoms. However, more research is necessary to determine the number of web-based coaching sessions that confer clinically significant improvements in anxiety and depressive symptoms in youth. ObjectiveThis study uses data from a pediatric DMHI to explore the number of web-based coaching sessions required to confer symptom improvements among children and adolescents with moderate or moderately severe symptoms of anxiety and depression. MethodsWe used retrospective data from a pediatric DMHI that offered web-based behavioral health coaching in tandem with self-guided access to asynchronous chat with practitioners, digital mental health resources, and web-based mental health symptom assessments. Children and adolescents who engaged in 3 or more sessions of exclusive behavioral health coaching for moderate to moderately severe symptoms of anxiety (n=66) and depression (n=59) were included in the analyses. Analyses explored whether participants showed reliable change (a decrease in symptom scores that exceeds a clinically established threshold) and stable reliable change (at least 2 successive assessments of reliable change). Kaplan-Meier survival analyses were performed to determine the median number of coaching sessions when the first reliable change and stable reliable change occurred for anxiety and depressive symptoms. ResultsReliable change in anxiety symptoms was observed after a median of 2 (95% CI 2-3) sessions, and stable reliable change in anxiety symptoms was observed after a median of 6 (95% CI 5-8) sessions. A reliable change in depressive symptoms was observed after a median of 2 (95% CI 1-3) sessions, and a stable reliable change in depressive symptoms was observed after a median of 6 (95% CI 5-7) sessions. Children improved 1-2 sessions earlier than adolescents. ConclusionsFindings from this study will inform caregivers and youth seeking mental health care by characterizing the typical time frame in which current participants show improvements in symptoms. Moreover, by suggesting that meaningful symptom improvement can occur within a relatively short time frame, these results bolster the growing body of research that indicates web-based behavioral health coaching is an effective form of mental health care for young people.

Abstract Adults with chronic kidney disease (CKD) are at increased risk for developing heart failure (HF). However, longitudinal cardiac remodeling in CKD has not been well-characterized and its association with HF outcomes remains unknown. We evaluated the association between change in echocardiographic parameters between baseline and year 4 with the subsequent risk of HF hospitalization and death using Cox proportional hazard models in a landmark analysis of a prospective multicenter CKD cohort. Among 2673 participants, mean ± SD age was 61 ± 11 years, with 45% women, and 56% non-white. A total of 472 hospitalizations for HF and 776 deaths occurred during a median (interquartile range) follow-up duration of 8.0 (6.3–9.1) years. Patients hospitalized for HF experienced larger preceding absolute increases in left ventricular (LV) volumes and decreases in LV ejection fraction. Adverse changes in LV ejection fraction, LV cavity volume, LV mass index, and LV geometry were independently associated with an increased risk of HF hospitalization and death. Among adults with CKD, deleterious cardiac remodeling occurs over a relatively short timeframe and adverse remodeling is associated with increased risk of HF-related morbidity and mortality.

Background and objectives: Mucormycosis is a complication in post-coronavirus disease 2019 (COVID-19) patients in India. This study was done to evaluate the prognostic value of clinical, histopathologic findings, microbiological features, and biochemical parameters such as D-dimer, lactate dehydrogenase, and serum ferritin in post- COVID-19-patients with rhino-orbital mucormycosis. Methods: This retrospective observational study was carried out on biopsies taken from 50 post-COVID-19 patients suspected of mucormycosis. The biopsy specimens were processed and stained with hematoxylin and eosin, periodic acid–schiff, and Wright-Giemsa. In addition, 10–20% potassium hydroxide wet mount and culture on sabouraud dextrose agar were performed to detect Mucor. The biochemical parameters were measured using ARCHITECT ci8200 chemistry analyzer. Results: Overall, 30 cases (60%) were positive for fungal elements, and growth of Mucor spp. was found in 28 cases (56%). In histopathology, 70% of cases (n=35) showed broad, aseptate, ribbon-like hyphae with wide-angled branching diagnostic of mucormycosis. There seemed to be a site-wise overlap between the nasal/maxillary sinus and rhino-orbital/rhino-cerebral variety. There was no difference between the patients in terms of gender. The most common risk factor was diabetes mellitus (observed in 80% of cases). In patients with invasive mucormycosis, inflammatory biomarkers such as serum ferritin, serum lactate dehydrogenase, C-reactive protein, and D-dimer were greater than the normal range, whereas procalcitonin was within the reference range. Conclusion: It can be concluded that raised metabolic markers, direct 10% KOH examination and histological features including angioinvasion as well as rhino-orbital and cerebral extension might assist doctors in diagnosis, progression, and survival rate.

Abstract Identifying systems failures and contributing to a safety culture is the Association of American Colleges (AAMC’s) thirteenth Entrustable Professional Activity (EPA). While most curricula teach Patient Safety (PS) and Quality Improvement (QI) principles, student participation in live QI/PS activities remains limited. This workshop enabled late Clerkship phase students to apply these Health Systems Science (HSS) principles to real adverse patient event cases through team-based simulation. This 3-h capstone included both a didactic review of QI, PS, and TeamSTEPPS® tools and an experiential component where student-led interactive small group discussions were augmented by resident and faculty preceptors. Collaboratively, students composed an adverse patient event report, conducted a Root Cause Analysis (RCA) during role-play, and proposed error prevention ideas after identifying systems problems. In April 2020, the in-person workshop became fully virtual due to the COVID-19 pandemic. A statistically significant increase in ability to identify Serious Safety Events, Escalation Chain of Command, and define a Plan-Do-Study-Act (PDSA) cycle was observed. Comfort with RCA increased from 48 to 87% and comfort with TeamSTEPPS® principles increased from 68% to 85.5% This novel capstone provided students with the tools to synthesize HSS concepts through problem-solving processes and recognize EPA 13’s importance. Their increased capability to identify appropriate chain of command, escalate concerns, and recognize serious adverse patient events also has training and practice readiness implications.

Abstract Background Systemic amyloidosis is group of disorders characterized by the accumulation of insoluble proteins in tissues. The most common form of systemic amyloidosis is light chain amyloidosis, which results from the accumulation of misfolded immunoglobulins. The disease is progressive, with treatment targeted at the underlying plasma cell dyscrasia. Since essentially any organ system can be affected, the presentation is variable and delays in diagnosis are common. Given this diagnostic difficulty, we discuss four different manifestations of light chain amyloidosis. Case presentations In this case series, we discuss four cases of light chain amyloidosis. These include cardiac, hepatic, and gastrointestinal as well as autonomic and peripheral nerve involvement with amyloidosis. The patients in our series are of Caucasian background and include a 69-year-old female, a 29-year-old female, a 68-year-old male, and a 70-year-old male, respectively. The case discussions highlight variability in presentation and diagnostic challenges. Conclusions Amyloidosis is a rare but serious disease that is often complicated by long delays in diagnosis. Morbidity and mortality can sometimes be limited if diagnosed earlier. We hope our real life cases will contribute to understanding and to early suspicion that can lead to early diagnosis and management.

Abstract Secondary neurologic decline (ND) after traumatic brain injury (TBI) is independently associated with outcome, but robust predictors of ND are lacking. In this retrospective analysis of consecutive isolated TBI admissions to the R. Adams Cowley Shock Trauma Center between November 2015 and June 2018, we aimed to develop a triage decision support tool to quantify risk for early ND. Three machine learning models based on clinical, physiologic, or combined characteristics from the first hour of hospital resuscitation were created. Among 905 TBI cases, 165 (18%) experienced one or more ND events (130 clinical, 51 neurosurgical, and 54 radiographic) within 48 h of presentation. In the prediction of ND, the clinical plus physiologic data model performed similarly to the physiologic only model, with concordance indices of 0.85 (0.824–0.877) and 0.84 (0.812–0.868), respectively. Both outperformed the clinical only model, which had a concordance index of 0.72 (0.688–0.759). This preliminary work suggests that a data-driven approach utilizing physiologic and basic clinical data from the first hour of resuscitation after TBI has the potential to serve as a decision support tool for clinicians seeking to identify patients at high or low risk for ND.

Background: Acute coronary syndrome (ACS) is witnessing a demographic transition with increasing prevalence among younger individuals (≤45 years). Hence, this study was designed to evaluate the clinical features, risk factors, and angiographic profile of young (aged ≤ 45 years) patients with ACS and to compare it with the older (aged >45 years) patients with ACS. Materials and Methods: An observational study was conducted at a tertiary care center in India from July 2020 to December 2021. A total of 157 patients were enrolled, among which 90 patients were included in cases (group-I). The inclusion criteria were patients presenting with ACS aged between 18 and 45 years. There were two control groups, including 34 patients with ACS (aged >45 years) in Group II and 33 healthy volunteers in Group III (aged 18–45 years). Baseline demographic details, risk factors, and angiographic profile of patients with ACS in each group were recorded and compared. Results: Mean age of Group I was 39.79 ± 5.15 years and of Group II was 59.74 ± 8.21 years. Smoking (P = 0.027) and family history of coronary artery disease (P = 0.022) were the significant risk factors of ACS in Group I. Compared to non-ST elevation myocardial infarction (16.7%), ST-elevation myocardial infarction (83.3%) was predominant among younger patients with ACS. Single-vessel disease was prevalent among younger patients (62.2%) as compared to older patients with ACS (41.20%). Conclusion: Younger patients with ACS exhibited a distinct clinical and angiographic profile compared to older patients with ACS.

The World Health Organisation declared the novel coronavirus known as severe acute respiratory syndrome coronavirus 2 a pandemic in March 2020. This virus has led to the deaths of more than 6 million people worldwide. Besides causing pneumonia, COVID-19 is linked to multiple organ dysfunction, including the kidneys, especially in individuals whose immune systems are already compromised. Consequently, individuals who are currently on a waiting list for a kidney transplant or who have recently received a kidney transplant are at a significantly increased risk for developing acute kidney injury and are severely impacted by the COVID-19 infection. The pandemic has negatively affected the transplantation process and led to a decrease in the number of organ donations as well as the volume of renal transplants. This review summarises the outcomes of COVID-19 infection in renal transplant patients, its pathophysiology, the challenges faced by the transplant community, and the management of immunosuppression.

Abstract Sero-surveillance can monitor and project disease burden and risk. However, SARS-CoV-2 antibody test results can produce false positive results, limiting their efficacy as a sero-surveillance tool. False positive SARS-CoV-2 antibody results are associated with malaria exposure, and understanding this association is essential to interpret sero-surveillance results from malaria-endemic countries. Here, pre-pandemic samples from eight malaria endemic and non-endemic countries and four continents were tested by ELISA to measure SARS-CoV-2 Spike S1 subunit reactivity. Individuals with acute malaria infection generated substantial SARS-CoV-2 reactivity. Cross-reactivity was not associated with reactivity to other human coronaviruses or other SARS-CoV-2 proteins, as measured by peptide and protein arrays. ELISAs with deglycosylated and desialated Spike S1 subunits revealed that cross-reactive antibodies target sialic acid on N-linked glycans of the Spike protein. The functional activity of cross-reactive antibodies measured by neutralization assays showed that cross-reactive antibodies did not neutralize SARS-CoV-2 in vitro. Since routine use of glycosylated or sialated assays could result in false positive SARS-CoV-2 antibody results in malaria endemic regions, which could overestimate exposure and population-level immunity, we explored methods to increase specificity by reducing cross-reactivity. Overestimating population-level exposure to SARS-CoV-2 could lead to underestimates of risk of continued COVID-19 transmission in sub-Saharan Africa.