The STRAT-PARK cohort: A personalized initiative to stratify Parkinson's disease.

The STRAT-PARK initiative aims to provide a platform for stratifying Parkinson's disease (PD) into biological subtypes, using a bottom-up, multidisciplinary biomarker-based and data-driven approach. PD is a heterogeneous entity, exhibiting high interindividual clinicopathological variability. This diversity suggests that PD may encompass multiple distinct biological entities, each driven by different molecular mechanisms. Molecular stratification and identification of disease subtypes is therefore a key priority for understanding and treating PD. STRAT-PARK is a multi-center longitudinal cohort aiming to recruit a total of 2000 individuals with PD and neurologically healthy controls from Norway and Canada, for the purpose of identifying molecular disease subtypes. Clinical assessment is performed annually, whereas biosampling, imaging, and digital and neurophysiological phenotyping occur every second year. The unique feature of STRAT-PARK is the diversity of collected biological material, including muscle biopsies and platelets, tissues particularly useful for mitochondrial biomarker research. Recruitment rate is ∼150 participants per year. By March 2023, 252 participants were included, comprising 204 cases and 48 controls. STRAT-PARK is a powerful stratification initiative anticipated to become a global research resource, contributing to personalized care in PD.

How Do Learners Receive Feedback on Note-Writing? A Scoping Review.

PURPOSE: The literature assessing the process of note-writing based on gathered information is scant. This scoping review investigates methods of providing feedback on learners' note-writing abilities. METHOD: Scopus and Web of Science were searched for studies that investigated feedback on student notes or reviewed notes written on an information or data-gathering activity in health care and other fields in August 2022. Of 426 articles screened, 23 met the inclusion criteria. Data were extracted on the article title, publication year, study location, study aim, study design, number of participants, participant demographics, level of education, type of note written, field of study, form of feedback given, source of the feedback, and student or participant rating of feedback method from the included articles. Then possible themes were identified and a final consensus-based thematic analysis performed. RESULTS: Themes identified in the 23 included articles were as follows: (1) Learners found faculty and peer feedback beneficial; (2) Direct written comments and evaluation tools, such as rubrics or checklists, were the most common feedback methods; (3) Reports on notes in real clinical settings were limited (simulated clinical scenarios in preclinical curriculum were the most studied); (4) Feedback providers and recipients benefit from having prior training on providing and receiving feedback; (5) Sequential or iterative feedback was beneficial for learners but can be time intensive for faculty and confounded by maturation effects; and (6) Use of technology and validated assessment tools facilitate the feedback process through ease of communication and improved organization. CONCLUSIONS: The various factors influencing impact and perception of feedback include the source, structure, setting, use of technology, and amount of feedback provided. As the utility of note-writing in health care expands, studies are needed to clarify the value of note feedback in learning and the role of innovative technologies in facilitating note feedback.

Effects of high bilirubin level in pregnancy in Crigler-Najjar syndrome type 2: An extremely rare but important clinical entity to recognize.

Crigler-Najjar is a rare genetic autosomal recessive disorder caused by deficiency of enzyme Uridine 5-Diphosphate Glucuronosyl Transferase (UDP-GT). We report the case of a 24-year-old female with two consecutive pregnancies with a high level of total bilirubin level of 15.1 mg/dl and a direct bilirubin level of 0.8 mg/dl during the first pregnancy. As she was diagnosed case of Crigler Najjar type 2, she was on phenobarbitone 60 mg daily. With careful monitoring, she continued with the same dose. We concluded that even with high bilirubin level (15.1 mg/dl) in pregnancy, no adverse effects to the baby and mother were seen.

Comparative proteomic investigation unravels the pathobiology of Mycobacterium fortuitum biofilm.

Biofilm formation by Mycobacterium fortuitum causes serious threats to human health due to its increased contribution to nosocomial infections. In this study, the first comprehensive global proteome analysis of M. fortuitum was reported under planktonic and biofilm growth states. A label-free Q Exactive Quadrupole-Orbitrap tandem mass spectrometry analysis was performed on the protein lysates. The differentially abundant proteins were functionally characterized and re-annotated using Blast2GO and CELLO2GO. Comparative analysis of the proteins among two growth states provided insights into the phenotypic switch, and fundamental pathways associated with pathobiology of M. fortuitum biofilm, such as lipid biosynthesis and quorum-sensing. Interaction network generated by the STRING database revealed associations between proteins that endure M. fortuitum during biofilm growth state. Hypothetical proteins were also studied to determine their functional alliance with the biofilm phenotype. CARD, VFDB, and PATRIC analysis further showed that the proteins upregulated in M. fortuitum biofilm exhibited antibiotic resistance, pathogenesis, and virulence. Heatmap and correlation analysis provided the biomarkers associated with the planktonic and biofilm growth of M. fortuitum. Proteome data was validated by qPCR analysis. Overall, the study provides insights into previously unexplored biochemical pathways that can be targeted by novel inhibitors, either for shortened treatment duration or for eliminating biofilm of M. fortuitum and related nontuberculous mycobacterial pathogens. KEY POINTS: • Proteomic analyses of M. fortuitum reveals novel biofilm markers. • Acetyl-CoA acetyltransferase acts as the phenotype transition switch. • The study offers drug targets to combat M. fortuitum biofilm infections.

Early virus clearance of SARS-CoV-2 among co-infection with malaria.

BACKGROUND AND OBJECTIVES: India has witnessed significant number of cases of co-infection of malaria or dengue with COVID-19, especially during the monsoon season. It has been speculated that anti-malarial immunity might have a protective role in co-infection. Retrospective analysis of co-infection of vector-borne diseases with COVID-19 was done for comparing their remission with matched controls with COVID-19 by means of epidemiological data. METHODS: Medical case records of patients with co-infection of malaria or dengue with COVID-19 admitted at TNMC and BYL Nair Charitable Hospital from 1 March 2020 to 31 October 2020 were analyzed retrospectively. Out of 91 cases of co-infection of SARS-CoV-2 infection with vector-borne diseases, virus clearance (VC) analysis was done for 61 co-infections with malaria. RESULTS: Median duration of VC for co-infection with malaria was 8 days whereas, it was 12 days for controls with COVID-19 (p=0.056). Young patients (≤50 years) with co-infection recovered faster than controls age (p=0.018). INTERPRETATION & CONCLUSION: Co-infection with malaria is associated with less severe disease and early recovery in the form of early VC. Genetic and immunological studies are necessary to confirm malaria protection against SARS-CoV-2 infection.

New physics searches at kaon and hyperon factories.

Rare meson decays are among the most sensitive probes of both heavy and light new physics. Among them, new physics searches using kaons benefit from their small total decay widths and the availability of very large datasets. On the other hand, useful complementary information is provided by hyperon decay measurements. We summarize the relevant phenomenological models and the status of the searches in a comprehensive list of kaon and hyperon decay channels. We identify new search strategies for under-explored signatures, and demonstrate that the improved sensitivities from current and next-generation experiments could lead to a qualitative leap in the exploration of light dark sectors.

Definitive chemoradiation in nonmetastatic squamous cell carcinoma anal canal: A single-institution experience.

Purpose: The purpose of the study was to analyze the survival outcomes and toxicities in squamous cell carcinoma anal canal treated with definitive chemoradiotherapy. Materials and Methods: Retrospective analysis of 51 patients with squamous cell carcinoma anal canal treated with chemoradiotherapy was done. Data were collected and analyzed for disease-free survival (DFS), colostomy-free survival (CFS), overall survival (OS), and acute/late toxicities. Results: Out of total 51 patients, only 44 patients had a follow-up of more than 36 months and were analyzed. After a median follow-up of 46 months (range 10-68 months), the 3-year DFS was 73.9%. Three patients developed locoregional recurrence, while one patient developed distant metastasis. At 3-year OS rate was 77%. Out of 44 patients, six patients lost to follow-up, while two patients died due to progressive disease and two due to noncancer causes. 3-year CFS rate was 59%. Most common grade >3 acute toxicities were skin reactions in nine (18%), followed by hematological in eight (16%) patients. Conclusion: Definitive chemoradiotherapy in anal canal results in good oncological outcomes with sphincter preservation. No severe treatment-related toxicities were observed.

The Impact of Internal Medicine Clerkship Characteristics and NBME Subject Exams on USMLE Step 2 Clinical Knowledge Exam Performance.

BACKGROUND: Residency program directors will likely emphasize the United States Medical Licensing Exam (USMLE) Step 2 clinical knowledge (CK) exam more during residency application given the recent USMLE Step 1 transition to pass/fail scoring. We examined how internal medicine clerkship characteristics and NBME subject exam scores affect USMLE Step 2 CK performance. DESIGN: The authors used univariable and multivariable generalized estimating equations to determine associations between Step 2 CK performance and internal medicine clerkship characteristics and NBME subject exams. The sample had 21,280 examinees' first Step 2 CK scores for analysis. RESULTS: On multivariable analysis, Step 1 performance (standardized ß = 0.45, p < .001) and NBME medicine subject exam performance (standardized ß = 0.40, p < .001) accounted for approximately 60% of the variance in Step 2 CK performance. Students who completed the internal medicine clerkship last in the academic year scored lower on Step 2 CK (Mdiff = -3.17 p < .001). Students who had a criterion score for passing the NBME medicine subject exam scored higher on Step 2 CK (Mdiff = 1.10, p = .03). There was no association between Step 2 CK performance and other internal medicine clerkship characteristics (all p > 0.05) nor with the total NBME subject exams completed (ß=0.05, p = .78). CONCLUSION: Despite similarities between NBME subject exams and Step 2 CK, the authors did not identify improved Step 2 CK performance for students who had more NBME subject exams. The lack of association of Step 2 CK performance with many internal medicine clerkship characteristics and more NBME subject exams has implications for future clerkship structure and summative assessment. The improved Step 2 CK performance in students that completed their internal medicine clerkship earlier warrants further study given the anticipated increase in emphasis on Step 2 CK.

Predictors of Severity and Mortality in Chronic Liver Disease Patients With COVID-19 During the Second Wave of the Pandemic in India.

Background Coronavirus disease 2019 (COVID-19) infection in chronic liver disease patients is associated with poor outcomes. In this study, we aimed to evaluate the predictors of severity and mortality in this group of patients during the second wave of the COVID-19 pandemic in India. In addition, we compared cirrhotic patients with COVID-19 with cirrhotic patients from the pre-COVID-19 period. Methodology This was a single-center observational study. We included data from 50 patients with cirrhosis and COVID-19 retrospectively from the discharge/death files. A comparison group of 100 patients with cirrhosis from the pre-COVID period was also analyzed retrospectively. Results The majority of patients had predominantly respiratory symptoms, with fever being the most common symptom (85%). The most common presentation was acute on chronic liver failure (ACLF). The most common form of decompensation was jaundice followed by hepatic encephalopathy. The overall mortality in cirrhotic patients with COVID-19 was double than that in cirrhotic patients from the pre-COVID-19 period. All patients with ACLF succumbed to multiorgan failure. Diabetes was the only comorbidity that was associated with severe infection. Higher creatinine on admission and high D-dimer levels correlated with severity. D-dimer was the only parameter that correlated with severity and mortality on multivariate analysis. None of the comorbidities predicted mortality. Among various composite scores, the Child-Turcotte-Pugh (CTP) score and CURB-65 correlated with mortality. On the area under the receiver operating characteristic analysis, a D-dimer level of >1.1 mg/L was associated with mortality. Conclusions COVID-19 infection in patients with cirrhosis is associated with poor outcomes. D-dimer levels of >1.1 mg/L on admission are a simple parameter to predict mortality. CTP and CURB-65 are composite scores that correlate with mortality in this group of patients.

Postinfectious SARS-CoV-2 Opsoclonus-Myoclonus-Ataxia Syndrome.

BACKGROUND: The opsoclonus-myoclonus-ataxia syndrome (OMAS) represents a pathophysiology and diagnostic challenge. Although the diverse etiologies likely share a common mechanism to generate ocular, trunk, and limb movements, the underlying cause may be a paraneoplastic syndrome, as the first sign of cancer, or may be a postinfectious complication, and thus, the outcome depends on identifying the trigger mechanism. A recent hypothesis suggests increased GABAA receptor sensitivity in the olivary-oculomotor vermis-fastigial nucleus-premotor saccade burst neuron circuit in the brainstem. Therefore, OMAS management will focus on immunosuppression and modulation of GABAA hypersensitivity with benzodiazepines. METHODS: We serially video recorded the eye movements at the bedside of 1 patient with SARS-CoV-2-specific Immunoglobulin G (IgG) serum antibodies, but twice-negative nasopharyngeal reverse transcription polymerase chain reaction (RT-PCR). We tested cerebrospinal fluid (CSF), serum, and nasopharyngeal samples. After brain MRI and chest, abdomen, and pelvis CT scans, we treated our patient with clonazepam and high-dose Solu-MEDROL, followed by a rituximab infusion after her formal eye movement analysis 10 days later. RESULTS: The recordings throughout her acute illness demonstrated different eye movement abnormalities. While on high-dose steroids and clonazepam, she initially had macrosaccadic oscillations, followed by brief ocular flutter during convergence the next day; after 10 days, she had bursts of opsoclonus during scotopic conditions with fixation block but otherwise normal eye movements. Concern for a suboptimal response to high-dose Solu-MEDROL motivated an infusion of rituximab, which induced remission. An investigation for a paraneoplastic etiology was negative. CSF testing showed elevated neuron-specific enolase. Serum IgG to Serum SARS-CoV2 IgG was elevated with negative RT-PCR nasopharyngeal testing. CONCLUSION: A recent simulation model of macrosaccadic oscillations and OMAS proposes a combined pathology of brainstem and cerebellar because of increased GABAA receptor sensitivity. In this case report, we report 1 patient with elevated CSF neuronal specific enolase, macrosaccadic oscillations, ocular flutter, and OMAS as a SARS-CoV-2 postinfectious complication. Opsoclonus emerged predominantly with fixation block and suppressed with fixation, providing support to modern theories on the mechanism responsible for these ocular oscillations involving cerebellar-brainstem pathogenesis.

Pattern of liver function test variations in COVID-19 infection & its clinical significance: A study from a dedicated COVID-19 tertiary care centre from India.

Background & objectives: Coronavirus disease 2019 (COVID-19) affects respiratory, gastrointestinal, cardiovascular and other systems disease. Studies describing liver involvement and liver function test (LFT) abnormalities are sparse from our population. This study was undertaken to estimate the LFT abnormalities in patients with COVID-19 in a tertiary care set up in India. Methods: In this retrospective study conducted at a tertiary care centre in Mumbai, India, all consecutive patients with proven COVID-19 by reverse transcriptase-PCR from March 23 to October 31, 2020 were enrolled. Of the 3280 case records profiled, 1474 cases were included in the study. Clinical characteristics, biochemical parameters and outcomes were recorded. Results: Overall 681 (46%) patient had deranged LFTs. Hepatocellular type of injury was most common (93%). Patients with deranged LFTs had more probability of developing severe disease (P<0.001) and mortality (P<0.001). Advanced age (P<0.001), male gender (P<0.001), diabetes mellitus (P<0.001), lower oxygen saturation levels at admission (P<0.001), higher neutrophil-lymphocyte ratio (P<0.001), history of diabetes mellitus and cirrhosiss were associated with deranged LFTs. Acute liver injury was seen in 65 (4.3%) cases on admission and 57 (3.5%) cases during hospital stay. On multivariate analysis for predicting mortality, age >60 yr serum creatinine >2 mg%, PaO2/FiO2 ratio ≤200 and raised AST >50 IU/l (OR: 2.34, CI: 1.59-3.48, P<0.001) were found to be significant. Interpretation & conclusions: In COVID-19, LFT abnormalities were common, and derangement increased as severity progressed. The presence of deranged LFT worsens the clinical outcome and predicts in-hospital mortality.

Is Increased BMI a Risk Factor for Developing Severe Clostridioides Difficile Infection? A Retrospective Study.

Background: Obesity is associated with a relative increase in bacterial phyla like firmicutes, which helps in the colonization of Clostridioides Difficile. Hypothesis: Individuals with increased BMI (greater than 25) are more susceptible to severe Clostridioides Difficile infection (CDI). Methods: Data was collected by retrospective chart query. Severe CDI was defined as a white blood cell count of more than 15,000 (x 109 cells/L) or serum creatinine levels greater than 1.5 mg/dL. To examine the association between the primary outcome (severe CDI) and BMI, the factors of age, gender, albumin level, ICU admission, antibiotic use within 3 months of admission, diabetes, and hypertension were also considered. Patients with chronic kidney disease, end-stage liver disease, pregnancy, inflammatory bowel disease, previous gastrointestinal surgeries, active malignancy, and immunosuppressed were excluded. Results: 219 patients were included in the final study. Of these 52.8% of patients had severe CDI, and 47.2% had non-severe CDI. Compared to normal-weight patients, risk of severe CDI was not influenced by being obese (OR = 1.26, p = 0.5119), overweight (OR = 1.65, p = 0.21), or underweight (OR = 1.05, p = 0.9383). Males had higher odds of having severe CDI when compared with females (OR = 1.76, 95% CI = 1.03 to 3.01, p = 0.0395). Albumin levels greater than 3.0 mg/dL were associated with lower odds of having severe CDI (OR = 0.41, 95% CI = 0.27 to 0.62, p< 0.0001). Conclusion: BMI of an individual does not appear to be associated with the severity of CDI.

A retrospective study on factors affecting the dropout rate among temporomandibular joint internal disc derangement patients in India - A single-institution experience.

Introduction: Patients suffering temporomandibular joint internal disc derangement (IDD) ignore appointments after the first examination or after the first or second sessions of initial treatment. The dropout rate for these patients varies from 36% to 78% as per literature. Unfortunately, very few studies have investigated the dropout rate of these patients. Hence, the present study was undertaken to find out the dropout rate among these kinds of patients. Material and Methods: A retrospective study was done from June 2008 to December 2017 by collecting the records of the patients who were diagnosed to have IDD. Outcome variables included were age, sex, distance traveled, occupation, and education. Results: Out of 1021 patients 766 patients were included in the study after fulfilling the inclusion and exclusion criteria. The data were analyzed using Chi-square test. The level of significance was set at <0.05. In this study, there is slight male predominance (52.8%) and 63.1% (21-40 years) were among young adults and the patients in the age group of 21-30 years had shown good compliance, Postgraduate has shown the highest follow-up rate when compared with graduates and school level and the difference was found to be statistically significant. People in the job had shown good compliance when compared with business class and retired people and the patients within 50 km had shown the maximum follow-up with a statistically significant difference (P < 0.01). Conclusion: This study has shown that the dropout rate of treatment in temporomandibular joint disorder is affected by age, sex, distance traveled, occupation, and education.

Recurrent arteriovenous graft thrombosis in COVID-19 positive patient.

Hypercoagulability is one of the common complications seen in COVID-19. It can lead to multiple thromboembolic complications. Recurrent arteriovenous graft thrombosis can be one of complications from this pathophysiology.

Deaths due to delayed presentation to the hospital from fear of contracting COVID-19 during lockdown period: a tertiary care center experience.

Background: Sudden rise in COVID-19 cases in March 2020 due to spread of pandemic led to immediate lockdown order in many states and cities across the USA. Everyone had to stay home to stop the spread of the virus. We investigated all deaths in our hospital during lockdown period and assessed how many presented and died from non-COVID-19-related illness. Among those deaths, we assessed how many presented late due to excessive fear of catching coronavirus in the hospital and succumbed to the same illness due to very late presentation. Methods: We retrospectively reviewed charts of every patient who expired in the hospital in a 45-day period, March-April 2020. Results: Three of 107 (2.8%) deaths during lockdown period in this hospital were clearly attributable to delayed presentation arising specifically from fear of coming to the hospital. All three died from non-COVID-19-related illnesses. Conclusions: Authors hereby propose enhanced efforts in the direction to alleviate unnecessary fear among public even during lockdown. People should be encouraged to continue to access health care for serious/fatal medical conditions regardless of the pandemic.

Arginine depriving enzymes: applications as emerging therapeutics in cancer treatment.

Cancer is the second leading cause of death globally. Chemotherapy and radiation therapy and other medications are employed to treat various types of cancer. However, each treatment has its own set of side effects, owing to its low specificity. As a result, there is an urgent need for newer therapeutics that do not disrupt healthy cells' normal functioning. Depriving nutrient or non/semi-essential amino acids to which cancerous cells are auxotrophic remains one such promising anticancer strategy. L-Arginine (Arg) is a semi-essential vital amino acid involved in versatile metabolic processes, signaling pathways, and cancer cell proliferation. Hence, the administration of Arg depriving enzymes (ADE) such as arginase, arginine decarboxylase (ADC), and arginine deiminase (ADI) could be effective in cancer therapy. The Arg auxotrophic cancerous cells like hepatocellular carcinoma, human colon cancer, leukemia, and breast cancer cells are sensitive to ADE treatment due to low expression of crucial enzymes argininosuccinate synthetase (ASS), argininosuccinate lyase (ASL), and ornithine transcarbamylase (OCT). These therapeutic enzyme treatments induce cell death through inducing autophagy, apoptosis, generation of oxidative species, i.e., oxidative stress, and arresting the progression and expansion of cancerous cells at certain cell cycle checkpoints. The enzymes are undergoing clinical trials and could be successfully exploited as potential anticancer agents in the future.