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.

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.

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.

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.

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.

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.

Production and characterization of a novel, thermotolerant fungal phytase from agro-industrial byproducts for cattle feed.

OBJECTIVE: The application of phytases helps in releasing bound phosphorus and other nutrients in cattle feed eventually reducing the need for supplementations. However, high production cost owing to the unavailability of cheaper sources of phytases has limited their usage in developing countries. Herein, firstly isolation, identification of a phytase from fungal isolate, Aspergillus niger NT7 was carried out followed by optimizing of all production parameters, through solid-state fermentation (SSF). Secondly, crude phytase was characterized and potential applicability of crude phytase was evaluated for dephytinization of wheat bran. RESULTS: The highest phytase production (208.30 ± 0.22 U/gds) was achieved using wheat bran as cheap agro-industrial substrate for SSF. The various physiological parameters were optimized including inoculum age and level (3-day old inoculum and 15 × 107 spores/ml), temperature (35 °C), a moistening agent (distilled water), medium pH (5), and supplementation of various biochemicals like sugar (Mannitol), nitrogen (ammonium sulphate) and detergent (Tween 80). Process optimization through one variable at a time (OVAT) approach increased the difference in productivity to more than 200%. The crude phytase of A. niger NT7 was thermostable, with optimal activity at 60 °C and also displayed optimal activity over a broad range of acidic pH. Further, enhancement in phytase activity was found specifically in the presence of Ca2+, Zn2+, and Co2+ ions, while other metal ions including Fe2+, Fe3+, Mn2+, Mg2+and Cu2+ inhibited its activity. Finally, the phytase showed efficient and sustained release of inorganic phosphate, proteins, and reducing sugars (> 60 h) from livestock feed. CONCLUSION: Overall, our report highlights the production of an efficient and thermotolerant phytase with potential as a low-cost animal feed supplement.

Expression of Ki-67 in early glottic carcinoma and its relation to oncological outcomes following CO2 laser microsurgery.

INTRODUCTION: The behavior of the laryngeal squamous cell carcinoma (LSCC) is marked by the degree of cell proliferation and differentiation. Ki-67 is regarded as a promising proliferation marker and has been correlated as a prognostic indicator. AIM: The aim of the present study is to determine the Ki-67 expression and its prognostic value in LSCC. MATERIALS AND METHODS: A total of eighty patients with early glottic carcinoma stage (Tis, T1, T2) N0 M0 were included. After preoperative workup, surgery was performed using LUMINES 40C CO2 laser and tumor resection was done which was sent for histopathological diagnosis and immunohistochemistry (IHC). IHC for Ki-67 expression could be done only on 65 specimens. RESULTS: All patients had microscopically confirmed squamous cell carcinoma. Forty-eight out of 65 specimens (75%) stained positive for Ki-67 and 17 (25%) stained negative. Out of total 48, 29 stained 2+, 11 stained 3+ and 8 stained 4+. No difference was found in Ki-67 expression in relation to age, sex, T stage, and histological grading. The association of Ki-67 with recurrence was found to be statistically significant. The association of Ki-67 with survival was also studied and Ki-67 positivity is associated with increased mortality rate, although it was not statistically significant. CONCLUSION: The proliferative index as measured by immunohistochemical staining of Ki-67 correlates with the tumor aggressiveness. High Ki-67 index is associated with early relapse and poor survival outcomes.

Combined repeat laparoscopy and transanal endolumenal repair (hybrid approach) in the early management of postoperative colorectal anastomotic leaks: technique and outcomes.

BACKGROUND: Few clear recommendations exist for the management of colorectal anastomotic leaks, often based on surgeon preferences or institutional protocols. The primary goal was to evaluate the feasibility and safety of the combined laparoscopic and transanal (hybrid) approach to treat postoperative colorectal anastomotic leaks. The secondary goals included comparison of outcomes following early (< 5 days after initial resection) versus late (≥ 5 days) detection of leaks. MATERIALS AND METHODS: Sixteen hemodynamically stable patients, with anastomotic dehiscence < 50% of the circumference after laparoscopic anterior resection underwent repeat laparoscopy (lavage/drainage) and transanal endolumenal repair (7 low (< 5 cm from the anal verge) with an ordinary anoscope and 9 high (≥ 5 cm from the anal verge) with a transanal endoscopic operations (TEO®) platform). RESULTS: The median delay to detection and management was 4.5 days. The procedure was feasible in 13/16 patients (3 patients required conversion to laparotomy). Primary healing of the anastomosis was obtained in 14 patients (13 with the combined procedure, one after conversion). Two patients (1 early, 1 late) sustained persistent purulent discharge via their drain, but the repair healed secondarily. All patients requiring conversion to laparotomy (n = 3) or sustaining intra-operative complications (n = 3) were in the delayed group. No patients required further intervention or died. Protective stomas, created either at index surgery (n = 7) or at re-operation (n = 9), were closed in 14/16 patients within 6 months and no anastomotic sinus, persistent or recurrent fistula, was noted at 1-year follow-up. LIMITATIONS: This is a single-center study consisting of small sample size. CONCLUSIONS: Combined repeat laparoscopy and transanal endolumenal repair is feasible and safe, potentially reducing postoperative morbidity associated with repeat laparotomy and anastomotic leaks. Early detection and re-intervention are fundamental to success. Currently missing from the International Study Group of Rectal Cancer recommendations, laparoscopy and endolumenal repair could be added as a therapeutic option in Grade B.

Initial retrocolic endoscopic tunnel approach (IRETA) for complete mesocolic excision (CME) with central vascular ligation (CVL) for right colonic cancers: technique and pathological radicality.

INTRODUCTION: The concept of complete mesocolic excision (CME) with central vascular ligation (CVL) for treatment of right colon cancer evolved over last one decade. It decreases local recurrences and improves the survival rates. We describe our novel technique which involves first posterior sharp dissection between planes of parietal and visceral fascia of mesocolon followed by ligation of ileocolic, right colic and middle colic pedicles at their origin. We highlight the technical variations with various techniques and advantages over conventional medial to lateral approach in current study. AIM: The outcomes were measured in terms of technical feasibility, short-term outcomes and pathological radicality of current laparoscopic technique (IRETA) for CME with CVL. MATERIALS AND METHODS: Two hundred twelve patients (163 males) who underwent laparoscopic CME for right colon cancer over the period of January 2009 to December 2013 were analysed via prospectively maintained database. RESULTS: 97.16 % of patients (n = 206) underwent laparoscopic CME while six patients required open conversion. Mean operative time was 142 ± 28.4 min with median hospital stay of 5 days (range 4-11). The median count of lymph node harvested were 24 (range 10-42). The complete mesocolic excision plane was achieved in 93.8 % patients. 84.4 % (n = 179) of our patients were having (T3, N+) disease on pathological examination. The overall morbidity (<30 days) was 9.9 %. CONCLUSION: Laparoscopic initial retrocolic endoscopic tunnel approach (IRETA) for CME with CVL in right colonic cancers is safe, simpler and feasible laparoscopic approach with minimal complications. Creation of retro colic tunnel is key highlight of IRETA approach. This approach becomes especially useful in patients with late presentations where complete mesocolic excision remains essential to enhance oncological radicality as per evidence available.

A single-centre experience of relaparoscopy in complications of laparoscopic inguinal hernia repair-feasibility and outcomes.

BACKGROUND: Management of complications of laparoscopic inguinal hernia repair remains challenging as well as debatable. Relaparoscopy in management of these complications is relatively newer concept. We tried to analyse the feasibility of relaparoscopy (transabdominal preperitoneal approach) in management of complications of laparoscopic inguinal hernia repair. MATERIALS AND METHODS: The study group included 61 patients (referral cases) from a prospectively maintained database of previous laparoscopic inguinal hernia surgery with majority of the patients of recurrence (n = 39). Other complications were mesh infections (n = 15), pubic osteitis (n = 3), migration of mesh into adjacent viscera (n = 3) and meralgia paresthetica (n = 1). All patients underwent transabdominal preperitoneal approach (TAPP) between January 2007 and December 2013. RESULTS AND OUTCOME: Most of the patients had previous TEP repair (n = 49) with variable complications detected in the range of 9 days to 38 months. Small-sized mesh (n = 12) and rolled up mesh (n = 10) were the causes of recurrence in 57 % cases. Mycobacterium tuberculosis (40 %) and mixed bacterial infections (33 %) strains were detected in the infected mesh. Pubic osteitis and meralgia paresthetica were tackers induced. All patients dealt with TAPP approach. Recurrent hernia cases underwent mesh placement and infected mesh was removed in mesh infection. Tackers were removed in cases of osteitis pubis and meralgia paraesthesia. Median operative time was 62 min (42-126 min) and hospital stay 3 days (2-13 days). The relaparoscopy was accomplished in 95.1 % of cases with no major intraoperative complications and minimal postoperative morbidity. CONCLUSION: Relaparoscopy through TAPP approach remains safe and feasible option to deal with primary laparoscopic hernia repair complications. Surgical techniques during primary laparoscopic repair are important cause for aforementioned complications. Though, surgical expertize remains warranted for relaparoscopy.

Retraction: Characterization of cellulolytic activities of newly isolated Thelephora sowerbyi from North-Western Himalayas on different lignocellulosic substrates.

Characterization of cellulolytic activities of newly isolated Thelephora sowerbyi from North-Western Himalayas on different lignocellulosic substrate J. Basic Microbiol. 2015, 55, 1-11 - DOI: 10.1002/jobm.201500107 The above article from the Journal of Basic Microbiology, published online on 08 June 2015 in Wiley Online Library as Early View (http://onlinelibrary.wiley.com/doi/10.1002/jobm.201500107/pdf), has been retracted by agreement between the authors, the Editor-in-Chief and Wiley-VCH GmbH & Co. KGaA. The retraction has been agreed because the microorganism studied in the described experiments has been identified as the fungus Cotylidia pannosa (Gene Accession No. KT008117) instead of Thelephora sowerbyi. The culture has been identified on the basis of the sequence of the amplified ITS region of the microorganism which was submitted by the authors to the NCBI database.

Minimally invasive Mckeown esophagectomy with modified three-field lymphadenectomy in case of situs inversus totalis with carcinoma mid esophagus.

Performing complex surgical procedures in patients with situs inversus totalis is a challenge because of the need to orient to the completely mirror transposed abdominal and thoracic viscera. We report our experience in performing a three phase minimally invasive (thoracoscopic and laparoscopic) esophagectomy for carcinoma of the mid esophagus in a patient with situs inversus totalis. We believe that this is the first reported case of this kind.

Structural and functional insights into an archaeal L-asparaginase obtained through the linker-less assembly of constituent domains.

Covalent linkers bridging the domains of multidomain proteins are considered to be crucial for assembly and function. In this report, an exception in which the linker of a two-domain dimeric L-asparaginase from Pyrococcus furiosus (PfA) was found to be dispensable is presented. Domains of this enzyme assembled without the linker into a conjoined tetrameric form that exhibited higher activity than the parent enzyme. The global shape and quaternary structure of the conjoined PfA were also similar to the wild-type PfA, as observed by their solution scattering profiles and X-ray crystallographic data. Comparison of the crystal structures of substrate-bound and unbound enzymes revealed an altogether new active-site composition and mechanism of action. Thus, conjoined PfA is presented as a unique enzyme obtained through noncovalent, linker-less assembly of constituent domains that is stable enough to function efficiently at elevated temperatures.

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 was 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.

Adequacy of sigmoidoscopy as compared to colonoscopy for assessment of disease activity in patients of ulcerative colitis: a prospective study.

Background/Aims: Patients of ulcerative colitis (UC) on follow-up are routinely evaluated by sigmoidoscopy. There is no prospective literature to support this practice. We assessed agreement between sigmoidoscopy and colonoscopy prospectively in patients with disease extent beyond the sigmoid colon. Methods: We conducted a prospective observational study at a tertiary care institute for agreement between sigmoidoscopy and colonoscopy. We assessed endoscopic activity using the Mayo Endoscopic Score (MES) and Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and histological activity using the Nancy Index (NI), Robarts Histopathology Index (RHI), and Simplified Geboes Score (SGS). Results: Sigmoidoscopy showed a strong agreement with colonoscopy for MES and UCEIS with a kappa (K) of 0.96 and 0.94 respectively. The misclassification rate for MES and UCEIS was 3% and 5% respectively. Sigmoidoscopy showed perfect agreement (K = 1.00) with colonoscopy for assessment of the presence of endoscopic activity in the colon using MES ??1 as activity criteria and strong agreement (K = 0.93) using MES > 1 as activity criteria. Sigmoidoscopy showed strong agreement with colonoscopy for assessment of the presence of endoscopic activity using UCEIS (K = 0.92). Strong agreement was observed between sigmoidoscopy and colonoscopy using NI (K = 0.86), RHI (K = 1.00), and SGS (K = 0.92) for the detection of histological activity. The misclassification rate for the detection of histological activity was 2%, 0%, and 1% for NI, RHI, and SGS respectively. Conclusions: Sigmoidoscopy showed strong agreement with colonoscopy for endoscopic and histologic disease activity. Sigmoidoscopy is adequate for assessment of disease activity in patients with UC during follow-up evaluation.