Complications of Percutaneous Nephrolithotomy: Experience From a Tertiary Care Center.

Introduction Renal stones are mineral concretions in the pelvicalyceal system. Their prevalence and recurrence are increasing globally. Percutaneous nephrolithotomy (PCNL) is a minimally invasive procedure for the removal of kidney stones. It is a safer technique offering the highest stone-free rates. However, a few complications may still occur. We aimed to evaluate our experiences of PCNL and classify the complications as intraoperative, early postoperative, and late postoperative events. We also aimed to find the predictors of complications in PCNL. Methods A single-center prospective observational study was conducted from June 2021 to October 2022 where all patients who were >18 years old with radiopaque calculus in the kidney and underwent PCNL were included. Statistical analysis was performed using the IBM Statistical Package for Social Sciences (SPSS) software (IBM SPSS Statistics, Armonk, NY). A p-value of <0.05 was considered significant. Results Two hundred one patients including 137 males and 64 females participated in the study. The overall rate of complications was 21.9%. Most of the patients (16.4%) experienced minor complications of Clavien grades 1 and 2. A Clavien grade of >3 included major complications and was noted in 5.5% of patients. No mortality was seen in the postoperative period. Female patients (p = 0.028), a stone burden of >3 cm (p = 0.003), stones in multiple calyces (p = 0.001), hydronephrosis (p = 0.001), history of recently treated urinary tract infection (UTI) (p < 0.001), longer operative time (>91 minutes) (p < 0.001), Guy's stone scores (GSS) III and IV (p < 0.001), complex renal calculi (staghorn) (p = 0.002), and multiple punctures (p = 0.001) were associated with higher complication rates after PCNL. Conclusion Most PCNL-related complications are minor and resolve with conservative or minimally invasive management. However, there are certain complications that can limit the surgical outcome. The overall complication rate in the current study is similar to that reported in the literature. Bleeding was the most common intraoperative complication, whereas hematuria was the most common early postoperative complication. A stone burden of >3 cm, hydronephrosis, longer operative time, higher GSS, and multiple punctures can all affect the rate of complications.

Incidence of and risk factors for small vulnerable newborns in north India: a secondary analysis of a prospective pregnancy cohort.

BACKGROUND: Globally, recent estimates have shown there have been 3·6 million stillbirths and neonatal deaths in 2022, with nearly 60% occurring in low-income and middle-income countries. The Small Vulnerable Newborn Consortium has proposed a framework combining preterm birth (<37 weeks of gestation), small for gestational age (SGA) by INTERGROWTH-21st standard, and low birthweight (<2500 g) under the category small vulnerable newborns (SVN). Reliable data on SVN from sub-Saharan Africa, central Asia, and south Asia are sparse. We aimed to estimate the incidence of SVN and its types, and quantify risk factors, both overall and trimester-specific, from a pregnancy cohort in north India. METHODS: In the GARBH-Ini (Interdisciplinary Group for Advanced Research on Birth Outcomes-DBT India Initiative) pregnancy cohort, 8000 participants were enrolled with less than 20 weeks' gestation between May 11, 2015, and Aug 8, 2020, at a secondary-care hospital in north India. The cohort was followed up across the antenatal period for a detailed study on preterm birth. We conducted a secondary analysis of cohort data for the outcome of SVN, classified into its types: preterm-SGA, preterm-nonSGA, and term-SGA. We estimated the relative risk and population attributable fraction of candidate risk factors for SVN (modified Poisson regression) and its types (multinomial regression). FINDINGS: 7183 (89·9%) of 7990 participants completed the study. Among 6206 newborns included for analysis, the incidence of SVN was 48·4% (35·1% term-SGA newborns [n=2179], 9·7% preterm-nonSGA newborns [n=605], and 3·6% preterm-SGA newborns [n=222]). Compared with term-nonSGA newborns, proportions of stillbirths and neonatal deaths within 72 h of birth among SVN were three times and 2·5 times higher, respectively. Preterm-SGA newborns had the highest incidence of stillbirth (15 [6·8%] of 222) and neonatal deaths (six [4·2%] of 142). Low body-mass index (BMI <18·5 kg/m2) of participants at the start of pregnancy was associated with higher risk for preterm-SGA (adjusted relative risk [RR] 1·61 [95% CI 1·17-2·22]), preterm-nonSGA (1·35 [1·09-1·68]), and term-SGA (1·44 [1·27- 1·64]), with population attributable fraction ranging from 8·7% to 13·8%. Pre-eclampsia (adjusted RR 1·48 [95% CI 1·30-1·71]), short cervical length (1·15 [1·04-1·26]), and bacterial vaginosis (1·13 [0·88-1·45]) were other important antenatal risk factors. INTERPRETATION: In a comprehensive analysis of SVN and its types from north India, we identified risk factors to guide prioritisation of interventions. Complemented with risk-stratification tools, this focused approach will enhance antenatal care, and accelerate achievement of Sustainable Development Goals-namely, to end preventable deaths of newborns and children younger than 5 years by 2030 (target 3·2). FUNDING: Department of Biotechnology, Government of India and Grand Challenges India-Biotechnology Industry Research Assistance Council, Government of India. TRANSLATION: For the Hindi translation of the abstract see Supplementary Materials section.

Indole-3-Carbinol and Its Derivatives as Neuroprotective Modulators.

Brain-derived neurotrophic factor (BDNF) and its downstream tropomyosin receptor kinase B (TrkB) signaling pathway play pivotal roles in the resilience and action of antidepressant drugs, making them prominent targets in psychiatric research. Oxidative stress (OS) contributes to various neurological disorders, including neurodegenerative diseases, stroke, and mental illnesses, and exacerbates the aging process. The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant responsive element (ARE) serves as the primary cellular defense mechanism against OS-induced brain damage. Thus, Nrf2 activation may confer endogenous neuroprotection against OS-related cellular damage; notably, the TrkB/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway, stimulated by BDNF-dependent TrkB signaling, activates Nrf2 and promotes its nuclear translocation. However, insufficient neurotrophin support often leads to the downregulation of the TrkB signaling pathway in brain diseases. Thus, targeting TrkB activation and the Nrf2-ARE system is a promising therapeutic strategy for treating neurodegenerative diseases. Phytochemicals, including indole-3-carbinol (I3C) and its metabolite, diindolylmethane (DIM), exhibit neuroprotective effects through BDNF's mimetic activity; Akt phosphorylation is induced, and the antioxidant defense mechanism is activated by blocking the Nrf2-kelch-like ECH-associated protein 1 (Keap1) complex. This review emphasizes the therapeutic potential of I3C and its derivatives for concurrently activating neuronal defense mechanisms in the treatment of neurodegenerative diseases.

Label-Free Tracking of Hepatitis B Virus Core Protein Capsid Assembly in Real-Time Using Protein Charge Transfer Spectra.

Hepatitis B virions are double-shelled particles, with a diameter of 40-42 nm, consisting of a nucleocapsid called the HBV core protein (HBV Cp). It is an ordered assembly of 90-120 homodimers arranged in an icosahedral symmetry. Both the full-length HBV Cp and the first-149 residue domain, HBV Cp149, can spontaneously assemble in vitro into capsids with 120 Cp dimers (T = 4) or 90 Cp dimers (T = 3), triggered by high ionic strength of 0.25-0.5 M NaCl. The assembly disassembly of HBV Cp149 capsids are generally studied by light scattering, size-exclusion chromatography, atomic force microscopy, transmission electron microscopy, and other high-end expensive techniques. Here, we report a simple, yet robust, label-free technique exploiting protein charge transfer spectra (ProCharTS) to monitor the capsid assembly in real-time. ProCharTS absorption in the near UV-visible region (250-800 nm) arises when photoinduced electron transfer occurs from HOMO of COO- in glutamate (donor) to LUMO of NH3+ in lysine or polypeptide backbone (acceptor) of the protein. Alternatively, it can also occur from polypeptide backbone (donor) to acceptor in arginine, histidine, or lysine cation. ProCharTS is observed profusely among proximal charge clusters in folded proteins. Here, we show that, ProCharTS absorption among growing HBV capsids is amplified when HBV Cp homodimers assemble, generating new contacts among charged residues in the dimer-dimer interface. We notice a time-dependent sigmoidal increase in ProCharTS absorbance and luminescence during capsid formation in comparison to pure dimers. Additionally, a combined approach of anisotropy-based fluorescence assay is reported, where an increased fluorescence anisotropy was observed in capsids as compared to native and unfolded dimers. We conclude that ProCharTS can serve as a sensitive label-free tool for rapid tracking of capsid assembly in real-time and characterize the assembled capsids from dimers.

Development and Validation of a Tool for Assessing Adherence to Gluten-Free Diet in Patients With Celiac Disease.

INTRODUCTION: Life-long adherence to gluten-free diet (GFD) and its assessment is essential for patients with celiac disease (CeD). We have developed and validated a tool for assessing adherence to GFD which can be used by both physicians and dietitians. METHODS: Phase 1: Development, content validation, and assessment of reliability of tool. Phase 2: Validation of tool against standard dietary evaluation (SDE) (gold standard), immunoglobulin A - anti-tissue transglutaminase antibodies (IgA anti-tTG Ab), and gluten immunogenic peptides in urine. Overall, 380 biopsy-confirmed patients with CeD (derivation cohort: n = 100 [phase 1], n = 210 [phase 2] and independent validation cohort, n = 70) were recruited. RESULTS: Of an initial 90-point questionnaire, 84 items (Celiac Disease: Compliance Assessment Test [CD-CAT.v1]) were retained after content validation and pilot testing. In phase 1, upon administering CD-CAT.v1 on 100 patients, a comprehensive 35-item tool (CD-CAT.v2; α = 0.86) was obtained after removing items with low test-retest reliability and item-rest correlation values. In phase 2, upon administering CD-CAT.v2 on 210 patients, 22 items were removed having low correlation values (R < 0.4) with SDE. Finally, a 13-item tool (CD-CAT.v3; α = 0.84) was obtained with high criterion validity with SDE ( r = 0.806, P < 0.001), moderate convergent validity with celiac disease adherence test ( r = 0.602, P = 0.007), and moderate to weak correlation with urine gluten immunogenic peptides ( r = 0.46, P = 0.001) and IgA anti-tTG Ab ( r = 0.39, P = 0.008), respectively. The final 13-item tool also strongly correlated with SDE ( r = 0.78, P < 0.001) in an independent validation cohort of 70 patients with CeD. Principal component analysis identified 3 relevant subscales with a cumulative variance of 62%. The sensitivity and specificity of CD-CAT.v3 were 80% and 91%, respectively, with an area under curve of 0.905 with SDE. The obtained cutoff score of <19 from the receiver operating characteristic curve was further categorized as 13 = excellent, 14-18 = very good, 19-28 = average, and >28 = poor adherence to GFD. DISCUSSION: CD-CAT is a new and rapid tool for monitoring dietary adherence to GFD with high sensitivity and specificity, which can be administered by both physicians and dietitians.

Acquired resistance to immunotherapy and chemoradiation in MYC amplified head and neck cancer.

The proto-oncogene MYC encodes a nuclear transcription factor that has an important role in a variety of cellular processes, such as cell cycle progression, proliferation, metabolism, adhesion, apoptosis, and therapeutic resistance. MYC amplification is consistently observed in aggressive forms of several solid malignancies and correlates with poor prognosis and distant metastases. While the tumorigenic effects of MYC in patients with head and neck squamous cell carcinoma (HNSCC) are well known, the molecular mechanisms by which the amplification of this gene may confer treatment resistance, especially to immune checkpoint inhibitors, remains under-investigated. Here we present a unique case of a patient with recurrent/metastatic (R/M) HNSCC who, despite initial response to nivolumab-based treatment, developed rapidly progressive metastatic disease after the acquisition of MYC amplification. We conducted comparative transcriptomic analysis of this patient's tumor at baseline and upon progression to interrogate potential molecular processes through which MYC may confer resistance to immunotherapy and/or chemoradiation and used TCGA-HNSC dataset and an institutional cohort to further explore clinicopathologic features and key molecular networks associated with MYC amplification in HNSCC. This study highlights MYC amplification as a potential mechanism of immune checkpoint inhibitor resistance and suggest its use as a predictive biomarker and potential therapeutic target in R/M HNSCC.

Annual rhythm in immune functions of blood leucocytes in an ophidian, Natrix piscator.

Annual variations in animal's physiological functions are an essential strategy to deal with seasonal challenges which also vary according to the time of year. Information regarding annual adaptations in the immune-competence to cope with seasonal stressors in reptiles is scarce. The present research plan was designed to analyze the presence of circannual immune rhythms in defense responses of the leucocytes in an ophidian, Natrix piscator. Peripheral blood leucocytes were obtained, counted, and superoxide anion production, neutrophil phagocytosis, and nitrite release were tested to assess the innate immune functions. Peripheral blood lymphocytes were separated by centrifugation (utilizing density gradient) and the cell proliferation was measured. The Cosinor rhythmometry disclosed the presence of significant annual rhythms in the number of leucocytes, superoxide anion production, nitric oxide production, and proliferation of stimulated lymphocytes. The authors found that respiratory burst activity and proliferative responses of lymphocytes were crucial immune responses that showed the annual rhythm. It was summarized that the immune function of the N. piscator is a labile attribute that makes the animal competent to cope with the seasonal stressor by adjustment in the potency of response.

A nutrient responsive lipase mediates gut-brain communication to regulate insulin secretion in Drosophila.

Pancreatic ß cells secrete insulin in response to glucose elevation to maintain glucose homeostasis. A complex network of inter-organ communication operates to modulate insulin secretion and regulate glucose levels after a meal. Lipids obtained from diet or generated intracellularly are known to amplify glucose-stimulated insulin secretion, however, the underlying mechanisms are not completely understood. Here, we show that a Drosophila secretory lipase, Vaha (CG8093), is synthesized in the midgut and moves to the brain where it concentrates in the insulin-producing cells in a process requiring Lipid Transfer Particle, a lipoprotein originating in the fat body. In response to dietary fat, Vaha stimulates insulin-like peptide release (ILP), and Vaha deficiency results in reduced circulatory ILP and diabetic features including hyperglycemia and hyperlipidemia. Our findings suggest Vaha functions as a diacylglycerol lipase physiologically, by being a molecular link between dietary fat and lipid amplified insulin secretion in a gut-brain axis.

Efficient removal of crystal violet dye from water using zinc ferrite-polyaniline nanocomposites.

Nanomaterials are widely employed in wastewater treatment, among which nanoferrites and their composites hold significant prominence. This study adopts a green approach to synthesize zinc ferrite nanoparticles, subsequently integrating them with polyaniline (PANI) to fabricate the ZnFe2O4-PANI nanocomposite. Characterization of the prepared ZnFe2O4-PANI nanocomposite was conducted using X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscopic (SEM) techniques. Using Scherrer's equation, the crystallite size of the synthesized zinc ferrite nanoparticles was found to be 17.67 nm. SEM micrographs of the ZnFe2O4-PANI nanocomposite revealed that in situ polymerization of ZnFe2O4 with polyaniline transforms the amorphous surface morphology of the polymer into a homogeneous nanoparticle structure. The adsorption of crystal violet (CV) dye onto the surface of the ZnFe2O4-PANI nanocomposite depends on pH, adsorbent dosage, temperature, concentration levels and duration. The Langmuir adsorption model fitted the data well, indicating adherence to a pseudo-second-order kinetic pattern. Thermodynamic values ΔG°, ΔH° and ΔS° indicated that the adsorption process occurred spontaneously. Advantages and disadvantages of the technique have also been highlighted. Mechanism of adsorption is discussed. From the obtained results, it is evident that the ZnFe2O4-PANI nanocomposite holds promise as a sorbent for the removal of dye from wastewater.

Reproductive functions and pregnancy outcome in female patients with celiac disease.

BACKGROUND AND AIM: Abnormalities in the reproductive functions are often ignored while evaluating a patient with celiac disease (CeD). We evaluated the entire reproductive functions in female patients with CeD. METHODS: In a case control study between 2020 and 2021 using detailed questionnaire, we evaluated reproductive functions (age at menarche, menstrual pattern, fertility, pregnancy outcome and menopause) in biopsy-proven female patients with CeD of age >10 years. The questionnaire was administered either in person or telephonically. Age-matched healthy female controls (twice the number) were also recruited. RESULTS: Of 1086 CeD patients, 470 were females and 288 were included. As compared with controls (n = 586), females with CeD had higher age at menarche (14.6 ± 2.0 vs 13.6 ± 1.5 years; P = 0.001), delayed menarche (30.8% vs 11.4%; P = 0.001), abnormal menstrual pattern (39.7% vs 25.8%; P < 0.001), involuntary delay in conception at > 1 year (33.8% vs 11.8%; P = 0.01), current infertility rate (10.5% vs 5.2%;P = 0.028), and poorer overall pregnancy outcomes (abortion [23.5% vs 12.8%; P = 0.001], pre-term birth [16.3% vs 3.7%; P = 0.001]). CONCLUSIONS: Either one or more aspect of reproductive functions and pregnancy outcome is affected adversely in three-fourth female patients with CeD.

Correlation between intestinal stem cell niche changes and small bowel crypt failure in patients with treatment-naïve celiac disease.

OBJECTIVES: We hypothesized that crypt failure in the small bowel results in villous flattening in patients with celiac disease (CeD). We investigated whether alterations in the stem cell niche (ISC) are responsible for this phenomenon. MATERIALS AND METHODS: We included 92 duodenal (D2/3) biopsies from treatment-naive patients of CeD and 37 controls. All underwent screening for serum anti-tissue transglutaminase and endoscopic upper small bowel biopsy. Immunohistochemical markers were used to investigate ISC niche alterations, including LGR5 for crypt basal cells (CBC), Bmi1 for position 4+ cells, ß-Defensin for Paneth cells, R-spondin1 as WNT activator, transcription factor-4 as WNT transcription factor, BMP receptor1A as WNT inhibitor, fibronectin-1 as periepithelial stromal cell marker, H2AX as apoptosis marker, and Ki67 as proliferation marker. We also analyzed IgA anti-tTG2 antibody deposits by using dual-color immunofluorescence staining. RESULTS: We found that in biopsies from patients with treatment-naive CeD with modified Marsh grade 3a-3c changes, the epithelial H2AX apoptotic index was upregulated than in controls. LGR5+ crypt basal cells were upregulated in all modified Marsh grades compared to controls. However, the Ki67 proliferation index, expressions of WNT-activator RSPO1, and position-4 cell marker Bmi1 did not significantly alter in patients' biopsies as compared to controls ( P = 0.001). We also observed depletion of pericrypt stromal fibronectin-1 in patients with CeD compared to controls. In addition, we identified IgA anti-TG2 antibody deposits in pericrypt stroma. CONCLUSIONS: Our data suggests that ISC niche failure is a plausible hypothesis for villous flattening in patients with CeD, resulting from pericrypt IgA anti-TG2 antibody complex-mediated stromal depletion.

Significance of histopathological features in the diagnosis of Budd-Chiari syndrome on liver biopsies.

Background: Budd-Chiari syndrome (BCS) requires a constellation of clinical, imaging, and histological findings for diagnosis. Liver biopsy serves as a tool for confirming the diagnosis, even though the histological characteristics are not pathognomonic. Aims: To determine which constellation of morphologic findings could aid in establishing a diagnosis of BCS in clinically suspected cases. Materials and Methods: A 5-year retrospective observational study was conducted. The clinical, laboratory, and histological findings of liver biopsies in patients with a clinical diagnosis of BCS were studied. Cases were segregated into two groups on the basis of the number of histological features present. A scoring system was then devised to assess the efficacy of the histological findings in diagnosing BCS. Statistical Analysis Used: The continuous variables were compared using the Mann-Whitney U-test, and categorical variables were compared using the Fisher-exact test. Results: The common histopathological findings were the presence of red blood cells in the space of disse (100%), peri-portal fibrosis (97.1%), sinusoidal dilation (97.1%), portal inflammation (67.6%), centrilobular necrosis (61.8%) and pericellular/sinusoidal fibrosis (61.8%). Comparison between the two groups showed that centrilobular necrosis, lobular inflammation, portal inflammation, central vein fibrosis, and pericellular/sinusoidal fibrosis were significant parameters. No correlation was found between the clinical and laboratory parameters and the two groups. Conclusions: The liver biopsy features in BCS are often nonspecific, and no single feature in isolation is characteristic. A constellation of features (centrilobular necrosis, lobular inflammation, portal inflammation, central vein fibrosis, and pericellular/sinusoidal fibrosis), when present together, indicate the possibility of BCS.

Insight into the Natural Biomolecules (BMs): Promising Candidates as Zika Virus Inhibitors.

Zika virus (ZIKV) is among the relatively new infectious disease threats that include SARS-CoV-2, coronavirus, monkeypox (Mpox) virus, etc. ZIKV has been reported to cause severe health risks to the fetus. To date, satisfactory treatment is still not available for the treatment of ZIKV infection. This review examines the last five years of work using natural biomolecules (BMs) to counteract the ZIKV through virtual screening and in vitro investigations. Virtual screening has identified doramectin, pinocembrin, hesperidins, epigallocatechin gallate, pedalitin, and quercetin as potentially active versus ZIKV infection. In vitro, testing has shown that nordihydroguaiaretic acid, mefloquine, isoquercitrin, glycyrrhetinic acid, patentiflorin-A, rottlerin, and harringtonine can reduce ZIKV infections in cell lines. However, in vivo, testing is limited, fortunately, emetine, rottlerin, patentiflorin-A, and lycorine have shown in vivo anti- ZIKV potential. This review focuses on natural biomolecules that show a particularly high selective index (>10). There is limited in vivo and clinical trial data for natural BMs, which needs to be an active area of investigation. This review aims to compile the known reference data and discuss the barriers associated with discovering and using natural BM agents to control ZIKV infection.

Barriers at various levels of human ecosystem for maintaining adherence to gluten free diet in adult patients with celiac disease.

INTRODUCTION: While lifelong and strict adherence to gluten-free diet (GFD) is essential for the successful treatment of celiac disease (CeD), only 30-50% of patients are able to maintain a good adherence to GFD. We determined factors influencing the adherence to GFD at various ecological levels including intra-personal, inter-personal, organizational, community and system-based levels in adult patients with CeD. METHODS: A questionnaire to assess the adherence was developed and it was administered in the CeD clinic to patients with CeD on GFD for >1 year. Adherence to GFD was assessed in a subset of patients (n = 320) using Celiac Disease Adherence Test (CDAT). RESULTS: Overall, 978 patients [median age: 29 years; females: 592] with CeD on GFD were recruited. They reported many barriers to adherence to GFD including intra-personal barriers such as lack of knowledge about GFD (19%), inadequate financial resources (27.2%) and lack of self-motivation/confidence (55.3%); inter-personal barriers such as intake of gluten-containing food upon forceful insistence of friends/family (23.4%); organizational barriers such as high cost (70.8%) and non-availability of GF-food products (48.6%); community-based barriers like consumption of gluten-containing food at religious occasions/festivals (11.1%) and social occasions (27.2%); and system-based barriers such as non-referral to dietitian for counseling (21.9%). As per CDAT, 204 (63.7%), 73(22.8%) and 43(13.4%) patients had good, average, and poor adherence to GFD, respectively. On multivariable analysis, occasional consumption of gluten, non-availability of GF-food while dining out and coercing by family and friends for consumption of GC-food were found to have highest odds for poor adherence to GFD. CONCLUSIONS: Non-referral to a dietitian for counseling, irregular follow-up visits, unavailability of flour mill, non-supportive family/friends, high cost and limited availability of GF-food are the most common barriers to adherence to GFD. There is a need to create infrastructure and develop strategies to overcome these diverse barriers at various levels of ecosystem and thereby facilitate better adherence to GFD.

Impact of delay in the diagnosis on the severity of celiac disease.

BACKGROUND AND AIM: Celiac disease (CeD) has now become a global disease with a worldwide prevalence of 0.67%. Despite being a common disease, CeD is often not diagnosed and there is a significant delay in its diagnosis. We reviewed the impact of the delay in the diagnosis on the severity of manifestations of CeD. METHODS: We reviewed clinical records of 726 consecutive patients with CeD from the Celiac Clinic database and the National Celiac Disease Consortium database. We extracted specific data including the demographics, symptoms at presentation, time of onset of symptoms, time to diagnosis from the onset of the symptoms, and relevant clinical data including fold-rise in anti-tissue transglutaminase antibody (IgA anti-tTG Ab) and severity of villous and crypt abnormalities as assessed using modified Marsh classification. RESULTS: The median duration between the onset of symptoms and the diagnosis of CeD was 27 months (interquartile range 12-60 months). A longer delay in the diagnosis of CeD from the onset of symptoms was associated with lower height for age, lower hemoglobin, higher fold rise in IgA Anti tTG titers, and higher severity of villous and crypt abnormalities. About 18% of patients presented with predominantly non-gastrointestinal complaints and had a longer delay in the diagnosis of CeD. CONCLUSIONS: There is a significant delay in the diagnosis of CeD since the onset of its symptoms. The severity of celiac disease increases with increasing delay in its diagnosis. There is a need to keep a low threshold for the diagnosis of CeD in appropriate clinical settings.

Nanotechnology-based theranostic and prophylactic approaches against SARS-CoV-2.

SARS-CoV-2 (COVID-19) pandemic has been an unpredicted burden on global healthcare system by infecting over 700 million individuals, with approximately 6 million deaths worldwide. COVID-19 significantly impacted all sectors, but it very adversely affected the healthcare system. These effects were much more evident in the resource limited part of the world. Individuals with acute conditions were also severely impacted. Although classical COVID-19 diagnostics such as RT-PCR and rapid antibody testing have played a crucial role in reducing the spread of infection, these diagnostic techniques are associated with certain limitations. For instance, drawback of RT-PCR diagnostics is that due to degradation of viral RNA during shipping, it can give false negative results. Also, rapid antibody testing majorly depends on the phase of infection and cannot be performed on immune compromised individuals. These limitations in current diagnostic tools require the development of nanodiagnostic tools for early detection of COVID-19 infection. Therefore, the SARS-CoV-2 outbreak has necessitated the development of specific, responsive, accurate, rapid, low-cost, and simple-to-use diagnostic tools at point of care. In recent years, early detection has been a challenge for several health diseases that require prompt attention and treatment. Disease identification at an early stage, increased imaging of inner health issues, and ease of diagnostic processes have all been established using a new discipline of laboratory medicine called nanodiagnostics, even before symptoms have appeared. Nanodiagnostics refers to the application of nanoparticles (material with size equal to or less than 100 nm) for medical diagnostic purposes. The special property of nanomaterials compared to their macroscopic counterparts is a lesser signal loss and an enhanced electromagnetic field. Nanosize of the detection material also enhances its sensitivity and increases the signal to noise ratio. Microchips, nanorobots, biosensors, nanoidentification of single-celled structures, and microelectromechanical systems are some of the most modern nanodiagnostics technologies now in development. Here, we have highlighted the important roles of nanotechnology in healthcare sector, with a detailed focus on the management of the COVID-19 pandemic. We outline the different types of nanotechnology-based diagnostic devices for SARS-CoV-2 and the possible applications of nanomaterials in COVID-19 treatment. We also discuss the utility of nanomaterials in formulating preventive strategies against SARS-CoV-2 including their use in manufacture of protective equipment, formulation of vaccines, and strategies for directly hindering viral infection. We further discuss the factors hindering the large-scale accessibility of nanotechnology-based healthcare applications and suggestions for overcoming them.

Sieving out non-celiac gluten sensitivity amongst patients with irritable bowel syndrome.

OBJECTIVES: It is challenging to make diagnosis of non-celiac gluten sensitivity/non-celiac wheat sensitivity (NCGS/NCWS) in clinical practice, since there is no biomarker and diagnosis is based on response to gluten-free-diet (GFD). We used anti-gliadin antibody (AGA) for screening patients with IBS for gluten-sensitivity. METHODS: 492 Adult-patients with IBS underwent screening for celiac disease and gluten-sensitivity using IgA anti-tissue transglutaminase antibody and IgA-AGA and IgG-AGA, respectively. Patients with positive AGA (IgA and/or IgG) were invited to follow GFD, those willing were put on GFD for 6-weeks. Responsive patients were given gluten re-challenge. Diagnosis of NCGS was confirmed if they had recurrence of symptoms. RESULTS: Of 492 patients with IBS, AGA was positive in 61(12.4 %), hence suspected to have gluten-sensitivity. Of 31 who agreed to participate and followed GFD for 6-weeks, 17 (54.8 %) had complete (>30 % improvement) and 10(32.2 %) had partial (>20 % improvement) response. All 17 complete-responders were given gluten re-challenge for 6-weeks, symptoms recurred in all and hence were confirmed to have NCGS/NCWS. Significant decrease in AGA levels occurred almost in all GFD-responders. CONCLUSIONS: 12.4 % IBS patients have biological evidence of gluten/wheat-sensitivity. Almost 87 % patients with IBS having AGA responded to GFD. The value of AGA may further be explored as a biomarker for screening for the presence of NCGS, before recommending this test for the clinical practice.

Job Burnout and Perceived Stress among Bank Officers of Meerut: A Cross Sectional Study.

Introduction: Burnout is often misconstrued for stress, whereas it is one of the consequences of stress when not managed prosperously. Stress leads to apprehensiveness, loss of energy, and the primary damage is physical. Whereas, burnout is characterized by disengagement where emotions are blunted thus fostering helplessness and hopelessness leading to detachment and despondence, loss of motivation and ideals with the primary damage being emotional. Objectives: To find out the prevalence and severity of stress and burnout among bank officers in Meerut District and to find the correlation between the two parameters. Methods: Banks were selected by simple random sampling through computer random table method for our study. Further, officer grade bank employees were approached for data collection. A prevalidated seven-point Likert scale Shriom-Melamed Burnout Questionnaire was used for the assessment of burnout. Data were analyzed using appropriate statistical tests by EPI Info and Microsoft Excel 2013. Result: 19.7% bank officers have pathological burnout followed by 55.1% of bank officers who are at the brink of developing burnout. Severe stress was found only among 7.9% bank officers, whereas burnout was present in 19.4%. A positive correlation was found between stress and burnout. Conclusion: It was found that stress and job burnout are linked but do not entirely overlap, with individuals having a high risk of job burnout experiencing only moderate stress. Therefore, perceived stress cannot be taken as the only indicator of risk of burnout.

A Data-Driven Framework for Direct Local Tensile Property Prediction of Laser Powder Bed Fusion Parts.

This article proposes a generalizable, data-driven framework for qualifying laser powder bed fusion additively manufactured parts using part-specific in situ data, including powder bed imaging, machine health sensors, and laser scan paths. To achieve part qualification without relying solely on statistical processes or feedstock control, a sequence of machine learning models was trained on 6299 tensile specimens to locally predict the tensile properties of stainless-steel parts based on fused multi-modal in situ sensor data and a priori information. A cyberphysical infrastructure enabled the robust spatial tracking of individual specimens, and computer vision techniques registered the ground truth tensile measurements to the in situ data. The co-registered 230 GB dataset used in this work has been publicly released and is available as a set of HDF5 files. The extensive training data requirements and wide range of size scales were addressed by combining deep learning, machine learning, and feature engineering algorithms in a relay. The trained models demonstrated a 61% error reduction in ultimate tensile strength predictions relative to estimates made without any in situ information. Lessons learned and potential improvements to the sensors and mechanical testing procedure are discussed.