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Abstract Increased intracranial pressure (ICP) ≥15 mmHg is associated with adverse neurological outcomes, but needs invasive intracranial monitoring. Using the publicly available MIMIC-III Waveform Database (2000–2013) from Boston, we developed an artificial intelligence-derived biomarker for elevated ICP (aICP) for adult patients. aICP uses routinely collected extracranial waveform data as input, reducing the need for invasive monitoring. We externally validated aICP with an independent dataset from the Mount Sinai Hospital (2020–2022) in New York City. The AUROC, accuracy, sensitivity, and specificity on the external validation dataset were 0.80 (95% CI, 0.80–0.80), 73.8% (95% CI, 72.0–75.6%), 73.5% (95% CI 72.5–74.5%), and 73.0% (95% CI, 72.0–74.0%), respectively. We also present an exploratory analysis showing aICP predictions are associated with clinical phenotypes. A ten-percentile increment was associated with brain malignancy (OR = 1.68; 95% CI, 1.09-2.60), intracerebral hemorrhage (OR = 1.18; 95% CI, 1.07–1.32), and craniotomy (OR = 1.43; 95% CI, 1.12–1.84; P

Lymph node metastasis (LNM) is one of the major prognostic factors in human gastrointestinal carcinomas (GICs). The lymph node-positive patients have poorer survival than node-negative patients. LNM is directly associated with the recurrence and poor survival of patients with GICs. The early detection of LNM in patients and designing effective therapies to suppress LNM may significantly impact the survival of these patients. The rapid progress made in proteomic technologies could be successfully applied to identify molecular targets for cancers at high-throughput levels. LC-MS/MS analysis enables the identification of proteins involved in LN metastasis, which can be utilized for diagnostic and therapeutic applications. This review summarizes the studies on LN metastasis in GICs using proteomic approaches to date.

BackgroundThe sale of loose cigarettes or bidis can undermine the purpose of requiring health warning labels (HWLs) on cigarette packs and bidi bundles by diminishing their visibility and legibility. ObjectiveThis mixed-methods study aims to examine the association between purchase behavior (loose vs pack or bundle), HWL exposure, and responses to HWLs among Indian adults who smoke. MethodsData were analyzed from the 2018-2019 India Tobacco Control Policy Survey and from 28 in-depth interviews conducted with Indian adults who smoked in 2022. The Tobacco Control Policy Survey sample included tobacco users who bought cigarettes (n=643) or bidis (n=730), either loose or in packs or bundles at their last purchase. Ordinal regression models were fit separately for cigarettes and bidis, whereby HWL variables (noticing HWLs, reading and looking closely at HWLs, forgoing a cigarette or bidi because of HWLs, thinking about health risks of smoking, and thinking about quitting smoking cigarettes or bidis because of HWLs) were regressed on last purchase (loose vs packs or bundles). In-depth interviews with participants from Delhi and Mumbai who purchased loose cigarettes in the last month were conducted, and thematic analysis was used to analyze the interview data. ResultsSurvey findings indicated that about 74.3% (478/643) of cigarette users and 11.8% (86/730) of bidi users reported having bought loose sticks at their last purchase. Those who purchased loose cigarettes (vs packs) noticed HWLs less often (estimate –0.830, 95% CI –1.197 to –0.463, P

Background: Alcoholic steatohepatitis (ASH) and non-alcoholic steatohepatitis (NASH) are significant forms of liver disease and may progress to end-stage liver disease, cirrhosis and potentially malignant complications. The most difficult aspect of establishing a diagnosis of NASH is distinguishing it from ASH. Laboratory markers such as AST, ALT and GGT lack sufficient sensitivity and specificity. Aim: To study the clinical, biochemical and histological differences between non-alcoholic steatohepatitis (NASH) and alcoholic steatohepatitis (ASH). Materials and Methods: Sixty histologically confirmed cases of non-alcoholic steatohepatitis and 38 cases of alcoholic steatohepatitis were included in the study. A modified form of scoring system proposed by Yip and Burt was used to grade histological features of NASH and ASH. Results: Mean age was 42.85 ± 12.36 years in ASH group and 35.07 ± 8.06 years for NASH group. Male: Female ratio was 37:1 in ASH and 4:1 in NASH. The mean ALT (P = 0.012), SAP (P = 0.003), serum bilirubin (P = 0.001), AST/ALT ratio (P = 0.03), steatosis (P < 0.001), ballooning degeneration of hepatocytes (P < 0.001), portal inflammation (P < 0.001), Mallory hyaline (P = 0.001), ductular proliferation and fibrosis (P < 0.001) showed a significant difference between ASH and NASH cases. Discussion: Older age, male sex, larger derangement of serum biochemistry, high serum bilirubin, AST/ALT > 1, more ballooning degeneration, portal inflammation, Mallory′s hyaline, hepatocytic and ductular cholestasis, ductular proliferation and higher stage of fibrosis favors a diagnosis of ASH. Younger age, high ALT, AST/ALT < 1, higher grade of steatosis and absence of extensive neutrophilic portal inflammation favors a diagnosis of NASH.

Xanthogranulomatous inflammation of gallbladder wall can extend and infiltrate adjacent organs which can be mistaken for malignancy on preoperative investigations and, intraoperatively, often leads to extensive surgical resections. Only the histopathologic examination of the specimen allows correct diagnosis. We hereby review clinicopathologic findings of six cases which underwent extensive surgeries on clinical, radiological and intraoperative suspicion of gallbladder carcinoma which turned out to be xanthogranulomatous cholecystitis (XGC). There was no evidence of malignancy on histopathologic examination. Xanthogranulomatous inflammation extended into liver, duodenum, colon and stomach in case 1; liver and colon in case 2; liver, duodenum, colon in case 3; stomach, duodenum, colon in case 4; stomach and duodenum in case 5 and duodenum and colon in case 6. Lymph nodes in all the six cases showed reactive hyperplasia. We present here the clinico-radiologic findings of these cases, techniques which may help differentiate between an XGC and a gallbladder carcinoma and also discuss the management of these cases.

Background: Tissue micro-array enables the analysis of a large number of tissues simultaneously. Widespread use of this technology is hampered by the high cost of commercial array instruments. We describe our experience of constructing tissue micro-array in a simple method using easily available and inexpensive instruments. Materials and Methods: We used an 11-19 gauge (G) bone marrow trephine biopsy needle/ small sized slotted screwdriver to punch holes in the wax blocks. Cores were taken from donor tissue blocks using a bone marrow trephine biopsy needle and arrayed into host paraffin wax blocks. A detailed database was constructed for each array constructed. Results: The array blocks were used over a period of one year as internal control for immunohistochemistry (IHC), quality control and research. It took about 10 minutes to construct a nine-dot array and about one hour for a 56-dot array. During IHC, the average loss of control dots was less than one per cent. We did not see any loss of antigenicity in the control sections even after four weeks storage. Discussion: Tissue array construction by the technique described here is inexpensive and reliable alternative to automated instruments. Because it is easy to modify the arrays by varying the core size, it is easy to adapt this to individual labs and requirements. We recommend using blocks with cores in 3 x 3 to 5 x 4 grids as controls in IHC and for standardizing antibodies and array blocks with a larger number of cores for research.

Background: Children have different natural history of Hepatitis B virus (HBV) infection. They commonly develop asymptomatic chronic carrier state which is less frequently seen in adults. We describe a rare case of acute on chronic liver failure (ACLF) in the course of concurrent autoimmune hepatitis (AIH) and HBV infection and replication of HBV following the treatment for autoimmune hepatitis. Case Report: A 15 year old male child presented with jaundice and altered sensorium. Physical examination showed hepatosplenomegaly. The liver function tests were markedly altered. Serology was positive for anti liver kidney microsomal antibody (LKM), hepatitis B surface antigen (HBsAg) and immunoglobulin M (IgM) anti hepatitis B core antigen (HBc Ag). Liver biopsy showed chronic hepatitis with features of acute exacerbation. Patient was started on treatment with azathioprine and prednisolone for AIH following which clinical and biochmemical improvement was noted. After two years of continued treatment a repeat biopsy performed showed fairly reduced histological activity, but marked replication of the HBV (immunohistochemistry for HBsAg and anti HBcAg showed diffuse cytoplasmic and nuclear positivity respectively). These findings suggest viral replication although the patient was clinically stable. At six months follow-up after the second biopsy and cessation of azathioprine and prednisolone, there were raised liver enzymes and viral load, hence the patient was started on antiviral drug Entecavir to which there was good response and the patient is presently doing well. Conclusion: We describethe rare co occurrence of HBV infection and AIH with marked HBV replication following the treatment for AIH

IntroductionBanning the sales of loose cigarettes is recommended by Article 16 of the World Health Organization – Framework Convention on Tobacco Control. This study aims to understand the perceptions of cigarette users and tobacco vendors regarding such a ban.MethodsUsing a systematic recruitment and interview protocol, we interviewed cigarette users (n = 28) and tobacco vendors (n = 28) from two Indian cities where sales of loose cigarettes were banned (Mumbai) or not banned (Delhi). Separate semi-structured interview guides were used for users and vendors. Interview questions focused on reasons for purchasing loose cigarettes, preference for buying and selling loose vs. packs, thoughts on the necessity of banning loose cigarettes, and the perceived impact of the policy ban for vendors and cigarette users. We performed thematic analysis and used NVivo for organizing transcript coding.ResultsThe main reasons users cited for purchasing loose cigarettes were financial constraints, social restrictions (fear of getting caught), and limiting cigarette consumption. In Mumbai, awareness of the existing ban was poor among both users and vendors. Those who were aware did not think the policy had been implemented. Users thought that loose cigarettes promoted smoking initiation and prevented them from quitting. Both users and vendors reported that a ban on loose cigarettes would reduce cigarette consumption and promote quit attempts as it would not be possible for everyone to purchase packs because of financial and social reasons.ConclusionUsers in both cities reported easy access to and widespread availability of loose cigarettes. Low awareness of the ban in Mumbai suggested inadequate enforcement. A country-wide ban on the sale of loose cigarettes could be highly effective in preventing smoking initiation and promoting quitting.

Objective: Age is the strongest contributor to 10-year predicted atherosclerotic cardiovascular disease (ASCVD) risk. Some older adults have a predicted ASCVD risk ≥7.5 %, without established risk factors. We sought to compare ASCVD incidence among adults with predicted ASCVD risk ≥7.5 %, with and without established ASCVD risk factors, to adults with predicted risk

Abstract Lymph node (LN) metastasis is the earliest sign of metastatic spread and an established predictor of poor outcome in gallbladder cancer (GBC). Patients with LN positive GBC have a significantly worse survival (median survival- 7 months) than patients with LN negative disease (median survival- ~ 23 months) in spite of standard treatment which includes extended surgery followed by chemotherapy, radiotherapy and targeted therapy. This study aims at understanding the underlying molecular processes associated with LN metastasis in GBC. Here, we used iTRAQ-based quantitative proteomic analysis using tissue cohort comprising of primary tumor of LN negative GBC (n = 3), LN positive GBC (n = 4) and non-tumor controls (Gallstone disease, n = 4), to identify proteins associated with LN metastasis. A total of 58 differentially expressed proteins (DEPs) were found to be specifically associated with LN positive GBC based on the criteria of p value ≤ 0.05, fold change ≥ 2 and unique peptides ≥ 2. These include the cytoskeleton and associated proteins such as keratin, type II cytoskeletal 7 (KRT7), keratin type I cytoskeletal 19 (KRT19), vimentin (VIM), sorcin (SRI) and nuclear proteins such as nucleophosmin Isoform 1 (NPM1), heterogeneous nuclear ribonucleoproteins A2/B1 isoform X1 (HNRNPA2B1). Some of them are reported to be involved in promoting cell invasion and metastasis. Bioinformatic analysis of the deregulated proteins in LN positive GBC using STRING database identified ‘neutrophil degranulation’ and ‘HIF1 activation’ to be among the top deregulated pathways. Western blot and IHC analysis showed a significant overexpression of KRT7 and SRI in LN positive GBC in comparison to LN negative GBC. KRT7, SRI and other proteins may be further explored for their diagnostics and therapeutic applications in LN positive GBC.

Background Right ventricular ejection fraction (RVEF) and end‐diastolic volume (RVEDV) are not readily assessed through traditional modalities. Deep learning–enabled ECG analysis for estimation of right ventricular (RV) size or function is unexplored. Methods and Results We trained a deep learning–ECG model to predict RV dilation (RVEDV >120 mL/m2), RV dysfunction (RVEF ≤40%), and numerical RVEDV and RVEF from a 12‐lead ECG paired with reference‐standard cardiac magnetic resonance imaging volumetric measurements in UK Biobank (UKBB; n=42 938). We fine‐tuned in a multicenter health system (MSHoriginal [Mount Sinai Hospital]; n=3019) with prospective validation over 4 months (MSHvalidation; n=115). We evaluated performance with area under the receiver operating characteristic curve for categorical and mean absolute error for continuous measures overall and in key subgroups. We assessed the association of RVEF prediction with transplant‐free survival with Cox proportional hazards models. The prevalence of RV dysfunction for UKBB/MSHoriginal/MSHvalidation cohorts was 1.0%/18.0%/15.7%, respectively. RV dysfunction model area under the receiver operating characteristic curve for UKBB/MSHoriginal/MSHvalidation cohorts was 0.86/0.81/0.77, respectively. The prevalence of RV dilation for UKBB/MSHoriginal/MSHvalidation cohorts was 1.6%/10.6%/4.3%. RV dilation model area under the receiver operating characteristic curve for UKBB/MSHoriginal/MSHvalidation cohorts was 0.91/0.81/0.92, respectively. MSHoriginal mean absolute error was RVEF=7.8% and RVEDV=17.6 mL/m2. The performance of the RVEF model was similar in key subgroups including with and without left ventricular dysfunction. Over a median follow‐up of 2.3 years, predicted RVEF was associated with adjusted transplant‐free survival (hazard ratio, 1.40 for each 10% decrease; P=0.031). Conclusions Deep learning–ECG analysis can identify significant cardiac magnetic resonance imaging RV dysfunction and dilation with good performance. Predicted RVEF is associated with clinical outcome.

Abstract Background Extramedullary plasmacytoma is an uncommon entity that most commonly involves nasopharynx or upper respiratory tract. Involvement of the gastrointestinal tract occurs in approximated 10% of cases. Isolated primary plasmacytoma of colon is rare and only 7 well documented cases have been reported in the literature. Case presentation We present a case of 42 year male who presented with diarrhea. Multiple colonic strictures were found on investigation. Colonoscopic biopsy was not helpful in making any specific diagnosis. Patient underwent subtotal colectomy. Isolated primary colonic plasmacytoma was found on histopathological examination. Conclusion Plasmacytoma is known to occur in extra osseous sites. Primary colonic plasmacytoma, however, is a rare clinical entity. Primary colonic plasmacytoma may have varying clinical presentations including multiple colonic strictures that may mimic colonic tuberculosis or inflammatory bowel disease. Although these cases are rare, treating physician as well as radiologist, and pathologist should be aware of this entity.

Background: A majority of the patients with gall bladder cancer (GBCa) present at an advanced stage and have poor survival. The aim is to retrospectively study the role of guided FNA in the diagnosis of GBCa in a superspecialty institute and to describe the cytomorphologic spectrum of gall bladder (GB) lesions in the North Indian population. Materials and Methods: All suspected cases of GBCa who underwent guided FNA from the primary GB mass or metastatic liver space-occupying lesion from 2017 to 2019 were included. The aspirate smears were retrieved and analyzed for cytomorphological features independently by two cytopathologists. The neoplastic lesions were classified according to the WHO 2019 classification. Results: Of 489 cases, fine needle aspiration cytology (FNAC) was diagnostic in 463 cases (94.6%), of which 417 (90.1%) were positive for malignancy, 35 (7.5%) were inflammatory, and 11 (2.4%) were inconclusive for malignancy. Adenocarcinoma not otherwise specified (NOS) was the most common type seen in 330 cases (79.1%) and 87 (20.9%) were unusual variants. These included papillary adenocarcinoma (22, 5.2%), mucinous adenocarcinoma (12, 2.8%), signet ring carcinoma (2,0.4%), adenosquamous carcinoma (8, 1.9%), squamous cell carcinoma (10, 2.4%), neuroendocrine neoplasms (7, 1.7%), undifferentiated carcinoma (24, 5.7%) and non-Hodgkin lymphoma (2,0.4%), respectively. Immunohistochemistry on the cell block confirmed the diagnosis wherever possible. Histopathology was discordant in 5 out of 33 cases. Conclusion: Guided FNAC is a sensitive investigation that plays a crucial role in confirming the diagnosis and deciding the further treatment options in advanced-stage GBCa patients. The uncommon variants of GBCa can be reliably categorized on cytology.

Schmincke described lymphoepithelioma as an undifferentiated carcinoma with abundant lymphoid stroma in the nasopharynx. Tumors with a similar histomorphology in extrapharyngeal areas have been referred to as lymphoepithelioma-like carcinoma (LELC). The association of an Ebstein-Barr virus (EBV) infection with lymphoepithelioma is well established in the nasopharynx but not so well at the extrapharyngeal sites. Only four cases of LELC have been reported in the gall bladder, of which all were negative for the EBV. This paper reports the first case of an EBV-associated mixed gall bladder carcinoma exhibiting a distinct phenotype of LELC and adenocarcinoma with mucinous differentiation. The EBV was confirmed by the strong granular membranous and cytoplasmic expression of LMP-1 (latent membrane protein-1) on immunohistochemistry and nuclear EBER RNA on chromogen in-situ hybridization in the tumor. This is the first case of LELC positive for EBV in the gall bladder. LELC has a more favorable prognosis than conventional adenocarcinoma or squamous cell carcinoma, irrespective of the site. Although a higher T stage and nodal metastasis were exceptional in the present case in contrast to the previous cases, the EBV-associated lymphocytic response might limit the disease spread and confer better overall survival and prognosis in these patients. Nevertheless, more prospective studies with a larger cohort will be needed to understand the pathogenesis, biological behavior, and prognosis of this rare entity.

BackgroundResearch clearly demonstrates social determinants of health (SDOH) impact health outcomes. Provider consideration of patient SDOH in prevention and treatment planning is critical for improved health care quality and health equity. Despite awareness of the connections between SDOH and improved population health, research demonstrates few providers document patient SDOH. ObjectiveThis qualitative study aimed to better understand the barriers and facilitators of SDOH assessment, documentation, and referral in different health care settings and roles. MethodsIndividual semistructured interviews were conducted with practicing health care providers in South Carolina between August 25, 2022, and September 2, 2022. Participants were recruited via community partners’ web-based newsletters or listservs using a purposive sampling design. An interview guide with 19 questions was used to explore the following research question: How do SDOH impact patient health and what are the facilitators and barriers experienced by multidisciplinary health care providers assessing and documenting patient SDOH? ResultsParticipants (N=5) included a neonatal intensive care unit registered nurse, a nurse practitioner, a certified nurse midwife, a family and preventive medicine physician, and a counselor (licensed clinical social worker) with careers spanning 12 to 32 years. Participant responses are presented according to the following 5 themes: participants’ understanding of SDOH for the patient population, assessment and documentation practices, referrals to other providers and community-based resources, barriers and facilitators of SDOH assessment and documentation, and SDOH assessment and documentation training preferences. Overall, participants were aware of the importance of including patient SDOH in assessment and intervention but noted a variety of institutional and interpersonal barriers to assessment and documentation, including time constraints, perceptions of stigma around discussion of SDOH, and limited referral protocols. ConclusionsIncentivizing inclusion of patient SDOH in health care must be facilitated from the top down, so assessment and documentation can be universally implemented in a pragmatic way that works for providers in a variety of roles and settings for the betterment of health care quality, health equity, and improved population health outcomes. Partnering with community organizations can serve to augment health care organizations’ resource and referral availability for addressing patients’ social needs.

Autoimmune hepatitis (AIH) is a chronic, relapsing and remitting, immune-mediated liver disease that progresses to cirrhosis if left untreated. A significant number of patients may present with acute hepatitis or acute liver failure, which are often misdiagnosed as toxic liver injury. AIH shows a preponderance in young women but may be seen in children and the elderly. Diagnosis requires the integration of clinical, biochemical, and serologic parameters, along with supportive liver histology and exclusion of other causes of liver disease. Liver biopsy is a prerequisite for diagnosis of AIH, to assess severity and stage of disease, exclude other entities, and recognize any concurrent morbidities. No single biomarker or histologic feature is pathognomonic for AIH. The diagnostic and histologic criteria have undergone several modifications since the original scoring system was proposed by the International Autoimmune Hepatitis Group (IAIHG) in 1993. Recently, the IAIHG has proposed consensus recommendations for histologic criteria, relevant for both acute and chronic AIH. This review article will describe the evolving diagnostic criteria for AIH, with their limitations and utility, and with an emphasis on the role of liver histology in the diagnosis and management of AIH.

Abstract The authors examined the proportion of US adults that would have their high blood pressure (BP) status changed if systolic BP (SBP) and diastolic BP (DBP) were measured with systematic bias and/or random error versus following a standardized protocol. Data from the 2017–2018 National Health and Nutrition Examination Survey (NHANES; n = 5176) were analyzed. BP was measured up to three times using a mercury sphygmomanometer by a trained physician following a standardized protocol and averaged. High BP was defined as SBP ≥130 mm Hg or DBP ≥80 mm Hg. Among US adults not taking antihypertensive medication, 32.0% (95%CI: 29.6%,34.4%) had high BP. If SBP and DBP were measured with systematic bias, 5 mm Hg for SBP and 3.5 mm Hg for DBP higher and lower than in NHANES, the proportion with high BP was estimated to be 44.4% (95%CI: 42.6%,46.2%) and 21.9% (95%CI 19.5%,24.4%). Among US adults taking antihypertensive medication, 60.6% (95%CI: 57.2%,63.9%) had high BP. If SBP and DBP were measured 5 and 3.5 mm Hg higher and lower than in NHANES, the proportion with high BP was estimated to be 71.8% (95%CI: 68.3%,75.0%) and 48.4% (95%CI: 44.6%,52.2%), respectively. If BP was measured with random error, with standard deviations of 15 mm Hg for SBP and 7 mm Hg for DBP, 21.4% (95%CI: 19.8%,23.0%) of US adults not taking antihypertensive medication and 20.5% (95%CI: 17.7%,23.3%) taking antihypertensive medication had their high BP status re‐categorized. In conclusions, measuring BP with systematic or random errors may result in the misclassification of high BP for a substantial proportion of US adults.

Gastric hyperplastic polyps (GHP) account for a majority of benign gastric polyps. Most of the GHPs are

Gallbladder cancer (GBC) is an aggressive malignancy of the gastrointestinal tract with a poor prognosis. It is important to understand the molecular processes associated with the pathogenesis of early stage GBC and identify proteins useful for diagnostic and therapeutic strategies. Here, we have carried out an iTRAQ-based quantitative proteomic analysis of tumor tissues from early stage GBC cases (stage I, n=7 and stage II, n=5) and non-tumor controls (n=6) from gallstone disease (GSD). We identified 357 differentially expressed proteins (DEPs) based on ≥ 2 unique peptides and ≥ 2 fold change with p value < 0.05. Pathway analysis using the STRING database showed, ‘neutrophil degranulation’ to be the major upregulated pathway that includes proteins such as MPO, PRTN3, S100A8, MMP9, DEFA1, AZU, and ‘ECM organization’ to be the major downregulated pathway that includes proteins such as COL14A1, COL1A2, COL6A1, COL6A2, COL6A3, BGN, DCN. Western blot and/or IHC analysis confirmed the elevated expression of MPO, PRTN3 and S100A8 in early stage of the disease. Based on the above results, we hypothesize that there is an increased neutrophil infiltration in tumor tissue and neutrophil degranulation leading to degradation of extracellular matrix (ECM) proteins promoting cancer cell invasion in the early stage GBC. Some of the proteins (MPO, MMP9, DEFA1) associated with ‘neutrophil degranulation’ showed the presence of ‘signal sequence’ suggesting their potential as circulatory markers for early detection of GBC. Overall, the study presents a protein dataset associated with early stage GBC.

Background and aims Although young children's gaze behaviors in experimental task contexts have been shown to be potential biobehavioral markers relevant to autism spectrum disorder (ASD), we know little about their everyday gaze behaviors. The present study aims (1) to document early gaze behaviors that occur within a live, social interactive context among children with and without ASD and their parents, and (2) to examine how children's and parents’ gaze behaviors are related for ASD and typically developing (TD) groups. A head-mounted eye-tracking system was used to record the frequency and duration of a set of gaze behaviors (such as sustained attention [SA] and joint attention [JA]) that are relevant to early cognitive and language development. Methods Twenty-six parent–child dyads (ASD group = 13, TD group = 13) participated. Children were between the ages of 3 and 8 years old. We placed head-mounted eye trackers on parents and children to record their parent- and child-centered views, and we also recorded their interactive parent–child object play scene from both a wall- and ceiling-mounted camera. We then annotated the frequency and duration of gaze behaviors (saccades, fixation, SA, and JA) for different regions of interest (object, face, and hands), and attention shifting. Independent group t-tests and ANOVAs were used to observe group comparisons, and linear regression was used to test the predictiveness of parent gaze behaviors for JA. Results The present study found no differences in visual experiences between children with and without ASD. Interestingly, however, significant group differences were found for parent gaze behaviors. Compared to parents of ASD children, parents of TD children focused on objects and shifted their attention between objects and their children's faces more. In contrast, parents of ASD children were more likely to shift their attention between their own hands and their children. JA experiences were also predicted differently, depending on the group: among parents of TD children, attention to objects predicted JA, but among parents of ASD children, attention to their children predicted JA. Conclusion Although no differences were found between gaze behaviors of autistic and TD children in this study, there were significant group differences in parents’ looking behaviors. This suggests potentially differential pathways for the scaffolding effect of parental gaze for ASD children compared with TD children. Implications The present study revealed the impact of everyday life, social interactive context on early visual experiences, and point to potentially different pathways by which parental looking behaviors guide the looking behaviors of children with and without ASD. Identifying parental social input relevant to early attention development (e.g., JA) among autistic children has implications for mechanisms that could support socially mediated attention behaviors that have been documented to facilitate early cognitive and language development and implications for the development of parent-mediated interventions for young children with or at risk for ASD. Note: This paper uses a combination of person-first and identity-first language, an intentional decision aligning with comments put forth by Vivanti (Vivanti, 2020), recognizing the complexities of known and unknown preferences of those in the larger autism community.

Gallbladder cancer (GBC) is the sixth most common gastrointestinal tract cancer with a very low overall survival and poor prognosis. Profiling of cancer-derived extracellular vesicles (EVs) is an emerging strategy for identification of candidate biomarkers for the detection and prognosis of the disease. The aim of the study was to analyse the protein content from GBC cell line- derived EVs with emphasis on proteins which could be used as candidate biomarkers for the detection of GBC. NOZ and OCUG-1 cell lines were cultured and EVs were isolated from conditioned media. LC-MS/MS analysis of total EV proteins led to the identification of a total of 268 proteins in both the cell lines. Of these, 110 proteins were identified with ≥2 unique peptides with ≥2 PSMs in at least two experimental and technical replicate runs. STRING (Search Tool for the Retrieval of Interacting Genes/Proteins) database was used to perform bioinformatics analysis of 110 proteins which showed ‘cell adhesion molecule binding’, ‘integrin binding’, ‘cadherin binding’ among the top molecular functions and ‘focal adhesion’ to be among the top pathways associated with the EV proteins. A total of 42 proteins including haptoglobin (HP), pyruvate kinase (PKM), annexin A2 (ANXA2), thrombospondin 1 (THBS1), were reported to be differentially abundant in GBC tissue. Of these, 16 proteins were reported to be differentially abundant in plasma and plasma-derived EVs. We infer these proteins to be highly important to be considered as potential circulatory biomarkers for the detection of GBC. To check the validity of this hypothesis, one of the proteins, haptoglobin (HP) as a representative case, was analysed in plasma by quantitative Enzyme- linked immunosorbent assay (ELISA) and we observed its increased levels in GBC in comparison to controls (p value= 0.0063). Receiver operating characteristic (ROC) curve analysis for GBC vs controls showed an Area under the ROC Curve (AUC) of 0.8264 for HP with 22% sensitivity against 100% specificity. We propose that HP along with other candidate proteins may be further explored for their clinical application.

Purpose The rapid spread of SARS-CoV-2, the virus that is responsible for causing COVID-19, has presented the medical community with another example of when convalescent plasma (CP) is still used today. The ability to standardize CP at the onset of a pandemic is unlikely to exist in a reliable and uniformly reproducible way. We hypothesized that CP of unknown strength given in a serial manner will promote health and reduce mortality in those inflicted with COVID-19. Methods Participants were given up to 8 CP-units depending on their condition upon entry into the study and their response. Results 102 out of 117 participants were given CP. The earlier a participant received CP corelated with survival (p = 0.0004). The number of CP-units given, throughout all the clinical severities, was not significant with outcomes, p = 0.3947. A higher number of CP-units given to the severe/critical participants (without biological immunosuppressants or restrictive lung disease) did correlate with survival p = 0.0116 (2.8 vs. 2 units). Lower platelets on admission corelated with mortality. Platelet levels increase correlated with CP infusions p

Introduction: Healthcare-associated infections (HAI) after viral illnesses are important sources of morbidity and mortality. This has not been extensively studied in hospitalized COVID-19 patients. Methods: This study included all COVID-19-positive adult patients (≥18 years) hospitalized between 01 March and 05 August 2020 at the current institution. The Centers for Disease Control and Prevention definition of HAI in the acute care setting was used. The outcomes that were studied were rates and types of infections and in-hospital mortality. Several multivariable logistic regression models were constructed to examine characteristics associated with development of HAI. Results: Fifty-nine (3.7%) of 1565 patients developed 140 separate HAIs from 73 different organisms: 23 were Gram-positive, 39 were Gram-negative and 11 were fungal. Patients who developed HAI did not have higher odds of death (OR 0.85, 95% CI 0.40–1.81, p = 0.69). HAIs were associated with the use of tocilizumab (OR 5.04, 95% CI 2.4–10.6, p

Abstract Background A subset of patients with serology suggesting celiac disease have an initially negative biopsy but subsequently develop histopathologic celiac disease. Here we characterize patients with potential celiac disease who progress to celiac disease. Methods We performed a retrospective analysis of children (0–18 years of age) with biopsy-confirmed celiac disease seen at St. Louis Children’s Hospital between 2013 and 2018. Results Three hundred sixteen of 327 (96%) children with biopsy-confirmed celiac disease were diagnosed on initial biopsy. The 11 children with potential celiac disease who progressed to celiac disease had lower anti-tissue transglutaminase (anti-TTG IgA) concentrations (2.4 (1.6–5) X upper limit of normal (ULN) vs. 6.41 (3.4–10.5) X ULN) at time of first biopsy. Their median anti-TTG IgA concentrations rose from 2.4 (1.6–5) X ULN to 3.6 (3.1–9.2) X ULN between biopsies. Conclusions Four percent of biopsy confirmed celiac patients initially had a negative biopsy, but later developed histopathologic celiac disease. This is likely an underestimate as no surveillance algorithm was in place. We recommend repeat assessment in children whose serology suggests celiac disease despite normal small bowel biopsy.

Abstract Background Early diagnosis is important for the timely treatment of gallbladder carcinoma (GBC) patients and may lead to increased survival outcomes. Here, we have applied serological proteome analysis (SERPA), an immunoproteomics approach, for the detection of ‘tumor-associated antigens (TAAs) that elicit humoral response’ in early stage GBC patients. Methods Total protein from pooled tumor tissue of GBC patients (n = 7) was resolved by two-dimensional gel electrophoresis (2-DE) followed by immunoblotting using pooled blood plasma from healthy volunteers (n = 11) or gallstone disease (GSD) cases (n = 11) or early stage GBC (Stage I and II) (n = 5) or GBC stage IIIA (n = 9). 2-D gel and immunoblot images were acquired and analyzed using PDQuest software to identify immunoreactive spots in GBC cases in comparison to controls. Proteins from immunoreactive spots were identified by liquid chromatography- tandem mass spectrometric analysis (LC-MS/MS). Autoantibody levels for two of the functionally relevant proteins were investigated in individual plasma samples (52 cases and 89 controls) by dot blot assay using recombinant proteins. Results Image analysis using PDQuest software identified 25 protein spots with significantly high or specific immunoreactivity in GBC cases. Mass spectrometric analysis of 8 corresponding protein spots showing intense immunoreactivity (based on densitometric analysis) in early stage GBC or GBC stage IIIA cases led to the identification of 27 proteins. Some of the identified proteins include ANXA1, HSPD1, CA1, CA2, ALDOA and CTSD. Among the two proteins, namely ANXA1 and HSPD1 verified using a cohort of samples, significantly elevated autoantibody levels against ANXA1 were observed in early stage GBC cases in comparison to healthy volunteers or GSD cases (unpaired t-test, p

Background and Aim Endoscopic biopsy is standard for the diagnosis of esophageal malignancy. However, few cases present with smooth stricture with repetitive negative biopsy results. We aimed to use linear endoscopic ultrasound (EUS) and fine‐needle aspiration (FNA) in the diagnosis of biopsy‐negative suspected malignant esophageal strictures. Methods We retrospectively analyzed the data from August 2017 to December 2018 of biopsy‐negative esophageal strictures. All adult patients with twice‐negative biopsies and with smooth overlying esophageal mucosa on endoscopy were included. Clinical, epidemiological, endoscopic, imaging, and EUS findings were noted and analyzed. Results Eighteen patients underwent EUS for suspicion of malignant esophageal stricture. Seven were excluded as they were submucosal tumors. Eleven patients showed the presence of malignancy on EUS FNA samples. Nine were males. Computed tomography showed esophageal wall thickening in eight (16–38 mm) and esophageal mass in three patients. EUS showed loss of a normal five‐layered wall structure of the esophagus in all patients. Fine‐needle aspiration cytology demonstrated squamous cell carcinoma (n = 4), adenocarcinoma (n = 4), poorly differentiated carcinoma (n = 2), and neuroendocrine carcinoma (n = 1). There were no complications. Conclusion EUS with FNA is effective and safe for the diagnosis of biopsy‐negative malignant esophageal strictures.

Objective: To examine content and readability of COVID-19 information on outpatient clinic websites in South Carolina.Participants: Thirty-three outpatient clinic websites.Methods: Using a multi-step search strategy, we located three COVID-19 information content sections from each website. Descriptive statistics were calculated for content section characteristics (focus, information source, target population/race, presence of graphics, mobilizing information). Flesch Reading Ease (FRE), Flesch Kincaid Grade Level (FKGL), and Simple Measure of Gobbledygook (SMOG) were used to calculate reading levels. Mann Whitney U and Kruskal Wallis tests were performed to examine readability levels by clinic type (primary care vs. specialty) and content section characteristics.Results: Twenty-six clinics offered COVID-19 information; 70 content sections across all 26 clinics were analyzed. Sections focused on COVID-19 clinic policies (48.4%), prevention (22.6%), testing (19.4%), and symptoms (9.7%). 93.5% lacked target population, 41.9% provided no information source, 38.7% had no graphics, and none mentioned racial/ethnic groups. MFRE = 54.3, MFKGL = 9.9, MSMOG = 9.5.Conclusion: COVID-19 information focused mainly on clinic policy and was written at a ninth-grade skill level. Findings suggest there is opportunity for clinics to update their online content to convey more plain language and sourced information, especially for high-risk groups.

Colorectal cancer (CRC) and cardiovascular diseases (CVD) share several risk factors. We examined the relationships between CRC screening and CVD history by race/ethnicity and sex. Data from 15 states across the United States with high age-adjusted CVD rates from the 2012–2016 Behavioral Risk Factor Surveillance System were used to examine prevalence of self-reported screening for CRC among 179,276 adults ages 50–75 years with and without history of CVD. Multivariable logistic regression was used to evaluate the association between socio-demographics and CRC screening in the expansion and stable phases of the Affordable Care Act (ACA) era. Prevalence of CRC screening was high among those with history of CVD. After multivariable adjustment, Whites and Hispanics with CVD had 19% (95%[CI]: 1.13–1.26) and 50% (95%[CI]: 1.10–2.06) higher odds for CRC screening, respectively, versus those without CVD. Individuals in both sexes with CVD had higher odds for CRC screening compared those without CVD. Strikingly, the odds for CRC screening in Hispanics with history of CVD were 72% higher in the stable phase of the ACA era for the fully adjusted model. Whites and Hispanics with history of CVD are more likely to undergo CRC screening, perhaps due to greater exposure to the healthcare system due to CVD. This association was not observed in Blacks. Interventions are needed to improve CRC screening rates among Blacks, especially due to their well-documented higher risk of CVD.

The role of extracorporeal membrane oxygenation (ECMO) in the management of critically ill patients with COVID-19 is evolving. Extracorporeal support independently confers an increased predilection for thrombosis, which can be exacerbated by COVID-19-associated coagulopathy. We present the successful management of a hypercoagulable state in two patients who required venovenous ECMO for the treatment of COVID-19. This included monitoring inflammatory markers (D-dimer and fibrinogen), performing a series of therapeutic plasma exchange procedures, and administering high-intensity anticoagulation therapy and thromboelastography- (TEG-) guided antiplatelet therapy. TPE was performed to achieve goal D-dimer less than 3000 ng/mL D-dimer units (N≤232 ng/mL D-dimer units) and goal fibrinogen less than 600 mg/dL (N=200-400 mg/dL). These therapies resulted in improved TEG parameters and normalized inflammatory markers. Patients were decannulated after 37 days and 21 days, respectively. Post-ECMO duplex ultrasound of the upper and lower extremities and cannulation sites revealed a nonsignificant deep venous thrombosis at the site of femoral cannulation in patient 2 and no deep venous thrombosis in patient 1. The results of this case report show successful management of a hypercoagulable state among COVID-19 patients requiring ECMO support by utilization of inflammatory markers and TEG.

OBJECTIVE:Fluid overload is common among critically ill patients and is associated with worse outcomes. We aimed to assess the effect of diuretics on urine output, vasopressor dose, acute kidney injury (AKI) incidence, and need for renal replacement therapies (RRT) among patients who receive vasopressors. PATIENTS AND METHODS:This is a single-center retrospective study of all adult patients admitted to the intensive care unit between January 2006 and December 2016 and received >6 hours of vasopressor therapy and at least one concomitant dose of diuretic. We excluded patients from cardiac care units. Hourly urine output and vasopressor dose for 6 hours before and after the first dose of diuretic therapy was compared. Rates of AKI development and RRT initiation were assessed with a propensity-matched cohort of patients who received vasopressors but did not receive diuretics. RESULTS:There was an increasing trend of prescribing diuretics in patients receiving vasopressors over the course of the study. We included 939 patients with median (IQR) age of 68(57, 78) years old and 400 (43%) female. The average hourly urine output during the first six hours following time zero in comparison with average hourly urine output during the six hours prior to time zero was significantly higher in diuretic group in comparison with patients who did not receive diuretics [81 (95% CI 73-89) ml/h vs. 42 (95% CI 39-45) ml/h, respectively; p

Abstract Racial disparities in cancer mortality still exist despite improvements in treatment strategies leading to improved survival for many cancer types. In this study, we described race/ethnic differences in patterns of de novo metastasis and evaluated the association between site of de novo metastasis and breast, prostate, and colorectal cancer mortality. Data were obtained from the Surveillance Epidemiology and Ends Results (SEER) database from 2010 to 2013 and included 520,147 patients ages ≥40 years with primary diagnosis of breast, colorectal, or prostate cancer. Site and frequency of de novo metastases to four sites (bone, brain, liver, and lung) were compared by race/ethnicity using descriptive statistics, and survival differences examined using extended Cox regression models in SAS 9.4. Overall, non‐Hispanic (NH) Blacks (11%) were more likely to present with de novo metastasis compared with NH‐Whites (9%) or Hispanics (10%). Among patients with breast cancer, NH‐Blacks were more likely to have metastasis to the bone, (OR: 1.25, 95% CI: 1.15–1.37), brain (OR: 2.26, 95% CI: 1.57–3.25), or liver (OR: 1.62, 95% CI: 1.35–1.93), while Hispanics were less likely to have metastasis to the liver (OR: 0.76, 95% CI: 0.60–0.97) compared with NH‐Whites. Among patients with prostate cancer, NH‐Blacks (1.39, 95% CI: 1.31–1.48) and Hispanics (1.39, 95% CI: 1.29–1.49) were more likely to have metastasis to the bone. Metastasis to any of the four sites evaluated increased overall mortality by threefold (for breast cancer and metastasis to bone) to 17‐fold (for prostate cancer and metastasis to liver). Racial disparities in mortality remained after adjusting for metastasis site in all cancer types evaluated. De novo metastasis is a major contributor to cancer mortality in USA with racial differences in the site, frequency, and associated survival.

A library of bile-acid-appended triazolyl aryl ketones was synthesized and characterized by detailed spectroscopic techniques such as 1H and 13C NMR, HRMS and HPLC. All the synthesized conjugates were evaluated for their cytotoxicity at 10 µM against MCF-7 (human breast adenocarcinoma) and 4T1 (mouse mammary carcinoma) cells. In vitro cytotoxicity studies on the synthesized conjugates against MCF-7 and 4T1 cells indicated one of the conjugate 6cf to be most active against both cancer cell lines, with IC50 values of 5.71 µM and 8.71 µM, respectively, as compared to the reference drug docetaxel, possessing IC50 values of 9.46 µM and 13.85 µM, respectively. Interestingly, another compound 6af (IC50 = 2.61 µM) was found to possess pronounced anticancer activity as compared to the reference drug docetaxel (IC50 = 9.46 µM) against MCF-7. In addition, the potent compounds (6cf and 6af) were found to be non-toxic to normal human embryonic kidney cell line (HEK 293), as evident from their cell viability of greater than 86%. Compound 6cf induces higher apoptosis in comparison to 6af (46.09% vs. 33.89%) in MCF-7 cells, while similar apoptotic potential was observed for 6cf and 6af in 4T1 cells. The pharmacokinetics of 6cf in Wistar rats showed an MRT of 8.47 h with a half-life of 5.63 h. Clearly, these results suggest 6cf to be a potential candidate for the development of anticancer agents.

Context: The use of aspirin in chronic kidney disease (CKD) patients has been shown to reduce myocardial infarction but may increase major bleeding. However, its effects in kidney transplant recipients are unclear. Evidence Acquisitions: A literature search was performed using MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews from inception through September 2016. We included studies that reported odd ratios, relative risks or hazard ratios comparing outcomes of aspirin use in kidney transplant recipients. Pooled risk ratios (RR) and 95% confidence interval (CI) were assessed using a random-effect, generic inverse variance method. Results: We included 9 studies; enrolling 19 759 kidney transplant recipients that compared aspirin with no treatment. Compared to no treatment, aspirin reduced the risk of allograft failure (4 studies; RR: 0.57, 95% CI: 0.33 to 0.99), allograft thrombosis (2 studies; RR: 0.11, 95% CI: 0.02 to 0.53), and major adverse cardiac events (MACEs) or mortality (2 studies; RR: 0.72, 95% CI: 0.59 to 0.88), but not allograft rejection (3 studies; RR: 0.86, 95% CI: 0.45 to 1.65) or delayed graft function (DGF) (2 studies; RR: 1.00, 95% CI: 0.58 to 1.72) in kidney transplant recipients. The data on risk of major or minor bleeding were limited. Conclusions: Our meta-analysis demonstrates that administration of aspirin in kidney transplant recipients is associated with reduced risks of allograft failure, allograft thrombosis, and MACEs or mortality, but not allograft rejection or DGF. Future studies are needed to assess the risk of bleeding, and ultimately weigh the overall risks and benefits of aspirin use in specific kidney transplant patient populations.

Abstract Background Jaundice within the first 1–2 weeks of a neonate’s life will generally self-resolve; however, if it lasts longer than this time frame it warrants further work up. Direct or conjugated hyperbilirubinemia can suggest neonatal cholestasis, which in turn reflects marked reduction in bile secretion and flow. The differential diagnosis for neonatal cholestasis is broad. Neonatal choledocholithiasis is a rare cause of neonatal cholestasis, but should be considered on the differential diagnosis for patients presenting with elevated conjugated bilirubin. Case presentation We describe an infant who presented with neonatal cholestasis. He subsequently underwent work up for biliary atresia, as this is one of the more time-sensitive diagnoses that must be made in neonates with conjugated hyperbilirubinemia. He was ultimately found to have choledocholithiasis on magnetic resonance cholangiopancreatography. He was managed conservatively with optimizing nutrition and ursodeoxycholic acid therapy. Conclusions We found that conservative management, specifically optimizing nutrition and treating with ursodeoxycholic acid, can be a sufficient approach to facilitating resolution of the choledocholithiasis and conjugated hyperbilirubinemia.

Abstract Gallbladder carcinoma (GBC) is a major cancer of the gastrointestinal tract with poor prognosis. Reliable and affordable biomarker-based assays with high sensitivity and specificity for the detection of this cancer are a clinical need. With the aim of studying the potential of the plasma-derived extracellular vesicles (EVs), we carried out quantitative proteomic analysis of the EV proteins, using three types of controls and various stages of the disease, which led to the identification of 86 proteins with altered abundance. These include 29 proteins unique to early stage, 44 unique to the advanced stage and 13 proteins being common to both the stages. Many proteins are functionally relevant to the tumor condition or have been also known to be differentially expressed in GBC tissues. Several of them are also present in the plasma in free state. Clinical verification of three tumor-associated proteins with elevated levels in comparison to all the three control types—5′-nucleotidase isoform 2 (NT5E), aminopeptidase N (ANPEP) and neprilysin (MME) was carried out using individual plasma samples from early or advanced stage GBC. Sensitivity and specificity assessment based on receiver operating characteristic (ROC) analysis indicated a significant association of NT5E and ANPEP with advanced stage GBC and MME with early stage GBC. These and other proteins identified in the study may be potentially useful for developing new diagnostics for GBC.

Improving health literacy is a national public health priority. Given the context of the COVID-19 pandemic, it is even more critical for health and medical information to be clear and understandable for patients and their families. Clinic-based programs to improve health literacy need to be pragmatic, feasible, and helpful for the implementing clinic and patients. This paper describes the development, implementation, and evaluation of a pragmatic, clinic-based health literacy intervention in a safety-net clinic that serves uninsured and indigent patients. Study methods are guided by a previous pilot study and components recommended for pragmatic interventions. An electronic readiness assessment was distributed to out-patient clinics affiliated with a statewide hospital association. The AskMe3 tool was used for the intervention as it is evidence informed and relatively easy to implement. Implementation included ongoing dialogue between the clinic and the academic research team. Within the implementing clinic, data collected from patients via verbally administered questionnaires was analyzed using descriptive statistics and chi-squares. Interview data collected from the clinic director was analyzed qualitatively for themes. The implementing clinic had some of the lowest average scores of the 34 clinics who participated in the initial readiness assessment. Despite this, they were able to successfully implement the health literacy intervention during a global pandemic. Eighty-eight participants completed patient questionnaires at this clinic. Most patients (96%) agreed the AskMe3 questions helped them talk with the doctor or nurse at their current appointment. Most (99%) also perceived the AskMe3 tool to be very helpful when used in a clinical setting. The clinic director offered that the staff initially thought the intervention would be difficult to implement. However, implementation by clinic volunteers with encouragement and prioritization of health literacy by the clinic director contributed to success. When considering interventions for clinical settings, a pragmatic approach can help with selection and implementation of a program that fits with the realities on the ground. Further, frequent technical assistance can help resolve implementation barriers. Interventions utilizing tools such as AskMe3, because of their simplicity, allow creative solutions to capacity issues for clinics who see a need for health literacy improvements.

Background Many patients with severe aortic stenosis (AS) and an indication for aortic valve replacement (AVR) do not undergo treatment. The reasons for this have not been well studied in the transcatheter AVR era. We sought to determine how patient‐ and process‐specific factors affected AVR use in patients with severe AS. Methods and Results We identified ambulatory patients from 2016 to 2018 demonstrating severe AS, defined by aortic valve area ≤1.0 cm2. Propensity scoring analysis with inverse probability of treatment weighting was used to evaluate associations between predictors and the odds of undergoing AVR at 365 days and subsequent mortality at 730 days. Of 324 patients with an indication for AVR (79.3±9.7 years, 57.4% men), 140 patients (43.2%) did not undergo AVR. The odds of AVR were reduced in patients aged >90 years (odds ratio [OR], 0.24 [95% CI, 0.08–0.69]; P=0.01), greater comorbid conditions (OR, 0.88 per 1‐point increase in Combined Comorbidity Index [95% CI, 0.79–0.97]; P=0.01), low‐flow, low‐gradient AS with preserved left ventricular ejection fraction (OR, 0.11 [95% CI, 0.06–0.21]), and low‐gradient AS with reduced left ventricular ejection fraction (OR, 0.18 [95% CI, 0.08–0.40]) and were increased if the transthoracic echocardiogram ordering provider was a cardiologist (OR, 2.46 [95% CI, 1.38–4.38]). Patients who underwent AVR gained an average of 85.8 days of life (95% CI, 40.9–130.6) at 730 days. Conclusions The proportion of ambulatory patients with severe AS and an indication for AVR who do not receive AVR remains significant. Efforts are needed to maximize the recognition of severe AS, especially low‐gradient subtypes, and to encourage patient referral to multidisciplinary heart valve teams.

The Indian Association of Pathologists and Microbiologists (IAPM) and Indian Society of Gastroenterology (ISG) decided to make a joint consensus recommendation for handling, processing, and interpretation of SI biopsies for the diagnosis and management of celiac disease (CD) recognizing the inhomogeneous practice of biopsy sampling, orientation, processing, and interpretation. A modified Delphi process was used to develop this consensus document containing a total of 42 statements and recommendations, which were generated by sharing the document draft, incorporating expert's opinion, followed by three cycles of electronic voting as well as a full-day face-to-face virtual ZOOM meeting and review of supporting literature. Of the 42 statements, 7 statements are on small intestinal (SI) biopsy in suspected patients of CD, site and the number of biopsies; 7 on handling, fixative, orientation, processing, and sectioning in pathology laboratories; 2 on histological orientation; 13 statements on histological interpretation and histological grading; 3 on the assessment of follow-up biopsies; 2 statements on gluten-free diet (GFD)-nonresponsive CD; 4 on challenges in the diagnosis of CD; 2 statements each on pathology reporting protocol and training and infrastructure in this area. The goal of this guideline document is to formulate a uniform protocol agreed upon both by the experienced pathologists and gastroenterologists to standardize the practice, improve the yield of small bowel biopsy interpretation, patients' compliance, overall management in CD, and generate unified data for patient care and research in the related field.

Over the last two decades, our knowledge and understanding regarding the pathogenesis and biology of autoimmune pancreatitis (AIP) have improved tremendously. Type 1 AIP or IgG4-related pancreatitis (IgG4-RP) is now believed to be the prototype of the multisystemic IgG4-related disease. In view of clinical features like obstructive jaundice and mass-forming lesions in the pancreas in elderly men, type 1 AIP often mimics pancreatic cancer. IgG4-related sclerosing cholangitis concomitantly involving the extrahepatic and intrahepatic biliary tree is the most common extrapancreatic involvement seen in up to 80% of these patients, which needs to distinguish from cholangiocarcinoma. Histology is characterised by lymphoplasmacytic inflammation, abundant IgG4 positive plasma cell infiltration, storiform fibrosis and obliterative phlebitis. Apart from histology, high serum IgG4 levels, pancreatic parenchymal and duct imaging findings and other organ involvement aid in diagnosis especially in cases where definitive histology is not evident. Also, these parameters lay the foundation of various diagnostic criteria proposed over last few years. On the contrary, histology alone is the mainstay for establishing diagnosis of idiopathic duct-centric pancreatitis (IDCP) as it lacks any specific serological marker or imaging. Since both types of AIP respond dramatically to corticosteroid treatment, a biopsy is crucial to establish the preoperative diagnosis and to exclude malignancy so as to avoid unnecessary surgery. This review discusses the morphologic spectrum, treatment and prognosis of IgG4-RP and IDCP with an emphasis on approach to diagnosis with relevant histologic features, differential diagnoses and the challenges faced during biopsy interpretation.

Endothelial-to-mesenchymal transition (EndMT) is a hallmark of diabetes-associated vascular complications. Epigenetic mechanisms emerged as one of the key pathways to regulate diabetes-associated complications. In the current study, we aimed to determine how abrupt changes in histone 3 lysine 4 tri-methylation (H3K4me3) upon hyperglycemia exposure reprograms endothelial cells to undergo EndMT. Through in vitro studies, we first establish that intermittent high-glucose exposure to EC most potently induced partial mesenchyme-like characteristics compared with transient or constant high-glucose-challenged endothelial cells. In addition, glomerular endothelial cells of BTBR Ob/Ob mice also exhibited mesenchymal-like characteristics. Intermittent hyperglycemia-dependent induction of partial mesenchyme-like phenotype of endothelial cells coincided with an increase in H3K4me3 level in both macro- and micro-vascular EC due to selective increase in MLL2 and WDR82 protein of SET1/COMPASS complex. Such an endothelial-specific heightened H3K4me3 level was also detected in intermittent high-glucose-exposed rat aorta and in kidney glomeruli of Ob/Ob mice. Elevated H3K4me3 enriched in the promoter regions of Notch ligands Jagged1 and Jagged2, thus causing abrupt expression of these ligands and concomitant activation of Notch signaling upon intermittent hyperglycemia challenge. Pharmacological inhibition and/or knockdown of MLL2 in cells in vitro or in tissues ex vivo normalized intermittent high-glucose-mediated increase in H3K4me3 level and further reversed Jagged1 and Jagged2 expression, Notch activation and further attenuated acquisition of partial mesenchyme-like phenotype of endothelial cells. In summary, the present study identifies a crucial role of histone methylation in hyperglycemia-dependent reprograming of endothelial cells to undergo mesenchymal transition and indicated that epigenetic pathways contribute to diabetes-associated vascular complications.

Background: Gall bladder carcinoma (GBC) is an aggressive malignancy with high mortality and aggressive course, with palliation as the only available option. Objectives: To evaluate frequency of HER-2/neu overexpression in GBC and to seek its correlation, if any with conventional clinicopathological parameters and survival. Methods: Immunohistochemistry (IHC) was performed on 200 cases of GBC, 32 cases of dysplasia, and 100 cases of chronic cholecystitis. Fluorescent in situ hybridization (FISH) was performed on 30 randomly selected cases of GBC to validate IHC. HER-2/neu overexpression (IHC 3+/FISH amplification ≥2.2) was correlated with clinicopathological parameters by Chi-square test.P

A 66-year-old male presented with chief complaints of anorexia associated with mild dull, intermittent epigastric pain for 6 months. The patient was a known diabetic on oral hypoglycemic and on routine checkup was found to have deranged liver function profile. On radiology, an ill-defined hypoechoic enhancing lesion involving head, neck, and uncinate process of pancreas was noted. Whipple's pancreaticodudenectomy was done and reported as IgG4-related autoimmune pancreatitis. Later, IgG (slightly) and IgG4 were found to be markedly raised. We report this case to highlight the importance of IgG4 evaluation prior to major surgery in uncertain pancreatic mass.

BackgroundAflatoxin suppresses cellular immunity and accentuates HIV-associated changes in T- cell phenotypes and B- cells.ObjectiveThis prospective study was conducted to examine the association of aflatoxin levels with CD4 T-cell count and antiretroviral therapy uptake over time.MethodsSociodemographic and food data were collected from antiretroviral therapy naïve HIV-infected patients. CD4+ counts were collected from participants' medical records. Plasma samples were tested for aflatoxin B1 albumin adducts, hepatitis B surface antigen, and HIV viral load. Participants were separated into high and low aflatoxin groups based on the median aflatoxin B1 albumin adduct level of 10.4 pg/ml for data analysis.ResultsParticipants with high aflatoxin B1 albumin adduct levels had lower mean CD4 at baseline and at each follow-up period. Adjusted multivariable logistic regression analysis showed that higher baseline aflatoxin B1 adduct levels were associated with statistically significant lower CD4 counts (est = -66.5, p = 0.043). Not starting ART and low/middle socioeconomic status were associated with higher CD4 counts (est = 152.2, pConclusionConsistent correlations of higher aflatoxin B1 adduct levels with lower CD4 over time indicate that there is an independent early and prolonged effect of aflatoxin on CD4 even with the initiation of antiretroviral therapy. The prospective study design, evaluation of baseline and follow-up measures, extensive control for potential confounders, and utilization of objective measures of aflatoxin exposure and CD4 count provide compelling evidence for a strong epidemiologic association that deserves careful attention in HIV care and treatment programs.

BackgroundMaintaining blood pressure (BP) control over time may contribute to lower risk for cardiovascular disease (CVD) among individuals who are taking antihypertensive medication.MethodsThe Jackson Heart Study (JHS) enrolled 5,306 African-American adults ≥21 years of age and was used to determine the proportion of African Americans that maintain persistent BP control, identify factors associated with persistent BP control, and determine the association of persistent BP control with CVD events. This analysis included 1,604 participants who were taking antihypertensive medication at Visit 1 and had BP data at Visits 1 (2000-2004), 2 (2005-2008), and 3 (2009-2013). Persistent BP control was defined as systolic BP ResultsAt Visit 1, 1,226 of 1,604 participants (76.4%) with hypertension had controlled BP. Overall, 48.9% of participants taking antihypertensive medication at Visit 1 had persistent BP control. After multivariable adjustment for demographic, socioeconomic, clinical, behavioral, and psychosocial factors, and access-to-care, participants were more likely to have persistent BP control if they were ConclusionLess than half of JHS participants taking antihypertensive medication had persistent BP control, putting them at increased risk for heart failure.

Background: Hypoxic-ischemic encephalopathy (HIE) is associated with disturbances in visceral blood flow velocities. Therapeutic Hypothermia (TH) is a standard of care; however, its impact on gastrointestinal blood flow in infants with HIE is unknown. The objective of this study was to assess gastrointestinal (GI) blood flow and left ventricle output (LVO) in infants with hypoxic-ischemic encephalopathy during whole body TH and after rewarming. Methods: Serial echocardiography and Doppler evaluation of intestinal blood flow (celiac (CA) and superior mesenteric (SMA) arteries) were prospectively performed in a cohort of 20 newborn infants with HIE at 4 time points during hypothermia and after rewarming. Demographic, clinical and biochemical data were collected and analyzed for their relevance. Results: Median gestational age and birth weight was 40 weeks (37–41) and 3410 g (2190–4950) respectively. Celiac and mesenteric artery flow remained low during hypothermia and rose significantly after rewarming [peak systolic velocity in CA (0.63 m/s to 0.77 m/s, p = 0.004) and SMA (0.43 m/s to 0.55 m/s, p = 0.001)]. This increase was temporally associated with increased left ventricular output (106 ml/kg/min to 149 ml/kg/min, p

Introduction: Renal transplant recipients now have better graft survival rates, but continue to develop opportunistic infections. The present study was aimed at finding the incidence of opportunistic infections in the tropical environment in live-related transplant recipients. Materials and Methods: The study was carried out retrospectively with the help of medical records at a tertiary care hospital in North India from 2006 to 2010. The demographic and transplant details were noted, and data were analyzed for any possible risk factor. Results: A total of 1270 patients were studied, of which 231 infectious episodes were detected in 196 (15.4%) patients. Within 1 month, 11.7% of patients had infection, whereas 68.4% of patients had at least one infectious episode within the first 6 months of transplant. Bacterial infection (5.9%) followed by tuberculosis (4.9%), viral (3.8%), and fungal (2.1%) were the infections encountered. Aspergillosis (32.1%) was the most common fungal infection, followed by candidiasis and mucormycosis. The most common site of involvement was lung (26.4%), followed by urinary tract (13.0%). The overall patient survival was nearly 90%. Only 20% of patients had functional graft on follow-up in whom the graft was directly involved by a particular infection. Conclusions: Posttransplant infections continue to affect graft and patient survival. Higher rates are seen in the first 6 months posttransplant.

Continuous urbanization and modernization have increased the burning of fossil fuels to meet energy needs across the globe, emanating environmental pollution and depleting fossil fuels. Therefore, a shift towards sustainable and renewable energy is necessary. Several techniques to exploit biomass to yield energy are trending, with pyrolysis one of them. Usually, a single feedstock is employed in pyrolysis for anoxygenic generation of biochar together with bio-oil at elevated temperatures (350–600 °C). Bio-oil produced through pyrolysis can be upgraded to crude oil after some modification. However, these modifications of bio-oil are one of the major drawbacks for its large-scale adoption, as upgradation increases the overall cost. Therefore, in recent years the scientific community has been researching co-pyrolysis technology that involves the pyrolysis of lignocellulosic biomass waste with non-biodegradable waste. Co-pyrolysis reduces the need for post-modification of bio-oil, unlike pyrolysis of a single feedstock. This review article discusses the recent advancements and technological challenges in waste biomass co-pyrolysis, the mechanism of co-pyrolysis, and factors that affect co-pyrolysis. The current study critically analyzes different recent research articles presented in databases such as PubMed, MDPI, ScienceDirect, Springer, etc. Hence, this review is one-of-a-kind in that it attempts to explain each and every aspect of the co-pyrolysis process and its current progress in the scientific field. Consequently, this review also compiles the remarkable achievements in co-pyrolysis and recommendations for the future.

The development of new antibiotics to treat multidrug-resistant (MDR) bacteria or possess broad-spectrum activity is one of the challenging tasks. Unfortunately, there are not many new antibiotics in clinical trials. So, the molecular hybridization approach could be an effective strategy to develop potential drug candidates using the known scaffolds. We synthesized a total of 31 diverse linezolid conjugates 3, 5, 7, 9, 11, 13, and 15 using our established benzotriazole chemistry with good yield and purity. Some of the synthesized conjugates exhibited promising antibacterial properties against different strains of bacteria. Among all the synthesized compounds, 5d is the most promising antibacterial agent with MIC 4.5 µM against S. aureus and 2.25 µM against B. subtilis. Using our experimental data pool, we developed a robust QSAR (R2 = 0.926, 0.935; R2cvOO = 0.898, 0.915; R2cvMO = 0.903, 0.916 for the S. aureus and B. subtilis models, respectively) and 3D-pharmacophore models. We have also determined the drug-like properties of the synthesized conjugates using computational tools. Our findings provide valuable insight into the possible linezolid-based antibiotic drug candidates.