Cannabis use and cyclical vomiting syndrome: An open debate.

INTRODUCTION: Cyclical vomiting syndrome (CVS) carries a significant financial burden on the U.S. healthcare system due to the recurrent emergency department visits and inpatient hospitalizations. We aimed to update the literature on the predictors of hospital utilization and readmission among individuals admitted with CVS. METHODS: This is a retrospective nationwide study of patients hospitalized with a primary diagnosis of CVS. Using weighted data from the National Inpatient Sample (NIS) and the National Readmission Database (NRD), we conducted a multivariate regression analysis to assess predictors of length of stay (LOS), and 30-day readmission. RESULTS: Primary admissions for CVS totaled 35,055 in the NIS, and 31,240 in the NRD. 2012 patients (6.4%) were readmitted within 30 days. On multivariate regression, cannabis use was associated with reduced LOS (adjusted Mean Difference (aMD) = -0.53 days, 95% CI: -0.68 to -0.38), and 30-day readmissions (adjusted Hazard Ratio (aHR) = 0.63, 95% CI: 0.54-0.73). DISCUSSION: Cannabis use among CVS admissions was associated with reduced LOS and 30-day readmissions; these results could be in fact driven by Cannabis Hyperemesis Syndrome (CHS)-related hospitalizations and the effect of cannabis cessation on decreased symptomatology. ICD-10 coding for CHS should be transitioned to specific codes to improve the differentiation between CVS and CHS-related hospitalizations.

Determinants and outcomes of acute pancreatitis in patients hospitalized for COVID-19: Early pandemic experience.

OBJECTIVES: To examine the predictors and outcomes associated with the development of acute pancreatitis (AP) in patients hospitalized with Coronavirus Disease 2019 (COVID-19). METHODS: This is an observational analysis of the 2020 National Inpatient Sample Database. The study includes adult patients who were admitted with a confirmed diagnosis of COVID-19 and stratifies them based on the presence or absence of AP during their hospitalization. Predictors of AP development between the two groups and differences in outcomes are examined. Multivariate logistic regression analysis using Stata/BE 17.0 is conducted, with adjustments made for age, sex, race, and Charlson Comorbidity Index (CCI). Statistical significance is determined at a p-value of <0.05. RESULTS: Significant factors associated with an increased risk of AP in COVID-19 patients include Hispanic ethnicity, higher Charlson Comorbidity Index (CCI) score, residence in states located in the southern region, history of chronic kidney disease, chronic liver disease, malnutrition, portal hypertension, and alcohol use. COVID-19 patients who developed AP were also found to be at higher risk of adverse outcomes, including mortality, acute coronary syndrome, acute kidney injury, sepsis, septic shock, in-hospital cardiac arrest, invasive mechanical ventilation, upper gastrointestinal bleeding, prolonged length of stay, and increased healthcare cost. CONCLUSIONS: In hospitalized patients with COVID-19, the presence of AP is associated with increased mortality and morbidity. Risk factors for developing AP in this population include Hispanic ethnicity, residence in the southern region, higher Charlson Comorbidity Index (CCI) score, history of chronic kidney disease, chronic liver disease, malnutrition, portal hypertension, and alcohol use.

Autoimmune Hepatitis and Obstetrical Outcomes: A Nationwide Assessment.

INTRODUCTION: Previous research identified AIH as linked to unfavorable obstetrical outcomes in a US nationwide retrospective study from 2012-2016. Our aim is to update the literature and strengthen the AIH-pregnancy outcomes relationship. METHODS: Using the National Inpatient Sample database in the US, from 2016 to 2020, we compared pregnant females with a diagnosis of AIH to those with and without other chronic liver diseases (CLD), using ICD-10-CM codes. Baseline characteristics were analyzed using T-test and Chi-Square, and multivariate regression was used to estimate the differences in maternal outcomes adjusted for age, race, insurance status, geographical location, hospital characteristics, and comorbid conditions. RESULTS: Out of 19,392,328 hospitalizations for pregnant females ≥ 18 years old from 2016 to 2020, 1095 had AIH, 179,655 had CLD, and 19,206,696 had no CLD. No mortality was observed among individuals with AIH. When compared to individuals without CLD, AIH was associated with an 82% increase in the odds of preterm delivery (AIH: 8% vs. Without CLD: 5%, adjusted Odds Ratio = 1.82, 95% CI 1.06-3.14), with no significant differences in gestational diabetes mellitus, hypertensive complications, and postpartum hemorrhage, and a 0.6 day longer hospital stay. Furthermore, there were no significant differences in outcomes between AIH and CLD. CONCLUSIONS: Our study reinforces the association of AIH with adverse obstetrical outcomes (e.g., preterm delivery), however, we found that there is no difference in GDM and hypertensive complications, as suggested in prior studies. Therefore, further investigations are needed to clarify the association between AIH and these obstetrical complications.

Pharmacological and non-pharmacological countermeasures to Space Motion Sickness: a systematic review.

Introduction: Space Motion Sickness (SMS) is a syndrome that affects around 70% of astronauts and includes symptoms of nausea, dizziness, fatigue, vertigo, headaches, vomiting, and cold sweating. Consequences range from discomfort to severe sensorimotor and cognitive incapacitation, which might cause potential problems for mission-critical tasks and astronauts and cosmonauts' well-being. Both pharmacological and non-pharmacological countermeasures have been proposed to mitigate SMS. However, their effectiveness has not been systematically evaluated. Here we present the first systematic review of published peer-reviewed research on the effectiveness of pharmacological and non-pharmacological countermeasures to SMS. Methods: We performed a double-blind title and abstract screening using the online Rayyan collaboration tool for systematic reviews, followed by a full-text screening. Eventually, only 23 peer-reviewed studies underwent data extraction. Results: Both pharmacological and non-pharmacological countermeasures can help mitigate SMS symptoms. Discussion: No definitive recommendation can be given regarding the superiority of any particular countermeasure approach. Importantly, there is considerable heterogeneity in the published research methods, lack of a standardized assessment approach, and small sample sizes. To allow for consistent comparisons between SMS countermeasures in the future, standardized testing protocols for spaceflight and ground-based analogs are needed. We believe that the data should be made openly available, given the uniqueness of the environment in which it is collected. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021244131.

Acute Immune Reconstitution Inflammatory Syndrome-HBV Flare in an HIV/HBV Coinfected Patient After Antiretroviral Therapy Initiation: Case Report and Literature Review.

BACKGROUND Immune reconstitution inflammatory syndrome (IRIS) is a well-recognized complication after antiretroviral therapy (ART) initiation among patients with HIV. Acute HBV flares after starting antiretroviral therapy have been reported in 20% to 25% of coinfected patients, among whom only 1% to 5% develop clinical hepatitis. Liver biopsy and serological evaluation help in diagnosis. CASE REPORT A 24-year-old man with history of HIV diagnosed in 2018 developed severe IRIS-related HBV flare after initiation of ART. He was taking ART since 2018 until his immigration to the United States in 2021. He came to establish care and was started on bictegravir/emtricitabine/tenofovir alafenamide (BIC/F/TAF). Three weeks later, he presented to the Emergency Department with polyarthralgia and loose stools; transaminases showed an increasing trend on follow-up. He was admitted for closer monitoring. Workup was remarkable for reactive HBsAg, HBeAg, and HBcIgM antibodies, with HBV viral load of 295 304 copies/mL. Abdominal imaging was unremarkable. ART was switched to rilpivirine/emtricitabine/tenofovir alafenamide (RPV/FTC/TAF), considering the hypothetical risk of hepatotoxicity from BIC/F/TAF. Despite therapy, transaminases were up-trending. He underwent computerized tomography-guided liver biopsy, showing moderate to severe acute hepatitis, compatible with IRIS. He received steroids, and ART was continued. Transaminases resolved, HBV load reduced significantly, HIV load became undetectable at 9 weeks, and he developed HBeAb (seroconversion) at 4 months after initiating ART. CONCLUSIONS Our case highlights the importance of early recognition and management of IRIS-HBV flares after initiation of ART among coinfected patients. Liver biopsy is indicated for definitive diagnosis. ART directed against both viruses should be continued.

Cognition in zero gravity: Effects of non-terrestrial gravity on human behaviour.

As humanity prepares for deep space exploration, understanding the impact of spaceflight on bodily physiology is critical. While the effects of non-terrestrial gravity on the body are well established, little is known about its impact on human behaviour and cognition. Astronauts often describe dramatic alterations in sensorimotor functioning, including orientation, postural control, and balance. Changes in cognitive functioning as well as in socio-affective processing have also been observed. Strikingly, no comprehensive theoretical model exists to outline the impact of non-terrestrial gravity on behaviour. Here, we have reviewed the key literature across the last 10 years and explored the impact of non-terrestrial gravity across three key functional domains: sensorimotor functioning, cognition, and socio-affective processing. We have proposed and preliminary validated a neurocognitive model to account for the effects of non-terrestrial gravity in these domains. Understanding the impact of non-terrestrial gravity on human behaviour has never been timelier and it will help mitigate against risks in both commercial and non-commercial spaceflight.

New-Onset Graves' Disease in the Background of Hashimoto's Thyroiditis: Spectrums of the Same Disease With Changing Autoantibodies.

Hashimoto's thyroiditis and Graves' disease represent two spectrums of the same autoimmune thyroiditis. Evolution from Graves' disease to Hashimoto's thyroiditis is a common scenario but conversion is a rare occurrence that we observed in the presented case of a 56-year-old Hispanic female with a history of Hashimoto's thyroiditis with positive anti-thyroperoxidase (TPO) antibodies who was euthyroid on levothbefore75 µg for six years prior to her presentation to the emergency department (ED) with complaints of palpitations, exertional dyspnea, and unintentional weight loss of 20 lbs for four months. The patient denied any recent change in levothyroxine dosage. The patient was noted to have tachycardia at rest, hyperdynamic circulation, and fine tremors on outstretched hands-on examination but no exophthalmos, thyromegaly, or pedal swellings. Her initial laboratory workup revealed thyroid-stimulating hormone of <0.01 mIU/L, with elevated free T3 and free T4 levels. Levothyroxine was held and beta-blockade therapy was started for symptom control. Further workup showed elevated thyroid-stimulating immunoglobulin and thyroid receptor antibody levels and normalization of anti-TPO antibody levels. The radioactive iodine uptake scan was initially delayed because the patient underwent a pulmonary angiogram in the ED. A later scan showed thyromegaly with heterogeneous uptake of 82% in both lobes. Hence, the patient was diagnosed with Graves' disease and managed with radioactive iodine ablation therapy. On follow-up, the patient developed post-ablation hypothyroidism; she was started back on levothyroxine therapy and became euthyroid. This case highlights that patients can develop Graves' disease in the background of a hypothyroid state, and this conversion might be postulated secondary to a combination of atypical destructive thyroiditis and a switch of autoantibodies from blocking to stimulating ones. Clinicians should suspect the possibility of changing antibodies when there is a change in the patient's euthyroid state.

Primary Endometrial Diffuse Large B-cell Lymphoma: A Rare Disease and Diagnostic Challenge in an Asymptomatic Postmenopausal Woman.

Primary endometrial lymphomas are rare malignancies because the female genital tract is usually involved as a secondary site. Here, we present a case of primary endometrial lymphoma diagnosed in a 49-year-old postmenopausal female who was referred to hematology/oncology service for the evaluation of incidental findings of malignant-looking cells on a Pap smear followed by a cervical polyp biopsy that was suggestive of high-grade B-cell lymphoma (Ki-67: 80-90%) on routine screening. The baseline laboratory assessment was unremarkable except for hypochromic normocytic anemia. A bone marrow biopsy was performed to rule out primary involvement and revealed no evidence of lymphoma both on morphology and immunophenotyping. Fluorescence in situ hybridization tests were also negative. Repeat endocervical biopsy with more tissue sampling revealed similar findings. Further workup was pursued including an initial staging positron emission tomography-computed tomography (PET-CT) scan that showed a 3.8 × 2.7 cm, with standardized uptake value (SUV)max of 30.4, malignant-appearing mass extending up to the left posterior cervix and an 11 mm left axillary lymph node with SUVmax of 2.9. An excisional biopsy of the axillary node was negative for malignancy and ruled out nodal involvement. A diagnosis of primary endometrial diffuse large B-cell lymphoma was made on biopsy of posterior cervical mass that revealed diffuse infiltration of large lymphoid cells, positive for B-cell markers, namely, B-cell lymphoma 6 (BCL6), paired box 5 (PAX5+), CD20, and CD19 with methoxyisobutyl isonitrile (MIBI) of 100%, and negative for T-cell and mesenchymal markers, namely, CD3, CD45, CD43, CD138, Melan A, S100, and Vimentin. The disease was staged as 1E (one extranodal site) according to the Ann Arbor staging system. The patient achieved remission after receiving four to six cycles of R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisone) therapy. Interval staging PET-CT scans, performed after the second cycle and at the completion of therapy to assess treatment response, were negative for new disease activity in the uterus. The patient remains in clinical remission to date and is on regular follow-up. This case is a good illustration of the fact that the female genital tract can be the primary site for B-cell lymphomas. If such an abnormality is found incidentally on routine screening, it should not be ignored and the patient should be evaluated further to make the definitive diagnosis so that timely management can be offered. Through this case, we also highlight the role of immunohistochemical studies using specific cell markers in ruling out other possibilities that could mimic lymphomas on tissue biopsy as treatment modalities differ.

Interaction Analysis of Adenovirus L5 Protein With Pancreatic Cancer Cell Surface Receptor to Analyze Its Affinity for Oncolytic Virus Therapy.

This study seeks to investigate the interaction profile of the L5 protein of oncolytic adenovirus with the overexpressed surface receptors of pancreatic cancer. This is an important area of research because pancreatic cancer is one of the most fatal malignancies with a very low patient survival rate. Multiple therapies to date to improve the survival rate are reported; however, they show a comparatively low success rate. Among them, oncolytic virus therapy is a type of immunotherapy that is currently under deliberation by researchers for multiple cancer types in various clinical trials. Talimogene laherparepvec (T-VEC) is the first oncolytic virus approved by the US Food and Drug Administration (FDA) for melanoma. The oncolytic virus not only kills cancer cells but also activates the anticancer immune response. Therefore, it is preferred over others to deal with aggressive pancreatic cancer. The efficacy of therapy primarily depends on how effectively the oncolytic virus enters and infects the cancer cell. Cell surface receptors and their interactions with virus coat proteins are a crucial step for oncolytic virus entry and a pivotal determinant. The L5 proteins of the virus coat are the first to interact with host cell surface receptors. Therefore, the objective of this study is to analyze the interaction profile of the L5 protein of oncolytic adenovirus with overexpressed surface receptors of pancreatic cancer. The L5 proteins of three adenovirus serotypes HAdV2, HAdV5, and HAdV3 were utilized in this study. Overexpressed pancreatic cancer receptors include SLC2A1, MET, IL1RAP, NPR3, GABRP, SLC6A6, and TMPRSS4. The protein structures of viral and cancer cell protein were docked using the High Ambiguity Driven protein-protein DOCKing (HADDOCK) server. The binding affinity and interaction profile of viral proteins against all the receptors were analyzed. Results suggest that the HAdV3 L5 protein shows better interaction as compared to HAdV2 and HAdV5 by elucidating high binding affinity with 4 receptors (NPR3, GABRP, SLC6A6, and TMPRSS4). The current study proposed that HAdV5 or HAdV2 virus pseudotyped with the L5 protein of HAdV3 can be able to effectively infect pancreatic cancer cells. Moreover, the current study surmises that the affinity maturation of HAdV3 L5 can enhance virus attachment with all the receptors of cancer cells.

Synthesis, structure and acetylcholinesterase inhibition activity of new diarylpyrazoles.

A variety of diarylpyrazole derivatives III-VI were synthesized and structurally characterized using FTIR, 1H and 13C NMR spectroscopy, and in case of compound VIb by X-ray single crystal analysis. The in vitro biological studies revealed that seven of the diarylpyrazole derivatives IIIa, IIIb, IIId, IIIe, IVa, IVb and IVd are highly potent inhibitors of acetylcholinesterase enzyme with IC50 values of 0.48 ± 0.092 µg/mL, 0.45 ± 0.093 µg/mL, 0.30 ± 0.014 µg/mL, 0.59 ± 0.072 µg/mL, 0.29 ± 0.084 µg/mL, 0.56 ± 0.010 µg/mL and 0.28 ± 0.096 µg/mL, respectively. All these seven products were more potent than the standard drug, donepezil (IC50 = 0.73 ± 0.015 µg/mL), while compounds IIIc (0.67 ± 0.099 µg/ml) and VIa (0.66 ± 0.069 µg/ml) are almost equipotent to the donepezil. Particularly, compounds IVa and IVd are highly active acetylcholinesterase enzyme inhibitors, demonstrating more than two-fold inhibitory activity than the reference inhibitor. Molecular docking studies were carried out to identify the possible binding modes of the diarylpyrazoles within the active pocket of the enzymes. The docking interactions of the synthesized compounds with acetylcholinesterase also provided high docking scores. These results clearly indicate the potential of these compound as powerful lead molecules for further investigations.

Reducing Cybersickness in 360-Degree Virtual Reality.

Despite the technological advancements in Virtual Reality (VR), users are constantly combating feelings of nausea and disorientation, the so-called cybersickness. Cybersickness symptoms cause severe discomfort and hinder the immersive VR experience. Here we investigated cybersickness in 360-degree head-mounted display VR. In traditional 360-degree VR experiences, translational movement in the real world is not reflected in the virtual world, and therefore self-motion information is not corroborated by matching visual and vestibular cues, which may trigger symptoms of cybersickness. We evaluated whether a new Artificial Intelligence (AI) software designed to supplement the 360-degree VR experience with artificial six-degrees-of-freedom motion may reduce cybersickness. Explicit (simulator sickness questionnaire and Fast Motion Sickness (FMS) rating) and implicit (heart rate) measurements were used to evaluate cybersickness symptoms during and after 360-degree VR exposure. Simulator sickness scores showed a significant reduction in feelings of nausea during the AI-supplemented six-degrees-of-freedom motion VR compared to traditional 360-degree VR. However, six-degrees-of-freedom motion VR did not reduce oculomotor or disorientation measures of sickness. No changes were observed in FMS and heart rate measures. Improving the congruency between visual and vestibular cues in 360-degree VR, as provided by the AI-supplemented six-degrees-of-freedom motion system considered, is essential for a more engaging, immersive and safe VR experience, which is critical for educational, cultural and entertainment applications.

Integrated Analysis of Microarray and RNA-Seq Data for the Identification of Hub Genes and Networks Involved in the Pancreatic Cancer.

Pancreatic cancer (PaCa) is the seventh most fatal malignancy, with more than 90% mortality rate within the first year of diagnosis. Its treatment can be improved the identification of specific therapeutic targets and their relevant pathways. Therefore, the objective of this study is to identify cancer specific biomarkers, therapeutic targets, and their associated pathways involved in the PaCa progression. RNA-seq and microarray datasets were obtained from public repositories such as the European Bioinformatics Institute (EBI) and Gene Expression Omnibus (GEO) databases. Differential gene expression (DE) analysis of data was performed to identify significant differentially expressed genes (DEGs) in PaCa cells in comparison to the normal cells. Gene co-expression network analysis was performed to identify the modules co-expressed genes, which are strongly associated with PaCa and as well as the identification of hub genes in the modules. The key underlaying pathways were obtained from the enrichment analysis of hub genes and studied in the context of PaCa progression. The significant pathways, hub genes, and their expression profile were validated against The Cancer Genome Atlas (TCGA) data, and key biomarkers and therapeutic targets with hub genes were determined. Important hub genes identified included ITGA1, ITGA2, ITGB1, ITGB3, MET, LAMB1, VEGFA, PTK2, and TGFß1. Enrichment analysis characterizes the involvement of hub genes in multiple pathways. Important ones that are determined are ECM-receptor interaction and focal adhesion pathways. The interaction of overexpressed surface proteins of these pathways with extracellular molecules initiates multiple signaling cascades including stress fiber and lamellipodia formation, PI3K-Akt, MAPK, JAK/STAT, and Wnt signaling pathways. Identified biomarkers may have a strong influence on the PaCa early stage development and progression. Further, analysis of these pathways and hub genes can help in the identification of putative therapeutic targets and development of effective therapies for PaCa.

Long non-coding RNAs and their targets as potential biomarkers in breast cancer.

Breast cancer is among the lethal types of cancer with a high mortality rate, globally. Its high prevalence can be controlled through improved analysis and identification of disease-specific biomarkers. Recently, long non-coding RNAs (lncRNAs) have been reported as key contributors of carcinogenesis and regulate various cellular pathways through post-transcriptional regulatory mechanisms. The specific aim of this study was to identify the novel interactions of aberrantly expressed genetic components in breast cancer by applying integrative analysis of publicly available expression profiles of both lncRNAs and mRNAs. Differential expression patterns were identified by comparing the breast cancer expression profiles of samples with controls. Significant co-expression networks were identified through WGCNA analysis. WGCNA is a systems biology approach used to elucidate the pattern of correlation between genes across microarray samples. It is also used to identify the highly correlated modules. The results obtained from this study revealed significantly differentially expressed and co-expressed lncRNAs and their cis- and trans-regulating mRNA targets which include RP11-108F13.2 targeting TAF5L, RPL23AP2 targeting CYP4F3, CYP4F8 and AL022324.2 targeting LRP5L, AL022324.3, and Z99916.3, respectively. Moreover, pathway analysis revealed the involvement of identified mRNAs and lncRNAs in major cell signalling pathways, and target mRNAs expression is also validated through cohort data. Thus, the identified lncRNAs and their target mRNAs represent novel biomarkers that could serve as potential therapeutics for breast cancer and their roles could also be further validated through wet labs to employ them as potential therapeutic targets in future.

Barriers to the early initiation of Insulin therapy among diabetic patients coming to diabetic clinics of tertiary care hospitals.

BACKGROUND AND OBJECTIVE: Initiation of Insulin therapy during earlier stages has proved to significantly improve health outcomes among diabetics in comparison to oral medications. Not only patients but physicians are also often resistant to early initiation of insulin therapy. The objective was to assess misconceptions and barriers to early initiation of insulin therapy among diabetic patients coming to a diabetic clinic. METHODS: This cross sectional study was conducted on 300 patients selected by convenience sampling arriving in Diabetes Outdoor Clinics of Mayo and Services Hospitals, Lahore during August 2017 to May 2018. The data was entered and analyzed by using SPSS version 17. RESULTS: Out of 300 patients included in study, 39% (n= 117) were males and 61% (n=183) were females. The mean age of the participants at presentation was 48.46±13.15 years with a range of 13 to 80 years. Study participants considered it embarrassing to inject insulin in public place (p-value 0.01). The fear associated with lifelong commitment to insulin therapy once it is started, was also found statistically significant (p-value 0.001)particularly in subjects who have long duration of DM (>5 years). CONCLUSION: Perceptions of diabetic patients about insulin therapy are still barriers to early initiation of therapy and tend to prevail in Pakistan and around the globe.

Gravity modulates behaviour control strategy.

Human behaviour is a trade-off between exploitation of familiar resources and exploration of new ones. In a challenging environment-such as outer space-making the correct decision is vital. On Earth, gravity is always there, and is an important reference for behaviour. Thus, altered gravitational signals may affect behaviour control strategies. Here, we investigated whether changing the body's orientation to the gravitational vector would modulate the balance between routine and novel behaviour. Participants completed a random number generation task while upright or supine. We found decreased randomness when participants were supine. In particular, the degree of equiprobability of pairs of consecutive responses was reduced in the supine orientation. Online gravitational signals may shape the balance between exploitation and exploration, in favour of more stereotyped and routine responses.