Molecular mechanism of synovial joint site specification and induction in developing vertebrate limbs.

The vertebrate appendage comprises three primary segments, the stylopod, zeugopod and autopod, each separated by joints. The molecular mechanisms governing the specification of joint sites, which define segment lengths and thereby limb architecture, remain largely unknown. Existing literature suggests that reciprocal gradients of retinoic acid (RA) and fibroblast growth factor (FGF) signaling define the expression domains of the putative segment markers Meis1, Hoxa11 and Hoxa13. Barx1 is expressed in the presumptive joint sites. Our data demonstrate that RA-FGF signaling gradients define the expression domain of Barx1 in the first presumptive joint site. When misexpressed, Barx1 induces ectopic interzone-like structures, and its loss of function partially blocks interzone development. Simultaneous perturbations of RA-FGF signaling gradients result in predictable shifts of Barx1 expression domains along the proximo-distal axis and, consequently, in the formation of repositioned joints. Our data suggest that during early limb bud development in chick, Meis1 and Hoxa11 expression domains are overlapping, whereas the Barx1 expression domain resides within the Hoxa11 expression domain. However, once the interzone is formed, the expression domains are refined and the Barx1 expression domain becomes congruent with the border of these two putative segment markers.

Matrixed CDR grafting: A neoclassical framework for antibody humanization and developability.

Discovery and optimization of a biotherapeutic monoclonal antibody requires a careful balance of target engagement and physicochemical developability properties. To take full advantage of the sequence diversity provided by different antibody discovery platforms, a rapid and reliable process for humanization of antibodies from nonhuman sources is required. Canonically, maximizing homology of the human variable region (V-region) to the original germline was believed to result in preservation of binding, often without much consideration for inherent molecular properties. We expand on this approach by grafting the complementary determining regions (CDRs) of a mouse anti-LAG3 antibody into an extensive matrix of human variable heavy chain (VH) and variable light chain (VL) framework regions with substantially broader sequence homology to assess the impact on complementary determining region-framework compatibility through progressive evaluation of expression, affinity, biophysical developability, and function. Specific VH and VL framework sequences were associated with major expression and purification phenotypes. Greater VL sequence conservation was correlated with retained or improved affinity. Analysis of grafts that bound the target demonstrated that initial developability criteria were significantly impacted by VH, but not VL. In contrast, cell binding and functional characteristics were significantly impacted by VL, but not VH. Principal component analysis of all factors identified multiple grafts that exhibited more favorable antibody properties, notably with nonoptimal sequence conservation. Overall, this study demonstrates that modern throughput systems enable a more thorough, customizable, and systematic analysis of graft-framework combinations, resulting in humanized antibodies with improved global properties that may progress through development more quickly and with a greater probability of success.

Recompensation of Chronic Hepatitis C-Related Decompensated Cirrhosis Following Direct-Acting Antiviral Therapy: Prospective Cohort Study From a Hepatitis C Virus Elimination Program.

BACKGROUND & AIMS: Chronic hepatitis C-related decompensated cirrhosis is associated with lower sustained virologic response (SVR)-12 rates and variable regression of disease severity after direct-acting antiviral agents. We assessed rates of SVR-12, recompensation (Baveno VII criteria), and survival in such patients. METHODS: Between July 2018 and July 2023, patients with decompensated chronic hepatitis C-related cirrhosis after direct-acting antiviral agents treatment were evaluated for SVR-12 and then had 6-monthly follow-up. RESULTS: Of 6516 patients with cirrhosis, 1152 with decompensated cirrhosis (age 53.2 ± 11.5 years; 63% men; Model for End-stage Liver Disease-Sodium [MELD-Na]: 16.5 ± 4.6; 87% genotype 3) were enrolled. SVR-12 was 81.8% after 1 course; ultimately SVR was 90.8% after additional treatment. Decompensation events included ascites (1098; 95.3%), hepatic encephalopathy (191; 16.6%), and variceal bleeding (284; 24.7%). Ascites resolved in 86% (diuretic withdrawal achieved in 24% patients). Recompensation occurred in 284 (24.7%) at a median time of 16.5 (interquartile range, 14.5-20.5) months. On multivariable Cox proportional hazards analysis, low bilirubin (adjusted hazard ratio [aHR], 0.6; 95% confidence interval [CI], 0.5-0.8; P < 0.001), international normalized ratio (aHR, 0.2; 95% CI, 0.1-0.3; P < 0.001), absence of large esophageal varices (aHR, 0.4; 95% CI, 0.2-0.9; P = 0.048), or gastric varices (aHR, 0.5; 95% CI, 0.3-0.7; P = 0.022) predicted recompensation. Portal hypertension progressed in 158 (13.7%) patients, with rebleed in 4%. Prior decompensation with variceal bleeding (aHR, 1.6; 95% CI, 1.2-2.8; P = 0.042), and presence of large varices (aHR, 2.9; 95% CI, 1.3-6.5; P < 0.001) were associated with portal hypertension progression. Further decompensation was seen in 221 (19%); 145 patients died and 6 underwent liver transplantation. A decrease in MELDNa of ≥3 was seen in 409 (35.5%) and a final MELDNa score of <10 was seen in 335 (29%), but 2.9% developed hepatocellular carcinoma despite SVR-12. CONCLUSIONS: SVR-12 in hepatitis C virus-related decompensated cirrhosis in a predominant genotype 3 population led to recompensation in 24.7% of patients over a follow-up of 4 years in a public health setting. Despite SVR-12, new hepatic decompensation evolved in 19% and hepatocellular carcinoma developed in 2.9% of patients. (ClinicalTrials.gov, Number: NCT03488485).

Endoscopic Ultrasound-Guided Rendezvous Technique Versus Precut Sphincterotomy as Salvage Technique in Patients With Benign Biliary Disease and Difficult Biliary Cannulation : A Randomized Controlled Trial.

BACKGROUND: The standard salvage technique used for difficult bile duct cannulation is precut sphincterotomy, whereas endoscopic ultrasound-guided rendezvous technique (EUS-RV) is a relatively newer method. Prospective comparative data between these 2 techniques as salvage for biliary access in patients with benign biliary disease and difficult bile duct cannulation is lacking. OBJECTIVE: To compare EUS-RV and precut sphincterotomy as salvage technique for difficult bile duct cannulation in benign biliary obstruction. DESIGN: Participant-masked, parallel-group, superiority, randomized controlled trial. (Clinical Trials Registry of India: CTRI/2020/07/026613). SETTING: Tertiary care academic institute from July 2020 to May 2021. PARTICIPANTS: All patients with benign biliary disease and difficult bile duct cannulation requiring salvage strategy. INTERVENTION: Patients were randomly assigned by computer-generated randomized blocks sequence in 1:1 fashion to either EUS-RV or precut sphincterotomy. Patients with failure in EUS-RV were crossed over to precut sphincterotomy and vice versa. MEASUREMENTS: The primary outcome measure was technical success. The other outcome measures included procedure time, radiation dose, and adverse events. RESULTS: In total, 100 patients were randomly assigned to EUS-RV (n = 50) and precut sphincterotomy (n = 50). The technical success rate (92% vs. 90%; P = 1.00; relative risk, 1.02 [95% CI, 0.90 to 1.16]), median procedure time (10.1 vs. 9.75 minutes), and overall complication rate (12% vs. 10%; relative risk, 1.20 [CI, 0.39 to 3.68]) were similar between the 2 groups. Five patients (10%) in the EUS-RV group and 5 patients (10%) in the precut sphincterotomy group had developed post-endoscopic retrograde cholangiopancreatography pancreatitis. All failed cases in either salvage group could be successfully cannulated when crossed over to the other group. LIMITATION: Single center study done by experts. CONCLUSION: Endoscopic ultrasound-guided rendezvous technique and precut sphincterotomy have similar success rates as salvage techniques in the technically challenging cohort of difficult bile duct cannulation for benign biliary disease, with acceptable complications rates. PRIMARY FUNDING SOURCE: None.

Analyzing Fusion Pore Dynamics and Counting the Number of Acetylcholine Molecules Released by Exocytosis.

Acetylcholine (ACh) is a critical neurotransmitter influencing various neurophysiological functions. Despite its significance, quantitative methods with adequate spatiotemporal resolution for recording a single exocytotic ACh efflux are lacking. In this study, we introduce an ultrafast amperometric ACh biosensor that enables 50 kHz electrochemical recording of spontaneous single exocytosis events at axon terminals of differentiated cholinergic human SH-SY5Y neuroblastoma cells with sub-millisecond temporal resolution. Characterization of the recorded amperometric traces revealed seven distinct current spike types, each displaying variations in shape, time scale, and ACh quantities released. This finding suggests that exocytotic release is governed by complex fusion pore dynamics in these cells. The absolute number of ACh molecules released during exocytosis was quantified by calibrating the sensor through the electroanalysis of liposomes preloaded with varying ACh concentrations. Notably, the largest quantal release involving approximately 8000 ACh molecules likely represents full exocytosis, while a smaller release of 5000 ACh molecules may indicate partial exocytosis. Following a local administration of bafilomycin A1, a V-ATPase inhibitor, the cholinergic cells exhibited both a larger quantity of ACh released and a higher frequency of exocytosis events. Therefore, this ACh sensor provides a means to monitor minute amounts of ACh and investigate regulatory release mechanisms at the single-cell level, which is vital for understanding healthy brain function and pathologies and optimizing drug treatment for disorders.

Aflatoxin exposure is associated with an increased risk of gallbladder cancer.

Gall bladder cancer (GBC) is common among the socioeconomically deprived populations of certain geographical regions. Aflatoxin is a genotoxic hepatocarcinogen, which is recognized to have a role in the pathogenesis of hepatocellular carcinoma. However, the role of aflatoxin in the pathogenesis of GBC is largely unknown. We determined serum AFB1-Lys albumin adduct (AAA) levels as a marker of aflatoxin exposure in the patients with GBC and compared to those without GBC. The relationship of AAA levels to cytogenetic (TP53mutation&HER2/neu amplification) and radiological characteristics of the tumor was assessed. We included GBC cases (n = 51) and non-GBC controls (n = 100). Mean serum AAA levels were higher in the GBC group (n = 51) than those without GBC (n = 100) (26.1 ± 12.2 vs. 13.1 ± 11.9 ng/mL; p < .001). HER2/neu expression was associated with higher AAA levels compared to those with equivocal or negative expression (43.9 ± 3 vs. 28.6 ± 10 vs. 19.3 ± 7 ng/mL; p < .001). Older age (age >50 years) (odds ratio [OR] = 3.2 [CI: 1.3-8.2]; p = .013), positive Helicobacter pylori serology (OR = 5.1 [CI: 1.4-17.8]; p = .012), presence of GS (OR = 5 [CI: 1.5-16.9]; p = .009) and detectable AAA levels (OR = 6.8 [CI: 1.3-35.7]; p = .024) were independent risk factors for the presence of the GBC among all study subjects. Among patients harboring GS, older age (age >50 years) (OR = 4.5 [CI: 1.3-14.9]; p = .015), female gender (OR = 3.8 [CI: 1.2-12.5]; p = .027), presence of multiple GS (OR = 21.9 [CI: 4.8-100.4]; p < .001) and high serum AAA levels (OR = 5.3 [CI: 1.6-17.3]; p = .006) were independent risk factors for the presence of the GBC. Elderly age >50 years (OR = 2.6 [CI: 1.3-5.2]; p = .010) and frequent peanut consumption (OR = 2.3 [CI: 1.1-4.9]; p = .030) were independent risk factors for high serum AAA levels. The current study has implications for the prevention of GBC through the reduction of dietary aflatoxin exposure.

Buprenorphine Versus Diclofenac for Pain Relief in Acute Pancreatitis: A Double-Blinded Randomized Controlled Trial.

BACKGROUND: Although both nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids are used for analgesia in acute pancreatitis (AP), the analgesic of choice is not known. We compared buprenorphine, an opioid, and diclofenac, an NSAID, for analgesia in AP. METHODS: In a double-blind randomized controlled trial, AP patients were randomized to receive intravenous diclofenac or intravenous buprenorphine. Fentanyl was used as rescue analgesia, delivered through a patient-controlled analgesia pump. Primary outcome was the difference in the dose of rescue fentanyl required. Secondary outcomes were the number of effective and ineffective demands of rescue fentanyl, pain-free interval, reduction in visual analogue scale (VAS) score, adverse events, and organ failure development. RESULTS: Twenty-four patients were randomized to diclofenac and 24 to buprenorphine. The 2 groups were matched at baseline. The total amount of rescue fentanyl required was significantly lower in the buprenorphine group:130 µg, interquartile range (IQR), 80-255 vs 520 µg, IQR, 380-1065 (P < .001). The number of total demands was 32 (IQR, 21-69) in the diclofenac arm vs 8 (IQR, 4-15) in the buprenorphine arm (P < .001). The buprenorphine group had more prolonged pain-free interval (20 vs 4 hours; P < .001), with greater reduction in the VAS score at 24, 48, and 72 hours compared with the diclofenac group. These findings were confirmed in the subgroup of moderately severe/severe pancreatitis. Adverse events profile was similar in the 2 groups. CONCLUSIONS: Compared with diclofenac, buprenorphine appears to be more effective and equally safe for pain management in AP patients, even in the subcohort of moderately severe or severe pancreatitis (Trial Registration number: CTRI/2020/07/026914).

A three-dimensional virtual mouse generates synthetic training data for behavioral analysis.

We developed a three-dimensional (3D) synthetic animated mouse based on computed tomography scans that is actuated using animation and semirandom, joint-constrained movements to generate synthetic behavioral data with ground-truth label locations. Image-domain translation produced realistic synthetic videos used to train two-dimensional (2D) and 3D pose estimation models with accuracy similar to typical manual training datasets. The outputs from the 3D model-based pose estimation yielded better definition of behavioral clusters than 2D videos and may facilitate automated ethological classification.

Cardiovascular medication adherence testing in patients living with HIV: A single-centre observational study.

INTRODUCTION: People with HIV (PWH) are at an increased risk of developing cardiovascular disease (CVD) compared to HIV-negative individuals. We sought to evaluate the adherence to medications for CVD in PWH and identify factors associated with non-adherence to these medications. METHODS: We conducted a cross-sectional study at the University Hospitals of Leicester NHS Trust between 16 April 2019 and 8 November 2022. We recruited consecutive PWH, who were attending a routine follow-up outpatient appointment and were prescribed at least one medication for CVD. In addition, we included urinary adherence results of patients with samples collected as part of routine clinical care. We used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to assess if their prescribed medications (antihypertensives, diuretics, beta-blockers, lipid-lowering agents, antiplatelets, anticoagulants, antidiabetic medications) were present in the participant's urine sample. Multivariable models were used to identify demographic or clinical features that were associated with non-adherence. RESULTS: A total of 162 PWH were included in the analysis. Median age was 55 [interquartile range (IQR): 50-61] years, 63% were male, average time living with HIV was 15 years (IQR: 11-19) and the majority (98%) had an undetectable HIV viral load. In approximately one-third of patients (59/162), at least one prescribed medication of interest was not detected in urine. Non-adherence to lipid-lowering agents was common (35/88, 40%). On multivariable logistic regression, the number of prescribed cardiovascular medications, was associated with medication non-adherence [medication non-adherence, per one medication increase: adjusted odds ratio (95% confidence interval) = 1.78 (1.34-2.36); p < 0.001]. CONCLUSION: We found sub-optimal adherence to medications for CVD in PWH. In order to maximize the clinical benefit of statin therapy in PWH, factors requiring consideration include: improved medication adherence, awareness of polypharmacy, educational interventions and quantitative assessment of sub-optimal adherence through chemical adherence testing.

Near-IR Capturing N-Methylbenzene Sulfonamide-Phenothiazine Incorporating Strong Electron Acceptor Push-Pull Systems: Photochemical Ultrafast Carrier Dynamics.

Unraveling the intriguing aspects of the intramolecular charge transfer (ICT) phenomenon of multi-modular donor-acceptor-based push-pull systems are of paramount importance considering their promising applications, particularly in solar energy harvesting and light-emitting devices. Herein, a series of symmetrical and unsymmetrical donor-acceptor chromophores 1-6, are designed and synthesized by the Corey-Fuchs reaction via Evano's condition followed by [2+2] cycloaddition retroelectrocyclic ring-opening reaction with strong electron acceptors TCNE and TCNQ in good yields (~60-85 %). The photophysical, electrochemical, and computational studies are investigated to explore the effect of incorporation of strong electron acceptors 1,1,4,4-tetracyanobuta-1,3-diene (TCBD) and dicyanoquinodimethane (DCNQ) with phenothiazine (PTZ) donor. An additional low-lying broad absorption band extended towards the near-infrared (NIR) region suggests charge polarization after the introduction of the electron acceptors in both symmetrical and asymmetrical systems, leading to such strong ICT bands. The electrochemical properties reveal that reduction potentials of 3 and 6 are lower than those of 2 and 5, suggesting DCNQ imparts more on the electronic properties and hence largely contributes to the stabilization of LUMO energy levels than TCBD, in line with theoretical observations. Relative positions of the frontier orbitals on geometry-optimized structures further support accessing donor-acceptor sites responsible for the ICT transitions. Eventually, ultrafast carrier dynamics of the photoinduced species are investigated by femtosecond transient absorption studies to identify their spectral characteristics and target analysis further provides information about different excited states photophysical events including ICT and their associated time profiles. The key findings obtained here related to excited state dynamical processes of these newly synthesized systems are believed to be significant in advancing their prospect of utilization in solar energy conversion and related photonic applications.

Dual-energy CT in differentiating benign gallbladder wall thickening from wall thickening type of gallbladder cancer.

OBJECTIVE: To evaluate the performance of dual-energy computed tomography (DECT) in differentiating non-acute benign from malignant gallbladder wall thickening (GBWT). METHODS: This prospective study comprised consecutive adults with GBWT who underwent late arterial phase (LAP) and portal venous phase (PVP) DECT between January 2022 and May 2023. The final diagnosis was based on histopathology or 3-6 months follow-up imaging. DECT images in LAP and PVP were assessed independently by two radiologists. The demographic, qualitative, and quantitative parameters were compared between two groups Multivariate logistic regression was performed to determine the association between the aforementioned factors and malignant GBWT. RESULTS: Seventy-five patients (mean age 56 ± 12.8 years, 46 females) were included. Forty-two patients had benign, and 33 had malignant GBWT. In the overall group, female gender (p = 0.018), lymphadenopathy (p = 0.011), and omental nodules (p = 0.044) were significantly associated with malignant GBWT. None of the DECT features differed significantly between benign and malignant GBWT in overall group. In the xanthogranulomatous cholecystitis (XGC, n = 9) vs. gallbladder cancer (GBC) (n = 33) subgroup, mean attenuation value at 140 keV LAP VMI was significantly associated with malignant GBWT [p = 0.023, area under curve 0.759 (95%CI 0.599-0.919)]. CONCLUSION: DECT-generated quantitative parameters do not add value in differentiating non-acute benign from malignant GBWT. However, DECT may have a role in differentiating XGC from GBC in a selected subgroup of patients. Further, larger studies may be necessary to confirm these findings. CLINICAL RELEVANCE STATEMENT: In patients with non-acute gallbladder wall thickening in whom there is suspicion of xanthogranulomatous cholecystitis (XGC), DECT findings may allow differentiation of XGC from wall thickening type of gallbladder cancer. KEY POINTS: Differentiation of benign and malignant gallbladder wall thickening (GBWT) at CT is challenging. Quantitative dual energy CT (DECT) features do not provide additional value in differentiating benign and malignant GBWT. DECT may be helpful in a subgroup of patients to differentiate xanthogranulomatous cholecystitis from gallbladder cancer.

Dithionite-Mediated Tandem Nitro Reduction/Imine Formation/Intramolecular Cyclization for the Synthesis of Dihydro-benzothiadiazine-1,1-dioxides.

A one-pot, tandem reductive annulation of 2-nitrobenzenesulfonamides with aldehydes to the synthesis of substituted 3,4-dihydro-2H-1,2,4-benzothiadiazine-1,1-dioxides in the presence of sodium dithionite (Na2S2O4) is reported under mild conditions. The method involves in situ reduction of the nitro group followed by condensation with aldehydes to form an imine, which upon subsequent intramolecular cyclization forms the product under one-pot conditions. The protocol features use of inexpensive Na2S2O4 as the exclusive reagent, appreciable functional group tolerance, broad substrate scope, high product yields, and scalability.

Modular synthesis of pyrrole-fused heterocycles via glucose-mediated nitro-reductive cyclization.

A novel biomass-derived glucose-mediated one-pot multicomponent nitro-reductive cyclization method is presented for the direct synthesis of diverse pyrrole-fused heterocycles. The process involves two-component reactions of alkyl (NH)-pyrrole-2-carboxylates and 2-fluoronitroarenes, yielding pyrrolo[1,2-a]quinoxalin-4(5H)-ones, as well as three-component reactions utilizing (NH)-pyrroles, nitroarenes, and DMSO as carbon sources, resulting in various pyrrolo[1,2-a]quinoxaline derivatives. High yields were achieved with broad substrate scope and gram-scale synthesis capability, including pharmaceuticals featuring pyrroloquinoxaline scaffolds. The method's key innovation lies in enabling three or four reactions in a single-pot setup, previously unexplored in pyrrole chemistry. The simplicity of nitro group reduction by biomass-derived glucose ensures practical safety during scale-up, while mechanistic insights from control experiments reveal a new paradigm in pyrrole chemistry. The tandem process demonstrates low PMI values and high step and atom economies, aligning well with green chemistry principles.

A high throughput immuno-affinity mass spectrometry method for detection and quantitation of SARS-CoV-2 nucleoprotein in human saliva and its comparison with RT-PCR, RT-LAMP, and lateral flow rapid antigen test.

OBJECTIVES: Many reverse transcription polymerase chain reaction (RT-PCR) methods exist that can detect SARS-CoV-2 RNA in different matrices. RT-PCR is highly sensitive, although viral RNA may be detected long after active infection has taken place. SARS-CoV-2 proteins have shorter detection windows hence their detection might be more meaningful. Given salivary droplets represent a main source of transmission, we explored the detection of viral RNA and protein using four different detection platforms including SISCAPA peptide immunoaffinity liquid chromatography-mass spectrometry (SISCAPA-LC-MS) using polyclonal capture antibodies. METHODS: The SISCAPA-LC MS method was compared to RT-PCR, RT-loop-mediated isothermal amplification (RT-LAMP), and a lateral flow rapid antigen test (RAT) for the detection of virus material in the drool saliva of 102 patients hospitalised after infection with SARS-CoV-2. Cycle thresholds (Ct) of RT-PCR (E gene) were compared to RT-LAMP time-to-positive (TTP) (NE and Orf1a genes), RAT optical densitometry measurements (test line/control line ratio) and to SISCAPA-LC-MS for measurements of viral protein. RESULTS: SISCAPA-LC-MS showed low sensitivity (37.7 %) but high specificity (89.8 %). RAT showed lower sensitivity (24.5 %) and high specificity (100 %). RT-LAMP had high sensitivity (83.0 %) and specificity (100.0 %). At high initial viral RNA loads (<20 Ct), results obtained using SISCAPA-LC-MS correlated with RT-PCR (R2 0.57, p-value 0.002). CONCLUSIONS: Detection of SARS-CoV-2 nucleoprotein in saliva was less frequent than the detection of viral RNA. The SISCAPA-LC-MS method allowed processing of multiple samples in <150 min and was scalable, enabling high throughput.

Artificial intelligence for discrimination of Crohn's disease and gastrointestinal tuberculosis: A systematic review.

BACKGROUND AND AIM: Discrimination of gastrointestinal tuberculosis (GITB) and Crohn's disease (CD) is difficult. Use of artificial intelligence (AI)-based technologies may help in discriminating these two entities. METHODS: We conducted a systematic review on the use of AI for discrimination of GITB and CD. Electronic databases (PubMed and Embase) were searched on June 6, 2022, to identify relevant studies. We included any study reporting the use of clinical, endoscopic, and radiological information (textual or images) to discriminate GITB and CD using any AI technique. Quality of studies was assessed with MI-CLAIM checklist. RESULTS: Out of 27 identified results, a total of 9 studies were included. All studies used retrospective databases. There were five studies of only endoscopy-based AI, one of radiology-based AI, and three of multiparameter-based AI. The AI models performed fairly well with high accuracy ranging from 69.6-100%. Text-based convolutional neural network was used in three studies and Classification and regression tree analysis used in two studies. Interestingly, irrespective of the AI method used, the performance of discriminating GITB and CD did not match in discriminating from other diseases (in studies where a third disease was also considered). CONCLUSION: The use of AI in differentiating GITB and CD seem to have acceptable accuracy but there were no direct comparisons with traditional multiparameter models. The use of multiple parameter-based AI models have the potential for further exploration in search of an ideal tool and improve on the accuracy of traditional models.

Effect of Soil-pH, temperature and moisture content on sorption dynamics of Metformin and Erythromycin.

The rising soil-groundwater quality issues due to pharmaceuticals and personal care products (PPCPs) have spurred significant concern. To understand the sorption characteristics of metformin (MTN) and erythromycin (ETM) in sandy and sandy loam soils with varying organic matter and particle composition, sorption kinetics (single and competitive), isotherms, and thermodynamics were studied. The effects of pH and soil moisture content (SMC) were also investigated at environmentally relevant concentrations. The equilibrium time of MTN and ETM sorption by the three soils in a competitive solute system was about 4 h, and the sorption process was in line with a pseudo-second-order model. The rate-determining step in the process involved both intraparticle diffusion and liquid film diffusion mechanisms for the two PPCPs. The highest pollutant uptake occurred in soils with higher organic matter, driven by enhanced H-bonding, electrostatic interactions, and π-π and n-π interactions facilitated by the organic matter. The equilibrium data in the three soils was well described by the Freundlich model and confirmed favourable adsorption (1/nf = 1.01 - 1.90). The sorption coefficient (Kd) on the three soils ranged from 2.1 to 332 L/kg for MTN and from 6.25 to 845 L/kg for ETM. The adsorption process was feasible at 293 K and 303 K (ΔG° = - 0.16 to -10.24 kJ/mol), physical and exothermic in nature (ΔH° = -75.21 to -10.30 kJ/mol) for both the contaminants. Observed alterations in Qe with pH confirmed the participation of electrostatic interactions. A low SMC favoured both MTN and ETM sorption onto the sandy soil. Overall, ETM exhibits higher expected sorption, whereas MTN has a greater tendency for migration in the soils and is thus liable to contaminate the groundwater. The study accentuates novel insights into the transport and fate of MTN and ETM in soil-groundwater systems at environmentally relevant concentrations.

Venous Thrombosis in Acute Pancreatitis: What to and Not to Do?

Acute pancreatitis is an acute inflammatory condition of the pancreas that has not only local but systemic effects as well. Venous thrombosis is one such complication which can give rise to thrombosis of the peripheral vasculature in the form of deep vein thrombosis, pulmonary embolism, and splanchnic vein thrombosis. The prevalence of these complications increases with the severity of the disease and adds to the adverse outcomes profile. With better imaging and awareness, more cases are being detected, although many at times it can be an incidental finding. However, it remains understudied and strangely, most of the guidelines on the management of acute pancreatitis are silent on this aspect. This review offers an overview of the incidence, pathophysiology, symptomatology, diagnostic work-up, and management of venous thrombosis that develops in AP.

Transverse versus longitudinal mucosal incision during POEM for esophageal motility disorders: a randomized trial.

BACKGROUND: Longitudinal incision is the commonly used incision for entry into the submucosal space during peroral endoscopic myotomy (POEM) for esophageal motility disorders. Transverse incision is another alternative for entry and retrospective data suggest it has less operative time and chance of gas-related events. METHODS: This was a single-center, randomized trial conducted at a tertiary care hospital. Patients undergoing POEM for esophageal motility disorders were randomized into group A (longitudinal incision) and group B (transverse incision). The primary objective was to compare the time needed for entry into the submucosal space. The secondary objectives were to compare the time needed to close the incision, number of clips required to close the incision, and development of gas-related events. The sample size was calculated as for a non-inferiority design using Kelsey method. RESULTS: Sixty patients were randomized (30 in each group). On comparing the 2 types of incisions, there was no difference in entry time [3 (2, 5) vs 2 (1.75, 5) min, p = 0.399], closure time [7 (4, 13.5) vs 9 (6.75, 19) min, p = 0.155], and number of clips needed for closure [4 (4, 6) vs 5 (4, 7), p = 0.156]. Additionally, the gas-related events were comparable between the 2 groups (capnoperitoneum needing aspiration-5 vs 2, p = 0.228, and development of subcutaneous emphysema-3 vs 1, p = 0.301). CONCLUSION: This randomized trial shows comparable entry time, closure time, number of clips needed to close the incision, and gas-related events between longitudinal and transverse incisions. REGISTRATION NUMBER: CTRI/2021/08/035829.

Imaging Diagnosis and Management of Fistulas in Pancreatitis.

Pancreatic fistula is a highly morbid complication of pancreatitis. External pancreatic fistulas result when pancreatic secretions leak externally into the percutaneous drains or external wound (following surgery) due to the communication of the peripancreatic collection with the main pancreatic duct (MPD). Internal pancreatic fistulas include communication of the pancreatic duct (directly or via intervening collection) with the pleura, pericardium, mediastinum, peritoneal cavity, or gastrointestinal tract. Cross-sectional imaging plays an essential role in the management of pancreatic fistulas. With the help of multiplanar imaging, fistulous tracts can be delineated clearly. Thin computed tomography sections and magnetic resonance cholangiopancreatography images may demonstrate the communication between MPD and pancreatic fluid collections or body cavities. Endoscopic retrograde cholangiography (ERCP) is diagnostic as well as therapeutic. In this review, we discuss the imaging diagnosis and management of various types of pancreatic fistulas with the aim to sensitize radiologists to timely diagnosis of this critical complication of pancreatitis.

Safety Assessment of Ultra High Dilutions of Camphora officinarum: A Preclinical Investigation.

Background: Camphora officinarum (CO) is a commonly used homeopathic remedy for treating colds, collapse, and recurrent eruptive illnesses. Objective: Due to the non-availability of safety data on CO, the current study intended to determine the oral toxicity of CO in its ethanol-potentized dilutions 6C, 30C, and 200C in Wistar albino rats as per OECD guidelines. Materials and methods: A single oral dose of CO-6C, 30C, and 200C (2000 µl/kg) was administered, and the animals were monitored for behavior and mortality for up to 14 days in an acute toxicity study. In the subacute study, the effects of daily oral administration of CO-6C, 30C, and 200C (200 µl/kg) for 28 days were observed for clinical signs, change in body weight, and mortality. Hematological, biochemical, and histopathological analyses were assessed and organ weights were determined. Results: Results indicate no mortality of CO in its potencies in the acute toxicity study and was found to be safe at 2000 µl/kg dosage in the subacute toxicity study. CO (200 µl/kg/day) did not show any signs of toxicity in the hematological, biochemical, and histopathological analyses, along with organ weights. Conclusion: In conclusion, the findings suggest that CO in potencies of 6C, 30C, and 200C is safe up to a single oral dose of 2000 µl/kg body weight, and the No Observed Adverse Effect Level (NOAEL) was determined to be greater than 200 µl/kg/day.