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.

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.

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.

Abbreviated magnetic resonance imaging in hepatocellular carcinoma surveillance: A review.

Hepatocellular carcinoma (HCC) is one of the most common primary malignancies of the liver and a leading cause for cancer-related deaths worldwide. HCC surveillance aims at early detection. The recommended strategy for screening HCC is biannual ultrasound with or without alpha-fetoprotein. However, this strategy is associated with sub-optimal sensitivity. Abbreviated magnetic resonance imaging (AMRI) is a promising alternative to ultrasound (US) for surveillance of HCC. The data regarding the role of AMRI in HCC screening is evolving. There are different AMRI protocols, each having its merits and disadvantages. In this review, we discuss the need for AMRI, protocols of AMRI and hindrances to widespread adoption of AMRI.

Applications of artificial intelligence in biliary tract cancers.

Biliary tract cancers are malignant neoplasms arising from bile duct epithelial cells. They include cholangiocarcinomas and gallbladder cancer. Gallbladder cancer has a marked geographical preference and is one of the most common cancers in women in northern India. Biliary tract cancers are usually diagnosed at an advanced, unresectable stage. Hence, the prognosis is extremely dismal. The five-year survival rate in advanced gallbladder cancer is < 5%. Hence, early detection and radical surgery are critical to improving biliary tract cancer prognoses. Radiological imaging plays an essential role in diagnosing and managing biliary tract cancers. However, the diagnosis is challenging because the biliary tract is affected by many diseases that may have radiological appearances similar to cancer. Artificial intelligence (AI) can improve radiologists' performance in various tasks. Deep learning (DL)-based approaches are increasingly incorporated into medical imaging to improve diagnostic performance. This paper reviews the AI-based strategies in biliary tract cancers to improve the diagnosis and prognosis.

Isolated cavernous venous malformation of the eyelid.

Cavernous hemangioma, currently known as "cavernous venous malformation," is a common, benign, non-infiltrative, slowly progressive vascular malformation of the orbit presenting in adults. We report the case of a 9-year-old girl who presented with a painless palpable mass over the right upper eyelid of 7 years' duration. A computed tomography scan of the orbits revealed a heterogeneously enhancing, well-circumscribed mass in the right upper eyelid with no orbital extension. A transcutaneous excisional biopsy with histopathology disclosed cavernous venous malformation. The majority of cavernous venous malformations are intraconal and present in the fourth to fifth decade of life.

Correlation of clinical and radiological scores for evaluation of activity in patients having thyroid-associated orbitopathy: A prospective observational study.

PURPOSE: To find a correlation between the clinical (vision-inflammation-strabismus-appearance [VISA] score) and radiological (apparent diffusion coefficient [ADC] values) scores for evaluating disease activity in patients with thyroid-associated orbitopathy. DESIGN: A prospective comparative study. METHODS: Our study was performed for consecutively diagnosed thyroid-associated orbitopathy (TAO) patients. Clinical evaluation included the VISA classification system with the basic thyroid workup. An inflammatory score of <4/8 was considered inactive and ≥4/8 as an active disease. Every included patient underwent a diffusion-weighted magnetic resonance imaging (DW-MRI) scan of the orbits. The orbital parameters evaluated on imaging included the proptosis, thickness, as well as the ADC values of extraocular muscles. RESULTS: We studied 33 consecutive patients (23 females, 69.7%) with a mean age of 41.8 years. The majority (n = 27, 81.8%) were hyperthyroid, four were hypothyroid, and two were euthyroid. In the VISA classification, nine patients had active TAO (≥4/8 inflammation score), while 24 had inactive disease. There was a positive correlation between the inflammation score and ADC values of medial rectus (MR), inferior rectus (IR) and lateral rectus (LR). We had nine patients with inflammation scores ≥4. With receiver operating characteristic (ROC) curve analysis, we found that the ADC value of IR can predict disease activity with 68% sensitivity and MR-ADC can predict active TAO with 87% sensitivity. CONCLUSION: The ADC parameters of DW-MRI are objective and less operator dependent than the clinical TAO activity scores like VISA classification. A randomized control trial may provide robust data on this correlation.

Anterior segment optical coherence tomography (AS-OCT) in strabismus following trauma.

We describe 3 cases of ocular trauma that presented with strabismus. Anterior segment optical coherence tomography was used to delineate the morphology of extraocular muscle insertions and proved helpful in diagnosis and management.

Field-scale assessment of soil, water, plant, and soil microbiome in and around Rania-Khan Chandpur Chromium contaminated site, India.

Rania-Khan Chandpur site, (Kanpur Dehat, Uttar Pradesh, India), one of the highly Chromium (Cr) contaminated sites in India due to Chromite Ore Processing Residue (COPR), has been investigated at the field-scale. We found that the area around the COPR dumps was hazardously contaminated with the Cr where its concentrations in the surface water and groundwater were > 40 mgL-1, its maximum contents in the COPRs and in the soils of the adjoining lands were 9.6 wt% and 3.83 wt%, respectively. By exploring the vegetation and microbial distribution across the site, we advocate the appropriateness of Cynodon dactylon, Chrysopogon zizanioides, Cyperus sp., and Typha angustifolia as the most suitable phytoremediation agent because their association with Cr remediating bacterial species (Pseudomonas sp., Clostridium sp. and Bacillus sp.) was strong. Using this remarkable information for the bioremediation projects, this site can be re-vegetated and bioaugmented to remediate Cr in soils, waterlogged ditches, surface water, and in groundwater systems.

Multifunctional 58S Bioactive Glass/Silver/Cerium Oxide-Based Biocomposites with Effective Antibacterial, Cytocompatibility, and Mechanical Properties.

58S bioactive glass (BG) has effective biocompatibility and bioresorbable properties for bone tissue engineering; however, it has limitations regarding antibacterial, antioxidant, and mechanical properties. Therefore, we have developed BGAC biocomposites by reinforcing 58S BG with silver and ceria nanoparticles, which showed effective bactericidal properties by forming inhibited zones of 2.13 mm (against Escherichia coli) and 1.96 mm (against Staphylococcus aureus; evidenced by disc diffusion assay) and an increment in the antioxidant properties by 39.9%. Moreover, the elastic modulus, hardness, and fracture toughness were observed to be increased by ∼84.7% (∼51.9 GPa), ∼54.5% (∼3.4 GPa), and ∼160% (∼1.3 MPam1/2), whereas the specific wear rate was decreased by ∼55.2% (∼1.9 × 10-11 m3/Nm). X-ray diffraction, high-resolution transmission electron microscopy, and field emission scanning electron microscopy confirmed the fabrication of biocomposites and the uniform distribution of the nanomaterials in the BG matrix. The addition of silver nanoparticles in the 58S BG matrix (in BGA) increased mechanical properties by composite strengthening and bactericidal properties by damaging the cytoplasmic membrane of bacterial cells. The addition of nanoceria in 58S BG (BGC) increased the antioxidant properties by 44.5% (as evidenced by the 2,2-diphenyl-1-picrylhydrazyl assay). The resazurin reduction assay and MTT assay confirmed the effective cytocompatibility for BGAC biocomposites against mouse embryonic fibroblast cells (NIH3T3) and mouse bone marrow stromal cells. Overall, BGAC resulted in mechanical properties comparable to those of cancellous bone, and its effective antibacterial and cytocompatibility properties make it a good candidate for bone healing.

Effect of Clemizole on Alpha-Synuclein-Preformed Fibrils-Induced Parkinson's Disease Pathology: A Pharmacological Investigation.

Parkinson's disease (PD) is a neurodegenerative disorder associated with mitochondrial dysfunctions and oxidative stress. However, to date, therapeutics targeting these pathological events have not managed to translate from bench to bedside for clinical use. One of the major reasons for the lack of translational success has been the use of classical model systems that do not replicate the disease pathology and progression with the same degree of robustness. Therefore, we employed a more physiologically relevant model involving alpha-synuclein-preformed fibrils (PFF) exposure to SH-SY5Y cells and Sprague Dawley rats. We further explored the possible involvement of transient receptor potential canonical 5 (TRPC5) channels in PD-like pathology induced by these alpha-synuclein-preformed fibrils with emphasis on amelioration of oxidative stress and mitochondrial health. We observed that alpha-synuclein PFF exposure produced neurobehavioural deficits that were positively ameliorated after treatment with the TRPC5 inhibitor clemizole. Furthermore, Clemizole also reduced p-alpha-synuclein and diminished oxidative stress levels which resulted in overall improvements in mitochondrial biogenesis and functions. Finally, the results of the pharmacological modulation were further validated using siRNA-mediated knockdown of TRPC5 channels, which also decreased p-alpha-synuclein expression. Together, the results of this study could be superimposed in the future for exploring the beneficial effects of TRPC5 channel modulation for other neurodegenerative disorders and synucleopathies.

Scrub Typhus: An Acute Precipitant for Acute on Chronic Liver Failure.

Acute-on-chronic liver failure (ACLF) is a clinical syndrome with high mortality. Many acute precipitating factors have been implicated in triggering the acute event of ACLF, with bacterial infections being a common precipitant. However, many other precipitants can cause ACLF; therefore, identification of these factors early in the golden window and their treatment can result in improved prognosis. Scrub typhus usually presents as uncomplicated acute febrile illness but rarely as complicated. Few case reports of scrub-typhus-induced acute liver failure have been reported but none with scrub-typhus-precipitating ACLF so far. Therefore, we are reporting a case of scrub-typhus-precipitating ACLF, where timely intervention with antibiotics results in improved outcome.

Effectiveness of biofeedback on blood pressure in patients with hypertension: systematic review and meta-analysis.

Hypertension is the leading modifiable risk factor for cardiovascular disease, but less than 50% have their blood pressure controlled. A possible avenue to support hypertension management is a holistic approach, using non-pharmacological interventions. Since hypertension is mediated in part by dysregulation of the autonomic nervous system (ANS), biofeedback may help improve hypertension management by targeted self-regulation and self-awareness of parameters that regulate the ANS. This systematic review aimed to assess the effectiveness of biofeedback on blood pressure in hypertensive patients. The review was pre-registered on PROSPERO and followed the PICO strategy. A total of 1782 articles were retrieved, 20 met the inclusion criteria. Sample sizes ranged from 15 to 301 participants; with a median age of 49.3 (43.3-55.0) years and 45% were female. There was a significant effect of biofeedback on systolic (-4.52, Z = 2.31, P = 0.02, CI [-8.35, -0.69]) and diastolic blood pressure (-5.19, Z = 3.54, P = 0.0004, CI [-8.07, -2.32]). Six different biofeedback modalities were used, with biofeedback delivered by psychologists, trained therapists and research assistants. There was no publication bias, heterogeneity was rated as substantial and data quality was rated to be poor. This review demonstrated that biofeedback had a significant effect on blood pressure. However, this should be viewed in the context of included studies being limited by heterogeneity and dated literature, meaning the research does not reflect the current biofeedback technology such as wearable devices. Future research should incorporate these technologies with robust methodology to fully understand the effect of biofeedback on hypertension.