ESTABLISHING A GRAFT-VERSUS-HOST DISEASE (GVHD)-FOCUSED MULTIDISCIPLINARY TELEHEALTH CLINIC.

Graft-versus-host disease (GVHD) is a complication following allogeneic hematopoietic cell transplant (allo-HCT) that frequently causes multiorgan affection and decrease in quality of life. Global assessment and care of these patients require a multidisciplinary approach, but access to focused clinics is limited given their scarcity and location in major cities, as well as mobility and transportation challenges that frequently affect these patients. Thus, we established a multispecialty GVHD telehealth (TH) clinic and hypothesized that a virtual platform will expand access to clinical care in children and adults. The clinic team members included BMT specialist, nursing, dermatologist, dentist, nutritionist, physiatrist, research personnel and others as needed. We evaluated all GVHD-related visits (in-person and TH) conducted in a single center from 01/2022 to 12/2022. Ninety-three patients received a total of 308 visits, and one-third were via TH. Approximately half of the in-person group had at least 1 TH visit, and 10 patients were seen exclusively via TH. Most patients had advanced chronic GVHD. More male patients were seen in GVHD clinic, but female patients had increased in clinic visits via TH (41% TH vs. 32% in-person). One-third of clinic visits were from patients of racial and ethnic minorities. While only 6% (n= 12/217) of in-person visits were for patients living >100 miles from the center, 34% (n= 31/91) of TH visits were from far distances including out-of-state. At baseline, the most common patient-reported symptoms in a subset of patients included fatigue, disturbed sleep, and distress. Fifteen patients completed a follow-up symptom survey and reported significantly reduced distress regarding their GVHD (p= 0.02), although other symptoms remained stable. A multidisciplinary TH clinic provided care for adult and pediatric patients with GVHD. We demonstrated preliminary feasibility of building a robust TH platform with a collaborative multispecialty approach that allowed access and continuity of medical care. Gender inequalities were reduced, and distance to our center represented a lesser barrier to attending specialized care via TH. Additionally, patients reported a significant reduction in distress. Our findings support the ongoing development of a virtual platform to improve access to specialized GVHD care.

Exploring the Link Between Somatic and Psychiatric Symptoms in Patients With Medically Unexplained Physical Symptoms: A Cross-Sectional Survey From North India.

BACKGROUND: The association between somatic symptoms and psychiatric co-morbidities remains unexplored among patients with medically unexplained physical symptoms (MUPS) in Asian populations. This study aims to bridge this gap by investigating psychiatric morbidities and their determinants among patients presenting with MUPS in an Indian setup. METHODOLOGY: This cross-sectional study, conducted in the outpatient department (OPD) of a tertiary care hospital in India, assessed 200 patients diagnosed with MUPS. Assessment tools, such as the Somatic Symptom Scale (SSS-8), Presumptive Stressful Life Event Scale (PSLES), and Depression, Anxiety, and Stress Scale (DASS), were administered to collect data. RESULTS: The study examined patients (mean age 36.51±9.82 years), predominantly comprising females (67.5%), presenting with MUPS. Common presenting symptoms were general (96.3%), musculoskeletal pain (91.7%), and gastrointestinal symptoms reported by 81.7%. Medium somatic symptom severity (57%) was more prevalent in females. Prevalent psychiatric co-morbid conditions included depression (mild: 22.0%, moderate: 26.5%), moderate anxiety (41.5%), and moderate stress (26%). Strong associations were observed between the SSS-8 score and depression (χ²(6, N = 200) = 49.26, p < 0.001), anxiety (χ²(8, N = 200) = 37.90, p < 0.001), stress (χ²(6, N = 200) = 44.45, p < 0.001), and the experience of stressful life events (χ²(3, N = 200) = 6.5, p < 0.05). CONCLUSION: The study indicates an intertwined association between MUPS and psychiatric disorders. Individuals with MUPS commonly experience heightened anxiety and depression, emphasizing the complex interplay between somatic symptoms and emotional well-being. Consideration of environmental and social factors may be crucial for a comprehensive understanding.

Foreign body pulmonary vessel embolism and granulomatosis in intravenous drug abuse: An autopsy study.

ABSTRACT: The abuse of illicit drugs causes a myriad of systemic complications. Intravenous (IV) injection of such drugs poses various additional threats, primarily due to the use of excipient materials in them. Pulmonary artery embolism with foreign material and granulomatosis may be encountered in the lungs on histopathological examination in such cases. In this study, we aimed to analyze the histopathological findings in lungs in postmortem specimens with suspected IV drug abuse. This was a retrospective study of 5 years in which 15 cases of known or suspected history of drug abuse were assessed. The clinical details were compiled, and the hematoxylin and eosin (H and E)-stained microscopic slides were retrieved from the archives for reviewing the histopathological features in lungs submitted for postmortem analysis. All the cases were male, aged 21 to 36 years (median: 27 years). Gross examination revealed edematous lungs in four cases (26.6%). On microscopic examination of the lungs, all the cases (100%) showed the presence of basophilic irregular structures to rod-like pale crystalline refractile material, which was accompanied by a granulomatous reaction in the lumen of the pulmonary arteries. Four of these cases (26.6%) showed birefringence on polarizing microscopy. The use of illicit drugs is becoming widespread, especially among young individuals. IV drug abuse increases the rate of morbidity and mortality by affecting primarily the pulmonary vasculature, particularly pulmonary arteries. An acquaintance with the various patterns of pulmonary involvement in IV drug abuse is essential to arrive at an accurate pathological diagnosis and provide a possible cause of death in such cases.

Paclitaxel in colon cancer management: from conventional chemotherapy to advanced nanocarrier delivery systems.

Paclitaxel, a potent chemotherapeutic agent derived from the bark of the Pacific yew tree, has demonstrated significant efficacy in the treatment of various cancers, including colon cancer. This comprehensive review delves into the conventional treatments for colon cancer, emphasizing the crucial role of paclitaxel in contemporary management strategies. It explores the intricate process of sourcing and synthesizing paclitaxel, highlighting the importance of its structural properties in its anticancer activity. The review further elucidates the mechanism of action of paclitaxel, its pharmacological effects, and its integration into chemotherapy regimens for colon cancer. Additionally, novel drug delivery systems, such as nanocarriers, liposomes, nanoparticles, microspheres, micelles, microemulsions, and niosomes, are examined for their potential to enhance the therapeutic efficacy of paclitaxel. The discussion extends to recent clinical trials and patents, showcasing advancements in paclitaxel formulations aimed at improving treatment outcomes. The review concludes with prospects in the field underscoring the ongoing innovation and potential breakthroughs in colon cancer therapy.

India's Pink-Eye Mystery: Decoding the 2023 Conjunctivitis Outbreak.

The pink eye outbreak in 2023 was caused due to humid weather conditions in most regions of India. The most affected states include Delhi, Gujrat (21% cases), Maharashtra (30%), Himachal Pradesh (4%) and Karnataka (4%). The epidemiological data indicates that males have a high prevalence rate as compared to females; urban areas were most affected, and professionals as well as students were the population group that had the highest prevalence rate. The most common clinical manifestations were the presence of red eye, eye discharge, grittiness, and eyelashes being stuck together. One of the hallmarks of histopathology is a cobblestone formation of flattened nodules with central vascular centers. Conjunctivitis is a virusmediated immune response accompanied by inflammation, which proceeds the immune reaction, giving rise to vasodilation, pseudo membrane formation, and conjunctivital discharge. The gold standard for the diagnosis of Conjunctivitis is the Adenoplus kit using PCR technology; apart from this slit lamp biomicroscope can be used for the evaluation. It is the need of the hour to spread awareness about the Pink Eye disease and the measures to prevent it.

Identification of a Novel Protein Phosphatase 2A Activator, PPA24, as a Potential Therapeutic for FOLFOX-Resistant Colorectal Cancer.

A series of compounds were designed utilizing molecular modeling and fragment-based design based upon the known protein phosphatase 2A (PP2A) activators, NSC49L and iHAP1, and evaluated for their ability to inhibit the viability of colorectal cancer (CRC) and folinic acid, 5-fluorouracil, and oxaliplatin (FOLFOX)-resistant CRC cells. PPA24 (19a) was identified as the most cytotoxic compound with IC50 values in the range of 2.36-6.75 µM in CRC and FOLFOX-resistant CRC cell lines. It stimulated PP2A activity to a greater extent, displayed lower binding energies through molecular docking, and showed higher binding affinity through surface plasmon resonance for PP2A catalytic subunit α than the known PP2A activators. PPA24 dose-dependently induced apoptosis and oxidative stress, decreased the level of c-Myc expression, and synergistically potentiated cytotoxicity when combined with gemcitabine and cisplatin. Furthermore, a PPA24-encapsulated nanoformulation significantly inhibited the growth of CRC xenografts without systemic toxicities. Together, these results signify the potential of PPA24 as a novel PP2A activator and a prospective therapeutic for CRC and FOLFOX-resistant CRC.

From nature's bounty to drug discovery: Leveraging phytochemicals and molecular approaches to combat multi-drug-resistant (MDR) tuberculosis.

A large number of people annually lose their lives to tuberculosis (TB), which is an age-old disease caused by the Mycobacterium tuberculosis. The global spread of TB is a concern for all regions. The south-east Asian region recorded 46% of all new TB cases in 2021, followed by the African and western Pacific regions with 23% and 18%, respectively. Researchers are always searching at natural substances for potential alternative therapeutics to tackle the worrisome growth in multi-drug-resistant (MDR) tuberculosis due to the high costs associated with developing new treatments and unfavourable side effects of currently used synthetic pharmaceuticals. Phytochemicals show promising results as a future health aid due to their multi-targeting ability on pathogen cells. In the search for new drug leads, the Ayurvedic and Siddha medical systems have made an extensive use of ethnomedicinal tools, including the use of plants like Amalaki (Emblica officinalis Gaertn.), Guduchi (Tinospora cordifolia willd.), Sariva (Hemidesmus indicus R.Br.), Kustha (Saussurea lappa Falc.), turmeric (Curcuma longa Mal.) and Green tea (Camellia sinensis Linn.). These sources are high in flavonoids, polyphenols, tannins and catechins, has been shown to reduce the risk of TB. In this overview, we look at how natural sources like plants, algae and mushrooms have helped researchers to find new drug leads, and how to back these natural sources through mapping the molecular approaches and other approaches has helped them to defeat MDR.

Awareness and adoption of farm biosecurity practices in commercial dairy, pig and poultry farms of Uttar Pradesh (India).

India's livestock sector has been facing significant losses due to episodes of disease outbreaks since time immemorial. Hence, biosecurity measures are very important to maintain and improve animal health along with prevention of disease outbreak. Keeping these facts into consideration, the study was proposed with an objective to assess the existing biosecurity practices adopted by the commercial dairy, pig and poultry farms. The current study was undertaken in the state of Uttar Pradesh as it is the leading state in milk and meat production. A total of 120 farmers were selected randomly including 40 each practicing commercial dairy, pig and poultry farming. An ex-post facto research methodology was used with face-to-face interview and observation to collect data. The biosecurity practices were assessed under seven dimensions such as, location and design of farm, restricted access, isolation and quarantine, cleaning and disinfection, management of feed and water, disposal of carcass, manure and waste, and health management. Results elicited that about 50% of the farmers had medium level of adoption who adopted 18-34 practices out of 51 practices. The average overall adoption score was 34.17 out of 51 (67%) which makes an overall adoption gap of 33%. Maximum adoption gap was seen in case of restricted access (43%) whereas minimum gap in adoption was seen in case of management of feed and water (27%). Pig and poultry farmers showed significantly higher biosecurity measures than dairy farmers (p < 0.05). The more significant contributors to the adoption of biosecurity measures were the level of knowledge of the farmers (p < 0.01). Other factors such as education, income, herd/flock size, Information and Communication Technology utilization, number of trainings also had a significant contribution (p < 0.05) in actual implementation of biosecurity. Hence, better understanding of these measures among the farmers must be ensured by hands on training along with proper demonstration of various procedures involved in maintaining farm biosecurity is need of the hour.

Spontaneous Intragastric Balloon Hyperinflation: Two Cases and Outcomes.

Endoscopic bariatric therapies can provide treatment options for obesity in non-surgical candidates, as a part of combination or serial treatment plans, and for the reduction of obesity-related comorbidities. Several complications of intragastric balloons have been documented, but spontaneous hyperinflation is a risk that has not been well reported previously. We describe two cases of spontaneous intragastric balloon hyperinflation and their outcomes.

Infrared spectroscopy of isomers of C3H4+ in superfluid helium droplets.

Superfluid helium nanodroplets are unique nanomatrices for the isolation and study of transient molecular species, such as radicals, carbenes, and ions. In this work, isomers of C3H4+ were produced upon electron ionization of propyne and allene molecules and interrogated via infrared spectroscopy inside He nanodroplet matrices. It was found that the spectrum of C3H4+ has at least three distinct groups of bands. The relative intensities of the bands depend on the precursor employed and its pickup pressure, which indicates the presence of at least three different isomers. Two isomers were identified as allene and propyne radical cations. The third isomer, which has several new bands in the range of 3100-3200 cm-1, may be the elusive vinylmethylene H2C=CH-CH+ radical cation. The observed bands for the allene and propyne cations are in good agreement with the results of density functional theory calculations. However, there is only moderate agreement between the new bands and the theoretically calculated vinylmethylene spectrum, which indicates more work is necessary to unambiguously assign it.

Corrigendum: A small molecule inhibitor of Notch1 modulates stemness and suppresses breast cancer cell growth.

[This corrects the article DOI: 10.3389/fphar.2023.1150774.].

Coumarin as an Elite Scaffold in Anti-Breast Cancer Drug Development: Design Strategies, Mechanistic Insights, and Structure-Activity Relationships.

Breast cancer is the most common cancer among women. Currently, it poses a significant threat to the healthcare system due to the emerging resistance and toxicity of available drug candidates in clinical practice, thus generating an urgent need for the development of new potent and safer anti-breast cancer drug candidates. Coumarin (chromone-2-one) is an elite ring system widely distributed among natural products and possesses a broad range of pharmacological properties. The unique distribution and pharmacological efficacy of coumarins attract natural product hunters, resulting in the identification of numerous natural coumarins from different natural sources in the last three decades, especially those with anti-breast cancer properties. Inspired by this, numerous synthetic derivatives based on coumarins have been developed by medicinal chemists all around the globe, showing promising anti-breast cancer efficacy. This review is primarily focused on the development of coumarin-inspired anti-breast cancer agents in the last three decades, especially highlighting design strategies, mechanistic insights, and their structure-activity relationship. Natural coumarins having anti-breast cancer efficacy are also briefly highlighted. This review will act as a guideline for researchers and medicinal chemists in designing optimum coumarin-based potent and safer anti-breast cancer agents.

Comprehensive Analysis of Omicron Subvariants: EG.5 Rise, Vaccination Strategies, and Global Impact.

The emergence of new variants of the SARS-CoV-2 virus during the COVID-19 pandemic has prompted significant developments in the understanding, monitoring, and response to these strains. This comprehensive review focuses on two prominent variants of interest (VoI), XBB. 1.5 (Kraken) and XBB.1.16 ("Arcturus"), along with seven variants under observation (VuM), including EG.5. The World Health Organization (WHO) identified these variants in July 2023, highlighting EG.5's noteworthy rise in prevalence. EG.5, also known as "Eris," has exhibited an increased effective reproductive rate, prompting concerns about its contagiousness and immune evasion capabilities. With an altered spike protein in the Receptor-Binding Domain (RBD), EG.5 shares similarities with XBB.1.5 but surpasses it in prevalence, constituting 20% of COVID-19 cases in the United States by late August. EG.5's subvariant, EG.5.1, poses challenges with mutations like Q52H and F456L, contributing to its ability to bypass neutralizing antibodies. The global distribution of SARS-CoV-2 variants presents a dynamic landscape, with XBB.1.16 and other strains gaining prominence. The advent of the BA.2.86 variant further complicates the scenario, with its notable spread in regions lacking robust viral surveillance. A thorough analysis of mutations reveals the evolving nature of the Omicron variant, with distinct amino acid changes characterizing XBB.1.5, XBB.1.16, and EG.5. The WHO designates EG.5 as a "variant of interest" due to its increased contagiousness and potential immune evasion, emphasizing the need for vigilant monitoring. The risk assessment of EG.5 underscores its rapid development and growing prevalence globally. While booster vaccines targeting XBB.1.5 are in development, antiviral medications like nirmatrelvir/ritonavir (Paxlovid) continue to exhibit efficacy. In the context of the evolving variants, the FDA has granted emergency use authorization for updated COVID-19 vaccines targeting circulating strains, reflecting the adaptability of vaccination strategies to address emerging challenges. This comprehensive overview provides a nuanced understanding of the diverse Omicron subvariants, their global impact, and the ongoing efforts to combat their spread through vaccination and therapeutic interventions.

Chronic pulmonary aspergillosis incidence in newly detected pulmonary tuberculosis cases during follow-up.

BACKGROUND: Chronic pulmonary aspergillosis (CPA) is known to complicate patients with post-tubercular lung disease. However, some evidence suggests that CPA might co-exist in patients with newly-diagnosed pulmonary tuberculosis (P.TB) at diagnosis and also develop during therapy. The objective of this study was to confirm the presence of CPA in newly diagnosed P.TB at baseline and at the end-of-TB-therapy. MATERIALS AND METHODS: This prospective longitudinal study included newly diagnosed P.TB patients, followed up at third month and end-of-TB-therapy with symptom assessment, anti-Aspergillus IgG antibody and imaging of chest for diagnosing CPA. RESULTS: We recruited 255 patients at baseline out of which 158 (62%) completed their follow-up. Anti-Aspergillus IgG was positive in 11.1% at baseline and 27.8% at end-of-TB-therapy. Overall, proven CPA was diagnosed in 7% at baseline and 14.5% at the end-of-TB-therapy. Around 6% patients had evidence of aspergilloma in CT chest at the end-of-TB-therapy. CONCLUSIONS: CPA can be present in newly diagnosed P.TB patients at diagnosis and also develop during anti-tubercular treatment. Patients with persistent symptoms or developing new symptoms during treatment for P.TB should be evaluated for CPA. Whether patients with concomitant P.TB and CPA, while receiving antitubercular therapy, need additional antifungal therapy, needs to be evaluated in future studies.

Developmental events in the mandibular salivary gland of Indian sheep (Ovis aries): Morphological and histochemical studies.

At 22nd day of fetal development, the primordial anlage of mandibular gland was first noticed as a solid epithelial bud from oral epithelium. The terminal buds were arranged in the form of clusters with undifferentiated epithelial cells and terminated in a bulb like structure in 28-day-old fetus. The lumenization and branching of the main cord was noticed at 35th day. The primary septa, which divide the glandular mass into lobes was observed from 53rd day onwards which resulted in the formation of distinct lobulation at 58th day. At 61st day, the capsule formation was initiated by the aggregation of mesenchymal tissue. The terminal tubules differentiated to form the secretory end pieces and the tubular portion leads to the formation of intercalated and striated ducts at 98th day. Predominantly mucous types of acinar cells were seen from 108th day onwards. The number of lobules increased with steep increase in parenchyma from 128th day onwards. Micrometrical studies revealed that the mean diameter of acinar cells and all ducts was increased with the advancement of age and the significant differences were observed between groups. Localization of acidic and neutral mucopolysaccharides was observed in mucous cells and goblet cells. RESEARCH HIGHLIGHTS: The primordial anlage of mandibular salivary gland was seen at 22nd day. Lobulation of gland was appeared at 53rd day of development, however; it was completed at 58th day. At 98th day, the terminal tubules differentiated to form the secretory end pieces. The parenchyma of the gland showed predominantly mucous type of cells from 108th day onwards. Myoepithelial cells were first appeared as flattened basal cells initially around the developing acinar cells at 132nd day. Localization of acidic as well as neutral mucopolysaccharides was observed in mucous cells and goblet cells. Fine lipid droplets were observed in intralobular as well as interlobular connective tissue, however; phospholipids were observed in the cell membrane of secretory cells and ducts.