Dexibuprofen enteric film-coated tablets: design, characterization and pharmacokinetic analysis in human volunteers.

OBJECTIVE: This study aimed to develop a stable and scalable enteric film-coated tablet for the gastric irritant dexibuprofen. METHODS: Utilizing direct compression with super-disintegration (crospovidone), the optimal core batches were coated with Opadry white seal coat and enterically coated with Eudragit®L100 with pigment (Talc), demonstrating a 12% weight increase; release and integrity were assessed using specific pH buffers and SEM, with stability testing confirming a six-month shelf life at 40 °C and 75% RH. RESULTS: The optimized formulation achieved 99.87% release in phosphate buffer within 60 min, maintained integrity for 120 min in acidic conditions, and exhibited superior bioavailability compared to Innovifen with relative bioavailability ≈of 121% and elevated Cmax (18.35 µg/ml compared to 11.1 µg/ml). CONCLUSION: These results highlight the potential of this formulation to enhance patient safety and efficacy through delayed enteric technology and fast intestinal release.

Antibacterial and Antibiofilm Potential of Chlorophyllin Against Streptococcus mutans In Vitro and In Silico.

BACKGROUND: Streptococcus mutans is a leading causative agent of dental caries and exerts pathogenicity by forming biofilms. Dental caries continues to be a significant public health issue worldwide, affecting an estimated 2.5 billion people, showing a 14.6% increase over the past decade. Herein, the antibacterial potential of Chlorophyllin extracted from Spinacia oleracea was evaluated against biofilm-forming S. mutans via in vitro and in silico studies. METHODOLOGY: The antimicrobial activity of chlorophyllin extract against S. mutans isolates was tested using the agar well diffusion method. Chlorophyllin extract was also tested against biofilm-forming isolates of S. mutans. Chlorophyllin was docked with the antigen I/II (AgI/II) protein of S. mutans to evaluate its antimicrobial mechanism. The chemical structure and canonical SMILES format of Chlorophyllin were obtained from PubChem. Additionally, adsorption, distribution, metabolism, excretion, and toxicity (ADMET) analyses of Chlorophyllin were performed using ADMETlab 2.0 to assess its pharmacokinetic properties. RESULTS: An agar well diffusion assay revealed that all S. mutans isolates were susceptible to Chlorophyllin extract and showed a variety of inhibition zones ranging from 32 to 41 mm. Chlorophyllin reduces the biofilm strength of four isolates from strong to moderate and six from strong to weak. The antibiofilm potential of Chlorophyllin was measured by a reduction in the number of functional groups observed in the Fourier Transform Infrared Spectrometer (FTIR) spectra of the extracellular polymeric substance (EPS) samples. Chlorophyllin showed binding with AgI/II proteins of S. mutans, which are involved in adherence to the tooth surface and initiating biofilm formation. The ADMET analysis revealed that the safety of Chlorophyllin exhibited favorable pharmacokinetic properties. CONCLUSIONS: Chlorophyllin stands out as a promising antibacterial and antibiofilm agent against biofilm-forming S. mutans, and its safety profile highlights its potential suitability for further investigation as a therapeutic agent.

Dapagliflozin: A Promising Strategy to Combat Cisplatin-Induced Hepatotoxicity in Wistar Rats.

Recognizing the challenges posed by chemotherapy, specifically the hepatotoxic effects of drugs like cisplatin, this study aimed to examine the hepatoprotective potential of dapagliflozin to mitigate cisplatin-induced hepatotoxicity in a rat model. This study focused on repurposing drugs such as dapagliflozin and natural agents like silymarin as potential interventions to address cisplatin-induced hepatotoxicity. Thirty adult female Wistar rats were distributed into five groups and treated with cisplatin alone, silymarin, dapagliflozin, or a combination of dapagliflozin and silymarin accordingly for 45 days. Body weight, fasting blood glucose levels, liver function tests, and histopathological analysis were conducted to evaluate the hepatoprotective effects. Cisplatin-induced hepatotoxicity significantly (p < 0.05) increased the serum levels of ALT, AST, TB, and reduced the TP and albumin levels. Dapagliflozin administration led to significant reductions in ALT, AST, TB, and increased albumin levels. Silymarin demonstrated comparable effects. Combining dapagliflozin and silymarin showed synergistic effects, further reducing the liver enzymes and improving albumin levels. Histopathological examination supported these findings, revealing the restoration of liver structure with dapagliflozin and silymarin treatment. Dapagliflozin and silymarin exhibited substantial hepatoprotective benefits against cisplatin-induced hepatotoxicity in rats. The combination therapy demonstrated synergistic effects, highlighting a potential therapeutic approach for mitigating chemotherapy-induced liver damage. Further research into molecular mechanisms and clinical translation is warranted, offering hope for improved clinical outcomes in cancer patients undergoing cisplatin-based chemotherapy.

Impact of Farm Management Practices on Tick Infestation in Punjab's Livestock: A Comprehensive Epidemiological Study.

Tick infestation poses an important challenge to livestock in Pakistan. Farm management practices and environmental variables can influence tick infestation prevalence in animals. To this end, a cross-sectional survey of 96 farms in four different geographical districts (24 farms from each district) was conducted in Punjab, Pakistan, between October 2021 and January 2022. An epidemiological questionnaire was designed focusing on farm management practices and their impact on tick infestations at these farms. Data were collected via in-person interviews. Regional and farm-specific variables' associations were evaluated using Pearson's chi-square test and Fischer's exact test, respectively. A multivariable logistic regression model was used to identify significant risk factors. This study identified that using soft bedding materials, e.g., wheat straw, leaf litter or plain soil posed a significant risk of tick infestation. Additionally, the absence of quarantine measures, open sheds and inadequate drainage were found as contributing factors in univariable analysis. Higher tick prevalence in the hotter seasons highlighted the influence of Punjab's extreme weather on tick infestation. Despite regular veterinary visits and the use of acaricidal drugs, the prevalence of tick infestation at these farms suggested potential drug resistance in the ticks. The study recommended establishing quarantine practices, improving farms' drainage systems and bedding and using a combination of chemical and traditional remedies to tackle drug resistance in ticks. Education and awareness programs on tick-borne diseases and control measures are advocated to reduce the tick infestation burden on animals. Further research on longitudinal studies to better understand tick population dynamics and develop effective acaricides is encouraged. This called for collaborative control efforts among farmers, veterinarians and research institutions.

Cost-Effectiveness of Routine Histopathological Analysis of Doughnuts after Colorectal Surgery Three-Year Single-Centre Experience.

Aim: This study aimed to assess the impact of routine histological examination of stapled colorectal anastomotic doughnuts in patients undergoing rectal cancer surgery (RCS). Justification of biopsy examination could form part of the strategies of NHS net zero practice with effort to reduce wastage and carbon footprint. Method: A data analysis of all patients undergoing RCS during 2019-2021 at our institute was performed. We also analysed the cost of preparing and reviewing histology slides. Results: 52 patients underwent anterior resection during the aforementioned period. Doughnuts were sent in 37 (71%) patients. 23 (62%) patients were male, and 14 (38%) were female. The median age at diagnosis was 68 (range 54-84) years. All resected specimens were adenocarcinomas. Of the 37 patients, 18 (49%) underwent low anterior resection and 19 (51%) underwent high anterior resection. Proximal doughnuts were sent in 26 (70%) patients, whereas distal doughnuts were sent in all cases. Mean distal microscopic resection margin from tumour was 22 mm (range 6-45 mm). Each doughnut required 3 slides, each costing £50 and requiring 82 minutes to fix and read. This incurred a cost of £13,650 and required 19,656 hours of preparation time. All of the doughnuts as well as resection margins were negative for malignancy. Conclusion: Routine histopathological examination of doughnuts is time and cost-intensive however provides little or no clinical value (particularly analysis of the proximal doughnut). Distal doughnuts should only be sent for histological examination in exceptional circumstances.

Fertilizer use and agricultural practices in the paradox of maize crop production and environmental sustainability.

The enduring existence of pollution presents a substantial danger to human health, natural systems, and social welfare. Human activities mostly generate greenhouse gas emissions, namely carbon dioxide, which negatively impacts the environment. This study used annual datasets to examine the association between maize crop production, maize yield, fertilizer consumption, agricultural land use, and environmental quality in China. In order to identify the positive and negative shocks with the assessment of short- and long-run dynamics, the study used an asymmetric Nonlinear Autoregressive Distributed Lag (NARDL) approach. A Robust Least Squares method was also used to locate the parameters nexus in order to assess the series' robustness. Results from the long-run interaction indicate that the maize crop production and agricultural land use has a positive impact on CO2 emissions with probability values of (0.000), (0.000), and (0.001), (0.780), respectively, via both positive and negative interruptions. Additionally, maize yield exposed a detrimental effect on environmental quality. Results of the robust least squares analysis showed that maize crop production, fertilizer consumption, and agricultural land use had a positive influence on environmental quality, with probability values of (0.000), (0.004), and (0.949), respectively. However, there is an unfavourable relationship between variable maize yields and CO2 emissions. China should play a significant role in seeking to reduce carbon dioxide emissions and adopt the beneficial policies necessary to ensure the environment's long-term sustainability, since these emissions are now a rising issue around the world.

Crossing horizons: unraveling perspectives on enhancing medical students' success through at-risk factor exploration.

BACKGROUND: Medical universities often face the ongoing challenge of identifying and supporting at-risk students to enhance retention rates and academic success. This study explores a comprehensive analysis of perceived at-risk factors impeding academic and career aspirations and compares the perspectives of students and faculty in a medical school. METHODS: We focused on first and second-year medical (MBBS) students and teaching faculty in an international medical college offering a twinning program in India and Malaysia. Our investigation involved a comprehensive assessment of 25 at-risk factors through Likert-type questionnaires distributed to 250 MBBS students and 50 teaching faculty. RESULTS: Our findings revealed distinct disparities in perceptions between faculty and students regarding mean scores of classroom engagement (p = 0.017), procrastination (p = 0.001), unrealistic goals (p = 0.026), emotional/behavioral problems (p = 0.008), limited key social skills (p = 0.023), and a non-supportive home environment (p = 0.001). These differences underscore the need for increased communication and understanding between faculty and students to address these risk factors effectively. In contrast, no significant disparities were observed among faculty and students' perceptions concerning mean scores of various potential at-risk factors, including academic unpreparedness, cultural/language barriers, individual guidance/mentoring, limited communication skills, racism/sexism, self-confidence, self-respect, self-concept, motivation, underprepared for current academic challenges, self-discipline, negative social network, negative peer culture, transportation time, college financial cost, college evaluation culture bias, broken college relationships, teaching methodology, and learning disabilities. However, varying degrees of influence were perceived by faculty and students, suggesting the importance of individualized support. CONCLUSION: This study contributes to the academic community by shedding light on the multifaceted nature of at-risk factors influencing student success. It underscores the need for proactive measures and tailored interventions to enhance student retention in higher education and academic achievement, fostering a sustainable foundation for lifelong learning and growth.

Risk factors associated with influenza A (H1N1)pdm09: a nested case control study of TB patients with ILI in Lahore District, Pakistan.

BACKGROUND: Co-morbidity with respiratory viruses including influenza A, cause varying degree of morbidity especially in TB patients compared to general population. This study estimates the risk factors associated with influenza A (H1N1)pdm09 in TB patients with ILI. METHODS: A cohort of tuberculosis (TB) patients who were admitted to and enrolled in a TB Directly Observed Therapy Program (DOTs) in tertiary care hospitals of Lahore (Mayo Hospital and Infectious Disease Hospital) were followed for 12 weeks. At the start of study period, to record influenza-like illness (ILI), a symptom card was provided to all the participants. Every participant was contacted once a week, in person. When the symptoms were reported by the participant, a throat swab was taken for the detection of influenza A (H1N1)pdm09. A nested case control study was conducted and TB patients with ILI diagnosed with influenza A (H1N1)pdm09 by conventional RT-PCR were selected as cases, while those who tested negative by conventional RT-PCR were enrolled as controls. All cases and controls in the study were interviewed face-to-face in the local language. Epidemiological data about potential risk factors were collected on a predesigned questionnaire. Logistic analysis was conducted to identify associated risk factors in TB patients with ILI. RESULTS: From the main cohort of TB patients (n = 152) who were followed during the study period, 59 (39%) developed ILI symptoms; of them, 39 tested positive for influenza A (H1N1)pdm09, while 20 were detected negative for influenza A (H1N1)pdm09. In univariable analysis, four factors were identified as risk factors (p < 0.05). The final multivariable model identified one risk factor (sharing of towels, P = 0.008)) and one protective factor (wearing a face mask, p = < 0.001)) for influenza A (H1N1)pdm09 infection. CONCLUSION: The current study identified the risk factors of influenza A (H1N1)pdm09 infection among TB patients with ILI.

Association of Different Anticoagulation Strategies With Outcomes in Patients Hospitalized With Acute Pulmonary Embolism.

Background Therapeutic anticoagulation is the cornerstone of treatment for pulmonary embolism (PE), but the impact of different anticoagulation strategies on patient outcomes remains unclear. In this study, we assessed the association of different anticoagulation strategies with the outcomes of patients with acute PE. Methods A retrospective chart review of 207 patients with acute PE who were admitted to one of three urban teaching hospitals in the Mount Sinai Health System (in New York City) from January 2020 to September 2022 was performed. Demographic, clinical, and radiographic data were recorded for all patients. Multivariate regression analyses were performed to assess the association of different outcomes with the approach of therapeutic anticoagulation used. Results The median age of the included patients was 65 years, and 50.2% were women. The most common approach (n = 153, 73.9%) to therapeutic anticoagulation was initial treatment with unfractionated or low molecular weight heparin followed by a direct-acting oral anticoagulant (DOAC), while heparin alone (either unfractionated or low molecular weight heparin) was used in 37 (17.9%) patients, and another 17 (8.2%) patients were treated with heparin followed by bridging to warfarin. Hospital length of stay was longer for patients in the "heparin to warfarin" group (risk-adjusted incidence rate ratio of 2.52). The rates of in-hospital bleeding, all-cause 30-day mortality, and all-cause 30-day re-admissions did not have any significant association with the therapeutic anticoagulation approach used. Conclusion Patients with acute PE who were initially treated with heparin and subsequently bridged to warfarin had a longer hospital stay. Rates of in-hospital bleeding, 30-day mortality, and 30-day re-admission were not associated with the strategy of therapeutic anticoagulation employed.

Unlocking Synergistic Hepatoprotection: Dapagliflozin and Silymarin Combination Therapy Modulates Nuclear Erythroid 2-Related Factor 2/Heme Oxygenase-1 Pathway in Carbon Tetrachloride-Induced Hepatotoxicity in Wistar Rats.

This study was aimed to investigate the hepatoprotective potential of dapagliflozin and silymarin alone and in combination to combat carbon tetrachloride (CCl4)-induced hepatotoxicity and the anticipated mechanisms. Thirty female Wistar rats were randomly allocated into five different groups. All the experimental animals except the normal control (Group I) were administered CCl4. Additionally, Groups II, III, IV, and V were treated with gum acacia, silymarin, dapagliflozin, and a combination of dapagliflozin and silymarin, respectively, for 14 days. Dapagliflozin, silymarin alone, and in combination, significantly reduced (p < 0.05) serum levels of ALT, AST, AST:ALT ratio, and total bilirubin compared to CCl4-intoxicated control rats. There was a notable reduction (p < 0.05) observed in the levels of IL-1beta, IL-6, TNF-alpha, nitrites, and 4-hydroxynonenal, accompanied by an elevation in catalase, superoxide dismutase, glutathione peroxidase, nuclear erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) in liver homogenates of the groups treated with dapagliflozin, silymarin alone, and in combination, as compared to the CCl4-intoxicated control group. Dapagliflozin in combination with silymarin showed a synergistic hepatoprotective effect. Our study reveals the profound hepatoprotective potential of dapagliflozin alone and in combination with silymarin in CCl4-intoxicated Wistar rats by modulating the Nrf2 and HO-1 signaling pathways.

Unveiling the power of MYB transcription factors: Master regulators of multi-stress responses and development in cotton.

Plants, being immobile, are subject to environmental stresses more than other creatures, necessitating highly effective stress tolerance systems. Transcription factors (TFs) play a crucial role in the adaptation mechanism as they can be activated by diverse signals and ultimately control the expression of stress-responsive genes. One of the most prominent plant TFs family is MYB (myeloblastosis), which is involved in secondary metabolites, developmental mechanisms, biological processes, cellular architecture, metabolic pathways, and stress responses. Extensive research has been conducted on the involvement of MYB TFs in crops, while their role in cotton remains largely unexplored. We also utilized genome-wide data to discover potential 440 MYB genes and investigated their plausible roles in abiotic and biotic stress conditions, as well as in different tissues across diverse transcriptome databases. This review primarily summarized the structure and classification of MYB TFs biotic and abiotic stress tolerance and their role in secondary metabolism in different crops, especially in cotton. However, it intends to identify gaps in current knowledge and emphasize the need for further research to enhance our understanding of MYB roles in plants.

Effect of supplementing epinephrine in maturation media on in-vitro developmental competence of cattle and buffalo oocytes.

During in-vitro maturation, the oocyte experiences stressful conditions that likely compromise its development. Epinephrine is a catecholamine that plays a vital role during cellular stress by scavenging free radicals. The hypothesis is that epinephrine addition in maturation media improves the developmental competence of oocytes in cattle and buffalo. The objectives of the experiments were to investigate the effect of epinephrine addition in maturation media on nuclear maturation, developmental competence, and oocyte mRNA abundance of genes related to antioxidants and growth pathways in cattle and buffalo. In experiment 1, cattle oocytes were matured for 24 h in maturation media supplemented with increasing concentrations of epinephrine 0, 0.01, 1.0, and 100 µM. Oocytes were cultured to assess cleavage at 48 h and blastocyst on day 7 of the culture. The cumulus-oocyte complexes (COCs) expansion, nuclear maturation, and oocyte mRNA abundance of genes (SOD1, GPX4, GDF9, CASP9) were evaluated. In experiment 2, buffalo oocytes were matured and assessed for development and mRNA abundance as described for cattle. In addition, the blastomere number was counted in the hatched blastocyst. The data were analyzed using GLIMMIX and MIXED procedures of SAS. Results revealed that the supplementation of epinephrine increased (P ≤ 0.03) the COCs expansion, nuclear maturation, and developmental competence of oocytes in cattle. Interestingly, all the responses were maximized (quadratic effect; P ≤ 0.08) at 1 µM concentrations. The mRNA abundance of genes in cattle oocytes was not affected by the treatment. The experiment in buffalo revealed that epinephrine increased blastocyst formation without affecting COCs expansion, and nuclear maturation. The higher blastocyst was achieved at 0.01 µM concentrations of epinephrine. Interestingly, the addition of epinephrine increased the mRNA abundance of genes related to antioxidant pathways (SOD1, GPX4). Moreover, supplementation of epinephrine increased the blastomere count of the hatched blastocyst in buffalo. In conclusion, epinephrine addition in maturation media benefited oocyte development in cattle and blastocyst yield in buffalo at 1 and 0.01 µM concentrations, respectively. It appears that the addition of epinephrine affected different cellular pathways, COCs expansion, and nuclear maturation in cattle and increased antioxidant genes for buffalo.

Association of race, ethnicity and insurance status with outcomes for patients with acute pulmonary embolism treated by PERT: a retrospective observational study.

BACKGROUND: Management of PE has become streamlined with the implementation of PE Response Teams (PERT). Race, ethnicity and insurance status are known to influence the outcomes of patients with acute PE. However, whether the implementation of PERT-based care mitigates these racial and ethnic disparities remains unknown. Our aim was to assess the association of race, ethnicity and insurance with outcomes for patients with acute PE managed by PERT. METHODS: We performed a retrospective chart review of 290 patients with acute PE, who were admitted to one of three urban teaching hospitals in the Mount Sinai Health System (New York, NY) from January 2021 to October 2023. A propensity score-weighted analysis was performed to explore the association of race, ethnicity and insurance status with overall outcomes. RESULTS: Median age of included patients was 65.5 years and 149 (51.4%) were female. White, Black and Asian patients constituted 56.2% (163), 39.6% (115) and 3.5% [10] of the cohort respectively. Patients of Hispanic or Latino ethnicity accounted for 8.3% [24] of the sample. The 30-day rates of mortality, major bleeding and 30-day re-admission were 10.3%, 2.1% and 12.8% respectively. Black patients had higher odds of major bleeding (odds ratio [OR]: 1.445; p < 0.0001) when compared to White patients. Patients of Hispanic or Latino ethnicity had lower odds of receiving catheter-directed thrombolysis (OR: 0.966; p = 0.0003) and catheter-directed or surgical embolectomy (OR: 0.906; p < 0.0001) when compared to non-Hispanic/Latino patients. Uninsured patients had higher odds of receiving systemic thrombolysis (OR: 1.034; p = 0.0008) and catheter-directed thrombolysis (OR: 1.059; p < 0.0001), and lower odds of receiving catheter-directed or surgical embolectomy (OR: 0.956; p = 0.015) when compared to insured patients, although the odds of 30-day mortality and 30-day major bleeding were not significantly different. CONCLUSION: Within a cohort of PE patients managed by PERT, there were significant associations between race, ethnicity and overall outcomes. Hispanic or Latino ethnicity and uninsured status were associated with lower odds of receiving catheter-directed or surgical embolectomy. These results suggest that disparities related to ethnicity and insurance status persist despite PERT-based care of patients with acute PE.

Bile acid/fatty acid integrated nanoemulsomes for nonalcoholic fatty liver targeted lovastatin delivery: stability, in-vitro, ex-vivo, and in-vivo analyses.

BACKGROUND: Controlled and targeted drug delivery to treat nonalcoholic fatty liver disease (NAFLD) can benefit from additive attributes of natural formulation ingredients incorporated into the drug delivery vehicles. METHODS: Lovastatin (LVN) loaded, bile acid (BA) and fatty acid (FA) integrated nanoemulsomes (NES) were formulated by thin layer hydration technique for synergistic and targeted delivery of LVN to treat NAFLD. Organic phase NES was comprised of stearic acid with garlic (GL) and ginger (GR) oils, separately. Ursodeoxycholic acid and linoleic acid were individually incorporated as targeting moieties. RESULTS: Stability studies over 90 days showed average NES particle size, surface charge, polydispersity index, and entrapment efficiency values of 270 ± 27.4 nm, -23.8 ± 3.5 mV, 0.2 ± 0.04 and 81.36 ± 3.4%, respectively. Spherical NES were observed under a transmission electron microscope. In-vitro LVN release depicted non-fickian release mechanisms from GL and GR oils-based NES. Ex-vivo permeation of BA/FA integrated NES through isolated rat intestines showed greater flux than non-integrated ones. CONCLUSION: Liver histopathology of experimental rats together with in-vivo lipid profiles and liver function tests illustrated that these NES possess the clinical potential to be promising drug carriers for NAFLD.

GhiPLATZ17 and GhiPLATZ22, zinc-dependent DNA-binding transcription factors, promote salt tolerance in upland cotton.

KEY MESSAGE: The utilization of transcriptome analysis, functional validation, VIGS, and DAB techniques have provided evidence that GhiPLATZ17 and GhiPLATZ22 play a pivotal role in improving the salt tolerance of upland cotton. PLATZ (Plant AT-rich sequences and zinc-binding proteins) are known to be key regulators in plant growth, development, and response to salt stress. In this study, we comprehensively analyzed the PLATZ family in ten cotton species in response to salinity stress. Gossypium herbaceum boasts 25 distinct PLATZ genes, paralleled by 24 in G. raimondii, 25 in G. arboreum, 46 in G. hirsutum, 48 in G. barbadense, 43 in G. tomentosum, 67 in G. mustelinum, 60 in G. darwinii, 46 in G. ekmanianum, and a total of 53 PLATZ genes attributed to G. stephensii. The PLATZ gene family shed light on the hybridization and allopolyploidy events that occurred during the evolutionary history of allotetraploid cotton. Ka/Ks analysis suggested that the PLATZ gene family underwent intense purifying selection during cotton evolution. Analysis of synteny and gene collinearity revealed a complex pattern of segmental and dispersed duplication events to expand PLATZ genes in cotton. Cis-acting elements and gene expressions revealed that GhiPLATZ exhibited salt stress resistance. Transcriptome analysis, functional validation, virus-induced gene silencing (VIGS), and diaminobenzidine staining (DAB) demonstrated that GhiPLATZ17 and GhiPLATZ22 enhance salt tolerance in upland cotton. The study can potentially advance our understanding of identifying salt-resistant genes in cotton.

Comparison of efficacy of neoadjuvant chemotherapy with gemcitabine plus cisplatin versus docetaxil, cisplatin, plus fluorouracil in locally advanced nasopharyngeal carcinoma.

Induction followed by concurrent chemoradiation (CCRT) is the standard of care for locally advanced nasopharyngeal carcinoma (LANPC). This study evaluated and compared the efficacy of two regimens of neoadjuvant chemotherapy along with CCRT in LANPC. Patients with LANPC were randomly divided in Group I (receiving neoadjuvant gemcitabine and cisplatin) and Group II (receiving neoadjuvant docetaxil, cisplatin and fluorouracil). Both groups also received concurrent single agent (i.e., cisplatin) chemotherapy and radiotherapy (70Gy). Treatment response was assessed at 8 weeks after the completion of CCRT using RECIST criteria. A total of 68 LANPC patients were enrolled. Group I comprised of 32 patients, with male to female ratio of 2.2, a mean (range, median) age of 38.6±11.3 (19-58, 36) years. Group II comprised of 36 patients, with male to female ratio of 3.5, mean (range, median) age of 40.9 ±11.6 (17-63, 40) years. The complete response was higher whereas the partial response was lower in Group I as compared to Group II (23/32 versus 16/36 and 06/32 versus 18/36, respectively). LANPC patients receiving gemcitabine plus cisplatin based neoadjuvant chemotherapy showed higher response, as compared with docetaxil, cisplatin and fluorouracil based neoadjuvant chemotherapy.

Toxicological review of micro- and nano-plastics in aquatic environments: Risks to ecosystems, food web dynamics and human health.

The increase of micro- and nano-plastics (MNPs) in aquatic environments has become a significant concern due to their potential toxicological effects on ecosystems, food web dynamics, and human health. These plastic particles emerge from a range of sources, such as the breakdown of larger plastic waste, consumer products, and industrial outputs. This review provides a detailed report of the transmission and dangers of MNPs in aquatic ecosystems, environmental behavior, and interactions within aquatic food webs, emphasizing their toxic impact on marine life. It explores the relationship between particle size and toxicity, their distribution in different tissues, and the process of trophic transfer through the food web. MNPs, once consumed, can be found in various organs, including the digestive system, gills, and liver. Their consumption by lower trophic level organisms facilitates their progression up the food chain, potentially leading to bioaccumulation and biomagnification, thereby posing substantial risks to the health, reproduction, and behavior of aquatic species. This work also explores how MNPs, through their persistence and bioaccumulation, pose risks to aquatic biodiversity and disrupt trophic relationships. The review also addresses the implications of MNPs for human health, particularly through the consumption of contaminated seafood, highlighting the direct and indirect pathways through which humans are exposed to these pollutants. Furthermore, the review highlights the recommendations for future research directions, emphasizing the integration of ecological, toxicological, and human health studies to inform risk assessments and develop mitigation strategies to address the global challenge of plastic pollution in aquatic environments.

Irinotecan dosing and pharmacogenomics: a comprehensive exploration based on UGT1A1 variants and emerging insights.

Irinotecan is a critical anticancer drug used to treat metastatic colorectal cancer and advanced pancreatic ductal adenocarcinoma by obstructing topoisomerase 1; however, it can cause minor-to-severe and life-threatening adverse effects. UDP glucuronosyltransferase family 1 member A1 (UGT1A1) polymorphisms increase the risk of irinotecan-induced neutropenia and diarrhea. Hence, screening for UGT1A1 polymorphisms before irinotecan-based chemotherapy is recommended to minimize toxicity, whereas liposomes offer the potential to deliver irinotecan with fewer side effects in patients with pancreatic ductal adenocarcinoma. This review presents a comprehensive overview of the effects of genotype-guided dosing of irinotecan on UGT1A1*28 and UGT1A1*6 variants, incorporating pharmacogenomic research, optimal regimens for metastatic colorectal and pancreatic cancer treatment using irinotecan, guidelines for toxicity reduction, and an evaluation of the cost-effectiveness of UGT1A1 genotype testing.

Transcriptome dynamics of Gossypium purpurascens in response to abiotic stresses by Iso-seq and RNA-seq data.

Gossypium purpurascens is a member of the Malvaceae family, holds immense economic significance as a fiber crop worldwide. Abiotic stresses harm cotton crops, reduce yields, and cause economic losses. Generating high-quality reference genomes and large-scale transcriptomic datasets across diverse conditions can offer valuable insights into identifying preferred agronomic traits for crop breeding. The present research used leaf tissues to conduct PacBio Iso-seq and RNA-seq analysis. We carried out an in-depth analysis of DEGs using both correlations with cluster analysis and principal component analysis. Additionally, the study also involved the identification of both lncRNAs and CDS. We have prepared RNA-seq libraries from 75 RNA samples to study the effects of drought, salinity, alkali, and saline-alkali stress, as well as control conditions. A total of 454.06 Gigabytes of transcriptome data were effectively validated through the identification of differentially expressed genes and KEGG and GO analysis. Overwhelmingly, gene expression profiles and full-length transcripts from cotton tissues will aid in understanding the genetic mechanism of abiotic stress tolerance in G. purpurascens.

Multidrug-Resistant Pathogens in Wound Infections: A Systematic Review.

This systematic review aimed to explore the antimicrobial activity of a silver-containing gelling fiber dressing against multidrug-resistant organisms (MDROs) in wound infections. It particularly focuses on burn wounds and evaluates its potential clinical significance in combating antimicrobial resistance. A comprehensive literature search was conducted across multiple databases over the past ten years. It is used to identify relevant studies addressing MDRO infections in wound care and exploring novel antimicrobial approaches. The included studies underwent rigorous methodological assessment. Additionally, the data were synthesized to evaluate the efficacy of silver-containing dressings in inhibiting MDRO growth and eradicating biofilm-associated bacteria. Moreover, this review revealed that silver-containing dressings have constant in vitro antimicrobial activity against 10 MDROs over seven days in simulated wound fluid. However, inhibitory and bactericidal effects were consistently observed against free-living and biofilm phenotypes. The findings suggest potential clinical significance in managing MDRO infections in wounds. This highlights its role in mitigating treatment failure and antimicrobial resistance. Despite the promising implications for wound management practices, this study acknowledges some limitations. In vitro models and the absence of direct clinical validation have also been included. However, the review explains the importance of new approaches. Nanotechnology has been used to address antimicrobial resistance in wound care. Thus, further research and innovation are needed to improve patient outcomes and combat antimicrobial resistance.