Molecular pathology and computational profiling of Janus kinase 2 (JAK2) mutation in acute lymphoblastic leukemia: insights from a Pakistani cohort.

BACKGROUND: JAK2 mutation plays a clinically significant role in the pathogenesis of acute lymphoblastic leukemia (ALL) by enhancing its oncogenicity. The study aimed to characterize the molecular pathology and computational profile of the JAK2 mutation in an ALL cohort of Pakistani origin. METHODS: Ninety-three patients were enrolled in the current study. The disease diagnosis was confirmed via flow cytometry and karyotyping of bone marrow aspirate/blood. For the identification of causative gene variations and assessment of their potential impact, the JAK2 gene underwent direct sequencing and predictive computational and in silico structural analysis, respectively. RESULTS: JAK2 mutations were detected in 10 (11%) patients. All mutations were missense with 1 being frameshift. Most mutations showed a similar pattern to the wild type but p.N673H+p.V674L+p.C675W (AAD699), p.V674F (AAD704), and p.V674L (AAD705) exhibited statistically significant stability loss. The triple mutation displayed reduced stability both globally and locally. CONCLUSION: The pattern of gene defects in JAK2 in the studied cohort showed a disruption in proper folding behavior, evident from increased gyration values, resulting in the hypothesis that these mutations may cause structural alterations in the JAK2 protein that lead to disease progression.

Experimental and simulation study of American saffron seed oil blended with diesel.

In a variety of industries, including transportation, agriculture, and manufacturing, diesel engines are often employed. Due of rising prices and environmental concerns, researchers examined whether biodiesels might replace diesel. The current study looks into American Saffron Oil's feasibility as a feedstock for biodiesel production. The transesterification technique is used to extract American saffron oil methyl este(ASOME), which is then examined for its physical and chemical properties in accordance with ASTM standards. Diesel fuel and American Saffron Oil methyl ester are mixed on a volume basis to create a variety of fuel blends, including B20, B40, and B60. The test results showed that the 20 % ASOME mix had better performance and reduced emissions. Also, utilizing DIESEL-RK simulation software, diesel engine tests are conducted for the B20, B40, and B60 under identical operating circumstances. Moreover, diesel engine testing for the B20, B40, and B60 are carried out using DIESEL-RK simulation software under comparable operating circumstances. Results of simulation software tests show improved engine performance and reduced pollutants. When experimental data is compared to DIESEL-RK modeling software, it is found that brake thermal efficiency increased by 5.7 % and emissions of hydrocarbon and carbon monoxide decreased by 2.5 % and 14.3 %, respectively.

Impact of Plastic Surgery and an Enhanced Prophylaxis Protocol on Cervical Spine Surgery Infection.

Background: Reduction of surgical site infections (SSIs) is important in improving cervical spine surgery outcomes. Plastic surgery involvement and an enhanced modified prophylaxis protocol may reduce infection rates. Methods: A total of 962 cervical spine operations were conducted by a single surgeon (TFC). An enhanced modified prophylaxis protocol and plastic surgery were used in some operations. Differences in infection rates, surgical approach, previous operations, prophylaxis use, and plastic surgery involvement were compared using Fisher's exact tests and multivariate linear regression. Results: Four patients (0.42%) experienced SSIs. All 4 infections involved the standard protocol, posterior approach, and did not involve plastic surgery. The infection rate was lower in the enhanced protocol group when compared to the standard protocol (ß -0.78, 95% CI -1.23 to -0.33, P = .0008). The enhanced protocol group had an increased percentage of operations with plastic surgery (ß 0.19, 95% CI 0.10 to 0.28, P < .0001). The infection rate among the plastics group was 0.00% compared to 0.60% for the non-plastics group (P = .32). The plastics group had a lower rate of anterior approach when compared to the non-plastics group (ß -0.20, 95% CI -0.24 to -0.15, P = .049). Among the posterior approach group, procedures with plastic surgery had an infection rate of 0.00% compared to 2.53% without plastic surgery (P = .13). Conclusion: The enhanced protocol was associated with a lower SSI rate and increased plastic surgery involvement. Posterior approaches were associated with increased infection rates and the likelihood of utilizing plastic surgery. Both the enhanced protocol and plastic surgery may decrease infection.

Contexte: La réduction des infections du site opératoire est importante pour améliorer les résultats de la chirurgie de la colonne cervicale. L'implication de la chirurgie plastique et d'un protocole amélioré de prophylaxie modifiée peuvent réduire les taux d'infection. Méthodes: Un total de 962 opérations sur la colonne cervicale a été effectué par un seul chirurgien (TFC). Un protocole amélioré de prophylaxie modifiée et la chirurgie plastique ont été utilisés au cours de certaines interventions. Les différences dans les taux d'infection, l'abord chirurgical, les opérations précédentes, l'utilisation de la prophylaxie et l'implication de la chirurgie plastique ont été évalués au moyen de tests exacts de Fisher et d'une régression linéaire multifactorielle. Résultats: Quatre patients (0.42%) ont présenté une infection de la cicatrice opératoire (ICO). Les quatre infections impliquaient le protocole standard, l'abord postérieur et l'absence de chirurgie plastique. Le taux d'infection a été moindre dans le groupe de protocole amélioré, comparativement au protocole standard (ß −0.78, IC à 95%: −1.23 à −0.33, P = .0008). Le pourcentage d'opérations avec chirurgie plastique était augmenté dans le groupe au protocole amélioré (ß 0.19, IC à 95%: 0.10 à 0.28, P < .0001). La fréquence des infections dans le groupe de chirurgie plastique était de 0.00%, comparée à 0.60% dans le groupe sans chirurgie plastique (P = .32). Le groupe avec chirurgie plastique avait un taux d'abord antérieur inférieur comparativement au groupe sans chirurgie plastique (ß −0.20, IC à 95%: −0.24 à −0.15, P = .049). Dans le groupe avec abord postérieur, le taux d'infections était de 0.00% avec chirurgie plastique contre 2.53% sans chirurgie plastique (P = .13). Conclusion: Le protocole amélioré a été associé à un taux d'OCI inférieur et à une plus grande implication de la chirurgie plastique. Un abord postérieur a été associé à des taux augmentés d'infection et à une plus grande probabilité d'utilisation de la chirurgie plastique. Le protocole amélioré et la chirurgie plastique peuvent tous deux réduire les infections.

Stress hyperglycemia is associated with longer ICU length of stay after endoscopic intracerebral hemorrhage evacuation.

BACKGROUND: Stress hyperglycemia has been linked to poor outcomes in intracerebral hemorrhage (ICH). Recent studies using the ratio of blood glucose to glycated hemoglobin (HbA1c) as a marker for stress hyperglycemia have demonstrated greater discriminative power in predicting poor outcomes for stroke inpatients compared to blood glucose alone. Therefore, we aimed to investigate whether the preoperative glucose-to-HbA1c ratio is a predictor of postoperative outcomes in patients who have undergone minimally invasive ICH evacuation. METHODS: Retrospective chart review was performed on ICH patients treated with minimally invasive surgery (MIS) in a single health system from 2015 to 2022. Stress hyperglycemia was defined as preoperative glucose-to-HbA1c ratio > calculated-median. Postoperative outcomes including modified Rankin Score (mRS) and length of stay (LOS) were collected. Univariate analyses were conducted to determine associations. Variables with p<0.05 were included in multivariate analyses. RESULTS: Of 192 patients who underwent minimally invasive ICH evacuation and had available glucose data, 96 demonstrated stress hyperglycemia (glucose-to-HbA1c ratio > 1.23). Patients with stress hyperglycemia were more likely to have a history of diabetes (43 % vs. 27 %, p=0.034), IVH (54 % vs. 33 %, p=0.007), higher preoperative hematoma volumes (46.8 ml vs. 38.6 mL, p=0.02), higher postoperative hematoma volumes (6 ml vs. 2.9 mL, p=0.008), smaller evacuation percentages (86.7 % vs. 92.7 %, p=0.048), longer procedure lengths (2.78 hrs vs. 2.23 hrs, p=0.015), and prolonged ICU LOS (9.44 days vs. 5.68 days, p=0.003). In a multivariate analysis, stress hyperglycemia remained predictive of prolonged ICU LOS (OR=2.44; p=0.026) when controlling for initial NIHSS, IVH, time to evacuation, procedure time, and diabetes. CONCLUSIONS: Stress hyperglycemia was strongly associated with prolonged ICU LOS after MIS for ICH. Understanding factors associated with LOS may provide predictive value for a patient's hospital course after minimally invasive ICH evacuation and further guide clinician expectations of recovery.

In silico analysis of DEL-1 and inflammation-related genes in lung squamous cell carcinoma.

AIM: Twenty to thirty percent of non-small cell lung cancers (NSCLC) are caused by lung squamous cell carcinoma (LUSC), especially in smokers and there has been limited study previously evaluating the situation in terms of the genome and gene expression profile, which demonstrates the relationship among DEL-1, leucocyte recruitment, and pro-inflammatory cytokines in LUSC. MATERIAL AND METHODS: In the current study, the m-RNA expression patterns and mutation profiles of our target genes, such as, pro-inflammatory cytokines, chemoattractant molecules, and DEL-1 genes, in 511 LUSC patients. To find the harmful mutations, the PolyPhen-2 and SNAP programs were employed. Not only gene expression was detected, but also survival analysis and correlation between DEL-1 and other target genes' expression levels were explored too. RESULTS: Target genes such as, DEL-1, TNF, IL-18, IL-1, CXCL8, CXCL13, and IL-6 were found to have a total genetic anomaly carrying rate of 16.4%. Seven mutations were found, and two of those mutations have a pathogenic aspect. Deep deletion and gene amplification of the genetic anomalies were also observed. According to gene expression analysis results in the LUSC patient group; DEL-1 and IL-6 levels were significantly lower than those of the control group, whereas the CXCL13 level was found to be higher. CONCLUSION: Findings of the current study revealed that, there is a significant role of DEL-1 in LUSC pathogenesis. Since present study is an in silico-centered study, this approach can give more insight on experimental studies. These events may support that one of the cancer improvement mechanisms depending on DEL-1 gene at the molecular level.

DFT, GC-MS analysis and biological evaluation of Limbarda crithmoides L. Dumort essential oil; an important edible halophyte grown in Pakistan.

Antimicrobial resistance is a major health burden in Pakistan, and therefore new herbal medicine-based therapeutic regimens are being largely investigated. Limbarda crithmoides essential oil was extracted by using hydrodistillation method. Chemical profiling of essential was evaluated by using FTIR and GC-MS analysis. A total of 20 components were identified including, p-xylene, o-xylene, ß-linalool, acetophenole and 3-isopropylphenyl methylcarbamate. The HOMO and LUMO analysis in DFT investigations presented that 3-isopropylphenyl methylcarbamate, p-xylene and o-xylene posess a substantial capacity to transfer charge through molecules. The antimicrobial potential of essential oil showed moderate inhibition against E. coli (MIC = 6.25 mg/mL), whereras a significant inhibition Staphylococos aureus was recorded (MIC = 3.12 mg/mL). Further, significant antioxidant activities were recorded in DPPH radical scavenging (IC50 = 80.5 µg/mL), H2O2 (64 ± 1.2%) and FRAP (60.3 µg ferrous equivalents) assays. It was therefore concluded that Limbarda crithmoides essential oil has potential antioxidant and anti-antimicrobial properties and can be used for further investigations.

A histopathological and epidemiological study of urothelial carcinoma at a tertiary care centre in Peshawar, Pakistan.

Bladder cancer is the ninth leading cause of death worldwide and 14th leading cause of death in Pakistan. The objective of this study was to determine the frequency of urothelial carcinoma in various age groups, its gender distribution, and grades. A total of 131 cases of urothelial carcinoma, received at Department of Pathology, Peshawar Medical College, Peshawar, between January 2017 to December 2022, were included in the study; of them 107 (81.6%) were males while 24 (18.3%) were females with a mean age of 62±13 years. The most common histological subtype was papillary urothelial carcinoma in 117(89.3%) cases, followed by Squamous and Glandular in 5(3.8%) cases. Majority of the urothelial carcinoma with high grade showed a statistically significant relation with muscle invasion 38 (50.66%). Males were four times more likely to have urothelial carcinoma while older age groups were more likely to have high grade urothelial carcinoma.

Efficacy of Chemotherapy-Free Regimens in the Treatment of Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Systematic Review and Meta-Analysis.

INTRODUCTION: The historical standard of care for Ph+ ALL is chemotherapy plus a tyrosine kinase inhibitor (TKI). Recently chemotherapy-free regimens have shown promising efficacy. We performed a meta-analysis to compare the efficacy of chemotherapy-free regimens for Ph+ ALL. METHODS: We searched PubMed and Embase for chemotherapy-free regimens for Ph+ ALL published between January 2000 and October 2023. Of the 5,348 articles screened, 9 nonrandomized clinical trials enrolling 413 patients were included. Two trials (N = 117) included treatment with 3 agents (blinatumomab, TKI, and steroid) and 7 trials (N = 248) included treatment with 2 agents (TKI and steroids). R software was used to conduct the meta-analysis (PROSPERO registration no. CRD42023482439). RESULTS: The pooled complete molecular response (CMR) rate of patients receiving a TKI, blinatumomab, and steroids was 81% (95%CI, 69%-89%). TKIs plus blinatumomab were nearly 6 times as likely to have CMR (odds ratio [OR], 5.98; 95%CI, 2.99-11.96) and more than 5 times as likely to be alive at 1-year (OR, 5.1; 95%CI, 1.74-14.9) as compared to TKIs alone. Patients receiving ponatinib were about twice as likely as those receiving dasatinib to achieve CMR (OR, 2.51; 95%CI, 0.72-8.72). CONCLUSION: Adding blinatumomab to TKIs and steroids significantly improved Ph+ ALL patients' response and survival rates. Regimens with ponatinib elicited higher molecular response rates than those with other TKIs. The high response and survival rates achieved with blinatumomab plus TKIs and steroids suggest that further studies are required to assess the need for intensive treatments such as chemotherapy or stem cell transplant in these patients.

Longitudinally extensive transverse myelitis as an initial manifestation of sarcoidosis: A rare case and its management.

Key Clinical Message: Sarcoidosis-induced LETM represents a rare but life-threatening neurological manifestation of sarcoidosis, characterized by spinal cord inflammation, and associated neurological deficits. Sarcoidosis should be included in the differential diagnosis of LETM, particularly in patients with no lung involvement. Prompt recognition and management are obligatory to optimize outcomes and prevent long-term disability. Abstract: Sarcoidosis is a multisystem inflammatory granulomatous disorder characterized by the formation of noncaseating granulomas. Although sarcoidosis commonly affects the skin, lymph nodes, and lungs, neurological involvement of sarcoidosis has also been reported. Longitudinally extensive transverse myelitis (LETM) is a rare but well-documented serious manifestation of neuroscoidosis. We report a case of LETM caused by sarcoidosis in a 53-year-old male who presented with progressive bilateral lower extremity weakness, urinary retention, and paresthesia. Laboratory evaluations revealed elevated inflammatory markers. Magnetic resonance imaging of the spine showed hyperintense signals consistent with transverse myelitis. Cerebrospinal fluid analysis revealed lymphocytic pleocytosis and elevated protein levels. Chest computed tomography showed hilar lymphadenopathy. A biopsy of the intrathoracic lymph node showed noncaseating granulomas consistent with sarcoidosis. A diagnosis of sarcoidosis-induced LETM was made after ruling out all other possible etiologies. His condition improved gradually after starting high-dose prednisone, mycophenolate, and rehabilitation strategies. Our case underscores the importance of prompt diagnosis and management of sarcoidosis-induced LETM and highlights that sarcoidosis must be included among differential diagnoses of LETM, especially in cases with no lung involvement.

Antithrombotics alter intracerebral hemorrhage presentation without affecting minimally invasive endoscopic evacuation.

OBJECTIVES: Intracerebral hemorrhages are associated with significant morbidity and mortality. While the ENRICH trial supports the efficacy of surgical evacuation for lobar hemorrhages, the impact of antithrombotic therapies on minimally invasive surgery outcomes remains unexplored. This study evaluates the effects of chronic anticoagulants and antiplatelets on the technical and longterm outcomes of minimally invasive intracerebral hemorrhage evacuation. MATERIALS AND METHODS: A prospectively collected registry of patients undergoing minimally invasive surgery for intracerebral hemorrhage from a single institution was analyzed (December 2015-September 2022). Data included key demographics, comorbidities, antithrombotic/reversal status, presenting clinical/radiographic characteristics, procedural metrics, and clinical outcomes. Patients were divided into control (neither therapy), antiplatelet-only, and anticoagulant-only groups, with antiplatelet/anticoagulant reversals conducted per current American Heart Association/American Stroke Association guidelines. Variables significant in univariate analyses (p<0.05) were advanced to multivariable regression models. RESULTS: Among 226 intracerebral hemorrhage patients treated with minimally invasive surgery, 41% (N=93) had antithrombotic medication history; 28% (N=64) received antiplatelets, and 9% (N=21) received anticoagulants. Patients on both therapies (N=6) were excluded. The antiplatelet group presented more frequently with lobar hemorrhages (56% vs. 37%; p=0.022), while patients on anticoagulants showed increased rates of intraventricular hemorrhage co-presentation (62% vs. 46%; p=0.011) compared to controls. Despite univariate analyses showing a higher postoperative hematoma volume (3.9 vs. 2.9 milliliters; p=0.020) and lower evacuation percentage (88% vs. 92%; p=0.019) for the antiplatelet group, and longer procedures for patients on anticoagulants (2.3 vs. 1.7 hours; p=0.042) compared to control, multivariable analyses indicated that antiplatelets and anticoagulants had no significant impact on these technical outcomes. Longitudinally, antithrombotics were not associated with increased rebleeding, less frequent discharge to home, lower 30-day mortality, or worse, 6-month Modified Rankin Scale scores. CONCLUSIONS: Patients on chronic antiplatelets and anticoagulants exhibited characteristic intracerebral hemorrhage phenotypes without worse technical or long-term outcomes after minimally invasive intracerebral hemorrhage evacuation, suggesting the procedure's safety for these patients.

ARISCAT and LAS VEGAS risk scores for predicting postoperative pulmonary complications after cardiac surgery: a cohort study.

Background: Postoperative pulmonary complications (PPCs) could lead to morbidity, mortality, and prolonged hospital stay. Different risk-scoring systems are used to predict the identification of patients at risk of developing PPCs. The diagnostic accuracies of the Assess Respiratory Risk in Surgical Patients in Catalonia (ARISCAT) and Local Assessment of Ventilatory Management During General Anaesthesia for Surgery (LAS VEGAS) risk scores are compared in prediction of PPCs taking pulmonary complication as the gold standard in cardiac surgery. Materials and methods: A prospective cohort study with consecutive sampling technique. A total of 181 patients were included. Quantitative data is presented as simple descriptive statistics giving mean and standard deviation, and qualitative variables are presented as frequency and percentages. Sensitivity, specificity, positive and negative predictive values, and diagnostic accuracies are also calculated. Results: Total 181 post-cardiac surgery patients were analyzed. The median [interquartile range] of age, height, weight, and BMI were 60.0 [52.0-67.0] years, 163.0 [156.0-168.0] cm, 71.0 [65.0-80.0] kg and 27.3 [24.2-30.4] kg/m2. 127 (70.2%) were male, and 54 (29.8%) were female. Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of ARISCAT for the prediction of PPCs were (94.9%, 4.65%, 76.1%, 22.9% and 73.4%), whereas LAS VEGAS were (97.1%, 4.65%, 76.5%, 33.3% and 75.1%), respectively. Conclusion: Both the ARISCAT and LAS VEGAS risk scores are of limited value in cardiac surgery patients for the prediction of postoperative pulmonary complications, based on the predicted scores in this study.

Outcomes of transarterial chemoembolization in patients with unresectable hepatocellular carcinoma: A tertiary center experience.

Objective: To assess the overall survival in patients with intermediate stage hepatocellular carcinoma following transarterial chemoembolization. Methods: It is a retrospective descriptive study carried out in the Department of Radiology of Liaquat National Hospital Karachi, Pakistan. Seventy-two patients were enrolled from July 2014 to December 2021 and had chemoembolization therapy. Patients were followed till their demise. Mean and Median survivals were calculated. Results: A total of 72 patients had a median survival of 15 months with 95% confidence interval (11 months was lower bound and 18 months was upper bound), 19 months was the mean survival time with 95% confidence interval (14.7 months was lower limit and 22.6 months the upper limit). The factors which had a significant impact on the median survival time were Child-Pugh classification, average size of tumor and embolization pattern. Conclusion: Transarterial chemoembolization (TACE) increases the median survival time effectively and safely in patients with hepatocellular carcinoma. However complete resolution of disease is not possible with TACE, with most patient eventually succumbing to the disease. The overall survival for TACE in this study correlates well with other studies. Child Pugh Class, tumor size and embolization pattern have significant effect on survival of patients.

Long-term Renal Function Outcomes After Stereotactic Ablative Body Radiotherapy for Primary Renal Cell Carcinoma Including Patients with a Solitary Kidney: A Report from the International Radiosurgery Oncology Consortium of the Kidney.

BACKGROUND AND OBJECTIVE: Renal function preservation is particularly important following nonoperative treatment of localized renal cell carcinoma (RCC) since patients are often older with medical comorbidities. Our objective was to report long-term renal function outcomes after stereotactic ablative radiotherapy (SABR) including patients with a solitary kidney. METHODS: Patients with primary RCC treated with SABR with ≥2 yr of follow-up at 12 International Radiosurgery Consortium for Kidney institutions were included. Renal function was measured by estimated glomerular filtration rate (eGFR). KEY FINDINGS AND LIMITATIONS: In total, 190 patients (56 with a solitary kidney) underwent SABR and were followed for a median of 5.0 yr (interquartile range [IQR]: 3.4-6.8). In patients with a solitary kidney versus bilateral kidneys, pre-SABR eGFR (mean [standard deviation]) was 61.1 (23.2) versus 58.0 (22.3) ml/min (p = 0.32) and the median tumor size was 3.65 cm (IQR: 2.59-4.50 cm) versus 4.00 cm (IQR: 3.00-5.00 cm; p = 0.026). At 5 yr after SABR, eGFR decreased by -14.5 (7.6) and -13.3 (15.9) ml/min (p = 0.67), respectively, and there were similar rates of post-SABR dialysis (3.6% [n = 2/56] vs 3.7% [n = 5/134]). A multivariable analysis demonstrated that increasing tumor size (odds ratio [OR] per 1 cm: 1.57; 95% confidence interval [CI]: 1.14-2.16, p = 0.0055) and baseline eGFR (OR per 10 ml/min: 1.30; 95% CI: 1.02-1.66, p = 0.034) were associated with an eGFR decline of ≥15 ml/min at 1 yr. CONCLUSIONS AND CLINICAL IMPLICATIONS: With long-term follow-up after SABR, kidney function decline remains moderate, with no observed difference between patients with a solitary kidney and bilateral kidneys. Tumor size and baseline eGFR are dominant factors predictive of long-term renal function decline. PATIENT SUMMARY: With long-term follow-up, stereotactic ablative radiotherapy (SABR) yields moderate long-term renal function decline and low dialysis rates even in patients with a solitary kidney. SABR thus represents a promising noninvasive, nephron-sparing option for patients with localized renal cell carcinoma.

Impact of dexamethasone on transplant-related mortality in pediatric patients: a multi-site, propensity score-weighted, retrospective assessment.

Dexamethasone use during hematopoietic cell transplant (HCT) conditioning varies between pediatric centers. This study aimed to estimate the difference in 1-year treatment-related mortality (TRM) between patients who did or did not receive dexamethasone during HCT conditioning. Secondary objectives were to estimate the difference between dexamethasone-exposed and dexamethasone-unexposed groups in 1-year event-free survival (EFS), time to neutrophil engraftment, acute graft-versus-host disease (aGVHD), and invasive fungal disease (IFD) at day + 100. This was a seven-site, international, retrospective cohort study. Patients < 18 years old undergoing their first allogeneic or autologous myeloablative HCT for hematologic malignancy or aplastic anemia between January 1, 2012, and July 31, 2017, were included. To control for potential confounders, propensity score weighting was used to calculate the standardized mean difference for all endpoints. Among 242 patients, 140 received dexamethasone during HCT conditioning and 102 did not. TRM was unaffected by dexamethasone exposure (1.7%; 95% CI - 7.4, 10.2%). Between-group differences in secondary outcomes were small. However, dexamethasone exposure significantly increased possible, probable, and proven IFD incidence (9.0%, 95% CI 0.8, 17.3%). TRM is not increased in pediatric patients who receive dexamethasone during HCT conditioning. Clinicians should consider potential IFD risk when selecting chemotherapy-induced vomiting prophylaxis for pediatric HCT patients.

The brown algae: Sargassum binderi sonder bears potential nephroprotective activity in in-vivo experimental model.

OBJECTIVES: This study aimed to investigate the protective activity of brown seaweed, the ethanolic and water extracts of Sargassum binderi (S. binderi) were examined. Anticancer drug, cisplatin is normally used for the treatment of solid tumors that cause acute kidney damage after assemblage in the renal tubules. MATERIAL AND METHODS: It was an acute nephrotoxicity study, animals were divided into several groups randomly, cisplatin (7mg/kg i.p.) and normal saline were used as positive and negative control respectively. The S. bindari ethanolic and water extract were given orally in a dose of 200mg/kg for 5days. Various biomarkers were assessed to observe the nephroprotective potential, while antioxidant activities were investigated using reduced glutathione, catalase and malondialdehyde as oxidative stress. GCMS was performed to validate the presence of important therapeutic moieties. RESULTS: The current result justified that pretreatment with S. binderi inhibited the elevation of antioxidant parameters and also showed protection against lipid peroxidation, induced by cisplatin challenge. The overall impact was the nephroprotection, which has been revealed from the results. GCMS evaluation of hexanes fraction revealed the presence of therapeutically important compounds including heptasiloxane, 3,7,11,15-tetramethyl-2-hexadecen-1-ol, hexadecamethyl, cyclooctasiloxane, and hexadecamethyl. These compounds have been reported for their antioxidant, antibacterial, anticancer, and antifungal activities. CONCLUSION: S. binderi showed reno-protective effect by checking their well-known biochemical parameters probably due to the antioxidant activity as confirmed by the presence of compounds.

Quercetin and Kaempferol as Multi-Targeting Antidiabetic Agents against Mouse Model of Chemically Induced Type 2 Diabetes.

Diabetes, a multifactorial metabolic disorder, demands the discovery of multi-targeting drugs with minimal side effects. This study investigated the multi-targeting antidiabetic potential of quercetin and kaempferol. The druggability and binding affinities of both compounds towards multiple antidiabetic targets were explored using pharmacokinetic and docking software (AutoDock Vina 1.1.2). Our findings showed that quercetin and kaempferol obey Lipinski's rule of five and exhibit desirable ADMET (absorption, distribution, metabolism excretion, and toxicity) profiles. Both compounds showed higher binding affinities towards C-reactive protein (CRP), interleukin-1 (IL-1), dipeptidyl peptidase-4 (DPP-IV), peroxisome proliferator-activated receptor gamma (PPARG), protein tyrosine phosphatase (PTP), and sodium-glucose co-transporter-1 (SGLT-1) compared to metformin (the positive control). Both quercetin and kaempferol inhibited α-amylase activity (in vitro) up to 20.30 ± 0.49 and 37.43 ± 0.42%, respectively. Their oral supplementation significantly reduced blood glucose levels (p < 0.001), improved lipid profile (p < 0.001), and enhanced total antioxidant status (p < 0.01) in streptozotocin-nicotinamide (STZ-NA)-induced diabetic mice. Additionally, both compounds significantly inhibited the proliferation of Huh-7 and HepG2 (cancer cells) (p < 0.0001) with no effect on the viability of Vero cell line (non-cancer). In conclusion, quercetin and kaempferol demonstrated higher binding affinities towards multiple targets than metformin. In vitro and in vivo antidiabetic potential along with the anticancer activities of both compounds suggest promise for further development in diabetes management. The combination of both drugs did not show a synergistic effect, possibly due to their same target on the receptors.

A Case of Deep Venous Thrombosis in an HIV-Infected Patient despite Therapeutic Anticoagulation.

Patients with human immunodeficiency virus (HIV) infection have an increased likelihood of venous thromboembolism (VTE) owing to factors such as acquired protein C and S deficiency, antiphospholipid antibody syndrome, and heightened levels of pro-inflammatory cytokines. This case report highlights an exceptionally uncommon occurrence of deep venous thrombosis in an HIV-infected patient receiving a therapeutic dose of enoxaparin. This underscores the need for cautious consideration of the risk of VTE in HIV-infected individuals, even with preventive or therapeutic anticoagulant treatment. Further research is recommended to investigate HIV as a potential risk factor of prophylactic anticoagulation.

Individual and interactive effects of amino acid and paracetamol on growth, physiological and biochemical aspects of Brassica napus L. under drought conditions.

Drought stress poses a significant threat to Brassica napus (L.), impacting its growth, yield, and profitability. This study investigates the effects of foliar application of individual and interactive pharmaceutical (Paracetamol; 0 and 250 mg L-1) and amino acid (0 and 4 ml/L) on the growth, physiology, and yield of B. napus under drought stress. Seedlings were subjected to varying levels of drought stress (100% field capacity (FC; control) and 50% FC). Sole amino acid application significantly improved chlorophyll content, proline content, and relative water contents, as well as the activities of antioxidative enzymes (such as superoxide dismutase and catalase) while potentially decreased malondialdehyde and hydrogen peroxide contents under drought stress conditions. Pearson correlation analysis revealed strong positive correlations between these parameters and seed yield (R2 = 0.8-1), indicating their potential to enhance seed yield. On the contrary, sole application of paracetamol exhibited toxic effects on seedling growth and physiological aspects of B. napus. Furthermore, the combined application of paracetamol and amino acids disrupted physio-biochemical functions, leading to reduced yield. Overall, sole application of amino acids proves to be more effective in ameliorating the negative effects of drought on B. napus.

Characterisation and Expression Analysis of LdSERK1, a Somatic Embryogenesis Gene in Lilium davidii var. unicolor.

The Lanzhou lily (Lilium davidii var. unicolor) is a variant of the Sichuan lily of the lily family and is a unique Chinese 'medicinal and food' sweet lily. Somatic cell embryogenesis of Lilium has played an important role in providing technical support for germplasm conservation, bulb propagation and improvement of genetic traits. Somatic embryogenesis receptor-like kinases (SERKs) are widely distributed in plants and have been shown to play multiple roles in plant life, including growth and development, somatic embryogenesis and hormone induction. Integrating the results of KEGG enrichment, GO annotation and gene expression analysis, a lily LdSERK1 gene was cloned. The full-length open reading frame of LdSERK1 was 1875 bp, encoding 624 amino acids. The results of the phylogenetic tree analysis showed that LdSERK1 was highly similar to rice, maize and other plant SERKs. The results of the subcellular localisation in the onion epidermis suggested that the LdSERK1 protein was localised at the cell membrane. Secondly, we established the virus-induced gene-silencing (VIGS) system in lily scales, and the results of LdSERK1 silencing by Tobacco rattle virus (TRV) showed that, with the down-regulation of LdSERK1 expression, the occurrence of somatic embryogenesis and callus tissue induction in scales was significantly reduced. Finally, molecular assays from overexpression of the LdSERK1 gene in Arabidopsis showed that LdSERK1 expression was significantly enhanced in the three transgenic lines compared to the wild type, and that the probability of inducing callus tissue in seed was significantly higher than that of the wild type at a concentration of 2 mg/L 2,4-D, which was manifested by an increase in the granularity of the callus tissue.

Emerging Novel Functional Imaging and Immunotherapy in Renal Cell Carcinoma and Current Treatment Sequencing Strategies After Immunotherapy.

The management of renal cell carcinoma (RCC) has advanced significantly in the past two decades. Many promising functional imaging modalities such as radiolabeled tracer targeting carbonic anhydrase IX and prostate-specific membrane antigen are under development to detect primary kidney tumors, stage systemic disease, and assess treatment response in RCC. Immune checkpoint inhibitors targeting PD-1 and cytotoxic T-cell lymphocyte-4 have changed the treatment paradigm in advanced RCC. Trials investigating novel mechanisms such as LAG-3 immune checkpoint inhibition, chimeric antigen receptor T-cell therapies, and T-cell engagers targeting RCC-associated antigens are currently ongoing. With the rapidly changing treatment landscape of RCC, the treatment sequence strategies will continue to evolve. Familiarity with the toxicities associated with the therapeutic agents and how to manage them are essential to achieve optimal patient outcomes. This review summarizes the recent developments of functional imaging and immunotherapy strategies in RCC, and the evidence supports treatment sequencing.