Randomized investigation of the MitraClip device in heart failure: Design and rationale of the RESHAPE-HF2 trial design.

AIMS: The safety and effectiveness of the MitraClip device to treat functional mitral regurgitation (FMR) has been tested in previous clinical trials yielding somewhat heterogeneous results in heart failure (HF) patients. Over time, the MitraClip device system has been modified and clinical practice evolved to consider also less severely diseased HF patients with FMR for this therapeutic option. The RESHAPE-HF2 trial aims to assess the safety and effectiveness of the MitraClip device system on top of medical therapy considered optimal in the treatment of clinically significant FMR in symptomatic patients with chronic HF. METHODS: The RESHAPE-HF2 is an investigator-initiated, prospective, randomized, parallel-controlled, multicentre trial designed to evaluate the use of the MitraClip device (used in the most up-to-date version as available at sites) plus optimal standard of care therapy (device group) compared to optimal standard of care therapy alone (control group). Eligible subjects have signs and symptoms of HF (New York Heart Association [NYHA] class II-IV despite optimal therapy), and have moderate-to-severe or severe FMR, as confirmed by a central echocardiography core laboratory; have an ejection fraction between ≥20% and ≤50% (initially 15-35% for NYHA class II patients, and 15-45% for NYHA class III/IV patients); have been adequately treated per applicable standards, and have received appropriate revascularization and cardiac resynchronization therapy, if eligible; had a HF hospitalization or elevated natriuretic peptides (B-type natriuretic peptide [BNP] ≥300 pg/ml or N-terminal proBNP ≥1000 pg/ml) in the last 90 days; and in whom isolated mitral valve surgery is not a recommended treatment option. The trial has three primary endpoints, which are these: (i) the composite rate of total (first and recurrent) HF hospitalizations and cardiovascular death during 24 months of follow-up, (ii) the rate of total (i.e. first and recurrent) HF hospitalizations within 24 months, and (iii) the change from baseline to 12 months in the Kansas City Cardiomyopathy Questionnaire overall score. The three primary endpoints will be analysed using the Hochberg procedure to control the familywise type I error rate across the three hypotheses. CONCLUSIONS: The RESHAPE-HF2 trial will provide sound evidence on the MitraClip device and its effects in HF patients with FMR. The recruitment was recently completed with 506 randomized patients.

Antioxidant and Anti-inflammatory Applications of Aerva persica Aqueous-Root Extract-Mediated Synthesis of ZnO Nanoparticles.

In the present study, ZnO nanoparticles were synthesized by using aqueous extracts of Aerva persica roots. Characterization of as-prepared ZnO nanoparticles was carried out using different techniques, including powder X-ray diffraction (XRD), UV-vis diffuse reflectance spectroscopy (DRS), Fourier transform infrared (FTIR) spectroscopy, field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM) and BET surface area analysis. Morphological analysis confirmed the small, aggregated flake-shaped morphology of as-synthesized ZnO nanostructures. The as-prepared ZnO nanoparticles were analyzed for their potential application as anti-inflammatory (using in vivo inhibition of carrageenan induced paw edema) and antioxidant (using in vitro radical scavenging activity) agents. The ZnO nanoparticles were found to have a potent antioxidant and anti-inflammatory activity comparable to that of standard ascorbic acid (antioxidant) and indomethacin (anti-inflammatory drug). Therefore, due to their ecofriendly synthesis, nontoxicity, and biocompatible nature, zinc oxide nanoparticles synthesized successfully from roots extract of the plant Aerva persica with potent efficiencies can be utilized for different biomedical applications.

Folk Knowledge and Perceptions about the Use of Wild Fruits and Vegetables-Cross-Cultural Knowledge in the Pipli Pahar Reserved Forest of Okara, Pakistan.

Wild fruits and vegetables (WFVs) have been vital to local communities for centuries and make an important contribution to daily life and income. However, traditional knowledge of the use of wild fruits is at risk of being lost due to inadequate documentation. This study aimed to secure this knowledge through intermittent field visits and a semi-structured questionnaire. Using various ethnobotanical data analysis tools and SPSS (IBM 25), this study identified 65 WFV species (52 genera and 29 families). These species, mostly consumed as vegetables (49%) or fruits (43%), were predominantly herbaceous (48%) in wild and semi-wild habitats (67%). 20 WFVs were known to local communities (highest RFC), Phoenix sylvestris stood out as the most utilized species (highest UV). Surprisingly, only 23% of the WFVs were sold at markets. The survey identified 21 unique WFVs that are rarely documented for human consumption in Pakistan (e.g., Ehretia obtusifolia, Euploca strigosa, Brassica juncea, Cleome brachycarpa, Gymnosporia royleana, Cucumis maderaspatanus, Croton bonplandianus, Euphorbia prostrata, Vachellia nilotica, Pongamia pinnata, Grewia asiatica, Malvastrum coromandelianum, Morus serrata, Argemone mexicana, Bambusa vulgaris, Echinochloa colonum, Solanum virginianum, Physalis angulata, Withania somnifera, Zygophyllum creticum, and Peganum harmala), as well as 14 novel uses and five novel edible parts. Despite their ecological importance, the use of WFVs has declined because local people are unaware of their cultural and economic value. Preservation of traditional knowledge through education on conservation and utilization could boost economies and livelihoods in this and similar areas worldwide.

Unveiling the mechanisms and challenges of cancer drug resistance.

Cancer treatment faces many hurdles and resistance is one among them. Anti-cancer treatment strategies are evolving due to innate and acquired resistance capacity, governed by genetic, epigenetic, proteomic, metabolic, or microenvironmental cues that ultimately enable selected cancer cells to survive and progress under unfavorable conditions. Although the mechanism of drug resistance is being widely studied to generate new target-based drugs with better potency than existing ones. However, due to the broader flexibility in acquired drug resistance, advanced therapeutic options with better efficacy need to be explored. Combination therapy is an alternative with a better success rate though the risk of amplified side effects is commonplace. Moreover, recent groundbreaking precision immune therapy is one of the ways to overcome drug resistance and has revolutionized anticancer therapy to a greater extent with the only limitation of being individual-specific and needs further attention. This review will focus on the challenges and strategies opted by cancer cells to withstand the current therapies at the molecular level and also highlights the emerging therapeutic options -like immunological, and stem cell-based options that may prove to have better potential to challenge the existing problem of therapy resistance. Video Abstract.

Band Gap Alteration of Halide Mixing in Hybrid Perovskites: A First-Principles Study with Statistical Analysis.

Despite numerous studies on the band gap of three-dimensional halide perovskites using the first-principles calculations, there are still significant discrepancies between theoretical and experimental values. Various solutions have been proposed, such as employing a system-specific hybrid functional with varying degrees of exact exchange and explicitly incorporating spin-orbit coupling effects. Our research involved a comprehensive investigation of three typical lead-containing three-dimensional perovskites MAPbI3, MAPbBr3, and MAPbCl3 (MA = CH3NH3). Through a statistical analysis comparing mean absolute error (MAE) with experimental results, we demonstrated that the nonlocal van der Waals (vdW) density functional corrections (i.e., optB86b) yielded the most approximate lattice parameters in comparison to experimental values. Furthermore, based on these lattice parameters, the HSE06 hybrid functional is the optimal estimation of the band gap among all the options. Moreover, we investigated three sets of mixed three-dimensional halide perovskites by varying the halide component. This exploration contributes to the identification of MAPb(Br0.333I0.667)3 and MAPb(Cl0.333I0.667)3 as exhibiting the smallest band gap of 1.315 (1.867) eV and 1.313 (1.885) eV for PBE (HSE06), respectively. These band gaps were determined using the HSE06 method with the optimized lattice by PBE considering the optB86b corrections. The approach employed in this work produced a band gap trend closely aligned with experimental observations, underscoring the importance of adopting a reliable and material-independent computational strategy when screening new halide perovskite materials for optoelectronic applications.

Concomitant transthyretin cardiac amyloidosis in patients undergoing TAVR for aortic stenosis: A systemic review and meta-analysis.

OBJECTIVE: Transcatheter aortic valve replacement (TAVR) is a successful treatment for aortic stenosis (AS) patients, and previous studies indicate favorable outcomes for those with concomitant aortic stenosis and transthyretin-associated cardiac amyloidosis (TTRCA-AS). However, the impact of TAVR on more adverse outcomes in TTRCA-AS patients compared to those with AS alone is still uncertain, with conflicting findings reported in the literature. METHODS: PubMed and Scopus were extensively searched from inception till August 2021. Studies were included if they reported data for prevalence and outcomes including mortality and cardiovascular-related hospitalization events in TTRCA-AS patients referred for TAVR. The data for these outcomes were pooled using a random effects model and forest plots were created. RESULTS: After initially screening 146 articles, 6 were shortlisted for inclusion in our analysis. Pooled analysis demonstrated a 13.3% [95% CI: 10.9-16.5; p = 0.307] prevalence of TTRCA in patients with AS undergoing TAVR. The incidence of mortality and cardiovascular (CV) hospitalization in patients with TTRCA-AS undergoing TAVR were 28.3% [95% CI: 18.7-39.0, p = 0.478] and 21.1% [95% CI: 10.2-34.5, p = 0.211], respectively. CONCLUSION: The overall pooled TTRCA-AS prevalence was reported to be 13.3% in AS patients who underwent TAVR. Furthermore, transthyretin-associated CA was found to be associated with an increased risk of mortality and hospitalization. Large patient population studies are required to assess the safety and efficacy of TAVR in TTRCA-AS patients, as current research report data from small patient cohorts.

Dual Fluorimetric Sensor for Tandem Detection of Cadmium and Cysteine: An Approach for Designing a Molecular Keypad Lock System.

A fluorimetric sensor for dual and sensitive detection of Cd2+ ion and Cysteine (based on 2-picolylamine platform) was developed.The sensor was designed and synthesized by simple condensation method and characterized by using common spectroscopic methods. The observations made from the kinetics of absorption and emission profile shows that probe Pdac behaves as ''ON-OFF'' fluorescent quenching sensor for cadmium ions. The probe exhibit selectivity in fluorescence quenching behaviour over other competitive metal ions, and also the Pdac-Cd2+ ensemble behave as an efficient ''OFF-ON'' type sensor for an essential amino acid Cysteine. Moreover, this dual sensing nature of the sensor makes it successfully applied for the designing of a molecular keypad lock system.

Oral glutamine: Is there a role in the amelioration of radiation-induced mucositis? A prospective case-control study at a tertiary care centre in North India.

BACKGROUND: The most frequently occurring painful and dose-limiting side effect of radiation therapy (RT) to the head and neck region is oral mucositis (OM). Several studies demonstrated that glutamine may reduce the severity and the duration of OM significantly during RT and chemo-radiotherapy in patients with head and neck cancer (HNC). MATERIALS AND METHODS: Between January 2021 and August 2022, a prospective single institutional case-control study compared the efficacy and safety of oral glutamine on radiation-induced mucositis in patients with HNC. Of 60 biopsy-proven patients with HNC, 30 patients in the study arm received oral glutamine suspension (10 g in 500 mL of water) orally once daily, 2 hours before RT, receiving definitive or adjuvant RT and chemo-radiotherapy, while as 30 patients in the control arm received placebo with the same dose and schedule (n = 30 in the study arm and n = 30 in the control arm). RESULTS AND ANALYSIS: A total of 27 (90%) in the glutamine arm and 28 (93.33%) patients in the control arm developed mucositis. Grade 3 mucositis (13.33%) and Grade 4 mucositis (6.66%), respectively, were significantly less (P = .040 and P = .004) in the glutamine arm. The mean duration of grade 3 and grade 4 mucositis was significantly less in the glutamine arm (8.94 days in the study arm vs. 14.54 in the control arm; P = .0001). The mean time of onset of OM was significantly delayed in the glutamine arm in comparison to the control arm with P < .001. CONCLUSION: Glutamine delays the onset of OM and decreases the severity of OM in patients of HNC receiving RT with or without chemotherapy.

Long-term efficacy of spinal cord stimulation for chronic primary neuropathic pain in the contemporary era: a systematic review and meta-analysis.

INTRODUCTION: Spinal cord stimulation (SCS) is a modern neuromodulation technique extensively proven to be an effective modality for treatment of chronic neuropathic pain. It has been mainly studied for complex regional pain syndrome (CRPS) and failed back surgery syndrome (FBSS) and recent data almost uniformly establishes its statistically significant positive therapeutic results. It has also been compared with other available treatment modalities across various studies. However, long term data on maintenance of its efficacious potential remains less explored. Few studies have reported data on long follow-up times (>= 12 months) and have compared its efficacy with other treatment options for chronic pain, respectively. Our study pools and analyzes the available data and compares SCS with other treatment options. It also analyzes the efficacy of SCS in long term management of patients with chronic pain. EVIDENCE ACQUISITION: We reviewed all the data available on MEDLINE, Embase and Cochrane CENTRAL using a search strategy designed to fit our pre-set inclusion and exclusion criteria. Both single-arm and double-arm studies were included. The primary outcome was defined as decrease of visual analogue scale (VAS) by >50% at 6, 12 and/or 24 months after SCS. EVIDENCE SYNTHESIS: According to the pooled data of double-arm studies, SCS has unanimously proven its superiority over other treatment options at 6 months follow-up; however it fails to prove statistically significant difference in results at longer treatment intervals. Dorsal root ganglion stimulation, a relatively recent technique with the same underlying physiologic mechanisms as SCS, showed far more promising results than SCS. Single-arm studies show around 70% patients experiencing greater than 50% reduction in their VAS scores at 6 and 12 months. CONCLUSIONS: SCS is a viable option for management of chronic neuropathic pain secondary to FBSS and CRPS. However, data available for its long term efficacy remains scarce and show no further statistically significant results.

The evaluation of bacterial-augmented floating treatment wetlands for concomitant removal of phenol and chromium from contaminated water.

Contamination of aquatic ecosystems with organic and inorganic contaminants is a global threat due to their hazardous effects on the environment and human health. Floating treatment wetland (FTW) technology is a cost-effective and sustainable alternative to existing treatment approaches. It consists of a buoyant mat in which wetland plants can grow and develop their roots in a suspended manner and can be implemented to treat stormwater, municipal wastewater, and industrial effluents. Here we explored the potential of bacterial-augmented FTWs for the concurrent remediation of phenol and hexavalent chromium (Cr6+) contaminated water and evaluated treated water toxicity using Triticum aestivum L. (wheat) as a test plant. The FTWs carrying Phragmites australis L. (common reed) were inoculated with a consortium of four bacterial strains (Burkholderia phytofirmans PsJN, Acinetobacter lwofii ACRH76, Pseudomonas aeruginosa PJRS20, Bacillus sp. PJRS25) and evaluated for their potential to simultaneously remove phenol and chromium (Cr) from contaminated water. Results revealed that the FTWs efficiently improved water quality by removing phenol (86%) and Cr (80%), with combined use of P. australis and bacterial consortium after 50 days. The phytotoxicity assay demonstrated that the germination of wheat seed (96%) was significantly higher where bacterial-augmented FTWs treated water was used compared to untreated water. This pilot-scale study highlights that the combined application of wetland plants and bacterial consortium in FTWs is a promising approach for concomitant abatement of phenol and Cr from contaminated water, especially for developing countries like Pakistan where the application of advanced and expensive technologies is limited.

This pilot-scale research provides new interventions and information required for establishing a large-scale remediation framework for the effective, sustainable and eco-friendly remediation of phenol and Cr co-contaminated aquatic ecosystems, using bacterial augmented floating wetlands technology (FTWs).

Diffusion-Weighted Imaging and Chemical Shift Imaging to Differentiate Benign and Malignant Vertebral Lesion: A Hospital-Based Cross-Sectional Study.

Objective The aim of this study was to evaluate the role of diffusion-weighted imaging (DWI) and chemical shift imaging (CSI) for the differentiation of benign and malignant vertebral lesions. Methods Patients with vertebral lesions underwent routine magnetic resonance imaging (MRI) along with DWI and CSI. Qualitative analysis of the morphological features was done by routine MRI. Quantitative analysis of apparent diffusion coefficient (ADC) from DWI and fat fraction (FF) from CSI was done and compared between benign and malignant vertebral lesions. Results Seventy-two patients were included. No significant difference was noted in signal intensities of benign and malignant lesions on conventional MRI sequences. Posterior element involvement, paravertebral soft-tissue lesion, and posterior vertebral bulge were common in malignant lesion, whereas epidural/paravertebral collection, absence of posterior vertebral bulge, and multiple compression fractures were common in benign vertebral lesion ( p < 0.001). The mean ADC value was 1.25 ± 0.27 mm 2 /s for benign lesions and 0.9 ± 0.19 mm 2 /s for malignant vertebral lesions ( p ≤ 0.001). The mean value of FF was 12.7 ± 7.49 for the benign group and 4.04 ± 2.6 for the malignant group ( p < 0.001). A receiver operating characteristic (ROC) curve analysis showed that an ADC cutoff of 1.05 × 10 -3 mm 2 /s and an FF cutoff of 6.9 can differentiate benign from malignant vertebral lesions, with the former having 86% sensitivity and 82.8% specificity and the latter having 93% sensitivity and 96.6% specificity. Conclusion The addition of DWI and CSI to routine MRI protocol in patients with vertebral lesions promises to be very helpful in differentiating benign from malignant vertebral lesions when difficulty in qualitative interpretation of conventional MR images arises.

The subset of peroxisomal tail-anchored proteins do not reach peroxisomes via ER, instead mitochondria can be involved.

Peroxisomes are membrane-enclosed organelles with important roles in fatty acid breakdown, bile acid synthesis and biosynthesis of sterols and ether lipids. Defects in peroxisomes result in severe genetic diseases, such as Zellweger syndrome and neonatal adrenoleukodystrophy. However, many aspects of peroxisomal biogenesis are not well understood. Here we investigated delivery of tail-anchored (TA) proteins to peroxisomes in mammalian cells. Using glycosylation assays we showed that peroxisomal TA proteins do not enter the endoplasmic reticulum (ER) in both wild type (WT) and peroxisome-lacking cells. We observed that in cells lacking the essential peroxisome biogenesis factor, PEX19, peroxisomal TA proteins localize mainly to mitochondria. Finally, to investigate peroxisomal TA protein targeting in cells with fully functional peroxisomes we used a proximity biotinylation approach. We showed that while ER-targeted TA construct was exclusively inserted into the ER, peroxisome-targeted TA construct was inserted to both peroxisomes and mitochondria. Thus, in contrast to previous studies, our data suggest that some peroxisomal TA proteins do not insert to the ER prior to their delivery to peroxisomes, instead, mitochondria can be involved.

A Rare Case of Pediatric Nasopharyngeal Rhabdomyosarcoma With Parameningeal Extension Presenting as a Thornwaldt Cyst.

Rhabdomyosarcoma (RMS) is a common soft tissue malignancy of the pediatric age group, frequently involving the head and neck region; however, nasopharyngeal RMS is a rare entity. By virtue of its parameningeal involvement and nonspecific presentations, nasopharyngeal RMS has become a clinical challenge to diagnose. We present a case of an eight-year-old boy presenting with signs and symptoms of nasal obstruction who was initially being treated for tonsillitis. Recurrent episodes led to detailed examination and radiologic imaging, and a diagnosis of Thornwaldt cyst was made. For the relief of symptoms, a debulking surgery was performed followed by a biopsy which revealed the mass to be a nasopharyngeal RMS. Our case highlights the importance of including nasopharyngeal RMS into the differentials of midline nasal masses along with the role of biopsy for confirming its diagnosis as treatment modalities for it are strikingly different than the other more common group of conditions, i.e., benign nasal masses. While surgery is usually delayed in the latter group, it can be of prime importance while treating nasal RMS, along with chemotherapy and radiotherapy.

Carcinoma cervix: A single institute experience from Kashmir, Northern India.

Background: Carcinoma cervix is the fourth most commonly diagnosed cancer worldwide, with an estimated 604,000 new cases and 342,000 deaths worldwide in 2020. Carcinoma cervix is an uncommon malignancy in Kashmir. In this retrospective study, we have tried to find clinicopathological characteristics of carcinoma cervix along with the survival rates at our tertiary care hospital. Materials and Methods: Case records of cervical cancer patients registered from January 1, 2015, to January 1, 2019, were retrieved. A total of 138 patients was registered. 22 had undergone surgery, and out of these 17 had received postoperative radiotherapy. 109 patients were treated with definitive chemoradiation and 13 with palliative radiotherapy. Descriptive statistics were used to summarize patient and treatment-related variables, and Kaplan-Meier analysis was performed for survival analysis. Results: A total of 138 cases that were registered from 2015 to 2019 were included in this study. The median age at the presentation was 56 years. Most of the patients had a performance status of 1 (98 patients (71.01)). Most of the patients 110 (79.71%) were married before 20 years of age, only 1 patient was unmarried, and 85 (61.59) patients were multiparous in our study group. Only 14 (10.14%) patients in our study group had a history of oral contraceptive use and most of them were non-smokers [124 (89.80%)]. Multiple marriages were present in 8 (5.79%) patients only. The most common presenting symptom was bleeding per vagina (78.26%), and the maximum number of patients fall in the post-menopausal group (67.39%). 116 patients had squamous cell carcinoma histology while 10 patients had adenocarcinoma histology. Most of the patients had stage II and stage III disease (85 patients). At last, follow up out of 138 patients 75 (54.35) were alive. 3 year disease-free survival was 54.34% and 3-year overall survival was 72.46%. Conclusion: Carcinoma cervix is an uncommon malignancy in Kashmir because of different socio-cultural and religious practices but the response to treatment, toxicity profile, and survival are similar to the rest of the world.

Safety and efficacy of insulin detemir vs. insulin NPH in pregnant women with diabetes: a systematic review and meta-analysis.

INTRODUCTION: The relative efficacy and safety of insulin neutral protamine Hagedorn (NPH) and detemir (IDet), in the management of diabetes in pregnancy remains unclear. We sought to conduct an updated systematic review and meta-analysis to study the effect of NPH versus IDet during pregnancy on clinically relevant maternal and fetal outcomes. EVIDENCE ACQUISITION: MEDLINE and Google Scholar were queried from inception till September 2022 for original studies comparing NPH with IDet for management of diabetes during pregnancy. Data was pooled using a random-effects model, to generate risk ratios (RR) for dichotomous outcomes and weighted mean differences (WMDs) for continuous outcomes, along with 95% confidence intervals (CIs). I2 test was used to assess the magnitude of heterogeneity. Sensitivity analysis was conducted to explore the potential source of heterogeneity. As less than ten studies were included in our analysis, funnel plots were not made to evaluate publication bias. A P value of ≤0.05 was considered significant in all cases. EVIDENCE SYNTHESIS: Our search of the literature yielded 1087 articles initially, of which seven articles comprising 1396 patients, were included in our analysis. All included articles were of reasonably high methodological quality. Our pooled analysis demonstrates no statistically significant difference between the efficacy of insulin Detemir and insulin NPH as assessed by the HbA1c values from baseline. For safety outcomes, insulin detemir was significantly associated with a greater gestational age at delivery (WMD=0.39, 95%CI: 0.07 to 0.71, P=0.02) and lower incidence of hypoglycemic events (RR=0.64, 95%CI: 0.48 to 0.86, P=0.003) in-contrast to insulin NPH. CONCLUSIONS: Our findings demonstrate that both, insulin IDet and insulin NPH have a similar efficacy in reducing HbA1c from baseline. However, insulin detemir was associated with lesser incidence of maternal hypoglycemic events and greater gestational age at delivery, compared to NPH.

Study of Involuntary Limb Movements as a Presenting Feature in Nonketotic Hyperglycemia.

Background Hyperglycaemia can rarely manifest as hemichorea/hemiballismus, which subsides with adequate control of blood sugar. Our study accounted for patients with abnormal, involuntary limb movements with high blood sugar, excluding other conditions leading to or mimicking such a clinical appearance. It is very important to identify such patients as chorea secondary to an underlying etiology like hyperglycemia, which can be cured. Material & methods This study was done in IMS & SUM Hospital for a duration of one year, from March 2019 to February 2020, with a total of 11 cases with abnormal limb movements with a blood sugar of 250 mg% and above. Results In this study, 36.36%( n=4) of patients were female, and 63.63% (n=7) were males. The mean age of the patients at presentation was 66.5 years. Eighteen point one percent (18.1%; n=2) of the patients showed hemiballismus, 36.3% (n=4) showed hemichorea, 18.1% (n=2) showed hemiathetosis, 9.1% (n=1) showed myoclonus, and 18.1% (n=2) showed hemiballismus with hemichorea. The mean duration to correct hyperglycemia was found to be 34 hours and the mean duration to correct abnormal limb movements was 90.54 hours. Eighty-one point eight percent (81.8%; n=9) of patients showed basal ganglia changes on brain imaging.

Bleeding Control in Advanced Gastric Cancer; Role of Radiotherapy.

Objectives: The aim of our study is to see the efficacy of palliative radiotherapy (RT) for bleeding control in patients with advanced gastric cancer (AGC). Materials and Methods: It is a retrospective review based on observations of 74 AGC patients with a median age of 60 years (range 50-82 years) who had active tumour bleeding and were treated with palliative RT. Treatment response was assessed by both subjective symptom relief and objective change in parameters. Objective response to RT was defined by an increase in the median haemoglobin (Hb) level of patients and a decrease in number of packed red blood cell (RBC) units needed by patients after RT. Results: Response to haemostatic RT was observed in 52 patients out of 74 patients (70.27%). We observed a significant increase in mean Hb level after palliative RT. Pre-RT mean Hb was 6.14 ± 1.01 and post-RT mean Hb was 7.19 ± 1.75 (P < 0.05). Response to RT was also evident in a significant decrease in the number of packed RBC units post-haemostatic RT. The mean number of pre-RT transfused packed RBC units was 8.28 ± 3.76 and post-RT, it was 4.34 ± 2.91 (P < 0.05). The median overall survival was 90 days and the median transfusion-free survival was 40 days. Conclusion: RT may be an effective treatment option for bleeding control in AGC. In our study, we observed fair and reasonably durable haemostasis. A success rate of 70.24% was documented with clinical palliation, a higher Hb level and fewer transfusions after RT. This modality for bleeding control is more important and reliable in situations where alternative modalities are not feasible.

Cancer metastasis: Molecular mechanisms and clinical perspectives.

Metastatic progression combined with non-responsiveness towards systemic therapy often shapes the course of disease for cancer patients and commonly determines its lethal outcome. The complex molecular events that promote metastasis are a combination of both, the acquired pro-metastatic properties of cancer cells and a metastasis-permissive or -supportive tumor micro-environment (TME). Yet, dissemination is a challenging process for cancer cells that requires a series of events to enable cancer cell survival and growth. Metastatic cancer cells have to initially detach themselves from primary tumors, overcome the challenges of their intravasal journey and colonize distant sites that are suited for their metastases. The implicated obstacles including anoikis and immune surveillance, can be overcome by intricate intra- and extracellular signaling pathways, which we will summarize and discuss in this review. Further, emerging modulators of metastasis, like the immune-microenvironment, microbiome, sublethal cell death engagement, or the nervous system will be integrated into the existing working model of metastasis.

Evaluation of Nootropic Potential of Aerva persica Roots against D-galactose-induced Memory Impairment.

BACKGROUND: The primary phytoconstituents reported to have neuroprotective effects are flavonoids and phenolic compounds. Aerva persica roots are reported to be rich in flavonoids and phenolic compounds. Therefore, this study aimed to explore the nootropic potential of Aerva persica roots. OBJECTIVE: The objective of this study was to evaluate the nootropic potential of Aerva persica roots against D-galactose-induced memory impairment. METHODS: In this study, the roots of Aerva persica were extracted with 70% ethanol. The obtained extract was evaluated for total phenolic content using the Folin-Ciocalteu method and total flavonoid content using the aluminium chloride colorimetric assay. Afterward, the acute oral toxicity of the extract was determined following the Organisation for Economic Co-operation and Development (OECD) guideline 423. Additionally, two doses of Aerva persica (100 and 200 mg/kg body weight (BW)) were evaluated for their nootropic potential against D-galactose-induced memory impairment. The nootropic potential of the crude extract was assessed through a behavioural study and brain neurochemical analysis. Behavioural studies involved the evaluation of spatial reference- working memory using the radial arm maze test and the Y-maze test. Neurochemical analysis was performed to determine the brain's acetylcholine, acetylcholinesterase, glutathione (GSH), and malondialdehyde (MDA) levels. RESULTS: The total phenolic content and total flavonoid content were found to be 179.14 ± 2.08 µg GAE/mg and 273.72 ± 3.94 µg QE/mg, respectively. The Aerva persica extract was found to be safe up to 2000 mg/kg BW. Following the safety assessment, the experimental mice received various treatments for 14 days. The behavioural analysis using the radial maze test showed that the extract at both doses significantly improved spatial reference-working memory and reduced the number of total errors compared to disease control groups. Similarly, in the Y-maze test, both doses significantly increased the alteration percentage and the percentage of novel arm entry (both indicative of intact spatial memory) compared to disease control. In neurochemical analysis, Aerva persica at 200 mg/kg significantly normalised the acetylcholine level (p<0.0001) and GSH level (p<0.01) compared to disease control. However, the same effect was not observed with Aerva persica at 100 mg/kg. Additionally, Aerva persica at 200mg/kg BW significantly decreased the acetylcholinesterase level (p<0.0001) and decreased the brain's MDA level (p<0.01) compared to the disease control, whereas the effect of Aerva persica at 100 mg/kg BW in reducing acetylcholinesterase was non-significant. CONCLUSION: Based on the results, it can be concluded that the nootropic potential of Aerva persica was comparable to that of the standard drug, Donepezil, and the effect might be attributed to the higher content of flavonoids and phenolic compounds.