Bench-to-bedside imaging in brain metastases: a road to precision oncology.

Radiology has seen tremendous evolution in the last few decades. At the same time, oncology has made great strides in diagnosing and treating cancer. Distant metastases of neoplasms are being encountered more often in light of longer patient survival due to better therapeutic strategies and diagnostic methods. Brain metastasis (BM) is a dismal manifestation of systemic cancer. In the present scenario, magnetic resonance imaging (MRI), computed tomography (CT) and positron emission tomography (PET) are playing a big role in providing molecular information about cancer. Lately, molecular imaging has emerged as a stirring arena of dynamic imaging techniques that have enabled clinicians and scientists to noninvasively visualize and understand biological processes at the cellular and molecular levels. This knowledge has impacted etiopathogenesis, detection, personalized treatment, drug development, and our understanding of carcinogenesis. This article offers insight into the molecular biology underlying brain metastasis, its pathogenesis, imaging protocols, and algorithms. It also discusses disease-specific molecular imaging features, focusing on common tumors that spread to the brain, such as lung, breast, colorectal cancer, melanoma, and renal cell carcinoma. Additionally, it covers various targeted treatment options, criteria for assessing treatment response, and the role of artificial intelligence in diagnosing, managing, and predicting prognosis for patients with brain metastases.

Cardiovascular risk factors and carotid intima-media thickness with neurocognitive dysfunction in people living with HIV on stable combination anti-retroviral therapy.

The goal of this clinical research was to determine the relationship between carotid intima-media thickness (cIMT), cardiovascular risk factors, and neuro-cognitive function in people living with HIV (PLHIV) and were on stable combination anti-retroviral therapy (cART). This is a cross-sectional study performed at a single center, including 149 patients who visited the anti-retroviral therapy center of our tertiary care hospital. Among the PLHIV of our research, 62.4% had at least one associated cardiovascular risk factor, and 61.1% of them had abnormally high cIMT (≥ 0.9 mm on any one side, p = 0.035). These factors and being the male gender (p = 0.028) were associated with a greater Framingham 10-year risk percentage. Hypercholesterolemia was observed in 30.9% of the PLHIV and a higher body mass index (≥ 25 kg/m2) was found in 26.8% of them. The cognitive impairment was milder in 71.8% of cases and moderate in 9.4% of PLHIV. The Chi-square test revealed that a higher proportion of participants who had lower HDL-C levels (p = 0.045), smokers (p = 0.029), systolic blood pressure ≥ 140 mmHg (p = 0.012), and lower educational status (p = 0.017) had a poorer cognitive performance. In our sample population, a higher prevalence of elevated cIMT, cardiovascular risk factors, and mild and moderate cognitive deficiency was observed in PLHIV, who were on stable cART. However, routine assessment of the neuropsychological functions and management of modifiable risk factors are not performed in our patients. Further exploration of the relationship between cardiovascular risks, cIMT, and cognitive impairment in PLHIV is essential to formulate the guidelines and delay the onset of neurocognitive disorders in these patients.

Management of plant nutrient dynamics under alkaline soils through graded application of pressmud and gypsum.

An incubation experiment was conducted to monitor the effect of different organic matter inputs with the graded application of gypsum at different time intervals on soil pH, sodium (Na) content and available plant nutrients like nitrogen (N) and sulphur (S) in alkaline soil. The experiment was formulated with nine treatments, i.e. control (T1), recommended dose of fertilizer (RDF) (T2), RDF+Gyp1 (T3), RDF+FYM5+Gyp2 (T4), RDF+FYM10+Gyp1 (T5), RDF+PM5+Gyp2 (T6), RDF+PM10+Gyp1 (T7), RDF+FYM2.5+PM2.5+Gyp2 (T8), RDF+FYM5+PM5+Gyp1 (T9) with three replications. Periodical soil samples were taken at six and twelve months intervals. Results showed that the addition of organic matter reduced the pH and Na content in the soil. More reduction was observed at one year period as compared to six months. The addition of farmyard manure (FYM) and pressmud (PM) at 10 t/ha with gypsum (1 t/ha) improved available N and available S content as compared to organic inputs (5 t/ha) with gypsum (2 t/ha) in soil. Pressmud application with FYM showed better availability of plant nutrients and a reduction of soil pH (8.39 to 7.79) and Na content from 626 to 391 mEq/L in the soil during the incubation period. During the study, the application of treatment T9 (FYM and PM in equal ratio with 1 t/ha gypsum) showed a better availability of available N (175 to 235 kg/ha) and S (15.44 to 23.24 kg/ha) and reduced the active ion concentration of Na. This study is very useful for the management of sodium toxicity, improving soil health and the mineralization rate of organic matter through the application of organic inputs for sustainable crop production.

Citrinin as a potential anti-cancer therapy: A comprehensive review.

Citrinin (CIT) is a polyketide-derived mycotoxin, which is produced by many fungal strains belonging to the gerena Monascus, Aspergillus, and Penicillium. It has been postulated that mycotoxins have several toxic mechanisms and are potentially used as antineoplastic agents. Therefore, the present study carried out a systematic review, including articles from 1978 to 2022, by collecting evidence in experimental studies of CIT antiplorifactive activity in cancer. The Data indicate that CIT intervenes in important mediators and cell signaling pathways, including MAPKs, ERK1/2, JNK, Bcl-2, BAX, caspases 3,6,7 and 9, p53, p21, PARP cleavage, MDA, reactive oxygen species (ROS) and antioxidant defenses (SOD, CAT, GST and GPX). These factors demonstrate the potential antitumor drug CIT in inducing cell death, reducing DNA repair capacity and inducing cytotoxic and genotoxic effects in cancer cells.

Implications of genetic variations, differential gene expression, and allele-specific expression on metformin response in drug-naïve type 2 diabetes.

PURPOSE: Metformin is widely used to treat type 2 diabetes mellitus (T2DM) individuals. Clinically, inter-individual variability of metformin response is of significant concern and is under interrogation. In this study, a targeted exome and whole transcriptome analysis were performed to identify predictive biomarkers of metformin response in drug-naïve T2DM individuals. METHODS: The study followed a prospective study design. Drug-naïve T2DM individuals (n = 192) and controls (n = 223) were enrolled. T2DM individuals were administered with metformin monotherapy and defined as responders and non-responders based on their glycated haemoglobin change over three months. 146 T2DM individuals were used for the final analysis and remaining samples were lost during the follow-up. Target exome sequencing and RNA-seq was performed to analyze genetic and transcriptome profile. The selected SNPs were validated by genotyping and allele specific gene expression using the TaqMan assay. The gene prioritization, enrichment analysis, drug-gene interactions, disease-gene association, and correlation analysis were performed using various tools and databases. RESULTS: rs1050152 and rs272893 in SLC22A4 were associated with improved response to metformin. The copy number loss was observed in PPARGC1A in the non-responders. The expression analysis highlighted potential differentially expressed targets for predicting metformin response (n = 35) and T2DM (n = 14). The expression of GDF15, TWISTNB, and RPL36A genes showed a maximum correlation with the change in HbA1c levels. The disease-gene association analysis highlighted MAGI2 rs113805659 to be linked with T2DM. CONCLUSION: The results provide evidence for the genetic variations, perturbed transcriptome, allele-specific gene expression, and pathways associated with metformin drug response in T2DM.

Reuse of poor-quality water for sustainable crop production in the changing scenario of climate.

The availability of freshwater is limited for agriculture systems across the globe. A fast-growing population demands need to enhance the food grain production from a limited natural resources. Therefore, researchers and policymakers have been emphasized on the production potential of agricultural crops in a sustainable manner. On the challenging side, freshwater bodies are shrinking with the pace of time further limiting crop production. Poor-quality water may be a good alternative for fresh water in water scarce areas. It should not contain toxic pollutants beyond certain critical levels. Unfortunately, such critical limits for different pollutants as well as permissible quality parameters for different wastewater types are lacking or poorly addressed. Marginal quality water and industrial effluent used in crop production should be treated prior to application in crop field. Hence, safe reuse of wastewater for cultivation of food material is necessary to fulfil the demands of growing population across the globe in the changing scenario of climate.

Primary adrenal plasmablastic lymphoma presenting as lymphomatous meningitis - A diagnostic perplexity.

A rare presentation of primary plasmablastic lymphoma (PBL) of the adrenal gland, as lymphomatous meningitis in a patient living with HIV.

Sustainability, productivity, profitability and soil health with conservation agriculture based sustainable intensification of oilseed brassica production system.

Conservation agriculture (CA) practices are getting space world-wide to answer many emerging challenges like; declining factor productivity, deteriorating soil health, water scarcity, climate change, and farm profitability and sustainability. Oilseed brassica (Indian mustard, Brassica juncea L.), a winter oilseed grown under rainfed agro-ecosystem is vulnerable to low yields, high production cost, degrading soil and water quality, and climatic vagaries. The present study was undertaken on CA-based sustainable intensification of Indian mustard for enhancing inputs efficiencies, farm profitability and sustainability. Permanent beds with residue retention (PB + R) improved mustard equivalent yield (11.4%) and system grain yield (10.6%) compared with conventional tillage without residue (CT - R). Maize-mustard rotation (Mz-M) increased system grain yield (142.9%) as well as mustard equivalent yield (60.7%) compared with fallow-mustard (F-M). Mz-M system under PB + R increased sustainable yield index (376.5%), production efficiency (177.2%), economic efficiency (94%) and irrigation water productivity (66%) compared with F-M under CT - R. PB + R increased soil organic carbon (SOC) stock at 0-15 cm (17.7%) and 15-30 cm (29.5%) soil depth compared with CT - R. Addition of green gram in rotation with mustard improved SOC at 0-15 cm (27.4%) and 15-30 cm (20.5%) compared with F-M system. CA-based cluster bean-mustard/GG-M system increased N productivity, whereas, P and K productivity improved with Mz-M system compared with F-M under CT - R. Thus, CA-based Mz-M system should be out-scaled in the traditional rainfed fallow-mustard system to improve the farm production and income on holistic basis to make the country self-sufficient in edible oils.

Maturity indices as an index to evaluate the quality of sulphur enriched municipal solid waste compost using variable byproduct of sulphur.

The aim of this study was to assess the maturity indicators of municipal solid waste compost (MSWC) enrichment with different byproduct of (sugar and fertilizer industry) sulphur (S). The concentration of total S (TS), water-soluble S (WSS), HCl extractable S and available S were significantly different in composts prepared through different byproduct of S with MSW. WSS varied from 4.6 to 5.9% of TS after 120 days of the composting period, whereas, available S varied from 14.5 - 8.6% of TS. S enriched MSW compost had lower C/N, C/S ratio and higher nitrification index as well as lower phyto-toxicity, demonstrating that composts are properly matured and stabilised. Highest compost quality index (0.97) was recorded with S1 compost. Arylsulphatase activity significantly increased with compost maturity. Results stated that all S enriched products maintained a superior amount of plant nutrients and quality indices, indicating that S enriched compost could be a possible substitute for expensive fertilizers.

Conceptualization of functional single nucleotide polymorphisms of polycystic ovarian syndrome genes: an in silico approach.

PURPOSE: Polycystic ovarian syndrome (PCOS) is a multi-faceted endocrinopathy frequently observed in reproductive-aged females, causing infertility. Cumulative evidence revealed that genetic and epigenetic variations, along with environmental factors, were linked with PCOS. Deciphering the molecular pathways of PCOS is quite complicated due to the availability of limited molecular information. Hence, to explore the influence of genetic variations in PCOS, we mapped the GWAS genes and performed a computational analysis to identify the SNPs and their impact on the coding and non-coding sequences. METHODS: The causative genes of PCOS were searched using the GWAS catalog, and pathway analysis was performed using ClueGO. SNPs were extracted using an Ensembl genome browser, and missense variants were shortlisted. Further, the native and mutant forms of the deleterious SNPs were modeled using I-TASSER, Swiss-PdbViewer, and PyMOL. MirSNP, PolymiRTS, miRNASNP3, and SNP2TFBS, SNPInspector databases were used to find SNPs in the miRNA binding site and transcription factor binding site (TFBS), respectively. EnhancerDB and HaploReg were used to characterize enhancer SNPs. Linkage Disequilibrium (LD) analysis was performed using LDlink. RESULTS: 25 PCOS genes showed interaction with 18 pathways. 7 SNPs were predicted to be deleterious using different pathogenicity predictions. 4 SNPs were found in the miRNA target site, TFBS, and enhancer sites and were in LD with reported PCOS GWAS SNPs. CONCLUSION: Computational analysis of SNPs residing in PCOS genes may provide insight into complex molecular interactions among genes involved in PCOS pathophysiology. It may also aid in determining the causal variants and consequently contributing to predicting disease strategies.

Effect of nitrate feeding strategies on lipid and biomass productivities in fed-batch cultures of Nannochloropsis gaditana.

Controlled nitrate feeding strategies for fed-batch cultures of microalgae were applied for the enhancement of lipid production and microalgal growth rates. In particular, in this study, the effect of nitrate feeding rates on lipid and biomass productivities in fed-batch cultures of Nannochloropsis gaditana were investigated using three feeding modes (i.e., pulse, continuous, and staged) and under two light variations on both lipid productivity and fatty acid compositions. Higher nitrate levels negatively affected lipid production in the study. Increasing the light intensity increased the lipid contents of the microalgae in all three fed-batch feeding modes. A maximum of 58.3% lipid- to dry weight ratio was achieved when using pulse-fed cultures at an illumination of 200 µmol photons m-2  s-1 and 10 mg/day of nitrate feeding. This condition also resulted in the maximum lipid productivity of 44.6 mg L-1  day-1 . The fatty acid compositions of the lipids consisted predominantly of long-chain fatty acids (C:16 and C:18) and accounted for 70% of the overall fatty acid methyl esters. Pulse feeding mode was found to significantly enhance the biomass and lipid production. The other two feeding modes (continuous and staged) were not ideal for lipid and biomass production. This study demonstrates the applicability of pulse feeding strategies in fed-batch cultures as an appropriate cultivation strategy that can increase both lipid accumulation and biomass production.

Schwannoma: An uncommon dweller in the adrenal gland.

An elderly adult woman presented with upper abdominal pain to the urology department. Imaging studies revealed a right adrenal lesion with central necrosis, abutting the large vessels and suggestive of malignancy. Histopathology showed an encapsulated spindle cell tumor with marked nuclear atypia, cystic change, and hemorrhage. S100 immunomarker was strongly and diffusely positive. Final diagnosis was ancient schwannoma with secondary change. Schwannomas are rare in the adrenal gland, with <50 cases reported in the literature. These incidentally detected nonfunctional adrenal tumors need confirmation with histopathology and ancillary studies.

The Adverse Effect of COVID Pandemic on the Care of Patients With Kidney Diseases in India.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has affected the care of patients with noncommunicable diseases, including those suffering from kidney-related ailments. Many parts of the world, including India, adopted lockdown to curb community transmission of disease. The lockdown affected transportation, access to health care facilities, and availability of medicines and consumables as well as outpatient and inpatient services. We aimed to analyze the effect of lockdown imposed due to the COVID-19 pandemic on the care of patients with kidney diseases in India. METHODS: We surveyed 19 major hospitals (8 in the public and 11 in the private sector) to determine the effect of lockdown on the care of patients with kidney disease, including those on dialysis after the first 3 weeks of lockdown. RESULTS: The total number of dialysis patients in these centers came down from 2517 to 2404. Approximately 710 (28.2%) patients missed 1 or more dialysis sessions, 69 (2.74%) required emergency dialysis sessions, 104 (4.13%) stopped reporting for dialysis, and 9 (0.36%) were confirmed to have died. Outpatient attendance in the surveyed hospital came down by 92.3%, and inpatient service reduced by 61%. Tele-consultation was started but was accessed by only a small number of patients. CONCLUSION: Lack of preparedness before lockdown resulted in an interruption in health care services and posed an immediate adverse effect on the outcome of dialysis patients and patients with kidney disease in India. The long-term impact on the health of patients with less severe forms of kidney disease remains unknown.

Confirmation of Induced Tolerance to Alternaria Blight Disease in Indian Mustard (Brassica juncea L.).

Indian mustard (Brassica juncea L.) is an important edible oilseed crop in India. Low productivity is the major concern which is adversely affected by biotic stresses. Alternaria blight (Alternaria brassicae) is one among major diseases that has no resistant cultivar until now. Keeping in view, an experiment was conducted for isolation of Alternaria blight-tolerant mutants in Indian mustard using gamma radiation and EMS mutagens during four consecutive years in Rabi (winter season). Furthermore, the morphologically and economically superior mutants of Brassica juncea were screened artificially at cotyledonary and adult stage against Alternaria blight. Tolerance to Alternaria blight is observed in DRMR-M-163 (11.7%), DRMR-M-158 (13.1%), DRMR-M-174 (13.8%) and DRMR-M-177 (18.6%) with minimum conidia in infected cotyledons. Mutant DRMR-M-178 (19.8%) had the highest radical scavenging activity, while DRMR-M-162 (104.9 mg/g AAE), DRMR-M-169 (96.9) and DRMR-M-161 (96.9) had higher antioxidant capacity that appears to act as defence to pathogen. DRMR-M-168 (8.4%), DRMR-M-173 (8.3), DRMR-M-171 (7.9), DRMR-M-165 (7.4), DRMR-M-175 (7.2) and DRMR-M-172 (6.9) had higher phenol content which may be responsive for resistance, although DRMR-M-161 (192.7 mg/g), DRMR-M-163 (187.7 mg/g), DRMR-M-164 (132.7 mg/g), DRMR-M-167 (149.3 mg/g), DRMR-M-173 (196.0 mg/g) and DRMR-M-178 (192.7 mg/g) mutants are found to contain low levels of total soluble sugar compared with susceptible Rohini (379.3). Based on biochemical parameter's similarity, mutants are grouped in 4 major clusters. Cluster 4 contained significantly different mutant DRMR-M-172. Relative expression of mitogen-activated protein kinase 3 (MAPK3) gene was found highest in DRMR-M-177, DRMR-M-174, DRMR-M-175, DRMR-M-178, DRMR-M-170, DRMR-M-176, DRMR-M-172 and DRMR-M-173 which resulted the better response to AB stress. Based on biochemical analysis, realtime PCR and cluster analysis, DRMR-M-172 mutant appears more tolerant to Alternaria. DRMR-M-178, DRMR-M-167 and DRMR-M-177 mutants seem tolerant and could be utilized for further breeding programme.

Effect of microwave pre-treatment on quality parameters in Indian mustard.

Demand for edible oil from crops like groundnut, mustard and soybean, is increasing and likely to increase further. In this regard, Indian mustard seeds were treated with microwaves (MW), to investigate the possibility of enhancing oil yield and nutritional content. MW pre-treatment was given to the seeds of two Indian mustard varieties i.e. PM21 (V1) and PDZ1 (V2) for 0, 2, 4 and 6 min (H0, H2, H4 and H6 min respectively). MW treatment with increasing exposure time showed a linear reduction in the glucosinolate and erucic acid content with concomitant increase in oil yield and moisture loss in both the varieties, as evident from correlation and principal component analysis. Antioxidant capacity has increased with the reduction in phytic acid content (1.82) in V2 at 6 min exposure time with respect to untreated control. Free radical scavenging activity was improved with increasing MW treatment in both the varieties. Therefore, from the obtained results, it is advisable to treat mustard seeds with MW before extraction of oil, because it gives a relatively good oil yield, with enhanced nutritional factors. Moreover, microwaving was effective in reducing glucosinolates and erucic acid also.

Mini-implant-supported twin-block appliance: An innovative modification.

Twin block is a commonly used appliance for correction of retrognathic mandible in growing patients. However, it has a drawback of causing lower incisor proclination, which reduces its potential of achieving maximum skeletal effects. Thus, we introduced a novel modification in the present design to facilitate greater anteroposterior effects in skeletal dimension. The aim of the present case reports is to evaluate the efficacy of this modified twin block. Here we present two cases treated with mini-implant-supported twin-block appliance, which successfully controlled the lower incisor position, thereby increasing the envelope for orthopedic correction in class II myofunctional therapy. This modification is useful in growing patients with retruded mandible to achieve maximum skeletal effects.

Municipal solid waste (MSW): Strategies to improve salt affected soil sustainability: A review.

Salt-induced soil degradation is a serious threat to global agriculture which is responsible for diminished productivity of agro-ecosystems. Irrigation with poor quality water and indiscriminate use of chemical fertilizers to increase crop productivity creates salt accumulation in soil profile thereby reducing crop sustainability. High concentration of salts in soil inhibits plant growth due to low osmotic potential of the soil solution, ion toxicity and imbalance reduces nutrient uptake, crop yields. Low productivity of saline soils is not only due to salt toxicity or excess amounts of soluble salts but also lack of available mineral nutrients especially nitrogen, phosphorus, potassium and soil organic matter. Hence, sustainable management of salt-affected soils are paramount importance to meet the demands of food grain production for an ever-rising population in the world. Recently, municipal solid waste has gained importance as an organic amendment for restoring soil fertility and finally contributing to productivity of salt-affected soils. This paper compares extant waste generation, their properties and standards pertinent to municipal solid waste in different countries and explores the unique recent history in some countries that shows high environmental regard and rapid changes and also suggests policy experiencing from high environmental regard and rapid changes from other countries, so that policy makers can propose new or revise current municipal solid waste standards for salt affected soils. Municipal solid waste compost improves soil biological, physical and chemical properties because of high soil organic matter and lower concentration of pollutants. Therefore, the use of municipal solid waste in salt-affected soils could be an alternative to costly chemical amendments as well as reduce the reliance on chemical fertilizers for increasing productivity of salt-affected soil. The municipal solid wastes significantly improve crop yields. However, further long-term experimental investigations are needed to re-validate the application of municipal solid waste compost in improving physical, chemical and biological properties and to step up organic fertilization use in a wide range of both saline and sodic soils. In future, research should be directed to address these issues globally to minimise ecological disturbances and to set environmental standards, and evaluate the feasibility of the policies in different countries and their impact on socio-economic conditions of local people.

Medication persistence and risk of fracture among female Medicare beneficiaries diagnosed with osteoporosis.

We examined the relationship between persistent osteoporosis medication use and fracture risk among female Medicare beneficiaries diagnosed with osteoporosis using Medicare claims, 2009-2012. Persistent use was associated with reduced risk of fracture and significantly lower total health care costs in the follow-up period. Results were consistent using different analytical methods. INTRODUCTION: This study aimed to examine the relationship between medication persistence and fracture risk among female Medicare beneficiaries diagnosed with osteoporosis. METHODS: Elderly female Medicare beneficiaries diagnosed with osteoporosis and initiated on osteoporosis medication January 1, 2009-June 30, 2011, were included. Persistent medication use was defined as continuous use (no gap ≥ 60 days) for 1 year or longer. The key outcome was fragility fracture. A difference-in-difference analysis was performed at the log scale of fracture rate using a Poisson regression model with months 1-6 before medication initiation as the pre-initiation period and up to 18 months after as the post-initiation period. Total health care costs were compared using a similar approach. Sensitivity analyses were conducted using different pre- and post-initiation periods. RESULTS: The study included 294,369 patients; 32.9% were persistent osteoporosis medication users and 67.1% non-persistent (< 12 months continuous use). Fracture incidence rates were 16.2 per 100 patient-years pre-initiation and 4.1 post-initiation for persistent users; corresponding rates for non-persistent users were 19.0 and 7.3 per 100 patient-years. The adjusted post-/pre-initiation fracture rate ratios were 0.284 for persistent and 0.411 for non-persistent users. The ratio of the two rate ratios was 0.692 (persistent vs. non-persistent, p < 0.0001), suggesting a significantly greater fracture rate reduction for persistent users. Adjusted cost ratios were significantly lower for persistent users. Sensitivity analyses results were similar. CONCLUSIONS: Persistent use of osteoporosis medications was associated with reduced risk of fracture and significantly lower total health care costs. Payers and patients would benefit from interventions aimed at improving medication persistence.

Rapid analysis of pharmaceutical drugs using LIBS coupled with multivariate analysis.

Type 2 diabetes drug tablets containing voglibose having dose strengths of 0.2 and 0.3 mg of various brands have been examined, using laser-induced breakdown spectroscopy (LIBS) technique. The statistical methods such as the principal component analysis (PCA) and the partial least square regression analysis (PLSR) have been employed on LIBS spectral data for classifying and developing the calibration models of drug samples. We have developed the ratio-based calibration model applying PLSR in which relative spectral intensity ratios H/C, H/N and O/N are used. Further, the developed model has been employed to predict the relative concentration of element in unknown drug samples. The experiment has been performed in air and argon atmosphere, respectively, and the obtained results have been compared. The present model provides rapid spectroscopic method for drug analysis with high statistical significance for online control and measurement process in a wide variety of pharmaceutical industrial applications.