Improved long-term survival rate in the responders to bortezomib, cyclophosphamide, dexamethasone induction therapy in a transplant-eligible cohort of predominantly middle-age multiple myeloma patients.

BACKGROUND: Multiple myeloma (MM) represents the second most common hematologic malignancy (15%). Induction with bortezomib, cyclophosphamide, and dexamthasone VCd (d: low dose dexamthasone) regimen is widely used due to its high effectiveness, low toxicity and good tolerability, particularly with renal impairment. Real-world data on the use of VCD in clinical practice is lacking. OBJECTIVES: Evaluate the real-world experience of the VCD regimen. DESIGN: Retrospective. SETTING: Tumor registry database of tertiary cancer care center. PATIENTS AND METHODS: newly diagnosed MM patients who received VCD induction and underwent autologous stem cell transplant (ASCT) from July 2007 to July 2020. MAIN OUTCOME MEASURES: response evaluation, progression-free survival (PFS) and overall survival (OS). SAMPLE SIZE: 87 patients. RESULTS: Of 102 patients who started induction with VCd, 87 patients experienced a partial response or more overall response rate of 85%). The median age of these 87 patients at diagnosis was 52 years, of which 29.9% presented with renal impairment and 60.3% of patients had stage 2 by the Revised International Staging System (R-ISS). Patients with a standard cytogenetic risk achieved a better response compared to those with a poor cytogenetic risk (P=.044). The post-induction response rates were 6.9% stringent complete remission (sCR), 35% complete remission (CR); 41.4% very good partial response (VGPR), and 16.1% partial response (PR), respectively; the response rates became greater for sCR and CR post-transplantation at day 100 with 16.1% sCR, 35.6% CR, 32.2% VGPR and 16.1% PR, respectively. The median PFS was 49 months and 5 years OS was 84%. PFS was better in patients who achieved sCR vs PR (83 vs 35 months, P=.037). High LDH, high-risk cytogenetic and stage 3 R-ISS showed a worse median PFS and OS. CONCLUSIONS: VCD induction in newly diagnosed MM is highly effective, convenient, tolerable and affordable regimen, especially in low and middle-income countries with limited resources, also with favorable outcomes and survival. while those who did not respond successfully shifted to VRD or VTD. LIMITATIONS: The usual limitations of a retrospective analysis using registry-level data, no data on quality of life.

Association of a single-nucleotide polymorphism in C12orf43 region with the risk of coronary artery disease.

The genetics of organisms play a vital role in the development of coronary artery disease (CAD), with its heritability estimated at approximately 50-60%. For this purpose, we examined the relationship between CAD risk and C12orf43/rs2258287 polymorphisms in the Pakistani population. In this study based on the genetic approach to dyslipidemia, a total of 200 subjects were included from the southern Punjab. The biochemical analysis of parameters (total cholesterol, triglycerides, blood glucose, high-density lipoprotein, and low-density lipoprotein) was carried out along with molecular analysis using an ARMS-PCR-based assay for single-nucleotide polymorphism (SNP) C12orf43/rs2258287 to identify the genotype. Genotypes showed a substantial correlation with both family history and metabolic markers. The cholesterol, low-density lipoprotein cholesterol (LDL-C), triglycerides and blood glucose levels were higher while the high-density lipoprotein cholesterol (HDL-C) level was lower significantly (p<0.05) in cases than in controls. Age, pulse rate, diabetes, physical activity, smoking, family history, and dietary habits were also significantly associated (p<0.05) with CAD individuals. The SNP C12orf43/rs2258287 also showed an association with CAD in the population of southern Punjab. Based upon this study, it could be concluded that CAD is characterized by an unfavorable lipid profile in association with SNP C12orf43/rs2258287.

Prevalence of soil-transmitted helminth infections in HIV patients: a systematic review and meta-analysis.

Soil-transmitted Helminth (STH) infections have been found associated with people living with human immunodeficiency virus (HIV) but little is known about the overall burden of STH coinfection in HIV patients. We aimed to assess the burden of STH infections among HIV patients. Relevant databases were systematically searched for studies reporting the prevalence of soil-transmitted helminthic pathogens in HIV patients. Pooled estimates of each helminthic infection were calculated. The odds ratio was also determined as a measure of the association between STH infection and the HIV status of the patients. Sixty-one studies were finally included in the meta-analysis, consisting of 16,203 human subjects from all over the world. The prevalence of Ascaris lumbricoides infection in HIV patients was found to be 8% (95% CI 0.06, 0.09), the prevalence of Trichuris trichiura infection in HIV patients was found to be 5% (95% CI 0.04, 0.06), the prevalence of hookworm infection in HIV patients was found to be 5% (95% CI 0.04, 0.06), and prevalence of Strongyloides stercoralis infection in HIV patients was found to be 5% (95% CI 0.04, 0.05). Countries from Sub-Saharan Africa, Latin America & Caribbean and Asia were identified with the highest burden of STH-HIV coinfection. Our analysis indicated that people living with HIV have a higher chance of developing Strongyloides stercoralis infections and decreased odds of developing hookworm infections. Our findings suggest a moderate level of prevalence of STH infections among people living with HIV. The endemicity of STH infections and HIV status both are partially responsible for the burden of STH-HIV coinfections.

A meta-analysis on the prevalence of Taenia solium and Taenia saginata infections in India.

Tapeworm infections in humans are considered to be a significant public health menace. Despite its public health importance, the data on tapeworm infection remains fragmented and underutilised. The present study reviews the overall burden and distribution of taeniasis and cysticercosis caused by Taenia solium and Taenia saginata in India by conducting a systematic review of the scientific literature based on Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Data from 19 eligible articles were analysed and the prevalence of T. solium-associated taeniasis/cysticercosis was found to be 11.06% (95% confidence interval [CI] 6.856 to 16.119) and the prevalence of T. saginata-associated taeniasis was found to be 4.7% (95% CI 3.301 to 6.301). This systematic review and meta-analysis provides a comprehensive analysis of the available literature on tapeworm infections and assesses the burden of Taenia infection from India, identifying areas of high prevalence requiring active surveillance and public health interventions.

Association of TNF-α polymorphisms (-857, -863 and -1031), TNF-α serum level and lipid profile with acne vulgaris.

BACKGROUND: Acne is an inflammatory condition principally affected by genetic and dietary factors. Investigation into functional polymorphisms of TNF-α gene and their association with acne vulgaris will be helpful in exploring genetic influence on skin immune mediated inflammatory events. In the present study, we analyzed association of TNF-α gene polymorphisms, its expression levels and lipid profiles in a large cohort of acne patients and controls. METHODS: We used PCR-RFLP to study association of TNF-α polymorphisms at -857C/T, -863C/A and -1031 T/C sites with acne vulgaris. Lipid profiles were measured using enzymatic end-point method. The serum levels of TNF-α and apolipoprotein a were measured using ELISA. NIH, LDlink was used to investigate patterns of linkage disequilibrium across south Asian reference genome (Punjabi from Lahore Pakistan). RESULTS: We found that TNF-α -863 polymorphism is strongly associated with acne in overall population as well as in gender and severity based groups of acne patients. Polymorphisms at -863 and -1031 position were in linkage disequilibrium. Importantly, TNF-α serum level was significantly increased in acne patients with severe disease symptoms. Furthermore, levels of total cholesterol (TC) and triglycerides (TG) were significantly increased, whereas high density lipoprotein cholesterol (HDL-C) level was significantly decreased in acne patients. The levels of apolipoprotein a varied widely in studied populations and no significant difference was found in the analyzed groups. CONCLUSION: In conclusion, we found that TNF-α expression increases in acne patients affected by TNF-α polymorphisms, and that the lipid profile is specifically disrupted in acne patients.

Improved survival in adolescents and young adults (AYA) patients aged 14-55 years with acute lymphoblastic leukemia using pediatric-inspired protocol - a retrospective analysis of a real-world experience in 79 of patients treated at a national tertiary care referral center.

BACKGROUND: Treating adolescents and young adults (AYA) patients with acute lymphoblastic leukemia (ALL) using pediatric-inspired protocols have shown improvement in outcomes. Most data available in the literature of such protocols is derived from well-controlled clinical trials. This report aims to provide a real-world experience from using a pediatric-inspired protocol in ALL-AYA population in larger number of patients treated at a national tertiary care referral center. METHODS: Newly diagnosed Philadelphia negative ALL-AYA patients ages between 14 and 55 years of age were treated on an institutional protocol (AYA-15 protocol) adopted from a modified version of Children's Cancer Group (CCG) 1900 protocol. At the time of this publication, a total of 79 patients were treated using the AYA-15 protocol between 2015 and 2020). Event-free survival (FFS), disease-free survival (DFS), and overall survival (OS) were analyzed using cumulative incidence and Kaplan-Meier methods. RESULTS: The median age at diagnosis was 18 years (14-51 years) with 63% male patients. Complete remission (CR) at day 28 of induction was achieved in 88.6% of which 73.4% were minimal residual disease (MRD) negative. At a median follow up of 5 years, EFS, DFS and OS were 57.5%, 69.2% and 75.8% respectively. Toxicities were within the expected range with infections and transaminitis being the most common adverse events. CONCLUSION: Our single-center experience real-world data in treating AYA-ALL patients with pediatric-inspired protocol demonstrates encouraging results of high survival rate and excellent tolerability for patients aged 18-55 years.

Surgical Anatomy and Prevalence of Intracranial Aneurysms in Patients With Spontaneous Subarachnoid Hemorrhage.

Objective To assess the surgical anatomy and prevalence of intracranial aneurysms in patients with spontaneous subarachnoid hemorrhage. Materials and methods The current research investigated a total of 119 individuals from Peshawar, Pakistan. All the adult patients in the age range of 30 to 60 years, of both genders, presenting with spontaneous subarachnoid hemorrhage were included. A thorough history was taken, as well as a full, general, physical, systemic, and neurological examination was done. All individuals who arrived with a rapid onset of severe headache, with or without loss of consciousness, and had a CT scan showing spontaneous subarachnoid hemorrhage were included. All patients were subjected to CT angiography in the hospital to ascertain any intracranial aneurysm. CT angiography was done by a consultant radiologist (FCPS) having at least five years of experience. All the above-mentioned information, including age, diabetes, obesity, smoking, gender, and hypertension, was recorded in a predesigned proforma. Results The current study found that among 119 patients, 24 (20%) were of age 30-40 years, 44 (37%) were between 41 and 50 years, and 51 (43%) were of age 51 to 60 years; 73 (61%) were male and 46 (39%) were female; 67 (56%) were obese and 52 (44%) were not obese; 81 (68%) patients were hypertensive and 38 (32%) patients were non-hypertensive; 75 (63%) patients were diabetic and 44 (37%) patients were non-diabetic; 49 (41%) patients were smokers and 70 (59%) patients were non-smokers. Moreover, 96 (81%) patients had intracranial aneurysms and 23 (19%) patients did not have intracranial aneurysms. Conclusion As has been observed, the prevalence of intracranial aneurysms and surgical anatomy was 81% in individuals from Peshawar, Pakistan, with spontaneous subarachnoid hemorrhage.

Insect venom peptides as potent inhibitors of Escherichia coli ATP synthase.

Insect venom peptides (IVPs) eumenitin, lasiocepsin, lycosin1, mastoparanB, panurgine1, and protonectin possess antibacterial properties, and the ubiquitous enzyme ATP synthase has a peptide-binding site. In the present study, we studied the effect of IVPs on binding and inhibition of three Escherichia coli strains (wild type, mutant, and null) and isolated E. coli ATP synthase. IVPs and their C-terminal amide (-NH2) analogs caused variable inhibition of membrane-bound F1Fo ATP synthase. While wild type E. coli growth was substantially hampered, null E. coli growth was near normal in the presence of IVPs and their C-terminal-NH2 analogs. The presence of C-terminal-NH2 groups on IVPs resulted in increased inhibition of ATP synthase and reduced growth of E. coli strains. Insignificant inhibition of the ßDELSEED-motif mutant enzyme with the ßAAAAAAA-motif confirmed that IVPs interact with the ßDELSEED-motif, also known as the peptide-binding site. The higher level of growth loss in E. coli strains by eumenitin, lasiocepsin, lycosin1, mastoparanB, panurgine1, and protonectin and their C-terminal-NH2 analogs suggested the likelihood of additional cellular or molecular targets. IVPs caused inhibition of E. coli strains, which demonstrates an association between antimicrobial traits of IVPs and bacterial ATP synthase.

Non-Toxic and Ultra-Small Biosilver Nanoclusters Trigger Apoptotic Cell Death in Fluconazole-Resistant Candida albicans via Ras Signaling.

Silver-based nanostructures are suitable for many biomedical applications, but to be useful therapeutic agents, the high toxicity of these nanomaterials must be eliminated. Here, we biosynthesize nontoxic and ultra-small silver nanoclusters (rsAg@NCs) using metabolites of usnioid lichen (a symbiotic association of algae and fungi) that exhibit excellent antimicrobial activity against fluconazole (FCZ)-resistant Candida albicans that is many times higher than chemically synthesized silver nanoparticles (AgNPs) and FCZ. The rsAg@NCs trigger apoptosis via reactive oxygen species accumulation that leads to the loss of mitochondrial membrane potential, DNA fragmentation, chromosomal condensation, and the activation of metacaspases. The proteomic analysis clearly demonstrates that rsAg@NCs exposure significantly alters protein expression. Most remarkable among the down-regulated proteins are those related to glycolysis, metabolism, free radical scavenging, anti-apoptosis, and mitochondrial function. In contrast, proteins involved in plasma membrane function, oxidative stress, cell death, and apoptosis were upregulated. Eventually, we also established that the apoptosis-inducing potential of rsAg@NCs is due to the activation of Ras signaling, which confirms their application in combating FCZ-resistant C. albicans infections.

Global distribution of NA1 genotype of respiratory syncytial virus and its evolutionary dynamics assessed from the past 11 years.

Respiratory syncytial virus (RSV) is a potent pathogen having global distribution. The main purpose of this study was to gain an insight into distribution pattern of the NA1 genotype of group A RSV across the globe together with its evolutionary dynamics. We focused on the second hypervariable region of the G protein gene and used the same for Phylogenetic, Bayesian and Network analyses. Eighteen percent of the samples collected from 500 symptomatic pediatric patients with acute respiratory tract infection (ARI) were found to be positive for RSV during 2011-15 from New Delhi, India. Of these, group B RSV was predominant and clustered into two different genotypes (BA and SAB4). Similarly, group A viruses clustered into two genotypes (NA1 and ON1). The data set from the group A viruses included 543 sequences from 23 different countries including 67 strains from India. The local evolutionary dynamics suggested consistent virus population of NA1 genotype in India during 2009 to 2014. The molecular clock analysis suggested that most recent common ancestor of group A and NA1 genotype have emerged in during the years 1953 and 2000, respectively. The global evolutionary rates of group A viruses and NA1 genotype were estimated to be 3.49 × 10-3 (95% HPD, 2.90-4.17 × 10-3) and 3.56 × 10-3 (95% HPD, 2.91 × 10-3-4.18 × 10-3) substitution/site/year, respectively. Analysis of the NA1 genotype of group A RSV reported during 11 years i.e. from 2004 to 2014 showed its dominance in 21 different countries across the globe reflecting its evolutionary dynamics. The Network analysis showed highly intricate but an inconsistent pattern of haplotypes of NA1 genotype circulating in the world. Present study seems to be first comprehensive attempt on global distribution and evolution of NA1 genotype augmenting the optimism towards the vaccine development.

Impact of Ethylene diurea (EDU) on growth, yield and proteome of two winter wheat varieties under high ambient ozone phytotoxicity.

The present study evaluated the impact of high ambient O3 on morphological, physiological and biochemical traits and leaf proteome in two high-yielding varieties of wheat using ethylene diurea (EDU) as foliar spray (200 and 300 ppm). Average ambient ozone concentration was 60 ppb which was more than sufficient to cause phytotoxic effects. EDU treatment resulted in less lipid peroxidation along with increased chlorophyll content, biomass and yield. EDU alleviated the negative effects of ozone by enhancing activities of antioxidants and antioxidative enzymes. Two dimensional electrophoresis (2DGE) analysis revealed massive changes in protein abundance in Kundan at vegetative stage (50% proteins were increased, 20% were decreased) and at flowering stage (25% increased, 18% decreased). In PBW 343 at both the developmental stages about 15% proteins were increased whereas 20% were decreased in abundance. Higher abundance of proteins related to carbon metabolism, defense and photorespiration conferred tolerance to EDU treated Kundan. In PBW343, EDU provided incomplete protection as evidenced by low abundance of many primary metabolism related proteins. Proteomic changes in response to EDU treatment in two varieties are discussed in relation to growth and yield.

Transgenic Analysis Reveals 5' Abbreviated OsRGLP2 Promoter(s) as Responsive to Abiotic Stresses.

Germins and germin-like proteins are ubiquitous, expressed at various developmental stages and in response to various abiotic and biotic stresses. In this study, to functionally validate the OsRGLP2 promoter, 5' deletion analysis of the promoter sequences was performed and the deletion fragments fused with the ß-glucuronidase (GUS) and green fluorescent protein reporter genes were used for transient expression in tobacco as well as for generating stable transgenic Arabidopsis plants. Very high level of GUS activity was observed in agroinfiltrated tobacco leaves by the construct carrying the P-1063 and P-565 when subjected to abiotic stresses. Histochemical analysis of transgenic Arabidopsis plants revealed expression of reporter gene in root, leaf and stem sections of plants harboring P-1063 and P-565. Real-time qPCR analysis of transiently expressed tobacco leaves and transgenic Arabidopsis plants subjected to several abiotic stresses supported histochemical data and showed that P-565 responded to all the stresses to which the full-length promoter was responsive. The data suggest that P-565 may be a good alternative to full-length promoter region that harbors the necessary cis-elements in providing stable and high level of expression in response to wound, salt and temperature stresses.

Efficacy Evaluation of SAVE for the Diagnosis of Superficial Neoplastic Lesion.

The detection of non-polypoid superficial neoplastic lesions using current standard of white light endoscopy surveillance and random biopsy is associated with high miss rate. The subtle changes in mucosa caused by the flat and depressed neoplasms often go undetected and do not qualify for further investigation, e.g., biopsy and resection, thus increasing the risk of cancer advancement. This paper presents a screening tool named the saliency-aided visual enhancement (SAVE) method, with an objective of highlighting abnormalities in endoscopic images to detect early lesions. SAVE is a hybrid system combining image enhancement and saliency detection. The method provides both qualitative enhancement and quantitative suspicion index for endoscopic image regions. A study to evaluate the efficacy of SAVE to localize superficial neoplastic lesion was performed. Experimental results for average overlap index >0.7 indicated that SAVE was successful to localize the lesion areas. The area under the receiver-operating characteristic curve obtained for SAVE was 94.91%. A very high sensitivity (100%) was achieved with a moderate specificity (65.45%). Visual inspection showed a comparable performance of SAVE with chromoendoscopy to highlight mucosal irregularities. This paper suggests that SAVE could be a potential screening tool that can substitute the application of burdensome chromoendoscopy technique. SAVE method, as a simple, easy-to-use, highly sensitive, and consistent red flag technology, will be useful for early detection of neoplasm in clinical applications.

Molecular Characterization of a MYB Protein from Oryza sativa for its Role in Abiotic Stress Tolerance

ABSTRACT The MYB family represents one of the most abundant classes of transcriptional regulators that perform pivotal role under different developmental processes and abiotic stresses. In present study, a MYB gene from Oryza sativa was selected for functional characterization. Bioinformatics analysis revealed that OsMYB1 cDNA encodes R2-R3 type DNA binding domain consisting of 413 amino acids having size of 44 kDa and pI of 6.24. DNA binding domain containing region was cloned and over-expressed in E. coli. Then, the survival of pGEX-OsMYB1 transformed E. coli cells was compared with control plasmid under different concentrations of NaCl, mannitol, high and low temperature. pGEX-OsMYB1 enhanced the survival of cells at high temperature and salinity. Electrophoretic mobility shift assays (EMSAs) have shown that recombinant OsMYB1 protein was able to bind with DIG labeled probe containing MYB binding site. RT-qPCR analysis revealed high MYB1 expression under wounding, salt, drought and heat stresses in rice. Expression was 23 fold higher in response to wounding demonstrating the worth of OsMYB1 up-regulation in wounding. Intrinsic disorder profile predicted that OsMYB1 exhibits 60% degree of intrinsic disorder proposing that these regions might be involved in DNA binding specificity and protein-protein interaction. The positive response of OsMYB1 suggests that its over-expression in crop plants may help in providing protection to plants to grow under abiotic stresses.

Unsupervised abnormality detection using saliency and Retinex based color enhancement.

An efficient and automated abnormality detection method can significantly reduce the burden of screening of the enormous visual information resulting from capsule endoscopic procedure. As a pre-processing stage, color enhancement could be useful to improve the image quality and the detection performance. Therefore, in this paper, we have proposed a two-stage automated abnormality detection algorithm. In the first stage, an adaptive color enhancement method based on Retinex theory is applied on the endoscopic images. In the second stage, an efficient salient region detection algorithm is applied to detect the clinically significant regions. The proposed algorithm is applied on a dataset containing images with diverse pathologies. The algorithm can successfully detect a significant percentage of the abnormal regions. From our experiment, it was evident that color enhancement method improves the performance of abnormality detection. The proposed algorithm can achieve a sensitivity of 97.33% and specificity of 79%, higher than state-of-the-art performance.

Sulfur alleviates arsenic toxicity by reducing its accumulation and modulating proteome, amino acids and thiol metabolism in rice leaves.

Arsenic (As) contamination of water is a global concern and rice consumption is the biggest dietary exposure to human posing carcinogenic risks, predominantly in Asia. Sulfur (S) is involved in di-sulfide linkage in many proteins and plays crucial role in As detoxification. Present study explores role of variable S supply on rice leaf proteome, its inclination towards amino acids (AA) profile and non protein thiols under arsenite exposure. Analysis of 282 detected proteins on 2-DE gel revealed 113 differentially expressed proteins, out of which 80 were identified by MALDI-TOF-TOF. The identified proteins were mostly involved in glycolysis, TCA cycle, AA biosynthesis, photosynthesis, protein metabolism, stress and energy metabolism. Among these, glycolytic enzymes play a major role in AA biosynthesis that leads to change in AAs profiling. Proteins of glycolytic pathway, photosynthesis and energy metabolism were also validated by western blot analysis. Conclusively S supplementation reduced the As accumulation in shoot positively skewed thiol metabolism and glycolysis towards AA accumulation under AsIII stress.

In vitro cadmium-induced alterations in growth and oxidative metabolism of upland cotton (Gossypium hirsutum L.).

Cadmium (Cd) is a toxic pollutant, which cause both dose- and time-dependent physiological and biochemical alterations in plants. The present in vitro study was undertaken to explore Cd-induced physiological and biochemical changes in cotton callus culture at 0, 550, 700, 850, and 1000 µM Cd for four different stress periods (7, 14, 21, and 28 days). At 1000 µM Cd, mean growth values were lower than their respective control. The cell protein contents decreased only after 7-day and 14-day stress treatment. At 550 µM Cd, malondialdehyde (MDA) contents decreased after various stress periods except 21-day period. Superoxide dismutase (SOD) activity at 1000 µM Cd improved relative to its respective controls in the first three stress regimes. Almost a decreasing trend in the hydrogen peroxide (H2O2) and peroxidase (POD) activities at all Cd levels after different stress periods was noticed. Ascorbate peroxidase (APX) activity descended over its relevant controls in the first three stress regimes except at 700 µM Cd after 14- and 21-day stress duration. Moreover, catalase (CAT) mean values significantly increased as a whole. From this experiment, it can be concluded that lipid peroxidation as well as reactive oxygen species (ROS) production was relatively higher as has been revealed by higher MDA contents and greater SOD, CAT activities.