Unilateral pulmonary artery atresia (UPAA), commonly detected in childhood, can occasionally present in adulthood with typical symptoms of recurrent pulmonary infections, dyspnoea on exertion and ...hemoptysis. An 18-year-old girl presented with complaints of cough, dyspnea on exertion and hemoptysis. Chest radiograph revealed dilated pulmonary trunk, signs of left sided volume loss and cavitating lesion in left lower zone. Pulmonary CT angiography found left pulmonary artery atresia. Endobronchial lung biopsy revealed granulomatous inflammation. Diagnosis of left sided UPAA with pulmonary tuberculosis was established. She responded well to the anti-tubercular therapy. This case highlights the importance of awareness about UPAA as a possible differential for exertional dyspnea, recurrent chest infections, hemoptysis and pulmonary hypertension in adults.
Neuropsychiatric disorders that affect the central nervous system cause considerable pressures on the health care system and have a substantial economic burden on modern societies. The present ...treatments based on available drugs are mostly ineffective and often costly. The molecular process of neuropsychiatric disorders is closely connected to modifying the genetic structures inherited or caused by damage, toxic chemicals, and some current diseases. Gene therapy is presently an experimental concept for neurological disorders. Clinical applications endeavor to alleviate the symptoms, reduce disease progression, and repair defective genes. Implementing gene therapy in inherited and acquired neurological illnesses entails the integration of several scientific disciplines, including virology, neurology, neurosurgery, molecular genetics, and immunology. Genetic manipulation has the power to minimize or cure illness by inducing genetic alterations at endogenous loci. Gene therapy that involves treating the disease by deleting, silencing, or editing defective genes and delivering genetic material to produce therapeutic molecules has excellent potential as a novel approach for treating neuropsychiatric disorders. With the recent advances in gene selection and vector design quality in targeted treatments, gene therapy could be an effective approach. This review article will investigate and report the newest and the most critical molecules and factors in neuropsychiatric disorder gene therapy. Different genome editing techniques available will be evaluated, and the review will highlight preclinical research of genome editing for neuropsychiatric disorders while also evaluating current limitations and potential strategies to overcome genome editing advancements.
Learning Disability Certification in India: Quo Vadis Gupta, Nitin; Goyal, Nishant; Sharma, Eesha
Journal of Indian Association for Child and Adolescent Mental Health,
10/2022, Letnik:
18, Številka:
4
Journal Article
A set of 96
-
introgression lines (ILs) were developed with genomic regions associated with
stem rot (
) resistance from a wild
species
. ILs were assessed for their resistance responses to stem ...inoculation with
, over three crop seasons (season I, 2011/2012; II, 2014/2015; III, 2016-2017). Initially, ILs were genotyped with transferable SSR markers and subsequently through genotyping by sequencing. SSR based association mapping identified six marker loci associated to resistance in both A and B genomes. Subsequent genome-wide association analysis (GWAS) of 84 ILs recognized a large number of SNPs associated to resistance, in chromosomes A03, A06, and B03. Chromosomes A03 and A06 harbored the maximum number of resistance related SNPs. Annotation of linked genomic regions highlighted an array of resistance mechanisms in terms of signal transduction pathways, hypersensitive responses and production of anti-fungal proteins and metabolites. Of major importance was the clustering of SNPs, encoding multiple resistance genes on small regions spanning approximately 885 kb region on chromosome A03 and 74 kb on B03. Five SNPs on chromosome A03 (6,390,210-381) were associated with LRR-RLK (receptor like kinases) genes that encode LRR-protein kinase family proteins. Genetic factors associated with pathogen-associated molecular patterns (PAMPs) and effector-triggered immunity (ETI) were predicted on chromosome A03, exhibiting 11 SNPs (6,274,763-994). These belonged to three R-Genes encoding TIR-NBS-LRR proteins. Marker trait associations (MTAs) identified will facilitate marker assisted introgression of these critical resistances, into new cultivars of
initially and, subsequently, into other crop
species.
The identification of viability‐associated long noncoding RNAs (lncRNAs) might be a promising rationale for new therapeutic approaches in liver cancer. Here, we applied an RNA interference screening ...approach in hepatocellular carcinoma (HCC) cell lines to find viability‐associated lncRNAs. Among the multiple identified lncRNAs with a significant impact on HCC cell viability, we selected cancer susceptibility 9 (CASC9) due to the strength of its phenotype, expression, and up‐regulation in HCC versus normal liver. CASC9 regulated viability across multiple HCC cell lines as shown by clustered regularly interspaced short palindromic repeats interference and single small interfering RNA (siRNA)–mediated and siRNA pool–mediated depletion of CASC9. Further, CASC9 depletion caused an increase in apoptosis and a decrease of proliferation. We identified the RNA binding protein heterogeneous nuclear ribonucleoprotein L (HNRNPL) as a CASC9 interacting protein by RNA affinity purification and validated it by native RNA immunoprecipitation. Knockdown of HNRNPL mimicked the loss‐of‐viability phenotype observed upon CASC9 depletion. Analysis of the proteome (stable isotope labeling with amino acids in cell culture) of CASC9‐depleted and HNRNPL‐depleted cells revealed a set of coregulated genes which implied a role of the CASC9:HNRNPL complex in AKT signaling and DNA damage sensing. CASC9 expression levels were elevated in patient‐derived tumor samples compared to normal control tissue and had a significant association with overall survival of HCC patients. In a xenograft chicken chorioallantoic membrane model, we measured decreased tumor size after knockdown of CASC9. Conclusion: Taken together, we provide a comprehensive list of viability‐associated lncRNAs in HCC; we identified the CASC9:HNRNPL complex as a clinically relevant viability‐associated lncRNA/protein complex which affects AKT signaling and DNA damage sensing in HCC.
Sixteen cycles of Brentuximab vedotin (BV) after autologous stem cell transplant (ASCT) in high-risk relapsed/refractory classical Hodgkin lymphoma demonstrated an improved 2-year progression-free ...survival (PFS) over placebo. However, most patients are unable to complete all 16 cycles at full dose due to toxicity. This retrospective, multicenter study investigated the effect of cumulative maintenance BV dose on 2-year PFS. Data were collected from patients who received at least one cycle of BV maintenance after ASCT with one of the following high-risk features: primary refractory disease (PRD), extra-nodal disease (END), or relapse <12 months (RL<12) from the end of frontline therapy. Cohort 1 had patients with >75% of the planned total cumulative dose, cohort 2 with 51-75% of dose, and cohort 3 with ≤50% of dose. The primary outcome was 2-year PFS. A total of 118 patients were included. Fifty percent had PRD, 29% had RL<12, and 39% had END. Forty-four percent of patients had prior exposure to BV and 65% were in complete remission before ASCT. Only 14% of patients received the full planned BV dose. Sixty-one percent of patients discontinued maintenance early and majority of those (72%) were due to toxicity. The 2-year PFS for the entire population was 80.7%. The 2-year PFS was 89.2% for cohort 1 (n=39), 86.2% for cohort 2 (n=33), and 77.9% for cohort 3 (n=46) (P=0.70). These data are reassuring for patients who require dose reductions or discontinuation to manage toxicity.
Introduction: Majority of the currently used diagnostic tests for Pulmonary Tuberculosis (PTB) have variability in sensitivity and specificity in diagnosing PTB. Therefore, evaluating new biomarkers ...in easily obtainable samples like serum and saliva can contribute to the diagnosis of PTB. Aim: To evaluate the role of Interleukins(IL)- 2,5,6,16,17,1β in the diagnosis of PTB by comparing their levels in Other Respiratory Diseases (ORD) group and monitoring the response to treatment in PTB group. Materials and Methods: This prospective observational study was conducted between January 2021 to May 2022 in a tertiary care hospital in New Delhi, India. A total of 80 cases were taken of which 40 cases of PTB and 40 cases having diagnosis of ORD were studied. IL-2,5,6,16,17,1β levels were measured in saliva and serum using Enzyme Linked Immune Sorbent Assay (ELISA) kits. These IL were also measured in diagnosed PTB patients in serum and saliva after two months of treatment. Statistical analysis was done using Statistical Package for the Social Sciences (SPSS) version 16.0. Kruskal Wallis H Test, Wilcoxon signed-rank sum test, Chi-square test and Fisher’s exact test were applied at appropriate areas and a p-value <0.05 was taken as significant. Results: On comparing the levels of IL between serum and saliva in PTB group at baseline, IL-2, IL-17 levels were higher in serum while IL-5, IL-1β levels were higher in saliva with these results being statistically significant (p-value <0.001). However, after two months of treatment, the levels of IL-2, IL16 decreased significantly in both serum and saliva whereas IL-17 level decreased significantly only in serum after treatment. None of the IL showed significant difference in levels between serum and saliva in PTB and ORD groups. Conclusion: The diagnostic role of IL in PTB could not be established whereas IL-2, IL-16 and IL-17 can be used for monitoring response to treatment as the levels decreased significantly with treatment.
Demand Response (DR) and Battery Energy Storage Systems (BESS) are promising options for system balancing in response to uncertainties arising from high penetration of renewable energy sources (RES) ...and grid contingencies. This paper presents a novel DR and BESS integrated, locational marginal price (LMP)-based day-ahead market (DAM) framework and mathematical model. The proposed model examines the participation of DR and BESS in an energy and spinning reserve (SR) co-optimized electricity market. It includes consumer preferences in providing DR, and a BESS cost model based on depth of discharge (DOD) and discharge rate. The mathematical model, formulated as a mixed integer programming (MIP) problem, is implemented on the IEEE Reliability Test System (RTS). Several case studies demonstrate the merits of the proposed framework and their impact on marginal prices, market settlement and system operation.
In recent decades, there has been a significant amount of research into breast cancer, with some important breakthroughs in the treatment of both primary and metastatic breast cancers. It's a ...well-known fact that treating breast cancer is still a challenging endeavour even though physicians have a fantastic toolset of the latest treatment options at their disposal. Due to limitations of current clinical treatment options, traditional chemotherapeutic drugs, and surgical options are still required to address this condition. In recent years, there have been several developments resulting in a wide range of treatment options. This review article discusses the cellular and molecular foundation of chemotherapeutic drugs, endocrine system-based treatments, biological therapies, gene therapy, and innovative techniques for treating breast cancer.
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