DEPRESSIVE SYMPTOMS AMONG PATIENTS WITH ACUTE EXACERBATIONS OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE

Background; chronic obstructive pulmonary disease (COPD) leads to significant morbidity and poor quality of life among patients. This study was conducted to evaluate depression among patients with COPD as there is no such study done in our population. Objective: To determine the frequency of depression among the patients with COPD presenting at a tertiary care hospital. Material and methods; A total of 196 patients with COPD were enrolled from department of Medicine, Nishtar Hospital, Multan, Pakistan in this cross-sectional study. The purpose of the study was explained to each patient and informed consent was obtained. Patient’s basic data and demography was noted. All patients were interviewed for depression using HADS scale. Data were entered and analyzed using SPSS. Results; Of these 196 study cases, 124 (63.3 %) were male patients while 72 (36.7%) were female patients. Mean age of our study cases was 53.89 ± 10.01 years (with minimum age of our study cases was 32 years while maximum age was 70 years). Mean age of the male patients was noted to be 56.82 ± 9.74 years while that female patients was 48.83 ± 8.37 years (p=0.000). Our study results have indicated that majority of our study cases i.e. 116 (59.2 %) were aged more than 50 years. Of these 196 study cases, 94 (48 %) belonged to rural areas and 102 (52 %) belonged to urban areas. Monthly family income up to 35000 rupees was noted in 123 (62.8%) and 73 (37.2%) had monthly family income more than 35000 rupees. Diabetes was presented in 51 (26.0 %) of our study cases. Hypertension was present in 87 (44.4 %) of our study cases. History of smoking was noted in 66 (33.7%) of our study cases. Mean disease duration was 19.68 ± 8.36 months and 129 (65.8%) had duration of illness more than 1 year. Mean HADS score was 10.51 ± 2.41 and depression was present in 131 (66.8%) of our study cases. Conclusion; High frequency of depression was noted in our study among patients having chronic obstructive pulmonary disease (COPD). Depression was significantly associated with gender, hypertension, smoking and prolonged disease duration. All clinicians treating such patients should check such patients for depression. Early diagnosis of depression followed by early treatment can help to improve clinical outcome and decrease disease related morbidity. Keywords; Frequency, depression, Chronic obstructive pulmonary disease

Analytical Method Development and Validation for Assay of Rufinamide Drug

A simple, rapid, sensitive, cost effective, and reproducible reverse phase high performance liquid chromatographic (RP-HPLC) method was developed and validated for the stability testing of rufinamide. The proposed RP-HPLC method was developed on phenome-nex LunaR C-18 5μm,250 mm × 4.6 mm id. Column (at ambient temperature) and a mobile phase consisting of phosphate buffer: acetonitrile (60:40) was delivered at a flow rate of 1.0ml/ min. The analyte was detected by using a UV detector at the wavelength of 293 nm. The method was found to be linear over the concentration range of 50- 150 μgml-1 (r2=0.999). 30. The retention time of rufinamide was 4.717 min. Most searchable Keywords assay method development, analytical method development, method development, analytical method development and validation, analytical method development introduction, development and validation of analytical methods, method development and validation, assay method validation, analytical method development in pharmaceuticals, pharmaceutical method development,&nbsp

Impact of different grades of anaemia severity during pregnancy on maternal and neonatal outcomes: a prospective study

Background: Anaemia in pregnancy is a universal health problem that may cause a number of obstetrical and neonatal complications. This prospective observational study aims to evaluate and compare maternal and neonatal outcomes in different grades of anaemia severity.Methods: A total of 400 pregnant women with anaemia in third trimester were classified into three groups according to haemoglobin (Hb) levels-group I with Hb:10-10.9 g/dl, group II with Hb:7-9.9g/dl and group III with Hb<7 g/dl. Maternal and neonatal outcomes of women with different severity of anaemia were analyzed and compared. Two groups means were compared by Student’s t-independent test and more than two groups means by one way analysis of variance test followed by post-hoc pairwise comparison using Bonferroni test.Results: The prevalence of anaemia in the study population was 35.2%. Mild, moderate and severe anaemia were found in 58% (n=232), 29.0% (n=116) and 13% (n=52) women respectively. A statistically significant difference in maternal outcomes such as Preterm labor (p=0.001), Prelabor premature rupture of membranes (p=0.044), Intrauterine growth restriction (p=0.002) and postpartum hemorrhage (p=0.001) was observed amongst the three groups. Cardiac failure occurred in 26.9% (n=14) and mortality in 13.4% (n=7) women with severe anaemia. Amongst the neonatal morbidities, the rate of low birth weight, preterm birth, respiratory distress syndrome, septicaemia, pneumonitis and jaundice revealed an increasing trend with rising severity of anaemia which was statistically significant.Conclusions: Targeted interventions addressing early detection and appropriate treatment in early pregnancy can prevent and avoid dismal maternal and neonatal consequences

A Review on Current Status of Blood Disorder: Thalassemia and its Treatment

The most prevalent hereditary monogenic disorders that claim millions of lives globally are thalassemic syndromes. A thalassemia is an inherited condition, at least one parent must carry the disease's gene. Perhaps a genetic mutation/ defective globin chain or the loss of specific important gene segments is the main cause. Thalassemic illnesses started to strain the healthcare systems of several nations worldwide. Management of thalassemia is now seen as a lifelong treatment that requires continuous monitoring. In this review, we seek to compile and analyze recent research on thalassemia diagnosis and treatment, including papers, studies, and clinical trials. We also intend to present a concise yet comprehensive study. A thalassemia is an inherited condition, at least one parent must carry the disease's gene. Perhaps a genetic mutation/ defective globin chain or the loss of specific important gene segments is the main cause

miR-10a-3p modulates adiposity and suppresses adipose inflammation through TGF-β1/Smad3 signaling pathway

BackgroundObesity is a multifactorial disease characterized by an enhanced amount of fat and energy storage in adipose tissue (AT). Obesity appears to promote and maintain low-grade chronic inflammation by activating a subset of inflammatory T cells, macrophages, and other immune cells that infiltrate the AT. Maintenance of AT inflammation during obesity involves regulation by microRNAs (miRs), which also regulate the expression of genes implicated in adipocyte differentiation. This study aims to use ex vivo and in vitro approaches to evaluate the role and mechanism of miR-10a-3p in adipose inflammation and adipogenesis.MethodsWild-type BL/6 mice were placed on normal (ND) and high-fat diet (HFD) for 12 weeks and their obesity phenotype, inflammatory genes, and miRs expression were examined in the AT. We also used differentiated 3T3-L1 adipocytes for mechanistic in vitro studies.ResultsMicroarray analysis allowed us to identify an altered set of miRs in the AT immune cells and Ingenuity pathway analysis (IPA) prediction demonstrated that miR-10a-3p expression was downregulated in AT immune cells in the HFD group as compared to ND. A molecular mimic of miR-10a-3p reduced expression of inflammatory M1 macrophages, cytokines, and chemokines, including transforming growth factor-beta 1 (TGF-β1), transcription factor Krüppel-like factor 4 (KLF4), and interleukin 17F (IL-17F) and induced expression of forkhead box P3 (FoxP3) in the immune cells isolated from AT of HFD-fed mice as compared to ND. In differentiated 3T3-L1 adipocytes, the miR-10a-3p mimics also reduced expression of proinflammatory genes and lipid accumulation, which plays a role in the dysregulation of AT function. In these cells, overexpression of miR-10a-3p reduced the expression of TGF-β1, Smad3, CHOP-10, and fatty acid synthase (FASN), relative to the control scramble miRs.ConclusionOur findings suggest that miR-10a-3p mimic mediates the TGF-β1/Smad3 signaling to improve metabolic markers and adipose inflammation. This study provides a new opportunity for the development of miR-10a-3p as a novel therapeutic for adipose inflammation, and its associated metabolic disorders

High Fat Diet-Induced CD8+ T Cells in Adipose Tissue Mediate Macrophages to Sustain Low-Grade Chronic Inflammation

Obesity in the United States and worldwide reached epidemic proportions within the last 20 years. Obesity is a very powerful health determinant or indicator that facilitates the development and progression of several metabolic diseases, insulin resistance, and low-grade chronic inflammation. Low-grade chronic inflammation in adipose tissue (AT) is marked by the accumulation of T cells, macrophages, and other immune cells and increased production of proinflammatory cytokines. During the onset of obesity but before the influx of macrophages, the AT is infiltrated by T cells that are strongly implicated in the initiation of obesity-associated inflammation. In comparing mice fed a high-fat diet (HFD) with those fed a normal diet (ND), we observed in HFD epididymal AT induction and infiltration of activated T cells, an accumulation and polarization of macrophages, and an increase in populations of activated CD4+ T cells and CD8+ T cells that express CXCR3 or killer cell lectin-like receptor subfamily G member 1 (KLRG1). Levels of inflammatory cytokines and leptin and the results of in vitro co-culture experiments revealed interactions among HFD- and ND-induced CD8+ T cells, macrophages, and adipocytes. Our findings suggest that obese tissues activate and induce both CD4+ and CD8+ CD69+ T cells and augment the expression of CXCR3 receptors, which promotes the recruitment and numbers of pro-inflammatory M1 macrophages to maintain low-grade chronic inflammation. The results support the hypothesis that CXCR3-expressing CD8+T cells play an essential role in the initiation and maintenance of adipose tissue inflammation

Gene-Centric Meta-Analysis of Lipid Traits in African, East Asian and Hispanic Populations

Meta-analyses of European populations has successfully identified genetic variants in over 100 loci associated with lipid levels, but our knowledge in other ethnicities remains limited. To address this, we performed dense genotyping of ∼2,000 candidate genes in 7,657 African Americans, 1,315 Hispanics and 841 East Asians, using the IBC array, a custom ∼50,000 SNP genotyping array. Meta-analyses confirmed 16 lipid loci previously established in European populations at genome-wide significance level, and found multiple independent association signals within these lipid loci. Initial discovery and in silico follow-up in 7,000 additional African American samples, confirmed two novel loci: rs5030359 within ICAM1 is associated with total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) $(p = 8.8×10^{−7} and p = 1.5×10^{−6}$ respectively) and a nonsense mutation rs3211938 within CD36 is associated with high-density lipoprotein cholesterol (HDL-C) levels $(p = 13.5×10^{−12})$. The rs3211938-G allele, which is nearly absent in European and Asian populations, has been previously found to be associated with CD36 deficiency and shows a signature of selection in Africans and African Americans. Finally, we have evaluated the effect of SNPs established in European populations on lipid levels in multi-ethnic populations and show that most known lipid association signals span across ethnicities. However, differences between populations, especially differences in allele frequency, can be leveraged to identify novel signals, as shown by the discovery of ICAM1 and CD36 in the current report

The International Natural Product Sciences Taskforce (INPST) and the power of Twitter networking exemplified through #INPST hashtag analysis

Background: The development of digital technologies and the evolution of open innovation approaches have enabled the creation of diverse virtual organizations and enterprises coordinating their activities primarily online. The open innovation platform titled "International Natural Product Sciences Taskforce" (INPST) was established in 2018, to bring together in collaborative environment individuals and organizations interested in natural product scientific research, and to empower their interactions by using digital communication tools. Methods: In this work, we present a general overview of INPST activities and showcase the specific use of Twitter as a powerful networking tool that was used to host a one-week "2021 INPST Twitter Networking Event" (spanning from 31st May 2021 to 6th June 2021) based on the application of the Twitter hashtag #INPST. Results and Conclusion: The use of this hashtag during the networking event period was analyzed with Symplur Signals (https://www.symplur.com/), revealing a total of 6,036 tweets, shared by 686 users, which generated a total of 65,004,773 impressions (views of the respective tweets). This networking event's achieved high visibility and participation rate showcases a convincing example of how this social media platform can be used as a highly effective tool to host virtual Twitter-based international biomedical research events

Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition

About half of all cancers have somatic integrations of retrotransposons. Here, to characterize their role in oncogenesis, we analyzed the patterns and mechanisms of somatic retrotransposition in 2,954 cancer genomes from 38 histological cancer subtypes within the framework of the Pan-Cancer Analysis of Whole Genomes (PCAWG) project. We identified 19,166 somatically acquired retrotransposition events, which affected 35% of samples and spanned a range of event types. Long interspersed nuclear element (LINE-1; L1 hereafter) insertions emerged as the first most frequent type of somatic structural variation in esophageal adenocarcinoma, and the second most frequent in head-and-neck and colorectal cancers. Aberrant L1 integrations can delete megabase-scale regions of a chromosome, which sometimes leads to the removal of tumor-suppressor genes, and can induce complex translocations and large-scale duplications. Somatic retrotranspositions can also initiate breakage–fusion–bridge cycles, leading to high-level amplification of oncogenes. These observations illuminate a relevant role of L1 retrotransposition in remodeling the cancer genome, with potential implications for the development of human tumors

Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1

Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value &lt; 1 × 10-5) in 2871 additional cases and 32,687 controls and performed further follow-up in 1491 AAA and 11,060 controls. In the discovery study, nine loci demonstrated association with AAA (p &lt; 1 × 10-5). In the replication sample, the lead SNP at one of these loci, rs1466535, located within intron 1 of low-density-lipoprotein receptor-related protein 1 (LRP1) demonstrated significant association (p = 0.0042). We confirmed the association of rs1466535 and AAA in our follow-up study (p = 0.035). In a combined analysis (6228 AAA and 49182 controls), rs1466535 had a consistent effect size and direction in all sample sets (combined p = 4.52 × 10-10, odds ratio 1.15 [1.10-1.21]). No associations were seen for either rs1466535 or the 12q13.3 locus in independent association studies of coronary artery disease, blood pressure, diabetes, or hyperlipidaemia, suggesting that this locus is specific to AAA. Gene-expression studies demonstrated a trend toward increased LRP1 expression for the rs1466535 CC genotype in arterial tissues; there was a significant (p = 0.029) 1.19-fold (1.04-1.36) increase in LRP1 expression in CC homozygotes compared to TT homozygotes in aortic adventitia. Functional studies demonstrated that rs1466535 might alter a SREBP-1 binding site and influence enhancer activity at the locus. In conclusion, this study has identified a biologically plausible genetic variant associated specifically with AAA, and we suggest that this variant has a possible functional role in LRP1 expression