Does diversification affect capital structure and profitability in Pakistan?

Diversification has become a common strategy of corporate risk management along with availing other potential benefits. The intent of this study is to identify and analyze the nature of relationship that exists between diversification and capital structure as well as profitability in Pakistan. For this purpose we use the 10 years’ (2000-2009) data of all the companies of chemical and food sector listed at the Karachi Stock Exchange (KSE). We find that the diversified firms are more profitable. Using independent variables of firm size, growth and tangibility the results show that whenever significant, the relationship is associated with greater amount of debt held by the firm

Willingness to pay for vaccination against hepatitis b and its determinants: the case study of an industrial district of Pakistan

Willingness to pay (WTP) for vaccination of hepatitis disease is a good measure to monetize the physical effects of a disease into monetary values. Therefore, the present study aims to find the willingness to pay for self-paid vaccines for hepatitis and its determinants in an industrial district Faisalabad, Pakistan. Primary data was collected from 200 nonpatients of hepatitis which were personally interviewed by using convenient sampling method. A scenario was presented to the selected respondents by using CVM technique. The respondents were randomly assigned to pre-chosen payment bids defined on the basis of prevailing market rates for vaccination at the time of survey. The multivariate linear regression was used to find the determinants of WTP. The results show that females are slightly more willing to pay as compared to males. The variables like age, income and awareness about hepatitis have positive impact on WTP for vaccination of hepatitis disease. About 57.3 percent people belonging to low income group wanted vaccination free of cost in Pakistan.Government should launch free vaccination programs for the most vulnerable group (poor) and must launch awareness campaign to increase knowledge about disease

Estimation of Nonalcoholic Fatty Liver Disease in Patients with Normal BMI on Ultrasound

Background: Non-Alcoholic fatty liver disease is common in adults and it is increasing in patients with normal BMI in Asian countries. Non-alcoholic fatty liver disease (NAFLD) occurs not only in obese individuals but also in non-obese ones. The association between NAFLD and metabolic events in a non-obese population is also evident.. Objective: To estimate nonalcoholic fatty liver disease in patients with normal BMI on ultrasound. Methodology: Analytical Cross-sectional prospective study in which 59 patients were enrolled in the research. All the patient’s data had been composed from indoor of hospital, outdoor of hospital, DHA Medical Center, Lahore. After well-versed consent, data was composed through ultrasound machine. The data, such as patient characteristics, hypertension, impaired fasting glucose, were extracted from medical records, and statistical analysis was performed. Results: The present study is retrospective cross sectional observational study.60 patients (29males 49.2% 31 female 50.8%) were enrolled in this study. According to abdominal ultrasonography, 72.9% of patients with normal BMI were diagnosed to have Non-alcoholic fatty liver disease and identified to have fatty changes in the liver. Conclusion: In our study we estimated that nonalcoholic fatty liver disease was present in patients with normal body mass index by imaging the echotexture of liver on ultrasound. Having increased echogenicity, due to poor diet and other associated diseases such as high blood pressure, impaired fasting glucose and low HDL cholesterol patients were getting NAFLD. Keywords: Nonalcoholic fatty liver disease (NAFLD), Body Mass Index (BMI), Ultrasonography (USG). DOI: 10.7176/JHMN/92-03 Publication date:August 31st 202

Evaluation of β-catenin inhibition of axitinib and nitazoxanide in human monocyte-derived dendritic cells

Modulation of β-catenin signaling has attractive therapeutic potential in cancer immunotherapy. Several studies have found that β-catenin can mediate immune evasion in cancer and promote anti-inflammatory features of antigen-presenting dendritic cells. Many small molecular compounds that inhibit Wnt/β-catenin signaling are currently in clinical development, but none have entered routine clinical use. New inhibitors of β-catenin signaling are consequently desirable. Here, we have tested, in monocyte-derived dendritic cells, the effects of two small molecular compounds, axitinib and nitazoxanide, that previously have been discovered to inhibit β-catenin signaling in colon cancer cells. Immature and lipopolysaccharide-matured dendritic cells prepared from healthy blood donor buffy coats were stimulated with 6-bromoindirubin-3′-oxime (6-BIO) to boost basal β-catenin activity, and the effects of axitinib and nitazoxanide were compared with the commercial β-catenin inhibitor ICG-001. Assays, including genome-wide RNA-sequencing, indicated that neither axitinib nor nitazoxanide demonstrated considerable β-catenin inhibition. Both compounds were found to be less toxic to monocyte-derived dendritic cells than either 6-BIO or ICG-001. Axitinib stimulated several aspects of dendritic cell function, such as IL12-p70 secretion, and counteracted IL-10 secretion, according to the present study. However, neither axitinib nor nitazoxanide were found to be efficient β-catenin inhibitors in monocyte-derived dendritic cells.publishedVersio

GM-CSF, Flt3-L and IL-4 affect viability and function of conventional dendritic cell types 1 and 2

Conventional type 1 dendritic cells (cDC1) and conventional type 2 dendritic cells (cDC2) have attracted increasing attention as alternatives to monocyte-derived dendritic cells (moDCs) in cancer immunotherapy. Use of cDCs for therapy has been hindered by their low numbers in peripheral blood. In the present study, we found that extensive spontaneous apoptosis and cDC death in culture within 24hrs represent an additional challenge. Different media conditions that maintain cDC viability and function were investigated. CD141+ cDC1 and CD1c+ cDC2 were isolated from healthy blood donor buffy coats. Low viabilities were found with CellGenix DC, RPMI-1640, and X-VIVO 15 standard culture media and with several supplements at 24hrs and 48hrs. Among multiple factors it was found that GM-CSF improved both cDC1 and cDC2 viability, whereas Flt3-L and IL-4 only increased viability of cDC1 and cDC2, respectively. Combinations of these three cytokines improved viability of both cDCs further, both at 24hrs and 48hrs time points. Although these cytokines have been extensively investigated for their role in myeloid cell differentiation, and are also used clinically, their effects on mature cDCs remain incompletely known, in particular effects on pro-inflammatory or tolerogenic cDC features. HLA-DR, CD80, CD83, CD86, PD-L1 and PD-L2 cDC membrane expressions were relatively little affected by GM-CSF, IL-4 and Flt3-L cytokine supplements compared to the strong induction following Toll-like receptor (TLR) stimulation for 24hrs. With minor exceptions the three cytokines appeared to be permissive to the TLR-induced marker expression. Allogeneic mixed leukocyte reaction showed that the cytokines promoted T-cell proliferation and revealed a potential to boost both Th1 and Th2 polarizing cytokines. GM-CSF and Flt3-L and their combination improved the capability of cDC1 for dextran uptake, while in cDC2, dextran capture was improved by GM-CSF. The data suggest that GM-CSF, IL-4 and Flt3-L and combinations might be beneficial for DC viability and function in vitro. Limited viability of cDCs could be a confounding variable experimentally and in immunotherapy.publishedVersio

Proteasome‐mediated regulation of GATA2 expression and androgen receptor transcription in benign prostate epithelial cells

GATA2 has been shown to be an important transcription factor together with androgen receptor (AR) in prostate cancer cells. Less is known about GATA2 in benign prostate epithelial cells. We have investigated if GATA2 exogenous expression in prostate epithelial basal-like cells could induce AR transcription or luminal differentiation. Prostate epithelial basal-like (transit amplifying) cells were transduced with lentiviral vector expressing GATA2. Luminal differentiation markers were assessed by RT-qPCR, Western blot and global gene expression microarrays. We utilized our previously established AR and androgen-dependent fluorescence reporter assay to investigate AR activity at the single-cell level. Exogenous GATA2 protein was rapidly and proteasome-dependently degraded. GATA2 protein expression was rescued by the proteasome inhibitor MG132 and partly by mutating the target site of the E3 ligase FBXW7. Moreover, MG132-mediated proteasome inhibition induced AR mRNA and additional luminal marker gene transcription in the prostate transit amplifying cells. Different types of intrinsic mechanisms restricted GATA2 expression in the transit amplifying cells. The appearance of AR mRNA and additional luminal marker gene expression changes following proteasome inhibition suggests control of essential cofactor(s) of AR mRNA expression and luminal differentiation at this proteolytic level.publishedVersio

Use of N-Acetylcysteine in Psychiatric Conditions among Children and Adolescents: A Scoping Review.

N-acetylcysteine (NAC) is a well-known antidote for acetaminophen toxicity and is easily available over the counter. It has antioxidant and anti-inflammatory properties and an established tolerance and safety profile. Owing to its neuroprotective effects, its clinical use has recently expanded to include the treatment of different psychiatric and non-psychiatric disorders. Although a number of randomized controlled trials have documented the clinical evidence for NAC, there are no reviews that summarize the evidence. The present scoping review summarizes the study designs, the patient characteristics, the evidence and the limitations in randomized controlled trials designed to explore the efficacy of NAC for psychiatric conditions in the pediatric population

Computational analysis and expression profiling of potassium transport-related gene families in mango (Mangifera indica) indicate their role in stress response and fruit development

Mango (Mangifera indica) fruit is known for its taste, health benefits, and drought tolerance. Potassium (K+) is one of the most abundant ions in a plant cell. It is important for various biological functions related to plant growth, development, and flowering/fruiting. It significantly contributes to fruit yield, quality, and drought tolerance in plants. However, molecular mechanisms comprising K+ transport in mango are least known. In the present study, 37 members of K+ transport-related genes (PTGs) were identified in mango, which include 22 K+ transporters (16 HAKs, 1 HKT, and 6 KEAs) and 15 K+ channels (6 TPKs and 8 Shakers). All PTGs were predicted to be expressed at the plasma membrane and possess characteristic motifs and domains. Phylogenetic analysis identified a strong kinship of PTGs among Oryza sativa, Arabidopsis thaliana, Cicer arietinum, Malus domestica, and M. indica. The promoter analysis identified 60 types of cis-elements related to various biological processes. RNA-seq-based expression profiling identified that MiTPK1.2, MiHAK1, MiHAK2.1, HAK6.1, and MiAKT1.1 were most upregulated in roots and that MiKEA2, MiAKT2, and MiAKT1 were upregulated in leaves. Moreover, MiAKT6, MiHAK1.1, MiKAT2, MiKAT2.1, MiHKT1, MiTPK1.1, MiHAK7, and MiHAK12 were highly expressed during the five growth stages of mango fruit. The current study is the first comprehensive report on K+ transport system in tropical fruits. Therefore, it will provide the foundation knowledge for the functional characterization of K+ genes in mango and related plants

SONOGRAPHIC EVALUATION OF ESTIMATED FETAL WEIGHT BY DIFFERENT METHOD AT TERM AND POST TERM

Objective: To determine fetal weight estimation by different method on ultrasound at term & to determine actual baby weight after birth Methodology: The research is conducted in Meer Children and Family Clinic Tajpura Lahore. 121 women participate in this study over a 4 month period from January 2021 to April 2021. Systematic random sampling was used to make the selection. The scanner has Hadlock, Shepard, shibozuka and warsof formula.  Results: Out of 70 pregnant women in which 36 (51.5%) nulliparous women and 34(48.5%) multiparous women. A total of 45(64.3%) by vaginal delivery while 25(35.7%) deliver by C – Section. The minimum maternal age for nulliparous women is 21 years and maximum maternal age for multiparous is 39 years. The minimum Actual birth weight i.e. 2.40 correlate with estimated fetal weight. The maximum Actual birth weight i.e. 4.00 correlate with estimated fetal weight. The mean Actual birth weight   is significantly increase with increase in both parity and maternal age at delivery Conclusion: For most pregnant women, estimated fetal weight based on multiple fetal parameters provides reliable and clinically useful information. Despite the fact that there is still an acceptable difference between the actual birth weight and the sonographically EFW. Keywords: Fetal Macrosomia, Term Pregnancy, Hadlocks Formula , Actual birth weight DOI: 10.7176/JHMN/91-11 Publication date:July 31st 202

A phase I prospective, non-randomized trial of autologous dendritic cell-based cryoimmunotherapy in patients with metastatic castration-resistant prostate cancer

Metastatic castration-resistant prostate cancer (mCRPC) is an immunologically cold disease with dismal outcomes. Cryoablation destroys cancer tissue, releases tumor-associated antigens and creates a pro-inflammatory microenvironment, while dendritic cells (DCs) activate immune responses through processing of antigens. Immunotherapy combinations could enhance the anti-tumor efficacy. This open-label, single-arm, single-center phase I trial determined the safety and tolerability of combining cryoablation and autologous immature DC, without and with checkpoint inhibitors. Immune responses and clinical outcomes were evaluated. Patients with mCRPC, confirmed metastases and intact prostate gland were included. The first participants underwent prostate cryoablation with intratumoral injection of autologous DCs in a 3 + 3 design. In the second part, patients received cryoablation, the highest acceptable DC dose, and checkpoint inhibition with either ipilimumab or pembrolizumab. Sequentially collected information on adverse events, quality of life, blood values and images were analyzed by standard descriptive statistics. Neither dose-limiting toxicities nor adverse events > grade 3 were observed in the 18 participants. Results indicate antitumor activity through altered T cell receptor repertoires, and 33% durable (> 46 weeks) clinical benefit with median 40.7 months overall survival. Post-treatment pain and fatigue were associated with circulating tumor cell (CTC) presence at inclusion, while CTC responses correlated with clinical outcomes. This trial demonstrates that cryoimmunotherapy in mCRPC is safe and well tolerated, also for the highest DC dose (2.0 × 108) combined with checkpoint inhibitors. Further studies focusing on the biologic indications of antitumor activity and immune system activation could be considered through a phase II trial focusing on treatment responses and immunologic biomarkers.publishedVersio