N-Acetyl Cysteine Inhibits Endothelin-1-Induced ROS Dependent Cardiac Hypertrophy through Superoxide Dismutase Regulation

Objective: Oxidative stress down regulates antioxidant enzymes including superoxide dismutase (SOD) and contributes to the development of cardiac hypertrophy. N-Acetyl cysteine (NAC) can enhance the SOD activity, so the aim of this study is to highlight the inhibitory role of NAC against endothelin-1 (ET-1)-induced cardiac hypertrophy. Materials and Methods: In this experimental study at QAU from January, 2013 to March, 2013. ET-1 (50 μg/kg) and NAC (50 mg/kg) were given intraperitoneally to 6-day old neonatal rats in combination or alone. All rats were sacrificed 15 days after the final injection. Histological analysis was carried out to observe the effects caused by both drugs. Reactive oxygen species (ROS) analysis and SOD assay were also carried out. Expression level of hypertrophic marker, brain natriuretic peptide (BNP), was detected by western blotting. Results: Our findings showed that ET-1-induced cardiac hypertrophy leading towards heart failure was due to the imbalance of different parameters including free radical-induced oxidative stress and antioxidative enzymes such as SOD. Furthermore NAC acted as an antioxidant and played inhibitory role against ROS-dependent hypertrophy via regulatory role of SOD as a result of oxidative response associated with hypertrophy. Conclusion: ET-1-induced hypertrophic response is associated with increased ROS production and decreased SOD level, while NAC plays a role against free radicals-induced oxidative stress via SOD regulation

Perception of healthcare workers regarding the psychological impact of COVID-19 on their children

Background and Objective: Pandemics like COVID-19 adversely affect children&rsquo;s behavior and psychological development by disrupting routine life activities. Children of healthcare workers are exposed additionally due to the fear of parental exposure to the virus. The objective of this study was to assess the perception of frontline healthcare workers (HCWs) regarding the psychological impact of the COVID-19 pandemic on their children. We also sought to identify the difference of the psychological impact on children of the male and female healthcare workers.Methods: A survey questionnaire was developed comprising 10 questions about the perception of HCWs regarding the psychological impact of COVID-19 on their children. It was distributed both online and face to face among 150 healthcare professionals, working in training and non-training posts in 4 public and 5 nongovernment hospitals of Pakistan. The mean and standard deviation were calculated for each survey item using Statistical Package for the Social Sciences 26.0. Results: The response rate was 71.3% and majority (64.2%) of the healthcare professionals were &ge;30 years of age. Ninety-two HCWs (85.98%) either agreed or strongly agreed that the parental separation from their kids for long hours during the pandemic had a negative psychological impact on their children. There was a significant difference in perceived psychological impact of COVID-19 on the children of male and female HCWs, with a mean survey score of 2.29 &plusmn; 1.82 and 1.69 &plusmn; 0.79, respectively (t = 2.29, p-value = 0.024).Conclusion: Children of the healthcare workers experience more stress and anxiety because of long duty hours and working in high-risk settings. Continuous psychological support and counseling services may be adopted formally to prevent unforeseen adverse events or any long-term negative impact on their physical and mental health.</p

Oral health related quality of life in head and neck cancer survivors within the first year following treatment: A cross-sectional study in Karachi, Pakistan

After completing treatment for head and neck cancer (HNC), patients often face oral complications like oral pain, limited mouth opening and dry mouth which significantly reduce their oral health related quality of life (OHRQoL). These issues impact their overall well-being, social activities and long-term survival. The primary objective of this study was to evaluate OHRQoL and its association with sociodemographic characteristics, oral hygiene practices and oral clinical parameters such as oral hygiene status and oral mucositis grade in patients who have completed treatment for head and neck cancer. This cross-sectional study involved 79 HNC-treated patients within first year after completion of cancer treatment attending ENT and dental clinics at outpatient department (OPD) setting in Karachi. Data was collected electronically using structured questionnaire comprising of EORTC QLQ H&N - 35 to measure OHRQoL, patients were also examined for oral hygiene status using oral hygiene index- simplified (OHI-s) and oral mucositis grade using WHO oral mucositis scale. Multiple linear regression was used to test OHRQoL associations with the sociodemographic and different clinical factors. The result showed an overall mean score for oral health related quality of life (OHRQoL) of 25.02 ± 15.86 (95% CI 21.46-28.57), with difficulty in mouth opening 53.16 ± 18.88 and dry mouth 45.14 ± 24.48 being predominant concerns for decline in the OHRQoL in the population. Male predilection was observed among participants n = 60 (75.9%), majority of the participants n = 41 (51.9%) were below 52 years of age. n = 63 (80%) participants received radiotherapy alongside surgery and chemotherapy. Most of participants n = 66 (83.5%) experienced moderate to severe oral mucositis with poor oral hygiene status n = 56 (71%). Significant associations were found between OHRQoL and BMI, OH status, marital status, monthly income, gender and fluoride toothpaste (p \u3c 0.05). These findings suggest that Quality of Life (QoL) among HNC treated patients is negatively impacted by their poor oral health, post cancer treatment. Therefore, it is important to evaluate and modify the current treatment modalities and involve multidisciplinary teams, to improve their OHRQoL thereby enhancing overall QoL

Supporting Depressed Mothers of Young Children with Intellectual Disability: Feasibility of an Integrated Parenting Intervention in a Low-Income Setting

As a lifelong condition, intellectual disability (ID) remains a public health priority. Parents caring for children with ID experience serious challenges to their wellbeing, including depression, anxiety, stress and health-related quality of life. Integrated parenting interventions, which have been well evidenced for depressed mothers, may also effectively support depressed parents with a child with ID in low-resource settings such as Pakistan, and in turn optimise child outcomes. We conducted a mixed-method rater-blind feasibility randomised controlled trial, which assessed the feasibility and acceptability of the Learning Through Play in My Own Way Plus (LTP-IMOW Plus) intervention. Mothers who screened positive for depression (n = 26) with a young child (age 3–6 years) with ID were recruited from two low-resource community settings. Participants in the intervention arm (n = 13) received 12 group sessions of LTP-IMOW Plus and others (n = 13) received routine care. The intervention was feasible and acceptable with 100% retention and 100% session attendance. The intervention improved depression, anxiety, parenting stress and child socialisation score outcomes relative to the routine care arm. The framework utilised to analyse the qualitative interviews with seven participants at pre-intervention identified a range of struggles experienced by the mothers, and at post-intervention, found improved knowledge of child development and practices, improved mother–child relationships, recommendations for the intervention and perceived practical barriers and facilitators. The findings highlight the prospects for a clinical and cost-effective trial of an integrated parenting intervention to manage long-term parental mental health needs and improve child outcomes

Interplay of N- acetyl cysteine and melatonin in regulating oxidative stress-induced cardiac hypertrophic factors and microRNAs

Early and specific diagnosis of oxidative stress linked diseases as cardiac heart diseases remains a major dilemma for researchers and clinicians. MicroRNAs may serve as a better tool for specific early diagnostics and propose their utilization in future molecular medicines. We aimed to measure the microRNAs expressions in oxidative stress linked cardiac hypertrophic condition induced through stimulants as Endothelin and Isoproterenol. Cardiac hypertrophic animal models were confirmed by BNP, GATA4 expression, histological assays, and increased cell surface area. High oxidative stress (ROS level) and decreased antioxidant activities were assessed in hypertrophied groups. Enhanced expression of miR-152, miR-212/132 while decreased miR-142-3p expression was observed in hypertrophic condition. Similar pattern of these microRNAs was detected in HL-1 cells treated with H2O2. Upon administration of antioxidants, the miRNAs expression pattern altered from that of the cardiac hypertrophied model. Present investigation suggests that oxidative stress generated during the cardiac pathology may directly or indirectly regulate anti-hypertrophy pathway elements through microRNAs including antioxidant enzymes, which need further investigation. The down-regulation of free radical scavengers make it easier for the oxidative stress to play a key role in disease progression.</p

Chemical profiling and evaluation of toxicological, antioxidant, anti-inflammatory, anti-nociceptive and tyrosinase inhibitory potential of Portulacaria afra using in-vitro, in-vivo and in-silico studies

Portulacaria afra Jacq (Portulacaceae) is a medicinal plant used traditionally in the treatment of pain and inflammation. This study aimed to evaluate the phytochemical composition, toxicity, antinociceptive, and enzyme inhibition potential of P. afra. The methanol extract (PAME) was prepared through maceration and fractionated with ethanol to ethanol fraction of P. afra (ETPA). Both PAME and ETPA were found to be rich in total phenolic (TPC) and total flavonoid contents (TFC). Similarly, PAME showed the highest antioxidant potential through ABTS 93.16 ± 0.05 mg TE /g of dry extract (D.E.) while ETPA showed maximum results (462 ± 1.44 mg TE/g) in the CUPRAC method. The RP-UHPLC-MS analysis of PAME showed tentative identification of 101 compounds in the positive mode and 14 compounds in the negative mode of ionization while GC–MS profiling gave a total of 15 compounds. The acute oral toxicity study of PAME revealed the safety and biocompatibility of the extract up to a dose of 5000 mg/kg orally in rats. In-vitro data revealed that varying concentrations of P. afra significantly (p < 0.05) inhibited heat-induced BSA denaturation compared to indomethacin in a concentration-dependent manner. PAME suppressed carrageenan-induced paw edema at the 4th hr with maximum inhibition. The analgesic efficacy of PAME was determined by the hotplate, writhing method, and tail-flicking rat models. In the hot plate method, PAME treated groups showed a significant effect (p < 0.0001). While in the writhing model, the PAME treated groups showed a significant (p < 0.0001) anti-nociceptive effect at 200 mg/kg and 400 mg/kg compared to the control group. Similarly, PAME treated groups in the tail flicking model showed a significant (p < 0.001) anti-nociceptive effect at 200 mg/kg and 400 mg/kg. A dose-dependent increase in latency time (8.78 ± 0.090 at (30 min), 11.39 ± 0.005 at (60 min), 12.14 ± 0.01 at (90 min) 15.19 ± 0.03 at (120 min), p < 0.0001 was observed, compared to the control group. Similarly, the extract and fraction showed significant inhibitory potential against tyrosinase in in vitro and in-silico studies. Conclusively the current study unveiled P. afra as a novel non-toxic source with good total antioxidant-mediated anti-inflammatory and analgesic potential

Results of logistic regression analysis for Genotype and allele frequency of SNPs rs11720822 in <i>PDIA5</i> and rs2754511 in <i>BIRC6</i> in POAG, PCAG and PEXG patients and control individuals.

a<p>Age and gender adjusted OR and (95%CI) from multivariate logistic regression analysis; p^bBonferoni corrected p values; ^cOR and (95%CI) from univariate logistic regression analysis; Est., estimates</p

Spectrum of recurrent <i>GJB2</i> mutations in Pakistani families with autosomal recessive non-syndromic hearing loss (ARNSHL).

<p>As reference sequence NM_004004.5 was employed. EVS, exome variant server;</p>#<p>The pathogenicity of this mutation is controversial.</p