Investigations into the Regulation of the Redox Activity of Protein Disulfide Isomerase by Active Site-Flanking Lysines

Protein disulfide isomerase (PDI) is crucial in the redox of disulfide bonds, where it catalyzes reductase, oxidase, and isomerase activity. The active site motif for PDI is CXXC, which is found in the a and a’ domain. PDI is mainly localized to the endoplasmic reticulum, where it plays a key role in the folding of new proteins through proper disulfide formation. With new studies about the regulation of protein activity by lysine acetylation, our group wished investigate this post-translational modification on PDI. Flanking each active site motif of PDI is a lysine residue. These active site-flanking lysine residues were mutated individually and together to observe if any catalytic change occurred. Mutation of the lysine residue to glutamine, alanine, or glutamic acid resulted in a decrease in activity, indicating the importance of the lysine residue for optimal PDI activity. Acetylation of PDI was performed by acetic anhydride, where through mass spectrometry, PDI was observed to be partially acetylated. The catalytic efficiency of the acetylated wt-PDI was observed to decrease in comparison to un-acetylated PDI. Indicating that acetylation of PDI may be a possible regulator of PDI redox activity

Gender-specific psychological and social impact of COVID-19 in Pakistan

Background: COVID-19 has rapidly spread across the world. Women may be especially vulnerable to depression and anxiety as a result of the pandemic.Aims: This study attempted to assess how gender affects risk perceptions, anxiety levels and behavioural responses to the COVID-19 pandemic in Pakistan, to recommend gender-responsive health policies.Methods: A cross-sectional online survey was conducted. Participants were asked to complete a sociodemographic data form, the Hospital Anxiety and Depression Scale, and questions on their risk perceptions, preventive behaviour and information exposure. Multiple logistic regression analysis was used to assess the effects of factors such as age, gender and household income on anxiety levels.Results: Of the 1391 respondents, 478 were women and 913 were men. Women considered their chances of survival to be relatively lower than men (59% v. 73%). They were also more anxious (62% v. 50%) and more likely to adopt precautionary behaviour, such as avoiding going to the hospital (78% v. 71%), not going to work (72% v. 57%) and using disinfectants (93% v. 86%). Men were more likely to trust friends, family and social media as reliable sources of COVID-19 information, whereas women were more likely to trust doctors.Conclusions: Women experience a disproportionate burden of the psychological and social impact of the pandemic compared with men. Involving doctors in healthcare communication targeting women might prove effective. Social media and radio programmes may be effective in disseminating COVID-19-related information to men

Sensitivity Analysis of Reinforcement Learning to Schedule the battery in Grid-tied microgrid

This research paper explores the application of offline reinforcement learning (RL) in controlling battery operation in a grid-connected microgrid. The study investigates the impact of different parameters on the performance of the RL algorithm, such as the number of discretization levels, gamma, and alpha values. The results show that the convergence time and optimality of the RL algorithm are affected by the choice of these parameters. The research concludes that carefully selecting the discretization levels of state-action spaces and RL hyperparameters is crucial for optimal RL algorithm performance. The benchmark offline sensitivity analysis can be compared in the future with other RL approaches, such as function approximation or DRL methods

Management of penetrating injury to thoracic inlet and lower neck with retained foreign body using video assisted thoracoscopic surgery

Penetrating neck and chest injuries are a common form of occupational injuries. We hereby report a unique case in which a metallic rod had penetrated the left chest and neck of a plastic factory worker. The patient was vitally stable when he presented to Emergency Room. Chest X-ray was performed and the patient was rushed to the operating room. VATS (video assisted thoracoscopic surgery) and neck dissection was done for retrieval of the metallic rod. On table, endoscopy was also done to rule out injury to oesophagus. No injury to vital structures was found and the subsequent recovery was uneventful

Pattern of presenting complaints recorded as near-drowning events in emergency departments: a national surveillance study from Pakistan.

Background: Drowning is a heavy burden on the health systems of many countries, including Pakistan. To date, no effective large-scale surveillance has been in place to estimate rates of drowning and near-drowning in Pakistan. The Pakistan National Emergency Department Surveillance (Pak-NEDS) study aimed to fill this gap. Method: Patients who presented with a complaint of “near-drowning” were analyzed to explore patterns of true near-drowning (unintentional) and intentional injuries that led to the “near-drowning” complaint. Bivariate analysis was done to establish patterns among patients treated in emergency departments, including socio-demographic information, injury-related information, accompanying injuries, and emergency department resource utilization. Result: A total of 133 patients (0.2% of all injury patients) with “near-drowning” as presenting complaints were recorded by the Pak-NEDS system. True near-drowning (50.0%) and intentional injuries that led to “near-drowning” complaints (50.0%) differed in nature of injuries. The highest proportion of true near-drowning incidents occurred among patients aged between 25-44 years (47.5%), and among males (77.5%). True near-drowning patients usually had other accompanying complaints, such as lower limb injury (40.0%). Very few patients were transported by ambulance (5.0%), and triage was done for 15% of patients. Eleven (27.5%) true near-drowning patients received cardiopulmonary resuscitation. Conclusion: There was major under-reporting of drowning and near-drowning cases in the surveillance study. The etiology of near-drowning cases should be further studied. Patients who experienced non-fatal drownings were more commonly sent for medical care due to other accompanying conditions, rather than near-drowning event itself. There is also need for recognizing true near-drowning incidents. The results of this study provide information on data source selection, site location, emergency care standardization, and multi-sector collaboration for future drowning prevention studies

Islamophobia in the West and Post 9/11 Era

The concept of Islamophobia started from the crusade when Christianity challenged Islam. After the attack on World Trade Center, the West manipulated the concept and socialized its people about the fear and threat from Islam which actually does not exists because radical Islam or few people who are not practical Muslims, are not the representatives of whole Muslim states. The trade sanctions, misinterpretations on media about Islam, conflicts in Muslim states which are not resolved even in the presence of international organizations, are the hatred regimes by the West at intellectual level. Ideological dispersal, exploitation, wars, distortion by different ideological regimes and insurgency created within the Muslim society are the clear picture of hatred regime in the West against Islam. Thus, Islamophobia is now a fact rather than utopian idea. Secondary data sources along with the theory of social constructivism are being carried out in this paper. Keywords: Islamophobia, Politics, Media, Misinterpretations, Organizations, Ideology, Campaigns, Dispersal, Utopia, crusade, hatred, regime DOI: 10.7176/IAGS/78-04 Publication date: December 31st 201

Helmet wearing saves the cost of motorcycle head injuries: A case study from Karachi, Pakistan

Purpose: To estimate the difference in healthcare cost of head injuries among motorcycle helmet users and non-users.Methods: Motorcycle crash victims with head injuries that were brought to a public, tertiary care emergency room in Karachi were studied through a descriptive cross-sectional design. A standard questionnaire was used to collect data on demographics, injury pattern, helmeting practice, length of hospital stay, out-of-pocket payments (OOPs), and healthcare service utilization at the facility to estimate total healthcare and other costs applying micro-costing methods during the hospitalization period.Results: A total of 323 motorcyclists involved in crash were brought to a public tertiary care ER, 112 patients had head injuries and were enrolled in the study. The helmeted motorcyclists had a significantly lower median total healthcare cost of PKR 10,796 ($69) [IQR 9851 ($63)-PKR 12,581 ($80)] compared to higher cost of PKR 12,113 ($77) [IQR 10,431 ($66)-50,545 ($322)] (p value = 0.046) in non-helmeted. Helmet users expended significantly less cost on laboratory tests, PKR 365 ($2) [IQR 365 ($2)-548 ($3)] compared to PKR 3650 ($23) [IQR 365 ($2)-5840 ($37)] (p value =0.027) among non-users. Furthermore, cost of radiological investigations was also low among helmeted patients compared to non-helmeted ones, median PKR 4096 ($26) [IQR 3166 ($20)-5678 ($36)] vs 4750 ($30) [3166 ($20)-11,358 ($72)] (p value =0.049). The out-of-pocket payments (OOPs) for healthcare services were lower among helmet users as compared to non-users, with cost of PKR 17,750 ($113) [IQR 16,650 ($106)-18,000 ($115)] vs PKR 19,800 ($126) [IQR 12,300 ($78)-30,900 ($197)] (p value =0.03), respectively.Conclusion: The result of this study demonstrates that helmet use among motorcyclists significantly reduced healthcare costs and healthcare resource utilizations during hospitalization for head injuries in Pakistan. Thus, it is important to implement strict helmet wearing laws to decrease head injuries and the cost burden on the healthcare facility and patients

Simultaneous determination of isoniazid and pyrazinamide in plasma by high performance liquid chromatography

Purpose: To develop and validate a new high performance liquid chromatographic (HPLC) method for the simultaneous determination of isoniazid (INH) and pyrazinamide (PZA) in plasma.Methods: A 150 μL aliquot of plasma was mixed with 75 μL of 10 % trichloroacetic acid containing 100 mg/L of acetanilide as the internal standard (IS). After vortex mixing and centrifugation, 100 μL of the supernatant was reacted with 20 μL of 0.1 % trans-cinnamaldehyde for 10 min, and then 40 μL of 1M ammonium acetate was added. Finally, 20 μL was injected into the HPLC system. HPLC analysis was performed on reversed phase C18 column. The initial composition of the mobile phase was 4 % acetonitrile, and 96 % of 20 mM 1-hexane sulfonic acid (PH 2.7) delivered at a flow rate 1 mL/min.Results: All calibration curves were linear (r2 > 0.997). The method was accurate, and relative error (RE) was < 4.5 % for both drugs. Intra-day and inter-day precision was good for both drugs, with the highest relative standard deviation (RSD) being 8.51 %. The lower limit of quantification was 0.60 mg/L for isoniazid and 3.00 mg/L for pyrazinamide.Conclusion: The method proposed here is precise, accurate, fast, simple and suitable for therapeutic drug monitoring of INH and PZA simultaneously.Keywords: HPLC, Isoniazid, Pyrazinamide, Plasma, Simultaneous analysi

Pattern of fall injuries in Pakistan: the Pakistan National Emergency Department Surveillance (Pak-NEDS) study.

Background: We aimed to analyse the frequency and patterns of fall-related injuries presenting to the emergency departments (EDs) across Pakistan.Methods: Pakistan National Emergency Departments surveillance system collected data from November 2010 to March 2011 on a 24/7 basis using a standardized tool in seven major EDs (five public and two private hospitals) in six major cities of Pakistan. For all patients presenting with fall-related injuries, we analysed data by intent with focus on unintentional falls. Simple frequencies were run for basic patient demographics, mechanism of falls, outcomes of fall injuries, mode of arrival to ED, investigations, and procedures with outcomes.Results: There were 3335 fall-related injuries. In cases where intent was available, two-thirds (n = 1186, 65.3%) of fall injuries were unintentional. Among unintentional fall patients presenting to EDs, the majority (76.9%) were males and between 15-44 years of age (69%). The majority of the unintentional falls (n = 671, 56.6%) were due to slipping, followed by fall from height (n = 338, 28.5%). About two-thirds (n = 675, 66.6%) of fall injuries involved extremities, followed by head/neck (n = 257, 25.4%) and face (n = 99, 9.8%). Most of the patients were discharged from the hospital (n = 1059, 89.3%). There were 17 (1.3%) deaths among unintentional fall cases.Conclusion: Falls are an important cause of injury-related visits to EDs in Pakistan. Most of the fall injury patients were men and in a productive age group. Fall injuries pose a burden on the healthcare system, especially emergency services, and future studies should therefore focus on safety measures at home and in workplaces to reduce this burden

Assessing emergency medical care in low income countries: A pilot study from Pakistan

Background: Emergency Medical Care is an important component of health care system. Unfortunately it is however, ignored in many low income countries. We assessed the availability and quality of facility-based emergency medical care in the government health care system at district level in a low income country - Pakistan. Methods: We did a quantitative pilot study of a convenience sample of 22 rural and 20 urban health facilities in 2 districts - Faisalabad and Peshawar - in Pakistan. The study consisted of three separate cross-sectional assessments of selected community leaders, health care providers, and health care facilities. Three data collection instruments were created with input from existing models for facility assessment such as those used by the Joint Commission of Accreditation of Hospitals and the National Center for Health Statistics in USA and the Medical Research Council in Pakistan. Results: The majority of respondents 43/44(98%), in community survey were not satisfied with the emergency care provided. Most participants 36/44(82%) mentioned that they will not call an ambulance in health related emergency because it does not function properly in the government system. The expenses on emergency care for the last experience were reported to be less than 5,000 Pakistani Rupees (equivalent to US$ 83) for 19/29(66%) respondents. Most health care providers 43/44(98%) were of the opinion that their facilities were inadequately equipped to treat emergencies. The majority of facilities 31/42(74%) had no budget allocated for emergency care. A review of medications and equipment available showed that many critical supplies needed in an emergency were not found in these facilities. Conclusion: Assessment of emergency care should be part of health systems analysis in Pakistan. Multiple deficiencies in emergency care at the district level in Pakistan were noted in our study. Priority should be given to make emergency care responsive to needs in Pakistan. Specific efforts should be directed to equip emergency care at district facilities and to organize an ambulance network