Development and validation of impact of early integration of palliative care and oncology(IEI PCO) questionnaire: a survey for medical oncologists and nurses.

OBJECTIVES: Many associations have recently recommended early integration of oncology and palliative care for more standard cancer care and better quality of life. We aimed to create a questionnaire to assess the opinion of medical oncologists and nurses about the clinical impact of the integrated palliative care and oncology (PCO) program. METHODS: A novel semi-structured questionnaire called Impact of Early Integration of Palliative Care Oncology (IEI PCO) questionnaire was developed and tested for validity and reliability then distributed to the oncologists and nurses working in Kuwait Cancer Control Center. RESULTS: After the pilot stage, testing the final questionnaire for validity and reliability was done with satisfactory results. Finally, the complete questionnaires were 170 out of 256 (response rate 66.41%). More awareness about the available palliative care services and the new available PCO services (p-value < 0.001 for all). Most of the oncologists and nurses agreed with the currently available structure of PCO, appreciated the patients' discharge plan and continuity of care of palliative medicine, admitted less work burden, a better attitude, and higher satisfaction (p-value for all < 0.001) toward palliative care. Significant improvements in symptoms were appreciated by oncologists and nurses after the integration of palliative care (p-value for all < 0.001. Oncologists and nurses valued repeated honest communication, discussion of the goals of care, dealing more effectively with ending active treatment, and higher acceptance of patients and families of PC policy of transfer, and significant progress in the care of end-of-life symptoms (p-value for all < 0.001). CONCLUSIONS: The IEI PCO questionnaire demonstrated the psychometric criteria for content, face, and construct validity and reliability. It provides a valuable tool to assess the impact of PCO integration. The opinion of medical oncologists and nurses was significantly positive toward the early integration of PCO in Kuwait in most aspects of care. This integration led to improved symptom control, end-of-life care, communication, and planned discharge and follow-up plans. Moreover, decreases the work burden, improves attitude, higher satisfaction of the oncology staff, and continuity of care.

Epidemiology and clinical characteristics of adult patients presenting to a low resource, tertiary care emergency department in Pakistan: Challenges & Outcomes.

Objectives: Emergency Departments (EDs) play a major role in managing acute and chronic illnesses, especially in low-to-middle-income countries like Pakistan, which lacks effective primary healthcare. This study reports the epidemiology and clinical characteristics of patients presenting over a two-year period at the Indus Hospital and Health Network (IHHN) adult ED in Karachi, Pakistan. Methods: This is a retrospective observational study conducted through chart review of 264,859 patients, aged 16 years and above, who presented to the IHHN ED, Korangi Campus, from January 2019 to December 2020 after obtaining approval from IHHN IRB. Results: Men were found to be the predominant presenting gender, with a slight rise in the number of women in 2020. The most frequent age group in 2019 was 15-25 (27.7%), whereas it was 25-35 years in 2020 (24.1%), with a decline in total number of elderly visits seen in comparison to previous years. The most frequently seen disposition was 'referral to clinic' in 2019 (48.4%) and 'discharged' in 2020 (39%). Out of all dispositions, maximum Length of stay (LOS) was seen in patients who left against medical advice in both years. Patient acuity showed the highest number of P3 (moderately ill) patients in both years. Infectious diseases accounted for greater than 10% of patients in both years (17.2% and16.5%), followed by gastrointestinal complaints (15.7% and 11.3%), genitourinary complaints (14.9% and 7.9%), and trauma (11.9% and 12.4%). Conclusion: Knowledge of epidemiology and clinical characteristics of patients can help facilitate timely planning of staff deployment and allocation of resources to avoid overcrowding, improve patient outcomes, and increase patient satisfaction through timely management.

Modulations in the host cell proteome by the hantavirus nucleocapsid protein.

Hantaviruses have evolved a unique translation strategy to boost the translation of viral mRNA in infected cells. Hantavirus nucleocapsid protein (NP) binds to the viral mRNA 5' UTR and the 40S ribosomal subunit via the ribosomal protein S19. NP associated ribosomes are selectively loaded on viral transcripts to boost their translation. Here we demonstrate that NP expression upregulated the steady-state levels of a subset of host cell factors primarily involved in protein processing in the endoplasmic reticulum. Detailed investigation of Valosin-containing protein (VCP/p97), one of the upregulated host factors, in both transfected and virus infected cells revealed that NP with the assistance of VCP mRNA 5' UTR facilitates the translation of downstream VCP ORF. The VCP mRNA contains a 5' UTR of 987 nucleotides harboring six unusual start codons upstream of the correct start codon for VCP which is located at 988th position from the 5' cap. In vitro translation of a GFP reporter transcript harboring the VCP mRNA 5' UTR generated both GFP and a short polypeptide of ~14 KDa by translation initiation from start codon located in the 5' UTR at 542nd position from the 5' cap. The translation initiation from 542nd AUG in the UTR sequence was confirmed in cells using a dual reporter construct expressing mCherry and GFP. The synthesis of 14KDa polypeptide dramatically inhibited the translation of the ORF from the downstream correct start codon at 988th position from the 5' cap. We report that purified NP binds to the VCP mRNA 5' UTR with high affinity and NP binding site is located close to the 542ndAUG. NP binding shuts down the translation of 14KDa polypeptide which then facilitates the translation initiation at the correct AUG codon. Knockdown of VCP generated lower levels of poorly infectious hantavirus particle in the cellular cytoplasm whose egress was dramatically inhibited in human umbilical vein endothelial cells. We demonstrated that VCP binds to the hantavirus glycoprotein Gn before its incorporation into assembled virions and facilitates viral spread to neighboring cells during infection. Our results suggest that ribosome engagement at the 542nd AUG codon in the 5' UTR likely regulates the endogenous steady state levels of VCP in cells. Hantaviruses interrupt this regulatory mechanism to enhance the steady state levels of VCP in virus infected cells. This augmentation facilitates virus replication, supports the transmission of the virus to adjacent cells, and promotes the release of infectious virus particles from the host cell.

A systematic review of literature on homicide followed by suicide and mental state of perpetrators.

BACKGROUND: Homicide followed by suicide is rare, devastating and perpetrated worldwide. It is commonly assumed that the perpetrator had a mental disorder, raising concomitant questions about prevention. Though events have been reported, there has been no previous systematic review of the mental health of perpetrators. AIMS: Our aims were twofold. First, to identify whether there are recognisable subgroups of homicide-suicides in published literature and, secondly, to investigate the relationship between perpetrator mental state and aspects of the incident. METHODS: We conducted a systematic review of published literature on studies of homicide followed within 24 h by suicide or serious suicide attempt that included measures of perpetrator mental state. RESULTS: Sixty studies were identified, most from North America or Europe. Methodologically, studies were too heterogeneous for meta-analysis. They fell into three main groups: family, mass shooter, and terrorist with an additional small mixed group. There was evidence of mental illness in a minority of perpetrators; its absence in the remainder was only partially evidenced. There was no clear association between any specific mental illness and homicide-suicide type, although depression was most cited. Social role disjunction, motive, substance misuse and relevant risk or threat behaviours were themes identified across all groups. Pre-established ideology was relevant in the mass shooter and terrorism groups. Prior trauma history was notable in the terrorist group. CONCLUSION: Research data were necessarily collected post-incident and in most cases without a standardised approach, so findings must be interpreted cautiously. Nevertheless, they suggest at least some preventive role for mental health professionals. Those presenting to services with depression, suicidal ideation, relationship difficulties and actual, or perceived, changes in social position or role would merit detailed, supportive assessment over time.

Self-reported preferences and barriers to continued professional development in primary care physicians: a cross-sectional web-based survey in Qatar.

INTRODUCTION: High quality and effective primary healthcare is a national priority in Qatar. Continuing professional development (CPD) for physicians is a cornerstone of this objective, yet little is known about physicians' preferences or barriers to CPD participation. METHOD: A needs assessment was conducted using a cross-sectional web-based survey of primary care physicians registered with the Department of Healthcare Practitioners (DHP) between March and June 2017. RESULTS: Two-hundred-and-eighty-one complete surveys were submitted representing physicians in both public (N = 129) and private sectors (N = 152). Physicians completed medical degrees and postgraduate training across multiple countries, and most had been practicing in Qatar for 5 years or less. 'Activities during working hours', 'cost' and 'work commitments' were the most common barriers. There was little consensus regarding the optimal timing of CPD activities, although public sector physicians were more likely to indicate weekend activities as a barrier to participation (30% vs. 9%). Over 90% of participants preferred traditional lectures, workshops, case-based sessions, small group and online self-paced learning as formats for CPD delivery, however alternative modes of delivery were also deemed acceptable (> 80% agreement). CONCLUSION: Understanding primary care physicians' barriers and preferences is an essential component of a larger necessitated needs assessment of CPD in primary care practitioners in Qatar. Further research is warranted to understand the underlying beliefs driving physicians' choices and the apparent variation between those working in the public and private sectors. CPD developers should consider approaches to mitigate perceived barriers and understand preferences to maximize the quality of participation.

Exploring cultural sensitivity during distance simulations in pediatric emergency medicine.

Background: Cultural sensitivity (CS) training is vital to pediatric emergency medicine (PEM) curricula. This study aimed to explore CS in Yale PEM fellows and emergency medicine (EM) residents at Indus Hospital and Health Network (IHHN) in Pakistan through distance simulation activities. Methods: This mixed-methods analysis of an educational intervention was conducted at Yale University in collaboration with IHHN. We approached seven U.S. PEM fellows and 22 Pakistani EM residents. We performed a baseline CS assessment using the Clinical Cultural Competency Questionnaire (CCCQ). Afterward, the U.S. PEM fellows facilitated the Pakistani EM residents through six distance simulation sessions. Qualitative data were collected through online focus groups. The CCCQ was analyzed using descriptive statistics, and content analysis was used to analyze the data from the focus groups. Results: Seven U.S. PEM fellows and 18 of 22 Pakistani EM residents responded to the CCCQ at the beginning of the module. The mean (±SD) CCCQ domain scores for the U.S. PEM fellows versus the Pakistani EM residents were 2.56 (±0.37) versus 2.87 (±0.72) for knowledge, 3.02 (±0.41) versus 3.33 (±0.71) for skill, 2.86 (±0.32) versus 3.17 (±0.73) for encounter/situation, and 3.80 (±0.30) versus 3.47 (±0.47) for attitude (each out of 5 points). Our qualitative data analysis showed that intercultural interactions were valuable. There is a common language of medicine among the U.S. PEM fellows and Pakistani EM residents. The data also highlighted a power distance between the facilitators and learners, as the United States was seen as the standard of "how to practice PEM." The challenges identified were time differences, cultural practices such as prayer times, the internet, and technology. The use of local language during debriefing was perceived to enhance engagement. Conclusion: The distance simulation involving U.S. PEM fellows and Pakistani EM residents was an effective approach in assessing various aspects of intercultural education, such as language barriers, technical challenges, and religious considerations.

Argininosuccinate lyase deficiency causes blood-brain barrier disruption via nitric oxide-mediated dysregulation of claudin expression.

Nitric oxide (NO) is a critical signaling molecule that has been implicated in the pathogenesis of neurocognitive diseases. Both excessive and insufficient NO production have been linked to pathology. Previously, we have shown that argininosuccinate lyase deficiency (ASLD) is a novel model system to investigate cell-autonomous, nitric oxide synthase-dependent NO deficiency. Humans with ASLD are at increased risk for developing hyperammonemia due to a block in ureagenesis. However, natural history studies have shown that individuals with ASLD have multisystem disease including neurocognitive deficits that can be independent of ammonia. Here, using ASLD as a model of NO deficiency, we investigated the effects of NO on brain endothelial cells in vitro and the blood-brain barrier (BBB) in vivo. Knockdown of ASL in human brain microvascular endothelial cells (HBMECs) led to decreased transendothelial electrical resistance, indicative of increased cell permeability. Mechanistically, treatment with an NO donor or inhibition of Claudin-1 improved barrier integrity in ASL-deficient HBMECs. Furthermore, in vivo assessment of a hypomorphic mouse model of ASLD showed increased BBB leakage, which was partially rescued by NO supplementation. Our results suggest that ASL-mediated NO synthesis is required for proper maintenance of brain microvascular endothelial cell functions as well as BBB integrity.

Impact of sequential capacity building on emergency department organisational flow during COVID-19 pandemic: a quasi-experimental study in a low-resource, tertiary care centre.

INTRODUCTION: A quasi-experimental study was conducted to estimate the impact of sequential emergency department (ED) capacity building interventions on key performance indicators such as patients' length of stay (LOS) and wait time (WT) during the COVID-19 pandemic. This was achieved through augmenting personnel education and head count, space restructuring and workflow reorganisation. SETTING AND PARTICIPANTS: This study included 268 352 patients presenting from January 2019 to December 2020 at Indus Hospital and Health network Karachi, a philanthropic tertiary healthcare facility in a city of 20 million residents. A follow-up study was undertaken from January to December 2021 with 123 938 participants. PRIMARY AND SECONDARY OUTCOME MEASURES: These included mean and median ED-LOS and WT for participants presenting in different cohorts. The results of the pre-COVID-19 year 2019 (phase 0) were compared with that of the COVID-19 year, 2020 (phases 1-3 corresponding to peaks, and phase 4 corresponding to reduction in caseloads). The follow-up was conducted in 2021 to see the sustainability of the sequential capacity building. RESULTS: Phases 1, 2 and 3 had a lower mean adjusted LOS (4.42, 3.92 and 4.40 hours) compared with phase 0 (4.78 hours, p<0.05) with the lowest numbers seen in phase 2. The same held true for WT with 45.1, 23.8 and 30.4 min in phases 1-3 compared with 49.9 in phase 0. However, phase 4 had a higher LOS but a lower WT when compared with phase 0 with a p<0.05. CONCLUSION: Sequential capacity building and improving the operational flow through stage appropriate interventions can be used to off-load ED patients and improve process flow metrics. This shows that models created during COVID-19 can be used to develop sustainable solutions and investment is needed in ideas such as ED-based telehealth to improve patient satisfaction and outcomes.

"To teach or not to teach- that is the question" The educational and clinical impact of introducing an outcome based, modular curriculum in Social Emergency Medicine (SEM) at a private tertiary care center in Karachi, Pakistan.

INTRODUCTION: An enhanced knowledge of Emergency Medicine (EM) personnel regarding negative Social Determinants of Health (SDH) can impact EM service provision in a resource limited country like Pakistan. Interventions to build capacity in identifying and addressing these SDH through education in Social Emergency Medicine (SEM) can be one of the ways in which EM key performance indicators (KPIs) can be improved. METHOD: A SEM based curriculum was administered to the EM residents at a tertiary care center in Karachi, Pakistan. Pre, post and delayed post-test was conducted for knowledge of EM residents and analyzed using Repeated Measures ANOVA (RMANOVA). Clinical impact of this intervention was assessed through the ability of the residents to identify the patients' SDH and determining appropriate disposition. Comparison of the bounce-back of patients in the pre-intervention (2020) and post-intervention year (2021) year was appreciated to see the clinical impact of this intervention. RESULT: A significant improvement was seen in post intervention (p < 0.001) and follow up knowledge (p < 0.001) of residents regarding negative SDH. Bounce-back rate was higher in the pre-SEM curriculum (43%) as compared to the post-SEM curriculum year (27.7%). Post-intervention, the residents were able to identify the unique Pakistani SDH, however appropriate patient disposition needs further reinforcement. CONCLUSION: The study highlights the beneficial impact of an educational intervention in SEM upon the knowledge of EM residents and the bounce-back of patients in the emergency department (ED) of a low resource setup. This educational intervention can be scaled up to other EDs across Pakistan for potential improvement in knowledge, EM process flow and KPIs.

Linum corymbulosum Protects Rats against CCl4-Induced Hepatic Injuries through Modulation of an Unfolded Protein Response Pathway and Pro-Inflammatory Intermediates.

Liver fibrosis is a major pathological feature of chronic liver disease and effective therapies are limited at present. The present study focuses on the hepatoprotective potential of L. corymbulosum against carbon tetrachloride (CCl4)-induced liver damage in rats. Analysis of Linum corymbulosum methanol extract (LCM) using high-performance liquid chromatography (HPLC) revealed the presence of rutin, apigenin, catechin, caffeic acid and myricetin. CCl4 administration lowered (p < 0.01) the activities of antioxidant enzymes and reduced glutathione (GSH) content as well as soluble proteins, whereas the concentration of H2O2, nitrite and thiobarbituric acid reactive substances was higher in hepatic samples. In serum, the level of hepatic markers and total bilirubin was elevated followed by CCl4 administration. The expression of glucose-regulated protein (GRP78), x-box binding protein-1 total (XBP-1 t), x-box binding protein-1 spliced (XBP-1 s), x-box binding protein-1 unspliced (XBP-1 u) and glutamate-cysteine ligase catalytic subunit (GCLC) was enhanced in CCl4-administered rats. Similarly, the expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and monocyte chemo attractant protein-1 (MCP-1) was strongly increased with CCl4 administration to rats. Co-administration of LCM along with CCl4 to rats lowered (p < 0.05) the expression of the above genes. Histopathology of the liver showed hepatocyte injury, leukocyte infiltration and damaged central lobules in CCl4-treated rats. However, LCM administration to CCl4-intoxicated rats restored the altered parameters towards the levels of control rats. These outcomes indicate the existence of antioxidant and anti-inflammatory constituents in the methanol extract of L. corymbulosum.

Clinical Outcomes Following the Implementation of a Novel One-Year Training Program in Emergency Medicine in Karachi, Pakistan.

Background: Most Emergency Departments (EDs) in low- and middle-income countries (LMICs), particularly in Pakistan, are staffed by physicians not formally trained in Emergency Medicine (EM). As of January 2022, there were only 13 residency training programs in EM throughout all of Pakistan. Therefore, an intermediate solution-a one-year training program in EM-was developed to build capacity. Objective: To determine the impact of a novel training program in EM on clinical metrics and outcomes. Methods: The first cohort of a novel, one-year training program-the Certification Program in Emergency Medicine (CPEM)-completed the program in June 2019. The program consisted of two arms: CPEM-Clinical (CPEM-C), which included physicians from the Indus Hospital and Health Network (IHHN) ED; and CPEM-Didactic (CPEM-D), which included physicians from EDs across Karachi. Both groups participated in weekly conferences, such as didactics, small group discussions, workshops, and journal clubs. CPEM-C learners also received clinical mentorship from local and international faculty. Mortality, length of stay (LOS), and time-to-evaluation, as well as metrics in four key areas-patients at risk for cardiovascular disease/acute coronary syndrome, sepsis, respiratory illness, and intra-abdominal trauma-were assessed before and after the initial cohort at IHHN and compared with other groups in IHHN. Findings and Conclusions: More than 125,000 patients were seen from July to December 2017 (pre-CPEM) and July to December 2019 (post-CPEM). Overall, there were significant improvements in all clinical metrics and outcomes, with the exception of LOS and time-to-evaluation, and a trend toward improved mortality. In comparing CPEM graduates to other groups in IHHN ED, most metrics and outcomes significantly improved or trended toward improvement, including mortality. Implementation of a medium-duration, intensive EM training program can help improve patient care and the development of EM as a new specialty in lower-resource settings.

Exploring Physical Characterization and Different Bio-Applications of Elaeagnus angustifolia Orchestrated Nickel Oxide Nanoparticles.

Elaeagnus angustifolia (EA) mediated green chemistry route was used for the biofabrication of NiONPs without the provision of additional surfactants and capping agents. The formation of NiONPs was confirmed using advanced different characterization techniques such as Scanning electron microscopy, UV, Fourier transmission-infrared, RAMAN, and energy dispersal spectroscopic and dynamic light scattering techniques. Further, different biological activities of EA-NiONPs were studied. Antibacterial activities were performed using five different bacterial strains using disc-diffusion assays and have shown significant results as compared to standard Oxytetracycline discs. Further, NiONPs exhibited excellent antifungal performance against different pathogenic fungal strains. The biocompatibility test was performed using human RBCs, which further confirmed that NiONPs are more biocompatible at the concentration of 7.51-31.25 µg/mL. The antioxidant activities of NiONPs were investigated using DPPH free radical scavenging assay. The NiONPs were demonstrated to have much better antioxidant potentials in terms of % DPPH scavenging (93.5%) and total antioxidant capacity (81%). Anticancer activity was also performed using HUH7 and HEP-G2 cancer cell lines and has shown significant potential with IC50 values of 18.45 µg/mL and 14.84 µg/mL, respectively. Further, the NiONPs were evaluated against Lesihmania tropica parasites and have shown strong antileishmanial potentials. The EA-NiONPs also showed excellent enzyme inhibition activities; protein kinase (19.4 mm) and alpha-amylase (51%). In conclusion, NiONPs have shown significant results against different biological assays. In the future, we suggest various in vivo activities for EA-NiONPs using different animal models to further unveil the biological and biomedical potentials.

Transmembrane 163 (TMEM163) protein interacts with specific mammalian SLC30 zinc efflux transporter family members.

Recently, we reported that TMEM163 is a zinc efflux transporter that likely belongs to the mammalian solute carrier 30 (Slc30/ZnT) subfamily of the cation diffusion facilitator (CDF) protein superfamily. We hypothesized that human TMEM163 forms functional heterodimers with certain ZNT proteins based on their overlapping subcellular localization with TMEM163 and previous reports that some ZNT monomers interact with each other. In this study, we heterologously expressed individual constructs with a unique peptide tag containing TMEM163, ZNT1, ZNT2, ZNT3, and ZNT4 (negative control) or co-expressed TMEM163 with each ZNT in cultured cells for co-immunoprecipitation (co-IP) experiments. We also co-expressed TMEM163 with two different peptide tags as a positive co-IP control. Western blot analyses revealed that TMEM163 dimerizes with itself but that it also heterodimerizes with ZNT1, ZNT2, ZNT3, and ZNT4 proteins. Confocal microscopy revealed that TMEM163 and ZNT proteins partially co-localize in cells, suggesting that they exist as homodimers and heterodimers in their respective subcellular sites. Functional zinc flux assays using Fluozin-3 and Newport Green dyes show that TMEM163/ZNT heterodimers exhibit similar efflux function as TMEM163 homodimers. Cell surface biotinylation revealed that the plasma membrane localization of TMEM163 is not markedly influenced by ZNT co-expression. Overall, our results show that the interaction between TMEM163 and distinct ZNT proteins is physiologically relevant and that their heterodimerization may serve to increase the functional diversity of zinc effluxers within specific tissues or cell types.

Evaluation of Phytochemistry and Pharmacological Properties of Alnus nitida.

In the current study, the anti-inflammatory and analgesic potential of Alnus nitida (leaves and fruits) was evaluated in the Sprague-Dawley rat. Traditionally, A. nitida was used for the treatment of inflammatory ailments. However, A. nitida leaves and fruits have not been yet reported regarding any potential medicinal effects. Leaves/fruits of A. nitida were extracted with methanol and fractionated to attain n-hexane, chloroform, ethyl acetate and aqueous fractions. These extracts were then evaluated for in vivo analgesic and anti-inflammatory potential. For in vivo anti-inflammatory activity, carrageenan-induced paw edema assay, Freunds' complete adjuvant-induced edema, xylene-induced ear edema and histamine-induced paw edema models were used in rats, which showed significant (p < 0.01) reduction (70−80%) in edema in comparison of inflammatory controls. On other hand, for the analgesic assessment, hot plate assay and acetic acid-induced writhing tests were used, which showed a significant (p < 0.01) rise in latency time (40−60%) as compared with pain-induced controls. These results were comparable with standard drugs in a concentration-dependent manner and no mortality or toxicity was observed during all experiments. Then, for the identification of chemical constituents gas chromatography−mass spectrometry (GC-MS) analysis was performed, which indicated the presence of neophytadiene, 3,7,11,15-Tetramethyl-2-hexadecen-1-ol, phytol and vitamin E, justifying the use of A. nitida to treat inflammatory disorders.

Functional Study of TMEM163 Gene Variants Associated with Hypomyelination Leukodystrophy.

Hypomyelinating leukodystrophies (HLDs) are a rare group of heterogeneously genetic disorders characterized by persistent deficit of myelin observed on magnetic resonance imaging (MRI). To identify a new disease-associated gene of HLD, trio-based whole exome sequencing was performed for unexplained patients with HLD. Functional studies were performed to confirm the phenotypic effect of candidate protein variants. Two de novo heterozygous variants, c.227T>G p.(L76R) or c.227T>C p.(L76P) in TMEM163 were identified in two unrelated HLD patients. TMEM163 protein is a zinc efflux transporter localized within the plasma membrane, lysosomes, early endosomes, and other vesicular compartments. It has not been associated with hypomyelination. Functional zinc flux assays in HeLa cells stably-expressing TMEM163 protein variants, L76R and L76P, revealed distinct attenuation or enhancement of zinc efflux, respectively. Experiments using a zebrafish model with knockdown of tmem163a and tmem163b (morphants) showed that loss of tmem163 causes dysplasia of the larvae, locomotor disability and myelin deficit. Expression of human wild type TMEM163 mRNAs in morphants rescues the phenotype, while the TMEM163 L76P and L76R mutants aggravated the condition. Moreover, poor proliferation, elevated apoptosis of oligodendrocytes, and reduced oligodendrocytes and neurons were also observed in zebrafish morphants. Our findings suggest an unappreciated role for TMEM163 protein in myelin development and add TMEM163 to a growing list of genes associated with hypomyelination leukodystrophy.

Just Like a Woman: Gender Role Stereotypes in Forensic Psychiatry.

The relationship between violence, gender and mental health is a complex one which is yet to be fully understood. Gender role stereotypes are social constructs that can powerfully influence and regulate human behaviour, including violence; and so it is likely that they also influence the nexus of violence management and mental health which is at the core of forensic psychiatry. In this article, we examine how gender role stereotypes might influence the practice of forensic psychiatry: specifically, in relation to women as violent offenders, as patients in secure psychiatric care and as clinicians working in forensic settings. We identify areas of development in women's forensic mental health services, and examine whether patriarchal influences and gender role stereotypes may have inadvertently impacted upon these changes. We also consider whether these changes may maintain pre-existing barriers to treatment for both men and women.

Combining Non-invasive Ventilation with timed position change in the Emergency Department to improve oxygenation and outcomes in patients with COVID-19: A prospective analysis from a low resource setup.

Background: Moving away from invasive ventilation towards timed position change and non-invasive ventilation is especially of benefit in low and middle income countries, where judicious use of the available healthcare resources is the need of the day. Our study was conducted prospectively to develop strategies for non-invasive ventilation in combination with timed position change of patients to see its impact on their outcome. Objectives: Non-invasive ventilation has proven to be of benefit in COVID-19 related acute lung injury. The objective of this prospective, cross sectional study was to develop a protocol for the use of non-invasive ventilation with timed position change to improve COVID-19 patients' outcomes in the Emergency Department (ED). Methods: All patients presenting with confirmed or suspected COVID-19 were enrolled in the study from March 2020 to October 2020. Data was collected to see the effect of timed position change and non-invasive ventilation on these patients and its effect on delaying or avoiding invasive ventilation. Results: Of the 207 COVID-19 patients presenting to the IHHN ED, 109(52.7%) had oxygen saturation in the nineties in supine position followed by right lateral in 37(17.9%), sitting up in 30(14.5%), left lateral in 29(14%) and prone position in 2(1%). Maximal oxygenation was achieved with non rebreather mask (NRM) and nasal prongs in 87(42%) of the patients, followed by the use of continuous positive airway pressure (CPAP) in 29(14%). Conclusion: Most of the patients preferred to stay in the supine position and described it as the position of comfort. When used in combination supine position, patients on NRM with nasal prongs and on CPAP, had oxygen saturation in the nineties. Central obesity was found to be the prime reason for the inability to prone our patients. This needs to be followed up in the current fourth wave of COVID-19 to see the effectiveness of the said modalities.

Patient perception regarding privacy and confidentiality: A study from the emergency department of a tertiary care hospital in Karachi, Pakistan.

Background and Objective: Maintaining privacy and ensuring confidentiality with patients is paramount to developing an effective patient-provider relationship. This is often challenging in over-crowded Emergency Departments (EDs). This survey was designed to explore patients' perceptions on maintenance of privacy and confidentiality and their subsequent interactions with providers in a busy tertiary care hospital in Karachi. Methods: Trained nursing staff conducted structured interviews with 571 patients who presented to The Indus Hospital (TIH) ED from January to December 2020. All patients were 14 years of age or older, could speak and understand Urdu, and provide informed consent. Patients were asked about their perceptions of privacy and confidentiality in the ED and whether this affected their interactions with providers. Results: Respondents were primarily men (64%) under the age of 45 (62%) presenting for the first time (49%). The majority of patients felt that privacy and confidentiality were maintained, however 10% of patients reported that they had rejected examination due to privacy concerns and 15% of patients reported that they had changed or omitted information provided to a provider due to confidentiality concerns. There was correlation between privacy and confidentiality concerns and patient-provider interactions (p<0.0001). Conclusions: Despite the often over-crowded and busy environment of the ED, patients generally felt that privacy and confidentiality were maintained. Given the correlation between perception and behavior and the importance of an effective patient-provider relationship, particularly in the acute setting when morbidity and mortality is high, initiatives that focus on maintaining privacy and confidentiality should be pursued.

Synthesis and evaluation of novel 1, 2, 4-substituted triazoles for urease and anti-proliferative activity.

1,2,4-triazoles are a major group of heterocyclic compounds. In the current work, a concise library of such triazoles synthesized through a multistep protocol. The synthesis involved hydrazinolysis of ethyl-2-(p-Cl-phenoxy) acetate followed by reflux with phenyl isothiocyanate to yield the intermediate 2-[2-(p-Cl-phenoxy)acetyl)-N-phenyl-hydrazinecarbothioamide. This intermediate was then cyclized to form 5-[p-(Cl-phenoxy)-methyl]-4-phenyl-4H-1,2,4-triazole-3-thiol (the parent moiety) at alkaline pH. In parallel, 3-bromopropionyl bromide was reacted with a series of phenylamines to yield N-(substituted-phenyl)bromopropanamides. In the final step, N-substitution of 5-[p-(Cl-phenoxy)-methyl]-4- phenyl-4H-1,2,4-triazole-3-thiol was carried out with N-(substituted-phenyl)bromopropanamides to give desired library of 3-[5-[(p-Cl-phenoxy)-methyl]-4- phenyl-4H-1,2,4-triazole-3-ylthio]-N-(substituted-phenyl) propan-amides (8a-l). The prepared moieties were identified via IR, NMR, & EIMS and evaluated for urease and anti-proliferative activities. 3-[5-[(p-Cl-phenoxy)-methyl]-4- phenyl-4H-1,2,4-triazole-3-ylthio]-N-(3-methyl-phenyl)propanamide 8k, was found to be most prominent hit as urease inhibitor (IC50= 42.57± 0.13 µM) using thiourea as standard (IC50= 21.25±0.15µM). The interaction of 8k with urease were studied using docking studies. Anti-proliferative activity results showed 8k as promising candidates and rest of the synthesized derivatives were found to be moderately anti-proliferative. Molecular docking results also displayed 8k, 8h, and 8c as potential hits for further study.

Chemical characterization and evaluation of the nephroprotective potential of Parrotiopsis jacquemontiana (Decne) Rehder and Periploca hydaspidis Falc crude extract in CCl4-induced Male Sprague-Dawley Rats.

Biochemical, antioxidant, serum, and urine profiles together with physical examination can deliver important information regarding animal health status, and are vital in the diagnosis and treatment of patients. CCl4, a potent nephrotoxin, was used for causing toxicity in rat kidneys. The present study aimed at exploring the nephroprotective potential of P. jacquemontiana leaves methanol extract (PJM) and P. hydaspidis whole-plant methanol extract (PHM) on kidney cells of male rats after oxidative stress and DNA damage was instigated by CCl4. Various parameters including enzymatic levels, serum profiles, urine profiles, genotoxicity, and histological studies were conducted. In renal samples of rats treated with CCl4, the antioxidant enzymes (POD, SOD, CAT), PH level, protein level, and glutathione contents were significantly (p < 0.05) declined whereas renal biochemicals (H2O2, TBARS, and nitrite), specific gravity, level of urea, urobilinogen, serum BUN and creatinine were markedly (p < 0.05) increased relative to control group. Co-administration of PJM and PHM with CCl4 displayed protective ability against CCl4 intoxication by restoring activities of antioxidant enzymes, urine profile, biochemical parameters, and serum profile in rats. CCl4 also induced prominent DNA damages and glomerular atrophy with abnormal appearance of glomerulus and Bowman's capsule. These damages results in impaired corticular sections, edema in Bowman's capsule, accumulation of necrotic cells, dilation of convoluted tubules, and narrowing of space between Bowman's capsule, which were successfully ameliorated after co-administration of PJM and PHM fractions in a dose-dependent manner (200 and 400 mg/kg b.w.). The results obtained suggest the therapeutic role of PJM and PHM in oxidative-stress related disorders of kidney and may be helpful in kidney trauma.