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Background and Objectives: Treatment of early breast cancer involves surgery, chemotherapy and radiation therapy. Present study was designed to describe the cosmetic outcome, prognosis, recurrence rate and complications after breast conservative surgery in patients with early breast carcinoma.Methods: A descriptive study was carried out at Surgical Unit III of Fatima Jinnah Medical University (FJMU), Lahore, Pakistan. A total of 54 female patients diagnosed with early breast carcinoma were included from July 2015 to January 2019. All of these patients underwent breast conservative surgery with axillary level II dissection or sentinel lymph node biopsy. Frozen section technique was used to evaluate clear surgical margins per operatively. These patients were followed up for a period of 12 months.Results: Mean age of the patients was 49.6 ± 11.3 years. Stage I disease was found in n = 17 (31.5%) females while stage II in n = 37 (68.5%) patients. Most of the patients had invasive ductal carcinoma. Tumor free surgical resection margin status was 1mm-20mm and it was >10mm in 32 (59.3%) patients. Post-operative good cosmetic outcome regarding symmetry of the breast (90.7%), shape of the breast (85.2%), shape of nipple (88.9%) and appearance of scar (81.4%) was observed. A total of 40 (74.1%) patients were satisfied with symmetry of breast, 41 (75.9%) patients were satisfied with shape of breast and 45 (83.3%) patients were satisfied with appearance of scar after breast conservative surgery through a validated questionnaire. Complications noted after the surgery were seroma in 1 (1.8%) and wound infection in 2 (3.7%) patients. Post Radiation oedema was seen in 44 (81.5%) and ulcers were seen in 6 (11.1%) patients. Local recurrence was developed in 2 patients (3.7%). Disease free survival was observedin 52 patients (96.3%).Conclusion: Breast conservative surgery for early breast carcinoma is cosmetically good regarding the scarand shape of the breast after surgery and satisfactory for the patients to accept. There were minimalpostoperative complications and low recurrence rate therefore breast conserving surgery in early breastcarcinoma can safely be recommended for early breast carcinoma.

Nazish Farooq,1,2 Niaz Ali,3 Shakir Ullah3,4 1Department of Hematology, Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan; 2Department of Pathology, Khyber Medical College, Peshawar, Pakistan; 3Department of Pharmacology, Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan; 4Department of Pharmacy, University of Malakand, Chakdara, PakistanCorrespondence: Niaz Ali; Shakir UllahDepartment of Pharmacology, Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, PakistanEmail niazpharmacist@yahoo.com; shakir.ibms@kmu.edu.pkBackground: Epilepsy is a treatable disease, but unfortunately a treatment gap exists in epileptic patients, especially in developing countries, due to adverse effects of antiepileptic drugs and polymorphisms in genes. Carbamazepine is the most commonly used medication in epilepsy, but is related to some serious and rare adverse effects. The aim of the study was to investigate the effect of folate metabolizing genes (MTHFR and DHFR) polymorphisms on different parameters of complete blood count in patients who were treated with carbamazepine and valproic acid.Materials and methods: Blood samples from 267 epileptic patients were collected on consent and surrogate consent forms. The blood was analyzed for changes in different parameters in complete blood count through a blood analyzer. The MTHFR gene was genotyped using the RFLP method. The data were analyzed using GraphPad Prism 6.Results: The homozygous mutant genotype (677CT) of the methylenetetrahydrofolate reductase enzyme (MTHFR C677T) gene significantly affects the level of hemoglobin (P=0.12), hematocrit (P=0.008) and mean corpuscular hemoglobin (P=0.01) compared to the homozygous wild genotype (677CC) and heterozygous mutant genotype (677CT) of the MTHFR (C677T) gene. However, the heterozygous genotype (1298AC) of MTHFR (A1298C) gene affect the total leukocyte count (P=0.037) level significantly.Conclusion: Changes in different parameters of complete blood count were statistically significant but clinically insubstantial decreases in different parameters of complete blood count indexes.Keywords: AEDs, epilepsy, complete blood count, carbamazepine, MTHFR gene, DHFR gene

Introduction and objectives There is an unmet need to develop high-quality evidence addressing tuberculosis (TB)-related mental health comorbidity, particularly in the context of lower-middle-income countries. This study aims to examine the effectiveness and cost-effectiveness of cognitive behavioural therapy (CBT) versus enhanced treatment as usual (ETAU) in improving depressive symptoms in people with TB and comorbid depression, enhancing adherence with anti-TB treatment (ATT) and its implementation in the real-world setting of Pakistan.Methods We will conduct a pragmatic parallel arm randomised control trial with an internal pilot. A brief psychological intervention based on CBT has been developed using a combination of qualitative and ethnographic studies. The inbuilt pilot trial will have a sample size of 80, while we plan to recruit 560 (280 per arm) participants in the definitive trial. Participants who started on ATT within 1 month of diagnosis for pulmonary and extrapulmonary TB or multidrug resistant TB (MDR-TB) and meeting the criteria for depression on Patient Health Questionnaire-9 (PHQ-9) will be randomised with 1:1 allocation to receive six sessions of CBT (delivered by TB healthcare workers) or ETAU. Data on the feasibility outcomes of the pilot will be considered to proceed with the definitive trial. Participants will be assessed (by a blinded assessor) for the following main trial primary outcomes: (1) severity of depression using PHQ-9 scale (interviewer-administered questionnaire) at baseline, weeks 8, 24 and 32 postrandomisation and (2) ATT at baseline and week 24 at the end of ATT therapy.Ethics and dissemination Ethical approval has been obtained from Keele University Research Ethics Committee (ref: 2023-0599-792), Khyber Medical University Ethical Review Board (ref: DIR/KMU-EB/CT/000990) and National Bioethics Committee Pakistan (ref: No.4–87/NBC-998/23/587). The results of this study will be reported in peer-reviewed journals and academic conferences and disseminated to stakeholders and policymakers.Trial registration number ISRCTN10761003.

IntroductionMental health Applications (MH Apps) can potentially improve access to high-quality mental health care. However, the recent rapid expansion of MH Apps has created growing concern regarding their safety and effectiveness, leading to the development of AETs (Assessment and Evaluation Tools) to help guide users. This article provides a critical, mixed methods analysis of existing AETs for MH Apps by reviewing the criteria used to evaluate MH Apps and assessing their effectiveness as evaluation tools.MethodsTo identify relevant AETs, gray and scholarly literature were located through stakeholder consultation, Internet searching via Google and a literature search of bibliographic databases Medline, APA PsycInfo, and LISTA. Materials in English that provided a tool or method to evaluate MH Apps and were published from January 1, 2000, to January 26, 2021 were considered for inclusion.ResultsThirteen relevant AETs targeted for MH Apps met the inclusion criteria. The qualitative analysis of AETs and their evaluation criteria revealed that despite purporting to focus on MH Apps, the included AETs did not contain criteria that made them more specific to MH Apps than general health applications. There appeared to be very little agreed-upon terminology in this field, and the focus of selection criteria in AETs is often IT-related, with a lesser focus on clinical issues, equity, and scientific evidence. The quality of AETs was quantitatively assessed using the AGREE II, a standardized tool for evaluating assessment guidelines. Three out of 13 AETs were deemed ‘recommended’ using the AGREE II.DiscussionThere is a need for further improvements to existing AETs. To realize the full potential of MH Apps and reduce stakeholders’ concerns, AETs must be developed within the current laws and governmental health policies, be specific to mental health, be feasible to implement and be supported by rigorous research methodology, medical education, and public awareness.

Convalescent sera, rich in pathogen-specific antibodies, offers passive immunity to patients with infectious diseases. Screening assays using convalescent sera are crucial for evaluating therapeutic efficacy, selecting suitable serum donors, and standardizing assays. They measure antibody levels, neutralizing potential, and specificity against viruses like SARS-CoV-2, ensuring therapeutic serum contains potent antibodies. Standardized procedures enable reliable results and wider adoption of serum therapy for COVID-19. We have developed a high-content image-based assay for screening convalescent sera against SARS-CoV-2 variants. Using various cell lines, we identified optimal candidates, employed immunofluorescence to visualize infected cells, and assessed neutralizing antibody efficacy. Screening convalescent sera for therapeutic potential identified neutralizing activity against SARS-CoV-2 variants. Dose–response analysis showed variable neutralizing activity, with some sera exhibiting broad neutralization. Additionally, we explored the synergy between neutralizing sera and β-d-N4-hydroxycytidine (NHC), an initial metabolite of molnupiravir. These assays enhance serum therapy’s benefits for COVID-19 treatment and aid in understanding neutralizing activity against SARS-CoV-2 variants, addressing viral challenges.

Abstract Background Self-harm is an important predictor of a suicide death. Culturally appropriate strategies for the prevention of self-harm and suicide are needed but the evidence is very limited from low- and middle-income countries (LMICs). This study aims to investigate the effectiveness of a culturally adapted manual-assisted problem-solving intervention (CMAP) for patients presenting after self-harm. Methods This was a rater-blind, multicenter randomised controlled trial. The study sites were all participating emergency departments, medical wards of general hospitals and primary care centres in Karachi, Lahore, Rawalpindi, Peshawar, and Quetta, Pakistan. Patients presenting after a self-harm episode (n = 901) to participating recruitment sites were assessed and randomised (1:1) to one of the two arms; CMAP with enhanced treatment as usual (E-TAU) or E-TAU. The intervention (CMAP) is a manual-assisted, cognitive behaviour therapy (CBT)-informed problem-focused therapy, comprising six one-to-one sessions delivered over three months. Repetition of self-harm at 12-month post-randomisation was the primary outcome and secondary outcomes included suicidal ideation, hopelessness, depression, health-related quality of life (QoL), coping resources, and level of satisfaction with service received, assessed at baseline, 3-, 6-, 9-, and 12-month post-randomisation. The trial is registered on ClinicalTrials.gov. NCT02742922 (April 2016). Results We screened 3786 patients for eligibility and 901 eligible, consented patients were randomly assigned to the CMAP plus E-TAU arm (n = 440) and E-TAU arm (N = 461). The number of self-harm repetitions for CMAP plus E-TAU was lower (n = 17) compared to the E-TAU arm (n = 23) at 12-month post-randomisation, but the difference was not statistically significant (p = 0.407). There was a statistically and clinically significant reduction in other outcomes including suicidal ideation (− 3.6 (− 4.9, − 2.4)), depression (− 7.1 (− 8.7, − 5.4)), hopelessness (− 2.6 (− 3.4, − 1.8), and improvement in health-related QoL and coping resources after completion of the intervention in the CMAP plus E-TAU arm compared to the E-TAU arm. The effect was sustained at 12-month follow-up for all the outcomes except for suicidal ideation and hopelessness. On suicidal ideation and hopelessness, participants in the intervention arm scored lower compared to the E-TAU arm but the difference was not statistically significant, though the participants in both arms were in low-risk category at 12-month follow-up. The improvement in both arms is explained by the established role of enhanced care in suicide prevention. Conclusions Suicidal ideation is considered an important target for the prevention of suicide, therefore, CMAP intervention should be considered for inclusion in the self-harm and suicide prevention guidelines. Given the improvement in the E-TAU arm, the potential use of brief interventions such as regular contact requires further exploration.

BackgroundMental health Applications (Mhealth Apps) can change how healthcare is delivered. However, very little is known about the efficacy of Mhealth Apps. Currently, only minimum guidance is available in Assessment and Evaluation Tools (AETs). Therefore, this project aims to understand AET developers' perspectives and end users' experiences and opinions on “how to choose a Mhealth App”.ObjectiveThe primary objectives were: (1) obtaining stakeholder's opinions and experiences of development and use of AETs for Mhealth Apps, their weaknesses and strengths, and barriers in their implementation of Mhealth Apps; (2) the experiences of App users, their analyzation and, obstacles in the use of apps; and (3) to quantify themes related to choosing a Mhealth App.MethodsThis qualitative study, used a sampling method to recruit six stakeholders (one App developer, two AET developers, an individual with lived experience of mental health illness, and two physicians) who were interviewed using a topic guide. These were examined by researchers (CT, WK, & FN) using thematic content analysis. Additionally, an anonymous online survey of 107 individuals was conducted.FindingsOur analyses revealed six main themes: (a) needs and opportunities; (b) views on Mhealth apps; (c) views & opinions on AETs; (d) implementation barriers; (e) system of evaluation and; (f) future directions. The first key concept was, all stakeholders agreed that Apps could significantly impact mental health and that end-users were unaware of mental health AETs and Apps. Secondly, due to commercial interests, end-users reliability of App evaluations requires clear conflict-free guidelines. Thirdly, AETs should be evaluated and developed through a rigorous methodology. Finally, stakeholders shared insights into future developments for AETs and Mhealth Apps. Additionally, online survey respondents chose a “health professional” as their preferred source of guidance in selecting a Mhealth app (84%) and best suited to develop guidelines (70%).ConclusionThe interviews and survey highlight the need for Mhealth Apps to be regulated and the importance of health professionals' engagement in the implementation process. Similarly, without well-defined roles for App evaluations within the health care system, it is unlikely that AETs will have wider spread use and impact without risk.

Accurate reorganization of harvested species is essential for appropriate fisheries monitoring but often unnoticed. In this study, an attempt was made to provide an accurate species description based on fish taxonomy and otolith shape parameters of nine sea catfishes living in Pakistan. The lapillus, the largest otolith of catfishes, includes the position of the umbo, the structure of the anterior mesial projection (amp), the incisura linea basalis (ilb) and sulcus lapilli marks (slm) in nine ariid catfishes were evaluated. Discriminant function analysis was performed using twenty-two morphometric parameters showed significant variations between the length of the maxillary barbel, adipose length and preorbital length, which were highlighted as basic discriminating characters. Species without barbells, such as Batrachocephalus mino and Osteogeneiosus militaris, were found to be distant. The taxonomic characters of the genera Netuma and Plicofollis overlapped due to a short adipose fin length. Nevertheless, species Arius arius, Sciades sona and Nemapterxy caelatus differed in a moderate adipose fin length. The preorbital length of Netuma bilineata has a short and rounded snout, while N. thalassina has a long and pointed snout, which is a distinguishing characteristic of both species. The coincident use of fish taxonomy and otolith shape parameters is an effective tool for catfish identification could be helpful in appropriate fisheries sampling programs and management in Pakistan whenever implemented.

Introduction: Type-2 diabetes (T2D) is a complex chronic condition associated with a lower quality of life due to disease specific distress. While there is growing support for personalized diabetes programs, care for mental health challenges is often fragmented and limited by access to psychiatry, and integration of care. The use of communication technology to improve team based collaborative care to bridge these gaps is promising but untested. Methods: We conducted an explanatory sequential mixed methods study to assess the feasibility and acceptability of the co-designed Technology-Enabled Collaborative Care for Diabetes and Mental Health (TECC-D) program. Participants included adults aged ≥18 years who had a clinical diagnosis of T2D, and self-reported mental health concerns. Results: 31 participants completed the 8-week virtual TECC-D program. Findings indicate that the program is feasible and acceptable and indicate that there is a role for virtual diabetes and mental health care. Discussion: The TECC-D program, designed through an iterative co-design process and supported by innovative, responsive adaptations led to good uptake and satisfaction. Conclusion: The TECC-D model is a feasible and scalable care solution that empowers individuals living with T2D and mental health concerns to take an active role in their care.

BackgroundFor individuals living with diabetes and its psychosocial comorbidities (eg, depression, anxiety, and distress), there remains limited access to interprofessional, integrated care that includes mental health support, education, and follow-up. Health technology, broadly defined as the application of organized knowledge or skill as software, devices, and systems to solve health problems and improve quality of life, is emerging as a means of addressing these gaps. There is thus a need to understand how such technologies are being used to support, educate, and help individuals living with co-occurring diabetes and mental health distress or disorder. ObjectiveThe purpose of this scoping review was to (1) describe the literature on technology-enabled integrated interventions for diabetes and mental health; (2) apply frameworks from the Mental Health Commission of Canada and World Health Organization to elucidate the components, type, processes, and users of technology-enabled integrated interventions for diabetes and mental health; and (3) map the level of integration of interventions for diabetes and mental health. MethodsWe searched 6 databases from inception to February 2022 for English-language, peer-reviewed studies of any design or type that used technology to actively support both diabetes and any mental health distress or disorder in succession or concurrently among people with diabetes (type 1 diabetes, type 2 diabetes, and gestational diabetes). Reviewers screened citations and extracted data including study characteristics and details about the technology and integration used. ResultsWe included 24 studies described in 38 publications. These studies were conducted in a range of settings and sites of care including both web-based and in-person settings. Studies were mostly website-based (n=13) and used technology for wellness and prevention (n=16) and intervention and treatment (n=15). The primary users of these technologies were clients and health care providers. All the included intervention studies (n=20) used technology for clinical integration, but only 7 studies also used the technology for professional integration. ConclusionsThe findings of this scoping review suggest that there is a growing body of literature on integrated care for diabetes and mental health enabled by technology. However, gaps still exist with how to best equip health care professionals with the knowledge and skills to offer integrated care. Future research is needed to continue to explore the purpose, level, and breadth of technology-enabled integration to facilitate an approach to overcome or address care fragmentation for diabetes and mental health and to understand how health technology can further drive the scale-up of innovative integrated interventions.

TNX-1800 is a synthetically derived live recombinant chimeric horsepox virus (rcHPXV) vaccine candidate expressing Wuhan SARS-CoV-2 spike (S) protein. The primary objective of this study was to evaluate the immunogenicity and efficacy of TNX-1800 in two nonhuman primate species challenged with USA-WA1/2020 SARS-CoV-2. TNX-1800 vaccination was well tolerated with no serious adverse events or significant changes in clinical parameters. A single dose of TNX-1800 generated humoral responses in African Green Monkeys and Cynomolgus Macaques, as measured by the total binding of anti-SARS-CoV-2 S IgG and neutralizing antibody titers against the USA-WA1/2020 strain. In addition, a single dose of TNX-1800 induced an interferon-gamma (IFN-γ)-mediated T-cell response in Cynomolgus Macaques. Following challenge with SARS-CoV-2, African Green and Cynomolgus Macaques exhibited rapid clearance of virus in the upper and lower respiratory tract. Future studies will assess the efficacy of TNX-1800 against newly emerging variants and demonstrate its safety in humans.

TNX-1800 is a preclinical stage synthetic-derived live attenuated chimeric horsepox virus vaccine engineered to express the SARS-CoV-2 spike (S) gene. The objectives of this study were to assess the safety, tolerability, and immunogenicity of TNX-1800 administration in Syrian golden hamsters and New Zealand white rabbits. Animals were vaccinated at three doses via percutaneous inoculation. The data showed that the single percutaneous administration of three TNX-1800 vaccine dose levels was well tolerated in both hamsters and rabbits. At all dose levels, rabbits were more decerning regarding vaccine site reaction than hamsters. Lastly, no TNX-1800 genomes could be detected at the site of vaccination. Post-vaccination, all animals had anti-SARS-CoV-2 spike protein IgG specific antibody responses. These data demonstrate that TNX-1800 infection was limited, asymptomatic, and cleared by the end of this study, and a single dose was able to generate immune responses.

Abstract Background Prevalence of post-traumatic stress disorder (PTSD) is high in Pakistan both due to natural disasters and ongoing conflicts. Offspring of trauma survivors are at increased risk for mental and physical illnesses. Parental PTSD has been linked to troubled parent–child relationships, behaviour problems, trauma symptoms, and depression in children. This study aims to explore the acceptability, feasibility and indications of the effectiveness of group learning through play plus trauma-focused cognitive behaviour therapy (LTP Plus TF-CBT) for parents experiencing PTSD. Methods/Design This is a two-arm pilot cluster randomised controlled trial (RCT). We aim to recruit 300 parents with a diagnosis of PTSD. The screening will be done using the Impact of Event Scale-Revised. Diagnosis of PTSD will be confirmed using the Clinician-Administered PTSD Scale-5 (CAPS-5). Union Councils from Peshawar and Karachi will be randomised into either group LTP Plus TF CBT arm or treatment as usual (TAU). The intervention includes 12 sessions of LTP Plus TF-CBT delivered weekly in the first 2 months and then fortnightly in a group setting by trained psychologists. The groups will be co-facilitated by the community health workers (CHWs). Parents will be assessed at baseline and 4th month (end of the intervention), using the Patient Health Questionnaire (PHQ-9), Generalised Anxiety Disorder (GAD-7) Scale, Client Service Receipt Inventory (CSRI), and Ages and Stages Questionnaire (ASQ-3) Discussion This trial would help build an understanding of the acceptability, feasibility and indications of the effectiveness of a low-cost parenting intervention.

Personality disorders (PDs) have a global prevalence of 7.8% and are associated with increased rates of morbidity and mortality. Most research on PDs has been conducted in High Income Countries (HICs). We conducted a systematic review to investigate the effectiveness of psychosocial and pharmacological interventions for personality disorders (PDs) in individuals from Low- and Middle-Income Countries (LMICs.) We systematically searched MEDLINE, Embase, APA PsycInfo, Web of Science, Cumulative Index of Nursing and Allied Health Literature (CINAHL), and The Cochrane Library from inception to January 5, 2023. Inclusion criteria were quantitative studies and grey literature where participants received a psychosocial or pharmacological intervention for PD. Exclusion criteria were qualitative studies, review articles, studies in which PD was not the primary condition, and articles not available in English. The Cochrane Risk of Bias tool version 2.0 and Joanna Briggs Institute instruments were used to measure risk of bias. Studies were pooled by type of study, PD investigated, type of intervention, assessment methods, and outcomes. Sixteen studies met inclusion criteria and were included. Fifteen were intervention studies related to borderline PD. Only one studied mixed PDs. Twelve studies were of psychotherapy, one pharmacotherapy, one combination of both, and two neurostimulation. Most of the studies showed improvement in symptoms though data was largely collected using self-report measures. There were only six RCTs. There is a dearth of literature on interventions for PDs in LMICs and funding bodies should prioritize research in LMICs. Systematic Review Registration Number: PROSPERO CRD42021233415.

Schizophrenia spectrum disorders (SSDs) are associated with significant functional impairments, disability, and low rates of personal recovery, along with tremendous economic costs linked primarily to lost productivity and premature mortality. Efforts to delineate the contributors to disability in SSDs have highlighted prominent roles for a diverse range of symptoms, physical health conditions, substance use disorders, neurobiological changes, and social factors. These findings have provided valuable advances in knowledge and helped define broad patterns of illness and outcomes across SSDs. Unsurprisingly, there have also been conflicting findings for many of these determinants that reflect the heterogeneous population of individuals with SSDs and the challenges of conceptualizing and treating SSDs as a unitary categorical construct. Presently it is not possible to identify the functional course on an individual level that would enable a personalized approach to treatment to alter the individual's functional trajectory and mitigate the ensuing disability they would otherwise experience. To address this ongoing challenge, this study aims to conduct a longitudinal multimodal investigation of a large cohort of individuals with SSDs in order to establish discrete trajectories of personal recovery, disability, and community functioning, as well as the antecedents and predictors of these trajectories. This investigation will also provide the foundation for the co-design and testing of personalized interventions that alter these functional trajectories and improve outcomes for people with SSDs.

BackgroundThe COVID-19 pandemic disrupted the delivery of diabetes care and worsened mental health among many patients with type 2 diabetes (T2D). This disruption puts patients with T2D at risk for poor diabetes outcomes, especially those who experience social disadvantage due to socioeconomic class, rurality, or ethnicity. The appropriate use of communication technology could reduce these gaps in diabetes care created by the pandemic and also provide support for psychological distress. ObjectiveThe purpose of this study is to test the feasibility of an innovative co-designed Technology-Enabled Collaborative Care (TECC) model for diabetes management and mental health support among adults with T2D. MethodsWe will recruit 30 adults with T2D residing in Ontario, Canada, to participate in our sequential explanatory mixed methods study. They will participate in 8 weekly web-based health coaching sessions with a registered nurse, who is a certified diabetes educator, who will be supported by a digital care team (ie, a peer mentor, an addictions specialist, a dietitian, a psychiatrist, and a psychotherapist). Assessments will be completed at baseline, 4 weeks, and 8 weeks, with a 12-week follow-up. Our primary outcome is the feasibility and acceptability of the intervention, as evident by the participant recruitment and retention rates. Key secondary outcomes include assessment completion and delivery of the intervention. Exploratory outcomes consist of changes in mental health, substance use, and physical health behaviors. Stakeholder experience and satisfaction will be explored through a qualitative descriptive study using one-on-one interviews. ResultsThis paper describes the protocol of the study. The recruitment commenced in June 2021. This study was registered on October 29, 2020, on ClinicalTrials.gov (Registry ID: NCT04607915). As of June 2022, all participants have been recruited. It is anticipated that data analysis will be complete by the end of 2022, with study findings available by the end of 2023. ConclusionsThe development of an innovative, technology-enabled model will provide necessary support for individuals living with T2D and mental health challenges. This TECC program will determine the feasibility of TECC for patients with T2D and mental health issues. Trial RegistrationClinicalTrials.gov NCT04607915; https://clinicaltrials.gov/ct2/show/NCT04607915 International Registered Report Identifier (IRRID)DERR1-10.2196/39724

Background Bipolar disorder is a source of marked disability, morbidity and premature death. There is a paucity of research on personalised psychosocial interventions for bipolar disorder, especially in low-resource settings. A pilot randomised controlled trial (RCT) of a culturally adapted psychoeducation intervention for bipolar disorder (CaPE) in Pakistan reported higher patient satisfaction, enhanced medication adherence, knowledge and attitudes regarding bipolar disorder, and improvement in mood symptom scores and health-related quality of life measures compared with treatment as usual (TAU). Aims The current protocol describes a larger multicentre RCT to confirm the clinical and cost-effectiveness of CaPE in Pakistan. Trial registration: NCT05223959. Method A multicentre individual, parallel-arm RCT of CaPE in 300 Pakistani adults with bipolar disorder. Participants over the age of 18, with a diagnosis of bipolar I or II disorder who are currently euthymic, will be recruited from seven sites: Karachi, Lahore, Multan, Rawalpindi, Peshawar, Hyderabad and Quetta. Time to recurrence will be the primary outcome assessed using the Longitudinal Interval Follow-up Evaluation (LIFE). Secondary measures will include mood symptoms, quality of life and functioning, adherence to psychotropic medications, and knowledge and attitudes regarding bipolar disorder. Results This trial will assess the effectiveness of the CaPE intervention compared with TAU in reducing the time to recurrence for people with bipolar disorder currently in remission in Pakistan and determine the effect on clinical outcomes, quality of life and functioning. Conclusions A successful trial might lead to rapid implementation of CaPE in clinical practice, not only in Pakistan, but also in other low-resource settings, including those in high-income countries, to improve clinical outcomes, social and occupational functioning, and quality of life in South Asian and other minority group patients with bipolar disorder.

Abstract Background Canadians of South Asian (SA) origin comprise the largest racialized group in Canada, representing 25.6% of what Statistics Canada terms “visible minority populations”. South Asian Canadians are disproportionately impacted by the social determinants of health, and this can result in high rates of mood and anxiety disorders. These factors can negatively impact mental health and decrease access to care, thereby increasing mental health inequities. Cognitive Behavioural Therapy (CBT) in its current form is not suitable for persons from the non-western cultural backgrounds. Culturally adapted Cognitive Behavioural Therapy (CaCBT) is an evidence-based practice. CaCBT is more effective than standard CBT and can reduce dropouts from therapy compared with standard CBT. Thus, CaCBT can increase access to mental health services and improve outcomes for immigrant, refugee and ethno-cultural and racialized populations. Adapting CBT for growing SA populations in Canada will ensure equitable access to effective and culturally appropriate interventions. Methods The primary aim of the study is to develop and evaluate CaCBT for Canadian South Asian persons with depression and anxiety and to gather data from stakeholders to develop guidelines to culturally adapt CBT. This mixed methods study will use three phases: (1) cultural adaptation of CBT, (2) pilot feasibility of CaCBT and (3) implementation and evaluation of CaCBT. Phase 1 will use purposive sampling to recruit individuals from four different groups: (1) SA patients with depression and anxiety, (b) caregivers and family members of individuals affected by anxiety and depression, (c) mental health professionals and (d) SA community opinion leaders. Semi-structured interviews will be conducted virtually and analysis of interviews will be informed by an ethnographic approach. Phase 2 will pilot test the newly developed CaCBT for feasibility, acceptability and effectiveness via quantitative methodology and a randomized controlled trial, including an economic analysis. Phase 3 will recruit therapists to train and evaluate them in the new CaCBT. Discussion The outcome of this trial will benefit health services in Canada, in terms of helping to reduce the burden of depression and anxiety and provide better care for South Asians. We expect the results to help guide the development of better services and tailor existing services to the needs of other vulnerable groups. Trial registration ClinicalTrials.gov NCT04010890. Registered on July 8, 2019

Background:The patient's follow-up is a significant challenge for managing the psychiatric illness, especially psychotic disorders. Although many factors affect patients' clinical non-attendance with psychosis, patients and their families' approach toward medication influences treatment follow-up. The study evaluates the patient's and family's approach regarding OPD follow-up and the effect of SMS reminder on OPD follow-up of patients with psychosis.Methodology:Thisstudy was conducted on a psychotic patient attending OPD at Karwan e Hayat, Karachi. A total of 248 patients were randomly dividedinto two groups, the SMS reminder group and the treatment-as-usual or control group. Computer-based SMS to improve patient follow-up was sent in Urdu and English to the SMS group. A total of four reminder messages were sent to the SMS group within 15 daysof each clinical appointment over a period of 24-weeks, while no message was sent to the control group. Results:All patients (Intervention & Control groups) were divided further into two groups based on the caring family approach reflected through several follow-ups, including a poor follow-up group with less than five visits and an appropriate follow-up group having five or more than five visits. The impact of SMS follow-up reminders on both groups was observed through OPD follow-ups. At baseline, all groups were comparable, but after a 3-month appropriate group of intervention were found with a significant(p=0.053) increase in the number of follow-ups compared to patients with poor follow-up groups.Conclusion:It is concluded from the study results thatSMS reminders are an effective intervention in those psychotic patients and families who have a positive approach to illness.

Abstract PIDD1 encodes p53-Induced Death Domain protein 1, which acts as a sensor surveilling centrosome numbers and p53 activity in mammalian cells. Early results also suggest a role in DNA damage response where PIDD1 may act as a cell-fate switch, through interaction with RIP1 and NEMO/IKKg, activating NF-κB signaling for survival, or as an apoptosis-inducing protein by activating caspase-2. Biallelic truncating mutations in CRADD—the protein bridging PIDD1 and caspase-2—have been reported in intellectual disability (ID), and in a form of lissencephaly. Here, we identified five families with ID from Iran, Pakistan, and India, with four different biallelic mutations in PIDD1, all disrupting the Death Domain (DD), through which PIDD1 interacts with CRADD or RIP1. Nonsense mutations Gln863* and Arg637* directly disrupt the DD, as does a missense mutation, Arg815Trp. A homozygous splice mutation in the fifth family is predicted to disrupt splicing upstream of the DD, as confirmed using an exon trap. In HEK293 cells, we show that both Gln863* and Arg815Trp mutants fail to co-localize with CRADD, leading to its aggregation and mis-localization, and fail to co-precipitate CRADD. Using genome-edited cell lines, we show that these three PIDD1 mutations all cause loss of PIDDosome function. Pidd1 null mice show decreased anxiety, but no motor abnormalities. Together this indicates that PIDD1 mutations in humans may cause ID (and possibly lissencephaly) either through gain of function or secondarily, due to altered scaffolding properties, while complete loss of PIDD1, as modeled in mice, may be well tolerated or is compensated for.

Introduction Suicide is a global health concern. Sociocultural factors have an impact on self-harm and suicide rates. In Pakistan, both self-harm and suicide are considered as criminal offence’s and are condemned on both religious and social grounds. The proposed intervention ‘Youth Culturally Adapted Manual Assisted Problem Solving Training (YCMAP)’ is based on principles of problem-solving and cognitive–behavioural therapy. YCMAP is a brief, culturally relevant, scalable intervention that can be implemented in routine clinical practice if found to be effective.Method and analysis A multicentre rater blind randomised controlled trial to evaluate the clinical and cost-effectiveness of YCMAP including a sample of 652 participants, aged 12–18 years, presenting to general physicians/clinicians, emergency room after self harm or self referrals. We will test the effectiveness of 8–10 individual sessions of YCMAP delivered over 3 months compared with treatment as usual. Primary outcome measure is repetition of self-harm at 12 months. The seconday outcomes include reduction in suicidal ideation, hopelessness and distress and improvement in health related quality of life. Assessments will be completed at baseline, 3, 6, 9 and 12 months postrandomisation. The nested qualitative component will explore perceptions about management of self-harm and suicide prevention among adolescents and investigate participants’ experiences with YCMAP. The study will be guided by the theory of change approach to ensure that the whole trial is centred around needs of the end beneficiaries as key stakeholders in the process.Ethics and dissemination Ethics approval has been obtained from the Ethics Committee of University of Manchester, the National Bioethics Committee in Pakistan. The findings of this study will be disseminated through community workshops, social media, conference presentations and peer-reviewed journals.Trial registration number NCT04131179.

Eastern equine encephalitis virus (EEEV) is mosquito-borne virus that produces fatal encephalitis in humans. We recently conducted a first of its kind study to investigate EEEV clinical disease course following aerosol challenge in a cynomolgus macaque model utilizing the state-of-the-art telemetry to measure critical physiological parameters. Here, we report the results of a comprehensive pathology study of NHP tissues collected at euthanasia to gain insights into EEEV pathogenesis. Viral RNA and proteins as well as microscopic lesions were absent in the visceral organs. In contrast, viral RNA and proteins were readily detected throughout the brain including autonomic nervous system (ANS) control centers and spinal cord. However, despite presence of viral RNA and proteins, majority of the brain and spinal cord tissues exhibited minimal or no microscopic lesions. The virus tropism was restricted primarily to neurons, and virus particles (~61–68 nm) were present within axons of neurons and throughout the extracellular spaces. However, active virus replication was absent or minimal in majority of the brain and was limited to regions proximal to the olfactory tract. These data suggest that EEEV initially replicates in/near the olfactory bulb following aerosol challenge and is rapidly transported to distal regions of the brain by exploiting the neuronal axonal transport system to facilitate neuron-to-neuron spread. Once within the brain, the virus gains access to the ANS control centers likely leading to disruption and/or dysregulation of critical physiological parameters to produce severe disease. Moreover, the absence of microscopic lesions strongly suggests that the underlying mechanism of EEEV pathogenesis is due to neuronal dysfunction rather than neuronal death. This study is the first comprehensive investigation into EEEV pathology in a NHP model and will provide significant insights into the evaluation of countermeasure. Author summary EEEV is an arbovirus endemic in parts of North America and is able to produce fatal encephalitis in humans and domesticated animals. Despite multiple human outbreaks during the last 80 years, there are still no therapeutic or vaccines to treat or prevent human disease. One critical obstacle in the development of effective countermeasure is the lack of insights into EEEV pathogenesis in a susceptible animal host. We recently conducted a study in cynomolgus macaques to investigate the disease course by measuring clinical parameters relevant to humans. Following infection, these parameters were rapidly and profoundly altered leading to severe disease. In this study, we examined the potential mechanisms that underlie pathogenesis to cause severe disease. The virus was present in many parts of the brain and spinal cord, however, minimal or no pathological lesions as well as active virus replication were observed. Additionally, neurons were the predominant target of EEEV infection and virus transport was facilitated via axonal transport system to spread neuron-to-neuron throughout the brain and spinal cord. These data show that EEEV likely hijacks essential transport system to rapidly spread in the brain and local/global neuronal dysfunction rather than neuronal death is the principal cause of severe disease.

The article describes the richness and structure of finfish species in the tidal-associated lagoons of Badin, Sindh, Northern Arabian Sea. Topics discussed include the diversity of fishes in lagoons, species in the family Ariidae including Mugilidae, Sparidae and Gobiidae, and the greatest similarity found in terms of diversity.

This study describes the diet composition, diet overlap and prey diversity in two economically and ecologically important marine catfish species: the bronze catfish ( Netuma bilineata) and the blacktip sea catfish ( Plicofollis dussumieri) collected between January and December 2015 from the northern Arabian Sea coast of Pakistan. Stomach data of 342 bronze catfish and 283 blacktip sea catfish were examined. Diet composition and feeding strategy of each species by identification of stomach contents were weighed and enumerated. Both species primarily consumed teleosts, Brachyura and small amounts of a wide variety of prey items; however, specialization was a more common trait for the bronze catfish than for the black tip sea catfish. The Morisita-Horn index showed considerable diet overlap in percentage of mean weights (0.847) than in numbers (0.612) between co-prey pairs of both species. The highest Bray-Curtis similarity between the southwest monsoon ( SWM) and south inter monsoon ( SIM) was observed in bronze catfish and lowest between autumn inter monsoon ( AIM) seasons in both species. While Bray-Curtis dissimilarity was observed, both species share diet niches and diet overlap. The present study evaluation of the feeding strategy and potential competition between two sympatric species of marine catfishes can provide the framework for their conservation and management in the region. [ABSTRACT FROM AUTHOR]

Abstract Purpose The purpose of this research work was to analyze the narcissism personality disorder in nurses and their impact on cognitive organizational cynicism with mediating role of psychological capital. Design/methodology/approach In the current study, constructs developed from existing theories, generate hypotheses, adopt strategies for data collection and perform test to prove the proposed hypothesis. The nursing carder is the unit of analysis in this research study. Descriptive statistics, correction, and mediation analysis through Baron and Kenny’s were performed for analysis. Findings This research concludes narcissism personality disorder has significant positive association with cognitive organizational cynicism. The role of psychological capital is mediating to minimize the negative employee’s behavior toward their bosses and organization. Practical implications In the light of findings, the current research work has implications at individual and organization levels. This research work will become as foundation stone to formulate strategies to overcome the organization cynicism in nursing profession. Furthermore, the organization formulates selection process more affective to find those candidates having narcissism disorder. Originality/value The current research work is designated first study to evaluate the relationship between narcissistic personality disorder and cognitive organization cynicism with mediating role of psychological capital in Pakistan.

Objectives The aim of the project was to examine the acceptability and feasibility of a mobile phone application-based intervention ‘TechCare’, for individuals with psychosis in the North West of England. The main objectives were to determine whether appropriate individuals could be identified and recruited to the study and whether the TechCare App would be an acceptable intervention for individuals with psychosis.Methods This was a mixed methods feasibility study, consisting of a test-run and feasibility evaluation of the TechCare App intervention.Setting Early Intervention Services (EIS) for psychosis, within an NHS Trust in the North West of England.Participants Sixteen participants (test-run n=4, feasibility study n=12) aged between 18 and 65 years recruited from the East, Central and North Lancashire EIS.Intervention A 6-week intervention, with the TechCare App assessing participants’ symptoms and responses in real-time and providing a personalised-guided self-help-based psychological intervention based on the principles of Cognitive Behaviorual Therapy (CBT).Results A total of 83.33% (n=10) of participants completed the 6-week feasibility study, with 70% of completers achieving the set compliance threshold of ≥33% engagement with the TechCare App system. Analysis of the qualitative data suggested that participants held the view that the TechCare was both an acceptable and feasible means of delivering interventions in real-time.Conclusion Innovative digital clinical technologies, such as the TechCare App, have the potential to increase access to psychological interventions, reduce health inequality and promote self-management with a real-time intervention, through enabling access to mental health resources in a stigma-free, evidence-based and time-independent manner.Trial registration number ClinicalTrials.gov Identifier: NCT02439619.

The cognitive model of negative symptoms suggests that some dysfunctional beliefs mediate the relationship between neurocognitive deficits and negative symptoms and disability. This study tested the hypothesis that dysfunctional performance beliefs mediate neurocognitive deficits, negative symptoms, and disability. We used a hierarchal component model with 85 men patients diagnosed with chronic schizophrenia. Results showed a moderate to strong correlation between dysfunctional performance beliefs, neurocognitive deficits, negative symptoms, and disability. These results support the Hierarchal component model (HCM) of the cognitive model of negative symptoms. Our results indicated that the disability in schizophrenia is mediated through dysfunctional performance beliefs, neurocognitive deficits, and negative symptoms pathway. Further, dysfunctional performance beliefs have a crucial role in this pathway. Therefore, targeting this vicious cycle of dysfunctional beliefs can improve disability in patients with schizophrenia.

Most alphaviruses are mosquito-borne and can cause severe disease in humans and domesticated animals. In North America, eastern equine encephalitis virus (EEEV) is an important human pathogen with case fatality rates of 30-90%. Currently, there are no therapeutics or vaccines to treat and/or prevent human infection. One critical impediment in countermeasure development is the lack of insight into clinically relevant parameters in a susceptible animal model. This study examined the disease course of EEEV in a cynomolgus macaque model utilizing advanced telemetry technology to continuously and simultaneously measure temperature, respiration, activity, heart rate, blood pressure, electrocardiogram (ECG), and electroencephalography (EEG) following an aerosol challenge at 7.0 log10 PFU. Following challenge, all parameters were rapidly and substantially altered with peak alterations from baseline ranged as follows: temperature (+3.0-4.2°C), respiration rate (+56-128%), activity (-15-76% daytime and +5-22% nighttime), heart rate (+67-190%), systolic (+44-67%) and diastolic blood pressure (+45-80%). Cardiac abnormalities comprised of alterations in QRS and PR duration, QTc Bazett, T wave morphology, amplitude of the QRS complex, and sinoatrial arrest. An unexpected finding of the study was the first documented evidence of a critical cardiac event as an immediate cause of euthanasia in one NHP. All brain waves were rapidly (~12-24 hpi) and profoundly altered with increases of up to 6,800% and severe diffuse slowing of all waves with decreases of ~99%. Lastly, all NHPs exhibited disruption of the circadian rhythm, sleep, and food/fluid intake. Accordingly, all NHPs met the euthanasia criteria by ~106-140 hpi. This is the first of its kind study utilizing state of the art telemetry to investigate multiple clinical parameters relevant to human EEEV infection in a susceptible cynomolgus macaque model. The study provides critical insights into EEEV pathogenesis and the parameters identified will improve animal model development to facilitate rapid evaluation of vaccines and therapeutics.

Introduction Individuals with schizophrenia are at a high risk of physical health comorbidities and premature mortality. Cardiovascular and metabolic causes are an important contributor. There are gaps in monitoring, documenting and managing these physical health comorbidities. Because of their condition, patients themselves may not be aware of these comorbidities and may not be able to follow a lifestyle that prevents and manages the complications. In many low-income and middle-income countries including Pakistan, the bulk of the burden of care for those struggling with schizophrenia falls on the families.Objectives To determine the rate of self-reported physical health disorders and risk factors, like body mass index (BMI) and smoking, associated with cardiovascular and metabolic disorders in cases of schizophrenia compared with a group of mentally healthy controls.Design A case-controlled, cross-sectional multicentre study of patients with schizophrenia in Pakistan.Settings Multiple data collection sites across the country for patients, that is, public and private psychiatric OPDs (out patient departments), specialised psychiatric care facilities, and psychiatric wards of teaching and district level hospitals. Healthy controls were enrolled from the community.Participants We report a total of 6838 participants’ data with (N 3411 (49.9%)) cases of schizophrenia compared with a group of healthy controls (N 3427 (50.1%)).Results BMI (OR 0.98 (CI 0.97 to 0.99), p=0.0025), and the rate of smoking is higher in patients with schizophrenia than in controls. Problems with vision (OR 0.13 (0.08 to 0.2), joint pain (OR 0.18 (0.07 to 0.44)) and high cholesterol (OR 0.13 (0.05 to 0.35)) have higher reported prevalence in controls. The cases describe more physical health disorders in the category ‘other’ (OR 4.65 (3.01 to 7.18)). This captures residual disorders not listed in the questionnaire.Conclusions Participants with schizophrenia in comparison with controls report more disorders. The access in the ‘other’ category may be a reflection of undiagnosed disorders.

Effect of the leaves suspension of Cassia occidentalis on the elimination of excess of iron from the artificially iron overloaded rabbits was studied. Leaves suspension of C. occidentalis (250mg/kg) were used for the elimination of iron from iron overloaded rabbits. Rabbits were divided into three groups; overloaded for five weeks and then treated with selected herb for four weeks. Iron concentrations in serum and body organs like heart, liver and kidneys were assayed in all groups of rabbits after iron overloading with jectosol plus injections as per dose of 0.3 ml (15 mg iron) per kg body weight intramuscularly daily for 5 weeks. There was a significant increase in iron concentration in the sera and organs studied. In iron overloaded animals changes, like loss of weight, loss of hair, loss of activity and increased heart rate were observed. After four weeks of herbal treatment (250mg/kg), there was a significant decrease in iron concentration in the serum and organs as compared with iron overloaded untreated with herb group. The decrease was more significant in kidneys and liver as compared to the heart. It was concluded that C. occidentalis leaves suspension was significantly effective in reducing the iron level from serum and organs studied. [ABSTRACT FROM AUTHOR]