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BackgroundHaving patients self-manage their health conditions is a widely promoted concept, but many patients struggle to practice it effectively. Moreover, few studies have analyzed the nature of work required from patients and how such work fits into the context of their daily life. ObjectiveThis study aimed to review the characteristics of patient work in adult patients. Patient work refers to tasks that health conditions impose on patients (eg, taking medications) within a system of contextual factors. MethodsA systematic scoping review was conducted using narrative synthesis. Data were extracted from PubMed, Excerpta Medica database (EMBASE), Cumulative Index to Nursing and Allied Health Literature (CINAHL), and PsycINFO, including studies from August 2013 to August 2018. The included studies focused on adult patients and assessed one or more of the following: (1) physical health–related tasks, (2) cognitive health–related tasks, or (3) contextual factors affecting these tasks. Tasks were categorized according to the themes that emerged: (1) if the task is always visible to others or can be cognitive, (2) if the task must be conducted collaboratively or can be conducted alone, and (3) if the task was done with the purpose of creating resources. Contextual factors were grouped according to the level at which they exert influence (micro, meso, or macro) and where they fit in the patient work system (the macroergonomic layer of physical, social, and organizational factors; the mesoergonomic layer of household and community; and the microergonomic triad of person-task-tools). ResultsIn total, 67 publications were included, with 58 original research articles and 9 review articles. A variety of patient work tasks were observed, ranging from physical and tangible tasks (such as taking medications and visiting health care professionals) to psychological and social tasks (such as creating coping strategies). Patient work was affected by a range of contextual factors on the micro, meso, or macro levels. Our results indicate that most patient work was done alone, in private, and often imposing cognitive burden with low amounts of support. ConclusionsThis review sought to provide insight into the work burden of health management from a patient perspective and how patient context influences such work. For many patients, health-related work is ever present, invisible, and overwhelming. When researchers and clinicians design and implement patient-facing interventions, it is important to understand how the extra work impacts one’s internal state and coping strategy, how such work fits into daily routines, and if these changes could be maintained in the long term.

BackgroundThere has been a recent spate of mobile health (mHealth) app use for immunizations and other public health concerns in low- and middle-income countries. However, recent evidence has largely focused on app development or before-and-after effects on awareness or service coverage. There is little evidence on the factors that facilitate adoption of mHealth programs, which is critical to effectively embed digital technology into mainstream health systems. ObjectiveThis study aimed to provide the qualitative experiences of frontline health staff and district managers while engaging with real-time digital technology to improve the coverage of routine childhood immunization in an underserved rural district in Pakistan. MethodsAn Android-based app was iteratively developed and used for a 2-year period in 11 union councils of the Tando Muhammad Khan district, an underserved rural district with poor immunization coverage in Pakistan. We used iterative methods to examine the (1) acceptability and operability of the app, (2) validity of the collected data, and (3) use of the collected data. In addition, we collected the barriers and enablers for uptake of the mHealth app. Each of these topics was further explored related to changes in work as well as the enabling factors for and barriers to app use. In-depth interviews were conducted with the 26 vaccinators posted in the 11 union councils and 7 purposively selected key informants (government district managers) involved with the Expanded Program for Immunization. Findings were triangulated in line with the three broad research areas. ResultsDigital immunization tracking was considered acceptable by vaccinators and district managers. Real-time immunization data were used to monitor vaccination volume, track children with incomplete vaccinations, develop outreach visit plans, correct existing microplans, and disburse a fuel allowance for outreach sessions. The validity of the app data was perceived to be superior to that of data from manual records. Ease of operability, satisfaction with data, personal recognition, links to field support, and a sense of empowerment served as powerful enablers. Taking twice the time to complete both manual and digital entries and outdated phones over time were considered constraints. An unintended knock-on effect was improved coordination and strengthening of Expanded Program for Immunization review platforms across district stakeholders through digitalized data. ConclusionsEmbedding digital technology into mainstream health systems relies on use by both end users and district stakeholders. Ease of operability, satisfaction with data reliability, personal recognition, links to field support, and empowerment are powerful enablers, whereas improved coordination as a result of easy, transparent data access can be an important by-product of digitalization. Findings are relevant not only for wide-scale implementation of immunization tracking apps in Pakistan but also for informing the use of digital technology for results-based delivery by frontline health workers.

BackgroundPakistan is the sixth most populous nation in the world and has an estimated 4 million stroke survivors. Most survivors are taken care of by community-based caregivers, and there are no inpatient rehabilitation facilities. ObjectiveThe objective of this study was to evaluate the effectiveness and safety of locally designed 5-min movies rolled out in order of relevance that are thematically delivered in a 3-month program to deliver poststroke education to stroke survivor and caregiver dyads returning to the community. MethodsThis study was a randomized controlled, outcome assessor–blinded, parallel group, single-center superiority trial in which participants (stroke survivor-caregiver dyads) with first-ever stroke (both ischemic and hemorrhagic) incidence were randomized within 48 hours of their stroke into either the video-based education intervention group or the control group. The video-based education intervention group had health education delivered through short videos that were shown to the participants and their caregivers at the time of admission, before discharge, and the first and third months of follow-up after discharge. The control group had standardized care including predischarge education and counseling according to defined protocols. All participants enrolled in the video education intervention and control groups were followed for 12 months after discharge for outcome assessment in the outpatient stroke clinics. The primary outcome measures were the proportion of participants achieving control of blood pressure, blood sugar, and blood cholesterol in the video intervention versus the control group. Several predefined secondary outcomes were included in this study, of which we report the mortality and functional disability in this paper. Analysis was by performed using the intention-to-treat principle. ResultsA total of 310 stroke survivors and their caregiver dyads (participant dyads) were recruited over a duration of 6 months. In total, 155 participant dyads were randomized into the intervention and control groups, each. The primary outcome of control of three major risk factors revealed that at 12 months, there was a greater percentage of participants with a systolic BP

Pain arising from trigeminal systems such as headache is common, debilitating, and current treatments (e.g., sumatriptan) are limited. New treatments that target novel mechanisms of action may be required to innovate both short- and long-term pain therapy. Fatty acid amide hydrolase and soluble epoxide hydrolase are two pain-related enzymes that regulate pain and inflammation via independent pathways. We have previously demonstrated that simultaneous inhibition of these enzymes using a novel dual inhibitor alleviates acute inflammatory pain in the hindpaw and does not depress wheel running in rats. Here, we expanded on these findings and performed structure-activity relationships of our lead compound, the 4-phenyl-thiazole-based dual inhibitor SW-17, to generate 18 analogs and tested them for their inhibition at both enzymes. Conversion of the sulfonamide group to a tertiary amine led to a general decrease in the potency for the sEH enzyme, while this change was well-tolerated at the FAAH enzyme yielding several strong inhibitors. Six selected inhibitors were evaluated in mouse and rat sEH inhibition assays and results showed a species difference, i.e. 4-phenyl-thiazole-based analogs are significantly less or not active in mouse sEH compared to human and rat enzymes. The most potent inhibitor, SW-17, was evaluated in a plasma stability assay in human and rat plasma and showed moderate stability. However, SW-17 did not alleviate orofacial inflammatory pain in female rats compared to the traditional anti-migraine agent sumatriptan. Although modification of 4-phenyl-thiazole-based dual inhibitor SW-17 changes potencies at both FAAH and sEH, these approaches may not produce antinociception against trigeminal pain. Key Words: polypharmacology, formalin, inflammation, enzyme inhibition, structure-activity relationship studies.

This article considers cookbooks written by two displaced Shia Ismaili Muslim women--Yasmin Alibhai-Brown's The Settler's Cookbook and four editions of Noorbanu Nimji's A Spicy Touch-- to discover how food becomes a means of placemaking in the diaspora. The authors fled East Africa in the 1970s when Idi Amin expelled Asians from Uganda and anti-Asian sentiment reverberated in other East African countries as well. They made their way to Europe and North America. Cookbooks were often the earliest texts penned by Ismaili women in the diaspora, yet they remain an understudied archive. This article considers such cookbooks as they give a rare account of this minority Muslim community's settlement in the West. Through the cookbooks we uncover women's contribution to the biological and cultural reproduction of this religious community and discover that placemaking has a culinary dimension. Indeed, studies of refugee placemaking often focus on the built environment; this article extends the definition of placemaking to include sensory experiences through which displaced people remember and craft new attachments. Cooking and eating are some such experiences. An examination of Muslim women's culinary placemaking thus enhances our understanding of refugee life and its intersection with religion. Keywords: cookbooks, culinary placemaking, feminist food studies, Ismaili Muslims, migration, Muslims in North America, When I visited my nani in Karachi during summer vacations, she would make me bhel puri. (1) Six-year-old me did not particularly like bhel puri (I was not allowed to [...]

Omar Khoja,1 Bárbara Silva-Passadouro,1 Elena Cristescu,2 Katie McEwan,3 Derek Doherty,4 Fiona O’Connell,5 Frederique Ponchel,1 Matthew Mulvey,6 Sarah Astill,7 Ai Lyn Tan,1,8 Manoj Sivan1,3,8 1Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK; 2Leeds Teaching Hospitals NHS Trust, Chapel Allerton Hospital, Leeds, UK; 3COVID Rehabilitation Service, Leeds Community Healthcare NHS Trust, Leeds, UK; 4School of Medicine, Trinity College Dublin, Trinity Translational Medicine Institute, St. James’s Hospital, Dublin, Ireland; 5Department of Surgery, Trinity St. James’s Cancer Institute, Trinity Translational Medicine Institute, St. James’s Hospital, Dublin, Ireland; 6Academic Unit of Palliative Care, Leeds Institute of Health Sciences, University of Leeds, Leeds, UK; 7School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, UK; 8NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UKCorrespondence: Manoj Sivan, Clinical Professor and Honorary Consultant, Leeds Institute of Rheumatic and Musculoskeletal Medicine, Floor D Martin Wing, Leeds General Infirmary, Leeds, LS1 3EX, UK, Tel +44 (0)113 3922564, Email M.Sivan@leeds.ac.ukPurpose: New-onset chronic musculoskeletal (MSK) pain is one of the common persistent symptoms in Long COVID (LC). This study investigated its clinical characteristics, underlying mechanisms, and impact on function, psychological health, and quality of life.Patients and Methods: Thirty adults (19 female, 11 male) with LC and new-onset chronic MSK pain underwent clinical examination, Quantitative Sensory Testing (QST), and blood tests for inflammatory markers and completed the following outcome measures: Timed Up and Go test (TUG), handgrip strength test, COVID-19 Yorkshire Rehabilitation Scale (C19-YRS), Brief Pain Inventory (BPI), Pain Self-Efficacy Questionnaire (PSEQ), Pain Catastrophizing Scale (PCS), International Physical Activity Questionnaire-short form (IPAQ-sf), Generalized Anxiety Disorder (GAD-7), Patient Health Questionnaire (PHQ-9), and EuroQol Five Dimensions health-related quality of life (EQ-5D-5L).Results: New-onset chronic MSK pain was widespread and continuous in nature, and worse in the joints. When compared to normative values reported in the literature: a) QST revealed mechanical hyperalgesia, heightened temporal summation of pain, and hypoesthesia to vibration stimuli, which is strongly suggestive of central sensitization; b) Plasma cytokine assays indicated distinct pro-inflammatory profiles; c) TUG time indicated reduced balance and mobility; d) handgrip strength revealed general weakness; e) physical activity was lower; and f) there were moderate levels of depression and anxiety with lower self-efficacy scores and lower levels of pain catastrophizing. LC symptoms were of moderate severity (44.8/100), moderate functional disability (22.8/50) and severely compromised overall health (2.6/10) when compared to pre-COVID scores.Conclusion: New-onset chronic MSK pain in LC tends to be widespread, constant, and associated with weakness, reduced function, depression, anxiety, and reduced quality of life. There is associated central sensitization and proinflammatory state in the condition. Further research is essential to explore the longitudinal progression and natural evolution of the new-onset chronic MSK pain in LC.Keywords: post-COVID-19 syndrome, post-COVID-19 condition, post-acute sequelae of COVID-19, chronic widespread pain

Abstract Among Arab-American women in Michigan, rates of cervical cancer screening are lower than those in non-Hispanic White and Black women in the state. A deep understanding of the Arab community’s perspective on cervical cancer screening is needed to address the disparity in rates across populations in Michigan. Arab and Chaldean women across Michigan were invited to participate in Zoom-based focus groups to understand the attitudes, acceptability, and barriers of cervical cancer screening among this population. Four focus groups with a total of 19 women aged 30 to 61 were conducted. The focus groups were conducted in English, Arabic, or both languages. The guided discussion was focused on knowledge of cervical cancer and Human papillomavirus (HPV) and its transmission, attitudes towards HPV vaccination, and attitudes towards cervical cancer screening. HPV self-sampling as an alternative to traditional provider-based screening was specifically discussed as this has been proposed as a way to increase screening in hard-to-reach populations. The conversations revealed insights related to barriers at the individual and community levels for screening and vaccination, attitudes towards preventive health care including screening, a need for accessible women’s health literature, and health education. The women also discussed vaccine hesitancy related to HPV and COVID-19, suggesting a need for targeted community interventions.

BackgroundIn Pakistan’s remote areas, quality health care and experienced professionals are scarce. Telehealth can bridge this gap by offering innovative services like teleconsultations. Schools can serve as effective platforms for introducing these services, significantly improving health service access in semirural communities. ObjectiveThis study aims to explore the feasibility of introducing school-based teleconsultation services (TCS) to strengthen community health in a semirural area of Karachi, Pakistan. MethodsThis study used a mixed methods design. A total of 393 students were enrolled for the quantitative component, while 35 parents, teachers, and community stakeholders participated in the qualitative arm (focused group discussion). Proportional computation for the quantitative data was done using SPSS (version 24; IBM Corp), while qualitative data underwent thematic analysis. ResultsA total of 1046 successful teleconsultations were provided for 393 students over 28 months. The demographic data showed that the mean age of the students availing TCS was 9.24 (SD 3.25) years, with the majority being males (59.3%, 233/393). Only 1.24% (13/1046) of cases required referrals. The qualitative analysis yielded three themes: (1) transformation of the health care experience, (2) escalating demands for teleconsultation, and (3) the psychological aspect of care. ConclusionsThis study demonstrated the efficacy of integrating TCS in a semiurban school in Karachi to address health care accessibility gaps. Implementing TCS through the school platform improved the overall health status of school children while reducing school absences and financial burdens on families. The study highlighted TCS’s cost-effectiveness, time efficiency, and quality, with community support for 24/7 availability, expansion to adults, and a reimbursement model. School health nurse-led TCS offers a scalable solution to health care challenges, enhancing health outcomes for school-going children in Pakistan and globally, particularly in low- and middle-income countries, where accessibility is a major issue.

Single-cell RNA sequencing (scRNA-seq) technology enables the precise analysis of individual cell transcripts with high sensitivity and throughput. When integrated with multiomics technologies, scRNA-seq significantly enhances the understanding of cellular diversity, particularly within the tumor microenvironment. Similarly, single-cell DNA sequencing has emerged as a powerful tool in cancer research, offering unparalleled insights into the genetic heterogeneity and evolution of tumors. In the context of breast cancer, this technology holds substantial promise for decoding the intricate genomic landscape that drives disease progression, treatment resistance, and metastasis. By unraveling the complexities of tumor biology at a granular level, single-cell DNA sequencing provides a pathway to advancing our comprehension of breast cancer and improving patient outcomes through personalized therapeutic interventions. As single-cell sequencing technology continues to evolve and integrate into clinical practice, its application is poised to revolutionize the diagnosis, prognosis, and treatment strategies for breast cancer. This review explores the potential of single-cell sequencing technology to deepen our understanding of breast cancer, highlighting key approaches, recent advancements, and the role of the tumor microenvironment in disease plasticity. Additionally, the review discusses the impact of single-cell sequencing in paving the way for the development of personalized therapies.

Neurexins (Nrxns) have been extensively studied for their role in synapse organization and have been linked to many neuropsychiatric disorders, including autism spectrum disorder (ASD), and epilepsy. However, no studies have provided direct evidence that Nrxns may be the key regulator in the shared pathogenesis of these conditions largely due to complexities among Nrxns and their non-canonical functions in different synapses. Recent studies identified NRXN2 mutations in ASD and epilepsy, but little is known about Nrxn2's role in a circuit-specific manner. Here, we report that conditional deletion of Nrxn2 from the hippocampus and cortex (Nrxn2 cKO) results in behavioral abnormalities, including reduced social preference and increased nestlet shredding behavior. Electrophysiological recordings identified an overall increase in hippocampal CA3→CA1 network activity in Nrxn2 cKO mice. Using intracranial electroencephalogram recordings, we observed unprovoked spontaneous reoccurring electrographic and behavioral seizures in Nrxn2 cKO mice. This study provides the first evidence that conditional deletion of Nrxn2 induces increased network activity that manifests into spontaneous recurrent seizures and behavioral impairments.

Abstract Neurexins (Nrxns) are critical for synapse organization and their mutations have been documented in autism spectrum disorder, schizophrenia, and epilepsy. We recently reported that conditional deletion of Nrxn2, under the control of Emx1Cre promoter, predominately expressed in the neocortex and hippocampus (Emx1-Nrxn2 cKO mice) induced stereotyped patterns of behavior in mice, suggesting behavioral inflexibility. In this study, we investigated the effects of Nrxn2 deletion through two different conditional approaches targeting presynaptic cortical neurons projecting to dorsomedial striatum on the flexibility between goal-directed and habitual actions in response to devaluation of action–outcome (A–O) contingencies in an instrumental learning paradigm or upon reversal of A–O contingencies in a water T-maze paradigm. Nrxn2 deletion through both the conditional approaches induced an inability of mice to discriminate between goal-directed and habitual action strategies in their response to devaluation of A–O contingency. Emx1-Nrxn2 cKO mice exhibited reversal learning deficits, indicating their inability to adopt new action strategies. Overall, our studies showed that Nrxn2 deletion through two distinct conditional deletion approaches impaired flexibility in response to alterations in A–O contingencies. These investigations can lay the foundation for identification of novel genetic factors underlying behavioral inflexibility.

Abstract Aim Biocultural legacy practices are intricately tied to forestry resources, ethnic identity, and social cohesiveness. This study aims to determine the plant cultural values of forest resources and identify plant cultural indicators in each ethnic group, which can aid in long-term natural resource management plans in the current debate on socio-environmental and ecological transitions. Methods Semi-structured interviews, focus group discussions, and field observations were employed to collect data for a comprehensive and systematic ethnobotanical survey from February 2018 to October 2022. Results A total of 330 informants reported 154 plant species from 65 families. Asteraceae was the most prominent botanical family, with herbaceous plant groups outnumbering trees and shrubs. The Gujjar and Pahari groups exhibited the highest level of overlap, followed by significant overlaps between the Gujjar and Kashmiri communities. The close affinity observed between the Gujjar and Pahari groups suggests the horizontal pattern of local plant knowledge between these communities, influenced by their sociocultural interactions and intermarriages. Notably, the Pahari community displayed a rich understanding of medicinal plants and shared unique uses for the reported taxa. This study affirms that both ecological factors and sociocultural influences have played significant roles in shaping local plant knowledge. A total of 31 plant species have been identified as plant cultural markers among all four ethnic groups. We observed a positive correlation between plant cultural values and plant use with the Gujjar and Kashmiri ethnic groups. Artemisia absinthium reported the highest use value of (0.57) with use reports of (189). Adonis aestivalis, Cynoglossum nervosum, Geum elatum, Geranium himalayense, Juncus inflexus, Oxalis acetosella, Polygonatum biflorum, and Salvia hians from the Himalayan region are among the plant taxa whose ethnomedicinal applications are described here for the first time. Conclusion Our data show that local and indigenous forest knowledge and practices could significantly contribute to forest conservation and ecological transition. This may happen if stakeholders generate clear frameworks and biocultural conservation strategies aimed at both dynamically preserve natural habitats and ways of traditional management of local natural resources.

This research investigates the synthesis and application of Losod-zeolite (LOS-Z), a crystalline hydrated sodium aluminosilicate (Na12Al12Si12O48.xH2O) as a potential photocatalyst for dye degradation and H2 production from dye-degraded water. The photocatalytic properties are enhanced by impregnating molybdenum (Mo) into LOS-Z (Mo@LOS-Z). XRD, FTIR, SEM, EDX, and elemental mapping were used to study the physicochemical properties of synthesized materials while UV–vis and PL were employed to explore the optoelectronic properties. The photocatalytic activities for dye degradation and H2 production were evaluated using methylene blue (MB) under visible light irradiation. An enhancement in the efficiency of dye degradation (56%–82%) and H2 production rate was demonstrated due to the competitive photocatalytic performance of 10% Mo@LOS-Z compared to the pristine LOS-Z and CFA-BFA blend. It exhibited 2.5 times higher (∼1200 μmol g−1h−1) H2 production than the LOS-Z (∼480 μmol g−1h−1) due to the synergistic effects of narrowed band gap and recombination rate. This study could pave the way forward into the synthesis of waste-derived photocatalysts for efficient dye degradation and H2 production.

Early life adversity (ELA) is a major health burden in the United States, with 62% of adults reporting at least one adverse childhood experience. These experiences during critical stages of brain development can perturb the development of neural circuits that mediate sensory cue processing and behavioral regulation. Recent studies have reported that ELA impaired the maturation of dendritic spines on neurons in the dorsolateral striatum (DLS) but not in the dorsomedial striatum (DMS). The DMS and DLS are part of two distinct corticostriatal circuits that have been extensively implicated in behavioral flexibility by regulating and integrating action selection with the reward value of those actions. To date, no studies have investigated the multifaceted effects of ELA on aspects of behavioral flexibility that require alternating between different action selection strategies or higher-order cognitive processes, and the underlying synaptic transmission in corticostriatal circuitries. To address this, we employed whole-cell patch-clamp electrophysiology to assess the effects of ELA on synaptic transmission in the DMS and DLS. We also investigated the effects of ELA on the ability to update action control in response to outcome devaluation in an instrumental learning paradigm and reversal of action-outcome contingency in a water T-maze paradigm. At the circuit level, ELA decreased corticostriatal glutamate transmission in male but not in female mice. Interestingly, in DMS, glutamate transmission is decreased in male ELA mice, but increased in female ELA mice. ELA impaired the ability to update action control in response to reward devaluation in a context that promotes goal-directedness in male mice and induced deficits in reversal learning. Overall, our findings demonstrate the sex- and region-dependent effects of ELA on behavioral flexibility and underlying corticostriatal glutamate transmission. By establishing a link between ELA and circuit mechanisms underlying behavioral flexibility, our findings will begin to identify novel molecular mechanisms that can represent strategies for treating behavioral inflexibility in individuals who experienced early life traumatic incidents.

Over the past 3 decades, the prevalence of autism spectrum disorder (ASD) has increased globally from 20 to 28 million cases making ASD the fastest-growing developmental disability in the world. Neurexins are a family of presynaptic cell adhesion molecules that have been increasingly implicated in ASD, as evidenced by genetic mutations in the clinical population. Neurexins function as context-dependent specifiers of synapse properties and critical modulators in maintaining the balance between excitatory and inhibitory transmission (E/I balance). Disrupted E/I balance has long been established as a hallmark of ASD making neurexins excellent starting points for understanding the etiology of ASD. Herein we review neurexin mutations that have been discovered in ASD patients. Further, we discuss distinct synaptic mechanisms underlying the aberrant neurotransmission and behavioral deficits observed in different neurexin mouse models, with focus on recent discoveries from the previously overlooked neurexin-2 gene (Nrxn2 in mice and NRXN2 in humans). Hence, the aim of this review is to provide a summary of new synaptic insights into the molecular underpinnings of ASD.

Attention deficit hyperactivity disorder (ADHD) is a clinically and genetically heterogeneous neurodevelopmental syndrome characterized by behavioral appearances such as impulsivity, inattention, and hyperactivity. The prevalence of ADHD is high in childhood when compared to adults. ADHD has been significantly advanced by genetic research over the past 25 years. However, it is logically conceivable that both genetic and/or non-genetic factors, such as postnatal environmental and social influences, are associated with ADHD phenotype in Arab populations. While genetic influences are strongly linked with the etiology of ADHD, it remains obscure how consanguinity which is an underlying factor for many genetic diseases, contributes to ADHD subtypes. Arabian Gulf Nations have one the highest rates of consanguineous marriages, and consanguinity plays an important contributing factor in many genetic diseases that exist in higher percentages in Arabian Gulf Nations. Therefore, the current review aims to shed light on the genetic variants associated with ADHD subtypes in Arabian Gulf nations and Saudi Arabia in particular. It also focuses on the symptoms and the diagnosis of ADHD before turning to the neuropsychological pathways and subgroups of ADHD. The impact of a consanguinity-based understanding of the ADHD subtype will help to understand the genetic variability of the Arabian Gulf population in comparison with the other parts of the world and will provide novel information to develop new avenues for future research in ADHD.

The concept of the vitamin D response index was developed based on vitamin D intervention studies conducted with Finnish cohorts. In this study, we challenged the concept by performing a single vitamin D3 bolus (80,000 IU) intervention with a cohort of 100 native Saudis. The change of serum levels of the proinflammatory cytokines interleukin 6, interleukin 8 and tumor necrosis factor measured directly before intervention in comparison to samples taken one and thirty days after vitamin D3 supplementation were used as biomarkers for distinguishing low, mid and high responders. Interestingly, we identified 39 % of the study participants as low responders. In contrast, when we used in a subset of 37 study participants whole blood expression changes of seven well-known vitamin D target genes one and thirty days after supplementation as alternative biomarkers, only 9 persons (24 %) were identified as low responders. In conclusion, in Saudi Arabia the rate of low vitamin D responders is equal or even higher than that in Finland. Therefore, similar to Nordic countries also in Saudi Arabia appropriate vitamin D3 supplementation is essential, in order to fulfill the needs of low responders.

ObjectiveTo evaluate the associations between 10 well-established ovarian cancer risk factors and risk of ovarian cancer among women with vs. without endometriosis.DesignPooled analysis of 9 case-control studies in the Ovarian Cancer Association Consortium.SettingPopulation-based.Patient(s)We included 8,500 women with ovarian cancer, 13,592 control women.Intervention(s)Ten well-established ovarian cancer risk factors.Main outcome measure(s)Risk of ovarian cancer for women with and without endometriosis.Result(s)Most risk factor-ovarian cancer associations were similar when comparing women with and without endometriosis, and no interactions were statistically significant. However, body mass index (BMI) 25-

Background: We hypothesized that there is an influence of socioeconomic status (SES) on association between pregnancy complications and premature coronary artery disease (PCAD) risk. Materials and Methods: This project involved a data linkage approach merging three databases of South Australian cohorts using retrospective, age-matched case?control study design. Cases (n?=?721), that is, women aged

Abstract Background The recent earthquake in Syria has caused widespread devastation, leading to extensive damage and loss of life. Considering the diverse range of disasters and conflicts that have affected Syrian society, health workers must possess essential competencies to effectively manage various types of disasters, including earthquakes. Therefore, this study was undertaken to identify the specific competencies required by Syrian health workers to respond efficiently and effectively to earthquakes. Methods An exploratory qualitative study was conducted at the Medical Education Program MEP of the Syrian Virtual University SVU. Nine members of the research team of the MEP, who represent various health specializations in medicine, dentistry, nursing, and pharmacy, accepted to take part in this study. Among these, three members have been actively involved in providing health care in hospitals and the field during the Syrian earthquake on 6 February 2023. The Delphi process was adopted to identify competencies. Health workers involved in earthquake response were categorized into nine groups including medical doctors, dentists, pharmacists, nurses, psychological support professionals, medical students, allied healthcare professionals, on-site disaster teams, and managers. The final list was accepted if it achieved more than 80% agreement among the participants in the first, second, and final rounds. Results The study identified 74 competencies (12 knowledge items, 35 skills, and 27 attitudes) essential for health workers to respond effectively to earthquakes. They are categorized into five domains: "Preparing the team for the rescue process during and, after earthquakes, Implementation of the rescue process, Education and psychological support, Research, and development". Conclusion A list of earthquake competencies was identified for health workers. It is hoped that this list will enhance a country’s resilience and will enable decision–makers to support health workers in acquiring these competencies within a very strained health system in Syria and other countries.

Creatine deficiency disorders are inborn errors of creatine metabolism, an energy homeostasis molecule. One of these, guanidinoacetate N-methyltransferase (GAMT) deficiency, has clinical characteristics that include features of autism, self-mutilation, intellectual disability, and seizures, with approximately 40% having a disorder of movement; failure to thrive can also be a component. Along with low creatine levels, guanidinoacetic acid (GAA) toxicity has been implicated in the pathophysiology of the disorder. Present-day therapy with oral creatine to control GAA lacks efficacy; seizures can persist. Dietary management and pharmacological ornithine treatment are challenging. Using an AAV-based gene therapy approach to express human codon-optimized GAMT in hepatocytes, in situ hybridization, and immunostaining, we demonstrated pan-hepatic GAMT expression. Serial collection of blood demonstrated a marked early and sustained reduction of GAA with normalization of plasma creatine; urinary GAA levels also markedly declined. The terminal time point demonstrated marked improvement in cerebral and myocardial creatine levels. In conjunction with the biochemical findings, treated mice gained weight to nearly match their wild-type littermates, while behavioral studies demonstrated resolution of abnormalities; PET-CT imaging demonstrated improvement in brain metabolism. In conclusion, a gene therapy approach can result in long-term normalization of GAA with increased creatine in guanidinoacetate N-methyltransferase deficiency and at the same time resolves the behavioral phenotype in a murine model of the disorder. These findings have important implications for the development of a new therapy for this abnormality of creatine metabolism.