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Objective: To determine the effect of Bryophyllum pinnatum treatment in modulating immune response and the pregnancy outcomes of pregnant pristane-induced lupus mice model. Methods: Sixteen Balb/c mice were intraperitoneally injected with single 0.5 cc pristane to induce lupus manifestations. After 12 weeks of injection, mice were mated and considered as gestational day 0 (GD0). Mice were divided into 4 groups based on the dosages of Bryophyllum pinnatum: control (no treatment), B1 (10.5 mg/kg), B2 (21 mg/kg), and B3 (42 mg/kg). The treatment was given orally every day started from GD9 until 9 days. At the end of the study, blood pressure and fetal size were measured. Serum anti-dsDNA and urine albumin levels were measured by ELISA. Spleen T helper (Th) and mature B cells percentages were measured by flow cytometry. Results: Administration of Bryophyllum pinnatum reduced the percentages of Th1 (p=0.006), Th2 (p=0.005), Th17 (p=0.000), and mature B cells (p=0.007) in dose-dependent manner. B1 and B2 had significantly lower of systolic blood pressure compared to control (p=0.026 and p=0.022 respectively). Significantly lower of anti-dsDNA levels were found in B1 group compared to control (p=0.014). However, no significantly different of urine albumin levels were found between groups. Bryophyllum pinnatum also significantly increased the fetus body weight in dose-dependent manner (p=0.000). Conclusion: Treatment of Bryophyllum pinnatum could improve the pregnancy outcome and modulate the immune response in pregnant pristane-induced lupus mice. Therefore, Bryophyllum pinnatum is a potential herb which can be developed as an immunosuppressive agent in the future.

Background: Curcumin, a polyphenolic compound derived from food spice turmeric has been widely used in Asian traditional medicine for its medicinal properties as antitumor, antioxidant, and anti-inflammatory properties. Meanwhile, intraperitoneal (i.p.) injection of the hydrocarbon oil pristane into normal mice leads to a lupus-like autoimmune syndrome. We aimed to investigate the effects of curcumin on systemic lupus erythematosus (SLE) clinical manifestation, adaptive immune system components, proinflammatory cytokines, and autoantibody production in pristane-induced lupus mice. Methods: Fifty female BALB/c mice, 6–8 weeks old were divided into 2 groups: Forty mice received a single i.p. injection of 0.5 cc pristane for lupus induction and ten mice as healthy controls. Starting at 16 weeks after injection, forty pristane-induced lupus mice were divided into four groups based on doses of curcumin received intragastrically: 0, 12.5, 50, and 200 mg/kg bw/day daily for 16 weeks. At 32 weeks after injection, all of mice were assessed for arthritis score, proteinuria level, body weights, adaptive immune system components (Th1, Th2, Th17, and Treg percentages) from spleen using flow cytometry; proinflammatory cytokines and autoantibody production, including interleukin-6 (IL-6), interferon-alpha (IFN-α), and antinuclear antibody (ANA) from serum using enzyme-linked immunosorbent assay. Results: Arthritis score and proteinuria level were decreased in curcumin-treated mice. However, body weights were not significantly different between the groups. The decreased of Th1, Th2, and Th17 percentages were seen after treatment with 200 mg/kg bw/day of curcumin (P = 0.031,P = 0.017, andP = 0.005, respectively). However, only slight increase of Treg percentages was seen after curcumin treatment. Treatment with 200 mg/kg bw/day of curcumin decreased serum IL-6 and IFN-α levels (P = 0.007 andP = 0.003). Furthermore, ANA levels were also decreased significantly after treatment with 200 mg/kg bw/day of curcumin (P = 0.013). Conclusion: Our findings suggested that curcumin could prove useful as a therapeutic intervention in SLE.

Objective: The objective of the study is to assess job satisfaction between groups of healthcare workers based on their work experience and monthly salary. Methodology: Healthcare workers (n=81) including clinicians, nurses and medical teachers were recruited from a private medical institute at Lahore. Job Satisfaction Survey (JSS) and Professional Quality of Life (ProQOL) Scale including its component scales of Compassion Satisfaction (CS), Burnout (BO) and Secondary Traumatic Stress (STS) were used to determine aspects of vocational quality of life and satisfaction. Kruskal-Wallis test was used to assess group differences. Spearman correlational analysis was done to assess correlation between income, work experience and job satisfaction. Results: Significantly higher professional satisfaction, lower burnout and stress scores were observed in experienced healthcare workers as compared to less-experienced ones (p value =0.039* for JSS, p value =0.011* for CS, p value =0.055* for BO and p value =0.027* for STS). Significantly higher satisfaction scores were found in workers with higher monthly income as compared to those with lower monthly salary (p value =0.006* for JSS and p value =0.032* for CS). Significant positive correlation was observed between healthcare workers’ job satisfaction and their experience and monthly salary. Conclusion: More experience at work is particularly associated with lower burnout and reduced occupational stress.

Background: Surgery to address parenchymal lung disease in children is rare. One of the complications of the surgery is a persistent air leak (PAL). Intrabronchial valves (IBV), which received FDA approval for treating PAL in recent years, limit or exclude the inflow of air towards the pleura and allow air and secretions to flow towards central airways. The valves have been effective in adults with PAL but little has been published on their use in children. Methods: Retrospective chart review was performed after IRB approval on patients treated with IBV after surgical excision of lung parenchyma. A literature review was then performed. Results: 2 pediatric patients are presented. Patient 1, a 10 year old girl underwent excision of a lung mass that developed persistent air leak. Traditional conservative methods did not seal the air leak for 23 days but an IBV sealed the leak in 24 h. Patient 2, a 6 year old boy underwent a pneumonectomy with post-operative bronhical leak. The bronchus was repaired but a leak persisted for 36 days. An IBV sealed the leak immediately. Conclusion: Intrabronchial valves can be used for the management of persistent pulmonary air leaks. We propose a tentative algorithm for using the devices in children with PAL. Keywords: Endobronchial valve, Intrabronchial valve, PAL, Persistent air leak, Pediatric

The article presents a study that describes gastrointestinal tuberculosis over the ten-year period 1967-1977, and obtains information that would help to characterized the symptoms and investigation that would assist future diagnosis in Bradford, England. It states that all the tubercle bacilli positively identified were of the hominis type. On the other hand, they conclude that clinical awareness and diagnostic vigilance remain the key to the diagnosis of gastrointestinal tuberculosis.

Modifiable risk factors of cardiovascular diseases (CVD) have their triggers in the neighborhood environments of communities. Studying the environmental triggers for CVD risk factors is important to understand the situation in a broader perspective. Young adults are influenced the most by the environment profile around them hence it is important to study this subset of the population.This was a descriptive study conducted using the EPOCH research tool designed by the authors of the PURE study. The study population consisted of young adults aged 18-25 in two areas of Karachi. The study setting was busy shopping malls frequented by young adults in the particular community being studied.Our total sample size was 120 individuals, who consented to be interviewed by our interviewers. Less than 50% of the population recognized some form of restriction regarding smoking in their communities. The largest contributor to tobacco advertising was actors smoking in movies and TV shows with 89% responses from both communities. Only 11.9% of the individuals disapproved of smoking cigarettes among men with wide acceptance of 'sheesha' across all age groups. Advertising for smoking and junk food was more frequent as compared to smoking cessation, healthy diet and exercise in both the areas. Unhealthy food items were more easily available in contrast to healthier options. The cost of healthy snack food options including vegetables and fruits was higher than sugary drinks and foods.This assessment showed that both communities were exposed to environments that promote risk factors for cardiovascular diseases.

The article offers information on the Sustainable Development Agenda (SDA) 2030 which focuses on the symbiotic relationship between health and development. The aim of the agenda's Sustainable Development Goal 3 (SDG3) is to ensure healthy lives and promote well-being for all at all ages. Areas covered by the other SDGs include poverty, hunger and education. The implication of the agenda for governments and development partners is addressed.

Abstract Background Delay in diagnosis and treatment of tuberculosis (TB) may enhance the chances of morbidity and mortality and play a key role in continuous transmission of the bacilli. The objective of this study was to describe health care seeking behavior of suspected TB patients and initial diagnostic work up prior to consultation and diagnosis at National TB Center (NTC). Findings Interviews of 252 sputum smear positive patients were taken from NTC, Rawalpindi. The duration between on-set of symptoms and start of treatment was considered as the total delay and correlated with general characteristics of TB patients. The proportion of males and females were 49.6% and 50.4% with median age of 25 and 24 years respectively. A median delay of 56 days (8 weeks) was observed which was significantly associated with age, cough and fever. More than 50% of the current patients had a history of contact with previously diagnosed TB patients. The majority of patients (63%) visited health care providers within three weeks of appearance of symptoms but only thirty five percent were investigated for TB diagnosis. Conclusion Cough and fever are being ignored as likely symptoms of TB by patients as well as health care providers resulting in delay. Engaging private practitioners through public private mix (PPM) approach for expansion of TB diagnosis and increasing public awareness could be more beneficial to reduce delay.

Cancer research has advanced tremendously with the identification of causative genes, proteins, and signaling pathways. Numerous antitumor drugs have been designed and screened for cancer therapeutics; however, designing target-specific drugs for malignant cells with minimal side effects is challenging. Recently, energy-sensing- and homeostasis-associated molecules and signaling pathways playing a role in proliferation, apoptosis, autophagy, and angiogenesis have received increasing attention. Energy-metabolism-based studies have shown the contribution of energetics to cancer development, where tumor cells show increased glycolytic activity and decreased oxidative phosphorylation (the Warburg effect) in order to obtain the required additional energy for rapid division. The role of energy homeostasis in the survival of normal as well as malignant cells is critical; therefore, fuel intake and expenditure must be balanced within acceptable limits. Thus, energy-sensing enzymes detecting the disruption of glycolysis, AMP, ATP, or GTP levels are promising anticancer therapeutic targets. Here, we review the common energy mediators and energy sensors and their metabolic properties, mechanisms, and associated signaling pathways involved in carcinogenesis, and explore the possibility of identifying drugs for inhibiting the energy metabolism of tumor cells. Furthermore, to corroborate our hypothesis, we performed meta-analysis based on transcriptomic profiling to search for energy-associated biomarkers and canonical pathways.

Competing Interests: Competing interests: None declared.

Breast and ovarian cancers are prevalent worldwide, with genetic factors such as BRCA1 and BRCA2 mutations playing a significant role. However, not all patients carry these mutations, making it challenging to identify risk factors. Researchers have turned to whole exome sequencing (WES) as a tool to identify genetic risk factors in BRCA-negative women. WES allows the sequencing of all protein-coding regions of an individual's genome, providing a comprehensive analysis that surpasses traditional gene-by-gene sequencing methods. This technology offers efficiency, cost-effectiveness and the potential to identify new genetic variants contributing to the susceptibility to the diseases. Interpreting WES data for disease-causing variants is challenging due to its complex nature. Machine learning techniques can uncover hidden genetic-variant patterns associated with cancer susceptibility. In this study, we used the extreme gradient boosting (XGBoost) and random forest (RF) algorithms to identify BRCA-related cancer high-risk genes specifically in the Saudi population. The experimental results exposed that the RF method scored superior performance with an accuracy of 88.16% and an area under the receiver-operator characteristic curve of 0.95. Using bioinformatics analysis tools, we explored the top features of the high-accuracy machine learning model that we built to enhance our knowledge of genetic interactions and find complex genetic patterns connected to the development of BRCA-related cancers. We were able to identify the significance of HLA gene variations in these WES datasets for BRCA-related patients. We find that immune response mechanisms play a major role in the development of BRCA-related cancer. It specifically highlights genes associated with antigen processing and presentation, such as HLA-B, HLA-A and HLA-DRB1 and their possible effects on tumour progression and immune evasion. In summary, by utilizing machine learning approaches, we have the potential to aid in the development of precision medicine approaches for early detection and personalized treatment strategies., Competing Interests: Sajjad Karim is an Academic Editor for PeerJ., (© 2024 Alganmi et al.)

Acute myeloid leukemia (AML) is hallmarked by the clonal proliferation of myeloid blasts. Mutations that result in the constitutive activation of the fms-like tyrosine kinase 3 ( FLT3 ) gene, coding for a class III receptor tyrosine kinase, are significantly associated with this heterogeneous hematologic malignancy. The fms-related tyrosine kinase 3 ligand binds to the extracellular domain of the FLT3 receptor, inducing homodimer formation in the plasma membrane, leading to autophosphorylation and activation of apoptosis, proliferation, and differentiation of hematopoietic cells in bone marrow. In the present study, we evaluated the association of FLT3 as a significant biomarker for AML and tried to comprehend the effects of specific variations on the FLT3 protein's structure and function. We also examined the effects of I836 variants on binding affinity to sorafenib using molecular docking. We integrated multiple bioinformatics tools, databases, and resources such as OncoDB, UniProt, COSMIC, UALCAN, PyMOL, ProSA, Missense3D, InterProScan, SIFT, PolyPhen, and PredictSNP to annotate the structural, functional, and phenotypic impact of the known variations associated with FLT3 . Twenty-nine FLT3 variants were analyzed using in silico approaches such as DynaMut, CUPSAT, AutoDock, and Discovery Studio for their impact on protein stability, flexibility, function, and binding affinity. The OncoDB and UALCAN portals confirmed the association of FLT3 gene expression and its mutational status with AML. A computational structural analysis of the deleterious variants of FLT3 revealed I863F mutants as destabilizers of the protein structure, possibly leading to functional changes. Many single-nucleotide variations in FLT3 have an impact on its structure and function. Thus, the annotation of FLT3 SNVs and the prediction of their deleterious pathogenic impact will facilitate an insight into the tumorigenesis process and guide experimental studies and clinical implications.

India is a large middle-income country and has surpassed China in overall population, comprising 20% of the global population (over 1.43 billion people). India is experiencing a major demographic shift in its aging population. Chronic diseases are common among older adults and can be persistent over the life course, lead to the onset of disability, and be costly. Among older adults in India, the existence of multiple comorbid chronic conditions (i.e., multimorbidity) is rapidly growing and represents a burgeoning public health burden. Prior research identified greater rates of multimorbidity (e.g., overweight/obesity diabetes, hypertension, cardiovascular disease, stroke, and malignancies) in minority populations in the United States (U.S.); however, limited studies have attempted to characterize multimorbidity among older adult sub-populations residing in India. To address this gap, we conducted a narrative review of studies on multimorbidity using the data from the Longitudinal Aging Study of India (LASI), the largest nationally representative longitudinal survey study of adults in India. Our definition of multimorbidity was the presence of more than two conditions in the same person. Our findings, based on 15 reviewed studies, aim to (1) characterize the definition and measurement of multimorbidity and to ascertain its prevalence in ethnically and culturally diverse sub-populations in India; (2) identify adverse outcomes associated with multimorbidity in the Indian adult population; and (3) identify gaps, opportunities, and future directions.

Background: Lipodystrophy is a relatively rare, complex disease characterised by a deficiency of adipose tissue and can present as either generalised lipodystrophy (GLD) or partial lipodystrophy (PLD). The prevalence of this disease varies by region. This study aimed to identify the genetic variations associated with lipodystrophy in the southern part of Saudi Arabia., Methodology:  We conducted a retrospective study by recruiting nine patients from six families, recruiting the proband whole exome sequencing results or any other genetic test results, screening other family members using Sanger sequencing and analysing the carrier status of the latter. These patients were recruited from the Endocrinology and Diabetes Clinic at Jazan General Hospital and East Jeddah Hospital, both in the Kingdom of Saudi Arabia., Result: Eight patients were diagnosed with GLD, and one was diagnosed with PLD. Of the six families, four were consanguineously married from the same tribe, while the remaining belonged to the same clan. The majority of GLD patients had an AGPAT2 c.158del mutation, but some had a BSCL2 c.942dup mutation. The single PLD case had a PPARG c.1024C > T mutation but no family history of the disease. In all families evaluated in this study, some family members were confirmed to be carriers of the mutation observed in the corresponding patient., Conclusion:  Familial screening of relatives of patients with rare, autosomal recessive diseases, such as lipodystrophy, especially when there is a family history, allows the implementation of measures to prevent the onset or reduced severity of disease and reduces the chances of the pathogenic allele being passed onto future generations. Creating a national registry of patients with genetic diseases and carriers of familial pathogenic alleles will allow the assessment of preventive measures and accelerate disease intervention via gene therapy., (© 2024. The Author(s).)

Iron (Fe) has been critically reported to act as a signal that can be interpreted to activate the molecular mechanisms involved in root developmental processes. Arsenic (As) is a well-known metalloid that restricts the growth and productivity of rice plants by altering their root architecture. Since root system architecture (RSA) under As stress targets WRKY transcription factors (TFs) and their interaction partners, the current investigation was carried out to better understand the Fe-dependent dynamics of RSA and its participation in this process. Here, we analyzed the effects of As and Fe (alone or in combination) exposed to hydroponically grown rice roots of 12-day-old plants. Our research showed that adding As to Fe changed how OsWRKY71 was expressed and improved the morphology and anatomy of the rice roots in Ratna and Lalat varieties. As + Fe treatment also manifested the biochemical parameters. OsWRKY71, revealed an up-regulation (Fe alone and As + Fe conditions) and down-regulation (As stress) in both varieties, in comparison to the controls. The improved root anatomy and root oxidizability indicated the enhanced capability of Lalat over the Ratna variety to induce OsWRKY71 for the better development of RSA during As + Fe treatment. Further, OsWRKY71 has revealed the presence of gibberellin-responsive cis-regulatory elements (GAREs) in its promoter region, indicating the involvement of OsWRKY71 in the gibberellin pathway. Molecular docking revealed that OsWRKY71 and SLR1 (DELLA protein) interact positively, which supports the hypothesis that Fe alters RSA by regulating OsWRKY71 through the gibberellin pathway in As-stressed rice., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Breast cancer is the leading cause of cancer-related mortality among women worldwide. Advanced stages are usually obstinate with chemotherapy, resulting in a poor prognosis; however, they are treatable if diagnosed early., Objective: Identifying biomarkers that can detect cancer early or have therapeutic significance is imperative., Methods: Herein, a comprehensive bioinformatics-based transcriptomics study of breast cancer for identifying differentially expressed genes (DEGs), followed by a screening of potential compounds by molecular docking, was performed. Genome-wide mRNA expression data of breast cancer patients (n=248) and controls (n=65) were retrieved from the GEO database for meta-analysis. Statistically significant DEGs were used for enrichment analysis based on ingenuity pathway analysis and protein-protein network analysis., Results: A total of 3096 unique DEGs (965 up-regulated and 2131 down-regulated) were mapped as biologically relevant. The most upregulated genes were COL10A1, COL11A1, TOP2A, BIRC5 (survivin), MMP11, S100P, RARA, and the most downregulated genes were ADIPOQ, LEP, CFD, PCK1 and HBA2. Transcriptomic and molecular pathway analyses identified BIRC5/survivin as a significant DEG. Kinetochore metaphase signaling is recognized as a prominent dysregulated canonical pathway. Protein-protein interaction study revealed that KIF2C, KIF20A, KIF23, CDCA8, AURKA, AURKB, INCENP, CDK1, BUB1 and CENPA are BIRC5-associated proteins. Molecular docking was performed to exhibit binding interactions with multiple natural ligands., Conclusion: BIRC5 is a promising predictive marker and a potential therapeutic target in breast cancer. Further large-scale studies are required to correlate the significance of BIRC5 in breast cancer, leading to a step toward the clinical translation of novel diagnostic and therapeutic options., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Many countries in the Eastern Mediterranean Region (EMR) have developed packages of services for achieving Universal Health Coverage (UHC), however, policymakers, especially in resource-constrained countries, still face challenges in delivering equitable, efficient and sustainable health services., Aims: To provide guidance for EMR countries and develop packages of services for UHC., Methods: We used information gathered from narrative reviews, national experiences and expert consultations to develop step-by-step guidance for the development of national packages of services for the achievement of UHC by countries in the EMR., Results: The processes used to develop packages of services varied between EMR countries and these processes may not have involved all relevant stakeholders. We highlight in this paper the iterative processes, including several phases and steps, to be used by EMR countries for developing packages of services for UHC. These processes also make provision for continuous monitoring and revision to make necessary improvements as morbidity patterns evolve., Conclusion: Developing a package of services for the achievement of UHC is a significant milestone for EMR countries and it is central to shaping the healthcare system for effective delivery of services., (Copyright: © Authors 2023; Licensee: World Health Organization. EMHJ is an open access journal. This paper is available under the Creative Commons Attribution Non-Commercial ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo).)

Arsenic (As) is a significant environmental element that restricts the growth and production of rice plants. Although the role of iron (Fe) to sequester As in rice is widely known, the molecular mechanism regarding As-Fe interaction remains opaque. Here, we show the differential response of two rice varieties (Ratna and Lalat) in terms of their morphological and biochemical changes in the presence of As and Fe. These results together with in-silico screening, gene expression analysis, and protein-protein interaction studies suggest the role of OsWRKY76 in Fe-mediated As stress alleviation. When OsWRKY76 is activated by MAPK signaling, it inhibits the gene expression of Fe transporters OsIRT1 and OsYSL2, which reduces the amount of Fe accumulated. However, MAPK signaling and OsWRKY76 remain down-regulated during Fe supplementation with As, which subsequently encourages the up-regulation of OsIRT1 and OsYSL2. This results in greater Fe content and decreased As accumulation and toxicity. The lower H 2 O 2 and SOD, CAT, and APX activities were likewise seen under the As + Fe condition. Overall, results revealed the molecular aspects of Fe-mediated control of OsWRKY76 signaling and showed that Ratna is a more As tolerant variety than Lalat. Lalat, however, performs better in As stress due to the presence of Fe., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Host-pathogen interactions are complex by nature, and the host developmental stage increases this complexity. By utilizing Caenorhabditis elegans larvae as the host and the bacterium Pseudomonas aeruginosa as the pathogen, we investigated how a developing organism copes with pathogenic stress. By screening 36 P. aeruginosa isolates, we found that the CF18 strain causes a severe but reversible developmental delay via induction of reactive oxygen species (ROS) and mitochondrial dysfunction. While the larvae upregulate mitophagy, antimicrobial, and detoxification genes, mitochondrial unfolded protein response (UPR mt ) genes are repressed. Either antioxidant or iron supplementation rescues the phenotypes. We examined the virulence factors of CF18 via transposon mutagenesis and RNA sequencing (RNA-seq). We found that non-phenazine toxins that are regulated by quorum sensing (QS) and the GacA/S system are responsible for developmental slowing. This study highlights the importance of ROS levels and mitochondrial health as determinants of developmental rate and how pathogens can attack these important features., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Targeting foam cells reduces the risk and pathophysiology of atherosclerosis, of which they are one of its early hallmarks. The precise mechanism of action of fucoidan, a potential anti-atherogenic drug, is still unknown. Our objective was to assess the ability of fucoidan to regulate expression of ATP-binding cassette transporter A1 (ABCA1) in ox-LDL-induced THP-1 macrophages. Molecular docking was used to predict how fucoidan interacts with anti-foam cell markers, and further in vitro experiments were performed to evaluate the protective effect of fucoidan on modulating uptake and efflux of lipids. THP-1 macrophages were protected by 50 µg/mL of fucoidan and were then induced to form foam cells with 25 µg/mL of ox-LDL. Expression levels were assessed using RT-qPCR, and an Oil Red O stain was used to observe lipid accumulation in THP-1 macrophages. In addition, ABCA1 protein was examined by Western blot, and cellular cholesterol efflux was determined using fluorescently labeled cholesterol. Under a light microscope, decreased lipid accumulation in ox-LDL-induced-THP-1 macrophages pre-treated with fucoidan showed a significant effect, although it did not affect the expression of scavenger receptors ( SR-AI and CD36 ). It is interesting to note that fucoidan dramatically increased the gene and protein expression of ABCA1 , perhaps via the liver X receptor-α ( LXR-α ). Moreover, fucoidan's ability to increase and control the efflux of cholesterol from ox-LDL-induced THP-1 macrophages revealed how it may alter ABCA1's conformation and have a major effect on how it interacts with apolipoprotein A (ApoA1). In vitro results support a rationale for predicting fucoidan and its interaction with its receptor targets' predicted data, hence validating its anti-atherogenic properties and suggesting that fucoidan could be promising as an atheroprotective.

Pakistan is the world's fifth most populous country, with large segments of its population at risk from non-communicable diseases caused by consumption of harmful products, including tobacco and sugar-sweetened beverages. Even though evidence exists that increased taxes on harmful products leads to consumption reductions as well as increased revenues, Pakistan's health taxes remain low. We seek to understand the reasons for the deficient health tax regime. Much of the existing literature emphasises industry tactics, resources and motivations. We take a different approach and instead focus on political institutions in Pakistan which could help explain deficiencies in the health taxes regime. We employed a mixed method design. We conducted: (1) a detailed analysis of media content, (2) semistructured interviews with key stakeholders (and attended relevant meetings) and (3) an analysis of primary and secondary literature, including legal and policy documents. We identify two key aspects of Pakistan's political institutions which may help explain deficiencies in health taxes. First, we identified structural issues in the design and functioning of key institutions responsible for health taxes, including with respect to federalism, intraelite conflict, interagency coordination and intra-agency fragmentation. Second, we found evidence of an entrenchment of industry interests within governmental institutions, which are characterised by weak frameworks for regulating conflicts of interest. We conclude that gaps and conflict within political institutions, owing to weak design, instability and fragmentation, create political opportunity for industry actors to influence the system to advance their interests. The findings of this research indicate towards needed interventions., Competing Interests: Competing interests: ZM served as Special Assistant to the Prime Minister for Health (2019-2020) equivalent to the State Minister of Health; however, there was no overlap between the aforesaid tenure and the research activity conducted for the present study., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Health taxes are effective policy instruments to save lives, raise government revenues and improve equity. Health taxes, however, directly conflict with commercial actors' interests. Both pro-tax health advocates and anti-tax industry representatives seek to frame health tax policy. Yet, little is known about which frames resonate in which settings and how framing can most effectively advance or limit policies. To fill this gap, we conducted qualitative research in 2022, including focus group discussions, in-depth interviews, document reviews and media analysis on the political economy of health taxes across eight low-income and middle-income countries. Studies captured multiple actors constructing context-specific frames, often tied to broader economic, health and administrative considerations. Findings suggest that no single frame dominates; in fact, a plurality of different frames exist and shape discourse and policymaking. There was no clear trade-off between health and economic framing of health tax policy proposals, nor a straightforward way to handle concerns around earmarking. Understanding how to best position health taxes can empower health policymakers with more persuasive framings for health taxes and can support them to develop broader coalitions to advance health taxes. These insights can improve efforts to advance health taxes by better appreciating political economy factors and constraining corporate power, ultimately leading to improved population-level health., Competing Interests: Competing interests: None declared., (© World Health Organization 2023. Licensee BMJ.)

Background: Pain is a significant problem for many people with advanced disease or a serious illness. Culture and ethnicity can affect the experience and management of pain. However, there is limited research in South Asian communities in the UK on their experiences of pain. The aim of this study is to explore the experiences and attitudes of patients and family carers from South Asian communities about pain and its management within advanced disease or serious illness., Methods: Qualitative thematic analysis based on descriptive phenomenology (Sundler et al. 2019). Qualitative semi-structured interviews with patients or family carers from South Asian communities (N = 15). Interviews were recorded, transcribed and analysed using an inductive approach. Public and Patient Involvement representatives from British South Asian communities were consulted for guidance., Results: There were five key themes from the interviews: The importance of communication about pain with healthcare professionals; Concerns about taking pain medication; Personal resilience, privacy and self-management; Gender, culture and pain; Home pain management as struggle and frustration., Conclusion: To improve pain management for people from South Asian communities with advanced disease or a serious illness, there are a number of important issues for healthcare professionals from palliative and primary care services to address. These include: greater awareness around people's fears and concerns about pain medication; their potential use of alternative pain management strategies; and cultural issues such as resilience, privacy, dignity and gender roles. Effective communication between doctors, patients and family members could be improved by using a 'cultural humility' model; providing clear and accessible pain medication information; understanding and taking account of people with both low, and medium levels, of English language proficiency; and improving patient trust. Additionally, improvements to out of hours services could improve pain management for all patients managing their pain at home., (© 2023. The Author(s).)

Background: Breast cancer (BC) is one of the most common female cancers. Clinical and histopathological information is collectively used for diagnosis, but is often not precise. We applied machine learning (ML) methods to identify the valuable gene signature model based on differentially expressed genes (DEGs) for BC diagnosis and prognosis., Methods: A cohort of 701 samples from 11 GEO BC microarray datasets was used for the identification of significant DEGs. Seven ML methods, including RFECV-LR, RFECV-SVM, LR-L1, SVC-L1, RF, and Extra-Trees were applied for gene reduction and the construction of a diagnostic model for cancer classification. Kaplan-Meier survival analysis was performed for prognostic signature construction. The potential biomarkers were confirmed via qRT-PCR and validated by another set of ML methods including GBDT, XGBoost, AdaBoost, KNN, and MLP., Results: We identified 355 DEGs and predicted BC-associated pathways, including kinetochore metaphase signaling, PTEN, senescence, and phagosome-formation pathways. A hub of 28 DEGs and a novel diagnostic nine-gene signature ( COL10A, S100P, ADAMTS5 , WISP1 , COMP , CXCL10 , LYVE1 , COL11A1 , and INHBA ) were identified using stringent filter conditions. Similarly, a novel prognostic model consisting of eight-gene signatures ( CCNE2 , NUSAP1 , TPX2 , S100P , ITM2A , LIFR , TNXA , and ZBTB16 ) was also identified using disease-free survival and overall survival analysis. Gene signatures were validated by another set of ML methods. Finally, qRT-PCR results confirmed the expression of the identified gene signatures in BC., Conclusion: The ML approach helped construct novel diagnostic and prognostic models based on the expression profiling of BC. The identified nine-gene signature and eight-gene signatures showed excellent potential in BC diagnosis and prognosis, respectively.

Background: A new coronavirus was identified in Jeddah, Saudi Arabia in 2012 and designated as Middle East Respiratory Syndrome Coronavirus (MERS-CoV). To date, this virus has been reported in 27 countries. The virus transmission to humans has already been reported from camels. Currently, there is no vaccine or antiviral therapy available against this virus., Methods: The siRNAs were in silico predicted, designed, and chemically synthesized by using the MERS-CoV-orf1ab region as a target. The antiviral activity was experimentally evaluated by delivering the siRNAs with Lipofectamine™ 2000 and JetPRIME R as transfection reagents in both Vero cell and HEK-293-T cell lines at two different concentrations (10.0 nM and 5.0 nM). The Ct value of quantitative Real-Time PCR (qRT-PCR) was used to calculate and determine the reduction of viral RNA level in both cell supernatant and cell lysate isolated from both cell lines., Results: The sequence alignment resulted in the selection of highly conserved regions. The orf1ab region was used to predict and design the siRNAs and a total of twenty-one siRNAs were finally selected from four hundred and twenty-six siRNAs generated by online software. Inhibition of viral replication and significant reduction of viral RNA was observed against selected siRNAs in both cell lines at both concentrations. Based on the Ct value, the siRNAs # 11, 12, 18, and 20 were observed to be the best performing in both cell lines at both concentrations., Conclusion: Based on the results and data analysis, it is concluded that the use of two different transfection reagents was significantly effective. But the Lipofectamine™ 2000 was found to be a better transfection reagent than the JetPRIME R for the delivery of siRNAs in both cell lines., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Chromosomal imbalance is implicated in developmental delay (DD), congenital malformations (CM), and intellectual disability (ID), and, thus, precise identification of copy number variations (CNVs) is essential. We therefore aimed to investigate the genetic heterogeneity in Saudi children with DD/CM/ID. High-resolution array comparative genomic hybridization (array CGH) was used to detect disease-associated CNVs in 63 patients. Quantitative PCR was done to confirm the detected CNVs. Giemsa banding-based karyotyping was also performed. Array CGH identified chromosomal abnormalities in 24 patients; distinct pathogenic and/or variants of uncertain significance CNVs were found in 19 patients, and aneuploidy was found in 5 patients including 47,XXY (n = 2), 45,X (n = 2) and a patient with trisomy 18 who carried a balanced Robertsonian translocation. CNVs including 9p24p13, 16p13p11, 18p11 had gains/duplications and CNVs, including 3p23p14, 10q26, 11p15, 11q24q25, 13q21.1q32.1, 16p13.3p11.2, and 20q11.1q13.2, had losses/deletions only, while CNVs including 8q24, 11q12, 15q25q26, 16q21q23, and 22q11q13 were found with both gains or losses in different individuals. In contrast, standard karyotyping detected chromosomal abnormalities in ten patients. The diagnosis rate of array CGH (28%, 18/63 patients) was around two-fold higher than that of conventional karyotyping (15.87%, 10/63 patients). We herein report, for the first time, the extremely rare pathogenic CNVs in Saudi children with DD/CM/ID. The reported prevalence of CNVs in Saudi Arabia adds value to clinical cytogenetics.

Identifying cancer biomarkers is imperative, as upregulated genes offer a better microenvironment for the tumor; hence, targeted inhibition is preferred. The theme of our study is to predict molecular interactions between cancer biomarker proteins and selected natural compounds. We identified an overexpressed potential molecular target (AKT1) and computationally evaluated its inhibition by four dietary ligands (isoliquiritigenin, shogaol, tehranolide, and theophylline). The three-dimensional structures of protein and phytochemicals were retrieved from the RCSB PDB database (4EKL) and NCBI's PubChem, respectively. Rational structure-based docking studies were performed using AutoDock. Results were analyzed based primarily on the estimated free binding energy (kcal/mol), hydrogen bonds, and inhibition constant, Ki, to identify the most effective anti-cancer phytomolecule. Toxicity and drug-likeliness prediction were performed using OSIRIS and SwissADME. Amongst the four phytocompounds, tehranolide has better potential to suppress the expression of AKT1 and could be used for anti-cancer drug development, as inhibition of AKT1 is directly associated with the inhibition of growth, progression, and metastasis of the tumor. Docking analyses reveal that tehranolide has the most efficiency in inhibiting AKT1 and has the potential to be used for the therapeutic management of cancer. Natural compounds targeting cancer biomarkers offer less rejection, minimal toxicity, and fewer side effects.

Terpenes and essential oils are materials of great commercial use due to their broad spectra of antibacterial, antifungal, membrane permeation enhancement and antioxidant biological properties, as well as for their use as flavors and fragrances. Yeast particles (YPs) are 3-5 µm hollow and porous microspheres, a byproduct of some food-grade yeast ( Saccharomyces cerevisiae) extract manufacturing processes, that have been used for the encapsulation of terpenes and essential oils with high payload loading capacity (up to 500% weight) and efficiency, providing stability and sustained-release properties. This review focuses on encapsulation approaches for the preparation of YP-terpene and essential oil materials that have a wide range of potential agricultural, food and pharmaceutical applications.

Middle East respiratory syndrome coronavirus (MERS-CoV) is caused by a well-known coronavirus first identified in a hospitalized patient in the Kingdom of Saudi Arabia. MERS-CoV is a serious pathogen affecting both human and camel health globally, with camels being known carriers of viruses that spread to humans. In this work, MERS-CoV genomic sequences were retrieved and analyzed by multiple sequence alignment to design and predict siRNAs with online software. The siRNAs were designed from the orf1ab region of the virus genome because of its high sequence conservation and vital role in virus replication. The designed siRNAs were used for experimental evaluation in selected cell lines: Vero cells, HEK-293-T, and Huh-7. Virus inhibition was assessed according to the cycle threshold value during a quantitative real-time polymerase chain reaction. Out of 462 potential siRNAs, we filtered out 21 based on specific selection criteria without off-target effect. The selected siRNAs did not show any cellular toxicity in the tested cell lines at various concentrations. Based on our results, it was obvious that the combined use of siRNAs exhibited a reduction in MERS-CoV replication in the Vero, HEK-293-T, and Huh-7 cell lines, with the highest efficacy displayed in the Vero cells.