Strength in silence: the journey of mothers raising children with hydrocephalus.

BACKGROUND: Raising a child with hydrocephalus can be very challenging, especially in low- and middle-income countries. In Pakistan, mothers being the primary caregivers for their hydrocephalic children are under tremendous stress. METHODS: This study explores the challenges faced by Pakistani mothers raising children with hydrocephalus, employing a qualitative methodology through focus group discussions comprising ten mothers of hydrocephalic babies at Tertiary Care Hospital in Pakistan. RESULTS: The findings highlight three main themes: emotional toll, social isolation, and financial strain. Mothers experience significant emotional stress due to societal stigma and a lack of support, particularly from their husbands and family. Social isolation is prevalent, as mothers fear sharing their burdens and face physical confinement due to their children's needs. Financial strain is another major issue, with high medical costs adding to their economic difficulties. CONCLUSION: The study emphasizes improved access to specialized care, awareness campaigns to reduce stigma, financial assistance, and stronger community support networks to support these mothers better. Addressing these unmet needs is crucial for empowering Pakistani mothers in their caregiving roles and improving the quality of life for their children with hydrocephalus.

Epidemiological trends and age-period-cohort effects on cardiovascular diseases burden attributable to ambient air pollution across BRICS.

Long-term exposure to ambient air pollution raises the risk of deaths and morbidity worldwide. From 1990 to 2019, we observed the epidemiological trends and age-period-cohort effects on the cardiovascular diseases (CVD) burden attributable to ambient air pollution across Brazil, Russia, India, China, and South Africa (BRICS). The number of CVD deaths related to ambient particulate matter (PM) pollution increased nearly fivefold in China [5.0% (95% CI 4.7, 5.2)] and India [5.7% (95% CI 5.1, 6.3)] during the study period. The age-standardized CVD deaths and disability-adjusted life years (DALYs) due to ambient PM pollution significantly increased in India and China but decreased in Brazil and Russia. Due to air pollution, the relative risk (RR) of premature CVD mortality (< 70 years) was higher in Russia [RR 12.6 (95% CI 8.7, 17.30)] and India [RR 9.2 (95% CI 7.6, 11.20)]. A higher period risk (2015-2019) for CVD deaths was found in India [RR 1.4 (95% CI 1.4, 1.4)] followed by South Africa [RR 1.3 (95% CI 1.3, 1.3)]. Across the BRICS countries, the RR of CVD mortality markedly decreased from the old birth cohort to young birth cohorts. In conclusion, China and India showed an increasing trend of CVD mortality and morbidity due to ambient PM pollution and higher risk of premature CVD deaths were observed in Russia and India.

Navigating the Alzheimer's Treatment Landscape: Unraveling Amyloid-Beta Complexities and Pioneering Precision Medicine Approaches.

A variety of cutting-edge methods and good knowledge of the illness's complex causes are causing a sea change in the field of Alzheimer's Disease (A.D.) research and treatment. Precision medicine is at the vanguard of this change, where individualized treatment plans based on genetic and biomarker profiles give a ray of hope for customized therapeutics. Combination therapies are becoming increasingly popular as a way to address the multifaceted pathology of Alzheimer's by simultaneously attacking Aß plaques, tau tangles, neuroinflammation, and other factors. The article covers several therapeutic design efforts, including BACE inhibitors, gamma- secretase modulators, monoclonal antibodies (e.g., Aducanumab and Lecanemab), and anti- Aß vaccinations. While these techniques appear promising, clinical development faces safety concerns and uneven efficacy. To address the complicated Aß pathology in Alzheimer's disease, a multimodal approach is necessary. The statement emphasizes the continued importance of clinical trials in addressing safety and efficacy concerns. Looking ahead, it suggests that future treatments may take into account genetic and biomarker traits in order to provide more personalized care. Therapies targeting Aß, tau tangles, neuroinflammation, and novel drug delivery modalities are planned. Nanoparticles and gene therapies are only two examples of novel drug delivery methods that have the potential to deliver treatments more effectively, with fewer side effects, and with better therapeutic results. In addition, medicines that target tau proteins in addition to Aß are in the works. Early intervention, based on precise biomarkers, is a linchpin of Alzheimer's care, emphasizing the critical need for detecting the disease at its earliest stages. Lifestyle interventions, encompassing diet, exercise, cognitive training, and social engagement, are emerging as key components in the fight against cognitive decline. Data analytics and art are gaining prominence as strategies to mitigate the brain's inflammatory responses. To pool knowledge and resources in the fight against Alzheimer's, international cooperation between scientists, doctors, and pharmaceutical companies is still essential. In essence, a complex, individualized, and collaborative strategy will characterize Alzheimer's research and therapy in the future. Despite obstacles, these encouraging possibilities show the ongoing commitment of the scientific and medical communities to combat A.D. head-on, providing a glimmer of hope to the countless people and families touched by this savage sickness.

Insight into CMC-PVA-fHNTs Nanocomposite Hydrogel as an Advance Carrier for Cefadroxil Monohydrate: Fabrication and Characterization/Angiogenic Potential Analysis.

Controlled drug delivery is a key strategy aimed at reducing both the frequency of therapeutic dosages and potential systemic side effects, particularly in the case of high drug concentrations. The nanocomposite hydrogel systems presented in this study were synthesized by combining carboxymethyl cellulose, polyvinyl alcohol, and (3-aminopropyl)triethoxysilane-functionalized halloysite nanotubes (fHNTs). This hydrogel system is a potential candidate for the controlled release of cefadroxil monohydrate. These hydrogels are analyzed by Fourier transform infrared spectroscopy, scanning electron microscopy, thermogravimetric analysis, and rheological measurements. Additionally, swelling properties, porosity, hydrophilicity, drug release, and in vitro and in vivo analyses were also evaluated. The observed trends in swelling and drug release demonstrated that the outcomes are dependent on the presence of fHNTs in the hydrogel matrix. Notably, fHNTs-loaded hydrogels displayed sustained drug release patterns. This innovative approach eliminates the need for traditional encapsulation and presents promising and translatable strategies for achieving more effective drug release.

Interleukin 6 Antagonists in Severe COVID-19 Disease: Cardiovascular and Respiratory Outcomes.

BACKGROUND: Inhibitors of interleukin 6 [IL-6] have been utilized to treat severe COVID-19 disease. Their immunosuppressive or immunomodulating impact may be beneficial in COVID-19. OBJECTIVES: To discuss the role of IL-6 inhibitors and assess various trials conducted to evaluate the efficacy of IL-6 inhibitors in COVID-19 disease. SUMMARY: Two of the most common causes of mortality in COVID-19-infected critically ill individuals are acute respiratory distress syndrome (ARDS) and multiorgan failure. Increased levels of inflammatory cytokines suggest that a cytokine storm, also known as cytokine release syndrome (CRS), is involved in the etiology of COVID-19. Most tissue damage, sepsis, and pulmonary and cardiovascular problems are caused mainly by the host defense system. Therefore, regulating this inflammatory cascade using immunomodulators is a prudent strategy. Although corticosteroids, as immunomodulators, are routinely used in COVID-19 management, interleukin (IL) inhibitors, especially IL-6 inhibitors, are also tested in many trials. Many studies have demonstrated that IL-6 inhibitors improve disease outcomes and decrease mortality, whereas others have shown that they are ineffective. In this paper, we briefly examined the role of IL-6 in COVID-19 pathogenesis and trials that support or refute the use of IL-6 inhibitors in treating COVID-19 disease. RESULTS: Though mixed results are coming from trials regarding the adjuvant use of IL-6 inhibitors and standard anti-viral therapy with dexamethasone, a consensus favors using IL-6 inhibitors in severely ill COVID-19 patients regardless of the outcome.

Minimum dietary diversity and associated determinants among children aged 6-23 months in Pakistan.

Pakistan is facing a high prevalence of malnutrition and Minimum Dietary Diversity (MDD) is one of the core indicators that remain below the recommended level. This study assesses MDD and its associated factors among children aged 6 to 23 months in Pakistan. The study uses a cross-sectional study using the dataset of the latest available Multiple Indicators Cluster Survey (MICS) for all provinces of Pakistan. Multistage sampling is used to select 18,699 children aged 6 to 23 months. The empirical method is the Logistic Regression Analysis and Chi-Square Test. The dataset is freely and publicly available with all identifier information removed, and no ethics approvals are required. About one-fifth (20%) of infants and young children aged 6 to 23 months had met MDD, this number varies from 17 to 29%, highest in Baluchistan and lowest in Punjab province of Pakistan. The age group (18-23) indicates a 2.45 times greater chance of having MDD. Age (< 0.001), diarrhea (0.01), prenatal care (0.06), mother's education (< 0.001), computer access (< 0.001), wealth quantile (< 0.001), and residence (< 0.001) were significantly associated with meeting MDD. However, gender (0.6) and mother's age (0.4) both were statistically insignificant in meeting MDD. Regarding mothers' education, compared to no education, the chance of MDD is 1.45 times greater for highly educated mothers in the Punjab province. Dietary diversity among children aged 6 to 23 months in Pakistan is low. It is recommended that mothers should be aware and encouraged to use dietary diverse food for infants and younger children.

An appraisal of traditional knowledge of plant poisoning of livestock and its validation through acute toxicity assay in rats.

Background: Kashmir Himalaya hosts the most diverse and rich flora in the world, which serves as grazing land for millions of small ruminants in the area. While most plant species are beneficial, some can be poisonous, causing economic losses and animal health issues for livestock. Consequently, this study is the first comprehensive report on the traditional phyto-toxicological knowledge in District Muzaffarabad and the assessment of its authenticity through experimental studies in rats. Methods: The data regarding traditional knowledge was gathered from 70 key respondents through semi-structured interviews, which was quantitatively analyzed and authenticated through plant extract testing on Wistar female rats and comparison with published resources. Results: A total of 46 poisonous plant species belonging to 23 families and 38 genera were reported to be poisonous in the study area. Results revealed that leaves were the most toxic plant parts (24 species, 52.1%), followed by the whole plant (18 species, 39.1%), stem (17 species, 36.9%), and seeds (10 species, 21.7%). At the organ level, liver as most susceptible affected by 13 species (28.2%), followed by the gastrointestinal tract (15 species, 32.6%), nervous system (13 species, 8.2%), dermis (8 species, 17.3%), renal (7 species, 15.2%), respiratory (4 species, 8.7%), cardiovascular system (3 species, 6.5%), and reproductive system (2 species, 4.3%). The poisonous plant species with high Relative frequency citation (RFC) and fidelity level (FL) were Nerium oleander (RFC, 0.6; FL, 100), Lantana camara (RFC, 0.6; FL, 100), and Ricinus communis (RFC, 0.6; FL, 100). Experimental assessment of acute toxicity assay in rats revealed that Nerium oleander was the most toxic plant with LD50 of (4,000 mg/kg), trailed by Ricinus communis (4,200 mg/kg), L. camara (4,500 mg/kg), and Datura stramonium (4,700 mg/kg); however, other plants showed moderate to mild toxicity. The major clinical observations were anorexia, piloerection, dyspnea, salivation, tachypnea, constipation, diarrhea, tremor, itchiness, and dullness. Conclusion: This study showed that numerous poisonous plants pose a significant risk to the livestock industry within Himalayan territory, leading to substantial economic losses. Consequently, it is of utmost importance to conduct further comprehensive studies on the phytotoxicity of plants.

Loss of primary cilia and dopaminergic neuroprotection in pathogenic LRRK2-driven and idiopathic Parkinson's disease.

Activating LRRK2 mutations cause Parkinson's disease. Previously, we showed that cholinergic interneurons and astrocytes but not medium spiny neurons of the dorsal striatum lose primary cilia in LRRK2 mutant mice. Single nucleus RNA sequencing shows that cilia loss in cholinergic interneurons correlates with higher LRRK2 expression and decreased glial derived neurotrophic factor transcription. Nevertheless, much higher LRRK2 expression is seen in medium spiny neurons that have normal cilia in mice and humans. In parallel with decreased striatal dopaminergic neurite density, LRRK2 G2019S neurons show increased autism-linked CNTN5 adhesion protein expression; glial cells show significant loss of ferritin heavy chain. Human striatal tissue from LRRK2 pathway mutation carriers and idiopathic Parkinson's disease show similar cilia loss in cholinergic interneurons and astrocytes and overall loss of such neurons. These data strongly suggest that loss of cilia in specific striatal cell types decreases neuroprotection for dopamine neurons in mice and human Parkinson's disease.

Factors associated with maternal health services utilization in Pakistan: Evidence from Pakistan maternal mortality survey, 2019.

BACKGROUND: This study investigates the factors associated with maternal health services utilization in Pakistan using two outcome indicators, ideal antenatal care (IANC), defined as the pregnant woman receiving all the essential services included in standard antenatal care, and skilled birth attendance (SBA). METHODS: This study used the Pakistan Maternal Mortality Survey 2019 data. The study utilized binary logistic regression models to investigate the adjusted association between the outcome variables, separately for IANC and SBA, and the independent variables, education, wealth, parity, and residence. RESULTS: Wealth showed a positive association with utilization of IANC (adjusted odds ratio [AOR] = 11.48, 95% CI = 7.76, 16.99) and SBA (AOR = 4.37, 95% CI = 3.30,5. 80). Maternal age was associated only with IANC for women aged 35 or more years (AOR = 1.31, 95% CI = 1.06, 1.62). Increased likelihood of utilization of IANC and SBA services was also observed for women with formal education. Women who had 3-5 previous live births had higher odds of using IANC and SBA than women who had 1-2 or more than five previous live births. Urban residency was not correlated with either IANC or SBA. CONCLUSION: When compared to the wealthy and educated quintile, women in the lower wealth quintile and those without any formal education were less likely to utilize ANC and SBA services. A comprehensive and multipronged approach from the health and education sectors is needed to improve maternal health in Pakistan.

Barriers experienced by community midwives to provide basic emergency obstetric and newborn care in rural Pakistan.

BACKGROUND: Considering the high maternal mortality rate, the government of Pakistan has deployed Community Midwives (CMWs) in rural areas of Pakistan. This relatively new cadre of community-based skilled birth attendants has previously reported to experience several challenges in providing maternal and child healthcare. However, what barriers they experience in providing basic emergency obstetric and newborn care needs to be further studied. METHODS: This was a cross-sectional study conducted in twelve districts in Sindh province, Pakistan, with poor maternal and child health indicators. A total of 258 CMWs participated in this study and completed the questionnaire on a pretested, validated tool in their community-based stations. The trained data collectors completed the questionnaires from the respondents. The problems identified were categorized into three major issues: financial, and transport and security related; and were analyzed accordingly. Ethical approval was obtained from the institutional review board (IRB) of Health Services Academy (HSA) Islamabad, Pakistan. RESULTS: The majority (90%) of 258 CMWs had formal training in maternal and neonatal care from the recognized institutions. Financial difficulties faced by CMWs were identified as the most frequent barriers and others were transport, security, and other issues. In univariate analysis, 38.1% and 61.9% of the community midwives who faced financial difficulties had completed a graduation or intermediate level of education, respectively (p = 0.006). Round-the-clock availability for emergencies was inversely associated with having financial difficulties, i.e., 71.4%, in contrast to 28.4% who had financial difficulties were available round-the-clock for emergency calls in their community clinics (p = 0.008). Formal training (p = 0.001), work experience (p = 0.015), longer duration of work (p = 0.003), and liaison with health workers and posting district (p = 0.001) had statistically significantly higher transport related issues. Security difficulties faced by CMWs and a set of correlates such as formal training (p = 0.019), working experience (p = 0.001), longer duration of work (p = 0.023), 24 h of availability on call (p = 0.004), liaison with traditional birth attendants (TBAs) in the community (p = 0.002), and district of posting (p = 0.001) were statistically significantly different. Other issues like working experience (p = < 0.001) and Liaison with TBAs in the community (p = < 0.001) were found statistically significant. CONCLUSION: Financial, transportation and security related barriers were commonly reported by community midwives in the delivery of basic emergency obstetric and newborn care in rural Pakistan.

Respectful Maternal Care Experience in Low- and Middle-Income Countries: A Systematic Review.

Background and Objectives: Respectful maternity care promotes practices that acknowledge women's preferences and women and newborns' needs. It is an individual-centered strategy founded on ethical and human rights principles. The objective of this systematic review is to identify the impact of income on maternal care and respectful maternity care in low- and middle-income countries. Materials and Methods: Data were searched from Google Scholar, PubMed, Web of Science, NCBI, CINAHL, National Library of Medicine, ResearchGate, MEDLINE, EMBASE database, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), and Maternity and Infant Care database. This review followed PRISMA guidelines. The initial search for publications comparing low- and middle-income countries with respectful maternity care yielded 6000 papers, from which 700 were selected. The review articles were further analyzed to ensure they were pertinent to the comparative impact of income on maternal care. A total of 24 articles were included, with preference given to those published from 2010 to 2023 during the last fourteen years. Results: Considering this study's findings, respectful maternity care is a crucial component of high-quality care and human rights. It can be estimated that there is a direct association between income and maternity care in LMICs, and maternity care is substandard compared to high-income countries. Moreover, it is determined that the evidence for medical tools that can enhance respectful maternity care is sparse. Conclusions: This review highlights the significance of improving maternal care experiences, emphasizing the importance of promoting respectful practices and addressing disparities in low- and middle-income countries.

A Randomized Controlled Trial of Blood Pressure Reduction Based on Disease Control Priorities 3 in Pakistan to Manage and Control Hypertension.

INTRODUCTION: According to American Heart Association standards, hypertension is classified into three stages based on blood pressure measurements: essential hypertension, stage 1 hypertension, and stage 2 hypertension. The global target is to reduce the prevalence of high blood pressure by 25% by the year 2025. Worldwide, the prevalence of high blood pressure among men and women aged 18 and above reported to be 24% and 20%, respectively. AIM: The aim of this study was to overall reduce high blood pressure of hypertensive patients to the recommended level of 140/90 mm of Hg through implementing a non-pharmacological and multi-component intervention based on Disease Control Priorities (3rd edition). METHODS: A randomized controlled trial in which a multi-component intervention for lowering high blood pressure was tested. This was pilot-tested for its acceptance, appropriateness, and relevance, explored through an earlier formative research and desk review conducted from the available evidence. A total of 240 study participants were enrolled after obtaining informed consent. Ethical approval was obtained from the Institutional Review Board of Health Services Academy and the trial was registered in clinicaltrials.gov number NCT04336631. SPSS software version 21 was used to enter and analyze the data. RESULTS: High blood pressure of hypertensive patients in a hospital setting during 03 months yielded -23.9 mm Hg of systolic blood pressure reduction (95% confidence interval, p ≤ 0.005). A significant reduction was observed in intervention group after delivering the intervention. Compared to patients in the usual care group, improved health outcomes were achieved for diet control, reducing salt intake and increased physical exercise. In the intervention group, the mean blood pressure among male hypertensive patients was 145/90 mm Hg and in female hypertensive patients, the mean blood pressure was recorded as 140/100 mm Hg. CONCLUSION: High blood pressure was significantly reduced in hypertensive patients who adhered to a low salt diet, weight loss measures, and increased physical activity.

Semi-Conservative Treatment Versus Radical Surgery in Abdominal Aortic Graft and Endograft Infections.

OBJECTIVE: Abdominal aortic graft and endograft infections (AGIs) are rare complications following aortic surgery. Radical surgery (RS) with resection of the infected graft and reconstruction with extra-anatomical bypass or in situ reconstruction is the preferred therapy. For patients unfit for RS, a semi-conservative (SC), graft preserving strategy is possible. This paper aimed to compare survival and infection outcomes between RS and SC treatment for AGI in a nationwide cohort. METHODS: Patients with abdominal AGI related surgery in Sweden between January 1995 and May 2017 were identified. The Management of Aortic Graft Infection Collaboration (MAGIC) criteria were used for the definition of AGI. Multivariable regression was performed to identify factors associated with mortality. RESULTS: One hundred and sixty-nine patients with surgically treated abdominal AGI were identified, comprising 43 SC (14 endografts; 53% with a graft enteric fistula [GEF] in total) and 126 RS (26 endografts; 50% with a GEF in total). The SC cohort was older and had a higher frequency of cardiac comorbidities. There was a non-significant trend towards lower Kaplan-Meier estimated five year survival for SC vs. RS (30.2% vs. 48.4%; p = .066). A non-significant trend was identified towards worse Kaplan-Meier estimated five year survival for SC patients with a GEF vs. without a GEF (21.7% vs. 40.1%; p = .097). There were significantly more recurrent graft infections comparing SC with RS (45.4% vs. 19.3%; p < .001). In a Cox regression model adjusting for confounders, there was no difference in five year survival comparing SC vs. RS (HR 1.0, 95% CI 0.6 - 1.5). CONCLUSION: In this national AGI cohort, there was no mortality difference comparing SC and RS for AGI when adjusting for comorbidities. Presence of GEF probably negatively impacts survival outcomes of SC patients. Rates of recurrent infection remain high for SC treated patients.

Determination of Copper at Extended Dose Levels of Copper (II)-acetylsalicylate and Pharmacokinetics Applications.

Rheumatoid arthritis has long been treated with acetylsalicylic acid, despite many side effects, including gastric ulcers. These side effects can be curtailed by preparing the metal complexes of8 acetylsalicylic acid, such as copper (II)-acetylsalicylate (CAS). Present study evaluates the pharmacokinetics parameters of CAS and the level of copper at extended dose levels using rabbit model. The concentrations of CAS and copper in plasma samples were determined by validated HPLC and atomic absorption spectroscopic (AAS) methods, respectively. Three doses, 1-3 mg Kg-1 were orally administered to six rabbits with two wash out periods. The blood samples were collected at different time intervals for 24 hours. The peak drug concentration (Cmax) for these doses at a time to peak drug concentration (tmax) 0.5 h was determined to be 0.38, 0.76 and 1.14 µg mL-1. The half-life of drug (t1/2) was 8.67, 8.73 and 8.81 h, which are perfect results for once a day dosing. The values of volume of distribution (Vd) and clearance (Cl) for CAS were 829, 833 and 837 L Kg-1 and 66.30, 66.74 and 66.95 L h-1, respectively. The AAS results showed that copper levels in rabbit blood plasma were increased with increasing the dosage of CAS, but still remains under the safer limit, which was twofold higher than the reported safe limit.

Synergistic effect of GO/ZnO loading on the performance of cellulose acetate/chitosan blended reverse osmosis membranes for NOM rejection.

Declining freshwater resources along with their pollution are threatening the life existence on earth. To meet the freshwater demand, one of the most appropriate and possible ways which has been adopted all over the world is to reuse wastewater by removing its impurities. Among many water pollutants, natural organic matter (NOM) is found to be responsible as major precursor for the formation of other pollutants. Removal of NOM from wastewater is being done by using membrane filtration systems incorporated with certain nanofillers to increase membranes efficiency and permeability. In this study, novel nanocomposite reverse osmosis (RO) membranes were prepared using cellulose acetate and chitosan in N,N-Dimethyl formamide. Graphene oxide (GO) nanosheets and zinc oxide (ZnO) in different concentration were loaded to modify the membranes for tuning their RO performance. The confirmation of the functional groups is demonstrated by Fourier transform infrared spectroscopy which revealed the specific peaks indicating the formation of the nano-composite membranes. The surface morphology was studied by scanning electronic microscopy which shows a gradual transformation of the membrane surface from voids-free to macro-voids filled surface up to threshold concentration of GO and ZnO. The thermal properties of GO based membranes were analyzed using thermogravimetric analysis and differential scanning calorimetry. The uniform interaction of the GO and ZnO with polymers induced the remarkable thermal properties of the synthesized membranes. Permeate flux and contact angle measurements were considered to estimate their water content (96%) capacity and NOM rejection (96%) using 0.1 ppm humic acid solution. The permeate flux, NOM rejection and the water content changed directly with GO and inversely with ZnO wt% in the membranes up to GO5 (GO:0.14: ZnO:0.03) whereas the contact angle exhibited the inverse relationship with GO and ZnO concentration in casting solution of the synthesized membranes. Hence it can be concluded that prepared RO membranes are suitable for NOM rejection and recommended for water treatment.

Pharmacological Features of 18ß-Glycyrrhetinic Acid: A Pentacyclic Triterpenoid of Therapeutic Potential.

Glycyrrhiza glabra L. (belonging to the family Leguminosae), commonly known as Licorice, is a popular medicinal plant that has been used in traditional medicine worldwide for its ethnopharmacological efficacy in treating several ailments. Natural herbal substances with strong biological activity have recently received much attention. The main metabolite of glycyrrhizic acid is 18ß-glycyrrhetinic acid (18ßGA), a pentacyclic triterpene. A major active plant component derived from licorice root, 18ßGA has sparked a lot of attention due to its pharmacological properties. The current review thoroughly examines the literature on 18ßGA, a major active plant component obtained from Glycyrrhiza glabra L. The current work provides insight into the pharmacological activities of 18ßGA and the potential mechanisms of action involved. The plant contains a variety of phytoconstituents such as 18ßGA, which has a variety of biological effects including antiasthmatic, hepatoprotective, anticancer, nephroprotective, antidiabetic, antileishmanial, antiviral, antibacterial, antipsoriasis, antiosteoporosis, antiepileptic, antiarrhythmic, and anti-inflammatory, and is also useful in the management of pulmonary arterial hypertension, antipsychotic-induced hyperprolactinemia, and cerebral ischemia. This review examines research on the pharmacological characteristics of 18ßGA throughout recent decades to demonstrate its therapeutic potential and any gaps that may exist, presenting possibilities for future drug research and development.

Adenosine 2 receptor regulates autophagy and apoptosis to alleviate ischemia reperfusion injury in type 2 diabetes via IRE-1 signaling.

PURPOSE: This study aimed to determine the effect and mechanism of action of adenosine 2 receptor (A2R) activation on myocardial ischemia reperfusion injury (MIRI) under diabetic conditions. METHODS: MIRI type 2 diabetic rats and H9C2 cardiomyocytes were treated with A2R agonist and then subjected to hypoxia for 6 h and reoxygenation for 18 h. Myocardial damage, and infarct size were determined by cardiac ultrasound. Indicators of cardiomyocyte injury, creatine kinase-MB and cardiac troponin I were detected by Enzyme Linked Immunosorbent Assay. Endoplasmic reticulum stress (ERS) was determined through measuring the expression levels of ERS related genes GRP78, p-IRE1/IRE1, and p-JNKJNK. The mechanism of A2R cardio protection in MIRI through regulating ERS induced autophagy was determined by investigating the ER resident protein IRE-1. The ER-stress inducer Tunicamycin, and the IRE-1 inhibitor STF in combination with the A2R agonist NECA were used, and the cellular responses were assessed through autophagy proteins expression Beclin-1, p62, LC3 and apoptosis. RESULTS: NECA improved left ventricular function post MIRI, limited myocardial infarct size, reduced myocardial damage, decreased cardiomyocytes apoptosis, and attenuated ERS induced autophagy through regulating the IRE-XBP1s-CHOP pathway. These actions resulted into overall protection of the myocardium against MIRI. CONCLUSION: In summary, A2R activation by NECA prior to ischemia attenuates apoptosis, reduces ERS induced autophagy and restores left ventricular function. This protective effect occurs through regulating the IRE1-XBPs-CHOP related mechanisms. NECA is thus a potential target for the treatment of MIRI in patient with type 2 diabetes.

Correlates of early initiation of breast feeding and prelacteal feeding: a cross-sectional study in Sindh province of Pakistan.

OBJECTIVES: The objective of this study was to determine the prevalence and correlates of early initiation of breast feeding and prelacteal feeding in highly disadvantaged districts in Pakistan. DESIGN: This cross-sectional study design. SETTINGS: This study was carried out in twelve districts of the Sindh province of Pakistan. PARTICIPANTS: A total of 4800 mothers with children under 2 years, selected through a multistage random sampling method. DATA ANALYSIS: Bivariate association, survival analysis (Kaplan-Meier and Cox proportional hazard techniques), multivariate linear regression and the ordinary least square model were used. RESULTS: The results show that the prevalence of early initiation of breast feeding was 68% and prelacteal feeding was 32%. Adequate treatment, proper guidance at antenatal care visits, postpartum health check, normal birth with skilled birth attendants, institutional birth, skin-to-skin contact at birth and birth size were all associated with early breastfeeding initiation (p<0.001). The odds of early initiation of breast feeding after birth are higher if the respondents received proper guidance (OR 2.05; 95% CI 1.02 to 4.11) or made skin-to-skin contact (OR 10.65; 95% CI 6.82 to 16.65). Bivariate association between the prelacteal feeding and a set of correlates suggests that all variables under study were significantly associated with the outcome variable of interest at a 95% or higher significance level. The factors which significantly reduced the odds of prelacteal feeding were adequate treatment (OR 0.29; 95% CI 0.23 to 0.37) and postpartum health check (OR 0.65; 95% CI 0.53 to 0.80). CONCLUSION: Sudy concludes that the correlates like adequate treatment of mothers during labour, postpartum health check-up, normal birth with skilled birth attendants, institutional births and skin-to-skin contact between mother and the baby determine the early initiation of breast feeding and prelecteal feeding. Early initiation of breast feeding needs to be encouraged, and communities must be educated against the use of prelacteal feeding.

Omicron variants breakthrough infection elicited higher specific memory immunity than third dose booster in healthy vaccinees.

Homologous booster, heterologous booster, and Omicron variants breakthrough infection (OBI) could improve the humoral immunity against Omicron variants. Questions concerning about memory B cells (MBCs) and T cells immunity against Omicron variants, features of long-term immunity, after booster and OBI, needs to be explored. Here, comparative analysis demonstrate antibody and T cell immunity against ancestral strain, Delta and Omicron variants in Omicron breakthrough infected patients (OBIPs) are comparable to that in Ad5-nCoV boosted healthy volunteers (HVs), higher than that in inactivated vaccine (InV) boosted HVs. However, memory B cells (MBCs) immunity against Omicron variants was highest in OBIPs, followed by Ad5-nCoV boosted and InV boosted HVs. OBIPs and Ad5-nCoV boosted HVs have higher classical MBCs and activated MBCs, and lower naïve MBCs and atypical MBCs relative to both vaccine boosted HVs. Collectively, these data indicate Omicron breakthrough infection elicit higher MBCs and T cells against SARS-CoV-2 especially Omicron variants relative to homologous InV booster and heterologous Ad5-nCoV booster.