Challenges of having a child with thalassemia in Pakistan: A phenomenological study.

BACKGROUND: Thalassemia is a persistent hemolytic disease and has debilitating effects on patients and their parents. Parents of these children experience pain and suffer from additional emotional strain as they provide daily and lifetime care and are mostly concerned about the health and future of their children. AIM: The study aimed to understand the experiences of parents of children with thalassemia related to their family, financial, social, treatment, and psychological issues in Pakistan. METHODS: This descriptive phenomenological study recruited 21 parents of children with thalassemia through purposive sampling until data saturation was achieved. Analysis of transcribed interviews was performed through Colaizzi's method and themes and subthemes revolving around diagnosis, challenges, and treatment issues were extracted. FINDINGS: A total of 21 Pakistani parents participated in this study. Most of the participants were females (n = 16, 76.19%), housewives/stay-at-home moms (n = 13 (61.90%), and were uneducated (n = 6, 28.57%). Regarding genetic traits, only three (14.28%) parents declared that they had genetic traits of thalassemia. The findings of our study revealed that thalassemia is enormously influenced by psychosocial and economic problems because of this disease in their families. CONCLUSION: Our findings indicated that parents of these children face multi-faceted challenges, such as physical, socio-emotional, financial, and familial. These findings may lead to an adequate understanding of their individual needs and efficient utilization of supportive and care programs. PRACTICE IMPLICATIONS: An understanding of such experiences, involving those distinctive to Pakistani culture, is especially vital to inform the care of these children and enhance their quality of life.

Vitamin E Analog Trolox Attenuates MPTP-Induced Parkinson's Disease in Mice, Mitigating Oxidative Stress, Neuroinflammation, and Motor Impairment.

Trolox is a potent antioxidant and a water-soluble analog of vitamin E. It has been used in scientific studies to examine oxidative stress and its impact on biological systems. Trolox has been shown to have a neuroprotective effect against ischemia and IL-1ß-mediated neurodegeneration. In this study, we investigated the potential protective mechanisms of Trolox against a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease mouse model. Western blotting, immunofluorescence staining, and ROS/LPO assays were performed to investigate the role of trolox against neuroinflammation, the oxidative stress mediated by MPTP in the Parkinson's disease (PD) mouse model (wild-type mice (C57BL/6N), eight weeks old, average body weight 25-30 g). Our study showed that MPTP increased the expression of α-synuclein, decreased tyrosine hydroxylase (TH) and dopamine transporter (DAT) levels in the striatum and substantia nigra pars compacta (SNpc), and impaired motor function. However, Trolox treatment significantly reversed these PD-like pathologies. Furthermore, Trolox treatment reduced oxidative stress by increasing the expression of nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). Lastly, Trolox treatment inhibited the activated astrocytes (GFAP) and microglia (Iba-1), also reducing phosphorylated nuclear factor-κB, (p-NF-κB) and tumor necrosis factor-alpha (TNF-α) in the PD mouse brain. Overall, our study demonstrated that Trolox may exert neuroprotection on dopaminergic neurons against MPTP-induced oxidative stress, neuroinflammation, motor dysfunction, and neurodegeneration.

Heavy metal(loid)s contaminations in soils of Pakistan: a review for the evaluation of human and ecological risks assessment and spatial distribution.

Heavy metal(loid)s (HM) contaminations in the soil poses threats to the human and ecological community due to their bioaccumulation, toxicity, and persistent nature in the ecosystem. This review was designed to know about the HM contamination in soils, ecological risk, distribution, and potential health risks. Soil HM concentrations published in the last 30 years were collected from Springer, Science Direct, Willey, Mendeley, ResearchGate, Google Scholar, etc. HM concentrations were used for the geo-accumulation index (Igeo), contamination factor, as well as integrated indices such as spatial distribution of ecological risk index. Similarly, the Igeo pattern was observed in Sindh > Baluchistan > Punjab > Khyber Pakhtunkhwa > Gilgit-Baltistan > Islamabad. Moreover, the high ecological risk mean values ranged (160 < ERI < 320) due to cadmium (Cd) was exhibited in the Punjab and Khyber Pakhtunkhwa provinces and Islamabad. Non-carcinogenic risk like hazard quotient was found higher for children (1.59) of Punjab due to arsenic (As) ingestion, whereas the lower risk was observed due to Zn (2.5E-08) for adults of Punjab province via inhalation pathway. Similarly, the health index (HI) from exposure to As (1.61) in soil was higher than the rest of the HM. Moreover, cancerous risk was determined and found in the tolerable range (10-4-10-6). This study recommended that HM contaminants in the soil need to be monitored on regular basis, especially in Baluchistan, Gilgit-Baltistan, and Sindh provinces.

Spatial distribution of potentially toxic elements contaminations and risk indices of water and sediments in the Darband and Samana streams, Pakistan.

This study examined potentially toxic elements (PTE) of water and sediments in the Darband and Samana streams of Hangu District. Darband and Samana streams are the main fluvial ecosystems of Hangu District, Pakistan, directly or indirectly affecting more than 0.52 Million people. Water and sediment samples were collected and analyzed for PTE utilizing inductively coupled plasma mass spectrometry (ICP-MS). Water characteristics of Darband and Samana streams were noted within the WHO drinking water guidelines, except for Turbidity and sulfate. Most water characteristics showed higher values in the Samana stream than in the Darband stream. Similarly, most of PTE showed higher concentrations in sediments collected from the Samana stream than the Darband stream. For ecological risk evaluation, several pollution indices were employed to assess the eco-toxicological consequences. The highest contamination factor (CF) value of 15 and 20 were exhibited by molybdenum (Mo) in the Samana and Darband streams showing very high contamination. Similarly, the pollution load index (PLI) showed that 24% of the sediment samples were polluted (PLI > 1). Furthermore, a high ecological risk in a range of 160 < ERI < 320 was observed for Mo, while a low ecological risk ERI < 40 was by As for the Darband and Samana streams sediments. Statistical techniques revealed that various anthropogenic sources primarily contaminated in water and sediment. Therefore, this study recommends regular monitoring PTE contaminations in the area to avoid any health hazards in the future.

Lupeol Treatment Attenuates Activation of Glial Cells and Oxidative-Stress-Mediated Neuropathology in Mouse Model of Traumatic Brain Injury.

Traumatic brain injury (TBI) signifies a major cause of death and disability. TBI causes central nervous system (CNS) damage under a variety of mechanisms, including protein aggregation, mitochondrial dysfunction, oxidative stress, and neuroinflammation. Astrocytes and microglia, cells of the CNS, are considered the key players in initiating an inflammatory response after injury. Several evidence suggests that activation of astrocytes/microglia and ROS/LPO have the potential to cause more harmful effects in the pathological processes following traumatic brain injury (TBI). Previous studies have established that lupeol provides neuroprotection through modulation of inflammation, oxidative stress, and apoptosis in Aß and LPS model and neurodegenerative disease. However, the effects of lupeol on apoptosis caused by inflammation and oxidative stress in TBI have not yet been investigated. Therefore, we explored the role of Lupeol on antiapoptosis, anti-inflammatory, and antioxidative stress and its potential mechanism following TBI. In these experiments, adult male mice were randomly divided into four groups: control, TBI, TBI+ Lupeol, and Sham group. Western blotting, immunofluorescence staining, and ROS/LPO assays were performed to investigate the role of lupeol against neuroinflammation, oxidative stress, and apoptosis. Lupeol treatment reversed TBI-induced behavioral and memory disturbances. Lupeol attenuated TBI-induced generation of reactive oxygen species/lipid per oxidation (ROS/LPO) and improved the antioxidant protein level, such as nuclear factor erythroid 2-related factor 2 (Nrf2) and heme-oxygenase 1 (HO-1) in the mouse brain. Similarly, our results indicated that lupeol treatment inhibited glial cell activation, p-NF-κB, and downstream signaling molecules, such as TNF-α, COX-2, and IL-1ß, in the mouse cortex and hippocampus. Moreover, lupeol treatment also inhibited mitochondrial apoptotic signaling molecules, such as caspase-3, Bax, cytochrome-C, and reversed deregulated Bcl2 in TBI-treated mice. Overall, our study demonstrated that lupeol inhibits the activation of astrocytes/microglia and ROS/LPO that lead to oxidative stress, neuroinflammation, and apoptosis followed by TBI.

Formulation Development of Mirtazapine Liquisolid Compacts: Optimization Using Central Composite Design.

Mirtazapine is a tetracyclic anti-depressant with poor water solubility. The aim of this study was to improve the dissolution rate of mirtazapine by delivering the drug as a liquisolid compact. Central composite design (CCD) was employed for the preparation of mirtazapine liquisolid compacts. In this, the impacts of two independent factors, i.e., excipient ratio (carrier:coating) and different drug concentration on the response of liquisolid system were optimized. Liquisolid compacts were prepared using propylene glycol as a solvent, microcrystalline cellulose as a carrier, and silicon dioxide (Aerosil) as the coating material. The crystallinity of the formulated drug and the interactions between the excipients were examined using X-ray powder diffraction (XRD) and Fourier-transform infrared spectroscopy (FTIR), respectively. The dissolution study for the liquisolid compact was carried out as per FDA guidelines. The results showed loss of crystallinity of the mirtazapine in the formulation and was completely solubilized in non-volatile solvent and equally dispersed throughout the powder system. Moreover, drug dissolution was found to be higher in liquisolid compacts than the direct compressed conventional tablets (of mirtazapine). The liquisolid technique appears to be a promising approach for improving the dissolution of poorly soluble drugs like mirtazapine.

Glycine, the smallest amino acid, confers neuroprotection against D-galactose-induced neurodegeneration and memory impairment by regulating c-Jun N-terminal kinase in the mouse brain.

BACKGROUND: Glycine is the smallest nonessential amino acid and has previously unrecognized neurotherapeutic effects. In this study, we examined the mechanism underlying the neuroprotective effect of glycine (Gly) against neuroapoptosis, neuroinflammation, synaptic dysfunction, and memory impairment resulting from D-galactose-induced elevation of reactive oxygen species (ROS) during the onset of neurodegeneration in the brains of C57BL/6N mice. METHODS: After in vivo administration of D-galactose (D-gal; 100 mg/kg/day; intraperitoneally (i/p); for 60 days) alone or in combination with glycine (1 g/kg/day in saline solution; subcutaneously; for 60 days), all of the mice were sacrificed for further biochemical (ROS/lipid peroxidation (LPO) assay, Western blotting, and immunohistochemistry) after behavioral analyses. An in vitro study, in which mouse hippocampal neuronal HT22 cells were treated with or without a JNK-specific inhibitor (SP600125), and molecular docking analysis were used to confirm the underlying molecular mechanism and explore the related signaling pathway prior to molecular and histological analyses. RESULTS: Our findings indicated that glycine (an amino acid) inhibited D-gal-induced oxidative stress and significantly upregulated the expression and immunoreactivity of antioxidant proteins (Nrf2 and HO-1) that had been suppressed in the mouse brain. Both the in vitro and in vivo results indicated that D-gal induced oxidative stress-mediated neurodegeneration primarily by upregulating phospho-c-Jun N-terminal kinase (p-JNK) levels. However, D-gal + Gly cotreatment reversed the neurotoxic effects of D-gal by downregulating p-JNK levels, which had been elevated by D-gal. We also found that Gly reversed D-gal-induced neuroapoptosis by significantly reducing the protein expression levels of proapoptotic markers (Bax, cytochrome c, cleaved caspase-3, and cleaved PARP-1) and increasing the protein expression level of the antiapoptotic protein Bcl-2. Both the molecular docking approach and the in vitro study (in which the neuronal HT22 cells were treated with or without a p-JNK-specific inhibitor (SP600125)) further verified our in vivo findings that Gly bound to the p-JNK protein and inhibited its function and the JNK-mediated apoptotic pathway in the mouse brain and HT22 cells. Moreover, the addition of Gly alleviated D-gal-mediated neuroinflammation by inhibiting gliosis via attenuation of astrocytosis (GFAP) and microgliosis (Iba-1) in addition to reducing the protein expression levels of various inflammatory cytokines (IL-1ßeta and TNFα). Finally, the addition of Gly reversed D-gal-induced synaptic dysfunction by upregulating the expression of memory-related presynaptic protein markers (synaptophysin (SYP), syntaxin (Syn), and a postsynaptic density protein (PSD95)) and markedly improved behavioral measures of cognitive deficits in D-gal-treated mice. CONCLUSION: Our findings demonstrate that Gly-mediated deactivation of the JNK signaling pathway underlies the neuroprotective effect of Gly, which reverses D-gal-induced oxidative stress, apoptotic neurodegeneration, neuroinflammation, synaptic dysfunction, and memory impairment. Therefore, we suggest that Gly (an amino acid) is a safe and promising neurotherapeutic candidate that might be used for age-related neurodegenerative diseases.

Vanillic Acid, a Bioactive Phenolic Compound, Counteracts LPS-Induced Neurotoxicity by Regulating c-Jun N-Terminal Kinase in Mouse Brain.

The receptor for advanced glycation end products (RAGE), a pattern recognition receptor signaling event, has been associated with several human illnesses, including neurodegenerative diseases, particularly in Alzheimer's disease (AD). Vanillic acid (V.A), a flavoring agent, is a benzoic acid derivative having a broad range of biological activities, including antioxidant, anti-inflammatory, and neuroprotective effects. However, the underlying molecular mechanisms of V.A in exerting neuroprotection are not well investigated. The present study aims to explore the neuroprotective effects of V.A against lipopolysaccharides (LPS)-induced neuroinflammation, amyloidogenesis, synaptic/memory dysfunction, and neurodegeneration in mice brain. Behavioral tests and biochemical and immunofluorescence assays were applied. Our results indicated increased expression of RAGE and its downstream phospho-c-Jun n-terminal kinase (p-JNK) in the LPS-alone treated group, which was significantly reduced in the V.A + LPS co-treated group. We also found that systemic administration of LPS-injection induced glial cells (microglia and astrocytes) activation and significantly increased expression level of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-KB) and secretion of proinflammatory cytokines including tumor necrosis factor alpha (TNF-α), interleukin-1 ß (IL1-ß), and cyclooxygenase (COX-2). However, V.A + LPS co-treatment significantly inhibited the LPS-induced activation of glial cells and neuroinflammatory mediators. Moreover, we also noted that V.A treatment significantly attenuated LPS-induced increases in the expression of AD markers, such as ß-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1) and amyloid-ß (Aß). Furthermore, V.A treatment significantly reversed LPS-induced synaptic loss via enhancing the expression level of pre- and post-synaptic markers (PSD-95 and SYP), and improved memory performance in LPS-alone treated group. Taken together; we suggest that neuroprotective effects of V.A against LPS-induced neurotoxicity might be via inhibition of LPS/RAGE mediated JNK signaling pathway; and encourage future studies that V.A would be a potential neuroprotective and neurotherapeutic candidate in various neurological disorders.

Potentially toxic elements' occurrence and risk assessment through water and soil of Chitral urban environment, Pakistan: a case study.

This study investigated the concentrations of potentially toxic elements (PTE) including copper (Cu), chromium (Cr), cobalt (Co), cadmium (Cd), nickel (Ni), iron (Fe), zinc (Zn), lead (Pb), molybdenum (Mo) and manganese (Mn) in water and soil of the Chitral city, Pakistan. For this purpose, water (n = 66) and soil (n = 48) samples were collected from various locations of the Chitral city and analyzed for the PTE concentrations. Determined PTE concentrations were evaluated for the human and ecological potential risk. Results revealed that hazard quotient through water consumption was less than the threshold limit (1). However, for soil, the Fe mean hazard index (HI > 1) value for children only surpassed the threshold limits. The mean cancer risk index values via soil exposure were higher (RI > 1 × 10-4) through consumption of Co, Ni and Cd for children and only Co for adults. Contamination factor (CF) values for Mo, Cd and Fe were found very high, considerable and moderate for 79%, 8% and 77% of sampling sites, respectively. Geoaccumulation index (Igeo) showed that soils were moderately-heavily polluted due to Mo. Potential ecological risk index (PERI) values exhibited considerable risk with an average risk index value in the range 190 < RI < 380. Higher values of CF, Igeo and PERI revealed the presence of pollution and pose risk to ecological environment.

Sleep disturbance among Malaysian patients with end-stage renal disease with pruritus.

BACKGROUND: Chronic kidney disease-associated pruritus (CKD-aP) is a well-recognized, frequent and compromising complication among patients on hemodialysis. Despite advancement in basic medical sciences, CKD-aP is still a major complication and a challenge for both physicians and patients to manage. The aim of this study was to estimate the prevalence of CKD-aP among hemodialysis patients in Malaysia, to determine the impact of CKD-aP on sleep quality and any factors associated with CKD-aP. METHOD: A multi-centered, cross-sectional study design was conducted from February 2017 to September 2017 at a tertiary hospital and its affiliated dialysis centers, in Kuala Lumpur, Malaysia. Included were patients > 18 years of age who were undergoing hemodialysis and could understand Malay. Participants were asked to fill the Malay 5D-itch scale and the Malay Pittsburgh sleep quality index (PSQI) upon recruitment. RESULTS: A total of 334/334 patients were recruited (response rate = 100%). The majority were male (59.6%) and Chinese (61.7%). A total of 61.3% had pruritus, of which most patients (63.4%) reported that their pruritus was mild. More than half (54.1%) reported that they slept > 6 h, and 93.2% experienced no sleep disturbances during the night. However; the overall PSQI median score [IQR] was 6.0 [5.0-9.0]. No significant association was found between demographic and clinical characteristics of patients with the severity of pruritus. Patients with moderate to severe pruritus were found to be 5.47 times more likely to experience poor sleep quality as compared to patients with mild or no pruritus. CONCLUSION: In Malaysia, the prevalence of CKD-aP was 61.3%, of which the majority reported that their pruritus was mild. Patients with moderate to severe pruritus were found to be 5.47 times more likely to experience poor sleep quality as compared to patients with mild or no pruritus.

Impact of Pruritus on Sleep Quality of Hemodialysis Patients: A Systematic Review and Meta-Analysis.

: Chronic kidney disease (CKD)-associated pruritus is a common and disturbing condition which has a negative impact on sleep quality, as well as overall health-related quality of life of patients receiving hemodialysis. To date, no systematic review has been undertaken, and there is a lack of concise evidence that statistically quantifies the impact of pruritus based on published data. A systematic search was done for original articles published in peer-reviewed English journals from database inception on 20 December, 2018, in the following databases: PubMed, MEDLINE, EMBASE, Ovid, CINHAL, ProQuest, and Scopus. A total of 9217 research articles were identified. After removal of duplicates and screening for titles and abstracts, 28 articles were selected. The prevalence of disturbed sleep was 4-94%, while the pooled proportion on random effect in the study was 40% (95% CI = 0.30 to 0.49); I2 = 99.8%. However, the prevalence of disturbed sleep quality and quantity due to pruritus was 9-76%, and the pooled proportion on random effect in the study was 50% (95% CI = 0.37 to 0.64); I2 = 99.8%. Patients undergoing hemodialysis who are affected by CKD-associated pruritus have a higher chance of experiencing sleep disturbances. The prevalence of disturbed sleep due to CKD-associated pruritus was found to be 9-76% in the included studies for patients receiving hemodialysis therapy.

Awareness and perception of seasonal influenza (Flu) among health science and Non-Health science university students in Pakistan: A nationwide survey.

Seasonal influenza is a highly contagious viral respiratory disorder. Prior knowledge of flu among general community is of paramount importance in order to mitigate its growing burden. In a pandemic, young adults are more likely to be infected increasing the potential for universities to be explosive disease outbreak centers. In this context, current study aims to assess the knowledge and perception of flu among university students from health sciences (HS) and non-HS background. Questionnaire-based cross sectional (August-December 2015) study was conducted among students of 65 universities across Pakistan. The students willing to participate were requested to fill out the self-administered questionnaire and responses were recorded and descriptively analyzed by SPSS. A total of 1694 students (age: 21.12 ± 2.13 years), 95% which belonged to age group 18-25 years, participated in the current study. Most of the participants (91.7%) had suffered from influenza during their life but only 55.7% correctly answered virus as causative agent of flu, while majority of participants, primarily from non-HS disciplines were not aware of flu cause. Very few participants (8.1%) believed that flu can cause death. About 20% students, mainly from non-HS disciplines reported that antibiotic can kill viruses. Similarly, 47.1% respondents agreed on the effectiveness of antibiotic in flu. A large proportion of study population preferred self-medication for influenza. Only 20.1% students were aware of influenza vaccine while majority of students (79.9%) from both disciplines reported that there is no such vaccine. Awareness and health literacy regarding seasonal influenza is poor among university students, especially from non-HS disciplines. These findings necessitate dire need to appropriately structured awareness programs in educational institutes to curb the growing burden of influenza.

Enrichment, spatial distribution of potential ecological and human health risk assessment via toxic metals in soil and surface water ingestion in the vicinity of Sewakht mines, district Chitral, Northern Pakistan.

This study focuses on enrichment, spatial distribution, potential ecological risk index (PERI) and human health risk of various toxic metals taken via soil and surface water in the vicinity of Sewakht mines, Pakistan. The samples of soils (n = 54) of different fields and surface water (n = 38) were analyzed for toxic metals including cadmium (Cd), cobalt (Co), chromium (Cr), copper (Cu), iron (Fe), manganese (Mn), lead (Pb), nickel (Ni), zinc (Zn) and molybdenum (Mo). Soil pollution level was evaluated using pollution indices including geo-accumulation index (Igeo), contamination factor (CF), degree of contamination (CD), enrichment factor (EF) and PERI. CF showed moderate contamination of soil with Cd, Co, Fe and Mo, while Igeo values indicated moderate accumulation of Cu. For Cd, EF> 1.5 was found in agricultural soils of the study area. PERI findings presented a very high ecological risk (PERI > 380) at two sites (4%), considerable ecological risk at four sites (7.4%). Non-carcinogenic risk from exposure to Fe in soil was higher than limit (HI > 1) for both children and adults. Moreover, carcinogenic risk postured by soil contaminants i.e. Cd, Cr, Co and Ni in children was higher than their limits (except Pb), while in adults only Co posed higher risk of cancer than the limit (10-4) through soil exposure. Non-carcinogenic risks in children due to Cd, Co, Mo via surface water intake were higher than their safe limits (HQ > 1), while in adults the risk order was Cr > Cd > Cu > Pb > Co > Mo. Moreover, carcinogenic risk exposure due to Co > Cd > Cr > Ni from surface water (except Pb) was higher than the tolerable limit (1 × 10-4) both for children and adults. However, Pb concentrations in both soil and surface water exposure were not likely to cause cancer risk in the local population.

Validity and reliability of the Urdu version of the 5D itching scale to assess pruritus among patients with chronic kidney disease in Pakistan.

BACKGROUND: Chronic kidney disease (CKD) has become a major public health issue worldwide in the past few years. Pruritus is a common, well-recognized complication often seen in patients with chronic renal failure. For assessment of pruritus, different tools are used but these tools are unable to identify the changes and variations in the severity of pruritus. The aim of our study was to validate the Urdu-version of the Urdu-version of the 5D itch scale among patients suffering from chronic kidney disease in Pakistan. METHOD: The 5D itch scale was translated from English into Urdu following translation guidelines for translation. Face and content validity was determined by a panel of experts and piloted. For retest, the Urdu version of the 5D itch scale was administered at baseline and two weeks. RESULTS: A total of 50 participants with end stage renal disease were recruited, and of these, 64% were males. Exploratory factor analysis revealed that the 5D-IS had 2-factor loadings: "Pattern and activity" and "Distribution" with Kaiser-Mayer-Olkin (KMO) = 0.802, Bartlett's test of sphericity was significant (df = 28, p < 0.001). At test re-test, Cronbach's alpha was 0.914, while the intra class correlation was 0.9160 (95% confidence interval 0.941-0.975), which is a highly significant correlation (p < 0.0001). CONCLUSION: The Urdu version of the 5D itch scale was found to be a valid and reliable instrument for assessing pruritus and its severity in patients with chronic kidney disease in Pakistan.

An assessment of healthcare professionals' knowledge about and attitude towards influenza vaccination in Freetown Sierra Leone: a cross-sectional study.

BACKGROUND: Vaccinating healthcare professionals against influenza is considered an effective infection control measure. However, there is a low uptake of influenza vaccine among healthcare professionals around the globe. Currently, it is unknown whether healthcare professionals in Sierra Leone are aware of, and have been vaccinated against influenza. Also, there is a paucity of research evidence on their level of knowledge and attitude toward influenza vaccination. This study assessed healthcare professionals' current influenza vaccine uptake rate, reasons for not getting vaccinated as well as their awareness, knowledge of, and attitude towards influenza vaccination in Freetown Sierra Leone. METHOD: A cross-sectional study was conducted between February and April 2016 among healthcare providers working in four public and two private health facilities in Freetown Sierra Leone. Linear regression analysis, one-way ANOVA and independent t-test were employed for data analysis. RESULTS: Among 706 respondents that participated in the study more than half were females 378 (53.6%), nurses 425 (60.4%), and the majority were between the age group of 20-39 years 600 (85.3%). Only 46 (6.5%) were vaccinated against influenza. Key reasons for not vaccinated against influenza were less awareness about influenza vaccination among HCPs 580 (82.73%) with (ß = 0.154; CI 0.058-0.163), the high cost of influenza vaccines and therefore not normally purchased 392 (55.92%) having (ß = 0.150; CI 0.063-0.186). More than half believed that HCPs are less susceptible to influenza infections than other people. Also, majority 585 (84.3%) of HCPs thought that influenza disease could be transmitted after symptoms appear. In addition, 579 (83.2%) of HCPs felt that symptoms usually appear 8-10 days after exposure. Close to half 321 (46.0%) of HCPs were not aware of the influenza immunisation guidelines published by the Advisory Committee on Immunization Practices and Centre for Disease Control. CONCLUSION: Influenza vaccine coverage among healthcare professionals in Freetown Sierra Leone was low. High cost, inadequate knowledge about influenza and its vaccine as well as the lack of awareness of vaccine availability were key barriers. Increasing access to influenza vaccine and the use of appropriate educational interventions to increase knowledge and awareness are required to improve influenza vaccination coverage among HCPs.

Association of anxiolytic drugs with Torsade de Pointes: a pharmacovigilance study of the Food and Drug Administration Adverse Event Reporting System.

Background: This study aimed to determine the association of Torsade de Pointes (TdP) with anxiolytic drugs and present a detailed overview of anxiolytic-induced cases of TdP reported to the Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: All cases of anxiolytic-induced TdP (n = 260) between 1990 and 2020 were retrieved from the FAERS database using the Preferred Term 'Torsade de Pointes, code: 10044066' from the Medical Dictionary for Regulatory Activities (MedDRA version 22). Four data-mining algorithms were used for disproportionality analysis: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Empirical Bayes Geometric Mean (EBGM), and Information Content (IC). Anxiolytics with ≥3 TdP cases were included. Results: Of a total of eight drugs, this study identified seven signals of TdP, of which six signals were new, namely for alprazolam, bromazepam, lorazepam, meprobamate, midazolam, and oxazepam. Based on disproportionality analysis, among new signals, the highest risk of TdP was observed with bromazepam and midazolam. Alprazolam showed the lowest risk for TdP, while diazepam did not reach significant disproportionality. Conclusions: This study identified six new signals of TdP among anxiolytic drugs, so warranting stringent clinical studies to ascertain the actual risk of TdP and ensure patient safety. Clinical Trial Registration: This study is registered at ClinicalTrials.gov (NCT.gov ID: NCT04293432).

Overview of a novel osmotin abolishes abnormal metabolic-associated adiponectin mechanism in Alzheimer's disease: Peripheral and CNS insights.

Alzheimer's disease (AD) is a degenerative brain disease that affects millions of people worldwide. It is caused by abnormalities in cholinergic neurons, oxidative stress, and inflammatory cascades. The illness is accompanied by personality changes, memory issues, and dementia. Metabolic signaling pathways help with fundamental processes like DNA replication and RNA transcription. Being adaptable is essential for both surviving and treating illness. The body's metabolic signaling depends on adipokines, including adiponectin (APN) and other adipokines secreted by adipose tissues. Energy homeostasis is balanced by adipokines, and nutrients. Overconsumption of nutrients messes with irregular signaling of adipokines, such as APN in both peripheral and brain which leads to neurodegeneration, such as AD. Despite the failure of traditional treatments like memantine and cholinesterase inhibitors, natural plant bioactive substances like Osmotin (OSM) have been given a focus as potential therapeutics due to their antioxidant properties, better blood brain barrier (BBB) permeability, excellent cell viability, and especially nanoparticle approaches. The review highlights the published preclinical literature regarding the role of OSM in AD pathology while there is a need for more research to investigate the hidden therapeutic potential of OSM which may open a new gateway and further strengthen its healing role in the pathogenesis of neurodegeneration, especially AD.

Physcion Mitigates LPS-Induced Neuroinflammation, Oxidative Stress, and Memory Impairments via TLR-4/NF-кB Signaling in Adult Mice.

Alzheimer's disease (AD) is the most predominant cause of dementia, considered a progressive decline in cognitive function that ultimately leads to death. AD has posed a substantial challenge in the records of medical science over the past century, representing a predominant etiology of dementia with a high prevalence rate. Neuroinflammation is a common characteristic of various central nervous system (CNS) pathologies like AD, primarily mediated by specialized brain immune and inflammatory cells, such as astrocytes and microglia. The present study aims to elucidate the potential mechanism of physcion that mitigates LPS-induced gliosis and assesses oxidative stress in mice. Physcion reduced the reactivity of Iba-1- and GFAP-positive cells and decreased the level of inflammatory cytokines like TNF-α and IL-1ß. Physcion also reversed the effect of LPS-induced oxidative stress by upregulating the expression of Nrf2 and HO-1. Moreover, physcion treatment reversed LPS-induced synaptic disorder by increasing the level of presynaptic protein SNAP-23 and postsynaptic protein PSD-95. Our findings may provide a contemporary theoretical framework for clinical investigations aimed at examining the pathogenic mechanisms and therapeutic approaches for neuroinflammation and AD.

Effectiveness of digital tools for smoking cessation in Asian countries: a systematic review.

AIM: The use of tobacco is responsible for many preventable diseases and deaths worldwide. Digital interventions have greatly improved patient health and clinical care and have proven to be effective for quitting smoking in the general population due to their flexibility and potential for personalization. However, there is limited evidence on the effectiveness of digital interventions for smoking cessation in Asian countries. METHODS: Three major databases - Web of Science (WOS), Scopus, and PubMed - for relevant studies published between 1 January 2010 and 12 February 2023 were searched for studies evaluating the effectiveness of digital intervention for smoking cessation in Asian countries. RESULTS: A total of 25 studies of varying designs were eligible for this study collectively involving a total of n = 22,005 participants from 9 countries. Among different digital tools for smoking cessation, the highest abstinence rate (70%) was reported with cognitive behavioural theory (CBT)-based smoking cessation intervention via Facebook followed by smartphone app (60%), WhatsApp (59.9%), and Pharmacist counselling with Quit US smartphone app (58.4%). However, WhatsApp was preferred over Facebook intervention due to lower rates of relapse. WeChat was responsible for 15.6% and 41.8% 7-day point prevalence abstinence. For telephone/text messaging abstinence rate ranged from 8-44.3% and quit rates from 6.3% to 16.8%. Whereas, no significant impact of media/multimedia messages and web-based learning on smoking cessation was observed in this study. CONCLUSION: Based on the study findings the use of digital tools can be considered an alternative and cost-effective smoking cessation intervention as compared to traditional smoking cessation interventions.

Heavy metal(loid)s contamination and potential risk assessment via groundwater consumption in the district of Hangu, Pakistan.

This study examined the concentration of heavy metal(loid)s (HM) in groundwater and associated health risks in the Hangu District, Pakistan. Seventy-one groundwater samples were selected from various sources to determine the concentration of twelve HM using the ICP-MS. The average concentrations of HM in groundwater were observed within acceptable guidelines proposed by the World Health Organization (WHO). Similarly, the groundwater of the study area based on the HM contamination index results was noted as an excellent group. Generally, the chronic daily intake (CDI) values for both adults and children were observed in the sequence of Fe > Zn > Ni > Mn > Cu > Sb > Cr > Mo > As > Pb > Co > Cd. The highest hazard quotient was computed for children through groundwater from the tube well. Moreover, both carcinogenic and non-carcinogenic hazards of groundwater were observed in the order of tube well > dug well > spring > bore well. The present study suggests that children were more susceptible to health risks than adults.