epa

Somaliland Prepares for Presidential Polls Amid Regional Tension

[VOA] Washington -- According to the Somaliland National Electoral Commission, more than 1 million registered and eligible voters head to the polls Wednesday to elect their president for the next five years.




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No Separation

Election is the highest expression of God’s love to sinful humanity. Some people hate this doctrine. They fight against it, try to explain it away, or claim it’s not fair. Some even claim it is a form of tyranny, or that it is fatalistic, or that it violates the human will. But in reality the doctrine of election is all about the eternal, inviolable love of God.

READ MORE




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Prince William receives new surprising title as he prepares to become King

Prince William receives new surprising title as he prepares to become KingPrince William, who's making headlines for his future role as monarch amid King Charles health crisis, has received a new title before taking the throne.The Prince of Wales has seemingly given Princess Kate a reason to laugh...




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Navigating the Waves: Strengthening Tsunami Preparedness in a Changing Climate

This year’s World Tsunami Awareness Day presents a moment of reflection 20 years on from the catastrophic Indian Ocean Tsunami in 2004. The tsunami resulted in 225,000 fatalities across 14 countries and emphasized the urgent need for effective tsunami preparedness, especially in the face of growing climate change challenges. Rising sea levels, increased ocean temperatures, […]





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color laserjet 4600 service repair manual

color laserjet 4600 service repair manual




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halasz gl1100 carburetor repair guide

halasz gl1100 carburetor repair guide




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color inkjet printer cp1700 series service repair manual




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1715a oscilloscope repair manual

1715a oscilloscope repair manual




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color laserjet 1600 service repair manual




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6500a plus repair manual

6500a plus repair manual




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color laserjet 2600n service repair manual




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color laserjet 2605dn repair manual




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470 repair manual




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540 and 541 notebook service and repair manual

540 and 541 notebook service and repair manual




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engineering corporation 199toyota camry repair manual free download

engineering corporation 199toyota camry repair manual free download




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65repair manual




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color laserjet 4345 mfp service repair manual




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7150 service and repair guide

7150 service and repair guide




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color laserjet 3100 3150 service repair manual




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Heterogeneous Effect of Out-Migration on Informal Employment in Rural Nepal

Migration may reinforce less productive forms of informal employment in rural Nepal.




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Preparing the Babeldaob Island Urban Resilience Project (formerly Strengthening Urban Planning and Management)

For approval in 2023.




epa

What preparing for an asteroid strike teaches us about climate change

Averting an asteroid strike will need many of the same skills we must hone to tackle climate change and future pandemics




epa

Slick trick separates oil and water with 99.9 per cent purity

Oil and water can be separated efficiently by pumping the mixture through thin channels between two semipermeable membranes




epa

Hepatitis E Vaccine Appears Safe, Effective

Title: Hepatitis E Vaccine Appears Safe, Effective
Category: Health News
Created: 8/23/2010 10:10:00 AM
Last Editorial Review: 8/24/2010 12:00:00 AM




epa

Most U.S. Schools Unprepared for Pandemics: Study

Title: Most U.S. Schools Unprepared for Pandemics: Study
Category: Health News
Created: 8/30/2012 10:05:00 AM
Last Editorial Review: 8/30/2012 12:00:00 AM




epa

New Drug Combo Helps Hard-to-Treat Hepatitis C

Title: New Drug Combo Helps Hard-to-Treat Hepatitis C
Category: Health News
Created: 8/27/2013 4:36:00 PM
Last Editorial Review: 8/28/2013 12:00:00 AM




epa

Health Tip: Preparing for the First Day of School

Title: Health Tip: Preparing for the First Day of School
Category: Health News
Created: 8/27/2014 7:35:00 AM
Last Editorial Review: 8/27/2014 12:00:00 AM




epa

Liver Damage From Hepatitis C More Widespread Than Thought

Title: Liver Damage From Hepatitis C More Widespread Than Thought
Category: Health News
Created: 8/27/2015 12:00:00 AM
Last Editorial Review: 8/27/2015 12:00:00 AM




epa

Health Tip: Keeping Foods Separate During Grilling

Title: Health Tip: Keeping Foods Separate During Grilling
Category: Health News
Created: 8/26/2016 12:00:00 AM
Last Editorial Review: 8/26/2016 12:00:00 AM




epa

Health Tip: Prepare for Your Child's Dental Procedure

Title: Health Tip: Prepare for Your Child's Dental Procedure
Category: Health News
Created: 8/31/2017 12:00:00 AM
Last Editorial Review: 8/31/2017 12:00:00 AM




epa

Test All U.S. Adults for Hepatitis C, Expert Panel Says

Title: Test All U.S. Adults for Hepatitis C, Expert Panel Says
Category: Health News
Created: 8/27/2019 12:00:00 AM
Last Editorial Review: 8/28/2019 12:00:00 AM




epa

Hepatitis (Viral Hepatitis A, B, C, D, E, G)

Title: Hepatitis (Viral Hepatitis A, B, C, D, E, G)
Category: Diseases and Conditions
Created: 12/31/1997 12:00:00 AM
Last Editorial Review: 8/8/2022 12:00:00 AM




epa

Hepatitis C Infection Can Kill, But Less Than a Third of Patients Get Treatment

Title: Hepatitis C Infection Can Kill, But Less Than a Third of Patients Get Treatment
Category: Health News
Created: 8/10/2022 12:00:00 AM
Last Editorial Review: 8/10/2022 12:00:00 AM




epa

Impact of COVID-19 on Chronic Ambulatory-Care-Sensitive Condition Emergency Department Use Among Older Adults

Background:

The COVID-19 pandemic social distancing requirements encouraged patients to avoid public spaces including in-office health care visits. Ambulatory-care-sensitive conditions (ACSCs) represent conditions that can be managed with quality primary care and when access is limited, these conditions can lead to avoidable emergency department (ED) visits.

Methods:

Using national data on ED visits from 2019 to 2021 in the National Hospital Ambulatory Care Survey, we examined the impact of COVID-19 pandemic on ACSC ED visits among older adults (aged ≥65).

Results:

The proportion of ED visits among older adults that were for ACSCs increased between 2019 (17.4%) and 2021 (18.5%). The trend in both rural (26.4%–28.6%) and urban areas (15.4%–16.8%) shows a significant jump from 2019 to 2021 (P < .001).

Conclusions:

This rise in ACSC ED use is consistent with a delay in normal primary care during the pandemic.




epa

Using Primary Health Care Electronic Medical Records to Predict Hospitalizations, Emergency Department Visits, and Mortality: A Systematic Review

Introduction:

High-quality primary care can reduce avoidable emergency department visits and emergency hospitalizations. The availability of electronic medical record (EMR) data and capacities for data storage and processing have created opportunities for predictive analytics. This systematic review examines studies which predict emergency department visits, hospitalizations, and mortality using EMR data from primary care.

Methods:

Six databases (Ovid MEDLINE, PubMed, Embase, EBM Reviews (Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, Cochrane Methodology Register, Health Technology Assessment, NHS Economic Evaluation Database), Scopus, CINAHL) were searched to identify primary peer-reviewed studies in English from inception to February 5, 2020. The search was initially conducted on January 18, 2019, and updated on February 5, 2020.

Results:

A total of 9456 citations were double-reviewed, and 31 studies met the inclusion criteria. The predictive ability measured by C-statistics (ROC) of the best performing models from each study ranged from 0.57 to 0.95. Less than half of the included studies used artificial intelligence methods and only 7 (23%) were externally validated. Age, medical diagnoses, sex, medication use, and prior health service use were the most common predictor variables. Few studies discussed or examined the clinical utility of models.

Conclusions:

This review helps address critical gaps in the literature regarding the potential of primary care EMR data. Despite further work required to address bias and improve the quality and reporting of prediction models, the use of primary care EMR data for predictive analytics holds promise.




epa

Family Medicine Must Prepare for Artificial Intelligence

Artificial Intelligence (AI) is poised to revolutionize family medicine, offering a transformative approach to achieving the Quintuple Aim. This article examines the imperative for family medicine to adapt to the rapidly evolving field of AI, with an emphasis on its integration in clinical practice. AI's recent advancements have the potential to significantly transform health care. We argue for the proactive engagement of family medicine in directing AI technologies toward enhancing the "Quintuple Aim."

The article highlights potential benefits of AI, such as improved patient outcomes through enhanced diagnostic tools, clinician well-being through reduced administrative burdens, and the promotion of health equity by analyzing diverse data sets. However, we also acknowledge the risks associated with AI, including the potential for automation to diverge from patient-centered care and exacerbate health care disparities. Our recommendations stress the need for family medicine education to incorporate AI literacy, the development of a collaborative for AI integration, and the establishment of guidelines and standards through interdisciplinary cooperation. We conclude that although AI poses challenges, its responsible and ethical implementation can revolutionize family medicine, optimizing patient care and enhancing the role of clinicians in a technology-driven future.




epa

Ontogeny of Hepatic Organic Cation Transporter-1 in Rat and Human [Articles]

The organic cation transporter (OCT)-1 mediates hepatic uptake of cationic endogenous compounds and xenobiotics. To date, limited information exists on how Oct1/OCT1 functionally develops with age in rat and human livers and how this would affect the pharmacokinetics of OCT substrates in children or juvenile animals. The functional ontogeny of rOct/hOCT was profiled in suspended rat (2–57 days old) and human hepatocytes (pediatric liver tissue donors: age 2–12 months) by determining uptake clearance of 4-[4-(dimethylamino)styryl]-N-methylpyridinium iodide (ASP+) as a known rOct/hOCT probe substrate. mRNA expression was determined in rat liver tissue corresponding to rat ages used in the functional studies, while hOCT1 mRNA expressions were determined in the same hepatocyte batches as those used for uptake studies. Maturation of rOct/hOCT activity and expression were evaluated by comparing values obtained at the various ages to the adult values. Relative to adult values (at 8 weeks), ASP+ uptake clearance in suspended rat hepatocytes aged 0, 1, 2, 3, 4, 5, and 6 weeks reached 26%, 29%, 33%, 37%, 72%, 63%, and 71%, respectively. Hepatic Oct1 mRNA expression was consistent with Oct activity (correlation coefficient of 0.92). In human hepatocytes, OCT1 activity was age dependent and also correlated with mRNA levels (correlation coefficient of 0.88). These data show that Oct1/OCT1 activities and expression mature gradually in rat/human liver, thereby mirroring the expression pattern of organic anion transporting polypeptide in rat. These high-resolution transporter ontogeny profiles will allow for more accurate prediction of the pharmacokinetics of OCT1/Oct1 substrates in pediatric populations and juvenile animals.

SIGNIFICANCE STATEMENT

Organic cation transporter-1 (OCT1) represents a major drug uptake transporter in human liver. This study provides high-resolution data regarding the age-dependent function of OCT1 in the liver, based on in vitro experiments with rat and human hepatocytes obtained from donors between birth and adulthood. These ontogeny profiles will inform improved age-specific physiologically based pharmacokinetic models for OCT1 drug substrates in neonates, infants, children, and adults.




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Exogenous Pregnane X Receptor Does Not Undergo Liquid-Liquid Phase Separation in Nucleus under Cell-Based In Vitro Conditions [Special Section on New and Emerging Areas and Technologies in Drug Metabolism and Disposition, Part II]

Pregnane X receptor (PXR) belongs to the nuclear receptor superfamily that plays a crucial role in hepatic physiologic and pathologic conditions. Phase separation is a process in which biomacromolecules aggregate and condense into a dense phase as liquid condensates and coexist with a dilute phase, contributing to various cellular and biologic functions. Until now, whether PXR could undergo phase separation remains unclear. This study aimed to investigate whether PXR undergoes phase separation. Analysis of the intrinsically disordered regions (IDRs) using algorithm tools indicated a low propensity of PXR to undergo phase separation. Experimental assays such as hyperosmotic stress, agonist treatment, and optoDroplets assay demonstrated the absence of phase separation for PXR. OptoDroplets assay revealed the inability of the fusion protein of Cry2 with PXR to form condensates upon blue light stimulation. Moreover, phase separation of PXR did not occur even though the mRNA and protein expression levels of PXR target, cytochrome P450 3A4, changed after sorbitol treatment. In conclusion, for the first time, these findings suggested that exogenous PXR does not undergo phase separation following activation or under hyperosmotic stress in nucleus of cells.

SIGNIFICANCE STATEMENT

PXR plays a critical role in hepatic physiological and pathological processes. The present study clearly demonstrated that exogenous PXR does not undergo phase separation after activation by agonist or under hyperosmotic stress in nucleus. These findings may help understand PXR biology.




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Establishment of the First Institution-Based Poison Information Center in Nepal Through a Multilateral International Partnership

ABSTRACTToxicological emergencies present a significant health challenge in Nepal. Despite the high burden, the country has inadequate formal toxicology training, medical toxicology expertise, and adequate poison control infrastructure. In recognition of this need, the Nepal Poison Information Center (PIC) was established as a collaborative effort involving local and international partners. Through a comprehensive partnership framework, the Nepal PIC provides 24 hours a day, 7 days a week expert guidance to health care workers, conducts educational webinars, and engages in research. Initial data from the pilot phase indicate successful consultation delivery. Challenges include bureaucratic hurdles and the need for sustainable funding. Despite these challenges, the Nepal PIC demonstrates early feasibility and potential for expansion into a comprehensive toxicology center, contributing to the advancement of clinical toxicology in Nepal. Long-term sustainability relies on governmental support and continued advocacy efforts.




epa

Glatiramer Acetate for the Treatment of Multiple Sclerosis: From First-Generation Therapy to Elucidation of Immunomodulation and Repair [Review Article]

Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system (CNS), with a putative autoimmune origin and complex pathogenesis. Modification of the natural history of MS by reducing relapses and slowing disability accumulation was first attained in the 1990 s with the development of the first-generation disease-modifying therapies. Glatiramer acetate (GA), a copolymer of L-alanine, L-lysine, L-glutamic acid, and L-tyrosine, was discovered due to its ability to suppress the animal model of MS, experimental autoimmune encephalomyelitis. Extensive clinical trials and long-term assessments established the efficacy and the safety of GA. Furthermore, studies of the therapeutic processes induced by GA in animal models and in MS patients indicate that GA affects various levels of the innate and the adaptive immune response, generating deviation from proinflammatory to anti-inflammatory pathways. This includes competition for binding to antigen presenting cells; driving dendritic cells, monocytes, and B-cells toward anti-inflammatory responses; and stimulating T-helper 2 and T-regulatory cells. The immune cells stimulated by GA reach the CNS and secrete in situ anti-inflammatory cytokines alleviating the pathological processes. Furthermore, cumulative findings reveal that in addition to its immunomodulatory effect, GA promotes neuroprotective repair processes such as neurotrophic factors secretion, remyelination, and neurogenesis. This review aims to provide an overview of MS pathology diagnosis and treatment as well as the diverse mechanism of action of GA.

Significance Statement

Understanding the complex MS immune pathogenesis provided multiple targets for therapeutic intervention, resulting in a plethora of agents, with various mechanisms of action, efficacy, and safety profiles. However, promoting repair beyond the body’s limited spontaneous extent is still a major challenge. GA, one of the first approved disease-modifying therapies, induces diverse immunomodulatory effects. Furthermore, GA treatment results in elevated neurotrophic factors secretion, remyelination and neurogenesis, supporting the notion that immunomodulatory treatment can support in situ a growth-promoting and repair environment.




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The 75-Year Anniversary of the Department of Physiology and Pharmacology at Karolinska Institutet--Examples of Recent Accomplishments and Future Perspectives [75th Anniversary Celebration Collection Special Section-Perspective]

Karolinska Institutet is a medical university encompassing 21 departments distributed across three departmental or campus groups. Pharmacological research has a long and successful tradition at the institute with a multitude of seminal findings in the areas of neuronal control of vasodilatation, cardiovascular pharmacology, neuropsychopharmacology, receptor pharmacology, and pharmacogenomics that resulted in, among many other recognitions, two Nobel prizes in Physiology and Medicine, one in 1970 to Ulf von Euler for his discovery of the processes involved in storage, release, and inactivation of neurotransmitters and the other in 1982 to Sune Bergström and Bengt Samuelsson for their work on prostaglandins and the discovery of leukotrienes. Pharmacology at Karolinska Institutet has over the last decade been ranked globally among the top 10 according to the QS World University Ranking. With the Department of Physiology and Pharmacology now celebrating its 75-year anniversary, we wanted to take this as an opportunity to showcase recent research achievements and how they paved the way for current activities at the department. We emphasize examples from preclinical and clinical research where the dpartment's integrative environment and robust infrastructure have successfully facilitated the translation of findings into clinical applications and patient benefits. The close collaboration between preclinical scientists and clinical researchers across various disciplines, along with a strong network of partnerships within the department and beyond, positions us to continue leading world-class pharmacological research at the Department of Physiology and Pharmacology for decades to come.

Significance Statement

Pharmacological research at Karolinska Institutet has a long and successful history. Given the 75-year anniversary of the Department of Physiology and Pharmacology, this perspective provides an overview of recent departmental achievements and future trajectories. For these developments, interdisciplinary and intersectoral collaborations and a clear focus on result translation are key elements to continue its legacy of world-leading pharmacological research.




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Seventy-Five Years of Interactions: The Department of Physiology and Pharmacology at Karolinska Institutet and Pharmacological Reviews [75th Anniversary Celebration Collection Special Section-Editorial]




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Novel pathogenic PDX1 gene variant in a Korean family with maturity-onset diabetes of the young [VARIANT DISCREPANCY RESOLUTION]

The diagnosis of maturity-onset diabetes of the young (MODY), a monogenic form of diabetes mellitus caused by a mutation in a single gene, is often uncertain until genetic testing is performed. We report a 13-yr-old Korean boy who was initially diagnosed with type 2 diabetes (T2DM). MODY was suspected because of his nonobese body habitus and family history of multiple affected members. Targeted panel sequencing of all MODY-related genes was performed using the NextSeq 550Dx platform (Illumina). Sanger sequencing was performed using blood samples from the parents, siblings, and other relatives. A frameshift variant in the 3' region of the last exon of PDX1 was detected in the patient and his family members with diabetes. PP1_Moderate criterion was applied and this variant was confirmed to be the genetic cause of diabetes in the family and classified as likely pathogenic. The study highlights the importance of genetic testing for nonobese, early-onset diabetic patients with multiple affected family members. Increased awareness and aggressive genetic testing for MODY are needed.




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Reclassification of the HPGD p.Ala13Glu variant causing primary hypertrophic osteoarthropathy [VARIANT DISCREPANCY RESOLUTION]

Here, we highlight the case of a 31-yr-old man who had clinical features of primary hypertrophic osteoarthropathy (PHOAR) and harbored a homozygous variant (c.38C > A, p.Ala13Glu) in the HPGD gene, as indicated by whole-exome sequencing (WES). This variant has been previously classified by our laboratory as a variant of uncertain significance (VUS). However, another patient with the same phenotype and the same homozygous variant in HPGD was subsequently reported. In reassessing the variant, the absence of this variant in the gnomAD population database, supporting computational predictions, observation in homozygosity in two probands, and specificity of the phenotype for HPGD, all provide sufficient evidence to reclassify the HPGD c.38C > A, p.Ala13Glu variant as likely pathogenic.




epa

Correction to "Opioid-related emergency department visits and deaths after a harm-reduction intervention: a retrospective observational cohort time series analysis"




epa

ESA prepares Hera mission to investigate aftermath of NASA DART impact

The European Space Agency's Hera spacecraft must be thoroughly tested before being sent to investigate the aftermath of the collision of NASA's DART probe with Dimorphos




epa

What preparing for an asteroid strike teaches us about climate change

Averting an asteroid strike will need many of the same skills we must hone to tackle climate change and future pandemics




epa

Slick trick separates oil and water with 99.9 per cent purity

Oil and water can be separated efficiently by pumping the mixture through thin channels between two semipermeable membranes