fec Confirmed Case of Coronavirus Reinfection Reported By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Confirmed Case of Coronavirus Reinfection ReportedCategory: Health NewsCreated: 8/25/2020 12:00:00 AMLast Editorial Review: 8/25/2020 12:00:00 AM Full Article
fec Microbes in Lungs Could Affect COVID-19 Outcomes By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Microbes in Lungs Could Affect COVID-19 OutcomesCategory: Health NewsCreated: 8/24/2020 12:00:00 AMLast Editorial Review: 8/25/2020 12:00:00 AM Full Article
fec You're Vaccinated But Get a Breakthrough Infection: What Next? By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: You're Vaccinated But Get a Breakthrough Infection: What Next?Category: Health NewsCreated: 8/26/2021 12:00:00 AMLast Editorial Review: 8/26/2021 12:00:00 AM Full Article
fec When Is a Person With COVID-19 Most Infectious? By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: When Is a Person With COVID-19 Most Infectious?Category: Health NewsCreated: 8/27/2021 12:00:00 AMLast Editorial Review: 8/27/2021 12:00:00 AM Full Article
fec A Third of Americans Were Infected With COVID-19 in 2020: Study By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: A Third of Americans Were Infected With COVID-19 in 2020: StudyCategory: Health NewsCreated: 8/26/2021 12:00:00 AMLast Editorial Review: 8/27/2021 12:00:00 AM Full Article
fec Neighborhood May Affect a Couple's Odds of Conceiving By www.medicinenet.com Published On :: Wed, 3 Aug 2022 00:00:00 PDT Title: Neighborhood May Affect a Couple's Odds of ConceivingCategory: Health NewsCreated: 8/3/2022 12:00:00 AMLast Editorial Review: 8/3/2022 12:00:00 AM Full Article
fec AHA News: Obstacles Didn't Stop This Heart Defect Survivor From Competing on 'American Ninja Warrior By www.medicinenet.com Published On :: Mon, 15 Aug 2022 00:00:00 PDT Title: AHA News: Obstacles Didn't Stop This Heart Defect Survivor From Competing on 'American Ninja WarriorCategory: Health NewsCreated: 8/12/2022 12:00:00 AMLast Editorial Review: 8/15/2022 12:00:00 AM Full Article
fec Fecal Transplant Treatments Could Transmit Monkeypox, FDA Warns By www.medicinenet.com Published On :: Thu, 25 Aug 2022 00:00:00 PDT Title: Fecal Transplant Treatments Could Transmit Monkeypox, FDA WarnsCategory: Health NewsCreated: 8/24/2022 12:00:00 AMLast Editorial Review: 8/25/2022 12:00:00 AM Full Article
fec COVID Breakthrough Infections More Likely in People Living With HIV By www.medicinenet.com Published On :: Thu, 9 Jun 2022 00:00:00 PDT Title: COVID Breakthrough Infections More Likely in People Living With HIVCategory: Health NewsCreated: 6/8/2022 12:00:00 AMLast Editorial Review: 6/9/2022 12:00:00 AM Full Article
fec Shorter Menstrual Cycles May Affect Timing of Menopause By www.medicinenet.com Published On :: Thu, 25 Aug 2022 00:00:00 PDT Title: Shorter Menstrual Cycles May Affect Timing of MenopauseCategory: Health NewsCreated: 8/25/2022 12:00:00 AMLast Editorial Review: 8/25/2022 12:00:00 AM Full Article
fec Yeast infections vs. STDs in Men and Women By www.medicinenet.com Published On :: Fri, 29 Jul 2022 00:00:00 PDT Title: Yeast infections vs. STDs in Men and WomenCategory: Diseases and ConditionsCreated: 1/8/2020 12:00:00 AMLast Editorial Review: 7/29/2022 12:00:00 AM Full Article
fec Vaccines Have Slashed Rates of HPV Infection in Young American Women By www.medicinenet.com Published On :: Tue, 23 Aug 2022 00:00:00 PDT Title: Vaccines Have Slashed Rates of HPV Infection in Young American WomenCategory: Health NewsCreated: 8/22/2022 12:00:00 AMLast Editorial Review: 8/23/2022 12:00:00 AM Full Article
fec Vaginal or C-Section, Method of Childbirth Won't Affect a Couple's Sex Life Later By www.medicinenet.com Published On :: Thu, 25 Aug 2022 00:00:00 PDT Title: Vaginal or C-Section, Method of Childbirth Won't Affect a Couple's Sex Life LaterCategory: Health NewsCreated: 8/24/2022 12:00:00 AMLast Editorial Review: 8/25/2022 12:00:00 AM Full Article
fec AHA News: How You Feel About Aging Could Affect Health. Here's How to Keep the Right Attitude. By www.medicinenet.com Published On :: Fri, 19 Aug 2022 00:00:00 PDT Title: AHA News: How You Feel About Aging Could Affect Health. Here's How to Keep the Right Attitude.Category: Health NewsCreated: 8/19/2022 12:00:00 AMLast Editorial Review: 8/19/2022 12:00:00 AM Full Article
fec Hepatitis C Infection Can Kill, But Less Than a Third of Patients Get Treatment By www.medicinenet.com Published On :: Wed, 10 Aug 2022 00:00:00 PDT Title: Hepatitis C Infection Can Kill, But Less Than a Third of Patients Get TreatmentCategory: Health NewsCreated: 8/10/2022 12:00:00 AMLast Editorial Review: 8/10/2022 12:00:00 AM Full Article
fec What Are 4 Symptoms of Seasonal Affective Disorder? By www.medicinenet.com Published On :: Wed, 6 Jul 2022 00:00:00 PDT Title: What Are 4 Symptoms of Seasonal Affective Disorder?Category: Diseases and ConditionsCreated: 12/10/2021 12:00:00 AMLast Editorial Review: 7/6/2022 12:00:00 AM Full Article
fec The effect of graded exercise therapy on fatigue in people with serious respiratory illness: a systematic review By err.ersjournals.com Published On :: 2024-10-09T00:15:15-07:00 Background In adults with serious respiratory illness, fatigue is prevalent and under-recognised, with few treatment options. The aim of this review was to assess the impact of graded exercise therapy (GET) on fatigue in adults with serious respiratory illness. Methods Electronic databases were searched to identify randomised controlled trials (RCTs) testing GET (involving incremental increases in exercise from an established baseline) in adults with serious respiratory illness. The primary outcome was fatigue and secondary outcomes were health-related quality of life (HRQoL) and adverse events. Two authors independently screened for inclusion, evaluated risk of bias and extracted data. Results 76 RCTs were included with 3309 participants, most with a diagnosis of COPD or asthma. Reductions in fatigue measured by the Chronic Respiratory Disease Questionnaire fatigue domain score were demonstrated following GET consisting of aerobic with/without resistance training (mean difference (MD) 0.53 points, 95% CI 0.41–0.65, 11 RCTs, 624 participants) and GET using resistance training alone (MD 0.58 points, 95% CI 0.21–0.96, two RCTs, 82 participants) compared with usual care. Although the mean effect exceeded the minimal important difference, the lower end of the confidence intervals did not always exceed this threshold so the clinical significance could not be confirmed. GET consistently improved HRQoL in people with a range of chronic respiratory diseases on multiple HRQoL measures. No serious adverse events related to GET were reported. Conclusion GET may improve fatigue alongside consistent improvements in HRQoL in people with serious respiratory illness. These findings support the use of GET in the care of people with serious respiratory illness. Full Article
fec Mutational scanning of CRX classifies clinical variants and reveals biochemical properties of the transcriptional effector domain [RESEARCH] By genome.cshlp.org Published On :: 2024-10-29T06:46:07-07:00 The transcription factor (TF) cone-rod homeobox (CRX) is essential for the differentiation and maintenance of photoreceptor cell identity. Several human CRX variants cause degenerative retinopathies, but most are variants of uncertain significance. We performed a deep mutational scan (DMS) of nearly all possible single amino acid substitutions in CRX using a cell-based transcriptional reporter assay, curating a high-confidence list of nearly 2000 variants with altered transcriptional activity. In the structured homeodomain, activity scores closely aligned to a predicted structure and demonstrated position-specific constraints on amino acid substitution. In contrast, the intrinsically disordered transcriptional effector domain displayed a qualitatively different pattern of substitution effects, following compositional constraints without specific residue position requirements in the peptide chain. These compositional constraints were consistent with the acidic exposure model of transcriptional activation. We evaluated the performance of the DMS assay as a clinical variant classification tool using gold-standard classified human variants from ClinVar, identifying pathogenic variants with high specificity and moderate sensitivity. That this performance could be achieved using a synthetic reporter assay in a foreign cell type, even for a highly cell type-specific TF like CRX, suggests that this approach shows promise for DMS of other TFs that function in cell types that are not easily accessible. Together, the results of the CRX DMS identify molecular features of the CRX effector domain and demonstrate utility for integration into the clinical variant classification pipeline. Full Article
fec Simulation in Mechanical Ventilation Training: Integrating Best Practices for Effective Education By rc.rcjournal.com Published On :: 2024-10-25T05:44:13-07:00 Full Article
fec Downstream Effects of Market Changes on Inhalers: Impacts on Individuals With Chronic Lung Disease By rc.rcjournal.com Published On :: 2024-10-25T05:44:13-07:00 COPD and asthma are two of the most common chronic lung diseases, affecting over 545 million people globally and 34 million in the United States. Annual health care costs related to chronic lung disease are estimated at €380 billion in the European Union, and $24–$50 billion in the United States averaging to $4,000 in out-of-pocket costs per person in the U.S. A full-text literature search was conducted for English publications between January 1, 2005–March 18, 2024. It returned over 5,000 publications that were further narrowed using key search words, resulting in 172 peer-reviewed articles. Using their experience and subject expertise, the authors further narrowed the peer-reviewed articles to 55 that were in their opinion relevant. Also, 38 recently published industry reports and news articles specific to downstream effects of inhaler market changes and the future impact were included. The literature suggests that individuals with chronic lung disease face increased challenges with access to inhaled medication due to rising medication costs, discontinuation of branded medications, introduction of generic medications not covered by insurance, exclusionary preferred drug list tactics that force health care providers into non-medical switching of medication or devices, and ongoing medication shortages. Providers experience ongoing hurdles in prescribing appropriate inhaled medications for individuals with chronic lung disease, including increased time and costs spent on administrative tasks due to inhaler denials, a loss of patient trust, and limits on their ability to prescribe appropriate inhaled medication for individuals with chronic lung disease. Full Article
fec Effects of Lung Injury and Abdominal Insufflation on Respiratory Mechanics and Lung Volume During Time-Controlled Adaptive Ventilation By rc.rcjournal.com Published On :: 2024-10-25T05:44:12-07:00 BACKGROUD:Lung volume measurements are important for monitoring functional aeration and recruitment and may help guide adjustments in ventilator settings. The expiratory phase of airway pressure release ventilation (APRV) may provide physiologic information about lung volume based on the expiratory flow-time slope, angle, and time to approach a no-flow state (expiratory time [TE]). We hypothesized that expiratory flow would correlate with estimated lung volume (ELV) as measured using a modified nitrogen washout/washin technique in a large-animal lung injury model.METHODS:Eight pigs (35.2 ± 1.0 kg) were mechanically ventilated using an Engström Carescape R860 on the APRV mode. All settings were held constant except the expiratory duration, which was adjusted based on the expiratory flow curve. Abdominal pressure was increased to 15 mm Hg in normal and injured lungs to replicate a combination of pulmonary and extrapulmonary lung injury. ELV was estimated using the Carescape FRC INview tool. The expiratory flow-time slope and TE were measured from the expiratory flow profile.RESULTS:Lung elastance increased with induced lung injury from 29.3 ± 7.3 cm H2O/L to 39.9 ± 15.1cm H2O/L, and chest wall elastance increased with increasing intra-abdominal pressures (IAPs) from 15.3 ± 4.1 cm H2O/L to 25.7 ± 10.0 cm H2O/L in the normal lung and 15.8 ± 6.0 cm H2O/L to 33.0 ± 6.2 cm H2O/L in the injured lung (P = .39). ELV decreased from 1.90 ± 0.83 L in the injured lung to 0.67 ± 0.10 L by increasing IAP to 15 mm Hg. This had a significant correlation with a TE decrease from 2.3 ± 0.8 s to 1.0 ± 0.1 s in the injured group with increasing insufflation pressures (ρ = 0.95) and with the expiratory flow-time slope, which increased from 0.29 ± 0.06 L/s2 to 0.63 ± 0.05 L/s2 (ρ = 0.78).CONCLUSIONS:Changes in ELV over time, and the TE and flow-time slope, could be used to demonstrate evolving lung injury during APRV. Using the slope to infer changes in functional lung volume represents a unique, reproducible, real-time, bedside technique that does not interrupt ventilation and may be used for clinical interpretation. Full Article
fec Effect of Fasting Prior to Extubation on Prevalence of Empty Stomach in Enterally Fed and Mechanically Ventilated Patients By rc.rcjournal.com Published On :: 2024-10-25T05:44:12-07:00 BACKGROUND:Practice on fasting prior to extubation in critically ill patients is variable. Efficacy of fasting in reducing gastric volume has not been well established. The primary objective of this study was to assess the effect of 4 h of fasting on prevalence of empty stomach using gastric ultrasonography in critically ill subjects who are fasted for extubation. The secondary objectives were to evaluate the change in gastric volumes during 4 h of fasting and to determine factors associated with empty stomach after fasting.METHODS:This was a single-center, prospective, observational study on adult ICU subjects who were enterally fed for at least 6 h continuously and mechanically ventilated. Gastric ultrasound was performed immediately prior to commencement of fasting, after 4 h of fasting, and after nasogastric (NG) aspiration after 4 h of fasting. An empty stomach was defined as a gastric volume ≤ 1.5 mL/kg.RESULTS:Forty subjects were recruited, and 38 (95%) had images suitable for analysis. The prevalence of empty stomach increased after 4 h of fasting (25 [65.8%] vs 31 [81.6%], P = .041) and after 4 h of fasting with NG aspiration (25 [65.8%] vs 34 [89.5%], P = .008). There was a significant difference in median (interquartile range) gastric volume per body weight between before fasting and 4 h after fasting (1.0 [0.5–1.8] mL/kg vs 0.4 [0.2–1.0] mL/kg, P < .001). No patient factors were associated with higher prevalence of empty stomach after 4 h of fasting.CONCLUSIONS:Most mechanically ventilated subjects had empty stomachs prior to fasting for extubation. Fasting for 4 h further increased the prevalence of empty stomach at extubation to > 80%. Full Article
fec Effects of Ultrasonic Use on Hearing Loss in Dental Hygienists: A matched pairs design study By jdh.adha.org Published On :: 2024-10-15T09:18:41-07:00 Purpose Dental professionals are exposed to hazardous noise levels on a daily basis in clinical practice. The purpose of this study was to compare the hearing status of dental hygienists who utilize ultrasonic scalers in the workplace compared to age-matched control participants (non-dental hygienists) who were not exposed to ultrasonic noise.Methods A convenience sample of nineteen dental hygienists (experimental) and nineteen non-dental hygienists (control) was recruited for this study. A matched pairs design was utilized; participants in each group were matched based on age and gender to eliminate confounding variables. The testing procedure consisted of an audiologist performing a series of auditory tests including otoacoustic emissions test, pure-tone audiometry, and tympanometry on the experimental and control groups.Results In the right ear, there were notable differences from 1000 Hz – 10,000 Hz and in the left ear from 6000 Hz – 10,000 Hz, with higher hearing thresholds in the experimental group of dental hygienists. While 56% of the univariate tests conducted on how many days were worked per week showed statistical significance, the regression line slope indicated those that worked more days had better hearing statuses. The variables for years in practice for dental hygienists, how many of those years were full-time employment, and how many years the dental hygienist had used an ultrasonic scaling device, also had many significant univariate tests for the experimental group only. These variables were more likely to serve as proxies representing true noise exposure. The paired t-test between the groups demonstrated statistically significant differences between the experimental and control group at 9000 Hz in both ears.Conclusion While results from this study demonstrated various qualitative differences in hearing status of the control group (non-dental hygienists) and experimental group (dental hygienists), age was found to be the most critical variable. Furthermore, this data demonstrated differences in hearing status based on various frequencies between dental hygienists and age-matched controls that should be further explored with a larger population. Full Article
fec The treatment of latent tuberculosis infection in migrants in primary care versus secondary care By erj.ersjournals.com Published On :: 2024-11-07T00:35:56-08:00 Extract With a disproportionate burden of tuberculosis (TB) amongst migrants in Europe [1], Burman et al. [2] have highlighted the pressing need for alternative approaches to make TB infection (TBI) screening comprehensive and accessible. Across high-income Organisation for Economic Co-operation and development countries, a median of 52% of TB cases occur in foreign-born individuals, who are at their highest risk of developing TB disease within the first 5 years of migration [3]. Molecular epidemiological studies indicate that the majority of these cases occur as a result of TBI reactivation, often acquired overseas [4]. Within the UK, overseas-born migrants have a 14-fold higher TB incidence than UK-born individuals [5]. The World Health Organization therefore recommends that migrants from countries with a high TB burden may be prioritised for TBI screening [6, 7]. Full Article
fec Decoding genetic susceptibility to Pseudomonas aeruginosa infections in cystic fibrosis By erj.ersjournals.com Published On :: 2024-11-07T00:35:56-08:00 Extract In cystic fibrosis (CF), Pseudomonas aeruginosa acquisition represents a turning point in disease progression. The presence of chronic P. aeruginosa infection is associated with worsening lung function and increased risk of earlier death, whereas treatment substantially improves lung function and survival [1, 2]. Efforts to diagnose and eradicate early P. aeruginosa provide lasting benefits for children with CF [3, 4]. However, the timing of infection varies considerably between individuals with CF, treatment centres [5, 6], and different birth cohorts of people with the disease [7, 8]. Full Article
fec Genome-wide association study of susceptibility to Pseudomonas aeruginosa infection in cystic fibrosis By erj.ersjournals.com Published On :: 2024-11-07T00:35:55-08:00 Background Pseudomonas aeruginosa is a common pathogen that contributes to progressive lung disease in cystic fibrosis (CF). Genetic factors other than CF-causing CFTR (CF transmembrane conductance regulator) variations contribute ~85% of the variation in chronic P. aeruginosa infection age in CF according to twin studies, but the susceptibility loci remain unknown. Our objective is to advance understanding of the genetic basis of host susceptibility to P. aeruginosa infection. Materials and methods We conducted a genome-wide association study of chronic P. aeruginosa infection age in 1037 Canadians with CF. We subsequently assessed the genetic correlation between chronic P. aeruginosa infection age and lung function through polygenic risk score (PRS) analysis and inferred their causal relationship through bidirectional Mendelian randomisation analysis. Results Two novel genome-wide significant loci with lead single nucleotide polymorphisms (SNPs) rs62369766 (chr5p12; p=1.98x10–8) and rs927553 (chr13q12.12; p=1.91x10–8) were associated with chronic P. aeruginosa infection age. The rs62369766 locus was validated using an independent French cohort (n=501). Furthermore, the PRS constructed from CF lung function-associated SNPs was significantly associated with chronic P. aeruginosa infection age (p=0.002). Finally, our analysis presented evidence for a causal effect of lung function on chronic P. aeruginosa infection age (β=0.782 years, p=4.24x10–4). In the reverse direction, we observed a moderate effect (β=0.002, p=0.012). Conclusions We identified two novel loci that are associated with chronic P. aeruginosa infection age in individuals with CF. Additionally, we provided evidence of common genetic contributors and a potential causal relationship between P. aeruginosa infection susceptibility and lung function in CF. Therapeutics targeting these genetic factors may delay the onset of chronic infections, which account for significant remaining morbidity in CF. Full Article
fec Treatment of latent tuberculosis infection in migrants in primary care versus secondary care By erj.ersjournals.com Published On :: 2024-11-07T00:35:55-08:00 Background Control of latent tuberculosis infection (LTBI) is a priority in the World Health Organization strategy to eliminate TB. Many high-income, low TB incidence countries have prioritised LTBI screening and treatment in recent migrants. We tested whether a novel model of care, based entirely within primary care, was effective and safe compared to secondary care. Methods This was a pragmatic cluster-randomised, parallel group, superiority trial (ClinicalTrials.gov: NCT03069807) conducted in 34 general practices in London, UK, comparing LTBI treatment in recent migrants in primary care to secondary care. The primary outcome was treatment completion, defined as taking ≥90% of antibiotic doses. Secondary outcomes included treatment acceptance, adherence, adverse effects, patient satisfaction, TB incidence and a cost-effectiveness analysis. Analyses were performed on an intention-to-treat basis. Results Between September 2016 and May 2019, 362 recent migrants with LTBI were offered treatment and 276 accepted. Treatment completion was similar in primary and secondary care (82.6% versus 86.0%; adjusted OR (aOR) 0.64, 95% CI 0.31–1.29). There was no difference in drug-induced liver injury between primary and secondary care (0.7% versus 2.3%; aOR 0.29, 95% CI 0.03–2.84). Treatment acceptance was lower in primary care (65.2% (146/224) versus 94.2% (130/138); aOR 0.10, 95% CI 0.03–0.30). The estimated cost per patient completing treatment was lower in primary care, with an incremental saving of GBP 315.27 (95% CI 313.47–317.07). Conclusions The treatment of LTBI in recent migrants within primary care does not result in higher rates of treatment completion but is safe and costs less when compared to secondary care. Full Article
fec Effects of Compound Probiotics on Pharmacokinetics of Cytochrome 450 Probe Drugs in Rats [Articles] By dmd.aspetjournals.org Published On :: 2024-10-16T09:02:03-07:00 Compound probiotics have been widely used and commonly coadministered with other drugs for treating various chronic illnesses, yet their effects on drug pharmacokinetics remain underexplored. This study elucidated the impact of VSL#3 on the metabolism of probe drugs for cytochrome P450 enzymes (P450s), specifically omeprazole, tolbutamide, midazolam, metoprolol, phenacetin, and chlorzoxazone. Male Wistar rats were administered drinking water containing VSL#3 or not for 14 days and then intragastrically administered a P450 probe cocktail; this was done to investigate the host P450’s metabolic phenotype. Stool, liver/jejunum, and serum samples were collected for 16S ribosomal RNA sequencing, RNA sequencing, and bile acid profiling. The results indicated significant differences in both α and β diversity of intestinal microbial composition between the probiotic and vehicle groups in rats. In the probiotic group, the bioavailability of omeprazole increased by 269.9%, whereas those of tolbutamide and chlorpropamide decreased by 28.1% and 27.4%, respectively. The liver and jejunum exhibited 1417 and 4004 differentially expressed genes, respectively, between the two groups. In the probiotic group, most of P450 genes were upregulated in the liver but downregulated in the jejunum. The expression of genes encoding metabolic enzymes and drug transporters also changed. The serum-conjugated bile acids in the probiotic group were significantly reduced. Shorter duodenal villi and longer ileal villi were found in the probiotic group. In summary, VSL#3 administration altered the gut microbiota, host drug–processing gene expression, and intestinal structure in rats, which could be reasons for pharmacokinetic changes. SIGNIFICANCE STATEMENT This study focused on the effects of the probiotic VSL#3 on the pharmacokinetic profile of cytochrome P450 probe drugs and the expression of host drug metabolism genes. Compared with previous studies, the present study provides a comprehensive explanation for the host drug metabolism profile modified by probiotics, combined here with the bile acid profile and histopathological analysis. Full Article
fec Quantitatively Predicting Effects of Exercise on Pharmacokinetics of Drugs Using a Physiologically Based Pharmacokinetic Model [Articles] By dmd.aspetjournals.org Published On :: 2024-10-16T09:02:03-07:00 Exercise significantly alters human physiological functions, such as increasing cardiac output and muscle blood flow and decreasing glomerular filtration rate (GFR) and liver blood flow, thereby altering the absorption, distribution, metabolism, and excretion of drugs. In this study, we aimed to establish a database of human physiological parameters during exercise and to construct equations for the relationship between changes in each physiological parameter and exercise intensity, including cardiac output, organ blood flow (e.g., muscle blood flow and kidney blood flow), oxygen uptake, plasma pH and GFR, etc. The polynomial equation P = aiHRi was used for illustrating the relationship between the physiological parameters (P) and heart rate (HR), which served as an index of exercise intensity. The pharmacokinetics of midazolam, quinidine, digoxin, and lidocaine during exercise were predicted by a whole-body physiologically based pharmacokinetic (WB-PBPK) model and the developed database of physiological parameters following administration to 100 virtual subjects. The WB-PBPK model simulation results showed that most of the observed plasma drug concentrations fell within the 5th–95th percentiles of the simulations, and the estimated peak concentrations (Cmax) and area under the curve (AUC) of drugs were also within 0.5–2.0 folds of observations. Sensitivity analysis showed that exercise intensity, exercise duration, medication time, and alterations in physiological parameters significantly affected drug pharmacokinetics and the net effect depending on drug characteristics and exercise conditions. In conclusion, the pharmacokinetics of drugs during exercise could be quantitatively predicted using the developed WB-PBPK model and database of physiological parameters. SIGNIFICANCE STATEMENT This study simulated real-time changes of human physiological parameters during exercise in the WB-PBPK model and comprehensively investigated pharmacokinetic changes during exercise following oral and intravenous administration. Furthermore, the factors affecting pharmacokinetics during exercise were also revealed. Full Article
fec Capacity-Building Through Digital Approaches: Evaluating the Feasibility and Effectiveness of eLearning to Introduce Subcutaneous DMPA Self-Injection in Senegal and Uganda By ghspjournal.org Published On :: 2024-10-29T12:28:39-07:00 ABSTRACTTraining health workers is one of the biggest challenges and cost drivers when introducing a new contraceptive method or service delivery innovation. PATH developed a digital training curriculum for family planning providers who are learning to offer subcutaneous DMPA (DMPA-SC), including through self-injection, as an option among a range of contraceptive methods. The DMPA-SC eLearning course for health workers includes 10 lessons with an emphasis on informed choice counseling and training clients to self-inject. In partnership with Ministries of Health in Senegal and Uganda, the course was rolled out in select areas in 2019–2020, including during the COVID-19 pandemic when physical distancing requirements restricted in-person training. We conducted evaluations in both countries to assess the practical application of this digital training approach for contraceptive introduction. The evaluation consisted of a post-training survey, an observational assessment conducted during post-training supportive supervision, and an estimation of training costs.In both countries, a majority (88.6% in Uganda and 64.3% in Senegal) scored above 80% on a DMPA-SC knowledge test following the training. In Senegal, where there was a comparison group of providers trained in person, those providers scored similar on the post-test to eLearners. Providers in both groups and in both countries felt more prepared to administer DMPA-SC or offer self-injection to clients after receiving a supervision visit (93%–98% of eLearners felt very prepared after supervision as compared to 45%–72% prior). The evaluation results suggest that digital approaches offer a number of benefits, can be cost-effective, and are most optimal when blended with in-person training and/or supportive supervision. Full Article
fec Effects of Dual Inhibition at Dopamine Transporter and {sigma} Receptors in the Discriminative-Stimulus Effects of Cocaine in Male Rats [Behavioral Pharmacology] By jpet.aspetjournals.org Published On :: 2024-10-18T07:04:15-07:00 Previous studies demonstrated that sigma receptor (R) antagonists alone fail to alter cocaine self-administration despite blocking various other effects of cocaine. However, R antagonists when combined with dopamine transporter (DAT) inhibitors substantially decrease cocaine self-administration. To better understand the effects of this combination, the present study examined the effects of R antagonist and DAT inhibitor combinations in male rats discriminating cocaine (10 mg/kg, i.p.) from saline injections. The DAT inhibitors alone [(–)-2-β-carbomethoxy-3-β-(4-fluorophenyl)tropane 1,5-naphthalenedisulfonate monohydrate (WIN 35,428) and methylphenidate] at low (0.1-mg/kg) doses that were minimally active failed to shift the dose-effect function for discriminative-stimulus effects of cocaine to the left more than 2-fold. At 0.32 mg/kg the DAT inhibitors alone shifted the cocaine dose-effect function leftward 24- or 6.6-fold, respectively. The R antagonists (BD1008, BD1047, and BD1063) failed to fully substitute for cocaine, although BD1008 and BD1047 substituted partially. At 10 mg/kg, BD1008, BD1047, or BD1063 alone shifted the cocaine dose-effect function leftward less than 6.0-fold. In combination with 0.1 mg/kg WIN 35,428, the 10 mg/kg doses of R antagonists shifted the cocaine dose-effect function from 12.3- to 36.7-fold leftward, and with 0.32 mg/kg WIN 35,428 from 14.3- to 440-fold leftward. In combination with 0.1 mg/kg methylphenidate, those R antagonist doses shifted the cocaine dose-effect function from 5.5- to 55.0-fold leftward, and with 0.32 mg/kg methylphenidate from 10.5- to 48.1-fold leftward. The present results suggest that dual DAT/R inhibition produces agonist-like subjective effects that may promote decreases in self-administration obtained in previous studies. SIGNIFICANCE STATEMENT There is currently no approved medication for treating stimulant abuse, although dopamine uptake inhibitors in combination with sigma receptor (R) antagonists decrease cocaine self-administration in laboratory animals. The present study assessed how this combination alters the discriminative-stimulus effects of cocaine in male rats. Results suggest that concurrent dopamine uptake inhibition and R antagonism together may promote decreases in self-administration, possibly by mimicking the subjective effects extant when subjects cease continued cocaine self-administration. Full Article
fec Alternative Reinforcers Enhance the Effects of Opioid Antagonists, but Not Agonists, on Oxycodone Choice Self-Administration in Nonhuman Primates [Behavioral Pharmacology] By jpet.aspetjournals.org Published On :: 2024-10-18T07:04:15-07:00 Clinical reports suggest that the most effective strategies for managing opioid use disorder comprise a comprehensive treatment program of both pharmacological and nonpharmacological approaches. However, the conditions under which these combinations are most effective are not well characterized. This study examined whether the presence of an alternative reinforcer could alter the efficacy of Food and Drug Administration–approved opioid antagonist or agonist medications, as well as the nonopioid flumazenil, in decreasing oxycodone choice self-administration in nonhuman primates. Adult squirrel monkeys (n = 7; four females) responded under concurrent second-order fixed-ratio (FR)-3(FR5:S);TO45s schedules of reinforcement for intravenous oxycodone (0.1 mg/kg) or saline on one lever and 30% sweetened condensed milk or water on the other. Doses of naltrexone (0.00032–1.0 mg/kg), nalbuphine (0.32–10 mg/kg), buprenorphine (0.0032–0.032 mg/kg), methadone (0.32–1.0 mg/kg), or flumazenil (1–3.2 mg/kg) were administered intramuscularly prior to oxycodone self-administration sessions that occurred with either milk or water as the alternative. Naltrexone, a μ-opioid receptor antagonist, was >30-fold more potent when milk was available compared with water and abolished oxycodone intake (injections/session) while concomitantly increasing milk deliveries at the highest dose tested. Pretreatment with the low-efficacy μ-agonist nalbuphine was most effective in the presence of milk compared with water, decreasing oxycodone preference to <50% of control values. The higher efficacy μ-agonists, methadone and buprenorphine, and the benzodiazepine antagonist flumazenil did not appreciably alter the reinforcing potency of oxycodone under either condition. These results suggest that antagonist medications used in combination with alternative reinforcers may be an effective strategy to curtail opioid abuse–related behaviors. SIGNIFICANCE STATEMENT Clinical treatment programs for opioid use disorder use a combination of pharmacological and nonpharmacological approaches. However, the conditions under which these combinations are most effective have not been fully characterized. This study examined whether the effectiveness of μ-opioid medications to decrease oxycodone self-administration is altered in the presence of an alternative reinforcer. The results suggest that alternative reinforcers enhance the effects of antagonist or low-efficacy partial agonists, suggesting they may be a more effective strategy to curtail opioid use. Full Article
fec Sex Differences in the Neural and Behavioral Effects of Acute High-Dose Edible Cannabis Consumption in Rats [Special Section: Cannabinoid Signaling in Human Health and Disease] By jpet.aspetjournals.org Published On :: 2024-10-18T07:04:15-07:00 The consumption of 9-tetrahydrocannabinol (THC)- or cannabis-containing edibles has increased in recent years; however, the behavioral and neural circuit effects of such consumption remain unknown, especially in the context of ingestion of higher doses resulting in cannabis intoxication. We examined the neural and behavioral effects of acute high-dose edible cannabis consumption (AHDECC). Sprague-Dawley rats (six males, seven females) were implanted with electrodes in the prefrontal cortex (PFC), dorsal hippocampus (dHipp), cingulate cortex (Cg), and nucleus accumbens (NAc). Rats were provided access to a mixture of Nutella (6 g/kg) and THC-containing cannabis oil (20 mg/kg) for 10 minutes, during which they voluntarily consumed all of the provided Nutella and THC mixture. Cannabis tetrad and neural oscillations were examined 2, 4, 8, and 24 hours after exposure. In another cohort (16 males, 15 females), we examined the effects of AHDECC on learning and prepulse inhibition and serum and brain THC and 11-hydroxy-THC concentrations. AHDECC resulted in higher brain and serum THC and 11-hydroxy-THC levels in female rats over 24 hours. AHDECC also produced: 1) Cg, dHipp, and NAc gamma power suppression, with the suppression being greater in female rats, in a time-dependent manner; 2) hypolocomotion, hypothermia, and antinociception in a time-dependent manner; and 3) learning and prepulse inhibition impairments. Additionally, most neural activity and behavior changes appear 2 hours after ingestion, suggesting that interventions around this time might be effective in reversing/reducing the effects of AHDECC. SIGNIFICANCE STATEMENT The effects of high-dose edible cannabis on behavior and neural circuitry are poorly understood. We found that the effects of acute high-dose edible cannabis consumption (AHDECC), which include decreased gamma power, hypothermia, hypolocomotion, analgesia, and learning and information processing impairments, are time and sex dependent. Moreover, these effects begin 2 hours after AHDECC and last for at least 24 hours, suggesting that treatments should target this time window in order to be effective.: Full Article
fec Low-Efficacy Mu Opioid Agonists as Candidate Analgesics: Effects of Novel C-9 Substituted Phenylmorphans on Pain-Depressed Behavior in Mice [Behavioral Pharmacology] By jpet.aspetjournals.org Published On :: 2024-10-18T07:04:15-07:00 Low-efficacy mu opioid receptor (MOR) agonists may serve as novel candidate analgesics with improved safety relative to high-efficacy opioids. This study used a recently validated assay of pain-depressed behavior in mice to evaluate a novel series of MOR-selective C9-substituted phenylmorphan opioids with graded MOR efficacies. Intraperitoneal injection of dilute lactic acid (IP acid) served as a noxious stimulus to depress locomotor activity by mice in an activity chamber composed of two compartments connected by an obstructed door. Behavioral measures included (1) crosses between compartments (vertical activity over the obstruction) and (2) movement counts quantified as photobeam breaks summed across compartments (horizontal activity). Each drug was tested alone and as a pretreatment to IP acid. A charcoal-meal test and whole-body-plethysmography assessment of breathing in 5% CO2 were also used to assess gastrointestinal (GI) inhibition and respiratory depression, respectively. IP acid produced a concentration-dependent depression in crosses and movement that was optimally alleviated by intermediate- to low-efficacy phenylmorphans with sufficient efficacy to produce analgesia with minimal locomotor disruption. Follow-up studies with two low-efficacy phenylmorphans (JL-2-39 and DC-1-76.1) indicated that both drugs produced naltrexone-reversible antinociception with a rapid onset and a duration of ~1 h. Potency of both drugs increased when behavior was depressed by a lower IP-acid concentration, and neither drug alleviated behavioral depression by a non-pain stimulus (IP lithium chloride). Both drugs produced weaker GI inhibition and respiratory depression than fentanyl and attenuated fentanyl-induced GI inhibition and respiratory depression. Results support further consideration of selective, low-efficacy MOR agonists as candidate analgesics. SIGNIFICANCE STATEMENT This study used a novel set of mu opioid receptor (MOR)-selective opioids with graded MOR efficacies to examine the lower boundary of MOR efficacy sufficient to relieve pain-related behavioral depression in mice. Two novel low-efficacy opioids (JL-2-39, DC-1-76.1) produced effective antinociception with improved safety relative to higher- or lower-efficacy opioids, and results support further consideration of these and other low-efficacy opioids as candidate analgesics. Full Article
fec The Odyssey of HOMER: Comparative Effectiveness Research on Medication for Opioid Use Disorder During the COVID-19 Pandemic [Special Report] By www.annfammed.org Published On :: 2024-09-23T14:00:14-07:00 The usual challenges of conducting primary care research, including randomized trials, have been exacerbated, and new ones identified, during the COVID-19 pandemic. HOMER (Home versus Office for Medication Enhanced Recovery; subsequently, Comparing Home, Office, and Telehealth Induction for Medication Enhanced Recovery) is a pragmatic, comparative-effectiveness research trial that aims to answer a key question from patients and clinicians: What is the best setting in which to start treatment with buprenorphine for opioid use disorder for this patient at this time? In this article, we describe the difficult journey to find the answer. The HOMER study began as a randomized trial comparing treatment outcomes in patients starting treatment with buprenorphine via induction at home (unobserved) vs in the office (observed, synchronous). The study aimed to enroll 1,000 participants from 100 diverse primary care practices associated with the State Networks of Colorado Ambulatory Practices and Partners and the American Academy of Family Physicians National Research Network. The research team faced unexpected challenges related to the COVID-19 pandemic and dramatic changes in the opioid epidemic. These challenges required changes to the study design, protocol, recruitment intensity, and funding conversations, as well as patience. As this is a participatory research study, we sought, documented, and responded to practice and patient requests for adaptations. Changes included adding a third study arm using telehealth induction (observed via telephone or video, synchronous) and switching to a comprehensive cohort design to answer meaningful patient-centered research questions. Using a narrative approach based on the Greek myth of Homer, we describe here the challenges and adaptations that have provided the opportunity for HOMER to thrive and find the way home. These clinical trial strategies may apply to other studies faced with similar cultural and extreme circumstances. Full Article
fec Family Medicine Presence on Labor and Delivery: Effect on Safety Culture and Cesarean Delivery [Original Research] By www.annfammed.org Published On :: 2024-09-23T14:00:14-07:00 PURPOSE Currently, 40% of counties in the United States do not have an obstetrician or midwife, and in rural areas the likelihood of childbirth being attended to by a family medicine (FM) physician is increasing. We sought to characterize the effect of the FM presence on unit culture and a key perinatal quality metric in Iowa hospital intrapartum units. METHODS Using a cross-sectional design, we surveyed Iowa physicians, nurses, and midwives delivering intrapartum care at hospitals participating in a quality improvement initiative to decrease the incidence of cesarean delivery. We linked respondents with their hospital characteristics and outcomes data. The primary outcome was the association between FM physician, obstetrician (OB), or both disciplines’ presence on labor and delivery and hospital low-risk, primary cesarean delivery rate. Unit culture was compared by hospital type (FM-only, OB-only, or Both). RESULTS A total of 849 clinicians from 39 hospitals completed the survey; 13 FM-only, 11 OB-only, and 15 hospitals with both. FM-only hospitals were all rural, with <1,000 annual births. Among hospitals with <1,000 annual births, births at FM-only hospitals had an adjusted 34.3% lower risk of cesarean delivery (adjusted incident rate ratio = 0.66; 95% CI, 0.52-.0.98) compared with hospitals with both. Nurses endorsed unit norms more supportive of vaginal birth and stronger safety culture at FM-only hospitals (P <.05). CONCLUSIONS Birthing hospitals staffed exclusively by FM physicians were more likely to have lower cesarean rates and stronger nursing-rated safety culture. Both access and quality of care provide strong arguments for reinforcing the pipeline of FM physicians training in intrapartum care. Full Article
fec [Evolutionary Biology] How Does Selfing Affect the Pace and Process of Speciation? By cshperspectives.cshlp.org Published On :: 2024-11-01T06:50:52-07:00 Surprisingly little attention has been given to the impact of selfing on speciation, even though selfing reduces gene flow between populations and affects other key population genetics parameters. Here we review recent theoretical work and compile empirical data from crossing experiments and genomic and phylogenetic studies to assess the effect of mating systems on the speciation process. In accordance with theoretical predictions, we find that accumulation of hybrid incompatibilities seems to be accelerated in selfers, but there is so far limited empirical support for a predicted bias toward underdominant loci. Phylogenetic evidence is scarce and contradictory, including studies suggesting that selfing either promotes or hampers speciation rate. Further studies are therefore required, which in addition to measures of reproductive barrier strength and selfing rate should routinely include estimates of demographic history and genetic divergence as a proxy for divergence time. Full Article
fec Correction to "Validity of diagnoses of SARS-CoV-2 infection in Canadian administrative health data: a multiprovince, population-based cohort study" By www.cmajopen.ca Published On :: 2024-07-02T06:35:26-07:00 Full Article
fec Necrotizing soft-tissue infections caused by invasive group A Streptococcus [Practice] By www.cmaj.ca Published On :: 2024-11-11T21:05:15-08:00 Full Article
fec Stunning Rangers and Celtic 3D chess sets are pitch perfect for Christmas By www.heraldscotland.com Published On :: Tue, 12 Nov 2024 12:50:00 +0000 3D Scotland are an innovative, Glasgow-based company who specialise in the design and manufacture of unique chess sets. Their sets have proved extremely popular as Christmas gifts, graduation gifts, fathers’ day gifts and everything in between. Full Article
fec RPG Cast – Episode 545: “Did You Infect My Game With Harvest Moon?” By rpgamer.com Published On :: Sat, 06 Jun 2020 18:57:40 +0000 With many media events getting pushed back, the news is a little trim this week. But we still manage to pull together our basket of zany personalities for a podcast we hope brings a smile to your face. The post RPG Cast – Episode 545: “Did You Infect My Game With Harvest Moon?” appeared first on RPGamer. Full Article News Podcasts RPG Cast Atelier Totori Trials of Mana Xenoblade Chronicles
fec Mass Effect TV Series has Been Greenlit by Amazon By www.vgchartz.com Published On :: Thu, 07 Nov 2024 21:02:18 GMT A TV series based on the video game series Mass Effect is officially in development at Amazon, according to a report from Variety. F9: The Fast Saga writer Daniel Casey will write and be an executive producer on the series. Karim Zreik will also be an executive producer under his Cedar Tree Productions, which is under an overall deal at Amazon. Ari Arad and BioWare's Michael Gamble will also be executive producers. Arad previously was a producer on other video game adaptations - Borderlands and Uncharted. Developer BioWare is developing a new entry in the Mass Effect series. A life-long and avid gamer, William D'Angelo was first introduced to VGChartz in 2007. After years of supporting the site, he was brought on in 2010 as a junior analyst, working his way up to lead analyst in 2012 and taking over the hardware estimates in 2017. He has expanded his involvement in the gaming community by producing content on his own YouTube channel and Twitch channel. You can contact the author on Twitter @TrunksWD.Full Article - https://www.vgchartz.com/article/463013/mass-effect-tv-series-has-been-greenlit-by-amazon/ Full Article Analysis Charts Industry
fec Dragon Age: The Veilguard won't get expansions, reports say, as BioWare move to the next Mass Effect By www.rockpapershotgun.com Published On :: Sat, 02 Nov 2024 22:22:11 +0000 BioWare currently has no plans for Dragon Age: The Veilguard expansions, according to reports. Instead the studio will support the fantasy RPG with smaller updates and otherwise turn their full attention towards Mass Effect 5. Read more Full Article Strategy Electronic Arts RPG Dragon Age: The Veilguard Action Adventure Single Player Bioware
fec No Man's Sky has a Mass Effect Normandy again, together with new cross-save functionality By www.rockpapershotgun.com Published On :: Thu, 07 Nov 2024 16:07:58 +0000 Back in the mists of 2021, No Man's Sky revealed its very own Normandy SR1 space frigate. "The Normandy in No Man's Sky?" you cry. "Why, that's a Mass Effect vessel. Some mistake here surely?" 1) My name's not Shirley, and 2) Indeed it is a Mass Effect ship, but HelloGames struck a time-limited deal with BioWare to create a version for their own space sim. "Blast, if only I'd noticed this at the time and acquired one," you mourn. "Ah, so many years I have wasted." Be of good cheer, my friend, for No Man's Sky has a Normandy once again, just in time for the latest N7 Day of assorted Mass Effect celebrations. For the next two weeks, you'll be able to get a-hold of it by way of a revised version of 2021's Beachhead Expedition. Tray-tray, away! Read more Full Article Nintendo Switch Indie Third person 505 Games Xbox Series X/S Action Adventure Single Player Xbox One PS4 No Man's Sky PS5 Simulation Hello Games Multiplayer Competitive Multiplayer Cooperative PC Virtual Reality First person Mass Effect 5 Mac RPG
fec Brits warned as spreading condition affecting young people earning above minimum wage By www.express.co.uk Published On :: Tue, 12 Nov 2024 11:51:00 +0000 New research has revealed a growing mental phenomena sweeping the UK, which may only affect those with a certain income Full Article Personal Finance
fec How E. coli infections wreak havoc on the body, causing dangerous disease — particularly in kids By www.cbc.ca Published On :: Thu, 14 Sep 2023 04:00:00 EDT Certain strains of E. coli are capable of causing severe disease, by rapidly spreading through the human digestive system, wreaking havoc throughout the bloodstream, and eventually damaging the delicate kidneys. That's the situation right now during a large outbreak in Alberta, with hundreds of children now affected. Full Article News/Health
fec Planetary Researchers Examine Tidal Effects on Interiors of Planets and Their Moons By www.sci.news Published On :: Thu, 07 Nov 2024 23:02:22 +0000 A team of scientists from the Lunar and Planetary Laboratory at the University of Arizona, TU Delft, and Caltech has developed a new method to compute how tides affect the interiors of planets and moons in the Solar System. The post Planetary Researchers Examine Tidal Effects on Interiors of Planets and Their Moons appeared first on Sci.News: Breaking Science News. Full Article Planetary Science Space Exploration Enceladus Europa Exoplanet Io Jupiter Mercury Moon NASA Planet Saturn Solar System Tidal deformation Tidal force Tidal heating
fec Intestinal parasites may reduce covid-19 vaccine effectiveness By www.newscientist.com Published On :: Wed, 21 Aug 2024 20:00:55 +0100 Around 25 per cent of the world’s population has intestinal parasite infections – these could hinder the effectiveness of covid-19 vaccines, according to research in mice Full Article
fec Does the structure of your brain affect your risk of depression? By www.newscientist.com Published On :: Wed, 04 Sep 2024 17:00:55 +0100 A network of neurons in the brain seems to be larger in people with depression, which could change how we think about the condition's causes Full Article
fec Bird flu virus that infected a person in Missouri had a rare mutation By www.newscientist.com Published On :: Wed, 18 Sep 2024 22:01:35 +0100 Genetic analysis of a bird flu virus detected in a person in Missouri who didn’t previously have contact with animals offers more details on the case, but experts say there isn’t substantial evidence to suggest human-to-human transmission is happening Full Article