ad AHA News: Helping Fathers Connect With Their Kids, Involved Dad's Name Says It All By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: AHA News: Helping Fathers Connect With Their Kids, Involved Dad's Name Says It AllCategory: Health NewsCreated: 8/26/2020 12:00:00 AMLast Editorial Review: 8/27/2020 12:00:00 AM Full Article
ad ADHD May Help Predict Adults' Car Crash Risk By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: ADHD May Help Predict Adults' Car Crash RiskCategory: Health NewsCreated: 8/27/2020 12:00:00 AMLast Editorial Review: 8/28/2020 12:00:00 AM Full Article
ad What Is More Deadly in the U.S.: Hot Weather or Cold? By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: What Is More Deadly in the U.S.: Hot Weather or Cold?Category: Health NewsCreated: 8/27/2020 12:00:00 AMLast Editorial Review: 8/28/2020 12:00:00 AM Full Article
ad AHA News: She Had a 20% Chance to Live First From a Stroke, Then From COVID-19 By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: AHA News: She Had a 20% Chance to Live First From a Stroke, Then From COVID-19Category: Health NewsCreated: 8/27/2020 12:00:00 AMLast Editorial Review: 8/28/2020 12:00:00 AM Full Article
ad Cancer Radiation Can Safely Proceed During COVID-19 Pandemic: Study By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Cancer Radiation Can Safely Proceed During COVID-19 Pandemic: StudyCategory: Health NewsCreated: 8/27/2020 12:00:00 AMLast Editorial Review: 8/28/2020 12:00:00 AM Full Article
ad Spotting the Signs of Deadly Melanoma Skin Cancers By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Spotting the Signs of Deadly Melanoma Skin CancersCategory: Health NewsCreated: 8/22/2021 12:00:00 AMLast Editorial Review: 8/23/2021 12:00:00 AM Full Article
ad No Change in Adolescent Drug, Alcohol Use During Pandemic By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: No Change in Adolescent Drug, Alcohol Use During PandemicCategory: Health NewsCreated: 8/24/2021 12:00:00 AMLast Editorial Review: 8/24/2021 12:00:00 AM Full Article
ad Moderna Readies for Full Vaccine Approval, as Pfizer Submits Data on Booster Shot By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Moderna Readies for Full Vaccine Approval, as Pfizer Submits Data on Booster ShotCategory: Health NewsCreated: 8/26/2021 12:00:00 AMLast Editorial Review: 8/26/2021 12:00:00 AM Full Article
ad Cases of Advanced Cervical Cancer Keep Rising Among U.S. Women By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Cases of Advanced Cervical Cancer Keep Rising Among U.S. WomenCategory: Health NewsCreated: 8/19/2022 12:00:00 AMLast Editorial Review: 8/22/2022 12:00:00 AM Full Article
ad First Lady Jill Biden Leaves Isolation After Testing Negative for COVID Twice By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: First Lady Jill Biden Leaves Isolation After Testing Negative for COVID TwiceCategory: Health NewsCreated: 8/22/2022 12:00:00 AMLast Editorial Review: 8/22/2022 12:00:00 AM Full Article
ad COVID Boosters Targeted to Latest Variants Could Be Ready After Labor Day By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: COVID Boosters Targeted to Latest Variants Could Be Ready After Labor DayCategory: Health NewsCreated: 8/24/2022 12:00:00 AMLast Editorial Review: 8/24/2022 12:00:00 AM Full Article
ad First Lady Jill Biden Tests Positive for COVID Again By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: First Lady Jill Biden Tests Positive for COVID AgainCategory: Health NewsCreated: 8/24/2022 12:00:00 AMLast Editorial Review: 8/25/2022 12:00:00 AM Full Article
ad Gene Therapy Makes Inroads Against a Form of Hemophilia By www.medicinenet.com Published On :: Fri, 22 Jul 2022 00:00:00 PDT Title: Gene Therapy Makes Inroads Against a Form of HemophiliaCategory: Health NewsCreated: 7/22/2022 12:00:00 AMLast Editorial Review: 7/22/2022 12:00:00 AM Full Article
ad Gabapentin vs. Tramadol By www.medicinenet.com Published On :: Fri, 22 Jul 2022 00:00:00 PDT Title: Gabapentin vs. TramadolCategory: MedicationsCreated: 3/22/2018 12:00:00 AMLast Editorial Review: 7/22/2022 12:00:00 AM Full Article
ad What's in Your CBD Product? Labels Often Mislead By www.medicinenet.com Published On :: Tue, 26 Jul 2022 00:00:00 PDT Title: What's in Your CBD Product? Labels Often MisleadCategory: Health NewsCreated: 7/26/2022 12:00:00 AMLast Editorial Review: 7/26/2022 12:00:00 AM Full Article
ad Premature Birth Tied to Higher Risk for ADHD By www.medicinenet.com Published On :: Tue, 16 Aug 2022 00:00:00 PDT Title: Premature Birth Tied to Higher Risk for ADHDCategory: Health NewsCreated: 8/16/2022 12:00:00 AMLast Editorial Review: 8/16/2022 12:00:00 AM Full Article
ad Acupuncture Might Ease Tension Headaches By www.medicinenet.com Published On :: Thu, 23 Jun 2022 00:00:00 PDT Title: Acupuncture Might Ease Tension HeadachesCategory: Health NewsCreated: 6/23/2022 12:00:00 AMLast Editorial Review: 6/23/2022 12:00:00 AM Full Article
ad What Gets Rid of Headaches Quickly? By www.medicinenet.com Published On :: Sun, 17 Jul 2022 00:00:00 PDT Title: What Gets Rid of Headaches Quickly?Category: Diseases and ConditionsCreated: 4/12/2016 12:00:00 AMLast Editorial Review: 7/17/2022 12:00:00 AM Full Article
ad Pandemic Brought More Woes for Kids Prone to Headaches By www.medicinenet.com Published On :: Wed, 10 Aug 2022 00:00:00 PDT Title: Pandemic Brought More Woes for Kids Prone to HeadachesCategory: Health NewsCreated: 8/9/2022 12:00:00 AMLast Editorial Review: 8/10/2022 12:00:00 AM Full Article
ad What Is the Best Homemade Baby Food? By www.medicinenet.com Published On :: Tue, 23 Aug 2022 00:00:00 PDT Title: What Is the Best Homemade Baby Food?Category: Health and LivingCreated: 7/13/2021 12:00:00 AMLast Editorial Review: 8/23/2022 12:00:00 AM Full Article
ad AHA News: People With Dementia May Be Less Likely to Receive an Advanced Treatment For Stroke By www.medicinenet.com Published On :: Wed, 24 Aug 2022 00:00:00 PDT Title: AHA News: People With Dementia May Be Less Likely to Receive an Advanced Treatment For StrokeCategory: Health NewsCreated: 8/24/2022 12:00:00 AMLast Editorial Review: 8/24/2022 12:00:00 AM Full Article
ad 'News Addiction' Is Common and Can Harm Your Mental Health By www.medicinenet.com Published On :: Thu, 25 Aug 2022 00:00:00 PDT Title: 'News Addiction' Is Common and Can Harm Your Mental HealthCategory: Health NewsCreated: 8/24/2022 12:00:00 AMLast Editorial Review: 8/25/2022 12:00:00 AM Full Article
ad What Are the 5 Warning Signs of Bladder Cancer? By www.medicinenet.com Published On :: Wed, 8 Jun 2022 00:00:00 PDT Title: What Are the 5 Warning Signs of Bladder Cancer?Category: Diseases and ConditionsCreated: 4/22/2021 12:00:00 AMLast Editorial Review: 6/8/2022 12:00:00 AM Full Article
ad Your Salt Shaker May Prove Deadly, Study Finds By www.medicinenet.com Published On :: Tue, 12 Jul 2022 00:00:00 PDT Title: Your Salt Shaker May Prove Deadly, Study FindsCategory: Health NewsCreated: 7/11/2022 12:00:00 AMLast Editorial Review: 7/12/2022 12:00:00 AM Full Article
ad Kids With ADHD Have Differences in 'Neural Flexibility,' Brain Study Shows By www.medicinenet.com Published On :: Mon, 1 Aug 2022 00:00:00 PDT Title: Kids With ADHD Have Differences in 'Neural Flexibility,' Brain Study ShowsCategory: Health NewsCreated: 7/29/2022 12:00:00 AMLast Editorial Review: 8/1/2022 12:00:00 AM Full Article
ad silver sulfadiazine By www.medicinenet.com Published On :: Tue, 2 Aug 2022 00:00:00 PDT Title: silver sulfadiazineCategory: MedicationsCreated: 8/2/2022 12:00:00 AMLast Editorial Review: 8/2/2022 12:00:00 AM Full Article
ad tramadol By www.medicinenet.com Published On :: Tue, 2 Aug 2022 00:00:00 PDT Title: tramadol Category: MedicationsCreated: 12/31/1997 12:00:00 AMLast Editorial Review: 8/2/2022 12:00:00 AM Full Article
ad Tramadol vs. Hydrocodone By www.medicinenet.com Published On :: Fri, 5 Aug 2022 00:00:00 PDT Title: Tramadol vs. HydrocodoneCategory: MedicationsCreated: 4/24/2017 12:00:00 AMLast Editorial Review: 8/5/2022 12:00:00 AM Full Article
ad Looking for Reliable Hay Fever Advice? It's Probably Not on YouTube By www.medicinenet.com Published On :: Tue, 16 Aug 2022 00:00:00 PDT Title: Looking for Reliable Hay Fever Advice? It's Probably Not on YouTubeCategory: Health NewsCreated: 8/16/2022 12:00:00 AMLast Editorial Review: 8/16/2022 12:00:00 AM Full Article
ad rimantadine By www.medicinenet.com Published On :: Thu, 16 Jun 2022 00:00:00 PDT Title: rimantadineCategory: MedicationsCreated: 1/25/1999 12:00:00 AMLast Editorial Review: 6/16/2022 12:00:00 AM Full Article
ad Postpartum Depression Can Hit Both Mom & Dad, Sometimes at Same Time By www.medicinenet.com Published On :: Tue, 28 Jun 2022 00:00:00 PDT Title: Postpartum Depression Can Hit Both Mom & Dad, Sometimes at Same TimeCategory: Health NewsCreated: 6/27/2022 12:00:00 AMLast Editorial Review: 6/28/2022 12:00:00 AM Full Article
ad Treating central sleep apnoea in heart failure: is positive airway pressure and adaptive servo-ventilation in particular the gold standard? By err.ersjournals.com Published On :: 2024-10-30T01:30:15-07:00 Extract We read with great interest the review article by Randerath et al. [1] recently published in the European Respiratory Review. We would like to congratulate the authors on this clearly structured review, which emphasises the urgent need for an increasingly differentiated view of central sleep apnoea (CSA) in the context of precision medicine. Full Article
ad The deadly dance of alveolar macrophages and influenza virus By err.ersjournals.com Published On :: 2024-10-30T01:30:15-07:00 Influenza A virus (IAV) is one of the leading causes of respiratory infections. The lack of efficient anti-influenza therapeutics requires a better understanding of how IAV interacts with host cells. Alveolar macrophages are tissue-specific macrophages that play a critical role in lung innate immunity and homeostasis, yet their role during influenza infection remains unclear. First, our review highlights an active IAV replication within alveolar macrophages, despite an abortive viral cycle. Such infection leads to persistent alveolar macrophage inflammation and diminished phagocytic function, alongside direct mitochondrial damage and indirect metabolic shifts in the alveolar micro-environment. We also discuss the "macrophage disappearance reaction", which is a drastic reduction of the alveolar macrophage population observed after influenza infection in mice but debated in humans, with unclear underlying mechanisms. Furthermore, we explore the dual nature of alveolar macrophage responses to IAV infection, questioning whether they are deleterious or protective for the host. While IAV may exploit immuno-evasion strategies and induce alveolar macrophage alteration or depletion, this could potentially reduce excessive inflammation and allow for the replacement of more effective cells. Despite these insights, the pathophysiological role of alveolar macrophages during IAV infection in humans remains understudied, urging further exploration to unravel their precise contributions to disease progression and resolution. Full Article
ad Patient-managed interventions for adults with bronchiectasis: evidence, challenges and prospects By err.ersjournals.com Published On :: 2024-10-30T01:30:15-07:00 Bronchiectasis is a chronic lung condition which is characterised by recurrent chest infections, chronic sputum production and cough, and limited exercise tolerance. While bronchiectasis may be caused by various aetiologies, these features are shared by most patients with bronchiectasis regardless of the cause. This review consolidates the existing evidence on patient-managed interventions for adults with bronchiectasis, while also outlining areas for future research. Airway clearance techniques and hyperosmolar agents are key components of the bronchiectasis management and consistently recommended for clinical implementation. Questions around their prescription, such as optimal sequence of delivery, are still to be answered. Pulmonary rehabilitation and exercise are also recommended for patients with bronchiectasis. Relatively strong evidence underpins this recommendation during a clinically stable stage of the disease, although the role of pulmonary rehabilitation following an exacerbation is still unclear. Additionally, self-management programmes feature prominently in bronchiectasis treatment, yet the lack of consensus regarding their definition and outcomes presents hurdles to establishing a cohesive evidence base. Moreover, cough, a cardinal symptom of bronchiectasis, warrants closer examination. Although managing cough in bronchiectasis may initially appear risky, further research is necessary to ascertain whether strategies employed in other respiratory conditions can be safely and effectively adapted to bronchiectasis, particularly through identifying patient responder populations and criteria where cough may not enhance airway clearance efficacy and its control is needed. Overall, there is a growing recognition of the importance of patient-managed interventions in the bronchiectasis management. Efforts to improve research methodologies and increase research funding are needed to further advance our understanding of these interventions, and their role in optimising patient care and outcomes. Full Article
ad 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
ad Contrasting and combining transcriptome complexity captured by short and long RNA sequencing reads [METHODS] By genome.cshlp.org Published On :: 2024-10-29T06:46:08-07:00 Mapping transcriptomic variations using either short- or long-read RNA sequencing is a staple of genomic research. Long reads are able to capture entire isoforms and overcome repetitive regions, whereas short reads still provide improved coverage and error rates. Yet, open questions remain, such as how to quantitatively compare the technologies, can we combine them, and what is the benefit of such a combined view? We tackle these questions by first creating a pipeline to assess matched long- and short-read data using a variety of transcriptome statistics. We find that across data sets, algorithms, and technologies, matched short-read data detects ~30% more splice junctions, such that ~10%–30% of the splice junctions included at ≥20% by short reads are missed by long reads. In contrast, long reads detect many more intron-retention events and can detect full isoforms, pointing to the benefit of combining the technologies. We introduce MAJIQ-L, an extension of the MAJIQ software, to enable a unified view of transcriptome variations from both technologies and demonstrate its benefits. Our software can be used to assess any future long-read technology or algorithm and can be combined with short-read data for improved transcriptome analysis. Full Article
ad Evolutionary dynamics of polyadenylation signals and their recognition strategies in protists [RESEARCH] By genome.cshlp.org Published On :: 2024-10-29T06:46:07-07:00 The poly(A) signal, together with auxiliary elements, directs cleavage of a pre-mRNA and thus determines the 3' end of the mature transcript. In many species, including humans, the poly(A) signal is an AAUAAA hexamer, but we recently found that the deeply branching eukaryote Giardia lamblia uses a distinct hexamer (AGURAA) and lacks any known auxiliary elements. Our discovery prompted us to explore the evolutionary dynamics of poly(A) signals and auxiliary elements in the eukaryotic kingdom. We use direct RNA sequencing to determine poly(A) signals for four protists within the Metamonada clade (which also contains G. lamblia) and two outgroup protists. These experiments reveal that the AAUAAA hexamer serves as the poly(A) signal in at least four different eukaryotic clades, indicating that it is likely the ancestral signal, whereas the unusual Giardia version is derived. We find that the use and relative strengths of auxiliary elements are also plastic; in fact, within Metamonada, species like G. lamblia make use of a previously unrecognized auxiliary element where nucleotides flanking the poly(A) signal itself specify genuine cleavage sites. Thus, despite the fundamental nature of pre-mRNA cleavage for the expression of all protein-coding genes, the motifs controlling this process are dynamic on evolutionary timescales, providing motivation for future biochemical and structural studies as well as new therapeutic angles to target eukaryotic pathogens. Full Article
ad Impact of COVID-19 on Chronic Ambulatory-Care-Sensitive Condition Emergency Department Use Among Older Adults By www.jabfm.org Published On :: 2024-10-25T09:26:14-07:00 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. Full Article
ad Headache Treatment Options By www.jabfm.org Published On :: 2024-10-25T09:26:14-07:00 Family medicine physicians often see headache as the chief complaint when meeting patients within their practice. The goal is to try different treatment modalities without having to send the patient to a specialist. Headaches affect different individuals during their lifetime. Before any treatment begins, it is best that one rules out possible causes of the headache, for example, drug interactions or structural cerebrum conditions. Nonpharmacological treatment is recommended first before attempting a stepwise approach to cost-effective pharmacological treatment options. Pharmacological treatment options should include preventive and on-demand options. A family physician has all the resources to assist patients with different types of headaches. Full Article
ad Assessing Patient Readiness for Hospital Discharge, Discharge Communication, and Transitional Care Management By www.jabfm.org Published On :: 2024-10-25T09:26:14-07:00 Background: Discharge communication between hospitalists and primary care clinicians is essential to improve care coordination, minimize adverse events, and decrease unplanned health services use. Health-related social needs are key drivers of health, and hospitalists and primary care clinicians value communicating social needs at discharge. Objective: To 1) characterize the current state of discharge communications between an academic medical center hospital and primary care clinicians at associated clinics; 2) seek feedback about the potential usefulness of discharge readiness information to primary care clinicians. Design: Exploratory, convergent mixed methods. Participants: Primary care clinicians from Family Medicine and General Internal Medicine of an academic medical center in the US Intermountain West. Approach: Literature-informed REDCap survey. Semistructured interview guide developed with key informants, grounded in current literature. Survey data were descriptively summarized; interview data were deductively and inductively coded, organized by topics. Results: Two key topics emerged: 1) discharge communication, with interrelated topics of transitional care management and follow-up appointment challenges, and recommendations for improving discharge communication; and 2) usefulness of the discharge readiness information, included interrelated topics related to lack of shared understanding about roles and responsibilities across settings and ethical concerns related to identifying problems that may not have solutions. Conclusions: While reiterating perennial discharge communication and transitional care management challenges, this study reveals new evidence about how these issues are interrelated with assessing and responding to patients’ lack of readiness for discharge and unmet social needs during care transitions. Primary care clinicians had mixed views on the usefulness of discharge readiness information. We offer recommendations for improving discharge communication and transitional care management (TCM) processes, which may be applicable in other care settings. Full Article
ad 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
ad Degradation of Obidoxime Chloride Solution for Injection upon Long-Term Storage under Field Conditions of Mediterranean Climate vs the Controlled Environment By journal.pda.org Published On :: 2024-10-22T08:20:35-07:00 Obidoxime chloride is an antidote for nerve gas intoxication. As an emergency medicine, it is being stored by the Israel Defense Forces (IDF) scattered throughout Israel in depots without a controlled environment (field conditions), thus being exposed to high and fluctuating temperatures. These conditions do not meet the manufacturer’s requirements. In addition, due to possible supply shortages, the utilization of expired batches was suggested. The current work investigated these matters. Long-term (15 years) storage under different conditions was initiated. Chemical stability and toxicity in rats were assessed. No difference was found between field conditions vs the controlled environment. The obidoxime assay remained >95% for 5 years and >90% for 7 years. The pH remained above the lower specification limit for 7–8 years. The major degradation product, 4-pyridinealdoxime, surpassed the allowed limit at 5 years. The content of total unknown impurities reached its maximum allowed by the IDF limit at 4–5 years. Threefold higher than clinically utilized doses of valid-to-date Toxogonin batches administered to rats did not cause any abnormality. However, expired batches produced significant toxic effects. Although no difference was found between storage of obidoxime ampoules when adhering to manufacturer’s recommendations vs field conditions, accumulation of degradants over the limit allowed by the IDF at 4–5 years of storage and the toxicity of the expired batches observed in rats led the IDF to a decision to shorten the shelf-life of this product from 5 to 4 years when stored in an uncontrolled environment of the Mediterranean climate. Full Article
ad The antivirulent Staphylococcal sRNA SprC regulates CzrB efflux pump to adapt its response to zinc toxicity [ARTICLE] By rnajournal.cshlp.org Published On :: 2024-10-16T07:18:13-07:00 Bacterial regulatory RNAs (sRNAs) are important players to control gene expression. In Staphylococcus aureus, SprC is an antivirulent trans-acting sRNA known to base-pair with the major autolysin atl mRNA, preventing its translation. Using MS2-affinity purification coupled with RNA sequencing, we looked for its sRNA-RNA interactome and identified 14 novel mRNA targets. In vitro biochemical investigations revealed that SprC binds two of them, czrB and deoD, and uses a single accessible region to regulate its targets, including Atl translation. Unlike Atl regulation, the characterization of the SprC-czrB interaction pinpointed a destabilization of the czrAB cotranscript, leading to a decrease of the mRNA level that impaired CzrB zinc efflux pump expression. On a physiological standpoint, we showed that SprC expression is detrimental to combat against zinc toxicity. In addition, phagocyctosis assays revealed a significant, but moderate, increase of czrB mRNA levels in a sprC-deleted mutant, indicating a functional link between SprC and czrB upon internalization in macrophages, and suggesting a role in resistance to both oxidative and zinc bursts. Altogether, our data uncover a novel pathway in which SprC is implicated, highlighting the multiple strategies used by S. aureus to balance virulence using an RNA regulator. Full Article
ad Accuracy of CAD4TB (Computer-Aided Detection for Tuberculosis) on paediatric chest radiographs By erj.ersjournals.com Published On :: 2024-11-07T00:35:56-08:00 Background Computer-aided detection (CAD) systems hold promise for improving tuberculosis (TB) detection on digital chest radiographs. However, data on their performance in exclusively paediatric populations are scarce. Methods We conducted a retrospective diagnostic accuracy study evaluating the performance of CAD4TBv7 (Computer-Aided Detection for Tuberculosis version 7) using digital chest radiographs from well-characterised cohorts of Gambian children aged <15 years with presumed pulmonary TB. The children were consecutively recruited between 2012 and 2022. We measured CAD4TBv7 performance against a microbiological reference standard (MRS) of confirmed TB, and also performed Bayesian latent class analysis (LCA) to address the inherent limitations of the MRS in children. Diagnostic performance was assessed using the area under the receiver operating characteristic curve (AUROC) and point estimates of sensitivity and specificity. Results A total of 724 children were included in the analysis, with confirmed TB in 58 (8%), unconfirmed TB in 145 (20%) and unlikely TB in 521 (72%). Using the MRS, CAD4TBv7 showed an AUROC of 0.70 (95% CI 0.60–0.79), and demonstrated sensitivity and specificity of 19.0% (95% CI 11–31%) and 99.0% (95% CI 98.0–100.0%), respectively. Applying Bayesian LCA with the assumption of conditional independence between tests, sensitivity and specificity estimates for CAD4TBv7 were 42.7% (95% CrI 29.2–57.5%) and 97.9% (95% CrI 96.6–98.8%), respectively. When allowing for conditional dependence between culture and Xpert assay, CAD4TBv7 demonstrated a sensitivity of 50.3% (95% CrI 32.9–70.0%) and specificity of 98.0% (95% CrI 96.7–98.9%). Conclusion Although CAD4TBv7 demonstrated high specificity, its suboptimal sensitivity underscores the crucial need for optimisation of CAD4TBv7 for detecting TB in children. Full Article
ad Multidisciplinary management of adult patients with chylothorax: a consensus statement By erj.ersjournals.com Published On :: 2024-11-07T00:35:55-08:00 The management of chylothorax remains challenging given the limited evidence and significant heterogeneity in practice. In addition, there are no practical guidelines on the optimal approach to manage this complex condition. We convened an international group of 27 experts from 20 institutions across five countries and four specialties (pulmonary, interventional radiology, thoracic surgery and nutrition) with experience and expertise in managing adult patients with chylothorax. We performed a literature and internet search for reports addressing seven clinically relevant PICO (Patient, Intervention, Comparison and Outcome) questions pertaining to the management of adult patients with chylothorax. This consensus statement, consisting of best practice statements based on expert consensus addressing these seven PICO questions, was formulated by a systematic and rigorous process involving the evaluation of published evidence, augmented with provider experience. Panel members participated in the development of the final best practice statements using the modified Delphi technique. Our consensus statement aims to offer guidance in clinical decision making when managing patients with chylothorax while also identifying gaps in knowledge and informing future research. Full Article
ad The Simultaneous Inhibition of Solute Carrier Family 6 Member 19 and Breast Cancer Resistance Protein Transporters Leads to an Increase of Indoxyl Sulfate (a Uremic Toxin) in Plasma and Kidney [Articles] By dmd.aspetjournals.org Published On :: 2024-10-16T09:02:03-07:00 Solute carrier family 6 member 19 (SLC6A19) inhibitors are being studied as therapeutic agents for phenylketonuria. In this work, a potent SLC6A19 inhibitor (RA836) elevated rat kidney uremic toxin indoxyl sulfate (IDS) levels by intensity (arbitrary unit) of 13.7 ± 7.7 compared with vehicle 0.3 ± 0.1 (P = 0.01) as determined by tissue mass spectrometry imaging analysis. We hypothesized that increased plasma and kidney levels of IDS could be caused by the simultaneous inhibition of both Slc6a19 and a kidney IDS transporter responsible for excretion of IDS into urine. To test this, we first confirmed the formation of IDS through tryptophan metabolism by feeding rats a Trp-free diet. Inhibiting Slc6a19 with RA836 led to increased IDS in these rats. Next, RA836 and its key metabolites were evaluated in vitro for inhibiting kidney transporters such as organic anion transporter (OAT)1, OAT3, and breast cancer resistance protein (BCRP). RA836 inhibits BCRP with an IC50 of 0.045 μM but shows no significant inhibition of OAT1 or OAT3. Finally, RA836 analogs with either potent or no inhibition of SLC6A19 and/or BCRP were synthesized and administered to rats fed a normal diet. Plasma and kidney samples were collected to quantify IDS using liquid chromatography–mass spectrometry. Neither a SLC6A19 inactive but potent BCRP inhibitor nor a SLC6A19 active but weak BCRP inhibitor raised IDS levels, whereas compounds inhibiting both transporters caused IDS accumulation in rat plasma and kidney, supporting the hypothesis that rat Bcrp contributes to the excretion of IDS. In summary, we identified that inhibiting Slc6a19 increases IDS formation, while simultaneously inhibiting Bcrp results in IDS accumulation in the kidney and plasma. SIGNIFICANCE STATEMENT This is the first publication to decipher the mechanism for accumulation of indoxyl sulfate (IDS) (a uremic toxin) in rats via inhibition of both Slc6a19 and Bcrp. Specifically, inhibition of Slc6a19 in the gastrointestinal track increases IDS formation, and inhibition of Bcrp in the kidney blocks IDS excretion. Therefore, we should avoid inhibiting both solute carrier family 6 member 19 and breast cancer resistance protein simultaneously in humans to prevent accumulation of IDS, a known risk factor for cardiovascular disease, psychic anxiety, and mortality in chronic kidney disease patients. Full Article
ad The Induction of Drug Uptake Transporter Organic Anion Transporting Polypeptide 1A2 by Radiation Is Mediated by the Nonreceptor Tyrosine Kinase v-YES-1 Yamaguchi Sarcoma Viral Oncogene Homolog 1 [Articles] By dmd.aspetjournals.org Published On :: 2024-10-16T09:02:03-07:00 Organic anion transporting polypeptides (OATP, gene symbol SLCO) are well-recognized key determinants for the absorption, distribution, and excretion of a wide spectrum of endogenous and exogenous compounds including many antineoplastic agents. It was therefore proposed as a potential drug target for cancer therapy. In our previous study, it was found that low-dose X-ray and carbon ion irradiation both upregulated the expression of OATP family member OATP1A2 and in turn, led to a more dramatic killing effect when cancer cells were cotreated with antitumor drugs such as methotrexate. In the present study, the underlying mechanism of the phenomenon was explored in breast cancer cell line MCF-7. It was found that the nonreceptor tyrosine kinase v-YES-1 Yamaguchi sarcoma viral oncogene homolog 1 (YES-1) was temporally coordinated with the change of OATP1A2 after irradiation. The overexpression of YES-1 significantly increased OATP1A2 both at the mRNA and protein level. The signal transducer and activator of transcription 3 (STAT3) pathway is likely the downstream target of YES-1 because phosphorylation and nuclear accumulation of STAT3 were both enhanced after overexpressing YES-1 in MCF-7 cells. Further investigation revealed that there are two possible binding sites of STAT3 localized at the upstream sequence of SLCO1A2, the encoding gene of OATP1A2. Electrophoretic mobility shift assay and chromatin immunoprecipitation analysis suggested that these two sites bound to STAT3 specifically and the overexpression of YES-1 significantly increased the association of the transcription factor with the putative binding sites. Finally, inhibition or knockdown of YES-1 attenuated the induction effect of radiation on the expression of OATP1A2. SIGNIFICANCE STATEMENT The present study found that the effect of X-rays on v-YES-1 Yamaguchi sarcoma viral oncogene homolog 1 (YES-1) and organic anion transporting polypeptides (OATP)1A2 was temporally coordinated. YES-1 phosphorylates and increases the nuclear accumulation of signal transducer and activator of transcription 3, which in turn binds to the upstream regulatory sequences of SLCO1A2, the coding gene for OATP1A2. Hence, inhibitors of YES-1 may suppress the radiation induction effect on OATP1A2. Full Article
ad Evaluating Drug-Drug Interaction Risk Associated with Peptide Analogs Using advanced In Vitro Systems [Special Section on New and Emerging Areas and Technologies in Drug Metabolism and Disposition, Part II] By dmd.aspetjournals.org Published On :: 2024-10-16T09:02:03-07:00 Drug–drug interaction (DDI) assessment of therapeutic peptides is an evolving area. The industry generally follows DDI guidelines for small molecules, but the translation of data generated with commonly used in vitro systems to in vivo is sparse. In the current study, we investigated the ability of advanced human hepatocyte in vitro systems, namely HepatoPac, spheroids, and Liver-on-a-chip, to assess potential changes in regulation of CYP1A2, CYP2B6, CYP3A4, SLCO1B1, and ABCC2 in the presence of selected therapeutic peptides, proteins, and small molecules. The peptide NN1177, a glucagon and GLP-1 receptor co-agonist, did not suppress mRNA expression or activity of CYP1A2, CYP2B6, and CYP3A4 in HepatoPac, spheroids, or Liver-on-a-chip; these findings were in contrast to the data obtained in sandwich cultured hepatocytes. No effect of NN1177 on SLCO1B1 and ABCC2 mRNA was observed in any of the complex systems. The induction magnitude differed across the systems (e.g., rifampicin induction of CYP3A4 mRNA ranged from 2.8-fold in spheroids to 81.2-fold in Liver-on-a-chip). Small molecules, obeticholic acid and abemaciclib, showed varying responses in HepatoPac, spheroids, and Liver-on-a-chip, indicating a need for EC50 determinations to fully assess translatability data. HepatoPac, the most extensively investigated in this study (3 donors), showed high potential to investigate DDIs associated with CYP regulation by therapeutic peptides. Spheroids and Liver-on-a-chip were only assessed in one hepatocyte donor and further evaluations are required to confirm their potential. This study establishes an excellent foundation toward the establishment of more clinically-relevant in vitro tools for evaluation of potential DDIs with therapeutic peptides. SIGNIFICANT STATEMENT At present, there are no guidelines for drug–drug interaction (DDI) assessment of therapeutic peptides. Existing in vitro methods recommended for assessing small molecule DDIs do not appear to translate well for peptide drugs, complicating drug development for these moieties. Here, we establish evidence that complex cellular systems have potential to be used as more clinically-relevant tools for the in vitro DDI evaluation of therapeutic peptides. Full Article
ad FP2020 and FP2030 Country Commitments: A Mixed Method Study of Adolescent and Youth Sexual and Reproductive Health Components By ghspjournal.org Published On :: 2024-10-29T12:28:39-07:00 ABSTRACTIntroduction:Family Planning 2020 (FP2020) was established in 2012 with the goal of expanding contraceptive access. By 2020, 46 countries had made commitments to FP2020. A sustained focus on adolescents and youth (AY) began in 2016. During the commitment formulation process, substantial support was offered to countries to develop AY commitments based on sound data, research evidence, and programmatic experience. This study assesses how country commitments under FP2020 and FP2030 have evolved over time with respect to improving attention to and focus on the needs of adolescents and youth sexual and reproductive health (AYSRH).Methods:We analyzed the content of FP2020 and FP2030 country commitments focusing on AY (aged 10–24 years) using a scoring guideline we developed to measure the AY commitments in terms of completeness, clarity, and quality.Results:This analysis shows that FP2030 commitments better articulate strategies and activities to reach AY with contraceptive information and services when compared to FP2020 commitments.Conclusion:FP2030 commitments are stronger in some areas on AYSRH, such as commitment to establish national or local policies, strategies, and guidance for AY programming, specifying the target audience of the AY commitment, and partnering with AY or youth-led organizations in commitments. However, more work remains to be done by countries to dedicate a budget for achieving AY objectives, including measurable targets for monitoring progress, identifying and addressing the root causes that impact AY access to and use of contraception, including child marriage and gender-based violence, and reducing financial barriers to access contraception. Full Article
ad Adapting the Social Norms Exploration Tool in the Democratic Republic of the Congo to Identify Social Norms for Behavior Change By ghspjournal.org Published On :: 2024-10-29T12:28:39-07:00 ABSTRACTIn the Democratic Republic of the Congo (DRC), male engagement, social norms, and social networks mitigate family planning behavior. We discuss the adaptation of the Social Norms Exploration Tool (SNET), which identifies relevant social norms and community members upholding these norms, to inform the development of family planning interventions in the DRC. The SNET provides activity tools and templates to guide users through the following steps: (1) plan and prepare, (2) identify reference groups, (3) explore social norms, (4) analyze results, and (5) apply findings.The SNET approach resulted in discussion of social norms, particularly around birth spacing and gender norms framing the man as the decision-maker. However, despite applying a methodology specifically designed to identify social norms, other factors limiting use of contraceptive methods were identified in the process, including lack of education, rumors, and misconceptions. Adaptations were needed to include the full range of reference groups due to narrow phrasing of primary questions, and some of the participatory methods were overly complicated. Feedback from experienced data collectors suggested that the social norms framework is not intuitive, is difficult to apply correctly, and may require that data collectors have a stronger foundation in the relevant concepts to produce valid and actionable results.Although the SNET provides language for discussing normative factors and techniques to identify reference groups and social norms, modifications to the implementation process are recommended when adapting the tool for research. Full Article