a c Making a COVID-19 Vaccine Is Tough, Distributing It Might Be Tougher By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Making a COVID-19 Vaccine Is Tough, Distributing It Might Be TougherCategory: Health NewsCreated: 8/25/2020 12:00:00 AMLast Editorial Review: 8/25/2020 12:00:00 AM Full Article
a c Could Yoga Calm Your A-Fib? Early Findings Suggest It Might By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Could Yoga Calm Your A-Fib? Early Findings Suggest It MightCategory: Health NewsCreated: 8/27/2020 12:00:00 AMLast Editorial Review: 8/27/2020 12:00:00 AM Full Article
a c President Trump Promises a COVID Vaccine Before the End of the Year By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: President Trump Promises a COVID Vaccine Before the End of the YearCategory: Health NewsCreated: 8/28/2020 12:00:00 AMLast Editorial Review: 8/28/2020 12:00:00 AM Full Article
a c Wife of California Congressman Died After Using Herbal Remedy for Diabetes, Weight Loss By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Wife of California Congressman Died After Using Herbal Remedy for Diabetes, Weight LossCategory: Health NewsCreated: 8/25/2022 12:00:00 AMLast Editorial Review: 8/25/2022 12:00:00 AM Full Article
a c 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
a c Breakfast Might Be Good for a Child's Emotional Health, Too By www.medicinenet.com Published On :: Wed, 24 Aug 2022 00:00:00 PDT Title: Breakfast Might Be Good for a Child's Emotional Health, TooCategory: Health NewsCreated: 8/24/2022 12:00:00 AMLast Editorial Review: 8/24/2022 12:00:00 AM Full Article
a c LSD Is Making a Comeback Among Young Americans By www.medicinenet.com Published On :: Tue, 23 Aug 2022 00:00:00 PDT Title: LSD Is Making a Comeback Among Young AmericansCategory: Health NewsCreated: 8/23/2022 12:00:00 AMLast Editorial Review: 8/23/2022 12:00:00 AM Full Article
a c Is Chlamydia Contagious? By www.medicinenet.com Published On :: Mon, 1 Aug 2022 00:00:00 PDT Title: Is Chlamydia Contagious?Category: Diseases and ConditionsCreated: 5/28/2015 12:00:00 AMLast Editorial Review: 8/1/2022 12:00:00 AM Full Article
a c 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
a c A Comprehensive Guide to Long-Acting Injectable Antipsychotics for Primary Care Clinicians By www.jabfm.org Published On :: 2024-10-25T09:26:14-07:00 We propose a paper that provides education on commonly used long-acting injectable antipsychotics (LAIs) to improve primary care based mental health interventions in patients with severe mental illnesses (SMIs) such as schizophrenia, schizoaffective disorder, and bipolar disorders. With the expanding interface of primary care and psychiatry across all healthcare settings, it has become increasingly important for primary care clinicians to have a broader understanding of common psychiatric treatments, including LAIs. Long-acting injectable antipsychotics have been shown to be helpful in significantly improving treatment adherence, preventing disease progression, improving treatment response, decreasing readmission rates, and reducing social impairment. We discuss evidence-based indications and guidelines for use of long-acting injectable antipsychotics. We provide an overview of the treatment of SMI with LAIs, mainly focusing on the most commonly used long-acting injectable antipsychotics, advantages and disadvantages of each, along with outlining important clinical pearls for ease of practical application. Equipped with increased familiarity and understanding of these essential therapies, primary care clinicians can better facilitate early engagement with psychiatric care, promote more widespread use, and thus significantly improve the wellbeing and quality of life of patients with severe mental illness. Full Article
a c Development and Validation of a Customized Amplex UltraRed Assay for Sensitive Hydrogen Peroxide Detection in Pharmaceutical Water By journal.pda.org Published On :: 2024-10-22T08:20:35-07:00 For clean-room technologies such as isolators and restricted access barrier systems (RABS), decontamination using hydrogen peroxide (H2O2) is increasingly attractive to fulfill regulatory requirements. Several approaches are currently used, ranging from manual wipe disinfection to vapor phase hydrogen peroxide (VPHP) or automated nebulization sanitization. Although the residual airborne H2O2 concentration can be easily monitored, detection of trace H2O2 residues in filled products is rather challenging. To simulate the filling process in a specific clean room, technical runs with water for injection (WfI) are popular. Thus, the ability to detect traces of H2O2 in water is an important prerequisite to ensure a safe and reliable use of H2O2 for isolator or clean room decontamination. The objective of this study was to provide a validated quantitative, fluorometric Amplex UltraRed assay, which satisfies the analytical target profile of quantifying H2O2 in WfI at low nanomolar to low micromolar concentrations (ppb range) with high accuracy and high precision. The Amplex UltraRed technology provides a solid basis for this purpose; however, no commercial assay kit that fulfills these requirements is available. Therefore, a customized Amplex UltraRed assay was developed, optimized, and validated. This approach resulted in an assay that is capable of quantifying H2O2 in WfI selectively, sensitively, accurately, precisely, and robustly. This assay is used in process development and qualification approaches using WfI in H2O2-decontaminated clean rooms and isolators. Full Article
a c A cellular identity crisis? Plasticity changes during aging and rejuvenation [Reviews] By genesdev.cshlp.org Published On :: 2024-10-16T07:18:56-07:00 Cellular plasticity in adult multicellular organisms is a protective mechanism that allows certain tissues to regenerate in response to injury. Considering that aging involves exposure to repeated injuries over a lifetime, it is conceivable that cell identity itself is more malleable—and potentially erroneous—with age. In this review, we summarize and critically discuss the available evidence that cells undergo age-related shifts in identity, with an emphasis on those that contribute to age-associated pathologies, including neurodegeneration and cancer. Specifically, we focus on reported instances of programs associated with dedifferentiation, biased differentiation, acquisition of features from alternative lineages, and entry into a preneoplastic state. As some of the most promising approaches to rejuvenate cells reportedly also elicit transient changes to cell identity, we further discuss whether cell state change and rejuvenation can be uncoupled to yield more tractable therapeutic strategies. Full Article
a c The area postrema: a critical mediator of brain-body interactions [Special Section: Symposium Outlook] By genesdev.cshlp.org Published On :: 2024-10-16T07:18:56-07:00 The dorsal vagal complex contains three structures: the area postrema, the nucleus tractus solitarii, and the dorsal motor nucleus of the vagus. These structures are tightly linked, both anatomically and functionally, and have important yet distinct roles in not only conveying peripheral bodily signals to the rest of the brain but in the generation of behavioral and physiological responses. Reports on the new discoveries in these structures were highlights of the symposium. In this outlook, we focus on the roles of the area postrema in mediating brain–body interactions and its potential utility as a therapeutic target, especially in cancer cachexia. Full Article
a c A circular split nanoluciferase reporter for validating and screening putative internal ribosomal entry site elements [METHOD] By rnajournal.cshlp.org Published On :: 2024-10-16T07:18:13-07:00 Internal ribosomal entry sites (IRESs) recruit the ribosome to promote translation, typically in an m7G cap-independent manner. Although IRESs are well-documented in viral genomes, they have also been reported in mammalian transcriptomes, where they have been proposed to mediate cap-independent translation of mRNAs. However, subsequent studies have challenged the idea of these "cellular" IRESs. Current methods for screening and discovering IRES activity rely on a bicistronic reporter assay, which is prone to producing false positive signals if the putative IRES sequence has a cryptic promoter or cryptic splicing sites. Here, we report an assay for screening IRES activity using a genetically encoded circular RNA comprising a split nanoluciferase (nLuc) reporter. The circular split nLuc reporter is less susceptible to the various sources of false positives that adversely affect the bicistronic IRES reporter assay and provides a streamlined method for screening IRES activity. Using the circular split nLuc reporter, we find that nine reported cellular IRESs have minimal IRES activity. Overall, the circular split nLuc reporter offers a simplified approach for identifying and validating IRESs and exhibits reduced propensity for producing the types of false positives that can occur with the bicistronic reporter assay. Full Article
a c High-resolution reconstruction of a C. elegans ribosome sheds light on evolutionary dynamics and tissue specificity [ARTICLE] By rnajournal.cshlp.org Published On :: 2024-10-16T07:18:13-07:00 Caenorhabditis elegans is an important model organism for human health and disease, with foundational contributions to the understanding of gene expression and tissue patterning in animals. An invaluable tool in modern gene expression research is the presence of a high-resolution ribosome structure, though no such structure exists for C. elegans. Here, we present a high-resolution single-particle cryogenic electron microscopy (cryo-EM) reconstruction and molecular model of a C. elegans ribosome, revealing a significantly streamlined animal ribosome. Many facets of ribosome structure are conserved in C. elegans, including overall ribosomal architecture and the mechanism of cycloheximide, whereas other facets, such as expansion segments and eL28, are rapidly evolving. We identify uL5 and uL23 as two instances of tissue-specific ribosomal protein paralog expression conserved in Caenorhabditis, suggesting that C. elegans ribosomes vary across tissues. The C. elegans ribosome structure will provide a basis for future structural, biochemical, and genetic studies of translation in this important animal system. Full Article
a c Characteristics of exacerbators in the US Bronchiectasis and NTM Research Registry: a cross-sectional study By beta.openres.ersjournals.com Published On :: 2024-11-11T01:50:25-08:00 Background Exacerbations of noncystic fibrosis bronchiectasis (bronchiectasis) are associated with reduced health-related quality of life and increased mortality, likelihood of hospitalisation and lung function decline. This study investigated patient clinical characteristics associated with exacerbation frequency. Methods A cross-sectional cohort study of patients ≥18 years with bronchiectasis enrolled in the US Bronchiectasis and Nontuberculous Mycobacteria (NTM) Research Registry (BRR) September 2008–March 2020. Patients were stratified by exacerbation frequency in their 2 years before enrolment. Patient demographics, respiratory symptoms, healthcare resource utilisation, microbiology, modified bronchiectasis severity index (mBSI) and select comorbidities were collected at enrolment. Patient characteristics associated with exacerbation frequency were assessed using a negative binomial model. Results The study included 2950 patients (mean age 65.6 years; 79.1% female). Frequency of moderate to severe airway obstruction (forced expiratory volume in 1 s (FEV1) % predicted <50%; most recent measure) was 15.9%, 17.8%, and 24.6% in patients with 1, 2, and ≥3 exacerbations versus 8.9% in patients with 0 exacerbations; severe disease (mBSI) was 27.8%, 24.2% and 51.1% versus 13.2%; respiratory hospitalisation was 24.5%, 33.0% and 36.5% versus 4.1%; and Pseudomonas aeruginosa infection was 18.8%, 23.4% and 35.2% versus 11.9%. In multivariable model analysis, respiratory hospitalisation, cough, haemoptysis, P. aeruginosa, younger age, lower FEV1% predicted, asthma, and gastro-oesophageal reflux disease were associated with more exacerbations. Conclusions These findings demonstrate a high disease burden, including increased respiratory symptoms, healthcare resource utilisation, and P. aeruginosa infection in patients with bronchiectasis and multiple exacerbations. Full Article
a c 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
a c A Cosmopolitan Argument for Temporary “Diagonal” Short-Term Surgical Missions as a Component of Surgical Systems Strengthening By ghspjournal.org Published On :: 2024-10-29T12:28:39-07:00 Full Article
a c Strengthening Capacity for Tailored Immunization Programs Using Adult Learning Principles: A Case Study from Nigeria By ghspjournal.org Published On :: 2024-10-29T12:28:39-07:00 ABSTRACTIntroduction: Nigeria has the highest number of children who have not received any vaccines in Africa. The training-of-trainers (TOT) model used to train program managers (PMs) and health care workers (HCWs) is ineffective for adult learning and limits immunization programs’ success. We incorporated adult learning principles (ALPs) in designing and delivering TOT for immunization PMs and HCWs to use data to engage communities for tailored immunization strategies.Methods: Our study was implemented in 3 local government areas (LGAs) of the Federal Capital Territory, Nigeria. A training curriculum was developed, integrating ALPs and technical and operational content based on best practices in delivering immunization training and the training needs assessment findings. State PMs (n=10), LGA PMs (n=30), and HCWs (n=42) were trained on the human-centered design for tailoring immunization programs (HCD-TIP) approaches using ALPs. We used interviews and surveys with purposively and conveniently sampled PMs and HCWs, respectively, and observations to assess participants’ satisfaction, knowledge and competence, behavior changes, and results. The interviews were analyzed thematically, and surveys were statistically.Results: There was a high level of satisfaction with the training among LGA PMs (100%), state PMs (91%), and HCWs (85%), with significant knowledge and competence improvements post-training (P<.001). The trained participants conducted 2 HCD sessions with 24 undervaccinated communities and co-designed 24 prototype solutions for testing. Results showed increased coverage of the pentavalent vaccine first dose (54%) and third dose (188%) across 12 participating communities. Improved community colaboration, communication skills, and data-driven approaches were the most cited behavior changes in practice.Conclusion: The application of ALPs in training, use of HCD-TIP approaches and tools, and supportive supervision enhanced PMs’ and HCWs’ capacity for tailored interventions. Countries should consider adopting a holistic approach that focuses on using these approaches in immunization programs to strengthen the health system for equitable vaccine coverage. Full Article
a c Development and Piloting of Implementation Strategies to Support Delivery of a Clinical Intervention for Postpartum Hemorrhage in Four sub-Saharan Africa Countries By ghspjournal.org Published On :: 2024-10-29T12:28:39-07:00 ABSTRACTIntroduction:Postpartum hemorrhage (PPH) remains the leading cause of maternal mortality. A new clinical intervention (E-MOTIVE) holds the potential to improve early PPH detection and management. We aimed to develop and pilot implementation strategies to support uptake of this intervention in Kenya, Nigeria, South Africa, and Tanzania.Methods:Implementation strategy development: We triangulated findings from qualitative interviews, surveys and a qualitative evidence synthesis to identify current PPH care practices and influences on future intervention implementation. We mapped influences using implementation science frameworks to identify candidate implementation strategies before presenting these at stakeholder consultation and design workshops to discuss feasibility, acceptability, and local adaptations. Piloting: The intervention and implementation strategies were piloted in 12 health facilities (3 per country) over 3 months. Interviews (n=58), case report forms (n=1,269), and direct observations (18 vaginal births, 7 PPHs) were used to assess feasibility, acceptability, and fidelity.Results:Implementation strategy development: Key influences included shortages of drugs, supplies, and staff, limited in-service training, and perceived benefits of the intervention (e.g., more accurate PPH detection and reduced PPH mortality). Proposed implementation strategies included a PPH trolley, on-site simulation-based training, champions, and audit and feedback. Country-specific adaptations included merging the E-MOTIVE intervention with national maternal health trainings, adapting local PPH protocols, and PPH trollies depending on staff needs. Piloting: Intervention and implementation strategy fidelity differed within and across countries. Calibrated drapes resulted in earlier and more accurate PPH detection but were not consistently used at the start. Implementation strategies were feasible to deliver; however, some instances of limited use were observed (e.g., PPH trolley and skills practice after training).Conclusion:Systematic intervention development, piloting, and process evaluation helped identify initial challenges related to intervention fidelity, which were addressed ahead of a larger-scale effectiveness evaluation. This has helped maximize the internal validity of the trial. Full Article
a c Chronic Administration of Cannabinoid Agonists ACEA, AM1241, and CP55,940 Induce Sex-Specific Differences in Tolerance and Sex Hormone Changes in a Chemotherapy-Induced Peripheral Neuropathy [Special Section: Cannabinoid Signaling in Human Health and Dise By jpet.aspetjournals.org Published On :: 2024-10-18T07:04:15-07:00 Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of chemotherapy treatment, routinely manifesting as increased pain sensitivity (allodynia) in distal extremities. Despite its prevalence, effective treatment options are limited. Cannabinoids are increasingly being evaluated for their ability to treat chronic pain conditions, including CIPN. While previous studies have revealed sex differences in cannabinoid-mediated antinociception in acute and chronic pain models, there is a paucity of studies addressing potential sex differences in the response of CIPN to cannabinoid treatment. Therefore, we evaluated the long-term antiallodynic efficacy of cannabinoid receptor type 1 (CB1)-selective, cannabinoid receptor type 2 (CB2)-selective, and CB1/CB2 mixed agonists in the cisplatin CIPN model, using both male and female mice. CB1 selective agonism was observed to have sex differences in the development of tolerance to antiallodynic effects, with females developing tolerance more rapidly than males, while the antiallodynic effects of selective CB2 agonism lacked tolerance development. Compound-specific changes to the female estrous cycle and female plasma estradiol levels were noted, with CB1 selective agonism decreasing plasma estradiol while CB2 selective agonism increased plasma estradiol. Chronic administration of a mixed CB1/CB2 agonist resulted in increased mRNA expression of proinflammatory cytokines and endocannabinoid regulatory enzymes in female spinal cord tissue. Ovarian tissue was noted to have proinflammatory cytokine mRNA expression following administration of a CB2 acting compound while selective CB1 agonism resulted in decreased proinflammatory cytokines and endocannabinoid regulatory enzymes in testes. These results support the need for further investigation into the role of sex and sex hormones signaling in pain and cannabinoid-mediated antinociceptive effects. SIGNIFICANCE STATEMENT CIPN is a common side effect of chemotherapy. We have found that both CB1 and CB2 receptor agonism produce antinociceptive effects in a cisplatin CIPN model. We observed that tolerance to CB1-mediated antinociception developed faster in females and did not develop for CB2-mediated antinociception. Additionally, we found contrasting roles for CB1/CB2 receptors in the regulation of plasma estradiol in females, with CB1 agonism attenuating estradiol and CB2 agonism enhancing estradiol. These findings support the exploration of cannabinoid agonists for CIPN. Full Article
a c Preoperative Assessment of Meningioma Consistency Using a Combination of MR Elastography and DTI [RESEARCH] By www.ajnr.org Published On :: 2024-11-07T15:14:12-08:00 BACKGROUND AND PURPOSE: Preoperative assessment of meningioma consistency is beneficial for optimizing surgical strategy and prognosis of patients. We aim to develop a noninvasive prediction model for meningioma consistency utilizing MR elastography and DTI. MATERIALS AND METHODS: Ninety-four patients (52 ± 22 years old, 69 women, 25 men) diagnosed with meningioma were recruited in the study. Each patient underwent preoperative T1WI, T2WI, DTI, and MR elastography. Combined MR elastography–DTI model was developed based on multiple logistic regression. Intraoperative tumor descriptions served as clinical criteria for evaluating meningioma consistency. The diagnostic efficacy in determining meningioma consistency was evaluated by using a receiver operating characteristic curve. Further validation was conducted in 27 stereotactic biopsies by using indentation tests and underlying mechanism was investigated by histologic analysis. RESULTS: Among all the imaging modalities, MR elastography demonstrated the highest efficacy with the shear modulus magnitude (|G*|) achieving an area under the curve (AUC) of 0.81 (95% CI: 0.699–0.929). When combined with DTI, the diagnostic accuracy further increased (AUC: 0.88, 95% CI: 0.784–0.971), surpassing any technique alone. Indentation measurement based on stereotactic biopsies further demonstrated that the MR elastography–DTI model was suitable for predicting intratumor consistency. Histologic analysis suggested that meningioma consistency may be correlated with tumor cell density and fibrous content. CONCLUSIONS: The MR elastography–DTI combined model is effective in noninvasive prediction of meningioma consistency. Full Article
a c High-Resolution MRA Cerebrovascular Findings in a Tri-Ethnic Population [CLINICAL PRACTICE] By www.ajnr.org Published On :: 2024-11-07T15:14:12-08:00 BACKGROUND AND PURPOSE: Incidental findings on brain MRI and variations of the circle of Willis (CoW) are relatively common among the general population. Ethnic differences have been described before, but few studies have explored the prevalence of incidental intracranial cerebrovascular findings and CoW variants in the setting of a single multiethnic cohort. The purpose of this investigation was to describe both incidental cerebrovascular findings and the morphology of the CoW on high-resolution 3T TOF-MRA in a UK tri-ethnic population-based cohort and to present updated prevalence estimates and morphologic reference values. MATERIALS AND METHODS: We studied participants from the UK Southall and Brent REvisited study who underwent 3T brain MRI between 2014 and 2018. TOF-MRA images were assessed for the presence of incidental cerebrovascular findings and used to determine CoW anatomy. RESULTS: Seven hundred fifty participants (mean age, 71.28 [SD, 6.46] years; range, 46–90 years; 337 women), 322 White Europeans, 253 South Asians, and 175 African Caribbeans were included. Incidental cerebrovascular findings were observed in 84 subjects (11.2%, 95% CI, 9.0%–13.7%; 36 women; 42.86%, 95% CI, 32.11%–54.12%), with cerebral aneurysms being the most frequent followed by intracranial arterial stenoses with the highest prevalence among South Asians compared with White European (OR: 2.72; 95% CI, 1.22–6.08; P = .015) and African Caribbean subjects (OR: 2.79; 95% CI, 1.00–7.82; P = .051). Other findings included arteriovenous malformations and infundibula. The CoW was found to be more often complete in women than in men (25.22% compared with 18.41%, P = .024) and in African Caribbean (34.86%) compared with White European (19.19%) and South Asian (14.23%) subjects (P < .001 each). CONCLUSIONS: Intracranial arterial stenoses were independently associated with ethnicity after adjusting for vascular risk factors, having the highest prevalence among South Asians. The prevalence of aneurysms was higher than that in previous population-based studies. We observed anatomic differences in the CoW configuration among women, men, and ethnicities. Full Article
a c The diagnostic odyssey of a patient with dihydropyrimidinase deficiency: a case report and review of the literature [RESEARCH REPORT] By molecularcasestudies.cshlp.org Published On :: 2024-01-10T08:13:38-08:00 Dihydropyrimidinase (DHP) deficiency is an autosomal recessive metabolic disorder caused by biallelic pathogenic variants of DPYS. Patients with DHP deficiency exhibit a broad spectrum of phenotypes, ranging from severe neurological and gastrointestinal involvement to cases with no apparent symptoms. The biochemical diagnosis of DHP deficiency is based on the detection of a significant amount of dihydropyrimidines in urine, plasma, and cerebrospinal fluid samples. Molecular genetic testing, specifically the identification of biallelic pathogenic variants in DPYS, has proven instrumental in confirming the diagnosis and facilitating family studies. This case study documents the diagnostic journey of an 18-yr-old patient with DHP deficiency, highlighting features at the severe end of the clinical spectrum. Notably, our patient exhibited previously unreported skeletal features that positively responded to bisphosphonate treatment, contributing valuable insights to the clinical characterization of DHP deficiency. Additionally, a novel DPYS variant was identified and confirmed pathogenicity through metabolic testing, further expanding the variant spectrum of the gene. Our case emphasizes the importance of a comprehensive diagnostic approach using genetic sequencing and metabolic testing for accurate diagnosis. Full Article
a c Prostate cancer patient stratification by molecular signatures in the Veterans Precision Oncology Data Commons [RESEARCH REPORT] By molecularcasestudies.cshlp.org Published On :: 2024-01-10T08:13:38-08:00 Veterans are at an increased risk for prostate cancer, a disease with extraordinary clinical and molecular heterogeneity, compared with the general population. However, little is known about the underlying molecular heterogeneity within the veteran population and its impact on patient management and treatment. Using clinical and targeted tumor sequencing data from the National Veterans Affairs health system, we conducted a retrospective cohort study on 45 patients with advanced prostate cancer in the Veterans Precision Oncology Data Commons (VPODC), most of whom were metastatic castration-resistant. We characterized the mutational burden in this cohort and conducted unsupervised clustering analysis to stratify patients by molecular alterations. Veterans with prostate cancer exhibited a mutational landscape broadly similar to prior studies, including KMT2A and NOTCH1 mutations associated with neuroendocrine prostate cancer phenotype, previously reported to be enriched in veterans. We also identified several potential novel mutations in PTEN, MSH6, VHL, SMO, and ABL1. Hierarchical clustering analysis revealed two subgroups containing therapeutically targetable molecular features with novel mutational signatures distinct from those reported in the Catalogue of Somatic Mutations in Cancer database. The clustering approach presented in this study can potentially be used to clinically stratify patients based on their distinct mutational profiles and identify actionable somatic mutations for precision oncology. Full Article
a c Rapid genome diagnosis of alveolar capillary dysplasia leading to treatment in a child with respiratory and cardiac failure [RESEARCH REPORT] By molecularcasestudies.cshlp.org Published On :: 2024-01-10T08:13:38-08:00 Alveolar capillary dysplasia (ACD) is a fatal disorder that typically presents in the neonatal period with refractory hypoxemia and pulmonary hypertension. Lung biopsy is traditionally required to establish the diagnosis. We report a 22-mo-old male who presented with anemia, severe pulmonary hypertension, and right heart failure. He had a complicated hospital course resulting in cardiac arrest and requirement for extracorporeal membrane oxygenation. Computed tomography of the chest showed a heterogenous pattern of interlobular septal thickening and pulmonary edema. The etiology of his condition was unknown, lung biopsy was contraindicated because of his medical fragility, and discussions were held to move to palliative care. Rapid whole-genome sequencing (rWGS) was performed. In 2 d it resulted, revealing a novel FOXF1 gene pathogenic variant that led to the presumptive diagnosis of atypical ACD. Cases of atypical ACD have been reported with survival in patients using medical therapy or lung transplantation. Based on the rWGS diagnosis and more favorable potential of atypical ACD, aggressive medical treatment was pursued. The patient was discharged home after 67 d in the hospital; he is currently doing well more than 30 mo after his initial presentation with only one subsequent hospitalization and no requirement for lung transplantation. Our case reveals the potential for use of rWGS in a critically ill child in which the diagnosis is unknown. rWGS and other advanced genetic tests can guide clinical management and expand our understanding of atypical ACD and other conditions. Full Article
a c Drosophila Cornmeal-Yeast Food By cshprotocols.cshlp.org Published On :: 2024-11-01T06:46:10-07:00 Full Article
a c Selection of Affibody Molecules Using Escherichia coli Display By cshprotocols.cshlp.org Published On :: 2024-11-01T06:46:10-07:00 Affibody molecules are small (6-kDa) affinity proteins generated by directed evolution for specific binding to various target molecules. The first step in this workflow involves the generation of an affibody library, which can then be used for selection via multiple display methods. This protocol describes selection from affibody libraries by Escherichia coli cell surface display. With this method, high-diversity libraries of 1011 can be displayed on the cell surface. The method involves two steps for selection of binders from high-diversity libraries: magnetic-activated cell sorting (MACS) and fluorescence-activated cell sorting (FACS). MACS is used first to enrich the library in target-binding clones and to decrease diversity to a size that can be effectively screened and sorted in the flow cytometer in a reasonable time (typically <107 cells). The protocol is based on methodology using an AIDA-I autotransporter for display on the outer membrane, but the general procedures can also be adjusted and used for other types of autotransporters or alternative E. coli display methods. Full Article
a c The Changing Role of a Chair and DA: Follow-Up from the 2023 ADFM Annual Conference Session [Family Medicine Updates] By www.annfammed.org Published On :: 2024-09-23T14:00:14-07:00 Full Article
a c Face-to-Face Relationships Still Matter in a Digital Age: A Call for a 5th C in the Core Tenets of Primary Care [Reflections] By www.annfammed.org Published On :: 2024-09-23T14:00:14-07:00 We primary care clinicians, scholars, and leaders ascribe value to Barbara Starfield’s core tenets of primary care—the 4 Cs: first contact, comprehensiveness, coordination, and continuity. In today’s era of rapid technological advancements and dwindling resources, what are the implications for face-to-face interactions of patient-clinician relationships? We propose adding a 5th C: "Contiguity." Contiguity—or physical proximity and presence—is a key dimension that not only enables the necessary technical aspects of a physical exam but also authenticates the most human aspects of a relationship and occurs specifically when we are physically vulnerable and responsible for the other before us. This, in turn, may best enable us to bridge difference and nurture trust with our patients. We measure what we value and, thus, naming Contiguity as a core tenet assures that we will not lose sight of this keystone in a patient’s relationship with their personal physician. Full Article
a c Family Medicine Resident Scholarly Activity Infrastructure, Output, and Dissemination: A CERA Survey [Original Research] By www.annfammed.org Published On :: 2024-09-23T14:00:14-07:00 PURPOSE Meeting scholarly activity requirements continues to be a challenge in many family medicine (FM) residency programs. Studies comprehensively describing FM resident scholarship have been limited. We sought to identify institutional factors associated with increased scholarly output and meeting requirements of the Accreditation Council for Graduate Medical Education (ACGME). OBJECTIVES Our goals were to: (1) describe scholarly activity experiences among FM residents compared with ACGME requirements; (2) classify experiences by Boyer’s domains of scholarship; and (3) associate experiences with residency program characteristics and scholarly activity infrastructure. METHODS This was a cross-sectional survey. The survey questions were part of an omnibus survey to FM residency program directors conducted by the Council of Academic Family Medicine Educational Research Alliance (CERA). All ACGME-accredited US FM residency program directors, identified by the Association of Family Medicine Residency Directors, were sampled. RESULTS Of the 691 eligible program directors, 298 (43%) completed the survey. The respondents reported that 25% or more residents exceeded ACGME minimum output, 17% reported that 25% or more residents published their work, and 50% reported that 25% or more residents delivered conference presentations. Programs exceeding ACGME scholarship requirements exhibit robust infrastructure characterized by access to faculty mentorship, scholarly activity curricula, Institutional Review Board, medical librarian, and statistician. CONCLUSIONS These findings suggest the need for codified ACGME requirements for scholarly activity infrastructure to ensure access to resources in FM residency programs. By fostering FM resident engagement in scholarly activity, programs help to create a culture of inquiry, and address discrepancies in funding and output among FM residency programs. Full Article
a c A Cluster-Randomized Study of Technology-Assisted Health Coaching for Weight Management in Primary Care [Original Research] By www.annfammed.org Published On :: 2024-09-23T14:00:14-07:00 PURPOSE We undertook a trial to test the efficacy of a technology-assisted health coaching intervention for weight management, called Goals for Eating and Moving (GEM), within primary care. METHODS This cluster-randomized controlled trial enrolled 19 primary care teams with 63 clinicians; 9 teams were randomized to GEM and 10 to enhanced usual care (EUC). The GEM intervention included 1 in-person and up to 12 telephone-delivered coaching sessions. Coaches supported goal setting and engagement with weight management programs, facilitated by a software tool. Patients in the EUC arm received educational handouts. We enrolled patients who spoke English or Spanish, were aged 18 to 69 years, and either were overweight (body mass index 25-29 kg/m2) with a weight-related comorbidity or had obesity (body mass index ≥30 kg/m2). The primary outcome (weight change at 12 months) and exploratory outcomes (eg, program attendance, diet, physical activity) were analyzed according to intention to treat. RESULTS We enrolled 489 patients (220 in the GEM arm, 269 in the EUC arm). Their mean (SD) age was 49.8 (12.1) years; 44% were male, 41% Hispanic, and 44% non-Hispanic Black. At 12 months, the mean adjusted weight change (standard error) was –1.4 (0.8) kg in the GEM arm vs –0.8 (1.6) kg in the EUC arm, a nonsignificant difference (P = .48). There were no statistically significant differences in secondary outcomes. Exploratory analyses showed that the GEM arm had a greater change than the EUC arm in mean number of weekly minutes of moderate to vigorous physical activity other than walking, a finding that may warrant further exploration. CONCLUSIONS The GEM intervention did not achieve clinically important weight loss in primary care. Although this was a negative study possibly affected by health system resource limitations and disruptions, its findings can guide the development of similar interventions. Future studies could explore the efficacy of higher-intensity interventions and interventions that include medication and bariatric surgery options, in addition to lifestyle modification. Full Article
a c First-of-Its-Kind Glowing Sea Creature Discovered in Ocean’s ‘Midnight Zone’ By gizmodo.com Published On :: Tue, 12 Nov 2024 17:00:20 +0000 A nudibranch from the midnight zone has fingers on its tail, collects food with a hood, and glows. Full Article Biology Animals DEEP SEA oceans slugs
a c You Have Less Than a Week to File a Claim for Cash App’s $2,500 Payouts By gizmodo.com Published On :: Tue, 12 Nov 2024 17:03:40 +0000 The deadline to claim part of the $15 million Cash App settlement is November 18. Here's what to know. Full Article Privacy and Security
a c Take Back Alberta completes take over of UCP board By rabble.ca Published On :: Mon, 06 Nov 2023 14:54:36 +0000 David Parker, TBA’s founder, chief ideologist and chief executive, tweeted “Veni, vedi, vici” last night. Just remember, Caesar said it first, and it sounded like “Weenie, Weedy, Weakie.” The post Take Back Alberta completes take over of UCP board appeared first on rabble.ca. Full Article Canadian Politics Alberta politics
a c Joanna Cherry says SNP rules won't stop Flynn 'double-jobbing' By www.heraldscotland.com Published On :: Tue, 12 Nov 2024 12:02:00 +0000 Former MP Joanna Cherry has said that the SNP rules which prevented her from standing for a seat at Holyrood would not block Stephen Flynn from doing the same. Full Article
a c RPG Cast – Episode 563: “Isn’t Compile Heart Jail Against the Geneva Convention?” By rpgamer.com Published On :: Sat, 14 Nov 2020 21:10:24 +0000 We can't believe we have to say this, but this week Chris tries to understand water vapor. Anna Marie takes a week off to go date some demons. Josh frequents a sex shop to pick up some weapons. Pascal starts vaping in his Xbox. And Robert and Kelley are testing the jiggle physics of sacks in World of Warcraft. The post RPG Cast – Episode 563: “Isn’t Compile Heart Jail Against the Geneva Convention?” appeared first on RPGamer. Full Article News Podcasts RPG Cast Disgaea 1 Complete Ghost of a Tale The Legend of Heroes: Trails of Cold Steel IV World of Warcraft: Battle for Azeroth Yakuza: Like a Dragon
a c RPG Cast – Episode 572: “Partly Cloudy Souls With a Chance of Roguelike” By rpgamer.com Published On :: Sat, 06 Feb 2021 22:55:03 +0000 Josh is having an Ys-y time. Anna Marie ranks all the slime families. Robert gets notified every time google kills a product. And Chris tells everyone to blink on cue. The post RPG Cast – Episode 572: “Partly Cloudy Souls With a Chance of Roguelike” appeared first on RPGamer. Full Article News Podcasts RPG Cast Children of Zodiarcs Dragon Quest Tact Final Fantasy Brave Exvius Giraffe and Annika Hyrule Warriors: Age of Calamity Suikoden V The Legend of Heroes: Trails of Cold Steel IV Ys IX
a c RPG Cast – Episode 584: “A Crater Sized Hole Filled with Funko Pops!” By rpgamer.com Published On :: Sun, 09 May 2021 00:15:28 +0000 Anna Marie wonders why we can't be friends. Jonathan becomes a Marbula One fan. Kelley engages "pants off, games on" mode. And Chris learns that the only person he's cheating is himself...and his dire gryphon. The post RPG Cast – Episode 584: “A Crater Sized Hole Filled with Funko Pops!” appeared first on RPGamer. Full Article News Podcasts RPG Cast Darkest Dungeon Fire Emblem: Three Houses Monster Hunter Rise Pokémon Snap World of Warcraft: The Burning Crusade Yakuza: Like a Dragon
a c RPG Cast – Episode 596: “I’m Not Into Tails Unless I’m Shooting Them Out of a Cannon” By rpgamer.com Published On :: Sat, 14 Aug 2021 17:44:45 +0000 Josh wishes on a monkey paw and gets a new Shining Force game. Chris's body isn't ready for Death's Door. And no expects the shadow drop of Boyfriend Dungeon. The post RPG Cast – Episode 596: “I’m Not Into Tails Unless I’m Shooting Them Out of a Cannon” appeared first on RPGamer. Full Article News Podcasts RPG Cast Disgaea 6 Fuga: Melodies of Steel
a c RPG Cast – Episode 599: “Serious Health Issues? No, Just a Cat” By rpgamer.com Published On :: Sat, 04 Sep 2021 18:37:30 +0000 The podcast trio is not at all ready for the flood of September releases. Anna Marie is kind of sick of the trigger, Chris insists Eclipse is owed an apology, and Kelley wants to know what is this garbage and how she can get more of it. The post RPG Cast – Episode 599: “Serious Health Issues? No, Just a Cat” appeared first on RPGamer. Full Article News Podcasts RPG Cast Hades Kitaria Fables NEO: The World Ends with You Quartet Shin Megami Tensei III: Nocturne Soul Nomad & the World Eaters
a c RPG Cast – Episode 619: “That One Time I Got Reincarnated as a Canadian Yankee in King Arthur’s Court” By rpgamer.com Published On :: Sat, 19 Feb 2022 19:40:58 +0000 Kelley graduates from Canada. Josh discovers Tactics Advance is an isekai. Meanwhile Chris calculates the skill check for suplexing a train. The post RPG Cast – Episode 619: “That One Time I Got Reincarnated as a Canadian Yankee in King Arthur’s Court” appeared first on RPGamer. Full Article News Podcasts RPG Cast Final Fantasy XIV: Endwalker Horizon Forbidden West Pokémon Legends Arceus
a c RPG Cast – Episode 739: “It’s a Cat Union” By rpgamer.com Published On :: Sat, 07 Sep 2024 22:24:23 +0000 Chris's lamp wasn't lamping. Kelley complains about alchemy themed high heels. Phil just shoots arrows. The post RPG Cast – Episode 739: “It’s a Cat Union” appeared first on RPGamer. Full Article News Podcasts RPG Cast Avengers Castlevania: Dawn of Sorrow World of Warcraft: The War Within
a c Thysiastery is an anime Legend Of Grimrock, and you can attack the dinosaur merchants if you’re a complete monster By www.rockpapershotgun.com Published On :: Mon, 04 Nov 2024 09:14:28 +0000 One of my lesser quality tests for an RPG is whether the shopkeepers complain at you for not buying anything. Grumpy shopkeepers, good RPG. This most specific of litmus tests has served me well, although I must admit that I’d happily upgrade it to ‘shopkeepers you can attack’, would that not disqualify 99% of games. But not turn based dungeon crawler Thysiastery, it turns out. This “dungeon crawler RPG featuring traditional roguelike and turn-based gameplay” apparently trusts you enough to let you recklessly batter its friendly wandering lizard merchants. You’d be a monster for it, of course, but it’s nice to have options. Read more Full Article RPG: Turn-based THYSIASTERY PC Indiescovery
a c No, you're not imagining Monster Hunter Wilds' beta combat feeling off - there's a good reason for it By www.rockpapershotgun.com Published On :: Mon, 04 Nov 2024 10:42:27 +0000 I didn’t get much further in the extremely popular beta for the haute-couture-asaurus action of Monster Hunter Wilds than perfecting the exact orange-to-white ratio of my cat. Not because I wasn’t having fun, but because I immediately started looking up GPU prices after playing for ten minutes. As such, I didn’t spend enough time with the combat to get a proper feel for it. Cultural osmosis has once again allowed me to form an uneducated take, however, and I’m getting the sense there’s been some mixed reactions re: bonk quality. According to a clip shared on X by user Blue Stigma, there's a good reason for those misgivings. It's all about frames, you see. Read more Full Article Third person Monster Hunter Wilds RPG Single Player Hack & Slash Capcom
a c Halo's most disgusting enemy was partly inspired by a children's book By www.rockpapershotgun.com Published On :: Mon, 11 Nov 2024 13:18:45 +0000 It was the 20-year anniversary of Halo 2 at the weekend, which saw the shooter's modern counterparts celebrating with classic multiplayer maps and long-lost levels. But also emerging from the dust of time are insights to the sequel's development back in 2004. Rolling Stone interviewed two key designers of the game and made a fun discovery. The Flood (the sickly pale alien infestation that briefly turns Halo into sci-fi horror) was partly inspired by a colourful and innocent children's book about a nice elephant. Read more Full Article 343 Industries Third person Microsoft Xbox Series X/S Action Adventure Single Player Xbox One Halo Infinite Science Fiction Halo: The Master Chief Collection Xbox Multiplayer Competitive Multiplayer Cooperative PC Microsoft Studios Shooter: First Person Blockbuster First person Xbox Game Studios Bungie Shooter Halo 2
a c Grand Theft Auto: The Definitive Edition trilogy on PC gets a classic lighting update from the mobile version By www.rockpapershotgun.com Published On :: Tue, 12 Nov 2024 13:44:27 +0000 My strongest and most enduring memory of Grand Theft Auto will always be creasing into complete hysterics watching my mate pile into a crumpled police officer with a wooden baseball bat in GTA 3 after school one time. Young’uns these days just don’t appreciate how revolutionary it was to be able to hit a cop with a thing after he’d already fallen over. Suffice it to say I’ve got good memories of the open world series’ nascent forays into 3D, though never enough to tempt me into revisiting them, especially given the poor reception to Grand Theft Auto: The Trilogy - The Definitive Edition. I can sympathise. I’m annoyed just having to type a semicolon and a dash in the same game name. If you’re in a similarly non-fussed position (I will never not be annoyed that ‘nonplussed’ doesn’t mean what it sounds like it should mean) I can’t imagine a lighting update that’s been available on the mobile versions for a while is enough to tempt you back. But what is a reporter's job if not pathetically treading water between chunklets of Grand Theft Auto news, upon the publishing of which Graham presses the button to release the nutritious pellets on which we all wholly subsist? I hope he doesn’t read that last sentence. I don’t get my pellet if the syntax becomes too convoluted. Moving swiftly on. Read more Full Article iOS Android Grand Theft Auto: The Trilogy - The Definitive Edition Nintendo Switch Rockstar Games Third person PS5 PC Simulation RPG Shooter Action Adventure Xbox Series X/S Single Player Xbox One Racing PS4
a c A black hole devouring a giant star gives clues to a cosmic mystery By www.newscientist.com Published On :: Fri, 09 Aug 2024 18:12:24 +0100 In the centre of a distant galaxy, a supermassive black hole has swallowed up a star 9 times the sun’s mass in the biggest and brightest such cosmic meal we’ve ever seen Full Article
a c Earth may be about to pass through the ion tail of a comet By www.newscientist.com Published On :: Thu, 10 Oct 2024 13:46:16 +0100 The ion tail of C/2023 A3 (Tsuchinshan-ATLAS) could appear as a blue streak across the northern hemisphere sky during October, in a rare event thought to happen only every few decades Full Article
a c Social media companies change their policies in the wake of bad press By www.newscientist.com Published On :: Fri, 26 Jul 2024 18:00:55 +0100 Between 2005 and 2021, Facebook, Twitter and YouTube were more likely to make policy changes in the weeks after negative stories in the media Full Article