ant FDA OKs New Antibacterial Drug By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: FDA OKs New Antibacterial DrugCategory: Health NewsCreated: 8/31/2017 12:00:00 AMLast Editorial Review: 8/31/2017 12:00:00 AM Full Article
ant Antibiotic Vabomere Approved By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Antibiotic Vabomere ApprovedCategory: Health NewsCreated: 8/30/2017 12:00:00 AMLast Editorial Review: 8/31/2017 12:00:00 AM Full Article
ant Health Tip: Food Safety for Pregnant and Nursing Mothers By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Health Tip: Food Safety for Pregnant and Nursing MothersCategory: Health NewsCreated: 8/27/2018 12:00:00 AMLast Editorial Review: 8/27/2018 12:00:00 AM Full Article
ant Alarming Rise in Antibiotic-Resistant UTIs in U.S.: Study By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Alarming Rise in Antibiotic-Resistant UTIs in U.S.: StudyCategory: Health NewsCreated: 8/28/2018 12:00:00 AMLast Editorial Review: 8/29/2018 12:00:00 AM Full Article
ant Brain Implant Puts the Brakes on Epileptic Seizures in Mice By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Brain Implant Puts the Brakes on Epileptic Seizures in MiceCategory: Health NewsCreated: 8/30/2018 12:00:00 AMLast Editorial Review: 8/31/2018 12:00:00 AM Full Article
ant Get Cooking With Elegant, Flavorful Scallops By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Get Cooking With Elegant, Flavorful ScallopsCategory: Health NewsCreated: 8/26/2019 12:00:00 AMLast Editorial Review: 8/26/2019 12:00:00 AM Full Article
ant Every Sudden Infant Death Deserves a Closer Look: Report By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Every Sudden Infant Death Deserves a Closer Look: ReportCategory: Health NewsCreated: 8/26/2019 12:00:00 AMLast Editorial Review: 8/27/2019 12:00:00 AM Full Article
ant Even a Little Drinking While Pregnant Ups Miscarriage Odds: Study By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Even a Little Drinking While Pregnant Ups Miscarriage Odds: StudyCategory: Health NewsCreated: 8/27/2019 12:00:00 AMLast Editorial Review: 8/28/2019 12:00:00 AM Full Article
ant Thousands of Kidneys Thrown Away by U.S. Transplant Centers By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Thousands of Kidneys Thrown Away by U.S. Transplant CentersCategory: Health NewsCreated: 8/27/2019 12:00:00 AMLast Editorial Review: 8/28/2019 12:00:00 AM Full Article
ant Mumps Outbreaks Hitting U.S. Migrant Detention Centers By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Mumps Outbreaks Hitting U.S. Migrant Detention CentersCategory: Health NewsCreated: 8/29/2019 12:00:00 AMLast Editorial Review: 8/30/2019 12:00:00 AM Full Article
ant How to Keep Your Kids Trim Through Quarantine By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: How to Keep Your Kids Trim Through QuarantineCategory: Health NewsCreated: 8/25/2020 12:00:00 AMLast Editorial Review: 8/26/2020 12:00:00 AM Full Article
ant Longer, Worse COVID Leaves Stronger Antibodies: Study By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Longer, Worse COVID Leaves Stronger Antibodies: StudyCategory: Health NewsCreated: 8/23/2021 12:00:00 AMLast Editorial Review: 8/23/2021 12:00:00 AM Full Article
ant Want That Healthy Skin Glow? These Foods Can Get You There By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Want That Healthy Skin Glow? These Foods Can Get You ThereCategory: Health NewsCreated: 8/21/2021 12:00:00 AMLast Editorial Review: 8/23/2021 12:00:00 AM Full Article
ant Delta Variant Has Americans' Stress Levels Rising Again: Poll By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Delta Variant Has Americans' Stress Levels Rising Again: PollCategory: Health NewsCreated: 8/20/2021 12:00:00 AMLast Editorial Review: 8/23/2021 12:00:00 AM Full Article
ant U.S. Kidney Transplant Outcomes Are Improving By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: U.S. Kidney Transplant Outcomes Are ImprovingCategory: Health NewsCreated: 8/24/2021 12:00:00 AMLast Editorial Review: 8/24/2021 12:00:00 AM Full Article
ant 'Dream Vaccine' for All COVID Variants By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: 'Dream Vaccine' for All COVID VariantsCategory: Health NewsCreated: 8/23/2021 12:00:00 AMLast Editorial Review: 8/24/2021 12:00:00 AM Full Article
ant For Better Breastfeeding, 'Lactation Consultants' Can Help By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: For Better Breastfeeding, 'Lactation Consultants' Can HelpCategory: Health NewsCreated: 8/25/2021 12:00:00 AMLast Editorial Review: 8/25/2021 12:00:00 AM Full Article
ant Smart Phones, Watches Can Mess With Implanted Pacemakers By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Smart Phones, Watches Can Mess With Implanted PacemakersCategory: Health NewsCreated: 8/26/2021 12:00:00 AMLast Editorial Review: 8/26/2021 12:00:00 AM Full Article
ant Fratelli Beretta Antipasto Trays Are the Source of Salmonella Outbreak: CDC By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Fratelli Beretta Antipasto Trays Are the Source of Salmonella Outbreak: CDCCategory: Health NewsCreated: 8/27/2021 12:00:00 AMLast Editorial Review: 8/27/2021 12:00:00 AM Full Article
ant Are You Among the 'Diet-Resistant'? By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Are You Among the 'Diet-Resistant'?Category: Health NewsCreated: 8/22/2022 12:00:00 AMLast Editorial Review: 8/22/2022 12:00:00 AM Full Article
ant Dr. Anthony Fauci Will Step Down in December By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Dr. Anthony Fauci Will Step Down in DecemberCategory: Health NewsCreated: 8/22/2022 12:00:00 AMLast Editorial Review: 8/23/2022 12:00:00 AM Full Article
ant COVID Incubation Shorter With Each New Variant By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: COVID Incubation Shorter With Each New VariantCategory: Health NewsCreated: 8/23/2022 12:00:00 AMLast Editorial Review: 8/23/2022 12:00:00 AM Full Article
ant 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
ant Another Study Shows COVID's Danger to Pregnant Women By www.medicinenet.com Published On :: Thu, 11 Aug 2022 00:00:00 PDT Title: Another Study Shows COVID's Danger to Pregnant WomenCategory: Health NewsCreated: 8/11/2022 12:00:00 AMLast Editorial Review: 8/11/2022 12:00:00 AM Full Article
ant COVID Vaccine Safe for Pregnant Women: Study By www.medicinenet.com Published On :: Mon, 15 Aug 2022 00:00:00 PDT Title: COVID Vaccine Safe for Pregnant Women: StudyCategory: Health NewsCreated: 8/15/2022 12:00:00 AMLast Editorial Review: 8/15/2022 12:00:00 AM Full Article
ant Here Are the Top 15 Anti-Inflammatory Foods for Your Diet To Reduce Inflammation By www.medicinenet.com Published On :: Fri, 26 Aug 2022 00:00:00 PDT Title: Here Are the Top 15 Anti-Inflammatory Foods for Your Diet To Reduce InflammationCategory: Health and LivingCreated: 8/26/2022 12:00:00 AMLast Editorial Review: 8/26/2022 12:00:00 AM Full Article
ant Are Plant Sterols Good for Lowering Cholesterol? By www.medicinenet.com Published On :: Thu, 12 May 2022 00:00:00 PDT Title: Are Plant Sterols Good for Lowering Cholesterol?Category: Diseases and ConditionsCreated: 5/12/2022 12:00:00 AMLast Editorial Review: 5/12/2022 12:00:00 AM Full Article
ant Many Who Need Opioid OD Antidote the Most Can't Afford It By www.medicinenet.com Published On :: Mon, 22 Aug 2022 00:00:00 PDT Title: Many Who Need Opioid OD Antidote the Most Can't Afford ItCategory: Health NewsCreated: 8/22/2022 12:00:00 AMLast Editorial Review: 8/22/2022 12:00:00 AM Full Article
ant Fecal Transplant Treatments Could Transmit Monkeypox, FDA Warns By www.medicinenet.com Published On :: Thu, 25 Aug 2022 00:00:00 PDT Title: Fecal Transplant Treatments Could Transmit Monkeypox, FDA WarnsCategory: Health NewsCreated: 8/24/2022 12:00:00 AMLast Editorial Review: 8/25/2022 12:00:00 AM Full Article
ant 84 People Now Sickened in E. Coli Outbreak Tied to Wendy's Restaurant Lettuce By www.medicinenet.com Published On :: Fri, 26 Aug 2022 00:00:00 PDT Title: 84 People Now Sickened in E. Coli Outbreak Tied to Wendy's Restaurant LettuceCategory: Health NewsCreated: 8/26/2022 12:00:00 AMLast Editorial Review: 8/26/2022 12:00:00 AM Full Article
ant Want to Live Longer? Exercise More, Study Confirms By www.medicinenet.com Published On :: Wed, 27 Jul 2022 00:00:00 PDT Title: Want to Live Longer? Exercise More, Study ConfirmsCategory: Health NewsCreated: 7/26/2022 12:00:00 AMLast Editorial Review: 7/27/2022 12:00:00 AM Full Article
ant Torn ACL (Anterior Cruciate Ligament Tear) By www.medicinenet.com Published On :: Mon, 15 Aug 2022 00:00:00 PDT Title: Torn ACL (Anterior Cruciate Ligament Tear)Category: Diseases and ConditionsCreated: 11/4/2010 12:00:00 AMLast Editorial Review: 8/15/2022 12:00:00 AM Full Article
ant Playing Football, Hockey in High School Ups Odds for Stimulant Abuse By www.medicinenet.com Published On :: Mon, 15 Aug 2022 00:00:00 PDT Title: Playing Football, Hockey in High School Ups Odds for Stimulant AbuseCategory: Health NewsCreated: 8/15/2022 12:00:00 AMLast Editorial Review: 8/15/2022 12:00:00 AM Full Article
ant Want to Maintain Muscle? Frequency of Workouts Is Key By www.medicinenet.com Published On :: Mon, 22 Aug 2022 00:00:00 PDT Title: Want to Maintain Muscle? Frequency of Workouts Is KeyCategory: Health NewsCreated: 8/22/2022 12:00:00 AMLast Editorial Review: 8/22/2022 12:00:00 AM Full Article
ant 9 in 10 Americans Want Their Health Info Kept Private By www.medicinenet.com Published On :: Tue, 2 Aug 2022 00:00:00 PDT Title: 9 in 10 Americans Want Their Health Info Kept PrivateCategory: Health NewsCreated: 8/2/2022 12:00:00 AMLast Editorial Review: 8/2/2022 12:00:00 AM Full Article
ant Want That Pill to Work Fast? Your Body Position Matters By www.medicinenet.com Published On :: Wed, 17 Aug 2022 00:00:00 PDT Title: Want That Pill to Work Fast? Your Body Position MattersCategory: Health NewsCreated: 8/17/2022 12:00:00 AMLast Editorial Review: 8/17/2022 12:00:00 AM Full Article
ant What Therapeutic Options Are Available for Treating an Antiretroviral Naive Patient? By www.medicinenet.com Published On :: Thu, 16 Jun 2022 00:00:00 PDT Title: What Therapeutic Options Are Available for Treating an Antiretroviral Naive Patient?Category: Diseases and ConditionsCreated: 6/16/2022 12:00:00 AMLast Editorial Review: 6/16/2022 12:00:00 AM Full Article
ant nitrofurantoin By www.medicinenet.com Published On :: Sat, 20 Aug 2022 00:00:00 PDT Title: nitrofurantoinCategory: MedicationsCreated: 3/26/1998 12:00:00 AMLast Editorial Review: 8/20/2022 12:00:00 AM Full Article
ant GERD (Acid Reflux) in Infants and Children By www.medicinenet.com Published On :: Thu, 18 Aug 2022 00:00:00 PDT Title: GERD (Acid Reflux) in Infants and ChildrenCategory: Diseases and ConditionsCreated: 1/31/2005 12:00:00 AMLast Editorial Review: 8/18/2022 12:00:00 AM Full Article
ant 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
ant Antibody-mediated protection against respiratory syncytial virus in children By err.ersjournals.com Published On :: 2024-10-09T00:15:15-07:00 Respiratory syncytial virus (RSV) is a major global pathogen, causing lower respiratory tract disease in at-risk populations including young children. Antibodies form a crucial layer of protection from RSV disease, particularly in immunologically naïve infants. Such antibodies are derived from the mother via transplacental transfer and breast milk, but may be particularly low in high-risk infants such as those born preterm. Maternally derived antibodies can now be supplemented by the administration of anti-RSV monoclonal antibodies, while a rising wave of maternal and paediatric vaccine strategies are approaching. The implementation of these prophylactics may profoundly decrease the healthcare burden of RSV. In this article, we review the role of antibody-mediated immunity in protecting children from RSV. We focus on maternally derived antibodies as the main source of protection against RSV and study factors that influence the scale of this transfer. The role of passive and active prophylactic approaches in protecting infants against RSV are discussed and knowledge gaps in our understanding of antibody-mediated protection against RSV are identified. Full Article
ant Mutational scanning of CRX classifies clinical variants and reveals biochemical properties of the transcriptional effector domain [RESEARCH] By genome.cshlp.org Published On :: 2024-10-29T06:46:07-07:00 The transcription factor (TF) cone-rod homeobox (CRX) is essential for the differentiation and maintenance of photoreceptor cell identity. Several human CRX variants cause degenerative retinopathies, but most are variants of uncertain significance. We performed a deep mutational scan (DMS) of nearly all possible single amino acid substitutions in CRX using a cell-based transcriptional reporter assay, curating a high-confidence list of nearly 2000 variants with altered transcriptional activity. In the structured homeodomain, activity scores closely aligned to a predicted structure and demonstrated position-specific constraints on amino acid substitution. In contrast, the intrinsically disordered transcriptional effector domain displayed a qualitatively different pattern of substitution effects, following compositional constraints without specific residue position requirements in the peptide chain. These compositional constraints were consistent with the acidic exposure model of transcriptional activation. We evaluated the performance of the DMS assay as a clinical variant classification tool using gold-standard classified human variants from ClinVar, identifying pathogenic variants with high specificity and moderate sensitivity. That this performance could be achieved using a synthetic reporter assay in a foreign cell type, even for a highly cell type-specific TF like CRX, suggests that this approach shows promise for DMS of other TFs that function in cell types that are not easily accessible. Together, the results of the CRX DMS identify molecular features of the CRX effector domain and demonstrate utility for integration into the clinical variant classification pipeline. Full Article
ant 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
ant Quantitative Computed Tomography and Response to Pronation in COVID-19 ARDS By rc.rcjournal.com Published On :: 2024-10-25T05:44:12-07:00 BACKGROUND:The use of prone position (PP) has been widespread during the COVID-19 pandemic. Whereas it has demonstrated benefits, including improved oxygenation and lung aeration, the factors influencing the response in terms of gas exchange to PP remain unclear. In particular, the association between baseline quantitative computed tomography (CT) scan results and gas exchange response to PP in invasively ventilated subjects with COVID-19 ARDS is unknown. The present study aimed to compare baseline quantitative CT results between subjects responding to PP in terms of oxygenation or CO2 clearance and those who did not.METHODS:This was a single-center, retrospective observational study including critically ill, invasively ventilated subjects with COVID-19–related ARDS admitted to the ICUs of Niguarda Hospital between March 2020–November 2021. Blood gas samples were collected before and after PP. Subjects in whom the PaO2/FIO2 increase was ≥ 20 mm Hg after PP were defined as oxygen responders. CO2 responders were defined when the ventilatory ratio (VR) decreased during PP. Automated quantitative CT analyses were performed to obtain tissue mass and density of the lungs.RESULTS:One hundred twenty-five subjects were enrolled, of which 116 (93%) were O2 responders and 51 (41%) CO2 responders. No difference in quantitative CT characteristics and oxygen were observed between responders and non-responders (tissue mass 1,532 ± 396 g vs 1,654 ± 304 g, P = .28; density −544 ± 109 HU vs −562 ± 58 HU P = .42). Similar findings were observed when dividing the population according to CO2 response (tissue mass 1,551 ± 412 g vs 1,534 ± 377 g, P = .89; density −545 ± 123 HU vs −546 ± 94 HU, P = .99).CONCLUSIONS:Most subjects with COVID-19–related ARDS improved their oxygenation at the first pronation cycle. The study suggests that baseline quantitative CT scan data were not associated with the response to PP in oxygenation or CO2 in mechanically ventilated subjects with COVID-19–related ARDS. Full Article
ant 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
ant Abolished frameshifting for predicted structure-stabilizing SARS-CoV-2 mutants: implications to alternative conformations and their statistical structural analyses [ARTICLE] By rnajournal.cshlp.org Published On :: 2024-10-16T07:18:13-07:00 The SARS-CoV-2 frameshifting element (FSE) has been intensely studied and explored as a therapeutic target for coronavirus diseases, including COVID-19. Besides the intriguing virology, this small RNA is known to adopt many length-dependent conformations, as verified by multiple experimental and computational approaches. However, the role these alternative conformations play in the frameshifting mechanism and how to quantify this structural abundance has been an ongoing challenge. Here, we show by DMS and dual-luciferase functional assays that previously predicted FSE mutants (using the RAG graph theory approach) suppress structural transitions and abolish frameshifting. Furthermore, correlated mutation analysis of DMS data by three programs (DREEM, DRACO, and DANCE-MaP) reveals important differences in their estimation of specific RNA conformations, suggesting caution in the interpretation of such complex conformational landscapes. Overall, the abolished frameshifting in three different mutants confirms that all alternative conformations play a role in the pathways of ribosomal transition. Full Article
ant The treatment of latent tuberculosis infection in migrants in primary care versus secondary care By erj.ersjournals.com Published On :: 2024-11-07T00:35:56-08:00 Extract With a disproportionate burden of tuberculosis (TB) amongst migrants in Europe [1], Burman et al. [2] have highlighted the pressing need for alternative approaches to make TB infection (TBI) screening comprehensive and accessible. Across high-income Organisation for Economic Co-operation and development countries, a median of 52% of TB cases occur in foreign-born individuals, who are at their highest risk of developing TB disease within the first 5 years of migration [3]. Molecular epidemiological studies indicate that the majority of these cases occur as a result of TBI reactivation, often acquired overseas [4]. Within the UK, overseas-born migrants have a 14-fold higher TB incidence than UK-born individuals [5]. The World Health Organization therefore recommends that migrants from countries with a high TB burden may be prioritised for TBI screening [6, 7]. Full Article
ant Treatment of latent tuberculosis infection in migrants in primary care versus secondary care By erj.ersjournals.com Published On :: 2024-11-07T00:35:55-08:00 Background Control of latent tuberculosis infection (LTBI) is a priority in the World Health Organization strategy to eliminate TB. Many high-income, low TB incidence countries have prioritised LTBI screening and treatment in recent migrants. We tested whether a novel model of care, based entirely within primary care, was effective and safe compared to secondary care. Methods This was a pragmatic cluster-randomised, parallel group, superiority trial (ClinicalTrials.gov: NCT03069807) conducted in 34 general practices in London, UK, comparing LTBI treatment in recent migrants in primary care to secondary care. The primary outcome was treatment completion, defined as taking ≥90% of antibiotic doses. Secondary outcomes included treatment acceptance, adherence, adverse effects, patient satisfaction, TB incidence and a cost-effectiveness analysis. Analyses were performed on an intention-to-treat basis. Results Between September 2016 and May 2019, 362 recent migrants with LTBI were offered treatment and 276 accepted. Treatment completion was similar in primary and secondary care (82.6% versus 86.0%; adjusted OR (aOR) 0.64, 95% CI 0.31–1.29). There was no difference in drug-induced liver injury between primary and secondary care (0.7% versus 2.3%; aOR 0.29, 95% CI 0.03–2.84). Treatment acceptance was lower in primary care (65.2% (146/224) versus 94.2% (130/138); aOR 0.10, 95% CI 0.03–0.30). The estimated cost per patient completing treatment was lower in primary care, with an incremental saving of GBP 315.27 (95% CI 313.47–317.07). Conclusions The treatment of LTBI in recent migrants within primary care does not result in higher rates of treatment completion but is safe and costs less when compared to secondary care. Full Article
ant Functional Characterization of Reduced Folate Carrier and Protein-Coupled Folate Transporter for Antifolates Accumulation in Non-Small Cell Lung Cancer Cells [Articles] By dmd.aspetjournals.org Published On :: 2024-10-16T09:02:03-07:00 Antifolates are important for chemotherapy in non–small cell lung cancer (NSCLC). They mainly rely on reduced folate carrier (RFC) and proton-coupled folate transporter (PCFT) to enter cells. PCFT is supposed to be the dominant transporter of the two in tumors, as it operates optimally at acidic pH and has limited transport activity at physiological pH, whereas RFC operates optimally at neutral pH. In this study, we found RFC showed a slightly pH-dependent uptake of antifolates, with similar affinity values at pH 7.4 and 6.5. PCFT showed a highly pH-dependent uptake of antifolates, with an optimum pH of 6.0 for pemetrexed and 5.5 for methotrexate. The Michaelis-Menten constant (Km) value of PCFT for pemetrexed at pH 7.4 was more than 10 times higher than that at pH 6.5. Interestingly, we found that antifolate accumulations mediated by PCFT at acidic pH were significantly affected by the efflux transporter, breast cancer resistance protein (BCRP). The highest pemetrexed concentration was observed at pH 7.0–7.4 after a 60-minute accumulation in PCFT-expressing cells, which was further evidenced by the cytotoxicity of pemetrexed, with the IC50 value of pemetrexed at pH 7.4 being one-third of that at pH 6.5. In addition, the in vivo study indicated that increasing PCFT and RFC expression significantly enhanced the antitumor efficacy of pemetrexed despite the high expression of BCRP. These results suggest that both RFC and PCFT are important for antifolates accumulation in NSCLC, although there is an acidic microenvironment and high BCRP expression in tumors. SIGNIFICANCE STATEMENT Evaluating the role of reduced folate carrier (RFC) and proton-coupled folate transporter (PCFT) on antifolates accumulation in non–small cell lung cancer (NSCLC) is necessary for new drug designs. By using cell models, we found both RFC and PCFT were important for antifolates accumulation in NSCLC. Breast cancer resistance protein (BCRP) significantly affected PCFT-mediated antifolates accumulation at acidic pH but not RFC-mediated pemetrexed accumulation at physiological pH. High expression of PCFT or RFC enhanced the cytotoxicity and antitumor effect of pemetrexed. Full Article
ant Investigations into the Concentrations and Metabolite Profiles of Doping Agents and Antidepressants in Human Seminal Fluid Using Liquid Chromatography-Mass Spectrometry [Articles] By dmd.aspetjournals.org Published On :: 2024-10-16T09:02:03-07:00 Exogenous substances, including drugs and chemicals, can transfer into human seminal fluid and influence male fertility and reproduction. In addition, substances relevant in the context of sports drug testing programs, can be transferred into the urine of a female athlete (after unprotected sexual intercourse) and trigger a so-called adverse analytical finding. Here, the question arises as to whether it is possible to distinguish analytically between intentional doping offenses and unintentional contamination of urine by seminal fluid. To this end, 480 seminal fluids from nonathletes were analyzed to identify concentration ranges and metabolite profiles of therapeutic drugs that are also classified as doping agents. Therefore, a screening procedure was developed using liquid chromatography connected to a triple quadrupole mass spectrometer, and suspect samples (i.e., samples indicating the presence of relevant compounds) were further subjected to liquid chromatography-high-resolution accurate mass (tandem) mass spectrometry. The screening method yielded 90 findings (including aromatase inhibitors, selective estrogen receptor modulators, diuretics, stimulants, glucocorticoids, beta-blockers, antidepressants, and the nonapproved proliferator-activated receptor delta agonist GW1516) in a total of 81 samples, with 91% of these suspected cases being verified by the confirmation method. In addition to the intact drug, phase-I and -II metabolites were also occasionally observed in the seminal fluid. This study demonstrated that various drugs including those categorized as doping agents partition into seminal fluid. Monitoring substances and metabolites may contribute to a better understanding of the distribution and metabolism of exogenous substances in seminal fluid that may be responsible for the impairment of male fertility. SIGNIFICANCE STATEMENT This study demonstrates that doping agents as well as clinically relevant substances are transferred/eliminated into seminal fluid to a substantial extent and that knowledge about drug levels (and potential consequences for the male fertility and female exposure) is limited. The herein generated new dataset provides new insights into an important and yet little explored area of drug deposition and elimination, and hereby a basis for the assessment of contamination cases by seminal fluid in sports drug testing. Full Article