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OBJECTIVE: To identify clinical characteristics that distinguish cannabinoid hyperemesis syndrome (CHS) from cyclic vomiting syndrome (CVS), 2 conditions marked by episodes of nausea, vomiting, and abdominal pain. STUDY DESIGN: We performed a retrospective chart review of patients admitted to a large children's health care system from 2015 through 2022. Patients with CHS and CVS were identified by the electronic medical record using International Classification of Diseases, Ninth and Tenth Revision codes. RESULTS: Of 201 patients screened, 125 were included. Patients with CHS were older than those with CVS (mean [SD] 18.06 [1.41] vs 14.50 [2.91] years, P < .001). There were no significant differences in sex, race, ethnicity, or hospital length of stay between groups. Patients with CHS were more likely to have a positive urine drug screen (86% vs 2.9%, P < .001), lower mean (SD) serum potassium (3.62 [0.77] vs 3.88 [0.49], P < .001), and greater mean (SD) serum creatinine (0.83 (0.41) vs 0.63 (0.17), P < .001). The average (SD) systolic blood pressure was significantly greater in patients with CHS (systolic blood pressure 124.46 [10.66] vs 118.55 [10.99], P = .032) compared with children of comparable age range with CVS. Imaging was obtained in 36% of all patients, and only 2.4% had abnormalities. CONCLUSIONS: Clinical features including older age, greater systolic blood pressure, positive urine drug screen, and select electrolyte findings might distinguish CHS from CVS. Abdominal imaging in both conditions is of low yield. These findings may allow for early recognition and appropriate therapy in CHS patients.
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Síndrome da Hiperêmese Canabinoide , Vômito , Adolescente , Criança , Feminino , Humanos , Masculino , Síndrome da Hiperêmese Canabinoide/diagnóstico , Canabinoides/efeitos adversos , Diagnóstico Diferencial , Náusea/induzido quimicamente , Estudos Retrospectivos , Vômito/induzido quimicamente , Vômito/diagnósticoRESUMO
OBJECTIVE: Semaglutide, a glucagon-like peptide-1 receptor agonist is approved for weight loss and diabetes treatment, but limited literature exists regarding semaglutide use in patients with advanced chronic kidney disease (CKD). Therefore, this project assessed the safety and efficacy of semaglutide among patients with estimated glomerular filtration rate (eGFR) 15-29 mL/min/1.73 m2 (CKD stage 4), eGFR<15 mL/min/1.73 m2 (CKD stage 5) or on dialysis. METHODS: This is a retrospective electronic medical record based analysis of consecutive patients with advanced CKD (defined as CKD 4 or greater) who were started on semaglutide (injectable or oral). Data was collected between January 2018 and January 2023. Investigators verified CKD diagnosis and manually extracted data. Data were analyzed using Fisher's exact test, paired t test, linear mixed effects models and Wilcoxon signed rank test. RESULTS: Seventy-six patients with CKD 4 or greater who initiated semaglutide were included. Most patients had a history of type 2 diabetes mellitus (96.0%), and most were males (53.9%). The mean age was 66.8 y (SD 11.5) with the mean body mass index was 36.2 (SD 7.5). The initial doses were 3 mg orally and 0.25 mg by injection. Maximum prescribed dose was 1 mg (injectable) in 28 (45.2%) patients and 14 mg (orally) in 2 (14.2%) patients. Patients received semaglutide for a median duration of 17.4 (IQR 0.43, 48.8) months. Forty-eight (63.1%) patients reported no adverse effects associated with the therapy. Mean weight decreased from 106.2 (SD 24.2) to 101.3 (SD 27.3) kg (P < .001). Eight patients (16%) with type 2 diabetes mellitus T2DM discontinued insulin after starting semaglutide. Mean hemoglobin A1c (HbA1c) decreased from 8.0% (SD 1.7) to 7.1% (SD 1.3) (P < .001). Adverse effects were the primary reason for semaglutide discontinuation (37.0%), with nausea, vomiting, and abdominal pain being the most common complaints. CONCLUSIONS: Based on this retrospective study semaglutide appears to be tolerated by most individuals with CKD 4 or greater despite associated gastrointestinal side effects similar to those observed in patients with better kidney function and leads to an improvement of glycemic control and insulin discontinuation in patients with T2DM. Modest weight loss (approximately 4.6% of the total body weight) was observed on the prescribed doses. Larger prospective randomized studies are needed to comprehensively assess the risks and benefits of semaglutide in patients with CKD 4 or greater and obesity.
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BACKGROUND: Functional somatic symptoms (FFS) and bodily distress disorders are highly prevalent across all medical settings. Services for these patients are dispersed across the health care system with minimal conceptual and operational integration, and patients do not currently access therapeutic offers in significant numbers due to a mismatch between their and professionals' understanding of the nature of the symptoms. New service models are urgently needed to address patients' needs and to align with advances in aetiological evidence and diagnostic classification systems to overcome the body-mind dichotomy. METHOD: A panel of clinical experts from different clinical services involved in providing aspects of health care for patients with functional symptoms reviewed the current care provision. This review and the results from a focus group exploration of patients with lived experience of functional symptoms were explored by the multidisciplinary expert group, and the conclusions are summarised as recommendations for best practice. RESULTS: The mapping exercise and multidisciplinary expert consultation revealed five themes for service improvement and pathway development: time/access, communication, barrier-free care, choice and governance. Service users identified four meta-themes for best practice recommendations: focus on healthcare professional communication and listening skills as well as professional attributes and knowledge base to help patients being both believed and understood in order to accept their condition; systemic and care pathway issues such as stronger emphasis on primary care as the first point of contact for patients, resources to reduce the length of the patient journey from initial assessment to diagnosis and treatment. CONCLUSION: We propose a novel, integrated care pathway for patients with 'functional somatic disorder', which delivers care according to and working with patients' explanatory beliefs. The therapeutic model should operate based upon an understanding of the embodied nature of patient's complaints and provide flexible access points to the care pathway.
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Prestação Integrada de Cuidados de Saúde , Sintomas Inexplicáveis , Transtornos Somatoformes , Humanos , Prestação Integrada de Cuidados de Saúde/organização & administração , Transtornos Somatoformes/terapia , Transtornos Somatoformes/diagnóstico , Grupos Focais , Participação dos Interessados , FemininoRESUMO
BACKGROUND: Women with human immunodeficiency virus (HIV) are at risk of unintended pregnancy and may experience barriers to accessing contraception such as social stigma, concern for drug-drug interactions with HIV regimens, cost, and access to care. As pharmacist prescriptive authority for contraception becomes more prevalent, pharmacists may play a role in expanding access to contraception for women with HIV. Little is known about perspectives in this population regarding pharmacists prescribing contraception. OBJECTIVES: The objective of our study was to explore participants' experiences with contraception and childbearing, identify barriers to receiving contraception and unmet needs for contraceptive services, and explore perspectives on pharmacists prescribing contraception among women with HIV receiving care at a specialty HIV clinic. METHODS: This qualitative study used semistructured phone interviews with female patients receiving care at the University of New Mexico Truman Health Services in Albuquerque, New Mexico (NM). Interviews were transcribed verbatim and analyzed by 2 independent coders using Dedoose software. RESULTS: Contraception use was high in our population, with 75% of participants reporting a current contraceptive method. Among our population, participants were supportive of pharmacists prescribing contraception. Participants appreciated that pharmacies were accessible and convenient and that pharmacists are well trained and able to manage drug-drug interactions. Participants expressed a preference for pharmacists to explain all available contraceptive options and to have a thorough understanding of their medical history and medications. Participants expressed concern about privacy and disclosure of their HIV status when receiving contraception from a pharmacist. CONCLUSION: Among our population of women with HIV receiving care at a specialty clinic in NM, participants were supportive of pharmacists prescribing contraception. Pharmacists should consider the preferences of this population when prescribing contraception. Further research is warranted in additional populations of women with HIV to further explore unique perspectives among non-English speaking patients and those who do not receive care at specialty clinics.
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Anticoncepção , Infecções por HIV , Gravidez , Humanos , Feminino , Anticoncepção/métodos , Anticoncepcionais , Pesquisa Qualitativa , Prescrições de Medicamentos , Farmacêuticos , Infecções por HIV/tratamento farmacológicoRESUMO
BACKGROUND: Obesity is intricately associated with type-2 diabetes (T2D) and other cardiovascular conditions, increasing morbidity, mortality, and health care costs. Metabolic and bariatric surgeries (MBS) have shown promising results in significant weight loss and T2D remission, but existing predictive scores for post-MBS diabetes remission do not consider insulin dosage, potentially overlooking a critical factor. METHODS: A retrospective analysis of patients with T2D who underwent Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG). The study focused on insulin dosage impact, divided into quartiles, on remission rates post-MBS. The effectiveness of RYGB vs SG was compared within insulin dose quartiles with up to 5 years of follow up. RESULTS: A total of 508 patients (64% female, 94.9% White, mean age 53.5 ± 10.5 years, BMI (46.0 ± 8.3 kg/m2) were included in the analysis. This study demonstrates a profound association between insulin dosage quartiles and T2D remission after MBS. Patients with lower insulin requirements showed superior remission rates; those in the lowest quartile had remission rates of 73%, 70%, and 62% at 1, 3, and 5 years, respectively, compared to 34%, 37%, and 36% in the highest quartile (P < 0.001 across all intervals). RYGB surgery showed a significantly better remission in the second and third insulin quartiles, suggesting its effectiveness over SG for patients with mid-range insulin requirements. CONCLUSION: This study underscores the importance of considering insulin dosage when predicting T2D remission post-MBS. The findings advocate for a more nuanced selection of MBS procedures based on individual insulin profiles, potentially enhancing diabetes remission outcomes.
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BACKGROUND AND AIMS: Randomized clinical trials have proven the efficacy and safety of Food and Drug Administration (FDA) approved anti-obesity medications (AOMs) for long-term use. It is unclear whether these outcomes can be replicated in real-world clinical practice where clinical complexities arise. The aim of this study was to evaluate the effectiveness and side effects of these medications in real-world multidisciplinary clinical practice settings. METHODS: We reviewed the electronic medical records (EMR) of patients with obesity who were prescribed an FDA-approved AOM for long-term use in academic and community multidisciplinary weight loss programs between January 2016 and January 2020. INTERVENTION: We assessed percentage total body weight loss (%TBWL), metabolic outcomes, and side effect profile up to 24 months after AOM initiation. RESULTS: The full cohort consisted of 304 patients (76% women, 95.2% White, median age of 50 years old [IQR, 39-58]). The median follow-up time was 9.1 months [IQR, 4.2-14.1] with a median number of 3 visits [IQR, 2-4]. The most prescribed medication was phentermine/topiramate extended-release (ER) (51%), followed by liraglutide (26.3%), bupropion/naltrexone sustained-release (SR) (16.5%), and lorcaserin (6.2%). %TBWL was 5.0%, 6.8%, 9.3%, 10.3%, and 10.5% at 3, 6, 12, 18, and 24 months. 60.2% of the entire cohort achieved at least 5% TBWL. Overall, phentermine/topiramate-ER had the most robust weight loss response during follow-up, with the highest %TBWL at 12 months of 12.0%. Adverse events were reported in 22.4% of patients. Only 9% of patients discontinued the medication due to side effects. CONCLUSIONS: AOMs resulted in significant long-term weight loss, that was comparable to outcomes previously reported in clinical trials.
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Fármacos Antiobesidade , Fentermina , Adulto , Fármacos Antiobesidade/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/tratamento farmacológico , Fentermina/uso terapêutico , Topiramato/uso terapêutico , Redução de PesoRESUMO
Background: Modern hepatitis C virus (HCV) treatment regimens yield cure rates greater than 90%. However, obtaining approval for treatment through the prior authorization (PA) process can be time consuming and require extensive documentation. Lack of experience with this complex process can delay HCV medication approval, ultimately increasing the amount of time before patients start treatment and in some cases, prevent treatment altogether. Objectives: Assess the impact of incorporating clinical pharmacists into specialty pharmacy and hepatology clinic services on medication access, patient adherence, and outcomes in patients being treated for HCV. Methods: We performed a retrospective cohort exploratory study of patients seen in an academic medical center hepatology clinic who had HCV prescriptions filled between 8/1/15 and 7/31/17. Patients were categorized by whether they filled prescriptions prior to (Pre-Group) or after (Post-Group) the implementation of a pharmacist in clinic. The Post-Group was further divided according to whether the patient was seen by a pharmacist in clinic (Post-Group 2) or if the patient was not seen by the pharmacist, but had their HCV therapy evaluated by the pharmacist before seeking insurance approval (Post-Group 1). Results: The mean time from the prescription being ordered to being dispensed was longer in the Pre-Group (50.8 ± 66.5 days) compared to both Post-Groups (22.2 ± 27.8 days in Post-Group 1 vs 18.9 ± 17.7 days in Post-Group 2; P < .05). The mean time from when the prescription was ordered to when the PA was submitted was longer in the Pre-Group (41.6 ± 71.9 days) compared to both Post-Groups (6.3 ± 16 in Post-Group 1 vs 4.1 ± 9.7 in Post-Group 2; P < .05). Rates of medication adherence and sustained virologic response were similar between all groups. Conclusion: Incorporation of clinical pharmacists into a hepatology clinic significantly reduced the time patients waited to start HCV treatment. In addition to improving access to medications, implementation of the model helped to maintain excellent medication adherence and cure rates.
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BACKGROUND & AIMS: Obese patients with nonalcoholic steatohepatitis (NASH) are at risk for cirrhosis if significant weight loss is not achieved. The single fluid-filled intragastric balloon (IGB) induces meaningful weight loss and might be used in NASH treatment. We performed an open-label prospective study to evaluate the effects of IGB placement on metabolic and histologic features of NASH. METHODS: Twenty-one patients with early hepatic fibrosis (81% female; mean age, 54 years; average body mass index, 44 kg/m2) underwent magnetic resonance elastography (MRE) and endoscopic ultrasound with core liver biopsy collection at time IGB placement and removal at a single center from October 2016 through March 2018. The primary outcome measure was the changes in liver histology parameters after IGB, including change in nonalcoholic fatty liver disease activity score (NAS) and fibrosis score. We also evaluated changes in weight, body mass index, waist to hip ratio, aminotransaminases, fasting levels of lipids, fasting glucose, glycosylated hemoglobin, and MRE-detected liver stiffness. RESULTS: Six months after IGB, patients' mean total body weight loss was 11.7% ± 7.7%, with significant reductions in HbA1c (1.3% ± 0.5%) (P = .02). Waist circumference decreased by 14.4 ± 2.2 cm (P = .001). NAS improved in 18 of 20 patients (90%), with a median decrease of 3 points (range, 1-4 points); 16 of 20 patients (80%) had improvements of 2 points or more. Fibrosis improved by 1.17 stages in 15% of patients, and MRE-detected fibrosis improved by 1.5 stages in 10 of 20 patients (50%). Half of patients reached endpoints approved by the Food and Drug Administration of for NASH resolution and fibrosis improvement. Percent total body weight loss did not correlate with reductions in NAS or fibrosis. Other than post-procedural pain (in 5% of patients), no serious adverse events were reported. CONCLUSION: In a prospective study, IGB facilitated significant metabolic and histologic improvements in NASH. IGB appears to be safe and effective for NASH management when combined with a prescribed diet and exercise program. ClinicalTrials.gov no: NCT02880189.
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Balão Gástrico , Hepatopatia Gordurosa não Alcoólica , Feminino , Balão Gástrico/efeitos adversos , Humanos , Fígado , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/terapia , Estudos Prospectivos , Redução de PesoRESUMO
Exchange processes which include conformational change, protonation/deprotonation, and binding equilibria are routinely studied by 2D exchange NMR techniques, where information about the exchange of nuclei between environments with different NMR shifts is obtained from the development of cross-peaks. Whereas 2D NMR enables the real time study of millisecond and slower exchange processes, 2D ESR in the form of 2D-ELDOR (two-dimensional electron-electron double resonance) has the potential for such studies over the nanosecond to microsecond real time scales. Cross-peak development due to chemical exchange has been seen previously for semiquinones in ESR, but this is not possible for most common ESR probes, such as nitroxides, studied at typical ESR frequencies because, unlike NMR, the exchanging states yield ESR signals that are not resolved from each other within their respective line widths. But at 95 GHz, it becomes possible to resolve them in many cases because of the increased g-factor resolution. The 95 GHz instrumental developments occurring at ACERT now enable such studies. We demonstrate these new capabilities in two studies: (A) the protonation/deprotonation process for a pH-sensitive imidazoline spin label in aqueous solution where the exchange rate and the population ratio of the exchanging states are controlled by the concentration and pH of the buffer solution, respectively, and (B) a nitroxide radical partitioning between polar (aqueous) and nonpolar (phospholipid) environments in multilamellar lipid vesicles, where the cross-peak development arises from the exchange of the nitroxide between the two phases. This work represents the first example of the observation and analysis of cross-peaks arising from chemical exchange processes involving nitroxide spin labels.
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Espectroscopia de Ressonância de Spin Eletrônica , Soluções Tampão , Concentração de Íons de Hidrogênio , Imidazolinas/química , Cinética , Espectroscopia de Ressonância Magnética , Fosfolipídeos/química , Prótons , Marcadores de Spin , Água/químicaRESUMO
The first selective oxidation of methane to methanol is reported herein for zinc-exchanged MOR (Zn/MOR). Under identical conditions, Zn/FER and Zn/ZSM-5 both form zinc formate and methanol. Selective methane activation to form [Zn-CH3 ]+ species was confirmed by 13 C MAS NMR spectroscopy for all three frameworks. The percentage of active zinc sites, measured through quantitative NMR spectroscopy studies, varied with the zeolite framework and was found to be ZSM-5 (5.7 %), MOR (1.2 %) and FER (0.5 %). For Zn/MOR, two signals were observed in the 13 C MAS NMR spectrum, resulting from two distinct [Zn-CH3 ]+ species present in the 12 MR and 8 MR side pockets, as supported by additional NMR experiments. The observed products of oxidation of the [Zn-CH3 ]+ species are shown to depend on the zeolite framework type and the oxidative conditions used. These results lay the foundation for developing structure-function correlations for methane conversion over zinc-exchanged zeolites.
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There is a lack of data describing the impact of the novel coronavirus 19 pandemic on the patients of chronic kidney disease stage V-dialysis (CKD V-D) from resource-limited countries. A growing body of literature describes an increased susceptibility of CKD V-D to COVID-19 with adverse outcomes in those with severe disease. In the current retrospective report, we elucidate the outcome in consecutive 37 CKD V-D patients with COVID-19 from two dialysis centres in Mumbai, India. Of the 37 patients included in the study, 56.7% of patients were asymptomatic or had mild disease and 27% presented with severe symptoms. The recovery rate was 63%, all those who presented with a severe disease succumbed to the infection. Thirty per cent of patients presented with an extended dialysis break due to various logistic and social issues. Though the overall clinical presentation and outcomes of this cohort from a limited resource setting mimic the global scenario, unique social and logistic issues are an additional burden to the patient, caregivers and the health-care facilities, which may worsen the outcomes in the future as the pandemic continues to spread.
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COVID-19/epidemiologia , Diálise Renal , Insuficiência Renal Crônica/terapia , SARS-CoV-2 , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: The rising incidence of infective endocarditis (IE) among people who inject drugs (PWID) has been a major concern across North America. The coincident rise in IE and change of drug preference to hydromorphone controlled-release (CR) among our PWID population in London, Ontario intrigued us to study the details of injection practices leading to IE, which have not been well characterized in literature. METHODS: A case-control study, using one-on-one interviews to understand risk factors and injection practices associated with IE among PWID was conducted. Eligible participants included those who had injected drugs within the last 3 months, were > 18 years old and either never had or were currently admitted for an IE episode. Cases were recruited from the tertiary care centers and controls without IE were recruited from outpatient clinics and addiction clinics in London, Ontario. RESULTS: Thirty three cases (PWID IE+) and 102 controls (PWID but IE-) were interviewed. Multivariable logistic regressions showed that the odds of having IE were 4.65 times higher among females (95% CI 1.85, 12.28; p = 0.001) and 5.76 times higher among PWID who did not use clean injection equipment from the provincial distribution networks (95% CI 2.37, 14.91; p < 0.001). Injecting into multiple sites and heating hydromorphone-CR prior to injection were not found to be significantly associated with IE. Hydromorphone-CR was the most commonly injected drug in both groups (90.9% cases; 81.4% controls; p = 0.197). DISCUSSION: Our study highlights the importance of distributing clean injection materials for IE prevention. Furthermore, our study showcases that females are at higher risk of IE, which is contrary to the reported literature. Gender differences in injection techniques, which may place women at higher risk of IE, require further study. We suspect that the very high prevalence of hydromorphone-CR use made our sample size too small to identify a significant association between its use and IE, which has been established in the literature.
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Endocardite/epidemiologia , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Abuso de Substâncias por Via Intravenosa/epidemiologia , Adulto , Estudos de Casos e Controles , Comorbidade , Feminino , Humanos , Incidência , Entrevistas como Assunto , Masculino , Ontário/epidemiologia , Fatores de Risco , Fatores SexuaisRESUMO
SETTING: Primary care is the first line of defence in healthcare, particularly during the coronavirus disease 2019 (COVID-19) pandemic. In the London-Middlesex region of Ontario, a critical shortage of personal protective equipment (PPE) was identified among primary care physicians (PCPs). INTERVENTION: With the help of the London-Middlesex Primary Care Alliance, volunteer administrators, physicians and medical students coordinated the acquisition and redistribution of community-donated PPE to PCPs across London-Middlesex. Our scope evolved to include PPE reusability and stewardship and PCP wellness. OUTCOME: Beginning on March 16, 2020, our initial four-week operation provided PPE to over 200 PCPs. We received 60 donations, including over 118,000 gloves, 13,700 masks, 700 wellness kits and reusable cloth masks and gowns. Each delivery included educational pamphlets, and our online PPE stewardship session was attended by over 30 physicians. IMPLICATIONS: In response to the PPE shortage in COVID-19, our efforts evolved into a complex adaptive system, supported by an organizational body with a pre-existing communication infrastructure, to great success. Our scope extended beyond simple PPE provision to PCPs. Furthermore, our initiative established a framework for a centralized response to PPE shortage in Ontario Health West.
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Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Equipamento de Proteção Individual/provisão & distribuição , Médicos de Atenção Primária , Pneumonia Viral/prevenção & controle , Betacoronavirus , COVID-19 , Humanos , Ontário , Equipamento de Proteção Individual/normas , SARS-CoV-2 , Estudantes de Medicina , VoluntáriosRESUMO
Cullin-RING ubiquitin ligases (CRLs) catalyze the ubiquitylation of substrates many of which are degraded by the 26S proteasome. Their modular architecture enables recognition of numerous substrates via exchangeable substrate receptors that competitively bind to a cullin scaffold with high affinity. Due to the plasticity of these interactions there is ongoing uncertainty how cells maintain a flexible CRL repertoire in view of changing substrate loads. Based on a series of in vivo and in vitro studies, different groups proposed that the exchange of substrate receptors is mediated by a protein exchange factor named Cand1. Here, we have performed mathematical modeling to provide a quantitative underpinning of this hypothesis. First we show that the exchange activity of Cand1 necessarily leads to a trade-off between high ligase activity and fast receptor exchange. Supported by measurements we argue that this trade-off yields an optimal Cand1 concentration in cells where the time scale for substrate degradation becomes minimal. In a second step we show through simulations that (i) substrates bias the CRL repertoire leading to preferential assembly of ligases for which substrates are available and (ii) differences in binding affinities or substrate receptor abundances create a temporal hierarchy for the degradation of substrates. Finally, we compare the Cand1-mediated exchange cycle with an alternative architecture lacking Cand1 which indicates superiority of a system with exchange factor if substrate receptors bind substrates and the cullin scaffold in a random order. Together, our results provide general constraints for the operating regimes of molecular exchange systems and suggest that Cand1 endows the CRL network with the properties of an "on demand" system allowing cells to dynamically adjust their CRL repertoire to fluctuating substrate abundances.
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Proteínas de Schizosaccharomyces pombe/química , Proteínas de Schizosaccharomyces pombe/metabolismo , Ubiquitina-Proteína Ligases/química , Ubiquitina-Proteína Ligases/metabolismo , Biologia Computacional , Simulação por Computador , Maleabilidade , Ligação Proteica , Proteínas de Schizosaccharomyces pombe/genética , Fatores de Transcrição , Ubiquitina-Proteína Ligases/genéticaRESUMO
AIMS: To compare the performance of population-based kinetics with that of directly measured C-peptide kinetics when used to calculate ß-cell responsivity indices, and to study people with and without acute insulin resistance to ensure that population-based kinetics apply to all conditions where ß-cell function is measured. METHODS: Somatostatin was used to inhibit endogenous insulin secretion in 56 people without diabetes. Subsequently, a C-peptide bolus was administered and the changing concentrations were used to calculate individual kinetic measures of C-peptide clearance. In addition, the participants were studied on 2 occasions in random order using an oral glucose tolerance test (OGTT). On one occasion, free fatty acid elevation, to cause insulin resistance, was achieved by infusion of Intralipid + heparin. The Disposition Index (DI) was then estimated by the oral minimal model using either population-based or individual C-peptide kinetics. RESULTS: There were marked differences in the exchange variables (k 12 and k 21 ) of the model describing C-peptide kinetics, but smaller differences in the fractional clearance; that is, the irreversible loss from the accessible compartment (k 01 ), obtained from population-based estimates compared with experimental measurement. Because it is predominantly influenced by k 01 , DI estimated using individual kinetics correlated well with DI estimated using population-based kinetics. CONCLUSIONS: These data support the use of population-based measures of C-peptide kinetics to estimate ß-cell function during an OGTT.
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Peptídeo C/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Resistência à Insulina/fisiologia , Células Secretoras de Insulina/fisiologia , Feminino , Glucose/farmacologia , Teste de Tolerância a Glucose , Glicerol/farmacologia , Hormônios/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Solventes/farmacologia , Somatostatina/farmacologia , Edulcorantes/farmacologiaRESUMO
The use of long-acting reversible contraception is on the rise across the United States and has contributed to a decrease in teen pregnancies. With the increased use of long-acting reversible contraception, physicians may encounter difficult insertions and removals of intrauterine devices (IUDs) and the contraceptive implant. Uterine structure (e.g., extreme anteversion or retroversion, uterine tone during the postpartum period and breastfeeding) can pose challenges during IUD insertion. Special consideration is also needed for IUD insertions in patients who are transgender or gender nonconforming, such as psychosocial support and management of vaginal atrophy. Missing IUD strings may complicate removal, possibly requiring ultrasonography and use of instruments such as thread retrievers, IUD hooks, and alligator forceps. Regarding implant removal, those that are barely palpable (e.g., because of an overly deep insertion or excessive patient weight gain), removal may require ultrasonography, use of vas clamps and skin hooks, and extra dissection.
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Remoção de Dispositivo , Complicações Intraoperatórias , Dispositivos Intrauterinos/efeitos adversos , Contracepção Reversível de Longo Prazo , Complicações Pós-Operatórias , Implantação de Prótese/efeitos adversos , Remoção de Dispositivo/instrumentação , Remoção de Dispositivo/métodos , Falha de Equipamento , Análise de Falha de Equipamento , Feminino , Humanos , Bombas de Infusão Implantáveis , Complicações Intraoperatórias/classificação , Complicações Intraoperatórias/etiologia , Contracepção Reversível de Longo Prazo/efeitos adversos , Contracepção Reversível de Longo Prazo/instrumentação , Contracepção Reversível de Longo Prazo/métodos , Complicações Pós-Operatórias/classificação , Complicações Pós-Operatórias/etiologia , Implantação de Prótese/métodosRESUMO
The T-cell factor/Lymphoid enhancer factor (TCF/LEF; hereafter TCF) family of transcription factors are critical regulators of colorectal cancer (CRC) cell growth. Of the four TCF family members, TCF7L1 functions predominantly as a repressor of gene expression. Few studies have addressed the role of TCF7L1 in CRC and only a handful of target genes regulated by this repressor are known. By silencing TCF7L1 expression in HCT116 cells, we show that it promotes cell proliferation and tumorigenesis in vivo by driving cell cycle progression. Microarray analysis of transcripts differentially expressed in control and TCF7L1-silenced CRC cells identified genes that control cell cycle kinetics and cancer pathways. Among these, expression of the Wnt antagonist DICKKOPF4 (DKK4) was upregulated when TCF7L1 levels were reduced. We found that TCF7L1 recruits the C-terminal binding protein (CtBP) and histone deacetylase 1 (HDAC1) to the DKK4 promoter to repress DKK4 gene expression. In the absence of TCF7L1, TCF7L2 and ß-catenin occupancy at the DKK4 promoter is stimulated and DKK4 expression is increased. These findings uncover a critical role for TCF7L1 in repressing DKK4 gene expression to promote the oncogenic potential of CRCs.
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Oxirredutases do Álcool/metabolismo , Neoplasias Colorretais/metabolismo , Proteínas de Ligação a DNA/metabolismo , Regulação Neoplásica da Expressão Gênica , Histona Desacetilase 1/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteína 1 Semelhante ao Fator 7 de Transcrição/metabolismo , Carcinogênese/metabolismo , Linhagem Celular Tumoral , Humanos , Proteínas Repressoras/metabolismoRESUMO
Since the 1990s, the Inter-agency field manual on reproductive health in humanitarian settings (IAFM) has provided authoritative guidance on reproductive health service provision during different phases of complex humanitarian emergencies. In 2018, the Inter-Agency Working Group on Reproductive Health in Crises will release a new edition of this global resource. In this article, we describe the collaborative and inter-sectoral revision process and highlight major changes in the 2018 IAFM. Key revisions to the manual include repositioning unintended pregnancy prevention within and explicitly incorporating safe abortion care into the Minimum Initial Service Package (MISP) chapter, which outlines a set of priority activities to be implemented at the outset of a humanitarian crisis; stronger guidance on the transition from the MISP to comprehensive sexual and reproductive health services; and the addition of a logistics chapter. In addition, the IAFM now places greater and more consistent emphasis on human rights principles and obligations, gender-based violence, and the linkages between maternal and newborn health, and incorporates a diverse range of field examples. We conclude this article with an outline of plans for releasing the 2018 IAFM and facilitating uptake by those working in refugee, crisis, conflict, and emergency settings.
Assuntos
Serviços de Saúde Materno-Infantil/organização & administração , Refugiados , Socorro em Desastres/organização & administração , Serviços de Saúde Reprodutiva/organização & administração , Nações Unidas , Conscientização , Fortalecimento Institucional , Anticoncepção/métodos , Comportamento Cooperativo , Feminino , Direitos Humanos , Humanos , Conhecimento , Serviços de Saúde Materno-Infantil/economia , Serviços de Saúde Materno-Infantil/provisão & distribuição , Políticas , Socorro em Desastres/economia , Serviços de Saúde Reprodutiva/economia , Serviços de Saúde Reprodutiva/provisão & distribuição , Educação Sexual , Saúde da MulherRESUMO
PURPOSE OF REVIEW: The worldwide prevalence of obesity is increasing. Obesity is strongly associated with many chronic health conditions that have been shown to improve with weight loss. However, counseling patients on weight loss can be challenging. Identifying specific aspects of weight management may personalize the conversation about weight loss and better address the individual patient's health goals and perceived barriers to change. RECENT FINDINGS: Physical and behavioral phenotypes are being identified to better tailor treatment recommendations, given lack of efficacy of currently available interventions. The current review provides a summary of the evidence behind the management of several recognized clinical phenotypes, to include body fat distribution (e.g., central obesity), muscle mass (e.g., sarcopenic obesity of the elderly), and problematic eating behaviors (e.g., cravings). Identifying specific aspects of weight management may personalize the conversation about weight loss and better address the individual patient's health goals and perceived barriers to change.