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1.
PLOS Glob Public Health ; 4(1): e0001638, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38190377

RESUMO

Type 1 Diabetes (T1D) is life-threatening without appropriate treatment. Though pediatric endocrinology care is limited in Rwanda, a decentralized health system allows access to local non-communicable disease (NCD) nurses through a network of 42 district hospitals. Recent rapid expansion of internet access in the country makes virtual diabetes education initiatives possible. We investigated whether Rwandan NCD nurses receiving diabetes education via online e-modules could make similar educational gains in insulin adjustment skills (IAS) compared to NCD nurses educated in a conference-style setting, and whether they would maintain equivalent competency at 1 year after education. We randomized 21 district hospitals and their NCD nurses to participate in a 1.5-day educational conference centered around care of type 1 diabetes (Group 1), while nurses from the remaining 21 hospitals (Group 2) received accommodation and access to equivalent educational materials in e-module form. Both groups were requested to review initial course materials at 4, 8, and 12 months. Ten-point IAS assessments were administered before and after education or review at each time point. Groups 1 and 2 had equal improvement after education (+2.0 vs. +2.0, p = 0.47) and equal final score at baseline (6.0 vs. 6.0, p = 0.74). However, both groups showed a diminishing improvement over time, so that any gains were lost by 4 months in Group 1 and 8 months in Group 2. Group 1 showed greater attrition in participation over time (19% vs 58% continued participation at one year, p = 0.002). Groups did not differ in subjective confidence in IAS after education. Both groups identified existing or potential access barriers to their respective educational method. While further modifications should be trialed to ensure equitable access and to maintain long-term engagement, online education is a feasible method to teach complex subspecialty skills to providers working in low-resource settings.

2.
J Am Board Fam Med ; 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38092438

RESUMO

PURPOSE: In efforts to improve patient care, collaborative approaches to care have been highlighted. The teamlet model is one such approach, in which a primary care clinician works consistently with the same clinical staff member. The purpose of this study is to identify the characteristics of high-performing primary care teamlets, defined as teamlets with low rates of ambulatory care sensitive emergency department (ACSED) visits and ambulatory care sensitive hospital admissions (ACSAs). METHODS: Twenty-six individual qualitative interviews were performed with physicians and their teamlet staff member across 13 teamlets. Potentially important characteristics related to high-performing primary care teamlets were identified, calibrated, and analyzed using qualitative comparative analysis (QCA). RESULTS: Key characteristics identified by the QCA that were often present in teamlets with low rates of ACSED visits and, to a lesser extent, ACSAs were staff proactiveness in anticipating physician needs and physician-reported trust in their staff member. CONCLUSION: This study suggests that physician trust in their staff and proactiveness of staff in anticipating physician needs are important in promoting high-performing teamlets in primary care. Additional studies are indicated to further explore the relationship between these characteristics and high-performing teamlets, and to identify other characteristics that may be important.

3.
JCEM Case Rep ; 1(3): luad055, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37908585

RESUMO

An 8-year, 7-month-old male presented with puberty symptoms, including a 1.5-year history of facial hair with 9 months of phallic growth, body odor, and acne. Physical examination revealed phallic enlargement but only 4 mL testes bilaterally. Laboratory evaluation revealed markedly elevated LH and testosterone, but a prepubertal FSH level and minimally elevated adrenal androgens. A magnetic resonance imaging scan of the head revealed an anterior pituitary adenoma, and after the patient failed to respond to leuprolide, he was initiated on spironolactone and anastrozole to minimize pubertal progression before transsphenoidal adenomectomy. Postoperatively, the patient had rapid reduction of LH and testosterone, with subsequent cessation of pubertal progression, confirming the diagnosis of an LH-secreting pituitary adenoma despite negative immunoreactivity for LH and FSH. Functioning gonadotroph adenomas are rare and have been documented only in small case series and case reports. When active, these most commonly secrete FSH or co-secrete FSH and LH, and only very rarely result in precocious puberty. Here, we describe a rare case of an isolated LH-secreting functioning gonadotroph adenoma resulting in precocious puberty. This case reinforces the need to critically analyze departures from the typical pubertal sequence and to expand one's differential to include etiologies that can cause unbalanced secretion of gonadotropins.

4.
Violence Against Women ; 29(15-16): 3072-3100, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37545388

RESUMO

Antirape scholarship has largely focused on survivors and their needs. However, little is known about victim advocates, who support survivors, and how advocates' identities can affect their work. This article draws on semistructured interviews with 23 LGBTQ+ advocates to explore how they navigate their sexual, gender, and racial identities at rape crisis centers today. Results show that LGBTQ+ advocates choose the ways that their sexual and gender identities are visible or invisible at their agency, usually to improve LGBTQ+ survivor services. By examining LGBTQ+ advocacy, this article critically evaluates normativity in antirape work and advocates for a queer transformation of rape victim services.


Assuntos
Estupro , Minorias Sexuais e de Gênero , Humanos , Identidade de Gênero , Comportamento Sexual , Sobreviventes
5.
J Gen Intern Med ; 38(6): 1384-1392, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36441365

RESUMO

BACKGROUND: Primary care "teamlets" in which a staff member and physician consistently work together might provide a simple, cost-effective way to improve care, with or without insertion within a team. OBJECTIVE: To determine the prevalence and performance of teamlets and teams. DESIGN: Cross-sectional observational study linking survey responses to Medicare claims. PARTICIPANTS: Six hundred eighty-eight general internists and family physicians. INTERVENTIONS: Based on survey responses, physicians were assigned to one of four teamlet/team categories (e.g., teamlet/no team) and, in secondary analyses, to one of eight teamlet/team categories that classified teamlets into high, medium, and low collaboration as perceived by the physician (e.g., teamlet perceived-high collaboration/no team). MAIN MEASURES: Descriptive: percentage of physicians in teamlet/team categories. OUTCOME MEASURES: physician burnout; ambulatory care sensitive emergency department and hospital admissions; Medicare spending. KEY RESULTS: 77.4% of physicians practiced in teamlets; 36.7% in teams. Of the four categories, 49.1% practiced in the teamlet/no team category; 28.3% in the teamlet/team category; 8.4% in no teamlet/team; 14.1% in no teamlet/no team. 15.7%, 47.4%, and 14.4% of physicians practiced in perceived high-, medium-, and low-collaboration teamlets. Physicians who practiced neither in a teamlet nor in a team had significantly lower rates of burnout compared to the three teamlet/team categories. There were no consistent, significant differences in outcomes or Medicare spending by teamlet/team or teamlet perceived-collaboration/team categories compared to no teamlet/no team, for Medicare beneficiaries in general or for dual-eligible beneficiaries. CONCLUSIONS: Most general internists and family physicians practice in teamlets, and some practice in teams, but neither practicing in a teamlet, in a team, or in the two together was associated with lower physician burnout, better outcomes for patients, or lower Medicare spending. Further study is indicated to investigate whether certain types of teamlet, teams, or teamlets within teams can achieve higher performance.


Assuntos
Médicos , Atenção Primária à Saúde , Idoso , Humanos , Estados Unidos/epidemiologia , Estudos Transversais , Medicare , Esgotamento Psicológico
6.
J Diabetes Complications ; 34(7): 107589, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32376087

RESUMO

AIMS: The Disposition Index (DI) is widely used in clinical studies of ß-cell function. However, direct physiologic interpretation of the DI value and the inverse exponential slope relating insulin secretion and insulin sensitivity terms is difficult. We evaluated a linearization of the relationship that allows separate evaluation of the DI term and the slope. METHODS: Insulin secretion and sensitivity indices were derived from standardized oral glucose tolerance testing, including commonly used terms and model-derived terms. The population included participants with normoglycemia, dysglycemia or Type 2 diabetes. Logarithmic transformation of the DI equation to linearize the secretion-sensitivity relationship was performed, and the resulting secretion-sensitivity relationships were evaluated using standard linear regression methods. RESULTS: Simple logarithmic transformation linearized the secretion-sensitivity relationships available from a variety of OGTT-derived metrics. In normoglycemic subjects the slopes approximated -1 in insulin-basedsecretion-sensitivity pairs, and approximated -0.6 in C-peptide based secretion-sensitivity pairs. Group differences in DI terms were observed as expected. These analyses also revealed differing secretion-sensitivity slopes, with IGT and T2D demonstrating progressively impaired coupling. CONCLUSIONS: Linearization of the secretion-sensitivity relationship provides simplified interpretation of the DI value and allows simple analysis and meaningful interpretation of the secretion-sensitivity slope. This linear relationship is amenable to standard statistical evaluations for comparisons of insulin secretion responses and of secretion-sensitivity coupling across groups.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Insulina/análise , Glicemia , Peptídeo C , Diabetes Mellitus Tipo 2/diagnóstico , Teste de Tolerância a Glucose , Humanos
7.
Ultrasound Med Biol ; 46(7): 1769-1782, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32376189

RESUMO

Renal volume has the potential to serve as a robust biomarker for tracking the onset and progression of renal diseases and also for quantifying renal function. We propose a method to estimate renal volumes using freehand ultrasound scans at the point of care. A conventional ultrasound probe was augmented with an Intel RealSense D435 i camera. Visual inertial simultaneous localization and mapping was used to localize the probe in free space. The acquired 2-D ultrasound images, segmented by trained clinicians, were combined with the estimated poses of the probe to yield accurate volumes. The method was tested on two ex vivo sheep kidneys embedded in gelatin phantoms. Four different scanning protocols were tested: transverse linear, transverse fan, longitudinal linear and longitudinal fan. The estimated renal volumes were compared with those obtained using the water displacement method, the ellipsoidal method and computed tomography imaging. The water displacement method yielded mean volumes of 66.00 and 66.20 mL for kidneys 1 and 2, respectively (ground truth). Freehand ultrasound scans produced mean volumes of 64.08 mL (2.90% error) and 65.25 mL (1.40% error); the ellipsoidal method yielded volumes of 57.49 mL (12.90% error) and 60.15 mL (9.13% error); and computed tomography yielded a volume of 63.00 mL (4.54% error).


Assuntos
Rim/diagnóstico por imagem , Ultrassonografia/métodos , Animais , Rim/anatomia & histologia , Rim/patologia , Nefropatias/diagnóstico por imagem , Nefropatias/patologia , Tamanho do Órgão , Imagens de Fantasmas , Testes Imediatos , Ovinos , Ultrassonografia/instrumentação
8.
J Pediatr Endocrinol Metab ; 31(12): 1367-1369, 2018 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-30433874

RESUMO

Background Limited information is available regarding baseline characteristics of children and adolescents with gender dysphoria (GD). The purpose of this retrospective study was to describe baseline characteristics of pediatric patients referred for GD. Methods A retrospective chart review of pediatric patients with GD referred to the pediatric endocrine clinic between 2002 and 2017 was conducted. Body mass index (BMI) percentiles and z-scores were calculated based on height and weight at the initial visit. Results Seventy-eight patients aged 14.9±2.37 years were identified. Of these, affirmed gender was more often male than female (63% vs. 37%, p=0.024). Although no difference was seen in average BMI z-scores between female to male (FTM) and male to female (MTF) patients, approximately 50% were overweight or obese. A higher incidence of anxiety was present in FTM compared with MTF youth (p=0.05). Fifty-six patients were referred in January 2014 or later, of whom 27% had a history of early expression of GD compared with 55% of those seen prior to 2014 (p=0.061). Conclusions The high prevalence of overweight in TG youth at baseline represents a potential risk for adverse health consequences. There appears to be a change in the age of first manifestation of GD over time.


Assuntos
Ansiedade/epidemiologia , Disforia de Gênero/diagnóstico , Sobrepeso/epidemiologia , Adolescente , Ansiedade/psicologia , Índice de Massa Corporal , Criança , Comorbidade , Feminino , Disforia de Gênero/epidemiologia , Disforia de Gênero/psicologia , Humanos , Incidência , Masculino , Sobrepeso/psicologia
9.
Annu Int Conf IEEE Eng Med Biol Soc ; 2018: 3128-3131, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30441057

RESUMO

This paper introduces a non-invasive, contrastenhanced ultrasound (CEUS) infusion method to quantify the health of viable donor livers. The method uses the infusion of microbubbles and their destruction and subsequent replenishment to measure the perfusion rate in the liver microvasculature. The proposed method improves on the previous parameter extraction approaches applied to the flashreplenishment technique by addressing the effects of the microbubble mixing within the perfusate bath and destruction rate. By doing so, the tissue perfusion rate can be extracted from the data even though the microbubble concentration is not constant throughout image acquisition. The measured changes in the tissue perfusion rate showed that CEUS infusion is a viable biomarker for assessing liver health.


Assuntos
Fígado , Animais , Meios de Contraste , Microbolhas , Perfusão , Suínos , Ultrassonografia
10.
Curr Diab Rep ; 18(8): 51, 2018 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-29909550

RESUMO

PURPOSE OF REVIEW: The oral glucose tolerance test (OGTT) is used both in clinical practice and research to assess glucose tolerance. In addition, the OGTT is utilized for surrogate measures of insulin sensitivity and the insulin response to enteral glucose and has been widely applied in the evaluation of ß-cell dysfunction in obesity, prediabetes, and type 2 diabetes. Here we review the use of the OGTT and the OGTT-derived indices for measurement of risk markers for type 2 diabetes in youth. RECENT FINDINGS: Advantages of using the OGTT for measures of diabetes risk include its accessibility and the incorporation of physiological contributions of the gut-pancreas axis in the measures of insulin response to glucose. Mathematical modeling expands the potential gains from the OGTT in physiology and clinical research. Disadvantages include individual differences in the rate of glucose absorption that modify insulin responses, imperfect control of the glycemic stimulus, and poor intraindividual reproducibility. Available research suggests the OGTT provides valuable information about the development of impaired glycemic control and ß-cell function in obese youth along the spectrum of glucose tolerance.


Assuntos
Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Adolescente , Diabetes Mellitus Tipo 2/fisiopatologia , Teste de Tolerância a Glucose , Humanos , Insulina/metabolismo , Resistência à Insulina , Modelos Biológicos , Fatores de Risco
11.
Diabetes Care ; 41(2): 318-325, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29183909

RESUMO

OBJECTIVE: Type 2 diabetes is a growing health problem among both adults and adolescents. To better understand the differences in the pathogenesis of diabetes between these groups, we examined differences in ß-cell function along the spectrum of glucose tolerance. RESEARCH DESIGN AND METHODS: We evaluated 89 adults and 50 adolescents with normal glucose tolerance (NGT), dysglycemia, or type 2 diabetes. Oral glucose tolerance test results were used for C-peptide and insulin/glucose minimal modeling. Model-derived and direct measures of insulin secretion and insulin sensitivity were compared across glycemic stages and between age-groups at each stage. RESULTS: In adolescents with dysglycemia, there was marked insulin resistance (insulin sensitivity index: adolescents, median [interquartile range] 1.8 [1.1-2.4] × 10-4; adults, 5.0 [2.3-9.9]; P = 0.01). The nature of ß-cell dysfunction across stages of dysglycemia differed between the groups. We observed higher levels of secretion among adolescents than adults (total insulin secretion: NGT, 143 [103-284] × 10-9/min adolescent vs. 106 [71-127], P = 0.001); adults showed stepwise impairments in static insulin secretion (NGT, 7.5 [4.0-10.3] × 10-9/min; dysglycemia, 5.0 [2.3-9.9]; type 2 diabetes, 0.7 [0.1-2.45]; P = 0.003), whereas adolescents showed diabetes-related impairment in dynamic secretion (NGT, 1,905 [1,630-3,913] × 10-9; dysglycemia, 2,703 [1,323-3,637]; type 2 diabetes, 1,189 [269-1,410]; P = 0.001). CONCLUSIONS: Adults and adolescents differ in the underlying defects leading to dysglycemia, and in the nature of ß-cell dysfunction across stages of dysglycemia. These results may suggest different approaches to diabetes prevention in youths versus adults.


Assuntos
Glicemia/metabolismo , Transtornos do Metabolismo de Glucose/fisiopatologia , Células Secretoras de Insulina/fisiologia , Obesidade/fisiopatologia , Sobrepeso/fisiopatologia , Adolescente , Adulto , Idoso , Criança , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Intolerância à Glucose/sangue , Intolerância à Glucose/fisiopatologia , Transtornos do Metabolismo de Glucose/sangue , Teste de Tolerância a Glucose , Humanos , Resistência à Insulina/fisiologia , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/patologia , Sobrepeso/sangue
12.
Artigo em Inglês | MEDLINE | ID: mdl-28588625

RESUMO

BACKGROUND: We aimed to determine the extent of post-treatment weight gain that occurs in pediatric patients in the first year following radioactive iodine (RAI) therapy for Graves disease (GD) and its relationship to clinical characteristics. METHODS: A retrospective chart review of patients receiving RAI therapy for GD between 1998-2015 was performed. Change in BMI SDS (∆BMI SDS) from baseline to one year after treatment was determined. We also investigated whether individual clinical and/or biochemical factors were associated with the weight trajectory in these patients. RESULTS: One hundred fifty seven patients aged 12.7 ± 3 years (80% girls) were included in the analysis. Average ∆BMI SDS was 0.70 ± 0.71 (p < 0.001) at 1 year. Patients with weight loss at presentation had a greater ∆BMI SDS than those without (0.92 vs 0.56, p = 0.005), whereas no association was seen with gender, pubertal status, use of antithyroid drugs, history of ADHD, or Down syndrome. Baseline BMI SDS was negatively correlated with ∆BMI SDS, with a stronger correlation in males. From baseline to 1 year, the proportion of overweight and obese patients increased from 9.6% to 18.5% and from 6.4% to 21%, respectively. In a subset of 81 patients, a positive correlation was noted between time to euthyroidism and ∆BMI SDS, particularly in boys. CONCLUSIONS: The number of our patients in the overweight category doubled and the number in the obese category more than tripled in the first year following RAI treatment for GD. Anticipatory guidance regarding this important issue is badly needed.

14.
Health Serv Res ; 51(5): 1796-813, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26846591

RESUMO

OBJECTIVES: To determine whether a shared panel management program was effective at improving quality of care for patients with uncontrolled chronic disease. DATA SOURCES: Data were extracted from electronic health records. STUDY DESIGN: Randomized controlled trial of a panel management program initiated by New York City Department of Health and Mental Hygiene. Patients from 20 practices with an uncontrolled chronic disease and a lapse in care were assigned to the intervention (a phone call requesting that the patient schedule a physician appointment) or usual care. Outcomes were visits to physician practices, body mass index measurement, blood pressure measurement and control, use of antithrombotics, and low-density lipoprotein measurement and control. PRINCIPAL FINDINGS: Panel managers were able to successfully speak with 1,676 patients (14.7 percent of the intervention group). There were no significant differences in outcomes between the intervention and usual care groups. Successfully contacted patients were more likely to have an office visit within 1 year of randomization (45.6 percent [95 percent CI: 22.8, 26.9] vs. 38.1 percent [95 percent CI: 36.8, 39.3]) and more likely to be on antithrombotics (24.4 percent [95 percent CI: 17.7, 31.0]) versus those in the usual care group (17.0 percent [95 percent CI: 13.9, 20.0]) but had no other difference in quality. CONCLUSIONS: A shared, low-intensity panel management program run by a city health department did not improve quality of care for patients with chronic illnesses and lapses in care.


Assuntos
Doença Crônica/terapia , Melhoria de Qualidade/organização & administração , Sistemas de Alerta/estatística & dados numéricos , Gerenciamento Clínico , Registros Eletrônicos de Saúde/estatística & dados numéricos , Feminino , Prática de Grupo/organização & administração , Disparidades em Assistência à Saúde , Humanos , Masculino , Pessoa de Meia-Idade
15.
J Adolesc Health ; 58(3): 369-71, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26903434

RESUMO

PURPOSE: Our Pediatric Endocrinology Clinic has seen a sharp increase in referrals for gender dysphoria (GD) during recent years. However, the frequency and characteristics of referrals have not been objectively examined. METHODS: A retrospective chart review of referrals for GD during the past 13 years was performed. Variables analyzed included numbers of referrals per year, patient characteristics, comorbid conditions, and hormonal therapy. Timing of referral and eligibility for treatment were measured against established recommendations. RESULTS: Of 38 patients, 74% were referred during the last 3 years. Most patients presented late in puberty before a GD-specific psychological evaluation and few were eligible for hormonal treatment at baseline. Over half had psychiatric and/or developmental comorbidities. CONCLUSIONS: A dramatic increase in referrals for GD since 2002 was confirmed. Enhanced provider education and outreach regarding care of patients with GD are needed.


Assuntos
Disforia de Gênero/epidemiologia , Maturidade Sexual , Adolescente , Criança , Feminino , Disforia de Gênero/psicologia , Disforia de Gênero/terapia , Terapia de Reposição Hormonal/métodos , Humanos , Indiana/epidemiologia , Masculino , Encaminhamento e Consulta/tendências , Estudos Retrospectivos
16.
Ann Fam Med ; 14(1): 16-25, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26755779

RESUMO

PURPOSE: In the turbulent US health care environment, many primary care physicians seek hospital employment. Large physician-owned primary care groups are an alternative, but few physicians or policy makers realize that such groups exist. We wanted to describe these groups, their advantages, and their challenges. METHODS: We identified 21 groups and studied 5 that varied in size and location. We conducted interviews with group leaders, surveyed randomly selected group physicians, and interviewed external observers-leaders of a health plan, hospital, and specialty medical group that shared patients with the group. We triangulated responses from group leaders, group physicians, and external observers to identify key themes. RESULTS: The groups' physicians work in small practices, with the group providing economies of scale necessary to develop laboratory and imaging services, health information technology, and quality improvement infrastructure. The groups differ in their size and the extent to which they engage in value-based contracting, though all are moving to increase the amount of financial risk they take for their quality and cost performance. Unlike hospital-employed and multispecialty groups, independent primary care groups can aim to reduce health care costs without conflicting incentives to fill hospital beds and keep specialist incomes high. Each group was positively regarded by external observers. The groups are under pressure, however, to sell to organizations that can provide capital for additional infrastructure to engage in value-based contracting, as well as provide substantial income to physicians from the sale. CONCLUSIONS: Large, independent primary care groups have the potential to make primary care attractive to physicians and to improve patient care by combining human scale advantages of physician autonomy and the small practice setting with resources that are important to succeed in value-based contracting.


Assuntos
Prática de Grupo/organização & administração , Atenção Primária à Saúde/organização & administração , Arizona , Atitude do Pessoal de Saúde , Colorado , Connecticut , Prática de Grupo/normas , Custos de Cuidados de Saúde , Humanos , Michigan , Ohio , Médicos de Atenção Primária/organização & administração , Médicos de Atenção Primária/psicologia , Atenção Primária à Saúde/normas , Autonomia Profissional , Melhoria de Qualidade , Estados Unidos , Aquisição Baseada em Valor
17.
Curr Pediatr Rep ; 4(4): 186-187, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29226028
18.
Cell Rep ; 11(4): 657-70, 2015 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-25892241

RESUMO

AMP-activated protein kinase (AMPK), whose activity is a critical determinant of cell health, serves a fundamental role in integrating extracellular and intracellular nutrient information into signals that regulate various metabolic processes. Despite the importance of AMPK, its specific roles within the different intracellular spaces remain unresolved, largely due to the lack of real-time, organelle-specific AMPK activity probes. Here, we present a series of molecular tools that allows for the measurement of AMPK activity at the different subcellular localizations and that allows for the rapid induction of AMPK inhibition. We discovered that AMPKα1, not AMPKα2, was the subunit that preferentially conferred spatial specificity to AMPK, and that inhibition of AMPK activity at the mitochondria was sufficient for triggering cytosolic ATP increase. These findings suggest that genetically encoded molecular probes represent a powerful approach for revealing the basic principles of the spatiotemporal nature of AMPK regulation.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Transferência Ressonante de Energia de Fluorescência/métodos , Proteínas Quinases Ativadas por AMP/genética , Animais , Células COS , Membrana Celular/metabolismo , Chlorocebus aethiops , Citosol/metabolismo , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Células HEK293 , Humanos , Microscopia de Fluorescência/métodos , Mitocôndrias/metabolismo , Transporte Proteico , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo
19.
Paediatr Drugs ; 17(4): 273-81, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25911294

RESUMO

Central precocious puberty (CPP) is characterized by the same biochemical and physical features as normally timed puberty but occurs at an abnormally early age. Most cases of CPP are seen in girls, in whom it is usually idiopathic. In contrast, ~50% of boys with CPP have an identifiable cause. The diagnosis of CPP relies on clinical, biochemical, and radiographic features. Untreated, CPP has the potential to result in early epiphyseal fusion and a significant compromise in adult height. Thus, the main goal of therapy is preservation of height potential. The gold-standard treatment for CPP is gonadotropin-releasing hormone (GnRH) analogs (GnRHa). Numerous preparations with a range of delivery systems and durations of action are commercially available. While the outcomes of patients treated for CPP have generally been favorable, more research about the psychological aspects, optimal monitoring, and long-term effects of all forms of GnRHa treatment is needed. Several potential therapeutic alternatives to GnRHa exist and await additional investigation.


Assuntos
Hormônio Liberador de Gonadotropina/análogos & derivados , Puberdade Precoce/terapia , Estatura , Feminino , Hormônio do Crescimento/uso terapêutico , Humanos , Masculino , Puberdade Precoce/diagnóstico
20.
Nat Chem Biol ; 8(5): 465-70, 2012 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-22446836

RESUMO

Using a newly synthesized gibberellin analog containing an acetoxymethyl group (GA(3)-AM) and its binding proteins, we developed an efficient chemically inducible dimerization (CID) system that is completely orthogonal to existing rapamycin-mediated protein dimerization. Combining the two systems should allow applications that have been difficult or impossible with only one CID system. By using both chemical inputs (rapamycin and GA(3)-AM), we designed and synthesized Boolean logic gates in living mammalian cells. These gates produced output signals such as fluorescence and membrane ruffling on a timescale of seconds, substantially faster than earlier intracellular logic gates. The use of two orthogonal dimerization systems in the same cell also allows for finer modulation of protein perturbations than is possible with a single dimerizer.


Assuntos
Giberelinas/química , Giberelinas/farmacologia , Multimerização Proteica/efeitos dos fármacos , Animais , Fluorescência , Células HeLa , Humanos , Camundongos , Células NIH 3T3 , Sirolimo/química
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