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We estimate the impact of the Ramadan fasting ritual on criminal sentencing decisions in Pakistan and India from half a century of daily data. We use random case assignment and exogenous variation in fasting intensity during Ramadan due to the rotating Islamic calendar and the geographical latitude of the district courts to document the large effects of Ramadan fasting on decision-making. Our sample comprises roughly a half million cases and 10,000 judges from Pakistan and India. Ritual intensity increases Muslim judges' acquittal rates, lowers their appeal and reversal rates, and does not come at the cost of increased recidivism or heightened outgroup bias. Overall, our results indicate that the Ramadan fasting ritual followed by a billion Muslims worldwide induces more lenient decisions.
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Ayuno , Islamismo , Humanos , Pakistán , IndiaRESUMEN
Experts and employees in many domains make multiple similar but independent decisions in sequence. Often, the serial position of the case in the sequence influences the decision. Explanations for these serial position effects focus on the role of decision-makers' fatigue, but these effects emerge also when fatigue is unlikely. Here, we suggest that serial position effects can emerge due to decision-makers' motivation to be or appear consistent. For example, to avoid having inconsistencies revealed, decisions may become more favorable toward the side that is more likely to put a decision under scrutiny. As a context, we focus on the legal domain in which many high-stakes decisions are made in sequence and in which there are clear institutional processes of decision scrutiny. We analyze two field data sets: 386,109 U.S. immigration judges' decisions on asylum requests and 20,796 jury decisions in 18th century London criminal court. We distinguish between five mechanisms that can drive serial position effects and examine their predictions in these settings. We find that consistent with motivation-based explanations of serial position effects, but inconsistent with fatigue-based explanations, decisions become more lenient as a function of serial position, and the effect persists over breaks. We further find, as is predicted by motivational accounts, that the leniency effect is stronger among more experienced decision-makers. By elucidating the different drivers of serial position effects, our investigation clarifies why they are common, when they are expected, and how to reduce them. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
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Fatiga , Motivación , Humanos , Toma de DecisionesRESUMEN
The liver, skeletal muscle, and adipose tissue are major insulin target tissues and key players in glucose homeostasis. We and others have described diverse insulin resistance (IR) phenotypes in people at risk of developing type 2 diabetes. It is postulated that identifying the IR phenotype in a patient may guide the treatment or the prevention strategy for better health outcomes in populations at risk. Here, we performed plasma metabolomics and lipidomics in a cohort of men and women living with obesity not complicated by diabetes (mean [SD] BMI 36.0 [4.5] kg/m2, n = 62) to identify plasma signatures of metabolites and lipids that align with phenotypes of IR (muscle, liver, or adipose tissue) and abdominal fat depots. We used 2-step hyperinsulinemic-euglycemic clamp with deuterated glucose, oral glucose tolerance test, dual-energy X-ray absorptiometry and abdominal magnetic resonance imaging to assess muscle-, liver- and adipose tissue- IR, beta cell function, body composition, abdominal fat distribution and liver fat, respectively. Spearman's rank correlation analyses that passed the Benjamini−Hochberg statistical correction revealed that cytidine, gamma-aminobutyric acid, anandamide, and citrate corresponded uniquely with muscle IR, tryptophan, cAMP and phosphocholine corresponded uniquely with liver IR and phenylpyruvate and hydroxy-isocaproic acid corresponded uniquely with adipose tissue IR (p < 7.2 × 10−4). Plasma cholesteryl sulfate (p = 0.00029) and guanidinoacetic acid (p = 0.0001) differentiated between visceral and subcutaneous adiposity, while homogentisate correlated uniquely with liver fat (p = 0.00035). Our findings may help identify diverse insulin resistance and adiposity phenotypes and enable targeted treatments in people living with obesity.
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ABSTRACT: Pediatric Achilles tendon injuries requiring surgical treatment are considered rare and have not been well described. A retrospective chart review was conducted from 2010 to 2020 to identify cases of acute Achilles tendon rupture or laceration that required surgical repair in individuals 19 years or younger. A total of 24 individuals with acute Achilles tendon ruptures (n = 8) and lacerations (n = 16) were identified. All spontaneous ruptures occurred in skeletally mature individuals during sports. One subject was on minocycline at the time of injury, while two had a body mass index (BMI) ≥ 99% for age. Another had a history of clubfoot surgery on the injured side. Patients with lacerations were younger (9.9 ± 3.3 vs 16.3 ± 1.6 years) and had lower BMI (17.3 ± 3.8 vs. 28.0 ± 9.4) than those with spontaneous ruptures. The majority of cases had good outcomes with no postoperative complications.
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Tendón Calcáneo , Traumatismos del Tobillo , Laceraciones , Traumatismos de los Tendones , Humanos , Adolescente , Niño , Rotura/cirugía , Tendón Calcáneo/cirugía , Tendón Calcáneo/lesiones , Estudios Retrospectivos , Rotura Espontánea/complicaciones , Traumatismos de los Tendones/cirugía , Traumatismos de los Tendones/etiología , Enfermedad Aguda , Resultado del TratamientoRESUMEN
Recent advances in economic theory, largely motivated by experimental findings, have led to the adoption of models of human behavior where decision-makers take into consideration not only their own payoff but also others' payoffs and any potential consequences of these payoffs. Investigations of deontological motivations, where decision-makers make their choice based on not only the consequences of a decision but also the decision per se, have been rare. We provide a formal interpretation of major moral philosophies and a revealed preference method to distinguish the presence of deontological motivations from a purely consequentialist decision-maker whose preferences satisfy first-order stochastic dominance.
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INTRODUCTION: Sport specialization has been shown to have negative effects on athletes but has not been studied within rock climbing. This study seeks to evaluate the proportion and impact of specialization in pediatric climbers. METHODS: Climbers (ages 8-18 y) were recruited from throughout the United States to complete a 1-time survey regarding climbing experience, training patterns, and injury history. The main outcome of proportion of climbers suffering an injury was assessed within the last 12 mo and within their entire climbing experience (defined as "lifetime" injury). Early specialization was defined as exclusive participation in climbing, with training for >8 moâ§y-1, prior to age 12 y (late specialization if after age 12 y). RESULTS: Participants (n=111, 14±3 y [mean±SD], 69 females) were high-level climbers. Fifty-five percent of participants specialized in climbing, and 69% of those specialized early. Hand and ankle injuries occurred most commonly. Seventy-eight percent of late specialized climbers had a lifetime injury. Late specialized climbers were 1.6 times (95% CI: 1.1-2.3) more likely than early specialized climbers to have had a lifetime injury and 1.8 times (95% CI: 1.1-2.8) more likely to have had an injury in the last 12 mo. No difference in overuse injuries was found between specialization groups. CONCLUSIONS: Early specialization is common among youth climbers but was not associated with an increase in injuries. Late specialization was associated with a higher likelihood of having had a climbing injury in the last 12 mo and during an entire climbing career.
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Traumatismos en Atletas , Trastornos de Traumas Acumulados , Montañismo , Deportes , Adolescente , Atletas , Traumatismos en Atletas/epidemiología , Traumatismos en Atletas/etiología , Niño , Trastornos de Traumas Acumulados/epidemiología , Trastornos de Traumas Acumulados/etiología , Femenino , Humanos , Montañismo/lesiones , Encuestas y Cuestionarios , Estados UnidosRESUMEN
COVID-19 has had worse health, education, and labor market effects on groups with low socioeconomic status (SES) than on those with high SES. Little is known, however, about whether COVID-19 has also had differential effects on noncognitive skills that are important for life outcomes. Using panel data from before and during the pandemic, we show that COVID-19 affects one key noncognitive skill, that is, prosociality. While prosociality is already lower for low-SES students prior to the pandemic, we show that COVID-19 infections within families amplify the prosociality gap between French high school students of high and low SES by almost tripling its size in comparison to pre-COVID-19 levels.
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COVID-19/economía , COVID-19/transmisión , Familia , SARS-CoV-2 , Conducta Social , Clase Social , Adolescente , HumanosRESUMEN
Importance: Mass incarceration is known to foster infectious disease outbreaks, amplification of infectious diseases in surrounding communities, and exacerbation of health disparities in disproportionately policed communities. To date, however, policy interventions intended to achieve epidemic mitigation in US communities have neglected to account for decarceration as a possible means of protecting public health and safety. Objective: To evaluate the association of jail decarceration and government anticontagion policies with reductions in the spread of SARS-CoV-2. Design, Setting, and Participants: This cohort study used county-level data from January to November 2020 to analyze COVID-19 cases, jail populations, and anticontagion policies in a panel regression model to estimate the association of jail decarceration and anticontagion policies with COVID-19 growth rates. A total of 1605 counties with data available on both jail population and COVID-19 cases were included in the analysis. This sample represents approximately 51% of US counties, 72% of the US population, and 60% of the US jail population. Exposures: Changes to jail populations and implementation of 10 anticontagion policies: nursing home visitation bans, school closures, mask mandates, prison visitation bans, stay-at-home orders, and closure of nonessential businesses, gyms, bars, movie theaters, and restaurants. Main Outcomes and Measures: Daily COVID-19 case growth rates. Results: In the 1605 counties included in this study, the mean (SD) prison population was 283.38 (657.78) individuals, and the mean (SD) population was 315.24 (2151.01) persons per square mile. An estimated 80% reduction in US jail populations, achievable through noncarceral management of nonviolent alleged offenses and in line with average international incarceration rates, would have been associated with a 2.0% (95% CI, 0.8%-3.1%) reduction in daily COVID-19 case growth rates. Jail decarceration was associated with 8 times larger reductions in COVID-19 growth rates in counties with above-median population density (4.6%; 95% CI, 2.2%- 7.1%) relative to those below this median (0.5%; 95% CI, 0.1%-0.9%). Nursing home visitation bans were associated with a 7.3% (95% CI, 5.8%-8.9%) reduction in COVID-19 case growth rates, followed by school closures (4.3%; 95% CI, 2.0%-6.6%), mask mandates (2.5%; 95% CI, 1.7%-3.3%), prison visitation bans (1.2%; 95% CI, 0.2%-2.2%), and stay-at-home orders (0.8%; 95% CI, 0.1%-1.6%). Conclusions and Relevance: Although many studies have documented that high incarceration rates are associated with communitywide health harms, this study is, to date, the first to show that decarceration is associated with population-level public health benefits. Its findings suggest that, among other anticontagion interventions, large-scale decarceration and changes to pretrial detention policies are likely to be important for improving US public health, biosecurity, and pandemic preparedness.
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COVID-19/epidemiología , Control de Enfermedades Transmisibles/métodos , Cárceles Locales/organización & administración , Prisioneros/estadística & datos numéricos , Estudios de Cohortes , Control de Enfermedades Transmisibles/legislación & jurisprudencia , Control de Enfermedades Transmisibles/estadística & datos numéricos , Humanos , Pandemias , SARS-CoV-2 , Estados UnidosRESUMEN
Black and Hispanic communities are disproportionately affected by both incarceration and COVID-19. The epidemiological relationship between carceral facilities and community health during the COVID-19 pandemic, however, remains largely unexamined. Using data from Cook County Jail, we examine temporal patterns in the relationship between jail cycling (i.e., arrest and processing of individuals through jails before release) and community cases of COVID-19 in Chicago ZIP codes. We use multivariate regression analyses and a machine-learning tool, elastic regression, with 1,706 demographic control variables. We find that for each arrested individual cycled through Cook County Jail in March 2020, five additional cases of COVID-19 in their ZIP code of residence are independently attributable to the jail as of August. A total 86% of this additional disease burden is borne by majority-Black and/or -Hispanic ZIPs, accounting for 17% of cumulative COVID-19 cases in these ZIPs, 6% in majority-White ZIPs, and 13% across all ZIPs. Jail cycling in March alone can independently account for 21% of racial COVID-19 disparities in Chicago as of August 2020. Relative to all demographic variables in our analysis, jail cycling is the strongest predictor of COVID-19 rates, considerably exceeding poverty, race, and population density, for example. Arrest and incarceration policies appear to be increasing COVID-19 incidence in communities. Our data suggest that jails function as infectious disease multipliers and epidemiological pumps that are especially affecting marginalized communities. Given disproportionate policing and incarceration of racialized residents nationally, the criminal punishment system may explain a large proportion of racial COVID-19 disparities noted across the United States.
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COVID-19/epidemiología , Disparidades en el Estado de Salud , Cárceles Locales/estadística & datos numéricos , Salud Pública/estadística & datos numéricos , Racismo/estadística & datos numéricos , COVID-19/etnología , COVID-19/prevención & control , COVID-19/transmisión , Chicago/epidemiología , Etnicidad/estadística & datos numéricos , Humanos , Incidencia , Prisioneros/estadística & datos numéricos , SARS-CoV-2 , Factores SocioeconómicosRESUMEN
Jails and prisons are major sites of novel coronavirus (SARS-CoV-2) infection. Many jurisdictions in the United States have therefore accelerated the release of low-risk offenders. Early release, however, does not address how arrest and pretrial detention practices may be contributing to disease spread. Using data from Cook County Jail-one of the largest known nodes of SARS-CoV-2 spread in the United States-in Chicago, Illinois, we analyzed the relationship between jailing practices and community infections at the ZIP code level. We found that jail-community cycling was a significant predictor of cases of coronavirus disease 2019 (COVID-19), accounting for 55 percent of the variance in case rates across ZIP codes in Chicago and 37 percent of the variance in all of Illinois. Jail-community cycling far exceeds race, poverty, public transit use, and population density as a predictor of variance. The data suggest that cycling people through Cook County Jail alone is associated with 15.7 percent of all documented COVID-19 cases in Illinois and 15.9 percent of all documented cases in Chicago as of April 19, 2020. Our findings support arguments for reduced reliance on incarceration and for related justice reforms both as emergency measures during the present pandemic and as sustained structural changes vital for future pandemic preparedness and public health.
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Control de Enfermedades Transmisibles/organización & administración , Infecciones por Coronavirus/epidemiología , Transmisión Vertical de Enfermedad Infecciosa/estadística & datos numéricos , Neumonía Viral/epidemiología , Prisioneros/estadística & datos numéricos , Prisiones/organización & administración , Salud Pública , COVID-19 , Chicago , Femenino , Humanos , Illinois , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Masculino , Pandemias/estadística & datos numéricos , Poblaciones VulnerablesRESUMEN
Predictive judicial analytics holds the promise of increasing efficiency and fairness of law. Judicial analytics can assess extra-legal factors that influence decisions. Behavioral anomalies in judicial decision-making offer an intuitive understanding of feature relevance, which can then be used for debiasing the law. A conceptual distinction between inter-judge disparities in predictions and inter-judge disparities in prediction accuracy suggests another normatively relevant criterion with regards to fairness. Predictive analytics can also be used in the first step of causal inference, where the features employed in the first step are exogenous to the case. Machine learning thus offers an approach to assess bias in the law and evaluate theories about the potential consequences of legal change.
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Insulin resistance in muscle, adipocytes and liver is a gateway to a number of metabolic diseases. Here, we show a selective deficiency in mitochondrial coenzyme Q (CoQ) in insulin-resistant adipose and muscle tissue. This defect was observed in a range of in vitro insulin resistance models and adipose tissue from insulin-resistant humans and was concomitant with lower expression of mevalonate/CoQ biosynthesis pathway proteins in most models. Pharmacologic or genetic manipulations that decreased mitochondrial CoQ triggered mitochondrial oxidants and insulin resistance while CoQ supplementation in either insulin-resistant cell models or mice restored normal insulin sensitivity. Specifically, lowering of mitochondrial CoQ caused insulin resistance in adipocytes as a result of increased superoxide/hydrogen peroxide production via complex II. These data suggest that mitochondrial CoQ is a proximal driver of mitochondrial oxidants and insulin resistance, and that mechanisms that restore mitochondrial CoQ may be effective therapeutic targets for treating insulin resistance.
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Tejido Adiposo/patología , Ataxia , Resistencia a la Insulina , Mitocondrias/patología , Enfermedades Mitocondriales/fisiopatología , Debilidad Muscular , Músculos/patología , Oxidantes/metabolismo , Ubiquinona/deficiencia , Adipocitos/fisiología , Animales , Humanos , Ratones , Sensibilidad y EspecificidadRESUMEN
Introduction: Muscle sympathetic nerve activity (MSNA) may play a role in insulin resistance in obesity. However, the direction and nature of the relationship between MSNA and insulin resistance in obesity remain unclear. We hypothesized that resting MSNA would correlate inversely with both muscle and liver insulin sensitivity and that it would be higher in insulin-resistant vs. insulin-sensitive subjects. Materials and methods: Forty-five non-diabetic obese subjects were studied. As no significant relationships were found in women, the data presented in on 22 men aged 48 ± 12 years. Two-step (15 and 80 mU/m2/min) hyperinsulinaemic-euglycaemic clamps were performed using deuterated glucose to determine liver and muscle insulin sensitivity. Clinical and metabolic parameters were assessed. MSNA was measured via a microelectrode inserted percutaneously into the common peroneal nerve. Results: MSNA burst frequency correlated inversely with liver insulin sensitivity (r = -0.53, P = 0.02) and positively with the hepatokines C-reactive protein (CRP) and fibroblast growth factor (FGF)-19 (r = 0.57, P = 0.006, and r = -0.47, P = 0.03, respectively). MSNA burst frequency was lower in Liversen compared to Liverres (27 ± 5 vs. 38 ± 2 bursts per minute; P = 0.03). Muscle insulin sensitivity was unrelated to MSNA. Discussion: Sympathetic neural activation is related to liver insulin sensitivity and circulating hepatokines CRP and FGF-19 in non-diabetic obese men. These results suggest a potential hepato-endocrine-autonomic axis. Future studies are needed to clarify the influence of MSNA on liver insulin sensitivity in men.
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Fibroblast growth factor-1 (FGF-1) promotes differentiation of human preadipocytes into mature adipocytes via modulation of a BMP and Activin Membrane-Bound Inhibitor (BAMBI)/Peroxisome proliferator-activated receptor (PPARγ)-dependent network. Here, we combined transcriptomic and functional investigations to identify novel downstream effectors aligned with complementary analyses of gene expression in human adipose tissue to explore relationships with insulin sensitivity. RNA-Seq and qRT-PCR analysis revealed significant down-regulation of carboxypeptidase A4 (CPA4) following FGF-1 treatment or induction of differentiation of human preadipocytes in a BAMBI/PPARγ-independent manner. siRNA-mediated knockdown of CPA4 resulted in enhanced differentiation of human preadipocytes. Furthermore, expression of CPA4 in subcutaneous adipose tissue correlated negatively with indices of local and systemic (liver and muscle) insulin sensitivity. These results identify CPA4 as a negative regulator of adipogenesis that is down-regulated by FGF-1 and a putative deleterious modulator of local and systemic insulin sensitivity. Further investigations are required to define the molecular mechanism(s) involved and potential therapeutic opportunities.
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Adipocitos/metabolismo , Adipogénesis , Carboxipeptidasas A/metabolismo , Factor 1 de Crecimiento de Fibroblastos/farmacología , Resistencia a la Insulina , Adipocitos/citología , Adipocitos/efectos de los fármacos , Adulto , Carboxipeptidasas A/genética , Células Cultivadas , Regulación hacia Abajo , Humanos , Hígado/metabolismo , Masculino , Proteínas de la Membrana/metabolismo , Persona de Mediana Edad , Músculo Esquelético/metabolismo , PPAR gamma/metabolismoRESUMEN
BACKGROUND & AIM: Western diets rich in animal protein and poor in fruit and vegetables increase the body acid load, a predictor of type 2 diabetes risk. The relationships between dietary acid load, mild metabolic acidosis and insulin resistance remain unclear. The objective of this study was to assess the association between dietary acid load, body acid/base markers and peripheral insulin resistance at baseline and following a short-term overfeeding intervention in healthy individuals. METHODS: In a cross-sectional study of 104 men and women, insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp. Plasma lactate, a marker of metabolic acidosis, was assessed and acid load scores (potential renal acid load, PRAL and net endogenous acid production, NEAP) derived from diet diaries. The cohort was grouped into lean and overweight/obese and the latter further classified as insulin-sensitive (Obsen) and insulin-resistant (Obres) based on hyperinsulinemic-euglycemic clamp glucose infusion rate (GIR, top tertile vs. bottom 2 tertiles). A subset of 40 individuals participated in an overfeeding intervention (+1250 kcal/day) for 28 days and studies repeated. RESULTS: Obsen and Obres were matched for adiposity (BMI and fat mass, both P = 1). Fasting plasma lactate was higher in Obres (0.78 [0.63-1.14] mmol/L) compared with both lean (0.71 [0.44-0.90] mmol/L, P = 0.02) and Obsen (0.67 [0.56-0.79] mmol/L, P = 0.04) and not different between lean and Obsen (P = 0.9). Overfeeding was characterized by an increase in dietary acid load scores PRAL (P = 0.003) and NEAP (P = 0.05), a reduction in GIR necessary to maintain euglycemia (P = 0.03) and an increase in fasting plasma lactate (P = 0.02). The change in lactate was inversely associated with the change in GIR (r = -0.36, P = 0.03). CONCLUSIONS: Mild metabolic acidosis, measured by plasma lactate, aligns with insulin resistance independent of obesity and is induced by short-term increases in energy and dietary acid load in healthy humans. Further studies are required to determine whether buffering mild metabolic acidosis improves insulin resistance and reduces diabetes risk.
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Acidosis/diagnóstico , Diabetes Mellitus Tipo 2/diagnóstico , Dieta Occidental/efectos adversos , Hiperfagia/sangre , Resistencia a la Insulina , Acidosis/etiología , Ácidos/sangre , Adiposidad , Adulto , Biomarcadores/sangre , Glucemia/metabolismo , Índice de Masa Corporal , Estudios Transversales , Diabetes Mellitus Tipo 2/etiología , Registros de Dieta , Femenino , Técnica de Clampeo de la Glucosa , Humanos , Hiperfagia/complicaciones , Insulina/sangre , Ácido Láctico/sangre , MasculinoRESUMEN
Herein, we report the first case of concomitant nesidioblastosis, pancreatic neuroendocrine tumor, and intraductal papillary mucinous neoplasia. The combination is significant as each of these pathological entities is independently very rare. The patient was a 33-year-old man who presented with symptomatic hyperinsulinemic hypoglycemia and no risk factors for pancreatic disease. Abdominal imaging showed an isolated 12 mm pancreatic lesion, whilst selective arterial calcium stimulation testing demonstrated multiple territories of insulin excess. He proceeded to subtotal pancreatectomy. Histopathology revealed an endocrine microadenoma, α and ß cell nesidioblastosis, and multifocal intraductal papillary mucinous neoplasia. The endocrine microadenoma and nesidioblastosis stained for insulin, suggesting both likely contributed to hypoglycemia. Glucagon immunohistochemistry was also positive, though there were no clinical features of glucagon excess. Hypoglycemia resolved postoperatively. This case and other evidence from the literature suggest that hyperplasia and neoplasia may occur sequentially in the pancreas, and that endocrine and exocrine tumorigenesis may be linked in some individuals. Further study is required to identify a unifying mechanism, and to elucidate potential ramifications in the management of patients with pancreatic neoplasms.
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Adenoma/complicaciones , Hiperinsulinismo/etiología , Hipoglucemia/etiología , Neoplasias Quísticas, Mucinosas y Serosas/complicaciones , Neoplasias Primarias Múltiples , Nesidioblastosis/complicaciones , Tumores Neuroendocrinos/complicaciones , Neoplasias Pancreáticas/complicaciones , Adenoma/patología , Adenoma/cirugía , Adulto , Biopsia , Glucemia/metabolismo , Diagnóstico Diferencial , Humanos , Hiperinsulinismo/sangre , Hiperinsulinismo/diagnóstico , Hipoglucemia/sangre , Hipoglucemia/diagnóstico , Inmunohistoquímica , Insulina/sangre , Masculino , Neoplasias Quísticas, Mucinosas y Serosas/patología , Neoplasias Quísticas, Mucinosas y Serosas/cirugía , Nesidioblastosis/diagnóstico , Nesidioblastosis/cirugía , Tumores Neuroendocrinos/diagnóstico , Tumores Neuroendocrinos/cirugía , Pruebas de Función Pancreática , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/cirugía , Valor Predictivo de las Pruebas , Factores de Riesgo , Factores de Tiempo , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
Skeletal muscles produce and contribute to circulating levels of IL-6 during exercise. However, when core temperature is reduced, the response is attenuated. Therefore, we hypothesized that hyperthermia may be an important and independent stimulus for muscle IL-6. In cultured C2C12 myotubes, hyperthermia (42°C) increased IL-6 gene expression 14-fold after 1 h and 35-fold after 5 h of 37°C recovery; whereas exposure to 41°C resulted in a 2.6-fold elevation at 1 h. IL-6 protein was secreted and significantly elevated in the cell supernatant. Similar but reduced responses to heat were seen in C2C12 myoblasts. Isolated soleus muscles from mice, exposed ex vivo to 41°C for 1 h, yielded similar IL-6 gene responses (>3-fold) but without a significant effect on protein release. When whole animals were exposed to passive hyperthermia, such that core temperature increased to 42.4°C, IL-6 mRNA in soleus increased 5.4-fold compared with time matched controls. Interestingly, TNF-α gene expression was routinely suppressed at all levels of hyperthermia (40.5-42°C) in the isolated models, but TNF-α was elevated (4.2-fold) in the soleus taken from intact mice exposed, in vivo, to hyperthermia. Muscle HSP72 mRNA increased as a function of the level of hyperthermia, and IL-6 mRNA responses increased proportionally with HSP72. In cultured C2C12 myotubes, when heat shock factor was pharmacologically blocked with KNK437, both HSP72 and IL-6 mRNA elevations, induced by heat, were suppressed. These findings implicate skeletal muscle as a "heat stress sensor" at physiologically relevant hyperthermia, responding with a programmed cytokine expression pattern characterized by elevated IL-6.
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Fiebre/metabolismo , Interleucina-6/metabolismo , Músculo Esquelético/metabolismo , Animales , Células Cultivadas , Regulación de la Expresión Génica/fisiología , Proteínas del Choque Térmico HSP72/genética , Proteínas del Choque Térmico HSP72/metabolismo , Interleucina-6/genética , Masculino , Ratones , Fibras Musculares Esqueléticas/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
BACKGROUND: Yersinia enterocolitica causes an estimated 116,716 illnesses annually in the United States. Black children have historically had the highest rates of infection, with incidence peaking in the winter. METHODS: The Foodborne Diseases Active Surveillance Network (FoodNet) conducts active surveillance for laboratory-confirmed Y. enterocolitica infections, defined as the isolation of Y. enterocolitica or unspeciated Yersinia from a human clinical specimen. We calculated the average annual crude incidence rate per 100,000 persons from 1996 through 2009 and described rates by age, race, and geographic site. To account for changes in the FoodNet catchment area, we used a negative binomial model to estimate statistical changes in incidence using the average annual incidence in 1996-1998 as the baseline. RESULTS: From 1996 through 2009, 2085 Y. enterocolitica infections were reported to FoodNet. The average annual crude incidence was 0.5 per 100,000 persons and was highest in blacks (0.9 per 100,000 persons). Over time, the rate in blacks declined from 3.9 to 0.4 per 100,000 persons. Declines among other racial groups were not as pronounced. The largest decline occurred in black children <5 years old (from 41.5 per 100,000 persons in 1996 to 3.5 per 100,000 persons in 2009). From 2007 through 2009, the highest rate of infection was in Asian children (5.1 per 100,000 persons). Compared with 1996-1998, the incidence in 2009 was 66% (95% confidence interval, 51%-77%) lower among children <5 years old. CONCLUSIONS: Y. enterocolitica infections in FoodNet sites have significantly declined since 1996. These declines were greatest in young black children, the group that initially had the highest incidence, possibly as the result of educational efforts in Georgia.