BACKGROUND: Emerging evidence suggests that poor dietary quality is an important risk factor for disability. However, few studies have compared adherence to dietary patterns and disability, and none among Puerto Rican adults.
OBJECTIVE: This study was designed to examine relationships between three dietary patterns, including DASH, Mediterranean (MeDS), and Healthy Eating Index (HEI-2010), and ∼6-y incidence of activities of daily living (ADL) and instrumental ADL (IADL) disability, and to assess potential mediation by handgrip strength.
METHODS: Data are from the Boston Puerto Rican Health Study (BPRHS), a longitudinal cohort of Puerto Rican adults aged 45-75 y (n=1502). Adherence to dietary pattern variables were derived from food frequency questionnaire (FFQ) data averaged at baseline and ∼2-y. Handgrip strength was assessed at baseline. Cox proportional hazards models were used to assess longitudinal associations between DASH, MeDS, HEI-2010, and incident ∼6-y ADL (and subscales) and IADL disability. Mediation by handgrip strength was also tested.
RESULTS: Participants with higher adherence DASH had lower risk of ADL, ADL mobility, and ADL manual dexterity disabilities (HR = 0.96, 95%CI: 0.91, 0.98; HR = 0.96, 95%CI: 0.92, 0.99; HR = 0.95, 95%CI: 0.92, 0.98, respectively).Higher adherence to MeDS was associated with lower risk of ADL and ADL mobility disabilities (HR = 0.89, 95%CI: 0.81, 0.98; HR = 0.90, 95%CI: 0.82, 1.00), and higher adherence to HEI with lower risk of ADL manual dexterity (HR = 0.98, 95%CI: 0.97, 0.99) in fully adjusted models. Only DASH tended to be associated with IADL (HR = 0.97, 95%CI: 0.94, 1.00). Baseline handgrip strength was a mediator between HEI and ADL manual dexterity (23.7% of the indirect effect was explained through handgrip strength).
CONCLUSIONS: Higher adherence to a healthy diet pattern may decrease risk of disability and may be an important prevention strategy for ADL and IADL disability associated with aging.

We report the results of three validation studies for a short measure of emotional, physical, and behavioral markers of eustress and distress as they occur when individuals encounter stressful events in academic and organizational settings. Given the importance of the distinction between \"positive\" and \"negative\" stress as well as the recent resurgence of research exploring the differences between challenge and hindrance stress and between eustress and distress, it is important to put forward a short, validated scale that evaluates these constructs. Our short measure-the MEDS-therefore has important theoretical as well as practical implications. By showing that the eustress and distress subscales have adequate internal consistency and good construct and criterion validity, we open new avenues for research that extends our knowledge and understanding of the antecedents and consequences of eustress and distress. We also discuss appropriate uses of the scale in educational and organizational settings.

Recently, an autosomal recessive disorder including the triad of microcephaly, infantile epileptic encephalopathy, and permanent neonatal diabetes syndrome (MEDS, OMIM#614231) has emerged as a new distinguishing syndrome. Eight cases of whom seven from Arab countries, have been reported in association with biallelic variants in the IER3IP1 gene (Immediate early response-3 interacting protein-1). Here, we describe a Tunisian boy who presented with permanent neonatal diabetes, microcephaly, generalized seizures and hypovirilized external genitalia consisting of a small genitalia and unilateral cryptorchidism. Chromosomal analysis indicated a 46, XY karyotype in all metaphases. Exome sequencing identified a homozygous missense variant (c.62 T > G; p. Val21Gly) in the IER3IP1 gene, that is predicted to alter the protein structure within the hydrophobic/transmembrane. This variant was previously reported in two cases associated with MEDS. This is the first reported case of MEDS in Tunisia. Our report focuses on the IER3IP1 related phenotypic spectrum and assumes abnormal genitalia as part of the syndrome. Consequently, we recommend to perform hormonal testing on this topic to understand the effect of the IER3IP1 variant on the male genital pathway.

BACKGROUND: Neural tube defects (NTDs) are among the most common and severe congenital defects in humans. Their genetic etiology is complex and remains poorly understood. The Mediator complex (MED) plays a vital role in neural tube development in animal models. However, no studies have yet examined the role of its human homolog in the etiology of NTDs.
METHODS: In this study, 48 pairs of neural lesion site and umbilical cord tissues from NTD and 21 case-parent trios were involved in screening for NTD-related somatic and germline de novo variants. A series of functional cell assays were performed. We generated a Med12 p.Arg1784Cys knock-in mouse using CRISPR/Cas9 technology to validate the human findings.
RESULTS: One somatic variant, MED12 p.Arg1782Cys, was identified in the lesion site tissue from an NTD fetus. This variant was absent in any other normal tissue from different germ layers of the same case. In 21 case-parent trios, one de novo stop-gain variant, MED13L p.Arg1760∗, was identified. Cellular functional studies showed that MED12 p.Arg1782Cys decreased MED12 protein level and affected the regulation of MED12 on the canonical-WNT signaling pathway. The Med12 p.Arg1784Cys knock-in mouse exhibited exencephaly and spina bifida.
CONCLUSIONS: These findings provide strong evidence that functional variants of MED genes are associated with the etiology of some NTDs. We demonstrated a potentially important role for somatic variants in the occurrence of NTDs. Our study is the first study in which an NTD-related variant identified in humans was validated in mice using CRISPR/Cas9 technology.

暂无摘要。

To build a model to predict 30-day mortality and compare it to prediction based on the Mortality in Emergency Department Sepsis (MEDS) score in patients aged 75 years or older treated for infection and systemic inflammatory response syndrome (SIRS) in the emergency department.
Prospective analysis of a convenience cohort of patients aged 75 years or older treated for infection and SIRS in 13 Spanish emergency departments in 2013. We recorded demographic variables; comorbidity; risk factors for poor outcome; functional dependence at baseline; site of infection; and hemodynamic, clinical and laboratory findings on start of care.The main outcome variable was 30-day all-cause mortality.
Three hundred seventy-nine patients with a mean (SD) age of 84 (5.8) years were included; 186 (49.,1%) were women, 150 (39.6%) had a high degree of comorbidity, and 113 (34.2%) had a high level of functional dependence. Seventy-nine (20.8%) died within 30 days. The model built by the infection working group (INFURG) of the Spanish Society of Emergency Medicine (SEMES) included the presence of metastasis from a solid tumor (odds ratio [OR], 5.4; 95% CI, 1.6-18.2; P=.006), respiratory insufficiency (OR, 3.02; 95% CI, 1.5-6.0; P=.002), renal insufficiency (OR, 2.4; 95% CI, 1.0-5.5; P=.045), arterial hypertension (OR, 2.4; 95% CI, 1.2-5.0; P=.015), and altered level of consciousness (OR, 2.9; 95% CI, 1.4-5.8; P=.003). The area under the receiver operating characteristic curve of the INFURG-OLDER model was 0.78 (95% CI, 0.72-0.84; P<.001) (vs 0.72 (95% CI, 0.64-0.80; P<.001 for the MEDS model).
The INFURG-OLDER model has good predictive ability for 30-day mortality in patients aged 75 years or older who are treated in emergency departments for SIRS.
. Diseñar un modelo de riesgo para predecir la mortalidad a los 30 días, y compararlo con la escala MEDS (Mortality in Emergency Department), en pacientes 75 años atendidos por infección con síndrome de respuesta inflamatoria sistémica (SIRS) en los servicios de urgencias (SU).
Estudio analítico de cohortes prospectivo que incluyó por oportunidad a pacientes 75 años atendidos por infección con SIRS en 13 SU españoles durante el año 2013. Se recogieron variables demográficas, comorbilidad, factores de riesgo de mala evolución, situación funcional basal, modelo de infección, y parámetros hemodinámicos, clínicos y analíticos en el momento de la primera atención. La variable de resultado principal fue mortalidad por cualquier causa a los 30 días.
Se incluyeron 379 pacientes con edad media de 84 (DE 5,8) años, 186 (49,1%) fueron mujeres, 150 (39,6%) tenían alto grado de comorbilidad y 113 (34,2%) dependencia funcional grave. Setenta y nueve pacientes (20,8%) fallecieron a los 30 días. El modelo INFURG-OLDER incluyó la presencia de tumor sólido con metástasis (OR = 5,4; IC95% 1,6- 18,2; p = 0,006), la insuficiencia respiratoria (OR = 3,02; IC95% 1,5-6,0; p = 0,002), la insuficiencia renal (OR = 2,4; IC95% 1,0-5,5; p = 0,045), la hipotensión arterial (OR = 2,4; IC95% 1,2-5,0; p = 0,015) y la disminución del nivel de consciencia (OR = 2,9; IC95% 1,4-5,8; p = 0,003). El área bajo la curva (ABC) del modelo INFURG-OLDER fue de 0,78 (IC95% 0,72- 0,84; p < 0,001) y el ABC de la escala MEDS fue de 0,72 (IC95% 0,64-0,80; p < 0,001).
El modelo INFURG-OLDER tiene buena capacidad para predecir la mortalidad a los 30 días en los pacientes 75 años atendidos por infección con SIRS en los SU.

OBJECTIVE: Scoring systems have been used to risk stratify in intensive care units (ICU), but not routinely used in emergency departments. The aim of this study was to determine accuracy for predicting mortality in emergency medicine with Sequential Organ Failure Assessment (SOFA), Mortality in ED Sepsis (MEDS) score and Simplified Acute Physiology Score (SAPSII).
METHODS: This is a prospective observational study. Patients presenting with evidence of sepsis were all included. SAPSII, MEDS, and SOFA scores were calculated. Analysis compared areas under the receiver operator characteristic (ROC) curves for 28-day mortality.
RESULTS: Two hundred patients were included; consisting of 31 (14.3%) septic shock. 138 (69%) severe sepsis and 31 (15.5%) infection without organ dysfunction. 53 (26.5%) patients died within 28 days. Area under the ROC curve for mortality was 0.76 for MEDS (0.69-0.82), 0.70 for SAPSII (0.62-0.78); and 1.68 for SOFA (0.60-0.76) scores. Pair wise comparison of AUC between MEDS, SAPSII, SOFA and Lactate were not significant.
CONCLUSIONS: According to our results; SOFA, SAPSII and MEDS were not sufficient to predict mortality. Also this result, MEDS was better than other scoring system.

暂无摘要。

OBJECTIVE: To investigate the prognostic performance of complement components in septic patients, complement 3, membrane attack complex (MAC) and mannose-binding lectin were measured and compared among adult patients with sepsis, severe sepsis and septic shock, as well as between in-hospital nonsurvivors and survivors.
METHODS: The prognostic value of complement components was compared with mortality in emergency department sepsis (MEDS) score.
RESULTS: Median complement 3, MAC and mannose-binding lectin increased directly with the sepsis, severe sepsis and septic shock groups, and were significantly higher in nonsurvivors than in survivors.
CONCLUSIONS: MEDS and MAC independently predicted in-hospital mortality. The prognostic performance of MAC was superior to MEDS as analyzed by receiver operating characteristic curve and area under the curve.

BACKGROUND: Soluble thrombomodulin (sTM) is a sensitive marker of endothelial damage. In this study we investigated the role of sTM in the evaluation of the severity and prognosis of septic patients in the emergency department (ED).
METHODS: A prospective, observational cohort study was performed in the ED of an urban, university hospital. Patients who had suspected infection with two or more criteria of systemic inflammatory response syndrome were consecutively enrolled. sTM, D-Dimer and procalcitonin levels were measured on enrollment, and the Mortality in Emergency Department Sepsis (MEDS) score was calculated. A 30-day follow-up was performed for all patients.
RESULTS: A total of 372 patients with sepsis, 210 patients with severe sepsis and 98 patients with septic shock were enrolled in this study. According to the disease severity, patients were divided into sepsis subgroup and severe sepsis subgroup (including septic shock). In addition, patients were divided into survivors subgroup and non-survivors subgroup according to the 30-day mortality. Plasma sTM levels in patients with severe sepsis were higher than those with sepsis (P<0.001). Compared with survivors, non-survivors has higher plasma sTM levels (P<0.001). Multivariate logistic regression analysis showed that sTM was an independent predictor of severe sepsis (odds ratio 1.11) and 30-day mortality (odds ratio 1.059). Receiver operating characteristic curve analysis showed that sTM was a useful parameter in prediction of severe sepsis (0.859) and 30-day mortality (0.78). Compared with the MEDS score alone, combination of sTM and the MEDS score can improve the accuracy in prediction of severe sepsis and 30-day mortality.
CONCLUSIONS: sTM is a valuable biomarker in the risk stratification and prognosis evaluation of ED sepsis. Furthermore, sTM can enhance the ability of the MEDS score in prediction of severe sepsis and 30-day mortality.