Detection of Zika virus in paired urine and amniotic fluid samples from symptomatic and asymptomatic women and their babies during a disease outbreak: association with neurological symptoms in newborns

Paired maternal and newborn urine and amniotic fluid from 138 subjects collected during a Zika virus (ZIKV) outbreak was analyzed for ZIKV by gene amplification (RT-qPCR), and the findings were correlated with clinical symptoms and neurological anomalies in the babies. ZIKV was detected in 1 of 9 symptomatic women (11.1%) and in 19 of 129 asymptomatic women (14.7%). Neurological manifestations were present in 19 babies (13.7%), 10 of 20 (50%) positive and 9 of 119 (7.6%) negative (p < 0.001) for ZIKV. Twelve (8.6%) urines collected during gestation were ZIKV-positive; only 2 remained positive for ZIKV postpartum. Six (4.1%) newborn urines collected within 1 day of delivery were ZIKV-positive cases. In 3 of these cases, ZIKV was detected in mother’s urine pre- and postpartum and in both mother’s urine and babies’ urine. Four of the amniotic fluid samples (2.9%) were ZIKV-positive. Among ZIKV-negative babies with neurological sequel, 87.5% were female; in contrast, 72.7% ZIKV-positive babies with neurological abnormalities were male (p = 0.019). We conclude that during a ZIKV outbreak, clinical symptoms and ZIKV detection in biological fluids are poor predictors of infection and adverse neurologic sequel in newborns.     

Donation Rates: What Matters?

IntroductionThe increase in the number of donors is the main objective of all transplantation organizations around the world. Further understanding of the factors involved in increasing donation rates is very important for planning future strategies to improve outcomes in each country.Objective and MethodWith this purpose we analyzed the relationship between social and economic factors of the countries and organizational aspects of health systems and institutions dedicated to transplantation in relation to the number of actual donors per million population. We analyzed rates of deceased donors per million population of Latin America, North America, and Europe (20 countries) and correlated them with the human development index and its most important indicators. We also studied the correlation with spending on health and organizational aspects of the health system.ResultsOn the one hand, we found that donation rates (DRs) per million population (pmp) were not statistically significantly correlated with the human development index (significant correlation 0.61 and 0.181). There is a correlation, albeit weak, between observed donation rates and gross domestic product (GDP) of each country (significance, 0.04; correlation, 0.46). On the other hand, there exists a strong correlation between the percentage of GDP spent on health and DRs pmp (significance, 0.01; correlation, 0.53). Those countries with an integrated national health system (P = .01) and a higher percentage of hospitals with intrahospital transplantation coordinators (P = .001) had higher DRs pmp.ConclusionsThe best DRs are closely linked to organizational aspects of the donation system in particular and the health system in general. There is a weak correlation between observed DRs and socio-economic and development indicators of countries. These data should be taken into account in planning future strategies to increase DRs, health plan policies, and investments.     

Mechanisms of glucagon secretion during insulin-induced hypoglycemia in man. Role of the beta cell and arterial hyperinsulinemia

To elucidate the mechanisms controlling the response of glucagon to hypoglycemia, a vital component of the counterregulatory hormonal response, the role of intraislet insulin was studied in seven normal subjects and five subjects with insulin-dependent diabetes mellitus (IDDM) (of less than 15-mo duration). In the normal subjects, hypoglycemia (arterial plasma glucose [PG] 53 +/- 3 mg/dl) induced by an intravenous insulin infusion (30 mU/m2 X min for 1 h, free immunoreactive insulin [FIRI] 58 +/- 2 microU/ml) elicited a 100% fall in insulin secretion and an integrated rise in glucagon of 7.5 ng/ml per 120 min. When endogenous insulin secretion was suppressed by congruent to 50 or congruent to 85% by a hyperinsulinemic-euglycemic clamp (FIRI 63 +/- 1.5 or 147 +/- 0.3 microU/ml, respectively) before hypoglycemia, the alpha cell responses to hypoglycemia were identical to those of the control study. When the endogenous insulin secretion was stimulated by congruent to 100% (hyperinsulinemic-hyperglycemic clamp, FIRI 145 +/- 1.5 microU/ml, PG 132 +/- 2 mg/dl) before hypoglycemia, the alpha cell responses to the hypoglycemia were also superimposable on those of the control study. Finally, in C-peptide negative diabetic subjects made euglycemic by a continuous overnight intravenous insulin infusion, the alpha cell responses to hypoglycemia were comparable to those of normal subjects despite absent beta cell secretion, and were not affected by antecedent hyperinsulinemia (hyperinsulinemic-euglycemic clamp for 2 h, FIRI 61 +/- 2 microU/ml). These results indicate that the glucagon response to insulin-induced hypoglycemia is independent of the level of both endogenous intraislet and exogenous arterial insulin concentration in normal man, and that this response may be normal in the absence of endogenous insulin secretion, in contrast to earlier reports. Thus, loss of beta cell function is not responsible for alpha cell failure during insulin-induced hypoglycemia in IDDM.     

Injuries in Youth Hockey

In brief Although popular reporting would indicate otherwise, overall injury rates in youth hockey have decreased during the past decade. Most injuries that do occur are not serious, but those that are demand prompt and skillful attention: The alarming increase in head, neck, and spine injuries, in addition to the death of a young player struck in the anterior chest by a high-velocity puck, emphasizes the need for a structured on-ice approach to stabilizing and managing injuries ranging from musculoskeletal to life-threatening. More injuries could be avoided by analyzing more injury data, improving both protective equipment and rink design, teaching injury prevention, and strictly enforcing the rules.     

Modified SH2 domain to phototrap and identify phosphotyrosine proteins from subcellular sites within cells

Spatial regulation of tyrosine phosphorylation is important for many aspects of cell biology. However, phosphotyrosine accounts for less than 1% of all phosphorylated substrates, and it is typically a very transient event in vivo. These factors complicate the identification of key tyrosine kinase substrates, especially in the context of their extraordinary spatial organization. Here, we describe an approach to identify tyrosine kinase substrates based on their subcellular distribution from within cells. This method uses an unnatural amino acid-modified Src homology 2 (SH2) domain that is expressed within cells and can covalently trap phosphotyrosine proteins on exposure to light. This SH2 domain-based photoprobe was targeted to cellular structures, such as the actin cytoskeleton, mitochondria, and cellular membranes, to capture tyrosine kinase substrates unique to each cellular region. We demonstrate that RhoA, one of the proteins associated with actin, can be phosphorylated on two tyrosine residues within the switch regions, suggesting that phosphorylation of these residues might modulate RhoA signaling to the actin cytoskeleton. We conclude that expression of SH2 domains within cellular compartments that are capable of covalent phototrapping can reveal the spatial organization of tyrosine kinase substrates that are likely to be important for the regulation of subcellular structures.     

PC-1 amino acid variant Q121 is associated with a lower glomerular filtration rate in type 2 diabetic patients with abnormal albumin excretion rates

OBJECTIVE: To study the relationships between the PC-1 K121Q variant and diabetic nephropathy (DN) in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 125 patients with type 2 diabetes and abnormal albumin excretion rate (AER) (range 20-5416 microg/min) were followed up for 4 years with repeated measurements of glomerular filtration rate (GFR). Genomic DNA was extracted from all patients, and the PC-1 K121Q polymorphism was determined by the PCR AvaII restriction enzyme. A subset of 64 patients underwent a percutaneous kidney biopsy at baseline, and glomerular structure was analyzed by electron microscopic morphometric analysis. At baseline, age (56 +/- 8 vs. 59 +/- 7 years), BMI (28.3 +/- 4.3 vs. 28.6 +/- 3.7 kg/m(2)), known duration of type 2 diabetes (11.1 +/- 7 vs. 11.9 +/- 8 years), and HbA(1c) (8.6 +/- 1.8 vs. 8.4 +/- 1.7%) were similar in K121K (KK, n = 87, 73 men/14 women) and XQ (35 K121Q + 3 Q121Q, n = 38, 27 men/11 women) patients. Baseline GFR was 96 +/- 28 ml. min(-1). 1.73 m(-2) and was related (P = 0.01-0.001) to age, known diabetes duration, and systolic blood pressure. RESULTS: XQ patients had lower GFR (P < 0.05) than KK patients (88 +/- 30 vs. 100 +/- 26 ml. min(-1). 1.73 m(-2)); this difference persisted also after factoring in age and known diabetes duration. The rate of progression of DN was similar in KK and XQ patients: %deltaGFR was 4.1/year (median, range: 22.9-30.6) vs. 4.2/year (9.8-26.7). Morphometric parameters of diabetic glomerulopathy were similar in the two genotype groups. CONCLUSIONS: Among patients with type 2 diabetes with abnormal AER, those carrying the Q PC-1 genotype have more severe DN but not a faster GFR decline than KK patients, thus suggesting faster DN development since diabetes diagnosis in XQ patients.     

Increased urinary albumin excretion, insulin resistance, and related cardiovascular risk factors in patients with type 2 diabetes: evidence of a sex-specific association

OBJECTIVE: While the relevant role of insulin resistance in the pathogenesis of increased urinary albumin excretion (UAE) is well established in type 1 diabetes, its contribution in type 2 diabetes is controversial. Our aim was to investigate whether insulin resistance was associated with increased UAE in a large cohort of patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 363 men and 349 women, aged 61 +/- 9 years, with a disease duration of 11 +/- 9 years and HbA(1c) levels of 8.6 +/- 2.0% were included. Insulin resistance was derived from the homeostasis model assessment of insulin resistance (HOMA(IR)), and UAE was derived from the albumin-to-creatinine ratio (ACR) defined as increased if the value was > or =2.5 mg/mmol in men and > or =3.5 mg/mmol in women. ACR was correlated with HOMA(IR) (r = 0.15, P = 0.0001), independently of age, disease duration, blood pressure, HbA(1c), triglycerides, waist circumference, and smoking. RESULTS: When the two sexes were investigated separately, a significant correlation between ACR and HOMA(IR) was reached in men (n = 363; r = 0.21, P = 0.0001) but not women (n = 349; r = 0.08, P = 0.14), suggesting that insulin resistance and sex may interact (P for interaction = 0.04) in determining UAE. When men were subgrouped into quartiles of HOMA(IR), those of the third and fourth quartile (i.e., the most insulin resistant) were at higher risk to have increased ACR than patients of the first quartile (third quartile: odds ratio 2.2 [95% CI 1.2-4.2], P = 0.01) (fourth quartile: 4.1 [2.2-7.9], P = 0.00002). Finally, ACR was significantly higher in men with two or more insulin resistance-related cardiovascular risk factors (i.e., abdominal obesity, dyslipidemia, and arterial hypertension) than in men with fewer than two insulin resistance-related cardiovascular risk factors (0.90 [0.2-115.1] vs. 1.56 [0.1-1367.6], respectively, P = 0.005). CONCLUSIONS: In type 2 diabetic patients, increased UAE is strongly associated with insulin resistance and related cardiovascular risk factors. This association seems to be stronger in men than in women.