Pediatric Quality of Life Inventory (PedsQL) 3.2 Diabetes Module for youth with Type 2 diabetes: reliability and validity.

AIM: To test the measurement properties of the revised and updated Pediatric Quality of Life Inventory (PedsQL) 3.2 Diabetes Module originally developed in Type 1 diabetes in youth with Type 2 diabetes. METHODS: The PedsQL 3.2 Diabetes Module and PedsQL Generic Core Scales were administered in a field test study to 100 young people aged 9-25 years with Type 2 diabetes. Factor analysis was conducted to determine the factor structure of the items. RESULTS: The 15-item Diabetes Symptoms Summary Score and 12-item Type 2-specific Diabetes Management Summary Score were empirically derived through factor analysis. The Diabetes Symptoms and Type 2-specific Diabetes Management Summary Scores showed acceptable to excellent reliability across the age groups tested (α = 0.85-0.94). The Diabetes Symptoms and Type 2-specific Diabetes Management Summary Scores evidenced construct validity through large effect size correlations with the Generic Core Scales Total Scale Score (r = 0.67 and 0.57, respectively). HbA1c was correlated with the Diabetes Symptoms and Type 2-specific Diabetes Management Summary Scores (r = -0.13 and -0.22). Minimal clinically important difference (MCID) scores were 5.91 and 7.39 for the Diabetes Symptoms and Type 2-specific Diabetes Management Summary Scores. CONCLUSIONS: The PedsQL 3.2 Diabetes Module Diabetes Symptoms Summary Score and Type 2-specific Diabetes Management Summary Score exhibited satisfactory measurement properties for use as youth self-reported diabetes symptoms and diabetes management outcomes for clinical research and clinical practice for young people with Type 2 diabetes.

Fetal blood-gas values during fetoscopic myelomeningocele repair performed under carbon dioxide insufflation.

Fetoscopic myelomeningocele (MMC) repair is performed using intrauterine carbon dioxide (CO2 ) insufflation. Sheep experiments have shown that CO2 insufflation is associated with significant fetal acidemia; however, corresponding data for human pregnancy are not available. We performed umbilical venous cord blood sampling in three patients during fetoscopic MMC repair at 25 + 1, 25 + 3 and 24 + 0 weeks' gestation, respectively. Fetal venous pH at the beginning of CO2 insufflation was 7.36, 7.46 and 7.37, respectively in the three fetuses, and repeat values were 7.28, 7.35 and 7.36 after 181, 159 and 149 min, respectively. The partial pressure of oxygen and CO2 was maintained in the normal range during these times, and pH decrease was less in Patient 3 who received humidified CO2 insufflation. Our observations suggest that, in contrast to sheep experiments, CO2 insufflation during fetoscopic myelomeningocele repair does not cause acidemia in human fetuses. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Maternal blood-pressure trends throughout pregnancy and development of pre-eclampsia in women receiving first-trimester aspirin prophylaxis.

OBJECTIVES: To study women who initiated aspirin in the first trimester for high risk of pre-eclampsia, and compare blood-pressure trends throughout pregnancy between those with normal outcome and those who subsequently developed pre-eclampsia. METHODS: Women were enrolled into a prospective observational study at 9-14 weeks' gestation. This was a secondary analysis of those who started daily doses of 81 mg of aspirin before 16 weeks for increased risk of pre-eclampsia based on maternal history and bilateral uterine artery notching. Enrollment characteristics and blood-pressure measurements throughout gestation were compared between women who did and those who did not develop pre-eclampsia. RESULTS: Of the 237 women who initiated first-trimester aspirin prophylaxis, 29 (12.2%) developed pre-eclampsia. A total of 2881 serial blood-pressure measurements obtained between 4 and 41 weeks' gestation (747 in the first trimester, 1008 in the second and 1126 in the third) showed that women with pre-eclampsia started pregnancy with higher blood pressure and maintained this trend despite taking aspirin (mean arterial blood pressure in women with pre-eclampsia = (0.13 × gestational age (weeks)) + 93.63, vs (0.11 × gestational age (weeks)) + 82.61 in those without; P < 0.005). First-trimester diastolic and second-trimester systolic blood pressure were independent risk factors for pre-eclampsia (ß = 1.087 and 1.050, respectively; r2  = 0.24, P < 0.0001). When average first-trimester diastolic blood pressure was >74 mmHg, the odds ratio for pre-eclampsia was 6.5 (95% CI, 2.8-15.1; P < 0.001) and that for pre-eclampsia before 34 weeks was 14.6 (95% CI, 1.72-123.5; P = 0.004). If, in addition, average second-trimester systolic blood pressure was >125 mmHg, the odds ratio for pre-eclampsia was 9.4 (95% CI, 4.1-22.4; P < 0.001) and that for early-onset disease was 34.6 (95% CI, 4.1-296.4; P = 0.004). CONCLUSION: In women treated with prophylactic aspirin from the first trimester, those who develop pre-eclampsia have significantly and sustained higher blood pressure from the onset of pregnancy compared with those who do not develop pre-eclampsia. This raises the possibility that mildly elevated blood pressure predisposes women to abnormal placentation, which then acts synergistically with elevated blood pressure to predispose such women to pre-eclampsia to a degree that is incompletely mitigated by aspirin. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Strain-specific antiviral activity of iminosugars against human influenza A viruses.

OBJECTIVES: Drugs that target host cell processes can be employed to complement drugs that specifically target viruses, and iminosugar compounds that inhibit host α-glucosidases have been reported to show antiviral activity against multiple viruses. Here the effect and mechanism of two iminosugar α-glucosidase inhibitors, N-butyl-deoxynojirimycin (NB-DNJ) and N-nonyl-deoxynojirimycin (NN-DNJ), on human influenza A viruses was examined. METHODS: The viruses examined were a recently circulating seasonal influenza A(H3N2) virus strain A/Brisbane/10/2007, an older H3N2 strain A/Udorn/307/72, and A/Lviv/N6/2009, a strain representative of the currently circulating pandemic influenza A(H1N1)pdm09 virus. RESULTS: The inhibitors had the strongest effect on Brisbane/10 and NN-DNJ was more potent than NB-DNJ. Both compounds showed antiviral activity in cell culture against three human influenza A viruses in a strain-specific manner. Consistent with its action as an α-glucosidase inhibitor, NN-DNJ treatment resulted in an altered glycan processing of influenza haemagglutinin (HA) and neuraminidase (NA), confirmed by MS. NN-DNJ treatment was found to reduce the cell surface expression of the H3 subtype HA. The level of sialidase activity of NA was reduced in infected cells, but the addition of exogenous sialidase to the cells did not complement the NN-DNJ-mediated inhibition of virus replication. Using reassortant viruses, the drug susceptibility profile was determined to correlate with the origin of the HA. CONCLUSIONS: NN-DNJ inhibits influenza A virus replication in a strain-specific manner that is dependent on the HA.

Visceral smooth muscle α-actin deficiency associated with chronic intestinal pseudo-obstruction in a Bengal cat (Felis catus x Prionailurus bengalensis).

An adult Bengal cat (Felis catus × Prionailurus bengalensis) with a prolonged history of partial anorexia, regurgitation, and weight loss and a clinical, radiographic, and ultrasonographic diagnosis of persistent megaesophagus and gastrointestinal ileus was submitted for necropsy. The intestinal tract was diffusely distended by gas and fluid with appreciable loss of muscle tone and an absence of luminal obstruction, consistent with the clinical history of chronic intestinal pseudo-obstruction. Histologically, the autonomic nervous system was intact, but the smooth muscle within the gastrointestinal wall exhibited a marked basophilia that was most pronounced in the jejunum. Immunohistochemistry for neurofilament, synaptophysin, CD117, and desmin demonstrated that the number of myenteric ganglia, number of interstitial cells, and leiomyocyte desmin content were similar when compared with the unaffected age- and species-matched control. Immunohistochemistry for smooth muscle α-actin demonstrated a striking loss of immunoreactivity, predominantly in the circular layer of the jejunum, that corresponded with the tinctorial change in leiomyocytes. Transmission electron microscopy revealed loss of myofibrils, loss of organelle polarity, and significantly larger central mitochondria (megamitochondria) in affected leiomyocytes, as well as nonspecific degenerative changes. Although the presence of a primary leiomyopathy and a causal relationship could not be confirmed in this case, leiomyopathies are considered a cause of chronic intestinal pseudo-obstruction in human medicine, and loss of smooth muscle α-actin immunoreactivity is one recognized marker for intestinal dysmotility.

A reduced-energy intake, well-balanced diet improves weight control in children with Prader-Willi syndrome.

BACKGROUND: Children with Prader-Willi syndrome (PWS) have a predictable pattern of weight gain, with obesity beginning in early childhood and worsening as they get older and hyperphagia increases. Data on the most effective dietary modifications are scant and primarily anecdotal. As part of a longitudinal study investigating the natural history of PWS, we evaluated the effect of a well-balanced, energy-restricted diet on body composition and weight in young children with PWS. METHODS: Sixty-three children, aged 2-10 years, with genetically proven PWS participated in the present study. These children had measurements of body composition by dual-energy X-ray absorptiometry and resting energy expenditure (REE), as well as a 3-day diet history analysis both before and after intervention. Energy calculations were based on the individual's REE, with the recommendation that the macronutrients of the diet consist of 30% fat, 45% carbohydrates and 25% protein, with at least 20 g of fibre per day. RESULTS: Thirty-three families adhered to our dietary recommendations for both energy intake and macronutrient distribution. Those 33 children had lower body fat (19.8% versus 41.9%; P < 0.001) and weight management (body mass index SD score 0.3 versus 2.23; P < 0.001) than those whose parents followed the energy intake recommendations but did not alter the macronutrient composition of the diet. Those who followed our recommendations also had a lower respiratory quotient (0.84 versus 0.95; P = 0.002). CONCLUSIONS: Our recommendation for an energy-restricted diet with a well-balanced macronutrient composition and fibre intake improves both weight and body composition in children with PWS compared to a simple energy-restricted diet.

Cellular immune responses persist and humoral responses decrease two decades after recovery from a single-source outbreak of hepatitis C.

As acute hepatitis C virus (HCV) infection is clinically inapparent in most cases, the immunologic correlates of recovery are not well defined. The cellular immune response is thought to contribute to the elimination of HCV-infected cells and a strong HCV-specific T-helper-cell (Th) response is associated with recovery from acute hepatitis C (ref. 2). However, diagnosis of resolved hepatitis C is based at present on the detection of HCV-specific antibodies and the absence of detectable HCV RNA, and detailed comparison of the humoral and cellular immune response has been hampered by the fact that patient cohorts as well as HCV strains are usually heterogeneous and that clinical data from acute-phase and long-term follow-up after infection generally are not available. We studied a cohort of women accidentally exposed to the same HCV strain of known sequence and found that circulating HCV-specific antibodies were undetectable in many patients 18-20 years after recovery, whereas HCV-specific helper and cytotoxic T-cell responses with an interferon (IFN)-gamma-producing (Tc1) phenotype persisted. The data indicate these HCV-specific CD4 + and CD8+ T cells are biomarkers for a prior HCV exposure and recovery. Because of undetectable antibodies against HCV, the incidence of self-limited HCV infections and recovery may be underestimated in the general population.

The influence of ankle joint movement on knee joint kinesthesia at various movement velocities.

The purpose of this study was to determine if gastrocnemius elongation or shortening and direction and velocity of knee movement influenced knee kinesthesia. Healthy volunteers sat with their knee flexed (20 degrees) and was then passively rotated (flexion or extension) at three velocities (0.5, 2, or 10 degrees/s) while the ankle was either fixed or rotated (dorsiflexed or plantar flexed at 0.17, 0.65, or 3.3 degrees/s) creating gastrocnemius elongation or shortening. Subjects activated a thumb switch, stopping motion once they detected onset and direction of the motion. Detection of passive movement sense (DPMS) was the angular movement before activation of a thumb-switch. Significant differences (P=0.003) in the rate of change in DPMS across a variety of movement velocities was observed but shortening or elongation of the gastrocnemius did not affect DPMS. Gastrocnemius elongation/shortening did not affect knee DPMS, simple reaction time plays an important role in testing kinesthesia especially at faster movements. While feedback from the gastrocnemius muscle plays a limited role in healthy subjects, differences in testing velocities may incorporate higher levels of central nervous system processing. Clinical measures of kinesthesia can be affected by both movement direction and movement velocity that are speed dependent.