Investigation of the effect of dietary intake of omega-3 polyunsaturated fatty acids on trauma-induced white matter injury with quantitative diffusion MRI in mice

Previous studies suggest that long-term supplementation and dietary intake of omega-3 polyunsaturated fatty acids (PUFAs) may have neuroprotective effects following brain injury. The objective of this study was to investigate potential neuroprotective effects of omega-3 PUFAs on white matter following closed-head trauma. The closed-head injury model of engineered rotational acceleration (CHIMERA) produces a reproducible injury in the optic tract and brachium of the superior colliculus in mice. Damage is detectable using diffusion tensor imaging (DTI) metrics, particularly fractional anisotropy (FA), with sensitivity comparable to histology. We acquired in vivo (n = 38) and ex vivo (n = 41) DTI data in mice divided into sham and CHIMERA groups with two dietary groups: one deficient in omega-3 PUFAs and one adequate in omega-3 PUFAs. We examined injury effects (reduction in FA) and neuroprotection (FA reduction modulated by diet) in the optic tract and brachium. We verified that diet did not affect FA in sham animals. In injured animals, we found significantly reduced FA in the optic tract and brachium (~10% reduction, p < 0.001), and Bayes factor analysis showed strong evidence to reject the null hypothesis. However, Bayes factor analysis showed substantial evidence to accept the null hypothesis of no diet-related FA differences in injured animals in the in vivo and ex vivo samples. Our results indicate no neuroprotective effect from adequate dietary omega-3 PUFA intake on white matter damage following traumatic brain injury. Since damage from CHIMERA mainly affects white matter, our results do not necessarily contradict previous findings showing omega-3 PUFA-mediated neuroprotection in gray matter.     

Fasting Capillary Glucose as a Screening Test for Ruling Out Gestational Diabetes Mellitus

ObjectiveA common approach to screening for gestational diabetes mellitus (GDM) is the testing of all pregnant women with a one-hour, 50 g glucose challenge test (GCT), followed by a diagnostic oral glucose tolerance test (OGTT) when the GCT is positive (≥ 7. 8 mmol/L). As only a small subset of those with a positive GCT will have GDM, many more women undergo the OGTT than may be necessary. In this context, we hypothesized that measurement of fasting capillary glucose (FCG) could provide a strategy for reducing the number of unnecessary OGTTs. Thus, we sought to identify a threshold level of FCG below which GDM could be ruled out following a positive GCT, without need for the OGTT.MethodsFollowing a positive GCT, 888 women underwent measurement of FCG prior to their OGTT. We evaluated the test characteristics of FCG for identifying the 209 women diagnosed with GDM on the OGTT.ResultsFasting capillary glucose was positively associated with each glucose measurement on the OGTT (all P < 0.001) and inversely related to insulin sensitivity and pancreatic beta-cell function (both P < 0. 001). As FCG increased, the prevalence of GDM progressively rose (P < 0. 001). However, the area under the curve of the receiver-operating characteristic curve for FCG in predicting GDM was modest (0.67). Although using an FCG threshold of 4.8 mmol/L could reduce the number of OGTTs by 28.4%, this approach would miss 18.2% of cases of GDM.ConclusionFasting capillary glucose is associated with glycemia, insulin sensitivity, and pancreatic beta-cell function. However, a single FCG measurement is insufficient for reliably ruling out GDM after an abnormal GCT.     

Female urinary incontinence and intravaginal electrical stimulation: an observational prospective study

Objective

To assess the efficacy of intravaginal electrical stimulation in the management of female urinary incontinence.

Study design

359 Women with urinary incontinence (207 with stress incontinence [group A], 33 with urge incontinence [group B] and 119 with mixed urinary incontinence [group C]) were included in this multicenter prospective observational study. Patients were managed by home intravaginal electrical stimulation of the pelvic floor for 20–30 min per day, 5 days a week, for a period of 10 weeks. Identical clinical assessments were performed before and after pelvic floor rehabilitation, comprising a voiding diary and validated symptom and quality of life scores.

Results

Objective assessment demonstrated an overall cure rate of 63.5% (228/359): 65.7% (136/207) for group A, 57.6% (19/33) for group B, and 61.3% (73/119) for group C. The overall significant improvement rate was 15.6% (56/359): 14.6% (30/207) for group A, 24.2% (8/33) for group B and 15.1% (18/119) for group C. All domains of quality of life were significantly improved after pelvic floor muscle training (p < 0.0001) with a patient satisfaction rate of 83.6%. Treatment was well tolerated with 1.4% (5/359) of patients describing pain at the highest stimulation intensities. No significant difference was observed between the various types of electrodes used (p < 0.0001).

Conclusion

The quantitative and qualitative efficacy in terms of social and psychological consequences and quality of life of home pelvic floor muscle training stimulators probably make this treatment modality one of the first-line treatments for female stress urinary incontinence.     

A two-stage,single-arm,phase II study of EGCG-enriched green tea drink as a maintenance therapy in women with advanced stage ovarian cancer

Objectives

A two-stage, single-arm, phase II study was conducted to assess the effectiveness and safety of an epigallocatechin gallate (EGCG)-enriched tea drink, the double-brewed green tea (DBGT), as a maintenance treatment in women with advanced stage serous or endometrioid ovarian cancer (clinicaltrials.gov, NCT00721890).

Methods

Eligible women had FIGO stage III-IV serous or endometrioid ovarian cancer. They had to undergo complete response after debulking surgery followed by 6 to 8 cycles of platinum/taxane chemotherapy at the Centre Hospitalier Universitaire de Québec. They all had to drink the DBGT, 500 mL daily until recurrence or during a follow-up of 18 months. The primary endpoint was the absence of recurrence at 18 months. Statistical analyses were done according to the principle of intention to treat. Using a two-stage design, the first stage consisted of 16 enrolled patients. At the end of the follow-up, if 7 or fewer patients were free of recurrence, the trial stopped. Otherwise, accrual would continue to a total of 46 patients.

Results

During the first stage of the study, only 5 of the 16 women remained free of recurrence 18 months after complete response. Accordingly, the clinical trial was terminated. Women's adherence to DBGT was high (median daily intake during intervention, 98.1%, interquartile range: 89.7–100%), but 6 women discontinued the intervention before the end of their follow-up. No severe toxicity was reported.

Conclusions

DBGT supplementation does not appear to be a promising maintenance intervention in women with advanced stage ovarian cancer after standard treatment.     

Predicting late-onset growth abnormalities using growth velocity between trimesters

Objectives.?To determine whether growth velocity parameters derived from routine prenatal ultrasound measurements at first, second and third trimester can identify normal growth at term as well as late-onset growth abnormalities.

Material and methods.?Longitudinal study of fetal growth in normal singleton pregnancies with three normal ultrasound examinations and delivered at term. Fetuses were classified into 3 groups (?<?10th percentile, 10–90th percentile, >?90th percentile) based on birth weight. Multiple regression on birth weight classification was used to build up a prediction equation of fetal growth potential (FGP) based on fetal biometry and fetal growth velocity parameters between ultrasound examinations. Best cut-off value for FGP predicting growth restriction and macrosomia were defined.

Results.?356 pregnancies were included. Fetal biometry growth velocities between examinations were calculated for all measurements. Using best cut-off values, the estimated sensitivity, specificity and odds ratio were: 60% [44;74], 91%[89;92] and 14.55 [6.30;33.98] and 53% [36;69], 89%[88;91] and 10 [4.27;23.49] for the prediction of growth restriction and macrosomia, respectively.

Discussion.?Fetal growth potential can be derived and calculated from standard ultrasound measurements. It can improve identification of these fetuses at risk for late-onset growth abnormalities and their related morbidity.     

Acknowledgement of Reviewers

Objective. Pregnant women with an abnormal screening glucose challenge test (GCT) but without gestational diabetes mellitus (GDM) on subsequent oral glucose tolerance test (OGTT) are at increased risk of delivering macrosomic and large for gestational age (LGA) neonates. We thus sought to evaluate the maternal constitutional and biochemical factors that determine infant birth weight in this patient population.

Methods. Women with an abnormal GCT were evaluated at the time of their OGTT in late pregnancy. This analysis was restricted to Caucasian women without GDM (N = 86). Maternal demographic and biochemical factors were evaluated in relation to infant birth weight and LGA.

Results. After adjustment for length of gestation, birth weight was positively associated with pre-pregnancy body mass index (BMI) (r = 0.31, p = 0.0063) and negatively correlated with maternal serum levels of the insulin-sensitizing protein adiponectin (r = ?0.30, p = 0.0084). On multiple linear regression analysis, pre-pregnancy BMI and weight gain in pregnancy were positive independent determinants of infant birth weight, while family history of diabetes emerged as a negative independent correlate. Logistic regression analysis confirmed that pre-pregnancy BMI was a positive predictor of LGA (odds ratio (OR) = 1.25, 95% confidence interval (CI) 1.05–1.49), whereas family history of diabetes was again identified as a negative determinant (OR = 0.10, 95% CI 0.02–0.59). In contrast, neither measures of glycemia nor insulin resistance/sensitivity were independently associated with birth weight or LGA.

Conclusion. In pregnant women with an abnormal GCT but without GDM, pre-gravid maternal obesity predicts increased infant birth weight, whereas family history of diabetes is independently associated with decreased infant size.     

Posterior Bearing Overhang Following Medial and Lateral Mobile Bearing Unicompartmental Knee Replacements

This study explores the extent of bearing overhang following mobile bearing Oxford unicompartmental knee replacement (OUKR) (Oxford Phase 3, Zimmer Biomet). The Oxford components are designed to be fully congruent, however knee movements involve femoral rollback, which may result in bearing overhang at the posterior margin of the tibial implant, with potential implications for; pain, wear, and dislocation. Movement is known to be greater, and therefore posterior overhang more likely to occur, with; lateral compared to medial implants, anterior cruciate ligament (ACL) deficiency (ACLD) compared to ACL intact (ALCI), and at extremes of movement. Twenty‐four medial, and 20 domed lateral, OUKRs underwent sagittal plane knee fluoroscopy during step‐up and forward lunge exercises. The bearing position was inferred from the relative position of the femoral and tibial components. On the basis of the individual component sizes and geometry the extent the posterior part of the bearing which overhung the posterior part of the tibial component was calculated. There was no significant posterior overhang in knees with medial implants. Knees with lateral domed implants exhibited overhang at flexion angles beyond 60°, the magnitude of which increased with increasing flexion angle, reaching a maximum of 50% of the bearing length at 140° (range 0–140°). This demonstrates a clear difference between the kinematics, and prevalence and extent of posterior bearing overhang between medial and lateral OUKRs. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1938–1945, 2019     

Bone turnover markers and bone mineral density response with risedronate therapy: Relationship with fracture risk and patient adherence

Surrogate markers of fracture risk—bone turnover markers (BTMs) and bone mineral density (BMD)—can be used to monitor treatment response. We assessed whether changes in these markers greater than the least significant change (LSC) were associated with fracture risk reduction and greater adherence. This secondary analysis of the Improving Measurements of Persistence on ACtonel Treatment (IMPACT) study—a multinational prospective, open‐label, cluster‐randomized study of postmenopausal women on oral risedronate 5 mg/d for 52 weeks—assessed adherence by electronic monitors. Urinary N‐terminal cross‐linked telopeptide of type 1 collagen (uNTX) and serum C‐terminal cross‐linked telopeptide of type 1 collagen (sCTX) levels were assessed at baseline and weeks 10 and 22, and BMD at baseline and week 52. Fractures were recorded as adverse events. In 2302 women, responses beyond LSC in BTMs (uNTX and sCTX) and BMD (spine only) were associated with a reduced risk of nonvertebral fractures (NVFs) and all fractures. NVF incidence was about 50% lower in patients with 30% or more of uNTX reduction at week 22 (1.6%) than in those with less than 30% reduction (3.2%, p = .015). NVFs also were reduced in patients with more than 3% spine BMD increase at 52 weeks than those with 3% or less. Responses greater than LSC in BTMs and BMD were associated with greater adherence, but there was no association between adherence and fracture outcomes at 52 weeks. Changes greater than the LSC in BTMs and BMD reflect better treatment adherence, were associated with fracture risk reduction, and identify differences in individual responsiveness to risedronate. © 2011 American Society for Bone and Mineral Research.     

Spectrum of mutations in Gitelman syndrome

Gitelman's syndrome (GS) is a rare, autosomal recessive, salt-losing tubulopathy caused by mutations in the SLC12A3 gene, which encodes the thiazide-sensitive NaCl cotransporter (NCC). Because 18 to 40% of suspected GS patients carry only one SLC12A3 mutant allele, large genomic rearrangements may account for unidentified mutations. Here, we directly sequenced genomic DNA from a large cohort of 448 unrelated patients suspected of having GS. We found 172 distinct mutations, of which 100 were unreported previously. In 315 patients (70%), we identified two mutations; in 81 patients (18%), we identified one; and in 52 patients (12%), we did not detect a mutation. In 88 patients, we performed a search for large rearrangements by multiplex ligation-dependent probe amplification (MLPA) and found nine deletions and two duplications in 24 of the 51 heterozygous patients. A second technique confirmed each rearrangement. Based on the breakpoints of seven deletions, nonallelic homologous recombination by Alu sequences and nonhomologous end-joining probably favor these intragenic deletions. In summary, missense mutations account for approximately 59% of the mutations in Gitelman's syndrome, and there is a predisposition to large rearrangements (6% of our cases) caused by the presence of repeated sequences within the SLC12A3 gene.     

Towards the bionic body

Global technological progress is enabling people to see their mutilated bodies assisted by sophisticated prostheses. Multi-disciplinary and associative care help patients relearn daily living activities and accomplish various exploits.