Success of Maternal and Child Health Pipeline Training Programs: Alumni Survey Results

Maternal and Child Health Journal - The Maternal and Child Health (MCH) Pipeline Training Program, promotes development of a diverse health workforce by training undergraduate students from...     

Association of antiviral prophylaxis and rituximab use with posttransplant lymphoproliferative disorders (PTLDs): A nationwide cohort study

Posttransplant lymphoproliferative disorder (PTLD) is a serious complication of solid organ transplantation (SOT). Most PTLD cases are associated with Epstein–Barr virus (EBV) infection. The role of antiviral prophylaxis or rituximab therapy for prevention of PTLD in SOT recipients is controversial. In a nationwide cohort, we assessed the incidence, presentation, and outcome of histologically proven PTLD. We included 4765 patients with a follow-up duration of 23 807 person-years (py). Fifty-seven PTLD cases were identified; 39 (68%) were EBV positive (EBV+ PTLD). Incidence rates for EBV+ PTLD at 1, 2, and 3 years posttransplant were 3.51, 2.24, and 1.75/1000 py and 0.44, 0.25, and 0.29/1000 py for EBV− PTLD. We did not find an effect of antiviral prophylaxis on early and late EBV+ PTLD occurrence (early EBV+ PTLD: SHR 0.535 [95% CI 0.199–1.436], p = .264; late EBV+ PTLD: SHR 2.213, [95% CI 0.751–6.521], p = .150). However, none of the patients (0/191) who received a rituximab-containing induction treatment experienced PTLD, but 57 of 4574 patients without rituximab induction developed PTLD. In an adjusted restricted mean survival time model, PTLD-free survival was significantly longer (0.104 years [95% CI 0.077–0.131]) in patients receiving rituximab as induction treatment. This study provides novel data on the association of rituximab induction and reduced risk for PTLD.     

Right Ventricular Function Predicts Clinical Response to Specific Vasodilator Therapy in Patients with Pulmonary Hypertension

Introduction: We followed patients with pulmonary arterial hypertension (PAH) receiving specific vasodilator therapy and tested for predictors of clinical outcome. Methods: Thirty‐two patients (mean age 39 ± 15 years, 22 women, diagnosed with pulmonary hypertension; PH): 29 with PAH and 3 patients with inoperable chronic thromboembolic PH received therapy with either bosentan, sildenafil, or both and were evaluated with clinical parameters, biomarkers (B‐type natriuretic peptide values), and echocardiography before receiving specific medication and every 3 months thereafter. A right heart catheterization was performed at baseline. A composite endpoint of death, worsening of functional class, or the need of a second vasodilator agent was used to define the clinical nonresponders. Results: Patients were followed for 14 months (7.5–21). The endpoint was reached by 15 patients: four patients died (two idiopathic PAH and two PAH in context of Eisenmenger syndrome), seven patients showed 1 functional class worsening, and four patients needed to be switched to combination therapy. Patients who remained clinically stable or improved had at baseline a better cardiac output with a less remodeled right ventricle (RV) and better functioning RV (all P < 0.05). A RV fractional area change (RVFAC) lower than 25.7% and a RV global strain value higher than ?13.4% predict with 87% sensitivity and 83% specificity (AUC 87.3%, P = 0.001) and 73% sensitivity and 91% specificity (AUC 84.2%, P = 0.003), respectively, patients who will deteriorate clinically under specific vasodilator therapy. A multivariate model showed RVFAC to be the only independent predictor of the endpoint with a HR of 0.87 (0.8–0.96), P = 0.007. Conclusions: Over an average period of 1 year, almost half of patients showed signs of clinical deterioration despite specific vasodilator therapy. Parameters of right ventricular morphology and function had prognostic value in these patients.     

Vaccination of dogs with canine parvovirus type 2b (CPV-2b) induces neutralising antibody responses to CPV-2a and CPV-2c

Since the identification of canine parvovirus type 2, three variants have subsequently been observed differing from the historical CPV-2 and each other by 1–2 amino acids only. As a result there has been considerable research into differential diagnostics, with some researchers indicating there is a need for new vaccines containing different strains of CPV-2.     

Intra-vaginal diazepam for high-tone pelvic floor dysfunction: a randomized placebo-controlled trial

Introduction and hypothesis

Intra-vaginal diazepam suppositories are commonly prescribed as a treatment option for high-tone pelvic floor myalgia. This triple-blinded placebo-controlled randomized trial sought to determine if 10 mg diazepam suppositories improve resting pelvic floor electromyography (EMG) compared with placebo.

Methods

Women ≥18 years of age with hypertonic pelvic floor muscles on examination, confirmed by resting EMG ≥2.0 microvolts (μv), administered vaginal suppositories containing either diazepam or placebo for 28 consecutive nights. Outcomes included vaginal surface EMG (four measurements), the Female Sexual Function Index (FSFI), the Short Form Health Survey 12 (SF-12), four visual analog scales (VAS), the Patient Global Impression of Severity (PGI-S), and the Patient Global Impression of Improvement (PGI-I). A priori sample size calculation indicated that 7 subjects in each group could detect a 2-μv difference in resting EMG tone with 90 % power.

Results

Twenty-one subjects were enrolled. The mean age was 36.1 (SD 13.9) years, mean body mass index was 28.56 (SD 9.4), and the majority (85.7 %) was Caucasian. When evaluating response to therapy, no difference was seen in any of the resting vaginal EMG assessments at any time point within subjects or between groups, nor was an interaction found. Additionally, no differences were noted in any of the validated questionnaires.

Conclusions

When used nightly over 4 weeks, 10 mg of vaginal diazepam was not associated with improvement in resting EMG parameters or subjective outcomes compared with placebo. This suggests such that therapy alone may be insufficient in treating high-tone pelvic floor dysfunction.     

The cellular HIV-1 Rev cofactor hRIP is required for viral replication

An important goal of contemporary HIV type 1 (HIV-1) research is to identify cellular cofactors required for viral replication. The HIV-1 Rev protein facilitates the cytoplasmic accumulation of the intron-containing viral gag-pol and env mRNAs and is required for viral replication. We have previously shown that a cellular protein, human Rev-interacting protein (hRIP), is an essential Rev cofactor that promotes the release of incompletely spliced HIV-1 RNAs from the perinuclear region. Here, we use complementary genetic approaches to ablate hRIP activity and analyze HIV-1 replication and viral RNA localization. We find that ablation of hRIP activity by a dominant-negative mutant or RNA interference inhibits virus production by mislocalizing Rev-directed RNAs to the nuclear periphery. We further show that depletion of endogenous hRIP by RNA interference results in the loss of viral replication in human cell lines and primary macrophages; virus production was restored to wild-type levels after reintroduction of hRIP protein. Taken together, our results indicate that hRIP is an essential cellular cofactor for Rev function and HIV-1 replication. Because hRIP is not required for cell viability, it may be an attractive target for the development of new antiviral strategies.     

Association of prevalent and incident knee cartilage defects with loss of tibial and patellar cartilage: a longitudinal study

OBJECTIVE: To describe the association between prevalent and incident knee cartilage defects and loss of knee cartilage in male and female adults. METHODS: A convenience sample of 325 subjects (mean age 45 years; age range 26-61 years) was evaluated at baseline and approximately 2 years later. Knee cartilage volume, cartilage defect scores (0-4 scale), and joint surface area were determined using T1-weighted fat-suppression magnetic resonance imaging techniques. Height, weight, and radiographic evidence of osteoarthritis were measured by standard protocols. RESULTS: Multivariable analysis revealed that baseline cartilage defect scores at the medial tibia, lateral tibia, and patella had a dose-response association with the annual rate of change in knee cartilage volume at the corresponding site (beta = -1.3% to -1.2% per grade; P < 0.05 for all comparisons). In addition, an increase in knee cartilage defect score (change of > or =1) was associated with higher rates of knee cartilage volume loss at all sites (beta = -1.9% to -1.7% per year; P < 0.01 for all comparisons). Furthermore, a decrease in the knee cartilage defect score (change of less than or equal to -1) was associated with an increase in knee cartilage volume at all sites (beta = 1.0% to 2.7% per year; P < 0.05 for all comparisons). CONCLUSION: Prevalent knee cartilage defects are predictive of compartment-specific cartilage loss over 2 years. Both increases and decreases in knee cartilage defects are associated with changes in knee cartilage volume, which implies a potential for reversal of knee cartilage loss.