Microphthalmia with linear skin defects (MLS) syndrome evaluated by prenatal karyotyping, FISH and array comparative genomic hybridization

OBJECTIVE: To explore the utility of comparative genomic hybridization to BAC arrays (array CGH) for prenatal diagnosis of microphthalmia and linear skin defects syndrome. METHODS: We used karyotype analysis, FISH and array CGH to investigate an X;Y translocation. Replication studies were done on cultured amniocytes and lymphoblasts. RESULTS: We describe a severe case of MLS syndrome that presented prenatally with multiple anomalies including cystic hygroma, microphthalmia, intrauterine growth restriction and a complex congenital heart defect. Cytogenetic analysis of amniocytes revealed an unbalanced de novo translocation between chromosomes X and Y [karyotype 46,X,der(X)t(X;Y)(p22.3;q11.2).ish der(X)(DXZ1+,DMD+,KAL-,STS-,SRY-),22q11.2 (Tuple1 x 2)]. MLS diagnosis was made at birth and the prenatal karyotype was confirmed. Replication studies showed the derivative X chromosome was the inactive X. Array CGH confirmed the X and Y imbalances seen in the karyotype and also showed twelve BACs in the MLS region were deleted as a result of the translocation. FISH with BAC clones verified the array findings and placed the X breakpoint in Xp22.2, resulting in the amended karyotype, 46,X,der(X)t(X;Y)(p22.2;q11.2).ish der(X)(DXZ1+,DMD+,KAL-,STS-,SRY-),22q11.2(Tuple1 x 2) arr cgh Xp22.33p22.2(LLNOYCO3M15D10 -->GS1-590J6)x 1,Yq11.222q23(RP11-20H21-->RP11-79J10)x 1. CONCLUSION: The sensitivity of array CGH was valuable in detecting monosomy of the MLS critical region. Array CGH should be considered for the prenatal diagnosis of this syndrome.     

Relationship between gastrointestinal and dysmenorrheic symptoms at menses

The relationship between gastrointestinal (GI) symptoms and uterine cramping pain at menses, controlling for affective states and prostaglandin synthesis inhibitor use, was examined. A total of 53 women completed a daily diary of symptoms, stool characteristics, and medication use for three consecutive menstrual cycles. There were significant across-women and within-woman relationships between stomach pain, nausea, and uterine cramping pain, but not between cramping pain and constipation, diarrhea, or stool characteristics. These results support the presence of a similar mechanism in the generation of distressing GI symptoms and uterine cramping pain at menses. © 1996 John Wiley & Sons, Inc.     

The effect of nettle (Urtica dioica) supplementation on the glycemic control of patients with type 2 diabetes mellitus: A systematic review and meta‐analysis

Type 2 diabetes mellitus (T2DM) is a major health problem, worldwide, that is associated with increased morbidity and mortality. Several randomized controlled clinical trials (RCTs) have investigated the effect of nettle (Urtica dioica) supplementation on markers of glycemic status in patients with T2DM, with conflicting results. Therefore, the present study assessed the effect of nettle on some glycemic parameters in patients with T2DM. A comprehensive search was conducted in PubMed, Scopus, Cochrane Library, and Web of Science, from database inception up to June 2019, to identify RCTs investigating the effect of nettle supplementation on glycemic markers, including fasting blood sugar (FBS) concentrations, insulin levels, homeostasis model assessment‐estimated insulin resistance index, and glycosylated hemoglobin percentage in adults with T2DM. The Cochrane Collaboration tool was used to assess the methodological quality of the included studies. Results of this meta‐analysis were reported based on the random effects model. Eight RCTs, comprising 401 participants, were included in the present systematic review and meta‐analysis. Based on the Cochrane Collaboration risk of bias tool, five studies were considered as good quality, one was fair, and two studies were poor, respectively. The results of the meta‐analysis revealed a significant reduction in FBS concentrations (weighted mean difference [WMD]: ?18.01 mg/dl, 95% confidence interval [CI]: ?30.04 to ?5.97, p < .001, I² = 94.6%) following nettle supplementation. However, no significant reduction was observed in insulin levels (WMD: 0.83 Hedges' g, 95% CI: ?0.26 to 1.92, p = .13, I² = 89.4%), homeostasis model assessment‐estimated insulin resistance index (WMD: ?0.22, 95% CI: ?0.83 to 0.40, p = .49, I² = 69.2%), or glycosylated hemoglobin percentage (WMD: ?0.77%, 95% CI: ?1.77 to 0.22, p = .12, I² = 83.0%). The findings of the present study suggest that nettle supplementation may be effective in controlling FBS for T2DM patients. However, further studies are needed to confirm the veracity of these results.     

Trimerization and cyclization of reactive P-functionalities confined within OCO pincers

In order to stabilize a 10–P–3 species with C_2v symmetry and two lone pairs on the central phosphorus atom, a specialized ligand is required. Using an NCN pincer, previous efforts to enforce this planarized geometry at P resulted in the formation of a C_s-symmetric, 10π-electron benzazaphosphole that existed as a dynamic “bell-clapper” in solution. Here, OCO pincers 1 and 2 were synthesized, operating under the hypothesis that the more electron-withdrawing oxygen donors would better stabilize the 3-center, 4-electron O–P–O bond of the 10–P–3 target and the sp³-hybridized benzylic carbon atoms would prevent the formation of aromatic P-heterocycles. However, subjecting 1 to a metalation/phosphination/reduction sequence afforded cyclotriphosphane 3, resulting from trimerization of the P(i) center unbound by its oxygen donors. Pincer 2 featuring four benzylic CF₃ groups was expected to strengthen the O–P–O bond of the target, but after metal–halogen exchange and quenching with PCl₃, unexpected cyclization with loss of CH₃Cl was observed to give monochlorinated 5. Treatment of 5 with (p-CH₃)C₆H₄MgBr generated crystalline P-(p-Tol) derivative 6, which was characterized by NMR spectroscopy, elemental analysis, and X-ray crystallography. The complex ¹⁹F NMR spectra of 5 and 6 observed experimentally, were reproduced by simulations with MestreNova.

Attempted synthesis of OCO-supported 10–P–3 species led to trimerization or cyclization.     

Sexual assault, sexual risks and gender attitudes in a community sample of South African men

Sexual assault against women and HIV infection are both prevalent and related social problems in South Africa. The current study examined hostile attitudes toward women, acceptance of violence against women and masculine ideological beliefs in relation to sexual assault history among men in a Cape Town township in South African. Men (n=435) completed anonymous surveys of sexual assault history, HIV risk history and gender-based attitudes. More than one in five men in this community sample reported that they had either threatened to use force or used force to gain sexual access to a woman in their lifetime. Men with a history of sexual assault were at significantly higher risk for HIV transmission than their non-sexually assaultive counterparts. Men with a history of sexual assault were also more likely to endorse hostile attitudes toward women and were more likely to accept violence against women, although these attitudes and beliefs were prevalent and pervasive across men with and without histories of sexual assault. These findings extend previous research to show that men who have a history of sexual assault also exhibit elevated risks for HIV infection and transmission. Interventions are needed to address hostile attitudes toward women, sexual assault and sexual risks for HIV among South African men.     

Articular responses to purified cartilage proteoglycans

To examine whether proteoglycans (PGs) liberated from cartilage might contribute to articular changes in arthritis, cartilage PGs were injected intraarticularly into rabbit knee joints. Twice-weekly injections of PG (2.5 mg) provoked synovial hypertrophy, synovitis, erosion of the articulating surfaces, and loss of metachromasia of the articular cartilage. These changes were accompanied by a marked elevation in the production of neutral collagenase and gelatinase by both synoviocytes and chondrocytes. The synoviocytes of experimental knee joints also produced factor(s), possibly related to interleukin-1, which provoked the activation of chondrocytes. Our data are consistent with the idea that free PG fragments mediate some of the pathophysiologic changes that occur in arthritic joints. This property may be particularly important in osteoarthritis.     

Cardiac Amyloidosis Shows Decreased Diastolic Function as Assessed by Echocardiographic Parameterized Diastolic Filling

Cardiac amyloidosis is a rare but serious condition with poor survival. One of the early findings by echocardiography is impaired diastolic function, even before the development of cardiac symptoms. Early diagnosis is important, permitting initiation of treatment aimed at improving survival. The parameterized diastolic filling (PDF) formalism entails describing the left ventricular filling pattern during early diastole using the mathematical equation for the motion of a damped harmonic oscillator. We hypothesized that echocardiographic PDF analysis could detect differences in diastolic function between patients with amyloidosis and controls. Pulsed-wave Doppler echocardiography of transmitral flow was measured in 13 patients with amyloid heart disease and 13 age- and gender matched controls. E- waves (2 to 3 per subject) were analyzed using in-house developed software. Nine PDF-derived parameters were obtained in addition to conventional echocardiographic parameters of diastolic function. Compared to controls, cardiac amyloidosis patients had a larger left atrial area (23.7 ± 7.5 cm² vs. 18.5 ± 4.8 cm², p = 0.04), greater interventricular septum wall thickness (14.4 ± 2.6 mm vs. 9.3 ± 1.3 mm, p < 0.001), lower e′ (0.06 ± 0.02 m/s vs. 0.09 ± 0.02 m/s, p < 0.001) and higher E/e′ (18.0 ± 12.9 vs. 7.7 ± 1.3, p = 0.001). The PDF parameter peak resistive force was greater in cardiac amyloidosis patients compared to controls (17.9 ± 5.7 mN vs. 13.1 ± 3.1 mN, p = 0.03), and other PDF parameters did not differ. PDF analysis revealed that patients with cardiac amyloidosis had a greater peak resistive force compared to controls, consistent with a greater degree of diastolic dysfunction. PDF analysis may be useful in characterizing diastolic function in amyloid heart disease.     

Are Serious Games a Good Strategy for Pharmacy Education?

Serious gaming is the use of game principles for the purposes of learning, skill acquisition, and training. Higher education is beginning to incorporate serious gaming into curricula, and health professions education is the most common area for serious game use. Advantages of serious gaming in pharmacy education include authentic, situated learning without risk of patient consequences, collaborative learning, ability to challenge students of all performance levels, high student motivation with increased time on task, immediate feedback, ability to learn from mistakes without becoming discouraged, and potential for behavior and attitude change. Development of quality games for pharmacy education requires content expertise as well as expertise in the science and design of gaming. When well done, serious gaming provides a valuable additional tool for pharmacy education.