Determination of the Kinetic Constants of the Telomerization of 10‐Undecenol with Alkyl Hydrogenphosphonate

Summary: The telomerization of 10‐undecenol with alkyl hydrogenphosphonate was studied in order to synthesize telomers of different molecular weights. The study showed that telomers from 10‐undecenol could be obtained despite the fact that the double bond has a low reactivity. The kinetic constant Kp²/K_Te was determined to be 7 × 10^?4 l · mol^?1 · s^?1 at 135 °C and the transfer constant C_T was 0.057. These values are normal for a low activity telogen such as hydrogenphosphonate and for slightly reactive monomers like 10‐undecenol.

SEC chromatogram of telomers obtained in the reaction of 10‐undecenol addition.     

Distribution of HLA class II alleles and haplotypes in insulin-dependent moroccan diabetics

HLA class II polymorphism in Moroccan IDDM patients has not been investigated so far. In this study, HLA-DRB1, -DQA1, and -DQB1 allele and haplotype frequencies were analyzed in 125 unrelated Moroccan IDDM patients and 93 unrelated healthy controls, all originating from the Souss region and mostly of Berber origin. Some common features with other Caucasian groups were observed, in particular, a predisposing effect of the DRB1^*03-DQA1^*0501-DQB1^*0201 and DRB1^*04-DQA1^*0301-DQB1^*0302 alleles or allelic combinations. The Moroccan IDDM group also presented with more specific characteristics. Among DRB1^*04 subtypes, DRB1^*0405 was associated with susceptibility to and DRB1^*0406 with protection from the disease. The haplotype and the relative predispositional effect (RPE) analyses indicated that the DRB1^*08-DQA1^*0401DQB1 ^*0402 haplotype was also associated with susceptibility to IDDM. Interestingly, the DRB1^*09DQA1 ^*0301-DQB1^*0201 haplotype, completely absent from the control group and very rare in North African populations, was observed in 7.2% of the Moroccan diabetics. Conversely, the DRB1^*07-DQA1^*0201DQB1 ^*0201 and DRB1^*15-DQA1^*0102-DQB1^*0602 haplotypes were associated with protection from IDDM. Finally, we observed an age-dependent genetic heterogeneity of IDDM, the frequencies of predisposing alleles being higher and those of protective alleles lower in childhood- than in adult-onset diabetics. Our data on Moroccan diabetics, together with data on European and Northern Mediterranean patients, suggest a gradient of various HLA class II predisposing and protective markers that link these populations     

A genetic and clinical study of individuals with nonsyndromic retinopathy consequent upon sequence variants in HGSNAT,the gene associated with Sanfilippo C mucopolysaccharidosis

Pathogenic variants in the gene HGSNAT (heparan‐α‐glucosaminide N‐acetyltransferase) have been reported to underlie two distinct recessive conditions, depending on the specific genotype, mucopolysaccharidosis type IIIC (MPSIIIC)—a severe childhood‐onset lysosomal storage disorder, and adult‐onset nonsyndromic retinitis pigmentosa (RP). Here we describe the largest cohort to‐date of HGSNAT‐associated nonsyndromic RP patients, and describe their retinal phenotype, leukocyte enzymatic activity, and likely pathogenic genotypes. We identified biallelic HGSNAT variants in 17 individuals (15 families) as the likely cause of their RP. None showed any other symptoms of MPSIIIC. All had a mild but significant reduction of HGSNAT enzyme activity in leukocytes. The retinal condition was generally of late‐onset, showing progressive degeneration of a concentric area of paramacular retina, with preservation but reduced electroretinogram responses. Symptoms, electrophysiology, and imaging suggest the rod photoreceptor to be the cell initially compromised. HGSNAT enzymatic testing was useful in resolving diagnostic dilemmas in compatible patients. We identified seven novel sequence variants [p.(Arg239Cys); p.(Ser296Leu); p.(Phe428Cys); p.(Gly248Ala); p.(Gly418Arg), c.1543‐2A>C; c.1708delA], three of which were considered to be retina‐disease‐specific alleles. The most prevalent retina‐disease‐specific allele p.(Ala615Thr) was observed heterozygously or homozygously in 8 and 5 individuals respectively (7 and 4 families). Two siblings in one family, while identical for the HGSNAT locus, but discordant for retinal disease, suggest the influence of trans‐acting genetic or environmental modifying factors.     

False results associated with darkground microscopy of subgingival plaque

This study considers false results which may arise due to problems in the preparation or examination of specimens for darkground microscopy of subgingival plaque. Subgingival plaque samples obtained with a sterile curette were placed in 0.1-0.3 ml sterile full or 1/4 strength Ringer's solution: 0.85% saline, 1% gelatin in 0.85% saline, formal saline or pyrogen-free water for injection. Test slides were prepared from the original dispersion, and control slides from the corresponding sterile solution. Optimal dispersion solution, syringe dispersion frequency and the effect on motility of delay in processing samples were tested. Slides were also prepared from dispersions of 11 representative subgingival "periodontopathic" organisms. Problems in sampling included variability in counts between sites with comparable pocket depths, contamination of the sample and reduction of the sample volume after scaling. Problems in dispersion included contamination, uneven distribution of the different morphotypes and destruction of delicate organisms. Problems in slide preparation included slide contamination, limitation in the number of samples that can be assessed by one examiner at a given time without loss of activity of motile cells, and preparation of a cell monolayer. Problems in identification and counting included confusion of Brownian movements with motility, coccoid particles with cocci, spirochetes with campylobacter, flagella with flagella-like structures, size of cocci, counting of fragmented spirochetes and non-motile flagellated organisms and motile cells, and also bias in counting. Problems in morphotype grouping included the observation that many (10 of the 11 representative) periodontitis-related organisms were in the non-motile groups and not all cells of the motile species (Campylobacter, Capnocytophaga) showed motility. The results indicate that each stage of subgingival plaque darkground microscopy, sampling, dispersion, slide preparation, counting, morphotype grouping and interpretation may lead to false results if not representative or reproducible. Procedures are suggested for the minimisation of problems in the preparation and examination of subgingival plaque specimens for darkground microscopy.     

Prevalence and predictors of symptoms of Perinatal Mood and anxiety Disorders among a sample of Urban Black Women in the South

Maternal and Child Health Journal - Data are scarce regarding the prevalence and predictors of perinatal mood and anxiety disorders (PMADs) among Black women. The purpose of this study was to...     

Effects of Maternal Nutritional Supplements and Dietary Interventions on Placental Complications: An Umbrella Review,Meta-Analysis and Evidence Map

The placenta is a vital, multi-functional organ that acts as an interface between maternal and fetal circulation during pregnancy. Nutritional deficiencies during pregnancy alter placental development and function, leading to adverse pregnancy outcomes, such as pre-eclampsia, infants with small for gestational age and low birthweight, preterm birth, stillbirths and maternal mortality. Maternal nutritional supplementation may help to mitigate the risks, but the evidence base is difficult to navigate. The primary purpose of this umbrella review is to map the evidence on the effects of maternal nutritional supplements and dietary interventions on pregnancy outcomes related to placental disorders and maternal mortality. A systematic search was performed on seven electronic databases, the PROSPERO register and references lists of identified papers. The results were screened in a three-stage process based on title, abstract and full-text by two independent reviewers. Randomized controlled trial meta-analyses on the efficacy of maternal nutritional supplements or dietary interventions were included. There were 91 meta-analyses included, covering 23 types of supplements and three types of dietary interventions. We found evidence that supports supplementary vitamin D and/or calcium, omega-3, multiple micronutrients, lipid-based nutrients, and balanced protein energy in reducing the risks of adverse maternal and fetal health outcomes. However, these findings are limited by poor quality of evidence. Nutrient combinations show promise and support a paradigm shift to maternal dietary balance, rather than single micronutrient deficiencies, to improve maternal and fetal health. The review is registered at PROSPERO (CRD42020160887).     

Evaluation of daily avanafil efficacy in improving the endothelial function in Egyptian males with erectile dysfunction

Avanafil is a highly selective and potent oral phosphodiesterase type 5 inhibitor. However, its impact on the soluble markers of endothelial function has not been investigated yet. This study was conducted to assess the effect of daily avanafil on the endothelial markers' serum level and erectile function in patients with erectile dysfunction. In this work, we randomly divided 140 males with erectile dysfunction and other diseases commonly associated with endothelial dysfunction like diabetes mellitus, hypertension and dyslipidaemia into two equal groups: treatment group, treated with 50mg daily oral avanafil, and control group, treated with placebo. The International Index of Erectile Function-5 score and the serum levels of nitric oxide, cyclic guanosine monophosphate and endothelin-1 as markers of endothelial function were measured at baseline and after four weeks of treatment in both groups. At the end of treatment period, those randomised to avanafil achieved statistically significant improvement in erectile function, nitric oxide, cyclic guanosine monophosphate and endothelin-1 levels from baseline versus placebo regardless the type and duration of associated comorbidity as well as the duration and severity of erectile dysfunction. These results permitted us to suggest that daily avanafil can improve the impaired endothelial function associated with the erectile dysfunction.     

Survival prediction of glioblastoma patients—are we there yet? A systematic review of prognostic modeling for glioblastoma and its clinical potential

Glioblastoma is associated with a poor prognosis. Even though survival statistics are well-described at the population level, it remains challenging to predict the prognosis of an individual patient despite the increasing number of prognostic models. The aim of this study is to systematically review the literature on prognostic modeling in glioblastoma patients. A systematic literature search was performed to identify all relevant studies that developed a prognostic model for predicting overall survival in glioblastoma patients following the PRISMA guidelines. Participants, type of input, algorithm type, validation, and testing procedures were reviewed per prognostic model. Among 595 citations, 27 studies were included for qualitative review. The included studies developed and evaluated a total of 59 models, of which only seven were externally validated in a different patient cohort. The predictive performance among these studies varied widely according to the AUC (0.58–0.98), accuracy (0.69–0.98), and C-index (0.66–0.70). Three studies deployed their model as an online prediction tool, all of which were based on a statistical algorithm. The increasing performance of survival prediction models will aid personalized clinical decision-making in glioblastoma patients. The scientific realm is gravitating towards the use of machine learning models developed on high-dimensional data, often with promising results. However, none of these models has been implemented into clinical care. To facilitate the clinical implementation of high-performing survival prediction models, future efforts should focus on harmonizing data acquisition methods, improving model interpretability, and externally validating these models in multicentered, prospective fashion.