De novo mutations in SMCHD1 cause Bosma arhinia microphthalmia syndrome and abrogate nasal development

Bosma arhinia microphthalmia syndrome (BAMS) is an extremely rare and striking condition characterized by complete absence of the nose with or without ocular defects. We report here that missense mutations in the epigenetic regulator SMCHD1 mapping to the extended ATPase domain of the encoded protein cause BAMS in all 14 cases studied. All mutations were de novo where parental DNA was available. Biochemical tests and in vivo assays in Xenopus laevis embryos suggest that these mutations may behave as gain-of-function alleles. This finding is in contrast to the loss-of-function mutations in SMCHD1 that have been associated with facioscapulohumeral muscular dystrophy (FSHD) type 2. Our results establish SMCHD1 as a key player in nasal development and provide biochemical insight into its enzymatic function that may be exploited for development of therapeutics for FSHD

Factors associated with stunting among children according to the level of food insecurity in the household: a cross-sectional study in a rural community of Southeastern Kenya

Background: Chronic malnutrition or stunting among children under 5 years old is affected by several household environmental factors, such as food insecurity, disease burden, and poverty. However, not all children experience stunting even in food insecure conditions. To seek a solution at the local level for preventing stunting, a cross-sectional study was conducted in southeastern Kenya, an area with a high level of food insecurity. Methods: The study was based on a cohort organized to monitor the anthropometric status of children. A structured questionnaire collected information on the following: demographic characteristics, household food security based on the Household Food Insecurity Access Scale (HFIAS), household socioeconomic status (SES), and child health status. The associations between stunting and potential predictors were examined by bivariate and multivariate stepwise logistic regression analyses. Furthermore, analyses stratified by level of food security were conducted to specify factors associated with child stunting in different food insecure groups. Results: Among 404 children, the prevalence of stunting was 23.3%. The percentage of households with severe food insecurity was 62.5%. In multivariative analysis, there was no statistically significant association with child stunting. However, further analyses conducted separately according to level of food security showed the following significant associations: in the severely food insecure households, feeding tea/porridge with milk (adjusted Odds Ratio [aOR]: 3.22; 95% Confidence Interval [95% CI]: 1.43-7.25); age 2 to 3 years compared with 0 to 5 months old (aOR: 4.04; 95% CI: 1.01-16.14); in households without severe food insecurity, animal rearing (aOR: 3.24; 95% CI: 1.04-10.07); SES with lowest status as reference (aOR range: from 0.13 to 0.22). The number of siblings younger than school age was not significantly associated, but was marginally associated in the latter household group (aOR: 2.81; 95% CI: 0.92-8.58). Conclusions: Our results suggest that measures against childhood stunting should be optimized according to food security level observed in each community

Anti-embolism stocking care protocol to prevent associated skin problems: A quasi-experimental study

Aim: The aim of this quasi-experimental study was to develop an anti-embolism stocking care protocol and assess its effectiveness in preventing associated skin problems on the legs. Materials and methods: The study was conducted between 02 March and July 20, 2016 in the surgical clinics of a private university hospital in Ankara, Turkey. The sample consisted of 27 nurses and 162 patients (three different patients were fitted of anti-embolism stockings by each of the 27 nurses; pre-protocol 81 patients and post-protocol 81 patients). Data were collected using data collection forms developed by the researchers. An anti-embolism stocking care protocol was developed and used. Nurses and patients were evaluated using an observational method. Results: Following implementation of the protocol, nurses’ mean knowledge (95.24 ± 5.60) and intervention skill (92.06 ± 10.42) scores were significantly higher than their pre-protocol knowledge (73.54 ± 14.26) and intervention skill (15.30 ± 6.84) scores. Nurses performed almost all steps of the care protocol correctly after the protocol was implemented. The rates of skin problems such as pressure ulcers, neurovascular problems and issues associated with wrinkles or creases in stockings were significantly reduced after implementation of the protocol. Conclusions: This study demonstrates that nurses’ knowledge and intervention skills are increased when a care protocol is used, together with the prevention of errors and improved patient outcomes. The use of care protocols guides nurses in practice, raises awareness and helps to achieve nursing care objectives by standardizing information. © 2020 Tissue Viability SocietyWe thank all nurses and patients who participated to the study

Evaluation of the synergistic effect of a combination of colistin and tigecycline against multidrug-resistant Acinetobacterbaumannii.

Objective: Acinetobacter baumannii species cause nosocomial infections and can subsequently develop multidrug resistance (MDR). The objective of this study was to evaluate the susceptibility of A. baumannii to a novel combination of colistin and tigecycline, which may provide a faster and more efficacious treatment via a synergistic effect. Methods: We included 50 MDR A. baumannii samples that were isolated in our clinics between 2009 and 2014. We used broth microdilution (BMD) and the E-test to evaluate the effects of colistin and tigecycline, and the E-test to assess the interaction of the colistin-tigecycline combination. The interaction between the two antibiotics was evaluated using the fractional inhibition concentration (FIC) index and was classified as follows: FIC?0.5, synergistic; 0.5<FIC<1, partially synergistic; FIC=1, additive; 1<FIC<4, indifferent; and FIC?4, antagonistic. Results: No tigecycline and colistin resistance was determined by BMD or E-test. The interaction between colistin and tigecycline, when used in combination, was 2% synergistic, 6% additive, 88% indifferent, and 4% antagonistic. Conclusion: Although combination therapy is suggested for MDR A. baumannii infections, our results suggest that the synergistic effect of the colistin-tigecycline combination is insufficient to make it an optimal treatment choice

Searching for Copy Number Changes in Nonsyndromic X-Linked Intellectual Disability

Intellectual disability (ID) has a prevalence of 2–3% with 0.3% of the population being severely retarded. Etiology is heterogeneous, owing to numerous genetic and environmental factors. Underlying etiology remains undetermined in 75–80% of mildly disabled patients and 20–50% of those severely disabled. Twelve percent of all ID is thought to be X-linked (XLID). This study covers copy number analysis of some of the known XLID genes, using multiplex ligation-dependent probe amplification (MLPA) in 100 nonsyndromic patients. One of the patients was found to have duplication in all exons of MECP2 gene, and another had duplication in the fifth exon of TM4SF2/TSPAN7 gene. Affymetrix® 6.0 whole-genome SNP microarray confirmed the duplication in MECP2 and showed duplication of exons 2–7 in TM4SF2/TSPAN7, respectively. MECP2 duplication has recently been recognized as a syndromic cause of XLID in males, whereas duplications in TM4SF2/TSPAN7 are yet to be determined as a cause of XLID. Being an efficient, rapid, easy-to-perform, easy-to-interpret, and cost-effective method of copy number analysis of specific DNA sequences, MLPA presents wide clinical utility and may be included in diagnostic workup of ID, particularly when microarrays are unavailable as a first-line approach

Investigation of the relationship of TNFRSF11A gene polymorphisms with breast cancer development and metastasis risk in patients with BRCA1 or BRCA2 pathogenic variants living in the Trakya region of Turkey

Modifying genes play an exclusive role in the genetic regulation of the risk of breast cancer development in women with a pathogenic variation of BRCA1 or BRCA2. Therefore, it has been suggested that TNFRSF11A, which is among those modifying genes present in breast cancer development, may have a significant role in patients with positive BRCA1 or BRCA2 variations. In our study, we investigated the probable effects of single nucleotide polymorphisms (SNPs) in the TNFRSF11A gene, such as rs4485469, rs9646629, rs34739845, rs17069904, rs 884205, rs4941129 on the risk of breast cancer in patients with BRCA1 or BRCA2 variations. A total of 23 breast cancer patients with pathogenic variations in the BRCA1 or BRCA2 genes, 28 patients with no pathogenic variations in the BRCA1 or BRCA2 genes, and 55 healthy women as a control group, were included in this study. The SNPs were determined with allelic discrimination analysis through the real-time polymerase chain reaction (qPCR) method. There was no statistically significant difference between the SNPs of the TNFRSF11A gene rs4485469, rs9646629, rs34739845, rs17069904, rs884205, rs4941129 and metastasis, estrogen receptor, progesterone receptor and CerB2 receptor positivity between patient and control group (p >0.05). However, the rs4485469 SNP was found to be borderline significant between the patient groups with and without BRCA1 or BRCA2 mutations (p = 0.059). In patients with BRCA1 or BRCA2 pathogenic variations living in the Trakya region of Turkey, we could not determine the relationship between TNFRSF11 SNPs with breast cancer risk