Ptosis as a unique hallmark for autosomal recessive WNT1-associated osteogenesis imperfecta

Osteogenesis imperfecta (OI) is a heritable connective tissue disorder, mainly characterized by bone fragility and low bone mass. Defects in the type I procollagen-encoding genes account for the majority of OI, but increasingly more rare autosomal recessive (AR) forms are being identified, which are caused by defects in genes involved in collagen metabolism, bone mineralization, or osteoblast differentiation. Bi-allelic mutations in WNT1 have been associated with a rare form of AR OI, characterized by severe osteoporosis, vertebral compression, scoliosis, fractures, short stature, and variable neurological problems. Heterozygous WNT1 mutations have been linked to autosomal dominant early-onset osteoporosis. In this study, we describe the clinical and molecular findings in 10 new patients with AR WNT1-related OI. Thorough revision of the clinical symptoms of these 10 novel patients and previously published AR WNT1 OI cases highlight ptosis as a unique hallmark in the diagnosis of this OI subtype

Genotypic identification and technological characterization of lactic acid bacteria isolated from traditional Turkish Kargi tulum cheese

Kargi tulum cheese is an artisanal cheese produced through the spontaneous fermentation of raw milk ripened inside a goat-skin bag. The objective of this study was to characterize the dominant species of natural lactic acid bacteria (LAB) found in Kargi tulum cheese. Some technologically important properties of LAB isolates were also determined. Seven samples of cheese of different levels of ripeness were taken from local producers and 97 isolates were obtained from these samples. Non-spore forming, Gram-positive, catalase- and oxidase-negative isolates were assessed as LAB. Based on genotypic characterization, the dominant LAB were identified as Lactobacillus paracasei (43.3%), Lactobacillus plantarum (23.7%), Enterococcus durans (6.2%), Streptococcus thermophilus (6.2%), Lactobacillus brevis (5.2%), Enterococcus faecium (5.2%), Lactobacillus fermentum (4.1%) and Lactobacillus pentosus (1%). Homofermentative strains such as L. paracasei, L. plantarum, S. thermophilus; E. durans and E. faecium were selected as probable starter cultures. These strains were tolerant to 6.5% salt. They are also characterized by acidification ability (from pH = 6.6 to 4.7 to 6.0, in 6 to 8 h), low proteinase and high peptidase, esterase, esterase-lipase, β-galactosidase and β- glucosidase activities. They also produce diacetyl and H2O2.Key words: Lactic acid bacteria, genotypic characterization, technological characterization, tulum cheese

Numerical analysis of performance uncertainty of heat exchangers operated with nanofluids

In this paper, we analyse the performance of two types of heat exchangers with nanofluid as the working fluid in turbulent flow regime ( 4, 000–180, 000). Based on the experimental uncertainty of the thermophysical properties of the nanofluids, we use the Stochastic Collocation Method in combination with a deterministic simulation programme to estimate the expected value and variance of the targeted engineering results. We find that the uncertainty in the thermal conductivity of the nanofluid has the largest impact on the uncertainty in the heat exchanger performance, while the uncertainty in the density can be neglected. The uncertainties in the Nusselt number, friction factor and several figures of merit are smaller than the change in these performance estimators due to a change in nanoparticle concentration. Predictions for heat exchanger performance agree much better with experimental data when used with empirical heat transfer correlations developed specifically for nanofluids than with the general Gnielinski correlation developed for pure fluids. We also perform a correlation analysis of the relationships between heat exchanger performance enhancement and pressure drop to show that they are strongly correlated. We find that the relationship between the concentration of nanoparticles and the Nusselt number is statistically insignificant. The relationship is significant, indicating the importance of flow conditions. The correlation between nanoparticle concentration and friction factor is significant and strong. This result suggests that the optimisation of the thermal-hydrodynamic behaviour should be sought in a parameter other than the nanoparticle volume fraction

The Causes of Acute Fever Requiring Hospitalization in Geriatric Patients: Comparison of Infectious and Noninfectious Etiology

Introduction. Infectious diseases may present with atypical presentations in the geriatric patients. While fever is an important finding of infections, it may also be a sign of noninfectious etiology. Methods. Geriatric patients who were hospitalized for acute fever in our infectious diseases unit were included. Acute fever was defined as presentation within the first week of fever above 37.3°C. Results. 185 patients were included (82 males and 103 females). Mean age was 69.7 ± 7.5 years. The cause of fever was an infectious disease in 135 and noninfectious disease in 32 and unknown in 18 of the patients. The most common infectious etiologies were respiratory tract infections (n = 46), urinary tract infections (n = 26), and skin and soft tissue infections (n = 23). Noninfectious causes of fever were rheumatic diseases (n = 8), solid tumors (n = 7), hematological diseases (n = 10), and vasculitis (n = 7). A noninfectious cause of fever was present in one patient with no underlying diseases and in 31 of 130 patients with underlying diseases. Conclusion. Geriatric patients with no underlying diseases generally had infectious causes of fever while noninfectious causes were responsible from fever in an important proportion of patients with underlying diseases

Mutations in XRCC4 cause primary microcephaly, short stature and increased genomic instability

DNA double-strand breaks (DSBs) are highly toxic lesions, which, if not properly repaired, can give rise to genomic instability. Non-homologous end-joining (NHEJ), a well-orchestrated, multistep process involving numerous proteins essential for cell viability, represents one major pathway to repair DSBs in mammalian cells, and mutations in different NHEJ components have been described in microcephalic syndromes associated, e.g. with short stature, facial dysmorphism and immune dysfunction. By using whole-exome sequencing, we now identified in three affected brothers of a consanguineous Turkish family a homozygous mutation, c.482G>A, in the XRCC4 gene encoding a crucial component of the NHEJ pathway. Moreover, we found one additional patient of Swiss origin carrying the compound heterozygous mutations c.25delG (p.His9Thrfs*8) and c.823C>T (p.Arg275*) in XRCC4. The clinical phenotype presented in these patients was characterized by severe microcephaly, facial dysmorphism and short stature, but they did not show a recognizable immunological phenotype. We showed that the XRCC4 c.482G>A mutation, which affects the last nucleotide of exon 4, induces defective splicing of XRCC4 pre-mRNA mainly resulting in premature protein truncation and most likely loss of XRCC4 function. Moreover, we observed on cellular level that XRCC4 deficiency leads to hypersensitivity to DSB-inducing agents and defective DSB repair, which results in increased cell death after exposure to genotoxic agents. Taken together, our data provide evidence that autosomal recessive mutations in XRCC4 induce increased genomic instability and cause a NHEJ-related syndrome defined by facial dysmorphism, primary microcephaly and short statur

The optimization of peritoneal dialysis training in long-term

Peritoneal dialysis is a home based therapy for patients with advanced chronic kidney disease. This method provides adequate clearance of uremic toxins and removal of excess fluid when a proper dialysis prescription is combined with patient adherence. Peritonitis is the most frequent infectious complication among these patients and may render the continuity of the treatment. Training patients and their caregivers have prime importance to provide proper treatment and prevent complications including infectious ones. The training methods before the onset of treatment are relatively well established. However, patients may break the rules in the long term and tend to take shortcuts. So, retraining may be necessary during follow-up. There are no established guidelines to guide the retraining of PD patients yet. This review tends to summarize data in the literature about retraining programs and also proposes a structured program for this purpose

Novel C16orf57 mutations in patients with Poikiloderma with Neutropenia: bioinformatic analysis of the protein and predicted effects of all reported mutations

<p>Abstract</p> <p>Background</p> <p>Poikiloderma with Neutropenia (PN) is a rare autosomal recessive genodermatosis caused by <it>C16orf57 </it>mutations. To date 17 mutations have been identified in 31 PN patients.</p> <p>Results</p> <p>We characterize six PN patients expanding the clinical phenotype of the syndrome and the mutational repertoire of the gene. We detect the two novel <it>C16orf57 </it>mutations, c.232C>T and c.265+2T>G, as well as the already reported c.179delC, c.531delA and c.693+1G>T mutations. cDNA analysis evidences the presence of aberrant transcripts, and bioinformatic prediction of C16orf57 protein structure gauges the mutations effects on the folded protein chain.</p> <p>Computational analysis of the C16orf57 protein shows two conserved H-X-S/T-X tetrapeptide motifs marking the active site of a two-fold pseudosymmetric structure recalling the 2H phosphoesterase superfamily. Based on this model C16orf57 is likely a 2H-active site enzyme functioning in RNA processing, as a presumptive RNA ligase.</p> <p>According to bioinformatic prediction, all known <it>C16orf57 </it>mutations, including the novel mutations herein described, impair the protein structure by either removing one or both tetrapeptide motifs or by destroying the symmetry of the native folding.</p> <p>Finally, we analyse the geographical distribution of the recurrent mutations that depicts clusters featuring a founder effect.</p> <p>Conclusions</p> <p>In cohorts of patients clinically affected by genodermatoses with overlapping symptoms, the molecular screening of <it>C16orf57 </it>gene seems the proper way to address the correct diagnosis of PN, enabling the syndrome-specific oncosurveillance.</p> <p>The bioinformatic prediction of the C16orf57 protein structure denotes a very basic enzymatic function consistent with a housekeeping function. Detection of aberrant transcripts, also in cells from PN patients carrying early truncated mutations, suggests they might be translatable. Tissue-specific sensitivity to the lack of functionally correct protein accounts for the main cutaneous and haematological clinical signs of PN patients.</p

Sports psychology in the English Premier League: ‘It feels precarious and is precarious’

This is the author accepted manuscript. The final version is available from SAGE Publications via the DOI in this record.This article gives a rare account of the working life of a sports psychologist in the English Premier League (EPL), the elite division in English professional football. It shows how members of emerging professions such as sports psychology are a new precariat. Martin is more successful than many sports psychologists, but his job security is dependent on his continued ability to navigate managerial change: using his skills as a psychologist in the defence of his own employment but simultaneously keeping the (potentially sensitive) ‘psychology’ label of the work he does hidden until circumstances are propitious