DOCK6 Mutations Are Responsible for a Distinct Autosomal-Recessive Variant of Adams-Oliver Syndrome Associated with Brain and Eye Anomalies

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Correlations between Income inequality and antimicrobial resistance.

Objectives: The aim of this study is to investigate if correlations exist between income inequality and antimicrobial resistance. This study's hypothesis is that income inequality at the national level is positively correlated with antimicrobial resistance within developed countries. Data collection and analysis: income inequality data were obtained from the Standardized World Income Inequality Database. Antimicrobial resistance data were obtained from the European antimicrobial Resistance Surveillance Network and outpatient antimicrobial consumption data, measured by Defined daily Doses per 1000 inhabitants per day, from the European Surveillance of antimicrobial Consumption group. Spearman's correlation coefficient (r) defined strengths of correlations of: > 0.8 as strong, > 0.5 as moderate and > 0.2 as weak. Confidence intervals and p values were defined for all r values. Correlations were calculated for the time period 2003-10, for 15 European countries. Results: income inequality and antimicrobial resistance correlations which were moderate or strong, with 95% confidence intervals > 0, included the following. Enterococcus faecalis resistance to aminopenicillins, vancomycin and high level gentamicin was moderately associated with income inequality (r= ≥0.54 for all three antimicrobials). Escherichia coli resistance to aminoglycosides, aminopenicillins, third generation cephalosporins and fluoroquinolones was moderately-strongly associated with income inequality (r= ≥0.7 for all four antimicrobials). Klebsiella pneumoniae resistance to third generation cephalosporins, aminoglycosides and fluoroquinolones was moderately associated with income inequality (r= ≥0.5 for all three antimicrobials). Staphylococcus aureus methicillin resistance and income inequality were strongly associated (r=0.87). Conclusion: as income inequality increases in European countries so do the rates of antimicrobial resistance for bacteria including E. faecalis, E. coli, K. pneumoniae and S. aureus. Further studies are needed to confirm these findings outside Europe and investigate the processes that could causally link income inequality and antimicrobial resistance

Chemical Basis of Prey Recognition in Thamnophiine Snakes: The Unexpected New Roles of Parvalbumins

Detecting and locating prey are key to predatory success within trophic chains. Predators use various signals through specialized visual, olfactory, auditory or tactile sensory systems to pinpoint their prey. Snakes chemically sense their prey through a highly developed auxiliary olfactory sense organ, the vomeronasal organ (VNO). In natricine snakes that are able to feed on land and water, the VNO plays a critical role in predatory behavior by detecting cues, known as vomodors, which are produced by their potential prey. However, the chemical nature of these cues remains unclear. Recently, we demonstrated that specific proteins–parvalbumins–present in the cutaneous mucus of the common frog (Rana temporaria) may be natural chemoattractive proteins for these snakes. Here, we show that parvalbumins and parvalbumin-like proteins, which are mainly intracellular, are physiologically present in the epidermal mucous cells and mucus of several frog and fish genera from both fresh and salt water. These proteins are located in many tissues and function as Ca2+ buffers. In addition, we clarified the intrinsic role of parvalbumins present in the cutaneous mucus of amphibians and fishes. We demonstrate that these Ca2+-binding proteins participate in innate bacterial defense mechanisms by means of calcium chelation. We show that these parvalbumins are chemoattractive for three different thamnophiine snakes, suggesting that these chemicals play a key role in their prey-recognition mechanism. Therefore, we suggest that recognition of parvalbumin-like proteins or other calcium-binding proteins by the VNO could be a generalized prey-recognition process in snakes. Detecting innate prey defense mechanism compounds may have driven the evolution of this predator-prey interaction

A study of a couple with type 2 diabetes: dyadic adjustment and psychological morbidity

Objective: this study assessed dyadic adjustment and psychological morbidity in type 2 diabetic patients and their partners, focusing on the role of gender. Methods: 214 diabetic patients and their partners participated in the cross-sectional study and were assessed on psychological morbidity (HADS) and marital adjustment (RDAS). Data was analyzed using dyadic analysis, a statistical process that studies the patient/partner dyads simultaneously. Results: results revealed that the negative relationship between dyadic adjustment and psychological morbidity in female patients was stronger than in male diabetic patients or in partners of male diabetic patients. On the other hand, the relationship between dyadic adjustment and psychological morbidity in partners of diabetic men was stronger than the same relationship in partners of diabetic women. Conclusion: since gender is a moderator, it is important to attend to the different needs of female and male patients and the education of diabetic patients should be centered on the patient/partner dyad.Fundação para a Ciência e a Tecnologia (FCT

Generation of human vascular smooth muscle subtypes provides insight into embryological origin-dependent disease susceptibility.

Heterogeneity of embryological origins is a hallmark of vascular smooth muscle cells (SMCs) and may influence the development of vascular disease. Differentiation of human pluripotent stem cells (hPSCs) into developmental origin-specific SMC subtypes remains elusive. Here we describe a chemically defined protocol in which hPSCs were initially induced to form neuroectoderm, lateral plate mesoderm or paraxial mesoderm. These intermediate populations were further differentiated toward SMCs (>80% MYH11(+) and ACTA2(+)), which displayed contractile ability in response to vasoconstrictors and invested perivascular regions in vivo. Derived SMC subtypes recapitulated the unique proliferative and secretory responses to cytokines previously documented in studies using aortic SMCs of distinct origins. Notably, this system predicted increased extracellular matrix degradation by SMCs derived from lateral plate mesoderm, which was confirmed using rat aortic SMCs from corresponding origins. This differentiation approach will have broad applications in modeling origin-dependent disease susceptibility and in developing bioengineered vascular grafts for regenerative medicine

The use of erlotinib in daily practice: a study on adherence and patients' experiences

<p>Abstract</p> <p>Background</p> <p>Adherence to pharmacological therapy is a complex and multi-factorial issue that can substantially alter the outcome of treatment. It has been shown that cancer patients, especially when using long-term medication, have similar adherence rates to those of patients with other diseases. The consequences of poor adherence are poor health outcomes and increased health care costs. Only few studies have focused on the use of oral anticancer agents in daily practice. Information about the reasons for non-adherence is essential for the development of interventions that may increase adherence. This paper presents the CAPER-erlotinib protocol, which is designed to study the relationship between adherence to erlotinib and both the plasma concentration and side-effects in patients with NSCLC. Further, the relationships between patient characteristics, disease characteristics, side-effects, quality of life, patient beliefs and attitude towards disease and medication, dose adjustments, reasons for discontinuation and plasma concentration of erlotinib will be explored.</p> <p>Methods/Design</p> <p>In this prospective observational cohort study 65 NSCLC patients of 18 years or older starting treatment with erlotinib will be followed for a period up to 16 weeks. The main study parameters are adherence, the plasma concentration of erlotinib and the number and grade of side-effects. At baseline and on erlotinib treatment in weeks 3-4, 8-9, 12 and 15-16, patients will be asked to fill out a questionnaire. In weeks 3-4, 8-9 and 15-16 blood samples are collected, which will be analysed for plasma concentration of erlotinib. Adherence will be measured using a medication event monitoring system.</p> <p>Discussion</p> <p>The present study aims to get more insight into patients' experiences with the use of erlotinib in daily practice and the various aspects that govern adherence. We hypothesize that side-effects play an important role in the way patients use erlotinib. We expect that the present study will provide valuable knowledge which will be useful for health care professionals to develop interventions to support patients. This approach will improve the adherence and persistence with the use of erlotinib in order to derive optimal benefit from the medication.</p> <p>Trial Registration</p> <p><a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1830">NTR1830</a></p

The genetics and neuropathology of frontotemporal lobar degeneration

Frontotemporal lobar degeneration (FTLD) is a heterogeneous group of disorders characterized by disturbances of behavior and personality and different types of language impairment with or without concomitant features of motor neuron disease or parkinsonism. FTLD is characterized by atrophy of the frontal and anterior temporal brain lobes. Detailed neuropathological studies have elicited proteinopathies defined by inclusions of hyperphosphorylated microtubule-associated protein tau, TAR DNA-binding protein TDP-43, fused-in-sarcoma or yet unidentified proteins in affected brain regions. Rather than the type of proteinopathy, the site of neurodegeneration correlates relatively well with the clinical presentation of FTLD. Molecular genetic studies identified five disease genes, of which the gene encoding the tau protein (MAPT), the growth factor precursor gene granulin (GRN), and C9orf72 with unknown function are most frequently mutated. Rare mutations were also identified in the genes encoding valosin-containing protein (VCP) and charged multivesicular body protein 2B (CHMP2B). These genes are good markers to distinguish underlying neuropathological phenotypes. Due to the complex landscape of FTLD diseases, combined characterization of clinical, imaging, biological and genetic biomarkers is essential to establish a detailed diagnosis. Although major progress has been made in FTLD research in recent years, further studies are needed to completely map out and correlate the clinical, pathological and genetic entities, and to understand the underlying disease mechanisms. In this review, we summarize the current state of the rapidly progressing field of genetic, neuropathological and clinical research of this intriguing condition