Bertramduffy8975

This is significant for the development of artificial spinning technology, novel silk biomaterials, and silk gland expression systems.The primary cilium, an important microtubule-based organelle, protrudes from nearly all the vertebrate cells. The motility of cilia is necessary for various developmental and physiological processes. Phosphoinositides (PIs) and its metabolite, PtdIns(4,5)P2, have been revealed to contribute to cilia assembly and disassembly. As an important kinase of the PI pathway and signaling, phosphatidylinositol 4-kinase β (PI4KB) is the one of the most extensively studied phosphatidylinositol 4-kinase isoform. However, its potential roles in organ development remain to be characterized. To investigate the developmental role of Pi4kb, especially its function on zebrafish ciliogenesis, we generated pi4kb deletion mutants using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 technique. The homozygous pi4kb mutants exhibit an absence of primary cilia in the inner ear, neuromasts, and pronephric ducts accompanied by severe edema in the eyes and other organs. Moreover, smaller otic vesicle, malformed semicircular canals, and the insensitivity on sound stimulation were characteristics of pi4kb mutants. At the protein level, both in vivo and in vitro analyses revealed that synthesis of Pi4p was greatly reduced owing to the loss of Pi4kb. In addition, the expression of the Pi4kb-binding partner of neuronal calcium sensor-1, as well as the phosphorylation of phosphatidylinositol-4-phosphate downstream effecter of Akt, was significantly inhibited in pi4kb mutants. Taken together, our work uncovers a novel role of Pi4kb in zebrafish inner ear development and the functional formation of hearing ability by determining hair cell ciliogenesis.Congenital hearing loss is a common disorder worldwide. Heterogeneous gene variation accounts for approximately 20-25% of such patients. We investigated a five-generation Chinese family with autosomal-dominant nonsyndromic sensorineural hearing loss (SNHL). No wave was detected in the pure-tone audiometry, and the auditory brainstem response was absent in all patients. Computed tomography of the patients, as well as of two sporadic SNHL cases, showed bilateral inner ear anomaly, cochlear maldevelopment, absence of the osseous spiral lamina, and an enlarged vestibular aqueduct. Such findings were absent in nonaffected persons. We used linkage analysis and exome sequencing and uncovered a heterozygous missense mutation in the PI4KB gene (p.Gln121Arg) encoding phosphatidylinositol 4-kinase β (PI4KB) from the patients in this family. In addition, 3 missense PI4KB (p.Val434Gly, p.Glu667Lys, and p.Met739Arg) mutations were identified in five patients with nonsyndromic SNHL from 57 sporadic cases. No such mutations were present within 600 Chinese controls, the 1000 genome project, gnomAD, or similar databases. Depleting pi4kb mRNA expression in zebrafish caused inner ear abnormalities and audiosensory impairment, mimicking the patient phenotypes. Moreover, overexpression of 4 human missense PI4KB mutant mRNAs in zebrafish embryos resulted in impaired hearing function, suggesting dominant-negative effects. Taken together, our results reveal that PI4KB mutations can cause SNHL and inner ear malformation. PI4KB should be included in neonatal deafness screening.Individuals exhibit a natural bias to approach positive social cues (e.g., smiling face) and to avoid negative ones, which may be altered in psychiatric conditions. Computerized approach/avoidance training to promote affectively congruent behavior has proven useful in modulating such biases. Here, we investigate how exposure to a higher rate of congruency impacts neural processing of social-affective cues. While undergoing functional magnetic resonance imaging (fMRI), twenty-four individuals completed two versions of the approach-avoidance task (AAT), in which they had to approach or avoid dynamic facial expressions of either happiness or disgust. In the high congruency condition, congruent responses (i.e. approaching happy faces, avoiding disgusted faces) were more frequent. The balanced condition had equal amounts of congruent and incongruent responses. Processing of congruent approach-avoidance actions towards social cues was associated with lower recruitment of the right anterior insula in the congruency-intensive relative to the balanced condition. Differential activation between the high congruency and balanced condition in the right hippocampus was negatively related to individuals' trait avoidance tendency. check details These findings are consistent with reduced affective neural processing of social cues when being exposed to congruent AAT contexts. These neural foci could be important targets when assessing the effectiveness of affective congruency training protocols.

Bisphosphonates (BPs) impact on the survival and cardiovascular safety of osteoporosis patients after acute coronary syndrome (ACS) or acute ischemic stroke (AIS) was evaluated.

A nationwide epidemiological study was conducted using the Taiwan National Health Insurance Research Database from 2000 to 2010. From the 1456 osteoporosis patients with previous ACS or AIS, mortality and cardiovascular safety was compared between 464 patients who used BPs and 464 patients who did not. Primary outcomes included all-cause mortality, and major adverse cardiovascular events.

The BPs group had a lower risk of all-cause mortality than the control group after the 8-year follow-up (HR, 0.64; 95% CI, 0.46-0.88; P=0.006). The risks of myocardial infarction, ischemic stroke, cardiovascular death, hospitalization for heart failure or other causes of mortality were similar across groups. However, there was a higher risk of hospitalization for atrial fibrillation in the BPs group than the control group (HR, 1.76; 95% CI, 1.26-2.46; P=0.001).

Among osteoporosis patients after ACS or AIS, BPs use was associated with a reduced risk of all-cause mortality. However, patients with previous cardiovascular disease who received BP treatment should be careful about the risk of atrial fibrillation.

Among osteoporosis patients after ACS or AIS, BPs use was associated with a reduced risk of all-cause mortality. However, patients with previous cardiovascular disease who received BP treatment should be careful about the risk of atrial fibrillation.The effect of the presence of food on the incorporation and excretion of silica particles was studied in this work using the biological model Caenorhabditis elegans and image analysis techniques. The experiment was based on two 24-hour phases exposure and depuration. During exposure, nematodes were maintained for 24 h in liquid medium with silica particles, but some with and others without food. During depuration, nematodes were transferred to medium without particles. Nematodes were analysed by an image analysis in both phases to quantify the properties of particle distributions in nematodes' bodies with time. No differences were found in the proportion of nematodes carrying particles in the exposure phase when food was present. However in the depuration phase, lack of food generated a high proportion of particle carriers. Particle distribution properties were also similar in the exposure phase. Nevertheless, lack of food produced particle accumulation due to decelerated excretion because digestive tube relaxed under these conditions. Thus after the depuration phase, lack of food led particles to persist in digestive tubes. According to these results, intake of silica particles had no retention effects when a food flux was provided, but particles were not easily excreted when the food flux was interrupted.

To describe and evaluate a consensus finding and expert validation process for the development of patient-centred communication assessments for a national Licensing Exam in Medicine.

A multi-professional team of clinicians and experts in communication, assessment and role-play developed communication assessments for the Swiss Federal Licensing Examination. The six-month process, informed by a preceding national needs-assessment, an expert symposium and a critical literature review covered the application of patient-centred communication frameworks, the development of assessment guides, concrete assessments and pilot-tests. The participants evaluated the process.

The multiple-step consensus process, based on expert validation of the medical and communication content, led to six high-stakes patient-centred communication OSCE-assessments. The process evaluation revealed areas of challenge such as calibrating rating-scales and case difficulty to the graduates' competencies and integrating differing opinions. Main success factors were attributed to the outcome-oriented process and the multi-professional exchange of expertise. A model for developing high stakes patient-centred communication OSCE-assessments was derived.

Consensus finding was facilitated by using well-established communication frameworks, by ensuring outcome-orientated knowledge exchange among multi-professional experts, and collaborative validation of content through experts.

We propose developing high-stakes communication assessments in a multi-professional expert consensus and provide a conceptual model.

We propose developing high-stakes communication assessments in a multi-professional expert consensus and provide a conceptual model.

There is a large amount of studies about interventions for promoting physical activity (PA) in persons with type 2 diabetes (T2D) as well as several systematic reviews referring to these studies. The objective of this contribution is to provide a systematic review of these systematic reviews.

PubMed, PsychInfo and the Cochrane Library were searched for systematic reviews and/or meta-analyses regarding interventions for promoting PA in persons with T2D. The individual reviews and the relationships between the reviews were analysed.

Eighteen reviews were included. Seventeen of these reviews contained references to included trials, amounting to 113 trials in total. Five of the reviews addressed PA interventions in general; six addressed specific devices for delivering the intervention; five addressed specific approaches for giving the participants feedback about their outcomes; and two addressed specific therapeutic approaches. Only 14 cross-references were found.

Giving feedback about outcomes and helping people to integrate PA in their daily lives seem to be the most effective intervention components. Basing intervention development on theories seems helpful.

Interventions should give feedback about outcomes and help to integrate PA in daily life. Intervention development should be theory-based.

Interventions should give feedback about outcomes and help to integrate PA in daily life. Intervention development should be theory-based.Age-related macular degeneration (AMD) is a leading cause of blindness. Laser-induced nonhuman primate choroidal neovascularization (CNV) is a widely used animal model of neovascular AMD. Subretinal fibrosis (SFb) is the major limiting factor of effective anti-VEGF therapy for neovascular AMD, yet SFb has never been systematically analyzed in the primate CNV model and if VEGF directly affect SFb is unknown. We recruited a large cohort of rhesus macaques to study the occurrence, multimodal imaging and electroretinography (ERG) features, and related cytokines of SFb. Here we show that among 33 rhesus macaques, 88% CNV eyes developed SFb. Spectral domain optical coherence tomography (SD-OCT) identified four types of subretinal hyper-reflective material (SHRM) of SFb in primate. Multimodal imaging is reliable for monitoring SFb and matches the histological results well. Reduced amplitude of oscillatory potentials correlates with the thinning of inner retina layers and is a possible SFb indicator. Iba1+ microglia/macrophage cells infiltrated in the fibrotic lesions, and aqueous cytokine analysis identified four fibrosis-related factors (GM-CSF, IL-10, TGFβ2 and VEGF).