Notes

CDK5 self-consciousness protects towards OGDR caused mitochondrial fragmentation and also apoptosis via regulation of Drp1S616 phosphorylation.
Mycoplasma genitalium is an emergent cause of sexually transmitted disease (STD). The first-line treatment is azithromycin, but macrolide resistance is increasing due to mutations in the 23S rRNA gene.

To determine the rates of M. genitalium infection and macrolide resistance in an area adjacent to Barcelona.

This 1 year prospective study was performed in a heterogenous population that included both low- and high-risk patients. M. genitalium was detected in all specimens sent to our institution for STD detection. Epidemiological and relevant clinical data were collected in the positive cases. Characterization of macrolide-associated resistance was performed by 23S rDNA sequencing.

Of the 3540 patients included, 132 (3.7%) were positive for M. genitalium. Another sexually transmitted bacteria was detected in 20.4% of the M. genitalium cases, and Chlamydia trachomatis (11%) was the most frequently co-detected microorganism. Only 61.4% of patients received an adequate initial treatment against M. genitalium. The test of cure (TOC) was performed in 42% of patients, and therapeutic failure was detected in 10 cases. The rate of macrolide resistance was 12.6% and the most prevalent mutation was A2058G. There was an association between macrolide resistance and a previous history of M. genitalium detection (P < 0.001).

Our results support the contribution of the previous use of macrolides in resistant strains. Given the difficulties in performing TOC in all patients, the inclusion of macrolide resistance in the detection test should be mandatory.
Our results support the contribution of the previous use of macrolides in resistant strains. Given the difficulties in performing TOC in all patients, the inclusion of macrolide resistance in the detection test should be mandatory.The International Commission on Radiological Protection (ICRP) publishes guidance on protection against radon exposure in homes and workplaces. ICRP Publication 137 recommends a dose coefficient of 3 mSv per mJ h m-3 (~10 mSv WLM-1) to be used in most circumstances of radon exposure, for workers in buildings and in underground mines. Recently, United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) reviewed radon epidemiology and dosimetry and concluded that its established dose coefficient of 1.6 mSv per mJ h m-3 (5.7 mSv WLM-1) should be retained for use in its comparisons of radiation exposures from different sources in a population. This paper explains and compares the reviews of the scientific evidence from UNSCEAR and ICRP. It is shown that the UNSCEAR and ICRP reviews are consistent and support the use of the ICRP reference dose coefficients for radiation protection purposes. It is concluded that the ICRP dose coefficient should be used to calculate doses to workers.The British Occupational Hygiene Society (BOHS) Covid-19 Working Group developed a control banding matrix to provide guidance for employers and others to help assess the risks of Covid-19 infection during the pandemic. The matrix was based on occupational hygiene principles and the judgement of the occupational health practitioners involved; since objective data on workers' exposure were unavailable. Users of the matrix identify one of five exposure categories based on generic job descriptions and example occupations, and these categories are linked to generic guidance on interventions at source, on the exposure pathway and for individual workers. The risk matrix was published on the BOHS website and the guidance has been downloaded more than 2000 times. The matrix has had limited evaluation for reliability, but the data suggest that the highest exposure ranked jobs were associated with higher age-standardized mortality in Britain during the pandemic. However, there was considerable variability in exposure assignments between assessors, which underlines the need for the control guidance to be precautionary. The BOHS calls on academic researchers to undertake further work to validate the reliability of the tool.How cells sense and respond to mechanical stimuli remains an open question. Recent advances have identified the translocation of Yes-associated protein (YAP) between nucleus and cytoplasm as a central mechanism for sensing mechanical forces and regulating mechanotransduction. We formulate a spatiotemporal model of the mechanotransduction signalling pathway that includes coupling of YAP with the cell force-generation machinery through the Rho family of GTPases. Considering the active and inactive forms of a single Rho protein (GTP/GDP-bound) and of YAP (non-phosphorylated/phosphorylated), we study the cross-talk between cell polarization due to active Rho and YAP activation through its nuclear localization. For fixed mechanical stimuli, our model predicts stationary nuclear-to-cytoplasmic YAP ratios consistent with experimental data at varying adhesive cell area. We further predict damped and even sustained oscillations in the YAP nuclear-to-cytoplasmic ratio by accounting for recently reported positive and negative YAP-Rho feedback. Extending the framework to time-varying mechanical stimuli that simulate cyclic stretching and compression, we show that the YAP nuclear-to-cytoplasmic ratio's time dependence follows that of the cyclic mechanical stimulus. The model presents one of the first frameworks for understanding spatiotemporal YAP mechanotransduction, providing several predictions of possible YAP localization dynamics, and suggesting new directions for experimental and theoretical studies.Black soldier fly, Hermetia illucens (L.) (Diptera Stratiomyidae), larvae are suspected to inhibit house flies, Musca domestica (L.) (Diptera Muscidae), seeking oviposition sites. However, the mechanisms regulating these interactions are not well known. In this study, a Y-tube olfactometer was used to determine whether black soldier fly eggs, larvae, puparia (without pupae inside), adult carcasses, or resulting frass of black soldier fly decrease attractiveness of adult house flies to an oviposition substrate (i.e., sugar and wheat bran diet, used as the control). Secondly, two symbiotic bacteria associated were isolated, identified, and tested for house fly attractiveness with a Y-tube olfactometer. Thirdly, volatile organic compounds produced by swine feed before and after black soldier fly, or house fly larval digestion were analyzed with gas chromatography-mass spectrometry (GC-MS). Results indicate feed mixed with black soldier fly larval frass, and symbiotic bacteria, Paenalcaligenes sp. associated with black soldier fly, were less attractive to house flies than the control. However, another symbiotic bacterium Lysinibacillus sp. associated with black soldier fly pupae was attractive. In total, 52 volatile organic compounds were identified from treatments previously described. Quantitative differences in volatile profiles across treatments potentially explain the mechanism regulating house fly substrate choices in the presence, or absence, of black soldier fly larvae.
General practitioners (GPs) face a diagnostic challenge when assessing acute abdominal pain in children. However, no information is available on the current diagnostic process or the diagnostic accuracy of history and physical examination in primary care settings.

To describe the diagnostic process for acute abdominal pain among children in primary care, focusing on appendicitis, and to assess the diagnostic accuracy of individual clinical features.

A retrospective cohort study in Dutch primary care, using the Integrated Primary Care Information database. Children are aged 4-18 years were included if they had no history of appendicitis and presented with acute abdominal pain during 2010-2016. We evaluated GP management and the diagnostic accuracy of clinical features for appendicitis. Pre- and post-test probabilities were calculated for each clinical feature and compared with the probability of appendicitis after GP assessment.

Out of 5691 children, 944 (16.6%) were referred and 291 (5.1%) had appendicitis, of whom 55 (18.9%) were initially misdiagnosed. The pre-test probability (i.e. of appendicitis in evaluated children) varied from 3% (rigidity) to 28% (migratory pain). Concerning post-test probabilities, positive values for rebound pain (32.1%) and guarding (35.8%) and the negative value for right lower quadrant tenderness (0.6%) were superior to overall GP assessment (29.6% and 1.1%, respectively).

GP assessment will miss almost one-fifth of children with appendicitis at their first presentation, and about two-third of GP referrals will be negative. The presence of specific signs can increase or decrease the likelihood of appendicitis, emphasising the importance of a physical examination.
GP assessment will miss almost one-fifth of children with appendicitis at their first presentation, and about two-third of GP referrals will be negative. The presence of specific signs can increase or decrease the likelihood of appendicitis, emphasising the importance of a physical examination.
Amongst psychostimulants, the dopamine transporter ligands amphetamine and cocaine display highest addictive potential; the adenosine receptor antagonist caffeine is most widely consumed, but less addictive. Psychostimulant actions of amphetamine were correlated with its ability to orchestrate ventral tegmental dopamine neuron activity with contrasting shifts in firing after single versus repeated administration. Whether caffeine might impinge onto dopamine neuron activity has remained elusive.

Population activity of ventral tegmental area dopamine neurons was determined by single-unit extracellular recordings and set in relation to mouse behaviour in locomotion and conditioned place preference experiments, respectively.

A single dose of caffeine reduced population activity as did amphetamine and the selective A2A antagonist KW-6002, but not the A1 antagonist DPCPX. Repeated administration of KW-6002 or amphetamine led to drug conditioned place preference and to unaltered or even enhanced population actn response to repeated caffeine intake.
Acute otitis media (AOM) is a common cause for antibiotic prescription. Most guidelines endorse abstaining from immediate antibiotic treatment ('watchful waiting', WW) in mild-moderate episodes. We studied adherence rates to the latest AOM guidelines (2013), in terms of antibiotic type and prescription options.

In this population-based study, AOM episodes were identified in Clalit Health Services-insured children aged 0-10 years between 2011 and 2018, using a data-sharing platform. After identifying the index, prescription and issuing dates for antibiotics for each AOM episode, treatment was categorized as immediate (≤2 days after diagnosis) or WW (antibiotic not prescribed/issued; prescribed ≤2 days after diagnosis but issued on Days 2-7; or prescribed/issued on Days 2-7). Guideline adherence was measured according to age.

Of the 491 106 episodes, 361 518 (73.6%) were treated with antibiotics. Following the 2013 guidelines, the ratio of episodes in children aged ≤6 months that were adherent (immediate treatment) was higher (OR = 1.22; 95% CI 1.15-1.29; P < 0.001), whereas the adherent episode ratio for children aged 6-24 months and 2-10 years (WW) was lower (OR = 0.87; 95% CI 0.85-0.88 and OR = 0.94; 95% CI 0.92-0.96, respectively; P < 0.001). Antibiotic prescription rates after 2013 for children aged ≤6 months were not different (OR = 1.03; 95% CI 0.96-1.1; P = 0.4), but were higher in children aged 6-24 months and 2-10 years (OR = 1.07; 95% CI 1.05-1.09; P < 0.001 and OR = 1.02; 95% CI 1.01-1.04; P = 0.015, respectively). Amoxicillin was the most common antibiotic, administered in 75.6% of episodes. Azithromycin was most commonly associated with treatment failure (6.6%).

Improved adherence to the 2013 guidelines was observed only in children aged ≤6 months and over-treatment with antibiotics was still high.
Improved adherence to the 2013 guidelines was observed only in children aged ≤6 months and over-treatment with antibiotics was still high.
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