Mapping interactions with the chaperone network reveals factors that protect against tau aggregation.

A network of molecular chaperones is known to bind proteins ('clients') and balance their folding, function and turnover. However, it is often unclear which chaperones are critical for selective recognition of individual clients. It is also not clear why these key chaperones might fail in protein-aggregation diseases. Here, we utilized human microtubule-associated protein tau (MAPT or tau) as a model client to survey interactions between ~30 purified chaperones and ~20 disease-associated tau variants (~600 combinations). From this large-scale analysis, we identified human DnaJA2 as an unexpected, but potent, inhibitor of tau aggregation. DnaJA2 levels were correlated with tau pathology in human brains, supporting the idea that it is an important regulator of tau homeostasis. Of note, we found that some disease-associated tau variants were relatively immune to interactions with chaperones, suggesting a model in which avoiding physical recognition by chaperone networks may contribute to disease

Saccadic reaction time in mirror image sectors across horizontal meridian in eye movement perimetry

In eye movement perimetry (EMP), the saccadic reaction time (SRT) to ‘seen’ visual stimuli are delayed in glaucoma. Evaluating SRT behaviour in hemi-field sectors could refine its clinical implication. The development phase included 60 controls retrospectively and for the test cohort in evaluation phase, another 30 healthy subjects and 30 glaucoma patients were recruited prospectively. The SRTs were used to calculate the normative limits within 5 predefined hemi-field sectors. Scores were assigned to probabilities for SRT at the level of 5%, 2.5% 1% and 0.5%. Per sector pair, a probability score limit (PSL) was calculated at each of the four levels and were compared with the scores obtained from the test cohort. The classification accuracy ‘normal versus abnormal’ was assessed for PSL in EMP and compared with glaucoma hemi-field test in standard automated perimetry. We found no statistically significant differences in SRTs between the mirror sectors in healthy subjects. The PSL at 2.5% had moderate classification accuracy with a specificity of 77% and sensitivity 70%. This could be suggestive of an SRT delay in the overall visual field in glaucoma

Triage Considerations for Patients Referred for Structural Heart Disease Intervention During the COVID-19 Pandemic: An ACC/SCAI Position Statement

The coronavirus disease-2019 (COVID-19) pandemic has strained health care resources around the world, causing many institutions to curtail or stop elective procedures. This has resulted in an inability to care for patients with valvular and structural heart disease in a timely fashion, potentially placing these patients at increased risk for adverse cardiovascular complications, including CHF and death. The effective triage of these patients has become challenging in the current environment as clinicians have had to weigh the risk of bringing susceptible patients into the hospital environment during the COVID-19 pandemic against the risk of delaying a needed procedure. In this document, the authors suggest guidelines for how to triage patients in need of structural heart disease interventions and provide a framework for how to decide when it may be appropriate to proceed with intervention despite the ongoing pandemic. In particular, the authors address the triage of patients in need of transcatheter aortic valve replacement and percutaneous mitral valve repair. The authors also address procedural issues and considerations for the function of structural heart disease teams during the COVID-19 pandemic

Triage Considerations for Patients Referred for Structural Heart Disease Intervention During the Coronavirus Disease 2019 (COVID-19) Pandemic: An ACC /SCAI Consensus Statement

The COVID-19 pandemic has strained health care resources around the world causing many institutions to curtail or stop elective procedures. This has resulted in the inability to care for patients valvular and structural heart disease (SHD) in a timely fashion potentially placing these patients at increased risk for adverse cardiovascular complications including congestive heart failure and death. The effective triage of these patients has become challenging in the current environment as clinicians have had to weigh the risk of bringing susceptible patients into the hospital environment during the COVID-19 pandemic versus the risk of delaying a needed procedure. In this document, we suggest guidelines as to how to triage patients in need of SHD interventions and provide a framework of how to decide when it may be appropriate to proceed with intervention despite the ongoing pandemic. In particular, we address the triage of patients in need of trans-catheter aortic valve replacement and percutaneous mitral valve repair. We also address procedural issues and considerations for the function of structural heart disease teams during the COVID-19 pandemic

Effect of age, sex, stimulus intensity, and eccentricity on saccadic reaction time in eye movement perimetry

Purpose: In eye movement perimetry (EMP), the extent of the visual field is tested by assessing the saccades using an eye tracker. The aim of the present study was to determine the effects of age and sex of the subjects, the eccentricity and intensity of the peripheral stimuli on saccadic reaction time (SRT), and the interaction between these parameters in healthy participants. Methods: Healthy participants aged between 20 to 70 years underwent a complete ophthalmic examination and an EMP test. SRT was determined from detected peripheral stimuli of four intensity levels. A multilevel mixed-model analysis was used to verify the influence of subject and stimulus characteristics on SRT within the tested visual field. Results: Ninety-five subjects (mean age 43.0 [15.0] years) were included. Age, stimulus intensity, and eccentricity had a statistically significant effect on SRT, not sex. SRTs were significantly faster with increasing stimulus intensity and decreasing eccentricity (P < 0.001). At the lowest stimulus intensity of 192 cd/m2, a significant interaction was found between age and eccentricity. Conclusions: The current study demonstrated significant SRT dependence across the visual field measured up to 278, irrespective of sex. The presented SRT values may serve as a first normative guide for EMP. Translational Relevance: This report of SRT interaction can aid in refining its use as a measure of visual field responsiveness

Searches for rare B-s(0) and B-0 decays into four muons

Searches for rare B-s(0) and B-0 decays into four muons are performed using proton-proton collision data recorded by the LHCb experiment, corresponding to an integrated luminosity of 9 fb(-1). Direct decays and decays via light scalar and J/psi resonances are considered. No evidence for the six decays searched for is found and upper limits at the 95% confidence level on their branching fractions ranging between 1.8 x 10(-10) and 2.6 x 10(-9) are set