Rising COVID-19 related acute pulmonary emboli but falling national chronic thromboembolic pulmonary hypertension referrals from a large national dataset.

The average rate of new #CTEPH referrals has dropped by 32% in the UK during the pandemic, despite the high incidence of #COVID19 related pulmonary emboli. There have been no recorded new cases of CTEPH caused by COVID-19. A prospective study is underway. https://bit.ly/37msP2G

Multidrug and extensively drug-resistant tuberculosis from a general practice perspective

Despite intensive efforts to eradicate the disease, tuberculosis continues to be a major threat to Indian society, with an estimated prevalence of 3.45 million cases in 2006. Emergence of multidrug-resistant tuberculosis has complicated eradication attempts in recent years. Incomplete and/inadequate treatment are the main causes for development of drug resistance. Directly observed therapy, short-course (DOTS) is the World Health Organization (WHO) strategy for worldwide eradication of tuberculosis, and our country achieved 100% coverage for DOTS through the Revised National Tuberculosis Control Program in 2006. For patients with multidrug-resistant tuberculosis, the WHO recommends a DOTS-Plus treatment strategy. Early detection and prompt treatment of multidrug-resistant tuberculosis is crucial to avoid spread of the disease and also because of the chances of development of potentially incurable extensively drug-resistant tuberculosis in these cases. This review discusses the epidemiologic, diagnostic, and therapeutic aspects of multidrug-resistant tuberculosis, and also outlines the role of primary care doctors in the management of this dangerous disease

Cardiovascular Variability, Sociodemographics, and Biomarkers of Disease: The MIDUS Study

Introduction: Like heart rate, blood pressure (BP) is not steady but varies over intervals as long as months to as short as consecutive cardiac cycles. This blood pressure variability (BPV) consists of regularly occurring oscillations as well as less well-organized changes and typically is computed as the standard deviation of multiple clinic visit-to-visit (VVV-BP) measures or from 24-h ambulatory BP recordings (ABPV). BP also varies on a beat-to-beat basis, quantified by methods that parse variation into discrete bins, e.g., low frequency (0.04–0.15 Hz, LF). However, beat-to-beat BPV requires continuous recordings that are not easily acquired. As a result, we know little about the relationship between LF-BPV and basic sociodemographic characteristics such as age, sex, and race and clinical conditions. Methods: We computed LF-BPV during an 11-min resting period in 2,118 participants in the Midlife in the US (MIDUS) study. Results: LF-BPV was negatively associated with age, greater in men than women, and unrelated to race or socioeconomic status. It was greater in participants with hypertension but unrelated to hyperlipidemia, hypertriglyceridemia, diabetes, elevated CRP, or obesity. LF-diastolic BPV (DBPV), but not-systolic BPV (SBPV), was negatively correlated with IL-6 and s-ICAM and positively correlated with urinary epinephrine and cortisol. Finally, LF-DBPV was negatively associated with mortality, an effect was rendered nonsignificant by adjustment by age but not other sociodemographic characteristics. Discussion: These findings, the first from a large, national sample, suggest that LF-BPV differs significantly from VVV-BP and ABPV. Confirming its relationship to sociodemographic risk factors and clinical outcomes requires further study with large and representative samples

Single Plasma Concentrations of 1′‐Hydroxymidazolam or the Ratio of 1′‐Hydroxymidazolam: Midazolam Do Not Predict Midazolam Clearance in Healthy Subjects

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97152/1/009127002237986.pd

Induction of Inflammation by West Nile virus Capsid through the Caspase-9 Apoptotic Pathway

West Nile virus (WNV) is a member of the Flaviviridae family of vector-borne pathogens. Clinical signs of WNV infection include neurologic symptoms, limb weakness, and encephalitis, which can result in paralysis or death. We report that the WNV-capsid (Cp) by itself induces rapid nuclear condensation and cell death in tissue culture. Apoptosis is induced through the mitochondrial pathway resulting in caspase-9 activation and downstream caspase-3 activation. Capsid gene delivery into the striatum of mouse brain or interskeletal muscle resulted in cell death and inflammation, likely through capsid-induced apoptosis in vivo. These studies demonstrate that the capsid protein of WNV may be responsible for aspects of viral pathogenesis through induction of the apoptotic cascade

Skeletal immaturity, rostral sparing, and disparate hip morphologies as biomechanical causes for Legg-Calvé-Perthes’ disease

Legg-Calvé-Perthes' (Perthes') disease is a developmental disease of the hip joint that may result in numerous short and long term problems. The etiology of the disease remains largely unknown, but the mechanism is believed to be vascular and/or biomechanical in nature. There are several anatomical characteristics that tend to be prevalent in children with Perthes' disease, namely: skeletal immaturity, reduced height, and rostral sparing. We present an overview of the literature, summarizing the current understanding of the pathogenesis, particularly related to how the formation of the vasculature to the femoral epiphysis places children aged 5–8 at a higher risk for Perthes' disease, how skeletal immaturity and rostral sparing could increase the probability of developing Perthes' disease, and how animal models have aided our understanding of the disease. In doing so, we also explore why Perthes' disease is correlated to latitude, with populations at higher latitudes having higher incidence rates than populations closer to the Equator. Finally, we present five hypotheses detailing how Perthes' disease could have a biomechanical cause. Clin. Anat. 29:759–772, 2016. © 2016 Wiley Periodicals, Inc

Predictive Models for Mechanical Properties of Hybrid Fibres reinforced Concrete Containing Bamboo and Basalt Fibres

The aim of this study was to investigate hybrid fibre reinforced concrete containing natural Bamboo and basalt fibres and forecasting the effect of these fibres on Mechanical properties. The contents of Basalt fibres were (0%, 0.25%, 0.50%, 0.75% and 1.00%). The mechanical performance of the hybrid fibre-reinforced concrete was studied in terms of compressive, splitting tensile and flexural strengths. All the samples were tested at the ages of 7, 14, and 28 days. The results showed that an increase in fibre percentages led to a reduction in the concrete slump. It was also found that 0.75% Basalt fibres with 1% bamboo fibres resulted in the optimum performance of the mechanical properties of the concrete. Based on regression models, it was found that bamboo fibres have negative impact on the compressive and splitting tensile strength while basalt fibres enhanced this strength, however, the negative effect of bamboo fibres reduces with the age of concrete. While the effect of bamboo fibres on flexural strength was positive and basalt fibres have negative impact on it. It was concluded that the bamboo and basalt fibre have good relation in overall improving the mechanical properties of hybrid fibre reinforced concrete

Limited Sampling Strategy to Predict AUC of the CYP3A Phenotyping Probe Midazolam in Adults: Application to Various Assay Techniques

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97211/1/00912700222011418.pd

A Novel Cold-Adapted Lipase from Sorangium cellulosum Strain So0157-2: Gene Cloning, Expression, and Enzymatic Characterization

Genome sequencing of cellulolytic myxobacterium Sorangium cellulosum reveals many open-reading frames (ORFs) encoding various degradation enzymes with low sequence similarity to those reported, but none of them has been characterized. In this paper, a predicted lipase gene (lipA) was cloned from S. cellulosum strain So0157-2 and characterized. lipA is 981-bp in size, encoding a polypeptide of 326 amino acids that contains the pentapeptide (GHSMG) and catalytic triad residues (Ser114, Asp250 and His284). Searching in the GenBank database shows that the LipA protein has only the 30% maximal identity to a human monoglyceride lipase. The novel lipA gene was expressed in Escherichia coli BL21 and the recombinant protein (r-LipA) was purified using Ni-NTA affinity chromatography. The enzyme hydrolyzed the p-nitrophenyl (pNP) esters of short or medium chain fatty acids (≤C10), and the maximal activity was on pNP acetate. The r- LipA is a cold-adapted lipase, with high enzymatic activity in a wide range of temperature and pH values. At 4 °C and 30 °C, the Km values of r-LipA on pNP acetate are 0.037 ± 0.001 and 0.174 ± 0.006 mM, respectively. Higher pH and temperature conditions promoted hydrolytic activity toward the pNP esters with longer chain fatty acids. Remarkably, this lipase retained much of its activity in the presence of commercial detergents and organic solvents. The results suggest that the r-LipA protein has some new characteristics potentially promising for industrial applications and S. cellulosum is an intriguing resource for lipase screening

Privacy-Preserving COVID-19 Contact Tracing App: A Zero-Knowledge Proof Approach

In this paper, we propose a privacy-preserving contact tracing protocol for smart phones, and more specifically Android and iOS phones. The protocol allows users to be notified, if they have been a close contact of a confirmed patient. The protocol is designed to strike a balance between privacy, security, and scalability. Specifically, the app allows all users to hide their past location(s) and contact history from the Government, without affecting their ability to determine whether they have close contact with a confirmed patient whose identity will not be revealed. A zero-knowledge protocol is used to achieve such a user privacy functionality. In terms of security, no user can send fake messages to the system to launch a false positive attack. We present a security model and formally prove the security of the protocol. To demonstrate scalability, we evaluate an Android and an iOS implementation of our protocol. A comparative summary shows that our protocol is the most comprehensive and balanced privacy-preserving contact tracing solution to-date