Angiopoietins as Prognostic Markers for Future Kidney Disease and Heart Failure Events After Acute Kidney Injury

Background The mechanisms underlying long-term sequelae following acute kidney injury (AKI) remain unclear. Vessel instability, an early response to endothelial injury, may reflect a shared mechanism and early trigger for chronic kidney disease (CKD) and heart failure. Methods To investigate whether plasma angiopoietins, markers of vessel homeostasis, are associated with CKD progression and heart failure admissions after hospitalization in patients with and without AKI, we conducted a prospective cohort study to analyze the balance between angiopoietin-1 (Angpt-1), which maintains vessel stability, and angiopoietin-2 (Angpt-2), which increases vessel destabilization. Three months after discharge, we evaluated the associations between angiopoietins and development of the primary outcomes of CKD progression and heart failure, as well as the secondary outcome of all-cause mortality 3 months after discharge or later. Results Median age for the 1503 participants was 65.8 years; 746 (50%) had AKI. Compared with the lowest quartile, the highest quartile of the Angpt-1:Angpt-2 ratio was associated with 72% lower risk of CKD progression (adjusted hazard ratio [aHR], 0.28; 95% confidence interval [95% CI], 0.15 to 0.51), 94% lower risk of heart failure (aHR, 0.06; 95% CI, 0.02 to 0.15), and 82% lower risk of mortality (aHR, 0.18; 95% CI, 0.09 to 0.35) for those with AKI. Among those without AKI, the highest quartile of Angpt-1:Angpt-2 ratio was associated with 71% lower risk of heart failure (aHR, 0.29; 95% CI, 0.12 to 0.69) and 68% less mortality (aHR, 0.32; 95% CI, 0.15 to 0.68). There were no associations with CKD progression. Conclusions A higher Angpt-1:Angpt-2 ratio was strongly associated with less CKD progression, heart failure, and mortality in the setting of AKI.

COVID-19 and the Homelessness Support Sector

This exploratory study sought to uncover service provider perspectives on the early response to COVID-19 in a small community in an advanced industrialized country - the homelessness support sector of the Central Okanagan, British Columbia. Following a case study approach, snowball sampling was utilized in May and June 2020 to achieve a sample size of 30 through a mix of one-on-one interviews and open-ended surveys. Qualitative thematic analysis was used to uncover commonalities among interview responses. Common themes are discussed in relation to three areas of questioning including challenges, successes, and mitigations/areas for future support. While the community came together to support the response, there were challenges and concerns regarding safety and personal protective equipment supplies, social distancing and knowledge transmission within the homeless community, access to food and water, and lack of space for isolating positive cases. The findings illustrate possible research, practice, public health policy, and emergency planning considerations within smaller communities.

Molecular Characterization and Response of Prolyl Hydroxylase Domain (PHD) Genes to Hypoxia Stress in Hypophthalmichthys molitrix

As an economically and ecologically important freshwater fish, silver carp (Hypophthalmichthys molitrix) is sensitive to low oxygen tension. Prolyl hydroxylase domain (PHD) proteins are critical regulators of adaptive responses to hypoxia for their function of regulating the hypoxia inducible factor-1 alpha subunit (HIF-1α) stability via hydroxylation reaction. In the present study, three PHD genes were cloned from H. molitrix by rapid amplification of cDNA ends (RACE). The total length of HmPHD1, HmPHD2, and HmPHD3 were 2981, 1954, and 1847 base pair (bp), and contained 1449, 1080, and 738 bp open reading frames (ORFs) that encoded 482, 359, and 245 amino acids (aa), respectively. Amino acid sequence analysis showed that HmPHD1, HmPHD2, and HmPHD3 had the conserved prolyl 4-hydroxylase alpha subunit homolog domains at their C-termini. Meanwhile, the evaluation of phylogeny revealed PHD2 and PHD3 of H. molitrix were more closely related as they belonged to sister clades, whereas the clade of PHD1 was relatively distant from these two. The transcripts of PHD genes are ubiquitously distributed in H. molitrix tissues, with the highest expressional level of HmPHD1 and HmPHD3 in liver, and HmPHD2 in muscle. After acute hypoxic treatment for 0.5 h, PHD genes of H. molitrix were induced mainly in liver and brain, and different from HmPHD1 and HmPHD2, the expression of HmPHD3 showed no overt tissue specificity. Furthermore, under continued hypoxic condition, PHD genes exhibited an obviously rapid but gradually attenuated response from 3 h to 24 h, and upon reoxygenation, the transcriptional expression of PHD genes showed a decreasing trend in most of the tissues. These results indicate that the PHD genes of H. molitrix are involved in the early response to hypoxic stress, and they show tissue-specific transcript expression when performing physiological regulation functions. This study is of great relevance for advancing our understanding of how PHD genes are regulated when addressing the hypoxic challenge and provides a reference for the subsequent research of the molecular mechanisms underlying hypoxia adaptation in silver carp.

Longitudinal Bowel Behavior Assessed by Bowel Ultrasound to Predict Early Response to Anti-TNF Therapy in Patients with Crohn's Disease: A Pilot Study

Background Early changes in bowel behavior during anti-TNF induction therapy in Crohn’s disease (CD) are relatively unknown. We determined (a) onset of changes in bowel behavior in CD patients receiving anti-TNF therapy by ultrasound; and (b) the feasibility of shear wave elastography (SWE) in predicting early response to anti-TNF therapy. Methods Consecutive ileal/ileocolonic CD patients programmed to initiate anti-TNF therapy were enrolled. Bowel ultrasound was performed at baseline, and at weeks 2, 6, and 14. Changes in bowel wall thickness, Doppler signals of the bowel wall (Limberg score), and SWE values were compared using a linear mixed model. Early response to anti-TNF therapy was based on a composite strategy of clinical and colonoscopy assessment at week 14. Results Of the 30 patients enrolled in this study, 20 patients achieved a response to anti-TNF therapy at week 14. The bowel wall thickness and SWE value of the response group showed a significant downward trend compared with the non-response group (P=0.003, P=0.011). Bowel wall thickness, the Limberg score, and SWE values were significantly reduced as early as week 2 compared with baseline (P<0.001, P<0.001, P=0.003) in the response group. Baseline SWE values (21.3±8.7 vs. 15.3±4.7 kPa, P=0.022) and bowel wall thickness (8.5±2.3 vs. 6.9±1.5 mm, P=0.027) in the non-response group were significantly higher than in the response group. Conclusions This pilot study suggested that changes in bowel ultrasound behavior could be assessed as early as week 2 after starting anti-TNF therapy. Bowel ultrasound together with elasticity imaging could predict early response to anti-TNF therapy.

The Effects of Foliar Application of Phenoxy and Imidazoline Family Herbicides on the Limitation of Primary Photosynthetic Processes in Galega orientalis L.

Fodder galega (Galega orientalis) is a perennial, wintering plant with great potential for agricultural development. The species has a large yield potential and exceptional adaptability to various environmental conditions. The sensitivity of G. orientalis to herbicides, however, as well as the photosynthetic performance of the species, are generally unknown. Our study aimed to evaluate the effects of the application of selected phenoxy herbicides (MCPA, MCPB) and the imidazoline family herbicide (IMA) on the parameters of primary photosynthetic processes as understood through fast chlorophyll fluorescence kinetics (OJIP). The effect of cultivation temperature was also investigated in the plants grown at 5, 18 and 25 °C. Time courses of OJIP-derived parameters describing photosystem II functioning after foliar application revealed that the plants showed negative responses to the herbicides in the order MCPB–MCPA–IMA within 24 h after the application. The application of herbicides decreased the values of maximum chlorophyll fluorescence (FM) and increased minimum fluorescence (F0), which led to a reduction in the maximal efficiency of PSII (FV/FM). Applications of MCPA and MCPB decreased variable chlorophyll fluorescence at 2 ms (VJ), 30 ms (VI) and VP, as well as the performance index (PIABS), which is considered a vitality proxy. The application increased absorption flux (ABS/RC), trapped energy flux (TRo/RC) and dissipated energy flux (DIo/RC). The effects were more pronounced in plants grown at 18 and 25 °C. The study revealed that the OJIP-derived parameters sensitively reflected an early response of G. orientalis to the foliar application of herbicides. Negative responses of PSII were more apparent in MCPA- and MCPB- exposed plants than IMA-exposed plants.

The risks and benefits of providing HIV services during the COVID-19 pandemic

Introduction The COVID-19 pandemic has caused widespread disruptions including to health services. In the early response to the pandemic many countries restricted population movements and some health services were suspended or limited. In late 2020 and early 2021 some countries re-imposed restrictions. Health authorities need to balance the potential harms of additional SARS-CoV-2 transmission due to contacts associated with health services against the benefits of those services, including fewer new HIV infections and deaths. This paper examines these trade-offs for select HIV services. Methods We used four HIV simulation models (Goals, HIV Synthesis, Optima HIV and EMOD) to estimate the benefits of continuing HIV services in terms of fewer new HIV infections and deaths. We used three COVID-19 transmission models (Covasim, Cooper/Smith and a simple contact model) to estimate the additional deaths due to SARS-CoV-2 transmission among health workers and clients. We examined four HIV services: voluntary medical male circumcision, HIV diagnostic testing, viral load testing and programs to prevent mother-to-child transmission. We compared COVID-19 deaths in 2020 and 2021 with HIV deaths occurring now and over the next 50 years discounted to present value. The models were applied to countries with a range of HIV and COVID-19 epidemics. Results Maintaining these HIV services could lead to additional COVID-19 deaths of 0.002 to 0.15 per 10,000 clients. HIV-related deaths averted are estimated to be much larger, 19–146 discounted deaths per 10,000 clients. Discussion While there is some additional short-term risk of SARS-CoV-2 transmission associated with providing HIV services, the risk of additional COVID-19 deaths is at least 100 times less than the HIV deaths averted by those services. Ministries of Health need to take into account many factors in deciding when and how to offer essential health services during the COVID-19 pandemic. This work shows that the benefits of continuing key HIV services are far larger than the risks of additional SARS-CoV-2 transmission.

Early Response of Antimicrobial Resistance and Virulence Genes Expression in Classical, Hypervirulent, and Hybrid hvKp-MDR Klebsiella pneumoniae on Antimicrobial Stress

Klebsiella pneumoniae is an increasingly important hospital pathogen. Classical K. pneumoniae (cKp) and hypervirulent K. pneumoniae (hvKp) are two distinct evolutionary genetic lines. The recently ongoing evolution of K. pneumoniae resulted in the generation of hybrid hvKP-MDR strains. K. pneumoniae distinct isolates (n = 70) belonged to 20 sequence types with the prevalence of ST395 (27.1%), ST23 (18.6%), ST147 (15.7%), and ST86 (7.1%), and 17 capsular types with the predominance of K2 (31.4%), K57 (18.6%), K64 (10.0%), K1 (5.7%) were isolated from patients of the Moscow neurosurgery ICU in 2014–2019. The rate of multi-drug resistant (MDR) and carbapenem-resistant phenotypes were 84.3% and 45.7%, respectively. Whole-genome sequencing of five selected strains belonging to cKp (ST395K47 and ST147K64), hvKp (ST86K2), and hvKp-MDR (ST23K1 and ST23K57) revealed blaSHV, blaTEM, blaCTX, blaOXA-48, and blaNDM beta-lactamase genes; acr, oqx, kpn, kde, and kex efflux genes; and K. pneumoniae virulence genes. Selective pressure of 100 mg/L ampicillin or 10 mg/L ceftriaxone induced changes of expression levels for named genes in the strains belonging to cKp, hvKp, and hybrid hvKp-MDR. Obtained results seem to be important for epidemiologists and clinicians for enhancing knowledge about hospital pathogens.