Dependence of hypoxic changes in macro- and micro-hemodynamics on the activity of adrenoreceptors in the skeletal muscle in hypothermia

Dependence of hypoxic changes of macro- and microcirculation on the activity of adrenergic receptors in the cooled organism was studied on decentralized shank of cat under perfusion with constant blood flow. After cooling of cat (to 30 degrees C) and blockade of alpha-adrenoreceptors hypoxic hypoxia (10% O2 in N2) caused (a) much greater reduction of precapillary resistance of shank, (b) more striking (by 3 times) increase of capillary filtration coefficient and (c) the increase of capillary pressure and postcapillary resistance in contrast to their decrease to hypoxia under hypothermia before alpha-blockade. Beta-adrenoreceptor blockade had no influence on the changes of the resistance and exchange function of skeletal muscle blood vessels evoked by hypoxia under cooling.     

Decrease in the effectiveness of a hypoxic stimulus during cooling of the vascular bed of an organ

Acute experiments on cats using perfusion of the innervated calf muscle and small intestinal vessels with self blood at a constant blood flow rate have established decreased sensitivity of vessels (cooled to 30 degrees C) to hypoxic stimulus effect (inhalation of 10% O2 in N2). The essence of the phenomenon consists in considerably smaller deviations of pre- and postcapillary resistance, capillary filtration coefficient, mean capillary pressure during simultaneous exposure to cold and hypoxia than during separate application of hypoxic or hypothermic stimuli. Organ distinctions in the degree and direction of changes in vascular resistance and metabolism have been observed.     

Microbiocenosis of the large intestine in acute complicated pneumonia in children

Fifty-six children of early age with pneumonia developed on the background of frequent respiratory infections were placed under observation. In 91.1% of these cases microecological disturbances in the intestine were detected, 46.6% of the patients having third-degree dysbacteriolysis. In such cases it is more correct to regard the "intestinal" syndrome as the clinical manifestation of disturbances in the biocenosis of the intestine, the state of its microflora. Intestinal dysbacteriosis aggravates the course of acute aggravated pneumonia in children and requires the inclusion of special therapy aimed at normalizing intestinal microflora.     

Intestinal microbiocenosis in children with intestinal enzymopathy

141 children with different kinds of intestinal enzymopathy were examined; of these, 33 had celiac disease, 39--the syndrome of celiac disease, 12--congenital lactase deficiency and 57--the syndrome of disaccharidase insufficiency. In these patients a significant decrease in the average characteristics of the main protective flora and the growth of hemolytic and lactose-negative enterobacteria were established. In all groups of patients increased amounts of Proteus were detected, which was indicative of profound dysbiosis. The content of bifidobacteria was found to be decreased in 89.5-97% of the patients and the content of lactic acid bacteria, in 15.8-33.3%. The decreased content of Escherichia coli with normal enzymatic activity (less than 10(7) colony-forming units) was noted in one-third of the patients with the syndrome of celiac disease and congenital lactase deficiency, in about a half of the patients with the syndrome of disaccharidase insufficiency and least of all in patients with celiac disease (9.1%). The association of opportunistic microbes was detected in 15.6% of the patients, more often in those with celiac disease, the syndrome of celiac disease and congenital lactase deficiency. The severity of disturbances in intestinal eubiosis was found to depend on the gravity of the patients' state.     

Effectiveness of Holistic Interventions for People with Severe Chronic Obstructive Pulmonary Disease: Systematic Review of Controlled Clinical Trials

Background

Despite a well-recognised burden of disabling physical symptoms compounded by co-morbidities, psychological distress and social isolation, the needs of people with severe chronic obstructive pulmonary disease (COPD) are typically poorly addressed.

Aim

To assess the effectiveness of interventions designed to deliver holistic care for people with severe COPD.

Methods

We searched 11 biomedical databases, three trial repositories (January 1990-March 2012; no language restrictions) and contacted international experts to locate published, unpublished and in-progress randomised controlled trials (RCTs), quasi-RCTs and controlled clinical trials (CCTs) that investigated holistic interventions to support patients with severe COPD in any healthcare context. The primary outcome was health-related quality of life (HRQoL). Quality assessment and data extraction followed Cochrane Collaboration methodology. We used a piloted data extraction sheet and undertook narrative synthesis.

Results

From 2,866 potentially relevant papers, we identified three trials: two RCTs (from United States and Australia), and one CCT (from Thailand): total 216 patients. Risk of bias was assessed as moderate in two studies and high in the third. All the interventions were led by nurses acting in a co-ordinating role (e.g. facilitating community support in Thailand, providing case-management in the USA, or co-ordinating inpatient care in Australia). HRQoL improved significantly in the Thai CCT compared to the (very limited) usual care (p<0.001), in two sub-domains in the American trial, but showed no significant changes in the Australian trial. Exercise tolerance, dyspnoea, and satisfaction with care also improved in the Thai trial.

Conclusions

Some 15 years after reports first highlighted the unmet needs of people with severe COPD, we have been unable to find robust trial evidence about interventions that can address those needs. There is an urgent need to develop and evaluate holistic care interventions designed improve HRQoL for people with severe COPD.

Systematic Review Registration

PROSPERO (CRD42012002430).     

Chemosensitive structures of the medulla oblongata participate in blood pressure regulation and belong to APUD-system

It was shown in 25 experiments on anesthetized spontaneously breathing and immobilized artificially ventilated cats that the cooling of the intermediate chemosensitive area of the ventral surface of medulla oblongata to 20-22 degrees C is followed by depressor reaction that is more pronounced after preliminary occlusion of the sinocarotid and vagus nerves. Two types of apudocytes were revealed in this brain area with the use of the histochemical and immunohistochemical techniques. The first type cells are typically nervous and contain noradrenaline. The second type apudocytes adjacent to the microvascular wall showed melatonin and its precursors. It is assumed that the cells detected participate in the arterial pressure control.     

TGF-β1-Mediated Differentiation of Fibroblasts Is Associated with Increased Mitochondrial Content and Cellular Respiration

Objectivs

Cytokine-dependent activation of fibroblasts to myofibroblasts, a key event in fibrosis, is accompanied by phenotypic changes with increased secretory and contractile properties dependent on increased energy utilization, yet changes in the energetic profile of these cells are not fully described. We hypothesize that the TGF-β1-mediated transformation of myofibroblasts is associated with an increase in mitochondrial content and function when compared to naive fibroblasts.

Methods

Cultured NIH/3T3 mouse fibroblasts treated with TGF-β1, a profibrotic cytokine, or vehicle were assessed for transformation to myofibroblasts (appearance of α-smooth muscle actin [α-SMA] stress fibers) and associated changes in mitochondrial content and functions using laser confocal microscopy, Seahorse respirometry, multi-well plate reader and biochemical protocols. Expression of mitochondrial-specific proteins was determined using western blotting, and the mitochondrial DNA quantified using Mitochondrial DNA isolation kit.

Results

Treatment with TGF-β1 (5 ng/mL) induced transformation of naive fibroblasts into myofibroblasts with a threefold increase in the expression of α-SMA (6.85 ± 0.27 RU) compared to cells not treated with TGF-β1 (2.52 ± 0.11 RU). TGF-β1 exposure increased the number of mitochondria in the cells, as monitored by membrane potential sensitive dye tetramethylrhodamine, and expression of mitochondria-specific proteins; voltage-dependent anion channels (0.54 ± 0.05 vs. 0.23 ± 0.05 RU) and adenine nucleotide transporter (0.61 ± 0.11 vs. 0.22 ± 0.05 RU), as well as mitochondrial DNA content (530 ± 12 μg DNA/10⁶ cells vs. 307 ± 9 μg DNA/10⁶ cells in control). TGF-β1 treatment was associated with an increase in mitochondrial function with a twofold increase in baseline oxygen consumption rate (2.25 ± 0.03 vs. 1.13 ± 0.1 nmol O₂/min/10⁶ cells) and FCCP-induced mitochondrial respiration (2.87 ± 0.03 vs. 1.46 ± 0.15 nmol O₂/min/10⁶ cells).

Conclusions

TGF-β1 induced differentiation of fibroblasts is accompanied by energetic remodeling of myofibroblasts with an increase in mitochondrial respiration and mitochondrial content.     

Telehealthcare for asthma: a Cochrane review

Background:

Telehealthcare has the potential to provide care for long-term conditions that are increasingly prevalent, such as asthma. We conducted a systematic review of studies of telehealthcare interventions used for the treatment of asthma to determine whether such approaches to care are effective.

Methods:

We searched the Cochrane Airways Group Specialised Register of Trials, which is derived from systematic searches of bibliographic databases including CENTRAL (the Cochrane Central Register of Controlled Trials), MEDLINE, Embase, CINAHL (Cumulative Index to Nursing and Allied Health Literature) and PsycINFO, as well as other electronic resources. We also searched registers of ongoing and unpublished trials. We were interested in studies that measured the following outcomes: quality of life, number of visits to the emergency department and number of admissions to hospital. Two reviewers identified studies for inclusion in our meta-analysis. We extracted data and used fixedeffect modelling for the meta-analyses.

Results:

We identified 21 randomized controlled trials for inclusion in our analysis. The methods of telehealthcare intervention these studies investigated were the telephone and video- and Internet-based models of care. Meta-analysis did not show a clinically important improvement in patients’ quality of life, and there was no significant change in the number of visits to the emergency department over 12 months. There was a significant reduction in the number of patients admitted to hospital once or more over 12 months (risk ratio 0.25 [95% confidence interval 0.09 to 0.66]).

Interpretation:

We found no evidence of a clinically important impact on patients’ quality of life, but telehealthcare interventions do appear to have the potential to reduce the risk of admission to hospital, particularly for patients with severe asthma. Further research is required to clarify the cost-effectiveness of models of care based on telehealthcare.There has been an increase in the prevalence of asthma in recent decades,^1–3 and the Global Initiative for Asthma estimates that 300 million people worldwide now have the disease.⁴ The highest prevalence rates (30%) are seen in economically developed countries.^5–8 There has also been an increase in the prevalence of asthma affecting both children and adults in many economically developing and transition countries.^9–11Asthma’s high burden of disease requires improvements in access to treatments.^7,12,13 Patterns of help-seeking behaviour are also relevant: delayed reporting is associated with morbidity and the need for emergency care.It is widely believed that telehealthcare interventions may help address some of the challenges posed by asthma by enabling remote delivery of care, facilitating timely access to health advice, supporting self-monitoring and medication concordance, and educating patients on avoiding triggers.^14–16 The precise role of these technologies in the management of care for people with long-term respiratory conditions needs to be established.¹⁷The objective of this study was to systematically review the effectiveness of telehealthcare interventions among people with asthma in terms of quality of life, number of visits to the emergency department and admissions to hospital for exacerbations of asthma.     

Menopausal hormone therapy and women’s health: An umbrella review

BackgroundThere remains uncertainty about the impact of menopausal hormone therapy (MHT) on women’s health. A systematic, comprehensive assessment of the effects on multiple outcomes is lacking. We conducted an umbrella review to comprehensively summarize evidence on the benefits and harms of MHT across diverse health outcomes.Methods and findingsWe searched MEDLINE, EMBASE, and 10 other databases from inception to November 26, 2017, updated on December 17, 2020, to identify systematic reviews or meta-analyses of randomized controlled trials (RCTs) and observational studies investigating effects of MHT, including estrogen-alone therapy (ET) and estrogen plus progestin therapy (EPT), in perimenopausal or postmenopausal women in all countries and settings. All health outcomes in previous systematic reviews were included, including menopausal symptoms, surrogate endpoints, biomarkers, various morbidity outcomes, and mortality. Two investigators independently extracted data and assessed methodological quality of systematic reviews using the updated 16-item AMSTAR 2 instrument. Random-effects robust variance estimation was used to combine effect estimates, and 95% prediction intervals (PIs) were calculated whenever possible. We used the term MHT to encompass ET and EPT, and results are presented for MHT for each outcome, unless otherwise indicated. Sixty systematic reviews were included, involving 102 meta-analyses of RCTs and 38 of observational studies, with 102 unique outcomes. The overall quality of included systematic reviews was moderate to poor. In meta-analyses of RCTs, MHT was beneficial for vasomotor symptoms (frequency: 9 trials, 1,104 women, risk ratio [RR] 0.43, 95% CI 0.33 to 0.57, p < 0.001; severity: 7 trials, 503 women, RR 0.29, 95% CI 0.17 to 0.50, p = 0.002) and all fracture (30 trials, 43,188 women, RR 0.72, 95% CI 0.62 to 0.84, p = 0.002, 95% PI 0.58 to 0.87), as well as vaginal atrophy (intravaginal ET), sexual function, vertebral and nonvertebral fracture, diabetes mellitus, cardiovascular mortality (ET), and colorectal cancer (EPT), but harmful for stroke (17 trials, 37,272 women, RR 1.17, 95% CI 1.05 to 1.29, p = 0.027) and venous thromboembolism (23 trials, 42,292 women, RR 1.60, 95% CI 0.99 to 2.58, p = 0.052, 95% PI 1.03 to 2.99), as well as cardiovascular disease incidence and recurrence, cerebrovascular disease, nonfatal stroke, deep vein thrombosis, gallbladder disease requiring surgery, and lung cancer mortality (EPT). In meta-analyses of observational studies, MHT was associated with decreased risks of cataract, glioma, and esophageal, gastric, and colorectal cancer, but increased risks of pulmonary embolism, cholelithiasis, asthma, meningioma, and thyroid, breast, and ovarian cancer. ET and EPT had opposite effects for endometrial cancer, endometrial hyperplasia, and Alzheimer disease. The major limitations include the inability to address the varying effects of MHT by type, dose, formulation, duration of use, route of administration, and age of initiation and to take into account the quality of individual studies included in the systematic reviews. The study protocol is publicly available on PROSPERO (CRD42017083412).ConclusionsMHT has a complex balance of benefits and harms on multiple health outcomes. Some effects differ qualitatively between ET and EPT. The quality of available evidence is only moderate to poor.

In an umbrella review, Guo-Qiang Zhang and colleagues comprehensively summarize evidence on the benefits and harms of menopausal hormone therapy across diverse health outcomes.     

The Impact of Telehealthcare on the Quality and Safety of Care: A Systematic Overview

Background

Telehealthcare involves the use of information and communication technologies to deliver healthcare at a distance and to support patient self-management through remote monitoring and personalised feedback. It is timely to scrutinise the evidence regarding the benefits, risks and costs of telehealthcare.

Methods and Findings

Two reviewers searched for relevant systematic reviews published from January 1997 to November 2011 in: The Cochrane Library, MEDLINE, EMBASE, LILACS, IndMed and PakMed. Reviewers undertook independent quality assessment of studies using the Critical Appraisal Skills Programme (CASP) tool for systematic reviews. 1,782 review articles were identified, from which 80 systematic reviews were selected for inclusion. These covered a range of telehealthcare models involving both synchronous (live) and asynchronous (store-and-forward) interactions between provider and patients. Many studies showed no differences in outcomes between telehealthcare and usual care. Several reviews highlighted the large number of short-term (<12 months) feasibility studies with under 20 participants. Effects of telehealthcare on health service indicators were reported in several reviews, particularly reduced hospitalisations. The reported clinical effectiveness of telehealthcare interventions for patients with long-term conditions appeared to be greatest in those with more severe disease at high-risk of hospitalisation and death. The failure of many studies to adequately describe the intervention makes it difficult to disentangle the contributions of technological and human/organisational factors on the outcomes reported. Evidence on the cost-effectiveness of telehealthcare remains sparse. Patient safety considerations were absent from the evaluative telehealthcare literature.

Conclusions

Policymakers and planners need to be aware that investment in telehealthcare will not inevitably yield clinical or economic benefits. It is likely that the greatest gains will be achieved for patients at highest risk of serious outcomes. There is a need for longer-term studies in order to determine whether the benefits demonstrated in time limited trials are sustained.