The effectiveness and safety of isometric resistance training for adults with high blood pressure: a systematic review and meta-analysis

High blood pressure (BP) is a global health challenge. Isometric resistance training (IRT) has demonstrated antihypertensive effects, but safety data are not available, thereby limiting its recommendation for clinical use. We conducted a systematic review of randomized controlled trials comparing IRT to controls in adults with elevated BP (systolic ≥130 mmHg/diastolic ≥85 mmHg). This review provides an update to office BP estimations and is the first to investigate 24-h ambulatory BP, central BP, and safety. Data were analyzed using a random-effects meta-analysis. We assessed the risk of bias with the Cochrane risk of bias tool and the quality of evidence with GRADE. Twenty-four trials were included (n = 1143; age = 56 ± 9 years, 56% female). IRT resulted in clinically meaningful reductions in office systolic (–6.97 mmHg, 95% CI –8.77 to –5.18, p < 0.0001) and office diastolic BP (–3.86 mmHg, 95% CI –5.31 to –2.41, p < 0.0001). Novel findings included reductions in central systolic (–7.48 mmHg, 95% CI –14.89 to –0.07, p = 0.035), central diastolic (–3.75 mmHg, 95% CI –6.38 to –1.12, p = 0.005), and 24-h diastolic (–2.39 mmHg, 95% CI –4.28 to –0.40, p = 0.02) but not 24-h systolic BP (–2.77 mmHg, 95% CI –6.80 to 1.25, p = 0.18). These results are very low/low certainty with high heterogeneity. There was no significant increase in the risk of IRT, risk ratio (1.12, 95% CI 0.47 to 2.68, p = 0.8), or the risk difference (1.02, 95% CI 1.00 to 1.03, p = 0.13). This means that there is one adverse event per 38,444 bouts of IRT. IRT appears safe and may cause clinically relevant reductions in BP (office, central BP, and 24-h diastolic). High-quality trials are required to improve confidence in these findings. PROSPERO (CRD42020201888); OSF (https://doi.org/10.17605/OSF.IO/H58BZ)

Jurassic shift from abiotic to biotic control on marine ecological success

Environmental change and biotic interactions both govern the evolution of the biosphere, but the relative importance of these drivers over geological time remains largely unknown. Previous work suggests that, unlike environmental parameters, diversity dynamics differ profoundly between the Palaeozoic and post-Palaeozoic eras. Here we use the fossil record to test the hypothesis that the influence of ocean chemistry and climate on the ecological success of marine calcifiers decreased throughout the Phanerozoic eon. Marine calcifiers build skeletons of calcite or aragonite, and the precipitation of these calcium carbonate polymorphs is governed by the magnesium-to-calcium ratio and temperature in abiotic systems. We developed an environmental forcing model based on secular changes of ocean chemistry and temperature and assessed how well the model predicts the proliferation of skeletal taxa with respect to calcium carbonate polymorphs. Abiotic forcing governs the ecological success of aragonitic calcifiers from the Ordovician to the Middle Jurassic, but not thereafter. This regime shift coincides with the proliferation of calcareous plankton in the mid-Mesozoic. The deposition of biomineralizing plankton on the ocean floor buffers CO2 excursions and stabilizes Earth’s biochemical cycle, and thus mitigates the evolutionary impact of environmental change on the marine biota

Beyond the Refugee Crisis how the UK news media represent asylum seekers across national boundaries

Migration is one of the most pressing, divisive issues in global politics today, and media play a crucial role in how communities understand and respond. This study examines how UK newspapers (n = 974) and popular news websites (n = 1044) reported on asylum seekers throughout 2017. It contributes to previous literature in two important ways. First, by examining the ‘new normal’ of daily news coverage in the wake of the 2015 ‘refugee crisis’ in Europe. Second, by looking at how asylum seekers from different regions are represented. The content analysis finds significant variations in how asylum seekers are reported, including terminology use and topics they are associated with. The paper also identifies important commonalities in how all asylum seekers are represented - most notably, the dominance of political elites as sources across all media content. It argues that Entman’s ‘cascade network model’ can help to explain this, with elites in one country able to influence transnational reports

Effects of Gabra2 Point Mutations on Alcohol Intake: Increased Binge-Like and Blunted Chronic Drinking by Mice

BACKGROUND: Alcohol use disorders are associated with single-nucleotide polymorphisms in GABRA2, the gene encoding the GABAA receptor α2-subunit in humans. Deficient GABAergic functioning is linked to impulse control disorders, intermittent explosive disorder, and to drug abuse and dependence, yet it remains unclear whether α2-containing GABAA receptor sensitivity to endogenous ligands is involved in excessive alcohol drinking. METHODS: Male wild-type (Wt) C57BL/6J and point-mutated mice rendered insensitive to GABAergic modulation by benzodiazepines (BZD; H101R), allopregnanolone (ALLO) or tetrahydrodeoxycorticosterone (THDOC; Q241M), or high concentrations of ethanol (EtOH) (S270H/L277A) at α2-containing GABAA receptors were assessed for their binge-like, moderate, or escalated chronic drinking using drinking in the dark, continuous access (CA) and intermittent access (IA) to alcohol protocols, respectively. Social approach by mutant and Wt mice in forced alcohol abstinence was compared to approach by EtOH-naïve controls. Social deficits in forced abstinence were treated with allopregnanolone (0, 3.0, 10.0 mg/kg, intraperitoneal [i.p.]) or midazolam (0, 0.56, 1.0 mg/kg, i.p.). RESULTS: Mice with BZD-insensitive α2-containing GABAA receptors (H101R) escalated their binge-like drinking. Mutants harboring the Q241M point substitution in Gabra2 showed blunted chronic intake in the CA and IA protocols. S270H/L277A mutants consumed excessive amounts of alcohol but, unlike wild-types, they did not show forced abstinence-induced social deficits. CONCLUSIONS: These findings suggest a role for: (i) H101 in species-typical binge-like drinking, (ii) Q241 in escalated chronic drinking, and (iii) S270 and/or L277 in the development of forced abstinence-associated social deficits. Clinical findings report reduced BZD-binding sites in the cortex of dependent patients; the present findings suggest a specific role for BZD-sensitive α2-containing receptors. In addition, amino acid residue 241 in Gabra2 is necessary for positive modulation and activation of GABAA receptors by ALLO and THDOC; we postulate that neurosteroid action on α2-containing receptor may be necessary for escalated chronic EtOH intake

Lymphocyte subsets and the role of Th1/Th2 balance in stressed chronic pain patients

Background: The complex regional pain syndrome (CRPS) and fibromyalgia (FM) are chronic pain syndromes occurring in highly stressed individuals. Despite the known connection between the nervous system and immune cells, information on distribution of lymphocyte subsets under stress and pain conditions is limited. Methods: We performed a comparative study in 15 patients with CRPS type I, 22 patients with FM and 37 age- and sex-matched healthy controls and investigated the influence of pain and stress on lymphocyte number, subpopulations and the Th1/Th2 cytokine ratio in T lymphocytes. Results: Lymphocyte numbers did not differ between groups. Quantitative analyses of lymphocyte subpopulations showed a significant reduction of cytotoxic CD8+ lymphocytes in both CRPS (p < 0.01) and FM (p < 0.05) patients as compared with healthy controls. Additionally, CRPS patients were characterized by a lower percentage of IL-2-producing T cell subpopulations reflecting a diminished Th1 response in contrast to no changes in the Th2 cytokine profile. Conclusions: Future studies are warranted to answer whether such immunological changes play a pathogenetic role in CRPS and FM or merely reflect the consequences of a pain-induced neurohumoral stress response, and whether they contribute to immunosuppression in stressed chronic pain patients. Copyright (c) 2008 S. Karger AG, Basel

The Second Transmembrane Domain of P2X7 Contributes to Dilated Pore Formation

Activation of the purinergic receptor P2X7 leads to the cellular permeability of low molecular weight cations. To determine which domains of P2X7 are necessary for this permeability, we exchanged either the C-terminus or portions of the second transmembrane domain (TM2) with those in P2X1 or P2X4. Replacement of the C-terminus of P2X7 with either P2X1 or P2X4 prevented surface expression of the chimeric receptor. Similarly, chimeric P2X7 containing TM2 from P2X1 or P2X4 had reduced surface expression and no permeability to cationic dyes. Exchanging the N-terminal 10 residues or C-terminal 14 residues of the P2X7 TM2 with the corresponding region of P2X1 TM2 partially restored surface expression and limited pore permeability. To further probe TM2 structure, we replaced single residues in P2X7 TM2 with those in P2X1 or P2X4. We identified multiple substitutions that drastically changed pore permeability without altering surface expression. Three substitutions (Q332P, Y336T, and Y343L) individually reduced pore formation as indicated by decreased dye uptake and also reduced membrane blebbing in response to ATP exposure. Three others substitutions, V335T, S342G, and S342A each enhanced dye uptake, membrane blebbing and cell death. Our results demonstrate a critical role for the TM2 domain of P2X7 in receptor function, and provide a structural basis for differences between purinergic receptors. © 2013 Sun et al

Colour assessment outcomes – a new approach to grading the severity of color vision loss

INTRODUCTION: Recent studies have shown that a significant percentage of subjects with anomalous, congenital trichromacy can perform the suprathreshold, colour-related tasks encountered in many occupations with the same accuracy as normal trichromats. In the absence of detailed, occupation-specific studies, an alternative approach is to make use of new findings and the statistical outcomes of past practices that have been considered safe to produce graded, justifiable categories of colour vision that can be enforced. METHODS: We analyzed traditional color assessment outcomes and measured severity of colour vision loss using the CAD test in 1363 subjects (336 normals, 705 deutan, 319 protan and 3 tritan). The severity of colour vision loss was measured in each subject and statistical, pass / fail outcomes established for each of the most commonly used, conventional colour assessment tests and protocols. RESULTS: The correlation between the number of Ishihara (IH) test plates subjects fail and the severity of RG colour vision loss was very poor. The 38 plates IH test has high sensitivity when no errors are allowed (i.e., only 0.71% deutans and 0.63% protans pass). Protocols based on zero errors are uncommon since 18.15% of normal trichromats fail. The most common protocols employ either the 24 or the 14 plates editions with two or less errors. These protocols pass almost all normal trichromats, but the deutans and some protans that also pass (when two or less errors are allowed) can be severely deficient. This is simply because the most challenging plates have not been included in the 24 and 14 plates editions. As a result, normals no longer fail, but the deutans and protans that pass have more severe loss of colour vision since they fail less challenging plates. The severity of colour vision loss was measured in each subject and statistical, pass / fail outcomes established for each of the most commonly used, conventional colour assessment tests and protocols. DISCUSSION: Historical evidence and new findings that relate severity of loss to the effective use of colour signals in a number of tasks provide the basis for a new colour grading system based on six categories. A single colour assessment test is needed to establish the applicant’s Colour Vision category which can range from ‘supernormal’ (CV0), for the most stringent, colour-demanding tasks, to ‘severe colour deficiency’, when red / green colour vision is either absent or extremely weak (CV5)