Isometric Resistance Training to Manage Hypertension: Systematic Review and Meta-analysis.

PURPOSE OF REVIEW: Hypertension is the primary risk factor for cardiovascular disease and adequate blood pressure control is often elusive. The objective of this work was to conduct a meta-analysis of trial data of isometric resistance training (IRT) studies in people with hypertension, to establish if IRT produced an anti-hypertensive effect. A database search (PubMed, CINAHL, Cochrane Central Register of Controlled Trials, and MEDLINE) identified randomised controlled and crossover trials of IRT versus a sedentary or sham control group in adults with hypertension. RECENT FINDINGS: We included 12 studies (14 intervention groups) in the meta-analyses, with an aggregate of 415 participants. IRT reduced systolic blood pressure (SBP), mean difference (MD) - 7.47 mmHg (95%CI - 10.10, - 4.84), P < 0.01; diastolic blood pressure (DBP) MD - 3.17 mmHg (95%CI - 5.29, - 1.04), P < 0.01; and mean arterial blood pressure (MAP) MD - 7.19 mmHg (95%CI - 9.06, - 5.32), P < 0.0001. Office pulse pressure and resting heart rate was not significantly reduced, neither were 24-h or day-time ambulatory blood pressures (SBP, DBP). Night-time blood pressures, however, were significantly reduced with SBP MD - 4.28 mmHg (95%CI - 7.88, - 0.67), P = 0.02, and DBP MD - 2.22 mmHg (95%CI - 3.55, - 0.88), P < 0.01. IRT does lower SBP, DBP and MAP office and night-time ambulatory SBP and DBP, but not 24-h mean ambulatory blood pressures in people with hypertension.

Multiethnic PDX models predict a possible immune signature associated with TNBC of African ancestry.

PURPOSE: Triple-negative breast cancer (TNBC) is an aggressive subtype most prevalent among women of Western Sub-Saharan African ancestry. It accounts for 15-25% of African American (AA) breast cancers (BC) and up to 80% of Ghanaian breast cancers, thus contributing to outcome disparities in BC for black women. The aggressive biology of TNBC has been shown to be regulated partially by breast cancer stem cells (BCSC) which mediate tumor recurrence and metastasis and are more abundant in African breast tumors. METHODS: We studied the biological differences between TNBC in women with African ancestry and those of Caucasian women by comparing the gene expression of the BCSC. From low-passage patient derived xenografts (PDX) from Ghanaian (GH), AA, and Caucasian American (CA) TNBCs, we sorted for and sequenced the stem cell populations and analyzed for differential gene enrichment. RESULTS: In our cohort of TNBC tumors, we observed that the ALDH expressing stem cells display distinct ethnic specific gene expression patterns, with the largest difference existing between the GH and AA ALDH+ cells. Furthermore, the tumors from the women of African ancestry [GH/AA] had ALDH stem cell (SC) enrichment for expression of immune related genes and processes. Among the significantly upregulated genes were CD274 (PD-L1), CXCR9, CXCR10 and IFI27, which could serve as potential drug targets. CONCLUSIONS: Further exploration of the role of immune regulated genes and biological processes in BCSC may offer insight into developing novel approaches to treating TNBC to help ameliorate survival disparities in women with African ancestry.

Potent leads based on CA-19L, an anti-HIV active HIV-1 capsid fragment.

Several anti-HIV-1 peptides have previously been found among overlapping fragment peptide libraries that contain an octa-arginyl moiety and cover the whole sequence of an HIV-1 capsid (CA) protein. Several derivatives based on a potent CA fragment peptide CA-19L have been synthesized. CA-19L overlaps with the Helix 9 region of the CA protein, which could be important for oligomerization of the CA proteins. Derivatives of CA-19L in which several amino acid residues were added to the N- and C-termini according to the natural CA sequence, were synthesized and their anti-HIV activity was evaluated. Some potent compounds were found, and these potential new anti-HIV agents are expected to be useful as new tools for elucidation of CA functions.

Three monthly doses of 60 mg/kg praziquantel for Schistosoma haematobium infection is a safe and effective treatment regimen.

BACKGROUND: Praziquantel (PZQ) is the standard treatment for Schistosomiasis in sub-Saharan Africa. However, there is evidence suggesting praziquantel treatment failure in Schistosome infections with associated potential renal impairment. The objective of this study was to determine the effect of three monthly doses of 60 mg/kg/day PZQ on schistosome egg count, liver and renal function during the treatment of urinary schistosomiasis in Ghana. METHODS: A nested case-control study was designed from a cohort screened for schistosomiasis; 28 schistosomiasis positive cases by microscopy matched with 53 healthy controls by age and gender. The study population was urban dwellers from the Asokwa sub-metropolitan area, Kumasi in Ghana. Participants were within the age range of 6 to 30 years. We assessed Schistosoma haematobium egg counts in urine and its associated impact on liver and renal function at baseline, treatment and post-treatment phases using serum. RESULTS: Of the 28 cases and 53 controls, 78.6% and 81.1% were males respectively. Globulin levels before treatment was higher in cases [36.7 (32.8, 40.1) vrs 30.5 (22.4, 33.8), p = 0.005] at pre-treatment but not at post-treatment [35.8 (31.2, 39.1) vrs 37.4 (29.7, 43.0), p = 0.767]. Estimated cure rate was 42.9, 46.4 and 96.4% after first, second and third dose respectively. Schistosome egg counts dropped significantly (p = 0.001) from before second dose to post-treatment. Similarly, levels of alanine aminotransferase (p = 0.001), aspartate aminotransferase (p = 0.028) and gamma glutamyl transferase (p = 0.001) significantly declined towards post-treatment. Estimated glomerular filtration rate significantly improved from before second dose to post-treatment using both the Chronic Kidney Disease Epidemiology Program (p = 0.001) and 4-variable Modification of Diet in Renal Disease (p = 0.002) equations. CONCLUSION: Treatment of urinary Schistosoma hematobium infections with a repeated high monthly dose of 60 mg/kg of praziquantel for 3 months is safe and effective.

Exploratory studies on CA-15L, an anti-HIV active HIV-1 capsid fragment.

Utilizing overlapping fragment peptide libraries covering the whole sequence of an HIV-1 capsid (CA) protein with the addition of an octa-arginyl moiety, we had previously found several peptides with anti-HIV-1 activity. Herein, among these potent CA fragment peptides, CA-15L was examined because this peptide sequence overlaps with Helix 7, a helix region of the CA protein, which may be important for oligomerization of the CA proteins. A CA-15L surrogate with hydrophilic residues, and its derivatives, in which amino acid sequences are shifted toward the C-terminus by one or more residues, were synthesized and their anti-HIV activity was evaluated. In addition, its derivatives with substitution for the Ser149 residue were synthesized and their anti-HIV activity was evaluated because Ser149 might be phosphorylated in the step of degradation of CA protein oligomers. Several active compounds were found and might become new anti-HIV agents and new tools for elucidation of CA functions.

Paenidigyamycin A, Potent Antiparasitic Imidazole Alkaloid from the Ghanaian Paenibacillus sp. DE2SH.

A new alkaloid paenidigyamycin A (1) was obtained from the novel Ghanaian Paenibacillus sp. isolated from the mangrove rhizosphere soils of the Pterocarpus santalinoides tree growing in the wetlands of the Digya National Park, Ghana. Compound 1 was isolated on HPLC at tR = 37.0 min and its structure determined by MS, 1D, and 2D-NMR data. When tested against L. major, 1 (IC50 0.75 µM) was just as effective as amphotericin B (IC50 0.31 µM). Against L. donovani, 1 (IC50 7.02 µM) was twenty-two times less active than amphotericin B (IC50 0.32 µM), reinforcing the unique effectiveness of 1 against L. major. For T. brucei brucei, 1 (IC50 0.78 µM) was ten times more active than the laboratory standard Coptis japonica (IC50 8.20 µM). The IC50 of 9.08 µM for 1 against P. falciparum 3d7 compared to artesunate (IC50 36 nM) was not strong, but this result suggests the possibility of using the paenidigyamycin scaffold for the development of potent antimalarial drugs. Against cercariae, 1 showed high anticercaricidal activity compared to artesunate. The minimal lethal concentration (MLC) and minimal effective concentration (MEC) of the compound were 25 and 6.25 µM, respectively, while artesunate was needed in higher quantities to produce such results. However, 1 (IC50 > 100 µM) was not active against T. mobilensis.

Antitrypanosomal Activities and Mechanisms of Action of Novel Tetracyclic Iridoids from Morinda lucida Benth.

Trypanosoma brucei parasites are kinetoplastid protozoa that devastate the health and economic well-being of millions of people in Africa through the disease human African trypanosomiasis (HAT). New chemotherapy has been eagerly awaited due to severe side effects and the drug resistance issues plaguing current drugs. Recently, there has been an emphasis on the use of medicinal plants worldwide. Morinda lucida Benth. is a popular medicinal plant widely distributed in Africa, and several research groups have reported on the antiprotozoal activities of this plant. In this study, we identified three novel tetracyclic iridoids, molucidin, ML-2-3, and ML-F52, from the CHCl3 fraction of M. lucida leaves, which possess activity against the GUTat 3.1 strain of T. brucei brucei The 50% inhibitory concentrations (IC50) of molucidin, ML-2-3, and ML-F52 were 1.27 µM, 3.75 µM, and 0.43 µM, respectively. ML-2-3 and ML-F52 suppressed the expression of paraflagellum rod protein subunit 2, PFR-2, and caused cell cycle alteration, which preceded apoptosis induction in the bloodstream form of Trypanosoma parasites. Novel tetracyclic iridoids may be promising lead compounds for the development of new chemotherapies for African trypanosomal infections in humans and animals.

Assessment of prison life of persons with disability in Ghana.

BACKGROUND: Persons with Disabilities (PWDs) are a unique group that are often overlooked in many developing countries due to systemic weaknesses, lack of political commitment and inadequate support from government and non-governmental agencies. The population of these individuals is however steadily on the increase and currently corresponds to 15 % of the world population. Although much data exist on lifestyle and conditions of prisoners with disabilities in the western world, scanty information is available in Africa. In Ghana, there is insufficient data on the occurrence and social characteristics of prisoners with disabilities. The purpose of this current study was therefore to identify the occurrence, types and causes of disabilities among prisoners serving sentences in Ghanaian prisons. METHODS: This study was a descriptive cross-sectional survey conducted in the Male and Female Regional Prisons in Kumasi, Sunyani and the Nsawam Medium Security Prison, from November to December 2011. PWDs were selected by prisons officers and interviewed using structured questionnaires on variables such as socio-demographic characteristics, causes of disabilities and accessibility to recreational facilities. Ethical approval was obtained from the security services and the Committee of Human Research Publications and Ethics (CHRPE) of the School of Medical Sciences, Kwame Nkrumah University of Science and Technology (KNUST). RESULTS: We screened 6114 records of prisoners of which 1852 (30.3 %) were from the Kumasi Central Prisons, 3483 (57 %) from the Nsawam Medium Security and 779 (12.8 %) from the Sunyani Central Prisons. A total of 99 PWDs were identified with the commonest disability being physical, followed by visual, hearing, speech, mental and albinism. Most of the disabilities were caused by trauma (68.8 %) followed by infection (16.7 %), and drug related mental disabilities (6.3 %). Fifty (50.5 %) out of the 99 PWDs were not provided with assistive devices although they admitted the need for such. CONCLUSION: The present study has demonstrated the occurrence and conditions of PWDs in Ghanaian prisons. Major stakeholders including government agencies and other organisations could develop policies that would improve the conditions and livelihood of prisoners with disabilities in Ghana.

Procyanidin trimer C1 derived from Theobroma cacao reactivates latent human immunodeficiency virus type 1 provirus.

Despite remarkable advances in combination antiretroviral therapy (cART), human immunodeficiency virus type 1 (HIV-1) infection remains incurable due to the incomplete elimination of the replication-competent virus, which persists in latent reservoirs. Strategies for targeting HIV reservoirs for eradication that involves reactivation of latent proviruses while protecting uninfected cells by cART are urgently needed for cure of HIV infection. We screened medicinal plant extracts for compounds that could reactivate the latent HIV-1 provirus and identified a procyanidin trimer C1 derived from Theobroma cacao as a potent activator of the provirus in human T cells latently infected with HIV-1. This reactivation largely depends on the NF-κB and MAPK signaling pathways because either overexpression of a super-repressor form of IκBα or pretreatment with a MEK inhibitor U0126 diminished provirus reactivation by C1. A pan-PKC inhibitor significantly blocked the phorbol ester-induced but not the C1-induced HIV-1 reactivation. Although C1-induced viral gene expression persisted for as long as 48 h post-stimulation, NF-κB-dependent transcription peaked at 12 h post-stimulation and then quickly declined, suggesting Tat-mediated self-sustainment of HIV-1 expression. These results suggest that procyanidin C1 trimer is a potential compound for reactivation of latent HIV-1 reservoirs.

New anti-trypanosomal active tetracyclic iridoid isolated from Morinda lucida Benth.

Human African trypanosomiasis (HAT), commonly known as sleeping sickness has remained a serious health problem in many African countries with thousands of new infected cases annually. Chemotherapy, which is the main form of control against HAT has been characterized lately by the viewpoints of toxicity and drug resistance issues. Recently, there have been a lot of emphases on the use of medicinal plants world-wide. Morinda lucida Benth. is one of the most popular medicinal plants widely distributed in Africa and several groups have reported on its anti-protozoa activities. In this study, we have isolated one novel tetracyclic iridoid, named as molucidin, from the CHCl3 fraction of the M. lucida leaves by bioassay-guided fractionation and purification. Molucidin was structurally elucidated by (1)H and (13)C NMR including HMQC, HMBC, H-H COSY and NOESY resulting in tetracyclic iridoid skeleton, and its absolute configuration was determined. We have further demonstrated that molucidin presented a strong anti-trypanosomal activity, indicating an IC50 value of 1.27 µM. The cytotoxicity study using human normal and cancer cell lines indicated that molucidin exhibited selectivity index (SI) against two normal fibroblasts greater than 4.73. Furthermore, structure-activity relationship (SAR) study was undertaken with molucidin and oregonin, which is identical to anti-trypanosomal active components of Alnus japonica. Overlapping analysis of the lowest energy conformation of molucidin with oregonin suggested a certain similarities of aromatic rings of both oregonin and molucidin. These results contribute to the future drug design studies for HAT.

Functional significance of single nucleotide polymorphisms in the lactase gene in diverse US patients and evidence for a novel lactase persistence allele at -13909 in those of European ancestry.

OBJECTIVES: Recent data from mainly homogeneous European and African populations implicate a 140-bp region 5' to the transcriptional start site of LCT (the lactase gene) as a regulatory site for lactase persistence and nonpersistence. Because there are no studies of US nonhomogeneous populations, we performed genotype/phenotype analysis of the -13910 and -22018 LCT single nucleotide polymorphisms (SNPs) in New England children, mostly of European ancestry. METHODS: Duodenal biopsies were processed for disaccharidase activities, RNA quantification by reverse transcription polymerase chain reaction (RT-PCR), allelic expression ratios by PCR, and genotyping and SNP analysis. Results were compared with clinical information. RESULTS: Lactase activity and mRNA levels, and sucrase-to-lactase ratios of enzyme activity and mRNA, showed robust correlations with genotype. None of the other LCT SNPs showed as strong a correlation with enzyme or mRNA levels as did -13910. Data were consistent, with the -13910 being the causal sequence variant instead of -22018. Four individuals heterozygous for -13910T/C had allelic expression patterns similar to individuals with -13910C/C genotypes; of these, 2 showed equal LCT expression from the 2 alleles and a novel variant (-13909C>A) associated with lactase persistence. CONCLUSIONS: The identification of -13910C/C genotype is likely to predict lactase nonpersistence, consistent with prior published studies. A -13910T/T genotype will frequently, but not perfectly, predict lactase persistence in this mixed European-ancestry population; a -13910T/C genotype will not predict the phenotype. A long, rare haplotype in 2 individuals with -13910T/C genotype but equal allele-specific expression contains a novel lactase persistence allele present at -13909.

Assessments of the transmission of Onchocerca volvulus by Simulium sanctipauli in the Upper Denkyira District, Ghana, and the intermittent disappearance of the vector.

Following studies on the transmission of Onchocerca volvulus (Leuckart) by Simulium sanctipauli Vajime & Dunbar (Diptera, Simuliidae) in Upper Denkyira District in Ghana in 2001 and 2002 (Kutin et al., Med Vet Ent 18:167-173, 2004), further assessments were carried out in 2006 and 2013/2014 to determine whether transmission parameters had changed since community-directed ivermectin treatment (CDTI) began in 1999. There were no marked changes of the transmission intensities in 2006. Only slight, but non-significant, reductions were observed in infection rates of parous flies with larval stages (L1-L3) of O. volvulus from 44.1 % (of 1672 parous flies) in 2001/2002 to 42.1 % (506) in 2006 and from 6.5 to 5.9 % of flies carrying infective larvae in their heads. This suggested that there was an ongoing transmission in the area and the parasite reservoir in the human population was still high. Unexpectedly, further assessments conducted in October 2013 and March and October 2014 revealed that the vector S. sanctipauli had apparently disappeared and transmission had ceased, probably as a result of intensified gold mining activities along the rivers Ofin and Pra. The water of both rivers was extremely turbid, heavily loaded with suspended solids, probably preventing the development of blackfly larvae. Some breeding and biting of Simulium yahense Vajime & Dunbar was observed in a small tributary of the Pra, the Okumayemfuo, which is not affected by gold mining. However, the infection rate of flies was low, only 3.7 % of 163 parous flies were infected with first stage (L1) larvae of O. volvulus.

Mouse telomerase reverse transcriptase (mTert) expression marks slowly cycling intestinal stem cells.

The intestinal epithelium is maintained by a population of rapidly cycling (Lgr5(+)) intestinal stem cells (ISCs). It has been postulated, however, that slowly cycling ISCs must also be present in the intestine to protect the genome from accumulating deleterious mutations and to allow for a response to tissue injury. Here, we identify a subpopulation of slowly cycling ISCs marked by mouse telomerase reverse transcriptase (mTert) expression that can give rise to Lgr5(+) cells. mTert-expressing cells distribute in a pattern along the crypt-villus axis similar to long-term label-retaining cells (LRCs) and are resistant to tissue injury. Lineage-tracing studies demonstrate that mTert(+) cells give rise to all differentiated intestinal cell types, persist long term, and contribute to the regenerative response following injury. Consistent with other highly regenerative tissues, our results demonstrate that a slowly cycling stem cell population exists within the intestine.

The evolution of media reportage on GMOs in Ghana following approval of first GM crop.

Ghana's parliament in 2011 passed the Biosafety Act to allow for the application of genetically modified organism (GMO) technology in the country's agriculture. In a vibrant democracy, there have been extensive media discussions on whether GM crops will benefit or harm citizens. In June 2022, the state GMO regulator, the National Biosafety Authority (NBA), approved the country's first GM crop (Bt cowpea) for environmental release, declaring the crop does not present an altered environmental risk or a food/feed safety concern. This study identified 3 of the country's most vibrant digital news outlets and did a content analysis of all GMO stories reported 18 months pre- and post-approval to assess whether the approval changed the focus of GMO issues the media reports on. 91 articles were identified. The results show media reports on the likely impact of GMOs on the country's food security shot up after the approval. However, media reports on the possible health, sociocultural, and environmental impact of GMOs declined. We observe the media and the public appear interested in deliberations on how the technology could address or worsen food insecurity and urge agricultural biotechnology actors in Ghana to focus on that in their sensitization activities.

An age-period-cohort analysis of hysterectomy incidence trends in Germany from 2005 to 2019.

Recent studies show declining trends in hysterectomy rates in several countries. The objective of this study was to analyse hysterectomy time trends in Germany over a fifteen-year period using an age-period-cohort approach. Using an ecological study design, inpatient data from Diagnoses Related Group on hysterectomies by subtype performed in Germany from 2005 to 2019 were retrieved from the German Statistical Office. Descriptive time trends and age-period-cohort analyses were then performed. A total of 1,974,836 hysterectomies were performed over the study period. The absolute number of hysterectomies reduced progressively from 155,680 (365 procedures/100,000 women) in 2005 to 101,046 (257 procedures/100,000 women) in 2019. Total and radical hysterectomy decreased by 49.7% and 44.2%, respectively, whilst subtotal hysterectomy increased five-fold. The age-period-cohort analysis revealed highest hysterectomy rates in women aged 45-49 for total and subtotal hysterectomy with 608.63 procedures/100,000 women (95% CI 565.70, 654.82) and 151.30 procedures/100,000 women (95% CI 138.38, 165.44) respectively. Radical hysterectomy peaked later at 65-69 years with a rate of 40.63 procedures/100,000 women (95% CI 38.84, 42.52). The risk of undergoing total or radical hysterectomy decreased over the study period but increased for subtotal hysterectomy. Although, overall hysterectomy rates have declined, subtotal hysterectomy rates have increased; reflecting changes in clinical practice largely influenced by the availability of uterus-sparing options, evolving guidelines and introduction of newer surgical approaches.

Effect of exercise training on the renin-angiotensin-aldosterone system: a meta-analysis.

Blood pressure (BP) management reduces the risk of cardiovascular disease (CVD). The renin-angiotensin-aldosterone system (RAAS) plays an important role in regulating and maintaining blood volume and pressure. This analysis aimed to investigate the effect of exercise training on plasma renin, angiotensin-II and aldosterone, epinephrine, norepinephrine, urinary sodium and potassium, BP and heart rate (HR). We systematically searched PubMed, Web of Science, and the Cochrane Library of Controlled Trials until 30 November 2022. The search strategy included RAAS key words in combination with exercise training terms and medical subject headings. Manual searching of reference lists from systematic reviews and eligible studies completed the search. A random effects meta-analysis model was used. Eighteen trials with a total of 803 participants were included. After exercise training, plasma angiotensin-II (SMD -0.71; 95% CI -1.24, -0.19; p = 0.008; n = 9 trials), aldosterone (SMD -0.37; 95% CI -0.65, -0.09; p = 0.009; n = 8 trials) and norepinephrine (SMD -0.82; 95% CI -1.18, -0.46; p < 0.001; n = 8 trials) were reduced. However, plasma renin activity, epinephrine, and 24-h urinary sodium and potassium excretion remained unchanged with exercise training. Systolic BP was reduced (MD -6.2 mmHg; 95% CI -9.9, -2.6; p = 0.001) as was diastolic BP (MD -4.5 mmHg; 95% CI -6.9, -2.1; p < 0.001) but not HR (MD -3.0 bpm; 95% CI -6.0, 0.4; p = 0.053). Exercise training may reduce some aspects of RAAS and sympathetic nervous system activity, and this explains some of the anti-hypertensive response.

An evidence-based guide to the efficacy and safety of isometric resistance training in hypertension and clinical implications.

More than 30 randomized controlled trials, supported by individual patient-level and group-level meta-analyses and a Delphi analysis of expert opinion, unequivocally show isometric resistance training (IRT) elicits antihypertensive benefits in healthy people and those with chronic illness. We aim to provide efficacy and safety evidence, and a guide for IRT prescription and delivery. Recommendations are made for the use of IRT in specific patient populations and appropriate methods for IRT delivery. Published data suggest IRT consistently elicits mean blood pressure reductions of 7.4/3.3 mmHg systolic blood pressure/diastolic blood pressure, equivalent to antihypertensive medication monotherapy. Blood pressure reductions of this size are associated with an approximate 13% to 22% reduction in major cardiovascular events. Moreover, IRT is safe in a range of patient populations. We suggest that IRT has the greatest potential benefit when used as an antihypertensive therapy in individuals unwilling and/or unable to complete aerobic exercise, or who have had limited adherence or success with it; individuals with resistant or uncontrolled hypertension, already taking at least two pharmacological antihypertensive agents; and healthy or clinical populations, as an adjunct to aerobic exercise and dietary intervention in those who have not yet attained control of their hypertension. IRT is efficacious and produces clinically meaningful blood pressure reductions (systolic blood pressure, 7 mmHg; diastolic blood pressure, 3 mmHg). IRT is safe and typical program delivery requires only about 17 min weekly. IRT should be used as an adjunct to other exercise modalities, in people unable to complete other types of exercise, or in resistant hypertension.

Dimerized fusion inhibitor peptides targeting the HR1-HR2 interaction of SARS-CoV-2.

Membrane fusion is a critical and indispensable step in the replication cycles of viruses such as SARS-CoV-2 and human immunodeficiency virus type-1 (HIV-1). In this step, a trimer of the heptad repeat 1 (HR1) region interacts with the three HR2 regions and forms a 6-helix bundle (6-HB) structure to proceed with membrane fusion of the virus envelope and host cells. Recently, several researchers have developed potent peptidic SARS-CoV-2 fusion inhibitors based on the HR2 sequence and including some modifications. We have developed highly potent HIV-1 fusion inhibitors by dimerization of its HR2 peptides. Here, we report the development of dimerized HR2 peptides of SARS-CoV-2, which showed significantly higher antiviral activity than the corresponding monomers, suggesting that the dimerization strategy can facilitate the design of potent inhibitors of SARS-CoV-2.

GATA factors regulate proliferation, differentiation, and gene expression in small intestine of mature mice.

BACKGROUND & AIMS: GATA transcription factors regulate proliferation, differentiation, and gene expression in multiple organs. GATA4 is expressed in the proximal 85% of the small intestine and regulates the jejunal-ileal gradient in absorptive enterocyte gene expression. GATA6 is co-expressed with GATA4 but also is expressed in the ileum; its function in the mature small intestine is unknown. METHODS: We investigated the function of GATA6 in small intestine using adult mice with conditional, inducible deletion of Gata6, or Gata6 and Gata4, specifically in the intestine. RESULTS: In ileum, deletion of Gata6 caused a decrease in crypt cell proliferation and numbers of enteroendocrine and Paneth cells, an increase in numbers of goblet-like cells in crypts, and altered expression of genes specific to absorptive enterocytes. In contrast to ileum, deletion of Gata6 caused an increase in numbers of Paneth cells in jejunum and ileum. Deletion of Gata6 and Gata4 resulted in a jejunal and duodenal phenotype that was nearly identical to that in the ileum after deletion of Gata6 alone, revealing common functions for GATA6 and GATA4. CONCLUSIONS: GATA transcription factors are required for crypt cell proliferation, secretory cell differentiation, and absorptive enterocyte gene expression in the small intestinal epithelium.

Safety, efficacy and delivery of isometric resistance training as an adjunct therapy for blood pressure control: a modified Delphi study.

Uncontrolled hypertension remains the major risk factor for cardiovascular disease. Isometric resistance training (IRT) has been shown to be a useful nonpharmacological therapy for reducing blood pressure (BP); however, some exercise physiologists and other health professionals are uncertain of the efficacy and safety of IRT. Experts' consensus was sought in light of the current variability of IRT use as an adjunct treatment for hypertension. An expert consensus-building analysis (Delphi study) was conducted on items relevant to the safety, efficacy and delivery of IRT. The study consisted of 3 phases: (1) identification of items and expert participants for inclusion; (2) a two-round modified Delphi exercise involving expert panelists to build consensus; and (3) a study team consensus meeting for a final item review. A list of 50 items was generated, and 42 international experts were invited to join the Delphi panel. Thirteen and 10 experts completed Delphi Rounds 1 and 2, respectively, reaching consensus on 26 items in Round 1 and 10 items in Round 2. The study team consensus meeting conducted a final item review and considered the remaining 14 items for the content list. A final list of 43 items regarding IRT reached expert consensus: 7/10 items on safety, 11/11 items on efficacy, 10/12 items on programming, 8/10 items on delivery, and 7/7 on the mechanism of action. This study highlights that while experts reached a consensus that IRT is efficacious as an antihypertensive therapy, some still have safety concerns, and there is also ongoing conjecture regarding optimal delivery.