The Impact of the Older Person's Grant Expansion on Hypertension Among Older Men in Rural South Africa: Findings From the HAALSI Cohort.

Background and Objectives: Hypertension is a major modifiable contributor to disease burden in sub-Saharan Africa. We exploited an expansion to age eligibility for men in South Africa's noncontributory public pension to assess the impact of pension eligibility on hypertension in a rural, low-income South African setting. Research Design and Methods: Data were from 1 247 men aged ≥60 in the population-representative Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa in 2014/2015. We identified cohorts of men from 0 (controls, aged ≥65 at pension expansion) through 5 years of additional pension eligibility based on their birth year. Using the modified Framingham Heart Study hypertension risk prediction model, and the Wand et al. model modified for the South African population, we estimated the difference in the probabilities of hypertension for men who benefitted from the pension expansion relative to the control. We conducted a negative control analysis among older women, who were not eligible for pension expansion, to assess the robustness of our findings. Results: Older men with 5 additional years of pension eligibility had a 6.9-8.1 percentage point greater probability of hypertension than expected without the pension expansion eligibility. After accounting for birth cohort effects through a negative control analysis involving older women reduced estimates to a 3.0-5.2 percentage point greater probability of hypertension than expected. We observed a mean 0.2 percentage point increase in the probability of hypertension per additional year of pension eligibility, but this trend was not statistically significant. Discussion and Implications: Although the Older Person's Grant is important for improving the financial circumstances of older adults and their families in South Africa, expanded pension eligibility may have a small, negative short-term effect on hypertension among older men in this rural, South African setting.

Plants as vectors for environmental prion transmission.

Prions cause fatal neurodegenerative diseases and exhibit remarkable durability, which engenders a wide array of potential exposure scenarios. In chronic wasting disease of deer, elk, moose, and reindeer and in scrapie of sheep and goats, prions are transmitted via environmental routes and the ability of plants to accumulate and subsequently transmit prions has been hypothesized, but not previously demonstrated. Here, we establish the ability of several crop and other plant species to take up prions via their roots and translocate them to above-ground tissues from various growth media including soils. We demonstrate that plants can accumulate prions in above-ground tissues to levels sufficient to transmit disease after oral ingestion by mice. Our results suggest plants may serve as vectors for prion transmission in the environment-a finding with implications for wildlife conservation, agriculture, and public health.

Challenges to hypertension and diabetes management in rural Uganda: a qualitative study with patients, village health team members, and health care professionals.

BACKGROUND: The prevalence of hypertension and diabetes are expected to increase in sub-Saharan Africa over the next decade. Some studies have documented that lifestyle factors and lack of awareness are directly influencing the control of these diseases. Yet, few studies have attempted to understand the barriers to control of these conditions in rural settings. The main objective of this study was to understand the challenges to hypertension and diabetes care in rural Uganda. METHODS: We conducted semi-structured interviews with 24 patients with hypertension and/or diabetes, 11 health care professionals (HCPs), and 12 community health workers (known as village health team members [VHTs]) in Nakaseke District, Uganda. Data were coded using NVivo software and analyzed using a thematic approach. RESULTS: The results replicated several findings from other settings, and identified some previously undocumented challenges including patients' knowledge gaps regarding the preventable aspects of HTN and DM, patients' mistrust in the Ugandan health care system rather than in individual HCPs, and skepticism from both HCPs and patients regarding a potential role for VHTs in HTN and DM management. CONCLUSIONS: In order to improve hypertension and diabetes management in this setting, we recommend taking actions to help patients to understand NCDs as preventable, for HCPs and patients to advocate together for health system reform regarding medication accessibility, and for promoting education, screening, and monitoring activities to be conducted on a community level in collaboration with village health team members.

Effect of recruitment maneuver on arterial oxygenation in patients undergoing robot-assisted laparoscopic prostatectomy with intraoperative 15 cmH2O positive end expiratory pressure.

BACKGROUND: This randomized, controlled study was designed to compare the effects of recruitment maneuvers (RMs) with a 15 cmH2O positive end-expiratory pressure (PEEP) on the systemic oxygenation and lung compliance of patients with healthy lungs following robot-assisted laparoscopic prostatectomy (RALP). METHODS: Sixty patients undergoing a RALP with an intraoperative 15 cmH2O PEEP were randomly allocated to an RM or a Control group. The patients in the RM group received a single RM through the application of a continuous positive airway pressure of 40 cmH2O for 40 s 15 min after being placed in the Trendelenburg position. The arterial oxygen tension (PaO2, primary endpoint) and the pulmonary dynamic and static compliances (secondary endpoints) were measured 10 min after the anesthetic induction (T1), 10 min after establishment of the pneumoperitoneum (T2), 10 min after establishment of the Trendelenburg position (T3), 10 min after the RM (T4), 60 min after the RM (T5), and 10 min after deflation of the pneumoperitoneum in the supine position (T6). RESULTS: The intergroup comparisons of the PaO2 showed significantly higher values in the RM group than in the Control group at T4 and T5 (193 ± 35 mmHg vs. 219 ± 33 mmHg, P = 0.015, 188 ± 41 mmHg vs. 214 ± 42 mmHg, P = 0.005, respectively). However, the PaO2 at T6 was similar in the two groups (211 ± 39 mmHg vs. 224 ± 41 mmHg, P = 0.442). Moreover, there were no statistical differences between the groups in the dynamic and static compliances of the lungs at any time point. CONCLUSIONS: The arterial oxygenation of the patients with a healthy lung function who had undergone a RALP with intraoperative 15 cmH2O PEEP was improved by a single RM. However, this benefit did not last long, and it did not lead to an amelioration of the lung mechanics.

In vitro prion protein conversion suggests risk of bighorn sheep (Ovis canadensis) to transmissible spongiform encephalopathies.

BACKGROUND: Transmissible spongiform encephalopathies (TSEs) affect both domestic sheep (scrapie) and captive and free-ranging cervids (chronic wasting disease; CWD). The geographical range of bighorn sheep (Ovis canadensis; BHS) overlaps with states or provinces that have contained scrapie-positive sheep or goats and areas with present epizootics of CWD in cervids. No TSEs have been documented in BHS, but the susceptibility of this species to TSEs remains unknown. RESULTS: We acquired a library of BHS tissues and found no evidence of preexisting TSEs in these animals. The prion protein gene (Prnp) in all BHS in our library was identical to scrapie-susceptible domestic sheep (A136R154Q171 genotype). Using an in vitro prion protein conversion assay, which has been previously used to assess TSE species barriers and, in our study appears to recollect known species barriers in mice, we assessed the potential transmissibility of TSEs to BHS. As expected based upon Prnp genotype, we observed BHS prion protein conversion by classical scrapie agent and evidence for a species barrier between transmissible mink encephalopathy (TME) and BHS. Interestingly, our data suggest that the species barrier of BHS to white-tailed deer or wapiti CWD agents is likely low. We also used protein misfolding cyclic amplification to confirm that CWD, but not TME, can template prion protein misfolding in A136R154Q171 genotype sheep. CONCLUSIONS: Our results indicate the in vitro conversion assay used in our study does mimic the species barrier of mice to the TSE agents that we tested. Based on Prnp genotype and results from conversion assays, BHS are likely to be susceptible to infection by classical scrapie. Despite mismatches in amino acids thought to modulate prion protein conversion, our data indicate that A136R154Q171 genotype sheep prion protein is misfolded by CWD agent, suggesting that these animals could be susceptible to CWD. Further investigation of TSE transmissibility to BHS, including animal studies, is warranted. The lack of reported TSEs in BHS may be attributable to other host factors or a lack of TSE surveillance in this species.

Cyclin-dependent kinase 1-dependent phosphorylation of cAMP response element-binding protein decreases chromatin occupancy.

The cyclic AMP response element-binding protein (CREB) initiates transcriptional responses to a wide variety of stimuli. CREB activation involves its phosphorylation on Ser-133, which promotes interaction between the CREB kinase-inducible domain (KID) and the KID-interacting domain of the transcriptional coactivator, CREB-binding protein (CBP). The KID also contains a highly conserved phosphorylation cluster, termed the ATM/CK cluster, which is processively phosphorylated in response to DNA damage by the coordinated actions of ataxia-telangiectasia-mutated (ATM) and casein kinases (CKs) 1 and 2. The ATM/CK cluster phosphorylation attenuates CBP binding and CREB transcriptional activity. Paradoxically, it was recently reported that DNA damage activates CREB through homeodomain-interacting protein kinase 2-dependent phosphorylation of Ser-271 near the CREB bZIP DNA binding domain. In this study we sought to further clarify DNA damage-dependent CREB phosphorylation as well as to explore the possibility that the ATM/CK cluster and Ser-271 synergistically or antagonistically modulate CREB activity. We show that, rather than being induced by DNA damage, Ser-270 and Ser-271 of CREB cophosphorylated in a CDK1-dependent manner during G2/M phase. Functionally, we show that phosphorylation of CREB on Ser-270/Ser-271 during mitosis correlated with reduced CREB chromatin occupancy. Furthermore, CDK1-dependent phosphorylation of CREB in vitro inhibited its DNA binding activity. The combined results suggest that CDK1-dependent phosphorylation of CREB on Ser-270/Ser-271 facilitates its dissociation from chromatin during mitosis by reducing its intrinsic DNA binding potential.

Regulation of ribosomal protein S6 phosphorylation by casein kinase 1 and protein phosphatase 1.

Ribosomal protein S6 (rpS6) is a critical component of the 40 S ribosomal subunit that mediates translation initiation at the 5'-m(7)GpppG cap of mRNA. In response to mitogenic stimuli, rpS6 undergoes ordered C-terminal phosphorylation by p70 S6 kinases and p90 ribosomal S6 kinases on four conserved Ser residues (Ser-235, Ser-236, Ser-240, and Ser-244) whose modification potentiates rpS6 cap binding activity. A fifth site, Ser-247, is also known to be phosphorylated, but its function and regulation are not well characterized. In this study, we employed phospho-specific antibodies to show that Ser-247 is a target of the casein kinase 1 (CK1) family of protein kinases. CK1-dependent phosphorylation of Ser-247 was induced by mitogenic stimuli and required prior phosphorylation of upstream S6 kinase/ribosomal S6 kinase residues. CK1-mediated phosphorylation of Ser-247 also enhanced the phosphorylation of upstream sites, which implies that bidirectional synergy between C-terminal phospho-residues is required to sustain rpS6 phosphorylation. Consistent with this idea, CK1-dependent phosphorylation of rpS6 promotes its association with the mRNA cap-binding complex in vitro. Additionally, we show that protein phosphatase 1 (PP1) antagonizes rpS6 C terminus phosphorylation and cap binding in intact cells. These findings further our understanding of rpS6 phospho-regulation and define a direct link between CK1 and translation initiation.