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Cerca de una cuarta parte de los adultos tienen hipertensión, el principal factor de riesgo de muerte (inclusive la causada por cardiopatía y accidente cerebrovascular). Existen políticas eficaces que podrían ayudar a las personas a elegir opciones saludables para prevenir el aumento de la presión arterial; si se las aplicara plenamente, se podría evitar en gran medida el desarrollo de hipertensión. La hipertensión es fácil de detectar y tratar, PERO solo alrededor de 50% de los adultos que presentan dicha afección son conscientes de su situación y solamente 1 de cada 7 de ellos recibe el tratamiento adecuado. La prevención y el control de la hipertensión es el mecanismo principal para prevenir y controlar las enfermedades no transmisibles y un modelo para evitar otros riesgos de presentar dichas enfermedades. La adopción de un modo de vida saludable y el tratamiento farmacológico efectivo podrían prevenir y controlar la hipertensión en la mayoría de las personas si se implementaran de manera sistemática en la población; en todos los entornos es posible aplicar intervenciones sencillas, que pueden usarse para mejorar la atención primaria. Es urgente adoptar medidas sostenidas para introducir cambios eficaces en las políticas públicas y los sistemas de salud pública con miras a prevenir y controlar la hipertensión.

Cerca de ¼ dos adultos têm hipertensão arterial, que é o fator de risco isolado mais importante para morte (incluídas as mortes por cardiopatia e acidente vascular cerebral). Existem políticas eficazes que poderiam facilitar escolhas pessoais saudáveis para evitar a elevação da pressão arterial e, se plenamente implementadas, podem prevenir a ocorrência da hipertensão arterial. É fácil rastrear e tratar a hipertensão, MAS somente cerca de 50% dos adultos hipertensos estão cientes de sua condição, e apenas cerca de 1 em cada 7 é tratado adequadamente. A prevenção e controle da hipertensão é o principal mecanismo de prevenção e controle das doenças não transmissíveis e um modelo para outros riscos de doenças não transmissíveis. Tratamentos eficazes com mudanças de estilo de vida e medicamentos poderiam prevenir e controlar a hipertensão arterial na maioria das pessoas se aplicados sistematicamente à população; as intervenções simples são viáveis em todos os ambientes e podem melhorar a atenção primária. É necessária a ação continuada e urgente a fim de obter mudanças efetivas nas políticas públicas e no sistema de saúde para prevenir e controlar a hipertensão arterial.

Summary: Background: Increased blood pressure is the biggest contributor to the global burden of disease and mortality. Data suggest that less than half of the population with hypertension is aware of it. May Measurement Month was initiated to raise awareness of the importance of blood pressure and as a pragmatic interim solution to the shortfall in screening programmes. Methods: This cross-sectional survey included volunteer adults (≥18 years) who ideally had not had their blood pressures measured in the past year. Each participant had their blood pressure measured three times and received a a questionnaire about demographic, lifestyle, and environmental factors. The primary objective was to raise awareness of blood pressure, measured by number of countries involved, number of people screened, and number of people who have untreated or inadequately treated hypertension (defined as systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg, or both, or on the basis of receiving antihypertensive medication). Multiple imputation was used to estimate the mean of the second and third blood pressure readings if these were not recorded. Measures of association were analysed using linear mixed models. Findings: Data were collected from 1 201 570 individuals in 80 countries. After imputation, of the 1 128 635 individuals for whom a mean of the second and third readings was available, 393 924 (34·9%) individuals had hypertension. 153 905 (17·3%) of 888 616 individuals who were not receiving antihypertensive treatment were hypertensive, and 105 456 (46·3%) of the 227 721 individuals receiving treatment did not have controlled blood pressure. Significant differences in adjusted blood pressures and hypertension prevalence were apparent between regions. Adjusted blood pressure was higher in association with antihypertensive medication, diabetes, cerebrovascular disease, smoking, and alcohol consumption. Blood pressure was higher when measured on the right arm than on the left arm, and blood pressure was highest on Saturdays. Interpretation: Inexpensive global screening of blood pressure is achievable using volunteers and convenience sampling. Pending the set-up of systematic surveillance systems worldwide, MMM will be repeated annually to raise awareness of blood pressure. Funding: International Society of Hypertension, Centers for Disease Control and Prevention, Servier Pharmaceutical Co.

Abstract The investigation of triggers causing the onset and intensification of Northern Hemisphere Glaciation (NHG) during the late Pliocene is essential for understanding the global climate system, with important implications for projecting future climate changes. Despite their critical roles in the global climate system, influences of land-ocean interactions on high-latitude ice sheets remain largely unexplored. Here, we present a high-resolution Asian dust record from Ocean Drilling Program Site 1208 in the North Pacific, which lies along the main route of the westerlies. Our data indicate that atmosphere-land-ocean interactions affected aeolian dust emissions through modulating moisture and vegetation in dust source regions, highlighting a critical role of terrestrial systems in initiating the NHG as early as 3.6 Myr ago. Combined with additional multi-proxy and model results, we further show that westerly wind strength was enhanced, mainly at low-to-middle tropospheric levels, during major glacial events at about 3.3 and 2.7 Myr ago. We suggest that coupled responses of Earth’s surface dynamics and atmospheric circulation in the Plio-Pleistocene likely involved feedbacks related to changes in paleogeography, ocean circulation, and global climate.

Degenerative cervical myelopathy (DCM) is the leading cause of spinal cord dysfunction in adults, representing substantial morbidity and significant financial and resource burdens. Typically, patients with progressive DCM will eventually receive surgical treatment. Nonetheless, despite advancements in pharmacotherapeutics, evidence for pharmacological therapy remains limited. Health professionals from various fields would find interest in pharmacological agents that could benefit patients with mild DCM or enhance surgical outcomes. This review aims to consolidate all clinical and experimental evidence on the pharmacological treatment of DCM. We conducted a comprehensive narrative review that presents all pharmacological agents that have been investigated for DCM treatment in both humans and animal models. Riluzole exhibits effectiveness solely in rat models, but not in treating mild DCM in humans. Cerebrolysin emerges as a potential neuroprotective agent for myelopathy in animals but had contradictory results in clinical trials. Limaprost alfadex demonstrates motor function improvement in animal models and exhibits promising outcomes in a small clinical trial. Glucocorticoids not only fail to provide clinical benefits but may also lead to adverse events. Cilostazol, anti-Fas ligand antibody, and Jingshu Keli display promise in animal studies, while erythropoietin, granulocyte colony-stimulating factor and limaprost alfadex exhibit potential in both animal and human research. Existing evidence mainly rests on weak clinical data and animal experimentation. Current pharmacological efforts target ion channels, stem cell differentiation, inflammatory, vascular, and apoptotic pathways. The inherent nature and pathogenesis of DCM offer substantial prospects for developing neurodegenerative or neuroprotective therapies capable of altering disease progression, potentially delaying surgical intervention, and optimizing outcomes for those undergoing surgical decompression.

Abstract We document an apparent downward displacement of the Matuyama‐Brunhes magnetic reversal by ∼20 m at Scotia Sea International Ocean Discovery Program Site U1538 (Pirie Basin) by comparison with the well‐defined paleomagnetic record at nearby Site U1537 (Dove Basin). Detailed stratigraphic correlation between the two sites is possible due to similar lithologic variations. However, the two sites have distinctly different porewater geochemistry. Notably, Site U1538 indicates a greater demand for electron acceptors to oxidize organic carbon and Fe2+ enrichment below the depth of SO42− depletion. Magnetic parameters indicate enrichment of an authigenic magnetic mineral with strong remanence properties around the depth of SO42− depletion (∼46 m at Site U1538) relative to magnetic parameters at correlative depths at Site U1537. Fe2+ enrichment below the depth of SO42− depletion is not predicted based on the energetically favorable order of electron acceptors for microbial respiration but is documented here and in other depositional settings. This indicates Fe2+ production exceeds the production of H2S by SO42− reduction, providing a geochemical environment that favors the production and preservation of ferrimagnetic remanence‐bearing iron sulfides over paramagnetic pyrite and, thus, a mechanism for deep chemical remanent magnetization acquisition at depths of tens of meters. The influence of authigenic ferrimagnetic iron sulfides on paleomagnetic signals can be difficult to demonstrate with magnetic properties alone; therefore, this finding has implications for evaluating the fidelity of magnetostratigraphic records with complementary geochemical data. Such situations should be considered in other depositional environments with similar porewater Fe2+ accumulation below the SO42− reduction depth.

Abstract High-resolution ice core records from coastal Antarctica are particularly useful to inform our understanding of environmental changes and their drivers. Here, we present a decadally resolved record of sea-salt sodium (a proxy for open-ocean area) and non-sea salt calcium (a proxy for continental dust) from the well-dated Roosevelt Island Climate Evolution (RICE) core, focusing on the time period between 40–26 ka BP. The RICE dust record exhibits an abrupt shift towards a higher mean dust concentration at 32 ka BP. Investigating existing ice-core records, we find this shift is a prominent feature across Antarctica. We propose that this shift is linked to an equatorward displacement of Southern Hemisphere westerly winds. Subsequent to the wind shift, data suggest a weakening of Southern Ocean upwelling and a decline of atmospheric CO2 to lower glacial values, hence making this shift an important glacial climate event with potentially important insights for future projections.

Abstract The economic repercussions of waiting for lumbar disc surgery have not been well studied. The primary goal of this study was to perform a cost-consequence analysis of patients receiving early vs late surgery for symptomatic disc herniation from a societal perspective. Secondarily, we compared patient factors and patient-reported outcomes. This is a retrospective analysis of prospectively collected data from the CSORN registry. A cost-consequence analysis was performed where direct and indirect costs were compared, and different outcomes were listed separately. Comparisons were made on an observational cohort of patients receiving surgery less than 60 days after consent (short wait) or 60 days or more after consent (long wait). This study included 493 patients with surgery between January 2015 and October 2021 with 272 patients (55.2%) in the short wait group and 221 patients (44.8%) classified as long wait. There was no difference in proportions of patients who returned to work at 3 and 12-months. Time from surgery to return to work was similar between both groups (34.0 vs 34.9 days, p = 0.804). Time from consent to return to work was longer in the longer wait group corresponding to an additional $11,753.10 mean indirect cost per patient. The short wait group showed increased healthcare usage at 3 months with more emergency department visits (52.6% vs 25.0%, p

Sedimentary ancient DNA can indicate ecosystem-wide changes. Here, the authors show association between warm phases and high diatom abundance in the Antarctic Scotia Sea, in addition to presenting ancient eukaryote sedimentary DNA spanning the last approximately 1 million years.

ObjectivesThis study aimed to examine whether preoperative cervical muscle size, composition, and asymmetry from magnetic resonance imaging (MRI) can predict post-operative outcomes in patients with degenerative cervical myelopathy (DCM).MethodsA total of 171 patients with DCM were included. Relative total cross-sectional area (RCSA), functional CSA (fat-free area, FCSA), ratio of FCSA/CSA (fatty infiltration) and asymmetry of the multifidus (MF) and semispinalis cervicis (SCer) together (MF + SCer), and cervical muscle as a group (MF, SCer, semispinalis capitis, and splenius capitis) were obtained from T2-weighted axial MR images at the mid-disk, at the level of maximum cord compression and the level below. Univariate and multivariate linear regression analyses were used to assess the relationship between baseline cervical muscle measurements of interest with the modified Japanese Orthopedic Association (mJOA), Nurick Classification, Neck Disability Index (NDI), and SF-36 health survey at 6-month and 12-month post-surgery.ResultsLower RCSA of MF + SCer, less CSA MF + SCer asymmetry and greater FCSA/CSA for the cervical muscle group (e.g., less fatty infiltration), and younger age were significant predictors of higher mJOA scores (e.g., less disability) at 6-month and 12-month post-surgery (all p

Targeted therapies such as venetoclax (VEN) (Bcl-2 inhibitor) have revolutionized the treatment of chronic lymphocytic leukemia (CLL). We previously reported that persister CLL cells in treated patients overexpress multiple antiapoptotic proteins and display resistance to proapoptotic agents. Here, we demonstrated that multidrug-resistant CLL cells in vivo exhibited apoptosis restriction at a pre-mitochondrial level due to insufficient activation of the Bax and Bak (Bax/Bak) proteins. Co-immunoprecipitation analyses with selective BH domain antagonists revealed that the pleiotropic proapoptotic protein (Bim) was prevented from activating Bax/Bak by “switching” interactions to other upregulated antiapoptotic proteins (Mcl-1, Bcl-xL, Bcl-2). Hence, treatments that bypass Bax/Bak restriction are required to deplete these resistant cells in patients. Protein phosphatase 2A (PP2A) contributes to oncogenesis and treatment resistance. We observed that small-molecule activator of PP2A (SMAP) induced cytotoxicity in multiple cancer cell lines and CLL samples, including multidrug-resistant leukemia and lymphoma cells. The SMAP (DT-061) activated apoptosis in multidrug-resistant CLL cells through induction of mitochondrial permeability transition pores, independent of Bax/Bak. DT-061 inhibited the growth of wild-type and Bax/Bak double-knockout, multidrug-resistant CLL cells in a xenograft mouse model. Collectively, we discovered multidrug-resistant CLL cells in patients and validated a pharmacologically tractable pathway to deplete this reservoir.

Background: While considered the mainstay of treatment for specific bone metastases, ZA is used predominantly to treat osteolytic lesions. The purpose of this network meta-analysis is to compare ZA to other treatment options in its ability to improve specific clinical outcomes in patients with bone metastases secondary to any primary tumor. Methods: PubMed, Embase and Web of Science were systematically searched from inception to May 5th, 2022. Keywords used were solid tumor, lung neoplasm, kidney neoplasm, breast neoplasm, prostate neoplasm, ZA and bone metastasis. Every randomized controlled trial and non-randomized quasi-experimental study of systemic ZA administration for patients with bone metastases and any comparator were included. A Bayesian network meta-analysis was done on the primary outcomes including number of SREs, time to developing a first on-study SRE, overall survival, and disease progression-free survival. Secondary outcome was pain at 3, 6 and 12 months after treatment. Results: Our search yielded 3861 titles with 27 meeting inclusion criteria. For the number of SRE, ZA in combination with chemotherapy or hormone therapy was statistically superior to placebo (OR 0.079; 95 % CrI: 0.022–0.27). For the time to the first on study SRE, the relative effectiveness of ZA 4 mg was statistically superior to placebo (HR 0.58; 95 % CrI:0.48–0.77). At 3 and 6 months, ZA 4 mg was significantly superior to placebo for reducing pain with a SMD of −0.85 (95 % CrI:-1.6, −0.0025) and −2.6 (95 % CrI:-4.7, −0.52) respectively. Conclusions: This systematic review shows the benefits of ZA in decreasing the incidence of SREs, increasing the time to the first on-study SRE, and reducing the pain level at 3 and 6 months.

Limitations of bone defect reconstruction include poor bone healing and osteointegration with acrylic cements, lack of strength with bone putty/paste, and poor osteointegration. Tissue engineering aims to bridge these gaps through the use of bioactive implants. However, there is often a risk of infection and biofilm formation associated with orthopedic implants, which may develop anti-microbial resistance. To promote bone repair while also locally delivering therapeutics, 3D-printed implants serve as a suitable alternative. Soft, nanoporous 3D-printed filaments made from a thermoplastic polyurethane and polyvinyl alcohol blend, LAY-FOMM and LAY-FELT, have shown promise for drug delivery and orthopedic applications. Here, we compare 3D printability and sustained antibiotic release kinetics from two types of commercial 3D-printed porous filaments suitable for bone tissue engineering applications. We found that both LAY-FOMM and LAY-FELT could be consistently printed into scaffolds for drug delivery. Further, the materials could sustainably release Tetracycline over 3 days, independent of material type and infill geometry. The drug-loaded materials did not show any cytotoxicity when cultured with primary human fibroblasts. We conclude that both LAY-FOMM and LAY-FELT 3D-printed scaffolds are suitable devices for local antibiotic delivery applications, and they may have potential applications to prophylactically reduce infections in orthopedic reconstruction surgery.

The collection of fish eggs is a commonly used technique for monitoring invasive carp. Genetic identification is the most trusted method for identifying fish eggs but is expensive and slow. Recent work suggests random forest models could provide an inexpensive method for identifying invasive carp eggs based on morphometric egg characteristics. While random forests provide accurate predictions, they do not produce a simple formula for obtaining new predictions. Instead, individuals must have knowledge of the R coding language, limiting the individuals who can use the random forests for resource management. We present WhoseEgg: a web-based point-and-click application that allows non-R users to access random forests via a point and click interface to rapidly identify fish eggs with an objective of detecting invasive carp (Bighead, Grass, and Silver Carp) in the Upper Mississippi River basin. This article provides an overview of WhoseEgg, an example application, and future research directions.

Theoretical models indicate that photoevaporative and magnetothermal winds play a crucial role in the evolution and dispersal of protoplanetary disks and affect the formation of planetary systems. However, it is still unclear what wind-driving mechanism is dominant or if both are at work, perhaps at different stages of disk evolution. Recent spatially resolved observations by Fang et al. of the [O i ] 6300 Å spectral line, a common disk wind tracer in TW Hya, revealed that about 80% of the emission is confined to the inner few astronomical units of the disk. In this work, we show that state-of-the-art X-ray-driven photoevaporation models can reproduce the compact emission and the line profile of the [O i ] 6300 Å line. Furthermore, we show that the models also simultaneously reproduce the observed line luminosities and detailed spectral profiles of both the [O i ] 6300 Å and the [Ne ii ] 12.8 μ m lines. While MHD wind models can also reproduce the compact radial emission of the [O i ] 6300 Å line, they fail to match the observed spectral profile of the [O i ] 6300 Å line and underestimate the luminosity of the [Ne ii ] 12.8 μ m line by a factor of 3. We conclude that, while we cannot exclude the presence of an MHD wind component, the bulk of the wind structure of TW Hya is predominantly shaped by a photoevaporative flow.

Purpose Event-based clinical outcome trials have shown limited evidence to support guidelines recommendations to lower blood pressure (BP) to

Purpose Available data of event-based clinical outcomes trials show that little evidence supports the guidelines recommendations to lower blood pressure (BP) to

Abstract We investigate chronology and age uncertainty for the middle to upper Pleistocene lower Bengal Fan using a novel age‐depth modeling approach that factors lithostratigraphic, magnetostratigraphic, biostratigraphic, cyclostratigraphic, and seismic stratigraphic constraints, based on results from the International Ocean Discovery Program Expedition 354 Bengal Fan and analysis of the GeoB97‐020/027 seismic line. The initial chronostratigraphic framework is established using regionally extensive hemipelagic sediment units, and only age‐depth models of fan deposits that respect the superposition of channel‐levee systems between sites are accepted. In doing so, we reconstruct signals of regional sediment accumulation rate and lithogenic sediment input through the perspective of a two‐dimensional ~320 km transect at 8°N that are consistent with more distal and more ambiguous regional records. This chronology allows us to discuss the depositional history of the middle to upper Pleistocene lower Bengal Fan within the context of sea level, climate, and tectonic controls. We hypothesize, based on the timing of accumulation rate changes, that progradation and intensification of the Bengal Fan's channel‐levee system at 8°N was largely driven by increases in sea level amplitude during this time. However, it is also possible this progradation was influenced by changes in Pleistocene climate and increased Himalayan erosion rates, driving greater sediment flux to the fan.

Abstract: De novo resistance and rapid recurrence often characterize responses of B-cell malignancies to ibrutinib (IBR), indicating a need to develop drug combinations that block compensatory survival signaling and give deeper, more durable responses. To identify such combinations, we previously performed a combinatorial drug screen and identified the Bcl-2 inhibitor venetoclax (VEN) as a promising partner for combination with IBR in mantle cell lymphoma (MCL). We have opened a multi-institutional clinical trial to test this combination. However, analysis of primary samples from patients with MCL as well as chronic lymphocytic leukemia (CLL) revealed unexpected heterogeneous de novo resistance even to the IBR+VEN combination. In the current study, we demonstrate that resistance to the combination can be generated by microenvironmental agonists: interleukin-10 (IL-10), CD40L and, most potently, cytosine guanine dinucleotide–oligodeoxynucleotides (CpG-ODNs), which is a surrogate for unmethylated DNA and a specific agonist for Toll-like receptor 9 (TLR9) signaling. Incubation with these agonists caused robust activation of NF-κB signaling, especially alternative NF-κB, which led to enhanced expression of the antiapoptotic proteins Mcl-1, Bcl-xL, and survivin, thus decreasing dependence on Bcl-2. Inhibitors of NF-κB signaling blocked overexpression of these antiapoptotic proteins and overcame resistance. Inhibitors of Mcl-1, Bcl-xL, or survivin also overcame this resistance, and showed synergistic benefit with the IBR+VEN combination. We conclude that microenvironmental factors, particularly the TLR9 agonist, can generate de novo resistance to the IBR+VEN combination in CLL and MCL cells. This signaling pathway presents targets for overcoming drug resistance induced by extrinsic microenvironmental factors in diverse B-cell malignancies.

Bisphosphonates (BPs) have recently been shown to have direct anti-tumor properties. Systemic treatment with BPs can have multiple adverse effects such as osteonecrosis of the jaw and BP induced bone fracturing and spine instability. While benefits of systemic BP treatments may outweigh risks, local treatment with BPs has been explored as an alternate strategy to reduce unwarranted risk. In the present study, we examined whether local delivery of BPs inhibits tumor-induced osteolysis and tumor growth more effectively than systemic treatment in an animal model of tumor-induced bone disease. Following establishment of an intra-tibial model of bone metastases in athymic mice, the experimental group was treated by local administration of zoledronate into the tibial lesion. A comparison of the effect of local versus systemic delivery of zoledronate on the formation of tumor-induced osteolysis was also carried out. A significant increase in mean bone volume/tissue volume % (BV/TV) of the locally treated group (12.30±2.80%) compared to the control group (7.13±1.22%) (P