Sex and adrenal hormones in association with insecticide biomarkers among adolescents living in ecuadorian agricultural communities.

BACKGROUND: Organophosphate, pyrethroid, and neonicotinoid insecticides have resulted in adrenal and gonadal hormone disruption in animal and in vitro studies; limited epidemiologic evidence exists in humans. We assessed relationships of urinary insecticide metabolite concentrations with adrenal and gonadal hormones in adolescents living in Ecuadorean agricultural communities. METHODS: In 2016, we examined 522 Ecuadorian adolescents (11-17y, 50.7% female, 22% Indigenous; ESPINA study). We measured urinary insecticide metabolites, blood acetylcholinesterase activity (AChE), and salivary testosterone, dehydroepiandrosterone (DHEA), 17ß-estradiol, and cortisol. We used general linear models to assess linear (ß = % hormone difference per 50% increase of metabolite concentration) and curvilinear relationships (ß2 = hormone difference per unit increase in squared ln-metabolite) between ln-metabolite or AChE and ln-hormone concentrations, stratified by sex, adjusting for anthropometric, demographic, and awakening response variables. Bayesian Kernel Machine Regression was used to assess non-linear associations and interactions. RESULTS: The organophosphate metabolite malathion dicarboxylic acid (MDA) had positive associations with testosterone (ßboys = 5.88% [1.21%, 10.78%], ßgirls = 4.10% [-0.02%, 8.39%]), and cortisol (ßboys = 6.06 [-0.23%, 12.75%]. Para-nitrophenol (organophosphate) had negatively-trending curvilinear associations, with testosterone (ß2boys = -0.17 (-0.33, -0.003), p = 0.04) and DHEA (ß2boys = -0.49 (-0.80, -0.19), p = 0.001) in boys. The neonicotinoid summary score (ßboys = 5.60% [0.14%, 11.36%]) and the neonicotinoid acetamiprid-N-desmethyl (ßboys = 3.90% [1.28%, 6.58%]) were positively associated with 17ß-estradiol, measured in boys only. No associations between the pyrethroid 3-phenoxybenzoic acid and hormones were observed. In girls, bivariate response associations identified interactions of MDA, Para-nitrophenol, and 3,5,6-trichloro-2-pyridinol (organophosphates) with testosterone and DHEA concentrations. In boys, we observed an interaction of MDA and Para-nitrophenol with DHEA. No associations were identified for AChE. CONCLUSIONS: We observed evidence of endocrine disruption for specific organophosphate and neonicotinoid metabolite exposures in adolescents. Urinary organophosphate metabolites were associated with testosterone and DHEA concentrations, with stronger associations in boys than girls. Urinary neonicotinoids were positively associated with 17ß-estradiol. Longitudinal repeat-measures analyses would be beneficial for causal inference.

Harnessing Passive Pulsatile Shear Stress for Alzheimer's Disease Prevention and Intervention.

 Alzheimer's disease (AD) affects more than 40 million people worldwide and is the leading cause of dementia. This disease is a challenge for both patients and caregivers and puts a significant strain on the global healthcare system. To address this issue, the Lancet Commission recommends focusing on reducing modifiable lifestyle risk factors such as hypertension, diabetes, and physical inactivity. Passive pulsatile shear stress (PPSS) interventions, which use devices like whole-body periodic acceleration, periodic acceleration along the Z-axis (pGz), and the Jogging Device, have shown significant systemic and cellular effects in preclinical and clinical models which address these modifiable risks factors. Based on this, we propose that PPSS could be a potential non-pharmacological and non-invasive preventive or therapeutic strategy for AD. We perform a comprehensive review of the biological basis based on all publications of PPSS using these devices and demonstrate their effects on the various aspects of AD. We draw from this comprehensive analysis to support our hypothesis. We then delve into the possible application of PPSS as an innovative intervention. We discuss how PPSS holds promise in ameliorating hypertension and diabetes while mitigating physical inactivity, potentially offering a holistic approach to AD prevention and management.

Post-Anesthesia Cognitive Dysfunction in Mice Is Associated with an Age-Related Increase in Neuronal Intracellular [Ca2+]-Neuroprotective Effect of Reducing Intracellular [Ca2+]: In Vivo and In Vitro Studies.

Background: Postoperative cognitive dysfunction (POCD) is a common disorder after general anesthesia in elderly patients, the precise mechanisms of which remain unclear. Methods: We investigated the effect of isoflurane with or without dantrolene pretreatment on intracellular calcium concentration ([Ca2+]i), reactive oxygen species (ROS) production, cellular lactate dehydrogenase (LDH) leak, calpain activity, and cognitive function using the Morris water maze test of young (3 months), middle-aged (12-13 months), and aged (24-25 months) C57BL6/J mice. Results: Aged cortical and hippocampal neurons showed chronically elevated [Ca2+]i compared to young neurons. Furthermore, aged hippocampal neurons exhibited higher ROS production, increased LDH leak, and elevated calpain activity. Exposure to isoflurane exacerbated these markers in aged neurons, contributing to increased cognitive deficits in aged mice. Dantrolene pretreatment reduced [Ca2+]i for all age groups and prevented or significantly mitigated the effects of isoflurane on [Ca2+]i, ROS production, LDH leak, and calpain activity in aged neurons. Dantrolene also normalized or improved age-associated cognitive deficits and mitigated the cognitive deficits caused by isoflurane. Conclusions: These findings suggest that isoflurane-induced cytotoxicity and cognitive decline in aging are linked to disruptions in neuronal intracellular processes, highlighting the reduction of [Ca2+]i as a potential therapeutic intervention.

In praise of fossil fuel subsidies (for cooking).

Households that burn biomass in inefficient open fires - a practice that results in $1.6 trillion in global damages from health impacts and climate-altering emissions yearly - are often unable to access cleaner alternatives, like gas, which is widely available but unaffordable, or electricity, which is unattainable for many due to insufficient supply and reliability of electricity services. Governments are often reluctant to make gas affordable. We argue that condemnation of all fossil fuel subsidies is short-sighted and does not adequately consider subsidizing gas for cooking as a potential strategy to improve public health and reduce greenhouse gas emissions.

Influenza vaccination mitigates severe complications in hospitalized patients: A ten-year observational study, Spain, 2009-2019.

BACKGROUND: Influenza epidemics annually impact a substantial portion of adults worldwide, leading to numerous hospitalizations and fatalities. While the primary goal of vaccination is to prevent influenza virus infection, breakthrough infections can still occur despite vaccination. Evaluating the vaccine effectiveness in preventing severe cases among hospitalized patients is crucial for enhancing vaccination strategies. METHODS: This single-center, observational, cross-sectional, and retrospective study analyzed data from 1,357 patients admitted to La Paz University Hospital for influenza infection between 2009 and 2019. Patients' demographics, clinical variables, comorbidities, vaccination status, and influenza-related outcomes were assessed. Logistic regression analysis was performed to determine the vaccine-independent protective effects. RESULTS: Influenza vaccination independently prevented severe complications, including pneumonia, bacterial superinfection, acute respiratory distress syndrome, and multiple organ failure in hospitalized patients (odds ratio = 0.61, 95% confidence interval: 0.47-0.76). Vaccinated patients had significantly lower intensive care unit admission rates (odds ratio = 0.42, 95% confidence interval: 0.18-0.92). However, there were no significant differences in mortality rates between vaccinated and unvaccinated patients (P = .385). CONCLUSIONS: Our study provides robust evidence supporting the influenza vaccine protective effect against severe outcomes in hospitalized patients during epidemic flu. Vaccination is associated with a significant reduction in severe complications and intensive care unit admissions, emphasizing its importance as a preventive measure. Improving vaccination coverage, especially in specific comorbidities and age groups, could further enhance the vaccine effectiveness in preventing severe influenza cases.

Enhancing Muscle Intracellular Ca2+ Homeostasis and Glucose Uptake: Passive Pulsatile Shear Stress Treatment in Type 2 Diabetes.

Type 2 diabetes mellitus (T2D) is a significant global public health problem that has seen a substantial increase in the number of affected individuals in recent decades. In a murine model of T2D (db/db), we found several abnormalities, including aberrant intracellular calcium concentration ([Ca2+]i), decreased glucose transport, increased production of reactive oxygen species (ROS), elevated levels of pro-inflammatory interleukins and creatine phosphokinase (CK), and muscle weakness. Previously, we demonstrated that passive pulsatile shear stress, generated by sinusoidal (headward-forward) motion, using a motion platform that provides periodic acceleration of the whole body in the Z plane (pGz), induces the synthesis of nitric oxide (NO) mediated by constitutive nitric oxide synthase (eNOS and nNOS). We investigated the effect of pGz on db/db a rodent model of T2D. The treatment of db/db mice with pGz resulted in several beneficial effects. It reduced [Ca2+]i overload; enhanced muscle glucose transport; and decreased ROS levels, interleukins, and CK. Furthermore, pGz treatment increased the expression of endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (p-eNOS), and neuronal nitric oxide synthase (nNOS); reduced inducible nitric oxide synthase (iNOS); and improved muscle strength. The cytoprotective effects of pGz appear to be mediated by NO, since pretreatment with L-NAME, a nonspecific NOS inhibitor, abolished the effects of pGz on [Ca2+]i and ROS production. Our findings suggest that a non-pharmacological strategy such as pGz has therapeutic potential as an adjunct treatment to T2D.

Urinary Glyphosate, 2,4-D and DEET Biomarkers in Relation to Neurobehavioral Performance in Ecuadorian Adolescents in the ESPINA Cohort.

BACKGROUND: Herbicides are the most used class of pesticides worldwide, and insect repellents are widely used globally. Yet, there is a dearth of studies characterizing the associations between these chemical groups and human neurobehavior. Experimental studies suggest that glyphosate and 2,4-dichlorophenoxyacetic acid (2,4-D) herbicides can affect neurobehavior and the cholinergic and glutamatergic pathways in the brain. We aim to assess whether herbicides and insect repellents are associated with neurobehavioral performance in adolescents. METHODS: We assessed 519 participants (11-17 years of age) living in agricultural communities in Ecuador. We quantified urinary concentrations of glyphosate, 2,4-D, and two N,N-diethyl-meta-toluamide (DEET) insect repellent metabolites [3-(diethylcarbamoyl)benzoic acid (DCBA) and 3-(ethylcarbamoyl)benzoic acid (ECBA)] using isotope-dilution mass spectrometry. We assessed neurobehavioral performance using 9 subtests across 5 domains (attention/inhibitory control, memory/learning, language, visuospatial processing, and social perception). We characterized the associations using generalized estimating equations and multiple imputation for metabolites below detection limits. Models were adjusted for demographic and anthropometric characteristics, urinary creatinine, and sexual maturation. Mediation by salivary cortisol, dehydroepiandrosterone, 17ß-estradiol, and testosterone was assessed using structural equation modeling. RESULTS: The mean of each neurobehavioral domain score was between 7.0 and 8.7 [standard deviation (SD) range: 2.0-2.3]. Glyphosate was detected in 98.3% of participants, 2,4-D in 66.2%, DCBA in 63.3%, and ECBA in 33.4%. 2,4-D was negatively associated with all neurobehavioral domains, but statistically significant associations were observed with attention/inhibition [score difference per 50% higher metabolite concentration (ß)=-0.19 95% confidence interval (CI): -0.31, -0.07], language [ß=-0.12 (95% CI: -0.23, -0.01)], and memory/learning [ß=-0.11 (95% CI: -0.22, 0.01)]. Glyphosate had a statistically significant negative association only with social perception [ß=-0.08 (95% CI: -0.14, -0.01)]. DEET metabolites were not associated with neurobehavioral performance. Mediation by gender and adrenal hormones was not observed. CONCLUSION: This study describes worse neurobehavioral performance associated with herbicide exposures in adolescents, particularly with 2,4-D. Replication of these findings among other pediatric and adult populations is needed. https://doi.org/10.1289/EHP11383.

Development of a novel in vitro model to study the modulatory role of the respiratory complex I in macrophage effector functions.

Increasing evidence demonstrate that the electron transfer chain plays a critical role in controlling the effector functions of macrophages. In this work, we have generated a Ndufs4-/- murine macrophage cell lines. The Ndufs4 gene, which encodes a supernumerary subunit of complex I, is a mutational hotspot in Leigh syndrome patients. Ndufs4-/- macrophages showed decreased complex I activity, altered complex I assembly, and lower levels of maximal respiration and ATP production. These mitochondrial respiration alterations were associated with a shift towards a pro-inflammatory cytokine profile after lipopolysaccharide challenge and improved ability to phagocytose Gram-negative bacteria.

Putative malignant hyperthermia mutation CaV1.1-R174W is insufficient to trigger a fulminant response to halothane or confer heat stress intolerance.

Malignant hyperthermia susceptibility (MHS) is an autosomal dominant pharmacogenetic disorder that manifests as a hypermetabolic state when carriers are exposed to halogenated volatile anesthetics or depolarizing muscle relaxants. In animals, heat stress intolerance is also observed. MHS is linked to over 40 variants in RYR1 that are classified as pathogenic for diagnostic purposes. More recently, a few rare variants linked to the MHS phenotype have been reported in CACNA1S, which encodes the voltage-activated Ca2+ channel CaV1.1 that conformationally couples to RyR1 in skeletal muscle. Here, we describe a knock-in mouse line that expresses one of these putative variants, CaV1.1-R174W. Heterozygous (HET) and homozygous (HOM) CaV1.1-R174W mice survive to adulthood without overt phenotype but fail to trigger with fulminant malignant hyperthermia when exposed to halothane or moderate heat stress. All three genotypes (WT, HET, and HOM) express similar levels of CaV1.1 by quantitative PCR, Western blot, [3H]PN200-110 receptor binding and immobilization-resistant charge movement densities in flexor digitorum brevis fibers. Although HOM fibers have negligible CaV1.1 current amplitudes, HET fibers have similar amplitudes to WT, suggesting a preferential accumulation of the CaV1.1-WT protein at triad junctions in HET animals. Never-the-less both HET and HOM have slightly elevated resting free Ca2+ and Na+ measured with double barreled microelectrode in vastus lateralis that is disproportional to upregulation of transient receptor potential canonical (TRPC) 3 and TRPC6 in skeletal muscle. CaV1.1-R174W and upregulation of TRPC3/6 alone are insufficient to trigger fulminant malignant hyperthermia response to halothane and/or heat stress in HET and HOM mice.

A Nonrandomized Trial of the Effects of Passive Simulated Jogging on Short-Term Heart Rate Variability in Type 2 Diabetic Subjects.

Background: Diabetes mellitus has reached global epidemic proportions, with type 2 diabetes (T2DM) comprising more than 90% of all subjects with diabetes. Cardiovascular autonomic neuropathy (CAN) frequently occurs in T2DM. Heart rate variability (HRV) reflects a neural balance between the sympathetic and parasympathetic autonomic nervous systems (ANS) and a marker of CAN. Reduced HRV has been shown in T2DM and improved by physical activity and exercise. External addition of pulses to the circulation, as accomplished by a passive simulated jogging device (JD), restores HRV in nondiseased sedentary subjects after a single session. We hypothesized that application of JD for a longer period (7 days) might improve HRV in T2DM participants. Methods: We performed a nonrandomized study on ten T2DM subjects (age range 44-73 yrs) who were recruited and asked to use a physical activity intervention, a passive simulated jogging device (JD) for 7 days. JD moves the feet in a repetitive and alternating manner; the upward movement of the pedal is followed by a downward movement of the forefoot tapping against a semirigid bumper to simulate the tapping of feet against the ground during jogging. Heart rate variability (HRV) analysis was performed using an electrocardiogram in each subject in seated posture on day 1 (baseline, BL), after seven days of JD (JD7), and seven days after discontinuation of JD (Post-JD). Time domain variables were computed, viz., standard deviation of all normal RR intervals (SDNN), standard deviation of the delta of all RR intervals (SDΔNN), and the square root of the mean of the sum of the squares of differences between adjacent RR intervals (RMSSD). Frequency domain measures were determined using a standard Fast Fourier spectral analysis, as well as the parameters of the Poincaré plots (SD1 and SD2). Results: Seven days of JD significantly increased SDNN, SDΔNN, RMSSD, and both SD1 and SD2 from baseline values. The latter parameters remained increased Post-JD. JD did not modify the frequency domain measures of HRV. Conclusion: A passive simulated jogging device increased the time domain and Poincaré variables of HRV in T2DM. This intervention provided effortless physical activity as a novel method to harness the beneficial effects of passive physical activity for improving HRV in T2DM subjects.

Smooth Muscle Cells of Dystrophic (mdx) Mice Are More Susceptible to Hypoxia; The Protective Effect of Reducing Ca2+ Influx.

Duchenne muscular dystrophy (DMD) is an inherited muscular disorder caused by mutations in the dystrophin gene. DMD patients have hypoxemic events due to sleep-disordered breathing. We reported an anomalous regulation of resting intracellular Ca2+ ([Ca2+]i) in vascular smooth muscle cells (VSMCs) from a mouse (mdx) model of DMD. We investigated the effect of hypoxia on [Ca2+]i in isolated and quiescent VSMCs from C57BL/10SnJ (WT) and C57BL/10ScSn-Dmd (mdx) male mice. [Ca2+]i was measured using Ca2+-selective microelectrodes under normoxic conditions (95% air, 5% CO2) and after hypoxia (glucose-free solution aerated with 95% N2-5% CO2 for 30 min). [Ca2+]i in mdx VSMCs was significantly elevated compared to WT under normoxia. Hypoxia-induced [Ca2+]i overload, which was significantly greater in mdx than in WT VSMCs. A low Ca2+ solution caused a reduction in [Ca2+]i and prevented [Ca2+]i overload secondary to hypoxia. Nifedipine (10 µM), a Ca2+ channel blocker, did not modify resting [Ca2+]i in VSMCs but partially prevented the hypoxia-induced elevation of [Ca2+]i in both genotypes. SAR7334 (1 µM), an antagonist of TRPC3 and TRPC6, reduced the basal and [Ca2+]i overload caused by hypoxia. Cell viability, assessed by tetrazolium salt (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, was significantly reduced in mdx compared to WT VSMCs. Pretreatment with SAR7341 increases cell viability in normoxic mdx (p < 0.001) and during hypoxia in WT and mdx VSMCs. These results provide evidence that the lack of dystrophin makes VSMCs more susceptible to hypoxia-induced [Ca2+]i overload, which appears to be mediated by increased Ca2+ entry through L-type Ca2+ and TRPC channels.

Characterization of endogenous Kv1.3 channel isoforms in T cells.

Voltage-dependent potassium channel Kv1.3 plays a key role on T-cell activation; however, lack of reliable antibodies has prevented its accurate detection under endogenous circumstances. To overcome this limitation, we created a Jurkat T-cell line with endogenous Kv1.3 channel tagged, to determine the expression, location, and changes upon activation of the native Kv1.3 channels. CRISPR-Cas9 technique was used to insert a Flag-Myc peptide at the C terminus of the KCNA3 gene. Basal or activated channel expression was studied using western blot analysis and imaging techniques. We identified two isoforms of Kv1.3 other than the canonical channel (54 KDa) differing on their N terminus: a longer isoform (70 KDa) and a truncated isoform (43 KDa). All three isoforms were upregulated after T-cell activation. We focused on the functional characterization of the truncated isoform (short form, SF), because it has not been previously described and could be present in the available Kv1.3-/- mice models. Overexpression of SF in HEK cells elicited small amplitude Kv1.3-like currents, which, contrary to canonical Kv1.3, did not induce HEK proliferation. To explore the role of endogenous SF isoform in a native system, we generated both a knockout Jurkat clone and a clone expressing only the SF isoform. Although the canonical isoform (long form) localizes mainly at the plasma membrane, SF remains intracellular, accumulating perinuclearly. Accordingly, SF Jurkat cells did not show Kv1.3 currents and exhibited depolarized resting membrane potential (VM ), decreased Ca2+ influx, and a reduction in the [Ca2+ ]i increase upon stimulation. Functional characterization of these Kv1.3 channel isoforms showed their differential contribution to signaling pathways involved in formation of the immunological synapse. We conclude that alternative translation initiation generates at least three endogenous Kv1.3 channel isoforms in T cells that exhibit different functional roles. For some of these functions, Kv1.3 proteins do not need to form functional plasma membrane channels.

Cardiovascular health worsening in patients with autoimmune rheumatological diseases during the COVID-19 pandemic.

Rheumatic autoimmune diseases are associated with a myriad of comorbidities. Of particular importance due to their morbimortality are cardiovascular diseases. COVID-19 greatly impacted the world population in many different areas. Patients with rheumatic diseases had to face changes in their healthcare, in addition to unemployment, a decrease in physical activity, social isolation, and lack of access to certain medications. This review summarizes the impact of COVID-19 pandemic on cardiovascular risk factors, comorbidities, and unhealthy behaviors in patients with rheumatic inflammatory autoimmune diseases, particularly focused on rheumatoid arthritis and systemic lupus erythematosus. Searches were carried out in MEDLINE/PubMed and Scopus from August to December 2022. Four reviewers screened the title and abstract of retrieved records. Potentially eligible reports were then reviewed in full text. Differences were reconciled by either consensus or discussion with an external reviewer. During the COVID-19 pandemic, patients with rheumatic diseases showed an increase in the prevalence of mental health disorders (43.2-57.7%), reduced physical activity (56.8%), and a worsening in eating behaviors. Alcohol intake increased (18.2%), especially in early phases of the pandemic. Smoking prevalence decreased (28.2%). Dyslipidemia and hypertension showed no changes. The pandemic and lockdown affected rheumatic patients not only in disease-related characteristics but in the prevalence of their cardiovascular comorbidities and risk factors. Lifestyle changes, such as healthy eating, physical activity, and optimal management of their rheumatic diseases and comorbidities, are essential to manage the long-lasting consequences of the COVID-19 outbreak. Key Points • During the COVID-19 pandemic, anxiety, depression, sedentarism, obesity, and a worsening in eating behaviors increased. •Patients with rheumatic diseases and comorbidities have worse clinical outcomes and a higher cardiovascular disease burden than those without them. •Comparative studies are necessary to precisely elucidate the pandemic's impact on the prevalence of cardiovascular disease, risk factors, and comorbidities in patients with rheumatoid arthritis and systemic lupus erythematosus.

Improving thromboprophylaxis in the medical inpatients: The role of the resident in an academic hospital.

INTRODUCTION: Venous thromboembolism (VTE) is one of the main causes of preventable in-hospital death. It is recommended for hospitals to have an appropriate thromboprophylaxis (TP) protocol to avoid VTE complications. OBJECTIVE: To determine the effect of the resident physician feedback to the staff physician in TP appropriateness after the Caprini RAM score implementation. METHODS: Caprini RAM was implemented by the residents in medical patients. Patients were divided in low, moderate, high, and highest-risk groups, with TP recommendation accordingly. In cases with inadequate TP, the resident provided feedback to the staff physician for adjustment. Change to appropriate TP was assessed retrospectively. RESULTS: A total of 265 records were included. Before intervention, 193 (72.8%) patients had appropriate TP and post-intervention, 207 (78.1%) patients received adequate TP (p < .001). CONCLUSIONS: Feedback from the internal medicine resident to staff physician improves appropriate TP in medical inpatients as a quality of care strategy.

Association of soluble cell adhesion molecules and lipid levels in rheumatoid arthritis patients.

OBJECTIVES: To evaluate the relationship between soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intracellular adhesion molecule-1 (sICAM-1), and lipid levels in rheumatoid arthritis (RA) patients with and without carotid plaque (CP). METHODS: Cross-sectional study nested of a RA cohort. RA patients without a previous cardiovascular event or statins' therapy, aged 40-75 years were recruited at an outpatient cardio-rheumatology clinic. Carotid ultrasound was performed in all study subjects. RA patients with CP were included and matched to RA patients without CP by age, gender, and traditional cardiovascular risk factors. Blood samples were drawn at the time of recruitment to measure sVCAM-1, sICAM-1, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and lipid levels. Correlations between cell adhesion molecules, disease activity indexes, ESR and CRP with lipid levels were assessed with Spearman's correlation coefficient (rs). RESULTS: We included 71 RA patients, 37 with CP and 34 without CP. RA (n = 71) patients had a moderate negative correlation of sVCAM-1 with total cholesterol (TC) (rs = - 0.366, p = 0.002) and low-density lipoprotein (LDL) (rs = - 0.316, p = 0.007), and a small negative correlation with high-density lipoprotein (rs = - 0.250, p = 0.036). ESR showed a small negative correlation with LDL (rs = - 0.247, p = 0.038). Patients with CP had a moderate negative correlation between sVCAM and TC (rs = - 0.405, p = 0.013). Patients without CP showed a moderate negative correlation between sVCAM with TC (rs = - 0.364, p = 0.034) and LDL (rs = - 0.352, p = 0.041), and sICAM with VLDL (rs = - 0.343, p = 0.047). CONCLUSIONS: RA patients showed an inverse association of sVCAM-1 and lipid levels. More studies are needed to define the precise role of sVCAM-1 in the lipid paradox of RA.

National Burden and Trends for 29 Groups of Cancer in Mexico from 1990 to 2019: A Secondary Analysis of the Global Burden of Disease Study 2019.

The global burden of cancer is on the rise, with varying national patterns. To gain a better understanding and control of cancer, it is essential to provide national estimates. Therefore, we present a comparative description of cancer incidence and mortality rates in Mexico from 1990 to 2019, by age and sex for 29 different cancer groups. Based on public data from the Global Burden of Disease Study 2019, we evaluated the national burden of cancer by analyzing counts and crude and age-standardized rates per 100,000 people with 95% uncertainty intervals for 2019 and trends using the annual percentage change from 1990 to 2019. In 2019, cancer resulted in 222,060 incident cases and 105,591 deaths. In 2019, the highest incidence of cancer was observed in non-melanoma skin cancer, prostate cancer, and breast cancer. Additionally, 53% of deaths were attributed to six cancer groups (lung, colorectal, stomach, prostate, breast, and pancreatic). From 1990 to 2019, there was an increasing trend in incidence and mortality rates, which varied by 10-436% among cancer groups. Furthermore, there were cancer-specific sex differences in crude and age-standardized rates. The results show an increase in the national cancer burden with sex-specific patterns of change. These findings can guide national efforts to reduce health loss due to cancer.

Non-Invasive Pulsatile Shear Stress Modifies Endothelial Activation; A Narrative Review.

The monolayer of cells that line both the heart and the entire vasculature is the endothelial cell (EC). These cells respond to external and internal signals, producing a wide array of primary or secondary messengers involved in coagulation, vascular tone, inflammation, and cell-to-cell signaling. Endothelial cell activation is the process by which EC changes from a quiescent cell phenotype, which maintains cellular integrity, antithrombotic, and anti-inflammatory properties, to a phenotype that is prothrombotic, pro-inflammatory, and permeable, in addition to repair and leukocyte trafficking at the site of injury or infection. Pathological activation of EC leads to increased vascular permeability, thrombosis, and an uncontrolled inflammatory response that leads to endothelial dysfunction. This pathological activation can be observed during ischemia reperfusion injury (IRI) and sepsis. Shear stress (SS) and pulsatile shear stress (PSS) are produced by mechanical frictional forces of blood flow and contraction of the heart, respectively, and are well-known mechanical signals that affect EC function, morphology, and gene expression. PSS promotes EC homeostasis and cardiovascular health. The archetype of inducing PSS is exercise (i.e., jogging, which introduces pulsations to the body as a function of the foot striking the pavement), or mechanical devices which induce external pulsations to the body (Enhanced External Pulsation (EECP), Whole-body vibration (WBV), and Whole-body periodic acceleration (WBPA aka pGz)). The purpose of this narrative review is to focus on the aforementioned noninvasive methods to increase PSS, review how each of these modify specific diseases that have been shown to induce endothelial activation and microcirculatory dysfunction (Ischemia reperfusion injury-myocardial infarction and cardiac arrest and resuscitation), sepsis, and lipopolysaccharide-induced sepsis syndrome (LPS)), and review current evidence and insight into how each may modify endothelial activation and how these may be beneficial in the acute and chronic setting of endothelial activation and microvascular dysfunction.