Diesel exhaust particles exposure exacerbates pro-thrombogenic plasma features ex-vivo after cerebral ischemia and accelerates tPA-induced clot-lysis in hypertensive subjects.

The combustion of fossil fuels, mainly by diesel engines, generates Diesel Exhaust Particles (DEP) which are the main source of Particulate Matter (PM), a major air pollutant in urban areas. These particles are a risk factor for stroke with 5.6% of cases attributed to PM exposure. Our aim was to evaluate the effect of DEP exposure on clot formation and lysis in the context of stroke. An ex-vivo clot formation and lysis turbidimetric assay has been conducted in human and mouse plasma samples from ischemic stroke or control subjects exposed to DEP or control conditions. Experimental DEP exposure was achieved by nasal instillation in mice, or by ex-vivo exposure in human plasma. Results show consistent pro-thrombogenic features in plasma after human ischemic stroke and mouse cerebral ischemia (distal MCAo), boosted by the presence of DEP. Otherwise, thrombolysis times were increased after ischemia in chronically exposed mice but not in the DEP exposed group. Finally, subjects living in areas with high PM levels presented accelerated thrombolysis compared to those living in low polluted areas. Overall, our results point at a disbalance of the thrombogenic/lytic system in presence of DEP which could impact on ischemic stroke onset, clot size and thrombolytic treatment.

Effect of a Caring-Based Training Program on Caring Behaviors of Indonesian Nurses as Perceived by Patients.

Background: A caring education program is proven effective in improving nurses' behavior in several countries. This study aimed to assess the effect of the Caring-Based Training Program (CBTP) on nurses' caring behaviors of Indonesian nurses as perceived by patients. Materials and Methods: This non-equivalent control group post-test-only design was conducted on 74 patients from a public hospital in Malang district, Indonesia, in 2019. The patients who only met the inclusion criteria were recruited through convenience sampling. The Caring Behaviors Inventory-24 (CBI-24) items were utilized to measure nurses' caring behaviors as perceived by patients. Data were analyzed using frequency, mean, standard deviation, t-test, and ANOVA test at 0.05 levels of significance. Results: The overall mean score of CBI-24 for the experimental group was higher than the control group (5.48 and 5.04, respectively). According to the patient's perception, these findings indicated that the caring behavior of nurses in the experimental group was better than that in the control group. The independent t-test showed a significant difference in the nurses' caring behaviors between the experimental and control groups (p-value = 0.001). Conclusions: The study demonstrated that a CBTP could improve nurses' caring behaviors. Therefore, the developed program is essential and required by Indonesian nurses to increase their caring behaviors.

High reproductive effort in a vulnerable lizard from high altitudes in Argentina: Reproductive biology and sexual dimorphism in Phymaturus extrilidus.

Reproductive biology is fundamental to understanding the ecology and evolution of lizards which, in turn, is essential for the definition of the species´ conservation status. We studied life-history traits related to the reproduction of the Phymaturus extrilidus lizard, including the male and female reproductive cycles, litter size, mean annual reproductive output, reproductive effort, sexual maturity size and sexual dimorphism, body condition, and fat body cycles. We found sexual dimorphism in size and shape, supporting the hypotheses of sexual and fecundity selection. Females exhibited biennial reproductive cycles synchronous with the annual prenuptial male cycle, adjusted for the maturation of the vitellogenic follicles of females. Females of P. extrilidus have the highest mean annual reproductive output (MARO=1.14) recorded in Phymaturus, and this is accompanied by the highest reproductive effort (C=0.28, C energetic =0.31). Births occur from late summer to early autumn. The female reproductive cycle, strictly biennial, like all species of the P. palluma group, and the vitellogenesis in particular, appear to be limited by body condition and the amount of fat body stored. This study presents the fundamental reproductive traits of P. extrilidus that can provide valuable information to be used in the evaluation of the conservation status of this species.

Silent brain infarcts, peripheral vascular disease and the risk of cardiovascular events in patients with hypertension.

BACKGROUND AND AIMS: We aimed to study the relationship between cerebral small vessel disease (cSVD) lesions, as markers of subclinical target organ damage (TOD) in the brain, and incident cardiovascular events (CVE). METHODS: Data from the ISSYS (Investigating Silent Strokes in hYpertensives Study), which is a longitudinal and observational study conducted in patients with hypertension aged 50-70 years, and stroke-free at the inclusion. At the baseline visit, participants underwent a clinical interview, a brain MRI, urine and blood sampling collection and vascular testing studies. Therefore, we obtained markers of TOD from the brain [white matter hyperintensities, silent brain infarcts (SBI), cerebral microbleeds and enlarged perivascular spaces (EPVS)], from kidney (microalbuminuria, glomerular filtration) and regarding large vessels [ankle-to-brachial index (ABI), carotid-femoral pulse wave velocity]. Survival analyses were used to assess the relationship between these predictors and the incidence of cardiovascular events (CVE). RESULTS: We followed-up 964 individuals within a median time of 5 years (4.7-5), representing 4377.1 persons-year. We found 73 patients presenting incident CVE, which corresponds to a rate of 8.2%. We found ABI less than 0.9 [hazard ratio, 2.2; 95% confidence interval (CI) 1.17-4.13, P value = 0.014] and SBI (hazard ratio, 2.9; 95% CI 1.47-5.58, P value = 0.002) independently associated with higher risk of incident CVE. The inclusion of both variables in a clinical model resulted in an increased discrimination of individuals with new CVE of 4.72%, according to the integrated discrimination index. CONCLUSION: Assessment of SBI and ABI less than 0.9 may refine the cardiovascular risk stratification in patients with hypertension.

MFG-E8 (LACTADHERIN): a novel marker associated with cerebral amyloid angiopathy.

Brain accumulation of amyloid-beta (Aß) is a crucial feature in Alzheimer´s disease (AD) and cerebral amyloid angiopathy (CAA), although the pathophysiological relationship between these diseases remains unclear. Numerous proteins are associated with Aß deposited in parenchymal plaques and/or cerebral vessels. We hypothesized that the study of these proteins would increase our understanding of the overlap and biological differences between these two pathologies and may yield new diagnostic tools and specific therapeutic targets. We used a laser capture microdissection approach combined with mass spectrometry in the APP23 transgenic mouse model of cerebral-ß-amyloidosis to specifically identify vascular Aß-associated proteins. We focused on one of the main proteins detected in the Aß-affected cerebrovasculature: MFG-E8 (milk fat globule-EGF factor 8), also known as lactadherin. We first validated the presence of MFG-E8 in mouse and human brains. Immunofluorescence and immunoblotting studies revealed that MFG-E8 brain levels were higher in APP23 mice than in WT mice. Furthermore, MFG-E8 was strongly detected in Aß-positive vessels in human postmortem CAA brains, whereas MFG-E8 was not present in parenchymal Aß deposits. Levels of MFG-E8 were additionally analysed in serum and cerebrospinal fluid (CSF) from patients diagnosed with CAA, patients with AD and control subjects. Whereas no differences were found in MFG-E8 serum levels between groups, MFG-E8 concentration was significantly lower in the CSF of CAA patients compared to controls and AD patients. Finally, in human vascular smooth muscle cells MFG-E8 was protective against the toxic effects of the treatment with the Aß40 peptide containing the Dutch mutation. In summary, our study shows that MFG-E8 is highly associated with CAA pathology and highlights MFG-E8 as a new CSF biomarker that could potentially be used to differentiate cerebrovascular Aß pathology from parenchymal Aß deposition.

New candidate blood biomarkers potentially associated with white matter hyperintensities progression.

We aimed to discover blood biomarkers associated with longitudinal changes in white matter hyperintensities (WMH). This study was divided into a discovery phase and a replication phase. Subjects in both studies were patients with hypertension, aged 50-70, who underwent two magnetic resonance imaging (MRI) sessions and blood extractions over a 4-year follow-up period. In the discovery phase, we screened 1305 proteins in 12 subjects with WMH progression and in 12 matched control subjects. We found that 41 proteins were differentially expressed: 13 were upregulated and 28 were downregulated. We subsequently selected three biomarkers for replication in baseline and follow-up samples in 80 subjects with WMH progression and in 80 control subjects. The selected protein candidates for the replication were MMP9 (matrix metalloproteinase-9), which was higher in cases, MET (hepatocyte growth factor receptor) and ASAH2 (neutral ceramidase), which were both lower in cases of WMH progression. Baseline biomarker concentrations did not predict WMH progression. In contrast, patients with WMH progression presented a steeper decline in MET over time. Furthermore, cases showed higher MMP9 and lower ASAH2 levels than controls at the follow-up. These results indicate that MMP9, MET, and ASAH2 are potentially associated with the progression of WMH, and could therefore be interesting candidates to validate in future studies.

Circulating AQP4 Levels in Patients with Cerebral Amyloid Angiopathy-Associated Intracerebral Hemorrhage.

Cerebral amyloid angiopathy (CAA) is a major cause of lobar intracerebral hemorrhage (ICH) in elderly patients. Growing evidence suggests a potential role of aquaporin 4 (AQP4) in amyloid-beta-associated diseases, including CAA pathology. Our aim was to investigate the circulating levels of AQP4 in a cohort of patients who had suffered a lobar ICH with a clinical diagnosis of CAA. AQP4 levels were analyzed in the serum of 60 CAA-related ICH patients and 19 non-stroke subjects by enzyme-linked immunosorbent assay (ELISA). The CAA-ICH cohort was divided according to the time point of the functional outcome evaluation: mid-term (12 ± 18.6 months) and long-term (38.5 ± 32.9 months) after the last ICH. Although no differences were found in AQP4 serum levels between cases and controls, lower levels were found in CAA patients presenting specific hemorrhagic features such as ≥2 lobar ICHs and ≥5 lobar microbleeds detected by magnetic resonance imaging (MRI). In addition, CAA-related ICH patients who presented a long-term good functional outcome had higher circulating AQP4 levels than subjects with a poor outcome or controls. Our data suggest that AQP4 could potentially predict a long-term functional outcome and may play a protective role after a lobar ICH.

Nursing Technologies Creativity as an Expression of Caring: A Grounded Theory Study.

Caring expression in nursing is rapidly changing to include the use of sophisticated healthcare technologies. Unfortunately, few nurses participate in developing healthcare technologies. The current study aimed to generate a theory of nursing grounded in the phenomenon of nursing technologies creativity in nursing practice. The study design used a constructivist grounded theory. Sixteen Indonesian nurses selected by purposive sampling were interviewed in-depth. Data analysis used constant comparative analysis through Charmaz's coding process. This study generated two core conceptual categories that included technological creativity and drivers for technological development. Five theoretical statements were developed leading to the Technological Creativity as Caring in Nursing Theory. This theory is a middle-range theory that focuses on technological creativity to express caring for patients, nurses, and management in nursing practice.

Ambulatory Blood Pressure Levels in the Prediction of Progression of Cerebral Small Vessel Disease.

OBJECTIVES: We aimed to study the value of ambulatory blood pressure monitoring (ABPM) in predicting the global progression of cerebral small vessel disease (cSVD). DESIGN: Longitudinal cohort study. SETTING: Data from the population-based Investigating Silent Strokes in Hypertensives study. PARTICIPANTS: Individuals with hypertension who were 50 to 70 years of age and stroke free at baseline. In baseline and follow-up visits, patients underwent magnetic resonance imaging and ABPM. MEASUREMENTS: Ambulatory systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels were studied as continuous variables and dichotomized according to good or poor control on the basis of 125/75 (24 hours), 130/80 (day), and 110/65 (night) mm Hg cutoff values. Whole cSVD progression was qualitatively scored with 1 point when an incident lesion (incident lacunar infarcts, deep cerebral microbleeds, white matter hyperintensities, and basal ganglia enlarged perivascular spaces) was detected. The score ranged from 0 to 4. RESULTS: We followed up 233 participants with a median age of 65 years within 4 years. A total of 61 (26.2%) and 23 (9.9%) subjects showed cSVD progression in one and two or more markers, respectively. Baseline ambulatory SBP and DBP and nighttime pulse pressure (PP) values were positively correlated with the number of incident cSVD lesions. Interestingly, patients without incident lesions showed greater differences between office and ambulatory BP, thus suggesting an increased white coat effect. Poor DBP control, nighttime PP, and DBP white coat effect were independently associated with cSVD progression. The inclusion of these metrics in a clinical model resulted in a significant increase in the prediction of incident lesions (integrated discrimination improvement = 9.09%; P value <.001). CONCLUSION: ABPM may help assess cSVD risk of progression, especially by the identification of poor BP control, masked hypertension, and increased nighttime PP. J Am Geriatr Soc 68:2232-2239, 2020.

Kidney function changes and their relation with the progression of cerebral small vessel disease and cognitive decline.

AIMS: We aimed to study whether worsening in markers of kidney function parallels the progression in cerebral small vessel disease (cSVD) and cognitive decline. METHODS: Data from the ISSYS (Investigating Silent Strokes in Hypertensives Study), a longitudinal population-based study in hypertensives aged 50-70 and dementia and stroke-free at baseline. At both visits, patients underwent a brain MRI, a cognitive diagnosis (normal aging or mild cognitive impairment, [MCI]) and urine and blood sampling collection. We assessed the incidence of infarcts and cerebral microbleeds, and the progression of white matter hyperintensities at periventricular (PVH) and deep areas. We determined changes in albumin-creatinine ratio and estimated glomerular filtration rate (eGFR). These changes were dichotomized into microalbuminuria at follow-up -either in subjects with or without baseline microalbuminuria- and significant decline in eGFR -lowest quintile of eGFR change (-10.57 mL/min/1.73m2)-. RESULTS: 360 patients were followed-up for 4 years. 80 (23%) patients presented microalbuminuria at follow-up and 68 (20.1%) experienced a significant eGFR decline. Considering cSVD change, we found a relationship between microalbuminuria at follow-up and progression in PVH (ß = 0.31, P-value = .01). Regarding cognitive decline, presence of microalbuminuria at follow-up related to a steeper decrease in memory function (ß = -0.36, P-value<.01). Moreover, patients with significant decline in eGFR were at higher risk of incident MCI (OR = 3.54, P-value = .02). These associations were independent of progression of cSVD. CONCLUSION: The worsening in markers of kidney function paralleled the decrease in cognition and the progression of cSVD, and this may be explained by common shared underlying risk factors.

Cognitive Impact of Cerebral Small Vessel Disease Changes in Patients With Hypertension.

Hypertension is one of the principal risk factors for cerebral small vessel disease progression and cognitive impairment. We aimed to investigate how changes in cerebral small vessel disease lesions relate to cognitive decline and incident mild cognitive impairment in hypertensive patients. Data were obtained from the ISSYS cohort (Investigating Silent Strokes in Hypertensives: a Magnetic Resonance Imaging Study)-a longitudinal population-based study on hypertensive patients aged 50 to 70 years without dementia and stroke at baseline. Patients underwent a brain magnetic resonance imaging, a cognitive screening test, and cognitive diagnosis (normal aging or mild cognitive impairment) at baseline and follow-up. We evaluated incident lacunar infarcts and cerebral microbleeds. Changes in the periventricular and deep white matter hyperintensities (WMH) were qualitatively defined as none, minor, or marked. We followed up 345 patients (median age, 65 [61-68]; 55.4% men) for 3.95 (3.83-4.34) years. Incident mild cognitive impairment was diagnosed in 9.1% of the sample. Considering the progression of cerebral small vessel disease, the prevalence of incident infarcts was 6.1% and that of incident cerebral microbleeds was 5.5%; progression of periventricular WMH was 22% and that of deep WMH was 48%. Patients with marked progression of periventricular WMH showed a significant decrease in global cognition compared with patients without progression (adjusted mean [SE], -0.519 [0.176] versus 0.057 [0.044], respectively; P value=0.004) and a higher risk of incident mild cognitive impairment (OR, 6.184; 95% CI, 1.506-25.370; P value=0.011). Therefore, our results indicate that hypertensive patients with progression of periventricular WMH have higher odds of cognitive impairment, even in the early stages of cognitive decline.

Pattern of infection with Parapharyngodon riojensis Ramallo, Bursey, Goldberg 2002 (Nematoda: Pharyngodonidae) in the lizard Phymaturus extrilidus from Puna region, Argentina

The pattern of infection with the nematode Parapharyngodon riojensis in the lizard Phymaturus extrilidus in a Puna area, central-west Argentina was studied. No significant prevalence differences were found between sexes or seasons sampled. However, there were differences in mean intensity between the summer (dry period) and autumn (wet period) seasons. Mean intensity was higher in the moistest season, associated with low body condition in P. extrilidus. The genus Parapharyngodon has a direct life cycle, and environmental moisture could favor higher intensity in the rainy period. The present study provides the first data on the parasitic ecology of P. extrilidus from Argentina.