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Background: Complexity and change in health care environments, the rapid pace of knowledge generation, and changing education policy have led to national calls for change in nursing education. Many nursing programs have adopted a concept-based curriculum (CBC) to address these challenges. Yet, much is still uncertain about the outcomes and effectiveness of CBC, which requires large scale, time-consuming, and resource-intensive change. Method: This integrative review assesses the outcomes of CBC in nursing higher education with a focus on the comparison of CBC to traditional curricula. Results: The four relevant themes that emerged after an extensive literature review were critical thinking/clinical judgment, NCLEX-RN© (National Council Licensure Examination for Registered Nurses) pass rates, graduation rates, and student satisfaction scores. Overall, the evidence base is not robust. A valid and reliable tool to measure clinical judgment is needed. The review specifically addresses CBC effects on student critical thinking and clinical judgment, traditional outcome metrics, (NCLEX-RN success, graduation rates, and student satisfaction), and other perceived benefits. Conclusion: The authors found promising results on the effect CBC may have on critical thinking and clinical judgment and other perceived benefits. Findings were inconclusive on traditional outcome metrics. [J Nurs Educ. 2024;63(11):725–729.] [ABSTRACT FROM AUTHOR]

Context. Solar active regions (ARs) are often surrounded by dark large areas of reduced emission compared to the quiet Sun, observed at various wavelengths corresponding to the chromosphere, transition region (TR), and corona, known as dark halos (DHs). The mechanisms behind the darker emission of DHs remain unclear and merit a wider scope of study. Aims. This study aims to investigate for the first time the fine structure of a DH observed by the EUV High Resolution Imager (HRIEUV) on board the ESA's Solar Orbiter (SO) mission and its appearance in the TR. Aims. We utilized the extensive 1 hour dataset from SO on 19 March 2022, which includes high-resolution observations of NOAA 12967 and part of the surrounding DH. We analyzed the dynamics of the HRIEUV DH fine structure and its appearance in the HRILyα image. We also analyzed the Spectral Imaging of the Coronal Environment (SPICE) Lyβ, C III, N VI, O VI, and Ne VIII lines, which sample the TR in the log T(K) ∼ 4.0–5.8 range. This analysis was complemented with a simultaneous BLOS magnetogram taken by the High Resolution Telescope (HRT). Methods. We report the presence of a peculiar fine structure that has not been observed for the quiet Sun. It is characterized by combined bright EUV bundles and dark regions, arranged and interconnected in such a way that they cannot be clearly separated. They form a spatial continuum extending approximately radially from the AR core, suggesting a deep connection between the DH and the AR. Additionally, we find that the bright EUV bundles are observed in all the SPICE TR lines and the HRILyα band and present photospheric BLOS footprints in the HRT magnetogram. This spatial correlation indicates that the origin of the 174 Å DH may lie in the low atmosphere: the photosphere and chromosphere. [ABSTRACT FROM AUTHOR]

Background: Global life expectancy is rising, with the 60 + age group projected to hit 2 billion by 2050. Aging impacts the immune system. A notable marker of immune system aging is the presence of Aging-Related Immune Cell Phenotypes (ARIPs). Despite their importance, links between immune cell phenotypes including ARIPs and mortality are underexplored. We prospectively investigated 16 different immune cell phenotypes using flow cytometry and IL-6 in relation to survival outcome among dementia-free Framingham Heart Study (FHS) offspring cohort participants who attended the seventh exam (1998–2001). Results: Among 996 participants (mean age 62 years, range 40 to 88 years, 52% female), the 19-year survival rate was 65%. Adjusting for age, sex, and cytomegalovirus (CMV) serostatus, higher CD4/CD8 and Tc17/CD8 + Treg ratios were significantly associated with lower all-cause mortality (HR: 0.86 [0.76–0.96], 0.84 [0.74–0.94], respectively), while higher CD8 regulatory cell levels (CD8 + CD25 + FoxP3 +) were associated with increased all-cause mortality risk (HR = 1.17, [1.03–1.32]). Elevated IL-6 levels correlated with higher all-cause, cardiovascular, and non-cardiovascular mortality (HR = 1.43 [1.26–1.62], 1.70 [1.31–2.21], and 1.36 [1.18–1.57], respectively). However, after adjusting for cardiovascular risk factors and prevalent cancer alongside age, sex, and CMV, immune cell phenotypes were no longer associated with mortality in our cohort. Nonetheless, IL-6 remained significantly associated with all-cause and cardiovascular mortality (HRs: 1.3 [1.13–1.49], 1.5 [1.12–1.99], respectively). Conclusions: In 19-year follow-up, higher Tc17/CD8 + Treg and CD4/CD8 ratios were associated with lower all-cause mortality, while the CD8 + CD25 + FoxP3 + (CD8 + Treg) phenotype showed increased risk. Elevated IL-6 levels consistently correlated with amplified mortality risks. These findings highlight the links between immune phenotypes and mortality, suggesting implications for future research and clinical considerations. [ABSTRACT FROM AUTHOR]

Background: Prolonged preoperative fasting may worsen postoperative outcomes. Cardiac surgery has higher perioperative risk, and longer fasting periods may be not well-tolerated. We analysed the postoperative metabolic and hemodynamic variables in patients undergoing elective coronary artery bypass grafting (CABG) according to their morning or afternoon schedule. Methods: Single-centre retrospective study at University teaching hospital (1-year data collection from electronic medical records). Using a mixed-effects linear regression model adjusted for several covariates, we compared metabolic (lactatemia, pH, and base deficit [BD]) and haemodynamic values (patients on vasoactive support, and vasoactive inotropic score [VIS]) at 7 prespecified time-points (admission to intensive care, and 1st, 3rd, 6th, 12th, 18th, and 24th postoperative hours). Results: 339 patients (n = 176 morning, n = 163 afternoon) were included. Arterial lactatemia and BD were similar (overall P = 0.11 and P = 0.84, respectively), while pH was significantly lower in the morning group (overall P < 0.05; mean difference -0.01). Postoperative urine output, fluid balance, mean arterial pressure, and central venous pressure were similar (P = 0.59, P = 0.96, P = 0.58 and P = 0.53, respectively). A subgroup analysis of patients with diabetes (n = 54 morning, n = 45 afternoon) confirmed the same findings. The VIS values and the proportion of patients on vasoactive support was higher in the morning cases at the 18th (P = 0.002 and p=0.04, respectively) and 24th postoperative hours (P = 0.003 and P = 0.04, respectively). Mean intensive care length of stay was 1.94 ± 1.36 days versus 2.48 ± 2.72 days for the afternoon and morning cases, respectively (P = 0.02). Conclusions: Patients undergoing elective CABG showed similar or better metabolic and hemodynamic profiles when scheduled for afternoon surgery. [ABSTRACT FROM AUTHOR]

Simulation for airway management allows for acquaintance with new devices and techniques. Endotracheal intubation (ETI), most commonly performed with direct laryngoscopy (DL) or video laryngoscopy (VLS), can be achieved also with combined laryngo-bronchoscopy intubation (CLBI). Finally, an articulating video stylet (ProVu) has been recently introduced. A single-center observational cross-sectional study was performed in a normal simulated airway scenario comparing DL, VLS-Glidescope, VLS-McGrath, CLBI and ProVu regarding the success rate (SR) and corrected time-to-intubation (cTTI, which accounts for the SR). Up to three attempts/device were allowed (maximum of 60 s each). Forty-two consultants with no experience with ProVu participated (15 ± 9 years after training completion). The DL was significantly faster (cTTI) than all other devices (p = 0.033 vs. VLSs, and p < 0.001 for CLBI and Provu), no differences were seen between the two VLSs (p = 0.775), and the VLSs were faster than CLBI and ProVu. Provu had a faster cTTI than CLBI (p = 0.004). The DL and VLSs showed similar SRs, and all the laryngoscopes had a higher SR than CLBI and ProVu at the first attempt. However, by the third attempt, the SR was not different between the DL/VLSs and ProVu (p = 0.241/p = 0.616); ProVu was superior to CLBI (p = 0.038). In consultants with no prior experience, ProVu shows encouraging results compared to DL/VLSs under simulated normal airway circumstances and further studies are warranted. [ABSTRACT FROM AUTHOR]

Sarcopenia is associated with NAFLD. It is unknown if the association is explained by shared risk factors. Our study sought to investigate the association between liver fat and sarcopenia in our cohort. Liver fat was measured on CT between 2008 and 2011. We excluded heavy alcohol use and missing covariates. Muscle mass in a subset (n = 485) was measured by 24 h urinary creatinine. Physical function was defined by h strength and walking speed. Sarcopenia was defined as low muscle mass and/or low physical function. We created multivariable-adjusted regression models to evaluate cross-sectional associations between liver fat and low muscle mass, grip strength, and walking speed. The prevalence of hepatic steatosis was 30% (n = 1073; 58.1% women; mean age 65.8 ± 8.6 years). There was a significant positive association between liver fat and muscle mass in linear regression models. The association was not significant after adjusting for BMI. The odds of sarcopenia increased by 28% for each SD in liver fat (OR 1.28; 95% CI 1.02, 1.60) and persisted after accounting for confounders in multivariable-adjusted models (OR 1.30, 95% CI 1.02, 1.67). Further studies are needed to determine if there is a causal relationship between liver fat and sarcopenia and whether treatment of sarcopenia improves liver fat. [ABSTRACT FROM AUTHOR]

Background: The aim of our study was to investigate the prevalence of perioperative hypotension after spinal anesthesia for cesarean section using non-invasive continuous hemodynamic monitoring and its correlation with neonatal well-being. Methods: We included 145 patients. Spinal anesthesia was performed with a combination of hyperbaric bupivacaine 0.5% (according to a weight/height scheme) and fentanyl 20 μg. Hypotension was defined as a mean arterial pressure (MAP) < 65 mmHg or <60 mmHg. We also evaluated the impact of hypotension on neonatal well-being. Results: Perioperative maternal hypotension occurred in 54.5% of cases considering a MAP < 65 mmHg and in 42.1% with the more conservative cut-off (<60 mmHg). Severe neonatal acidosis occurred in 1.4% of neonates, while an Apgar score ≥ 9 was observed in 95.9% at 1 min and 100% at 5 min. Conclusions: Continuous non-invasive hemodynamic monitoring allowed an early detection of maternal hypotension leading to a prompt treatment with satisfactory results considering neonatal well-being. [ABSTRACT FROM AUTHOR]

While frailty is a prominent risk factor in an aging population, the underlying biology of frailty is incompletely described. Here, we integrate 979 circulating proteins across a wide range of physiologies with 12 measures of frailty in a prospective discovery cohort of 809 individuals with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation. Our aim was to characterize the proteomic architecture of frailty in a highly susceptible population and study its relation to clinical outcome and systems‐wide phenotypes to define potential novel, clinically relevant frailty biology. Proteomic signatures (specifically of physical function) were related to post‐intervention outcome in AS, specifying pathways of innate immunity, cell growth/senescence, fibrosis/metabolism, and a host of proteins not widely described in human aging. In published cohorts, the "frailty proteome" displayed heterogeneous trajectories across age (20–100 years, age only explaining a small fraction of variance) and were associated with cardiac and non‐cardiac phenotypes and outcomes across two broad validation cohorts (N > 35,000) over ≈2–3 decades. These findings suggest the importance of precision biomarkers of underlying multi‐organ health status in age‐related morbidity and frailty. [ABSTRACT FROM AUTHOR]

Inflammatory protein biomarkers induced by immune responses have been associated with cognitive decline and the pathogenesis of Alzheimer's disease (AD). Here, we investigate associations between a panel of inflammatory biomarkers and cognitive function and incident dementia outcomes in the well‐characterized Framingham Heart Study Offspring cohort. Participants aged ≥40 years and dementia‐free at Exam 7 who had a stored plasma sample were selected for profiling using the OLINK proteomics inflammation panel. Cross‐sectional associations of the biomarkers with cognitive domain scores (N = 708, 53% female, 22% apolipoprotein E (APOE) ε4 carriers, 15% APOE ε2 carriers, mean age 61) and incident all‐cause and AD dementia during up to 20 years of follow‐up were tested. APOE genotype‐stratified analyses were performed to explore effect modification. Higher levels of 12 and 3 proteins were associated with worse executive function and language domain factor scores, respectively. Several proteins were associated with more than one cognitive domain, including IL10, LIF‐R, TWEAK, CCL19, IL‐17C, MCP‐4, and TGF‐alpha. Stratified analyses suggested differential effects between APOE ε2 and ε4 carriers: most ε4 carrier associations were with executive function and memory domains, whereas most ε2 associations were with the visuospatial domain. Higher levels of TNFB and CDCP1 were associated with higher risks of incident all‐cause and AD dementia. Our study found that TWEAK concentration was associated both with cognitive function and risks for AD dementia. The association of these inflammatory biomarkers with cognitive function and incident dementia may contribute to the discovery of therapeutic interventions for the prevention and treatment of cognitive decline. [ABSTRACT FROM AUTHOR]

Mitochondria carry their own circular genome and disruption of the mitochondrial genome is associated with various aging-related diseases. Unlike the nuclear genome, mitochondrial DNA (mtDNA) can be present at 1000 s to 10,000 s copies in somatic cells and variants may exist in a state of heteroplasmy, where only a fraction of the DNA molecules harbors a particular variant. We quantify mtDNA heteroplasmy in 194,871 participants in the UK Biobank and find that heteroplasmy is associated with a 1.5-fold increased risk of all-cause mortality. Additionally, we functionally characterize mtDNA single nucleotide variants (SNVs) using a constraint-based score, mitochondrial local constraint score sum (MSS) and find it associated with all-cause mortality, and with the prevalence and incidence of cancer and cancer-related mortality, particularly leukemia. These results indicate that mitochondria may have a functional role in certain cancers, and mitochondrial heteroplasmic SNVs may serve as a prognostic marker for cancer, especially for leukemia. Mitochondrial DNA is known to exhibit heterogeneity of variants, even within a single cell. Here, the authors assessed this heteroplasmy of mitochondrial DNA within the UK Biobank cohort and showed that the presence of heteroplasmy and a functional score generated from heteroplasmic SNVs were associated with all-cause mortality and certain cancers. [ABSTRACT FROM AUTHOR]

Introduction: Cardiometabolic risk factors and epigenetic patterns, increased in physically inactive individuals, are associated with an accelerated brain aging process. Objective: To determine whether cardiometabolic risk factors and epigenetic patterns mediate the association of physical inactivity with unfavorable brain morphology. Methods: We included dementia and stroke free participants from the Framingham Heart Study Third Generation and Offspring cohorts who had accelerometery and brain MRI data (n = 2,507, 53.9% women, mean age 53.9 years). We examined mediation by the 2017-revised Framingham Stroke Risk Profile (FSRP, using weights for age, cardiovascular disease, atrial fibrillation, diabetes and smoking status, antihypertension medications, and systolic blood pressure) and the homeostatic model of insulin resistance (HOMA-IR) in models of the association of physical inactivity with brain aging, adjusting for age, age-squared, sex, accelerometer wear time, cohort, time from exam-to-MRI, and season. We similarly assessed mediation by an epigenetic age-prediction algorithm, GrimAge, in a smaller sample of participants who had DNA methylation data (n = 1,418). Results: FSRP and HOMA-IR explained 8.3–20.5% of associations of higher moderate-to-vigorous physical activity (MVPA), higher steps, and lower sedentary time with higher brain volume. Additionally, FSRP and GrimAge explained 10.3–22.0% of associations of physical inactivity with lower white matter diffusivity and FSRP explained 19.7% of the association of MVPA with lower free water accumulation. Conclusion: Our results suggest that cardiometabolic risk factors and epigenetic patterns partially mediate the associations of physical inactivity with lower brain volume, higher white matter diffusivity, and aggregation of free water in the extracellular compartments of the brain. [ABSTRACT FROM AUTHOR]

Background Dysfunction in blood vessel dynamics may contribute to changes in muscle measures. Therefore, we examined associations of vascular health measures with grip strength and gait speed in adults from the Framingham Heart Study. Methods The cross-sectional study (1998–2001) included participants with 1 measure of grip strength (kg, dynamometer) or gait speed (4-m walk, m/s) and at least 1 measure of aortic stiffness (carotid–femoral pulse wave velocity, brachial pulse pressure, and brachial flow pulsatility index) or brachial artery structure and function (resting flow velocity, resting brachial artery diameter, flow-mediated dilation %, hyperemic brachial blood flow velocity, and mean arterial pressure [MAP]) assessed by tonometry and brachial artery ultrasound. The longitudinal study included participants with ≥1 follow-up measurement of gait speed or grip strength. Multivariable linear regression estimated the association of 1 standard deviation (SD) higher level of each vascular measure with annualized percent change in grip strength and gait speed, adjusting for covariates. Results In cross-sectional analyses (n = 2 498, age 61 ± 10 years; 56% women), higher resting brachial artery diameter (β ± standard error [ SE ] per 1 SD : 0.59 ± 0.24, p =.01) and MAP (β ± SE : 0.39 ± 0.17, p =.02) were associated with higher grip strength. Higher brachial pulse pressure (β ± SE : −0.02 ± 0.01, p =.07) was marginally associated with slower gait speed. In longitudinal analyses (n = 2 157), higher brachial pulse pressure (β ± SE : −0.19 ± 0.07, p =.005), was associated with slowing of gait speed but not with grip strength. Conclusions Higher brachial artery pulse pressure (measure of aortic stiffness) was associated with loss of physical function over ~11 years, although we found no evidence that microvascular function contributed to the relation. [ABSTRACT FROM AUTHOR]

Over the last fifteen years, with the approval of the first molecular treatments, a breakthrough era has begun for patients with cystic fibrosis (CF), the rare genetic disease caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). These molecules, known as CFTR modulators, have led to unprecedented improvements in the lung function and quality of life of most CF patients. However, the efficacy of these drugs is still suboptimal, and the clinical response is highly variable even among individuals bearing the same mutation. Furthermore, not all patients carrying rare CFTR mutations are eligible for CFTR modulator therapies, indicating the need for alternative and/or add-on therapeutic approaches. Because the second messenger 3′,5′-cyclic adenosine monophosphate (cAMP) represents the primary trigger for CFTR activation and a major regulator of different steps of the life cycle of the channel, there is growing interest in devising ways to fine-tune the cAMP signaling pathway for therapeutic purposes. This review article summarizes current knowledge regarding the role of cAMP signalosomes, i.e., multiprotein complexes bringing together key enzymes of the cAMP pathway, in the regulation of CFTR function, and discusses how modulating this signaling cascade could be leveraged for therapeutic intervention in CF. [ABSTRACT FROM AUTHOR]

We analyzed state-of-the-art observations of the solar atmosphere to investigate the dependence of the Ca ii K brightness of several solar features on spectral bandwidth and spatial resolution of the data. In particular, we study data obtained at the Swedish Solar Telescope with the Crisp Imaging Spectropolarimeter and Chromospheric Imaging Spectrometer instruments. The analyzed data, which are characterized by a spectral bandwidth of 0.12 Å and a spatial resolution of 0.″078, were acquired close to the disk center by targeting a quiet-Sun area and an active region. We convolved the original observations with Gaussian kernels to degrade their spectral bandwidth and spatial resolution to the instrumental characteristics of the most prominent series of Ca ii K observations available to date. We then studied the effect of data degradation on the observed regions and on parameters derived from Ca ii K line measurements that are largely employed as diagnostics of the solar and stellar chromospheres. We find that the effect of degrading the spectral resolution of Ca ii K observations and line profiles depends on both the employed bandwidth and observed solar region. Besides, we found that the spatial degradation impacts the data characterized by a broad bandwidth to a larger extent compared to those acquired with a narrow band. However, the appearance of the observed solar regions is only slightly affected by the spatial resolution of data with bandwidths up to 1 Å and in the range [3,10] Å. Finally, we derived relationships that can be used to intercalibrate results from observations taken with different instruments in diverse regions of the solar atmosphere. [ABSTRACT FROM AUTHOR]

In patients undergoing caesarean section (CS) with spinal anesthesia, the superiority of one intrathecal opioid over another one is not fully established. In order to investigate this, we joined the PAIN OUT Project (NCT02083835) for a two-year period. We surveyed patients undergoing elective CS with intrathecal anesthesia. Patients were asked to complete an anonymous questionnaire. Primary outcomes were: worst pain experienced, time spent in severe pain, relief received by treatment, satisfaction about pain management, wish for more pain treatment. We included 144 patients. The two main pain management combinations used were: bupivacainemorphine (B-M, n=100) and bupivacaine-fentanyl (B-F, n=32). There were no differences in any of the primary outcomes between the groups. The B-F population received more intravenous/intramuscular opioids during the intraoperative (p<0.01) and the postoperative (p<0.001) period. The choice of morphine or fentanyl as adjunct to local anesthetic in spinal anesthesia for CS does not affect the patient's experience with regards to pain management. [ABSTRACT FROM AUTHOR]

Long-term use of digital devices is critical for successful clinical or research use, but digital health studies are challenged by a rapid drop-off in participation. A nested e-cohort (eFHS) is embedded in the Framingham Heart Study and uses three system components: a new smartphone app, a digital blood pressure (BP) cuff, and a smartwatch. This study aims to identify factors associated with the use of individual eFHS system components over 1-year. Among 1948 eFHS enrollees, we examine participants who returned surveys within 90 days (n = 1918), and those who chose to use the smartwatch (n = 1243) and BP cuff (n = 1115). For each component, we investigate the same set of candidate predictors for usage and use generalized linear mixed models to select predictors (P < 0.1, P value from Z test statistic), adjusting for age, sex, and time (app use: 3-month period, device use: weekly). A multivariable model with the predictors selected from initial testing is used to identify factors associated with use of components (P < 0.05, P value from Z test statistic) adjusting for age, sex, and time. In multivariable models, older age is associated with higher use of all system components. Female sex and higher education levels are associated with higher completion of app-based surveys whereas higher scores for depressive symptoms, and lower than excellent self-rated health are associated with lower use of the smartwatch over the 12-month follow-up. Our findings show that sociodemographic and health related factors are significantly associated with long-term use of digital devices. Future research is needed to test interventional strategies focusing on these factors to evaluate improvement in long-term engagement. [ABSTRACT FROM AUTHOR]

Background: Extracorporeal membrane oxygenation (ECMO) represents an advanced option for supporting refractory respiratory and/or cardiac failure. Systemic anticoagulation with unfractionated heparin (UFH) is routinely used. However, patients with bleeding risk and/or heparin‐related side effects may necessitate alternative strategies: among these, nafamostat mesilate (NM) has been reported. Methods: We conducted a systematic literature search (PubMed and EMBASE, updated 12/08/2021), including all studies reporting NM anticoagulation for ECMO. We focused on reasons for starting NM, its dose and the anticoagulation monitoring approach, the incidence of bleeding/thrombosis complications, the NM‐related side effects, ECMO weaning, and mortality. Results: The search revealed 11 relevant findings, all with retrospective design. Of these, three large studies reported a control group receiving UFH, the other were case series (n = 3) or case reports (n = 5). The main reason reported for NM use was an ongoing or high risk of bleeding. The NM dose varied largely as did the anticoagulation monitoring approach. The average NM dose ranged from 0.46 to 0.67 mg/kg/h, but two groups of authors reported larger doses when monitoring anticoagulation with ACT. Conflicting findings were found on bleeding and thrombosis. The only NM‐related side effect was hyperkalemia (n = 2 studies) with an incidence of 15%–18% in patients anticoagulated with NM. Weaning and survival varied across studies. Conclusion: Anticoagulation with NM in ECMO has not been prospectively studied. While several centers have experience with this approach in high‐risk patients, prospective studies are warranted to establish the optimal space of this approach in ECMO. [ABSTRACT FROM AUTHOR]

Inflammatory cytokines and chemokines related to the innate and adaptive immune system have been linked to neuroinflammation in Alzheimer's Disease, dementia, and cognitive disorders. We examined the association of 11 plasma proteins (CD14, CD163, CD5L, CD56, CD40L, CXCL16, SDF1, DPP4, SGP130, sRAGE, and MPO) related to immune and inflammatory responses with measures of cognitive function, brain MRI and dementia risk. We identified Framingham Heart Study Offspring participants who underwent neuropsychological testing (n = 2358) or brain MRI (n = 2100) within five years of the seventh examination where a blood sample for quantifying the protein biomarkers was obtained; and who were followed for 10 years for incident all-cause dementia (n = 1616). We investigated the association of inflammatory biomarkers with neuropsychological test performance and brain MRI volumes using linear mixed effect models accounting for family relationships. We further used Cox proportional hazards models to examine the association with incident dementia. False discovery rate p-values were used to account for multiple testing. Participants included in the neuropsychological test and MRI samples were on average 61 years old and 54% female. Participants from the incident dementia sample (average 68 years old at baseline) included 124 participants with incident dementia. In addition to CD14, which has an established association, we found significant associations between higher levels of CD40L and myeloperoxidase (MPO) with executive dysfunction. Higher CD5L levels were significantly associated with smaller total brain volumes (TCBV), whereas higher levels of sRAGE were associated with larger TCBV. Associations persisted after adjustment for APOE ε4 carrier status and additional cardiovascular risk factors. None of the studied inflammatory biomarkers were significantly associated with risk of incident all-cause dementia. Higher circulating levels of soluble CD40L and MPO, markers of immune cell activation, were associated with poorer performance on neuropsychological tests, while higher CD5L, a key regulator of inflammation, was associated with smaller total brain volumes. Higher circulating soluble RAGE, a decoy receptor for the proinflammatory RAGE/AGE pathway, was associated with larger total brain volume. If confirmed in other studies, this data indicates the involvement of an activated immune system in abnormal brain aging. [ABSTRACT FROM AUTHOR]

Cerebrovascular ischemia is a common clinical disease encompassing a series of complex pathophysiological processes in which oxidative stress plays a major role. The present study aimed to evaluate the effects of Dexmedetomidine, Clonidine, and Propofol in a model of hypoxia/reoxygenation injury. Microglial cells were exposed to 1%hypoxia for 3 h and reoxygenated for 3 h, and oxidative stress was measured by ROS formation and the expression of inflammatory process genes. Mitochondrial dysfunction was assessed by membrane potential maintenance and the levels of various metabolites involved in energetic metabolism. The results showed that Propofol and α2-agonists attenuate the formation of ROS during hypoxia and after reoxygenation. Furthermore, the α2-agonists treatment restored membrane potential to values comparable to the normoxic control and were both more effective than Propofol. At the same time, Propofol, but not α2-agonists, reduces proliferation (Untreated Hypoxia = 1.16 ± 0.2, Untreated 3 h Reoxygenation = 1.28 ± 0.01 vs. Propofol hypoxia = 1.01 ± 0.01 vs. Propofol 3 h Reoxygenation = 1.12 ± 0.03) and microglial migration. Interestingly, all of the treatments reduced inflammatory gene and protein expressions and restored energy metabolism following hypoxia/reoxygenation (ATP content in hypoxia/reoxygenation 3 h: Untreated = 3.11 ± 0.8 vs. Propofol = 7.03 ± 0.4 vs. Dexmedetomidine = 5.44 ± 0.8 vs. Clonidine = 7.70 ± 0.1), showing that the drugs resulted in a different neuroprotective profile. In conclusion, our results may provide clinically relevant insights for neuroprotective strategies in intensive care units. [ABSTRACT FROM AUTHOR]

Objective: Women have a higher lifetime risk of Alzheimer's disease (AD) than men. Among cognitively normal (CN) older adults, women exhibit elevated tau positron emission tomography (PET) signal compared with men. We explored whether menopause exacerbates sex differences in tau deposition in middle‐aged adults. Methods: 328 CN participants from the Framingham Study (mean age = 57 years (±10 years), 161 women, of whom, 104 were post‐menopausal) underwent tau and β‐amyloid (Aβ)‐PET neuroimaging. We examined global Aβ‐PET, and tau‐PET signal in 5 regions identified a priori as demonstrating significant sex differences in older adults (in temporal, inferior parietal, middle frontal, and lateral occipital regions). We examined sex and menopause status‐related differences in each region‐of‐interest, using linear regressions, as well as interactions with Aβ and APOEε4 genotype. Results: Women exhibited higher tau‐PET signal (p < 0.002), and global Aβ‐PET (p = 0.010), than men in inferior parietal, rostral middle frontal, and lateral occipital regions. Compared with age‐matched men, post‐menopausal women showed significantly higher tau‐PET signal in parieto‐occipital regions (p < 0.0001). By contrast, no differences in tau‐PET signal existed between pre‐menopausal women and men. Aβ‐PET was not associated with menopausal status or age. Neither Aβ‐PET nor APOEε4 status moderated sex or menopause associations with tau‐PET. Interpretation: Clear divergence in tauopathy between the sexes are apparent approximately 20 years earlier than previously reported. Menopause status moderated sex differences in Aβ and tau‐PET burden, with tau first appearing post‐menopause. Sex and menopause differences consistently appeared in middle frontal and parieto‐occipital regions but were not moderated by Aβ burden or APOEε4, suggesting that menopause‐related tau vulnerability may be independent of AD‐related pathways. ANN NEUROL 2022;92:11–22 [ABSTRACT FROM AUTHOR]

Background: Peripheral inflammation is associated with increased risk for dementia. Neutrophil to lymphocyte ratio (NLR), red cell distribution width (RDW), and mean platelet volume (MPV), are easily measured circulating blood cell phenotypes reflecting chronic peripheral inflammation, but their association with dementia status is unclear.Objective: We sought to investigate the cross-sectional association of these inflammatory measures with neuropsychological (NP) test performance, and brain magnetic resonance imaging (MRI) measures in the Framingham Heart Study (FHS) Offspring, Third-generation, and Omni cohorts.Methods: We identified FHS participants who attended an exam that included a complete blood cell count (CBC) and underwent NP testing (n = 3,396) or brain MRI (n = 2,770) within five years of blood draw. We investigated the association between NLR, RDW, and MPV and NP test performance and structural MRI-derived volumetric measurements using linear mixed effect models accounting for family relationships and adjusting for potential confounders.Results: Participants were on average 60 years old, 53% female, and about 80% attended some college. Higher NLR was significantly associated with poorer performance on visual memory, and visuospatial abilities, as well as with larger white matter hyperintensity volume. We also observed associations for higher RDW with poorer executive function and smaller total cerebral brain volume.Conclusion: Chronic peripheral inflammation as measured by NLR and RDW was associated with worse cognitive function, reduced brain volume, and greater microvascular disease in FHS participants. If confirmed in other samples, CBC may provide informative and cost-effective biomarkers of abnormal brain aging in the community. [ABSTRACT FROM AUTHOR]

Background: Non-genetic factors contribute to differences in diabetes risk across race/ethnic and socioeconomic groups, which raises the question of whether effects of predictors of diabetes are similar across populations. We studied diabetes incidence in the primarily non-Hispanic White Framingham Heart Study (FHS, N = 4066) and the urban, largely immigrant Hispanic Community Health Study/Study of Latinos (HCHS/SOL, N = 6891) Please check if the affiliations are captured and presented correctly.Methods: Clinical, behavioral, and socioeconomic characteristics were collected at in-person examinations followed by seven-day accelerometry. Among individuals without diabetes, Cox proportional hazards regression models (both age- and sex-adjusted, and then multivariable-adjusted for all candidate predictors) identified predictors of incident diabetes over a decade of follow-up, defined using clinical history or laboratory assessments.Results: Four independent predictors were shared between FHS and HCHS/SOL. In each cohort, the multivariable-adjusted hazard of diabetes increased by approximately 50% for every ten-year increment of age and every five-unit increment of body mass index (BMI), and was 50-70% higher among hypertensive than among non-hypertensive individuals (all P < 0.01). Compared with full-time employment status, the multivariable-adjusted hazard ratio (HR) and 95% confidence interval (CI) for part-time employment was 0.61 (0.37,1.00) in FHS and 0.62 (0.41,0.95) in HCHS/SOL. Moderate-to-vigorous physical activity (MVPA) was an additional predictor in common observed in age- and sex-adjusted models, which did not persist after adjustment for other covariates (compared with MVPA ≤ 5 min/day, HR for MVPA level ≥ 30 min/day was 0.48 [0.31,0.74] in FHS and 0.74 [0.56,0.97] in HCHS/SOL). Additional predictors found in sex- and age-adjusted analyses among the FHS participants included male gender and lower education, but these predictors were not found to be independent of others in multivariable adjusted models, nor were they associated with diabetes risk among HCHS/SOL adults.Conclusions: The same four independent predictors - age, body mass index, hypertension and employment status - were associated with diabetes risk across two disparate US populations. While the reason for elevated diabetes risk in full-time workers is unclear, the findings suggest that diabetes may be part of the work-related burden of disease. Our findings also support prior evidence that differences by gender and socioeconomic position in diabetes risk are not universally present across populations. [ABSTRACT FROM AUTHOR]

Cyclic adenosine 3′,5′-monophosphate (cAMP)–elevating agents, such as β2-adrenergic receptor (β2-AR) agonists and phosphodiesterase (PDE) inhibitors, remain a mainstay in the treatment of obstructive respiratory diseases, conditions characterized by airway constriction, inflammation, and mucus hypersecretion. However, their clinical use is limited by unwanted side effects because of unrestricted cAMP elevation in the airways and in distant organs. Here, we identified the A-kinase anchoring protein phosphoinositide 3-kinase γ (PI3Kγ) as a critical regulator of a discrete cAMP signaling microdomain activated by β2-ARs in airway structural and inflammatory cells. Displacement of the PI3Kγ-anchored pool of protein kinase A (PKA) by an inhaled, cell-permeable, PI3Kγ mimetic peptide (PI3Kγ MP) inhibited a pool of subcortical PDE4B and PDE4D and safely increased cAMP in the lungs, leading to airway smooth muscle relaxation and reduced neutrophil infiltration in a murine model of asthma. In human bronchial epithelial cells, PI3Kγ MP induced unexpected cAMP and PKA elevations restricted to the vicinity of the cystic fibrosis transmembrane conductance regulator (CFTR), the ion channel controlling mucus hydration that is mutated in cystic fibrosis (CF). PI3Kγ MP promoted the phosphorylation of wild-type CFTR on serine-737, triggering channel gating, and rescued the function of F508del-CFTR, the most prevalent CF mutant, by enhancing the effects of existing CFTR modulators. These results unveil PI3Kγ as the regulator of a β2-AR/cAMP microdomain central to smooth muscle contraction, immune cell activation, and epithelial fluid secretion in the airways, suggesting the use of a PI3Kγ MP for compartment-restricted, therapeutic cAMP elevation in chronic obstructive respiratory diseases. PI3K-ing a mimetic: Increasing cyclic adenosine monophosphate (cAMP) in the airways of patients with obstructive lung diseases can reduce airway inflammation and constriction. However, current therapies can induce treatment-limiting systemic side effects. Here, Ghigo and colleagues found that phosphoinositide 3-kinase γ (PI3Kγ) negatively regulated the β2-adrenergic receptor signaling pathway to decrease cAMP. They created a PI3Kγ mimetic peptide that increased local cAMP concentrations and, when administered intratracheally in a mouse model of asthma, induced airway relaxation and reduced neutrophil infiltration. Further, in airway epithelial cells from patients with cystic fibrosis, it triggered gating of the cystic fibrosis transmembrane conductance regulator (CFTR) channel and enhanced the effects of CFTR modulators, suggesting that the PI3Kγ mimetic peptide may be used to treat obstructive lung diseases in humans. [ABSTRACT FROM AUTHOR]

Social isolation might be considered as a marker of poor health and higher mortality. The aim of our analysis was to assess the association of social network index (SNI) with incident AF and death. We selected participants aged ≥ 55 years without prevalent AF from the Framingham Heart Study. We evaluated the association between social isolation measured by the Berkman-Syme Social Network Index (SNI), incident AF, and mortality without diagnosed AF. We assessed the risk factor-adjusted associations between SNI (the sum of 4 components: marriage status, close friends/relatives, religious service attendance, social group participation), incident AF, and mortality without AF by using Fine-Gray competing risk regression models. We secondarily examined the outcome of all-cause mortality. We included 3454 participants (mean age 67 ± 10 years, 58% female). During 11.8 ± 5.2 mean years of follow-up, there were 686 incident AF cases and 965 mortality without AF events. Individuals with fewer connections had lower rates of incident AF (P = 0.04) but higher rates of mortality without AF (P = 0.03). Among SNI components, only social group participation was associated with higher incident AF (subdistribution hazards ratio [sHR] 1.35, 95% CI 1.16–1.57, P = 0.0001). For mortality without AF, social group participation (sHR = 0.81, 95% CI 0.71–0.93, P = 0.002) and regular religious service attendance sHR = 0.76, 95% CI 0.67–0.87, P < 0.0001) were associated with lower risk of death. Social isolation was associated with a higher rate of mortality without diagnosed AF. In contrast to our hypothesis, we observed that poor social connectedness was associated with a lower rate of incident AF. This finding should be interpreted cautiously since there were very few participants in the lowest social connectedness group. Additionally, the seemingly protective effect of social isolation on AF incidence may be simply an artifact of the strong association between social isolation and increased mortality rate in combination with the large number of deaths as compared to AF events in our study. Further study is warranted. [ABSTRACT FROM AUTHOR]

The electromagnetic energy flux in the lower atmosphere of the Sun is a key tool to describe the energy balance of the solar atmosphere. Current investigations on energy flux in the solar atmosphere focus primarily on the vertical electromagnetic flux through the photosphere, ignoring the Poynting flux in other directions and its possible contributions to local heating. Based on a realistic Bifrost simulation of a quiet-Sun (coronal hole) atmosphere, we find that the total electromagnetic energy flux in the photosphere occurs mainly parallel to the photosphere, concentrating in small regions along intergranular lanes. Thereby, it was possible to define a proxy for this energy flux based on only variables that can be promptly retrieved from observations, namely, horizontal velocities of the small-scale magnetic elements and their longitudinal magnetic flux. Our proxy accurately describes the actual Poynting flux distribution in the simulations, with the electromagnetic energy flux reaching 1010 erg cmâˆ'2 sâˆ'1. To validate our findings, we extended the analysis to Sunrise /IMaX data. First, we show that Bifrost realistically describes photospheric quiet-Sun regions, as the simulation presents similar distributions for line-of-sight magnetic flux and horizontal velocity field. Second, we found very similar horizontal Poynting flux proxy distributions for the simulated photosphere and observational data. Our results also indicate that the horizontal Poynting flux in the observations is considerably larger than the vertical electromagnetic flux from previous observational estimates. Therefore, our analysis confirms that the electromagnetic energy flux in the photosphere is mainly horizontal and is most intense in localized regions along intergranular lanes. [ABSTRACT FROM AUTHOR]

Duration of Clinical Benefit Produced by Intraoperative Ketamine Administration in Bariatric Surgery: More Research Is Warranted! Dear Editor, Hung et al. [[1]] conducted a clinically relevant meta-analysis investigating the advantages of intraoperative ketamine administration on postoperative pain scores and opioid consumption after bariatric surgery. Its analgesic effects in the early postoperative period seem rather robust; however, more research is needed to evaluate if ketamine can produce positive analgesic effects lasting longer and extending to the initial 24 h after bariatric surgery. [Extracted from the article]

Background Frailty occurs in 10–15% of community-living older adults and inflammation is a key determinant of frailty. Though diet is a modulator of inflammation, there are few prospective studies elucidating the role of diet-associated inflammation on frailty onset. Objectives We sought to determine whether a proinflammatory diet was associated with increased odds of frailty in adults from the Framingham Heart Study (FHS). Design and Methods This study was nested in a prospective cohort that included individuals without frailty. Diet was assessed in 1998–2001 using a valid FFQ, and frailty was measured in 2011–2014. FFQ-derived energy-adjusted dietary inflammatory index (E-DII®) scores were computed, with higher E-DII scores indicating a more proinflammatory diet. Frailty was defined as fulfilling ≥3 of 5 Fried Phenotype criteria. Information on potential mediators, serum IL-6 and C-reactive protein was obtained in 1998–2001. Logistic regression estimated ORs and 95% CIs for E-DII (as continuous and in quartiles) and frailty onset adjusting for relevant confounders. Results Of 1701 individuals without frailty at baseline (mean ± SD age: 58 ± 8 y; range: 33–81 y; 55% female), 224 developed frailty (13% incidence) over ∼12 y. The mean ± SD E-DII score was −1.95 ± 2.20; range: −6.71 to +5.40. After adjusting for relevant confounders, a 1-unit higher E-DII score was associated with 16% increased odds of developing frailty (95% CI: 1.07, 1.25). In categorical analyses, participants in the highest (proinflammatory) compared with lowest quartile of E-DII had >2-fold increased odds of frailty (ORquartile4vs.1: 2.22; 95% CI: 1.37, 3.60; P -trend < 0.01). IL-6 and C-reactive protein were not major contributors in the pathway. Conclusions In this cohort of middle-aged and older adults, a proinflammatory diet was associated with increased odds of frailty over ∼12 y of follow-up. Trials designed to increase consumption of anti-inflammatory foods for frailty prevention are warranted. [ABSTRACT FROM AUTHOR]

Although theoretically predicted, the simultaneous excitation of several resonant modes in sunspots has not been observed. Like any harmonic oscillator, a solar magnetic flux tube can support a variety of resonances, which constitute the natural response of the system to external forcing. Apart from a few single low order eigenmodes in small scale magnetic structures, several simultaneous resonant modes were not found in extremely large sunspots. Here we report the detection of the largest-scale coherent oscillations observed in a sunspot, with a spectrum significantly different from the Sun's global acoustic oscillations, incorporating a superposition of many resonant wave modes. Magnetohydrodynamic numerical modeling agrees with the observations. Our findings not only demonstrate the possible excitation of coherent oscillations over spatial scales as large as 30–40 Mm in extreme magnetic flux regions in the solar atmosphere, but also paves the way for their diagnostic applications in other astrophysical contexts. Co-existence of several magnetohydrodynamic oscillations modes on the Sun were predicted earlier. Here, the authors show large-scale coherent oscillations in a sunspot, with a spectrum different than solar global acoustic oscillations, incorporating a superposition of many resonant wave modes. [ABSTRACT FROM AUTHOR]

Background: One of the mechanisms suggested to link physical activity (PA) to favorable brain health is through stimulation of neural growth factors such as brain-derived neurotrophic factor (BDNF). Acute bouts of PA stimulate circulating BDNF levels.Objective: In this investigation, we assessed whether habitual, accelerometer-measured PA levels were related to circulating BDNF levels in a middle-aged cohort.Methods: In the Framingham Heart Study Third Generation cohort, 1,769 participants provided reliable accelerometry data and were not missing BDNF measurement or platelet counts. In a cross-sectional analysis, using multivariable regression, we related PA measures to serum BDNF levels, adjusting for age, sex, smoking status, platelet count, depression status, and accelerometer wear time.Results: Our study participants (mean age 47±9 years, 50.8% women) spent an average of 22.3 mins/day in moderate-to-vigorous (MV)PA. Most PA variables (steps, MVPA, light activity, and sedentary time) were not related to BDNF levels (p > 0.05). We observed a non-linear trend, where 15-50 mins/week vigorous activity was associated with lower BDNF compared to those with 0 min vigorous activity (β= -0.049±0.024, p = 0.05), but with no significant associations at lower or higher vigorous activity levels. In smokers, MVPA was also associated with lower BDNF levels (β= -0.216±0.079, p = 0.01).Conclusion: Our study reveals that circulating BDNF is not chronically elevated in individuals with higher levels of habitual PA in middle-aged adults from the community and may even be chronically suppressed with higher PA in subgroups, including current smokers. These results do not contradict previous studies demonstrating that circulating BDNF rises acutely after PA. [ABSTRACT FROM AUTHOR]

Aims While greater physical activity (PA) is associated with improved health outcomes, the direct links between distinct components of PA, their changes over time, and cardiorespiratory fitness are incompletely understood. Methods and results Maximum effort cardiopulmonary exercise testing (CPET) and objective PA measures [sedentary time (SED), steps/day, and moderate-vigorous PA (MVPA)] via accelerometers worn for 1 week concurrent with CPET and 7.8 years prior were obtained in 2070 Framingham Heart Study participants [age 54 ± 9 years, 51% women, SED 810 ± 83 min/day, steps/day 7737 ± 3520, MVPA 22.3 ± 20.3 min/day, peak oxygen uptake (VO2) 23.6 ± 6.9 mL/kg/min]. Adjusted for clinical risk factors, increases in steps/day and MVPA and reduced SED between the two assessments were associated with distinct aspects of cardiorespiratory fitness (measured by VO2) during initiation, early-moderate level, peak exercise, and recovery, with the highest effect estimates for MVPA (false discovery rate <5% for all). Findings were largely consistent across categories of age, sex, obesity, and cardiovascular risk. Increases of 17 min of MVPA/day [95% confidence interval (CI) 14–21] or 4312 steps/day (95% CI 3439–5781; ≈54 min at 80 steps/min), or reductions of 249 min of SED per day (95% CI 149–777) between the two exam cycles corresponded to a 5% (1.2 mL/kg/min) higher peak VO2. Individuals with high (above-mean) steps or MVPA demonstrated above average peak VO2 values regardless of whether they had high or low SED. Conclusions Our findings provide a detailed assessment of relations of different types of PA with multidimensional cardiorespiratory fitness measures and suggest favourable longitudinal changes in PA (and MVPA in particular) are associated with greater objective fitness. [ABSTRACT FROM AUTHOR]

Introduction. COVID-19 is a complex syndrome caused by SARS-Cov-2. It mainly affects the respiratory system, but it could cause serious harm during pregnancy. An increase in stillbirths and preterm births has been highlighted by many authors. Although WHO and Royal College of Obstetrics and Gynecology don't recommend elective cesarean section in women with confirmed infection, cesarean sections were performed by many clinicians. This short narrative review aims to analyze pieces of evidence found in literature about the effectiveness of cesarean section in preventing stillbirths in COVID-19 positive mothers. Methods. Studies included in the present review were retrieved searching MEDLINE (last access August 5th, 2021) with the following keywords: "pregnant woman with covid-19", "Caesarean section", "Abdominal Delivery" and "Stillbirth". Studies regarding the mode of delivery in pregnant women infected with COVID-19 and neonatal outcomes were included. Studies about biology, anesthesiology and necroscopy were excluded. Filters for "human" and "English" were applied. Results. Searching MEDLINE, 24 references were found. Other 103 articles were found searching bibliography. Two references were excluded after duplicate removal, 77 references after the title screen and 27 after the abstract screen. The final number of references included was 23. Most of the included studies were case reports. Most of them were from China. Discussion. Many authors highlighted the increased risk of fetal death in pregnancies complicated with SARS-Cov-2 infection, but it is not clear if Caesarean Section could reduce this risk. Pieces of evidence show that most clinicians choose to perform an elective cesarean section mostly because of maternal conditions or the fear of possible vertical transmission. Data show that mode of delivery doesn't affect the neonatal outcome and Caesarean Section doesn't reduce the positivity rate among neonates. Different opinions were found about the possible infection of amniotic fluid, cord blood and placenta. The risk of vertical transmission is considered moderate or low by most of the authors. Positivity to SARS-Cov-2 isn't an indication of elective cesarean section by itself, but this mode of delivery should be optioned in patients with other obstetrical indications or with severe conditions due to COVID. The recent increase in stillbirths could be related to the overall deterioration of maternal conditions. [ABSTRACT FROM AUTHOR]

Lymphedema is a chronic devastating disease characterized by the accumulation of fluid in the extremities, tissue progressive changes such as adipose tissue deposition and fibrosis. To restore the functionality and structural integrity of the damaged lymphatic vessels, autologous peripheral blood mononuclear cells (PBMNC) was implanted in 3 sessions, 4 weeks apart, in the affected limb. Each patient was followed for 6 months, monitoring changes in the limb volume. Lymphangiogenesis was evaluated by lymphoscintigraphy, and the monitoring of quality of life. A rapid reduction in the volume of the limbs was observed: Twenty-four point 5 percent of volume reduction after the first implant, 18.5% after the second, and 15.3% at 6 months after the third (p<0.05 vs baseline). Lymphoscintigraphy showed a hyper fixation of the tracer along the ipsilateral iliac axis not appreciable at baseline. Implants of autologous PBMNC in patients with primary lower limb lymphedema seems to be a feasible, effective therapy option. [ABSTRACT FROM AUTHOR]

The aim of this study is to demonstrate the use and the effectiveness of cephalometry and golden proportions analysis of the face in planning prosthetic treatments in totally edentulous patients. In order to apply this method, latero-lateral and posterior-anterior X-rays must be performed in addition to the common procedure. Two main concerns for totally edentulous patients are the establishment of the vertical dimension and the new position of the occlusal plane. The divine proportion analysis was carried out by the use of a golden divider. The prosthetic protocol was divided into three steps and a case was selected for better understanding. Referring to the golden relations, if the distance from the chin to the wing of the nose is 1.0, the distance from the nose to eye is 0.618. This proportion is useful and effective in determining the correct prosthetic vertical dimension. The incisal margin of the lower incisor must be positioned between Point A (A) and protuberance menti (Pm) according to the gold ratio 0.618 of the total height A-Pm. Posteriorly the occlusal plane must be placed 2 mm below the divine occlusal plane (traced from the incisal margin of lower incisors to Xi point). A prosthesis made in accordance with cephalometric parameters and divine proportions of the face helps to improve the patient's aesthetics, function and social personality. [ABSTRACT FROM AUTHOR]

Background: All-cause mortality following atrial fibrillation (AF) has decreased over time. Data regarding temporal trends in causes of death among individuals with AF are scarce. The aim of our study was to analyze temporal trends in cause-specific mortality and predictors for cardiovascular (CVD) and non-CVD deaths among participants with incident AF in the Framingham Heart Study.Methods: We categorized all newly diagnosed AF cases according to age at AF diagnosis (< 70, 70 to < 80, and ≥ 80 years) and epoch of AF diagnosis (< 1990, 1990-2002, and ≥ 2003). We followed participants until death or the last follow-up. We categorized death causes into CVD, non-CVD, and unknown causes. For each age group, we tested for trends in the cumulative incidence of cause-specific death across epochs. We fit multivariable Fine-Gray models to assess subdistribution hazard ratios (HR) between clinical risk factors at AF diagnosis and cause-specific mortality.Results: We included 2125 newly diagnosed AF cases (mean age 75.5 years, 47.8% women). During a median follow-up of 4.8 years, 1657 individuals with AF died. There was evidence of decreasing CVD mortality among AF cases diagnosed < 70 years and 70 to < 80 years (ptrend < 0.001) but not ≥ 80 years (p = 0.76). Among the cases diagnosed < 70 years, the cumulative incidence of CVD death at 75 years was 67.7% in epoch 1 and 13.9% in epoch 3; among those 70 to < 80 years, the incidence at 85 years was 58.9% in epoch 1 and 18.9% in epoch 3. Advancing age (HR per 1 SD increase 6.33, 95% CI 5.44 to 7.37), prior heart failure (HR 1.49, 95% CI 1.14-1.94), and prior myocardial infarction (HR 1.44, 95% CI 1.15-1.80) were associated with increased rate of CVD death.Conclusions: In this community-based cohort, CVD mortality among AF cases decreased over time. Most deaths in individuals with AF are no longer CVD-related, regardless of age at AF diagnosis. [ABSTRACT FROM AUTHOR]

Background: Post-operative pulmonary complications (PPC) can develop in up to 13% of patients undergoing neurosurgical procedures and may adversely affect clinical outcome. The use of intraoperative lung protective ventilation (LPV) strategies, usually including the use of a low Vt, low PEEP and low plateau pressure, seem to reduce the risk of PPC and are strongly recommended in almost all surgical procedures. Nonetheless, feasibility of LPV strategies in neurosurgical patients are still debated because the use of low Vt during LPV might result in hypercapnia with detrimental effects on cerebrovascular physiology. Aim of our study was to determine whether LPV strategies would be feasible compared with a control group in adult patients undergoing cranial or spinal surgery. Methods: This single-centre, pilot randomized clinical trial was conducted at the University Hospital "Maggiore della Carità" (Novara, Italy). Adult patients undergoing major cerebral or spinal neurosurgical interventions with risk index for pulmonary post-operative complications > 2 and not expected to need post-operative intensive care unit (ICU) admission were considered eligible. Patients were randomly assigned to either LPV (Vt = 6 ml/kg of ideal body weight (IBW), respiratory rate initially set at 16 breaths/min, PEEP at 5 cmH2O and application of a recruitment manoeuvre (RM) immediately after intubation and at every disconnection from the ventilator) or control treatment (Vt = 10 ml/kg of IBW, respiratory rate initially set at 6–8 breaths/min, no PEEP and no RM). Primary outcomes of the study were intraoperative adverse events, the level of cerebral tension at dura opening and the intraoperative control of PaCO2. Secondary outcomes were the rate of pulmonary and extrapulmonary complications, the number of unplanned ICU admissions, ICU and hospital lengths of stay and mortality. Results: A total of 60 patients, 30 for each group, were randomized. During brain surgery, the number of episodes of intraoperative hypercapnia and grade of cerebral tension were similar between patients randomized to receive control or LPV strategies. No difference in the rate of intraoperative adverse events was found between groups. The rate of postoperative pulmonary and extrapulmonary complications and major clinical outcomes were similar between groups. Conclusions: LPV strategies in patients undergoing major neurosurgical intervention are feasible. Larger clinical trials are needed to assess their role in postoperative clinical outcome improvements. Trial registration: registered on the Australian New Zealand Clinical Trial Registry (www.anzctr.org.au), registration number ACTRN12615000707561. [ABSTRACT FROM AUTHOR]

Sunspots are the most prominent feature of the solar magnetism in the photosphere. Although they have been widely investigated in the past, their structure remains poorly understood. Indeed, due to limitations in observations and the complexity of the magnetic field estimation at chromospheric heights, the magnetic field structure of sunspot above the photosphere is still uncertain. Improving the present knowledge of sunspot is important in solar and stellar physics, since spot generation is seen not only on the Sun, but also on other solar-type stars. In this regard, we studied a large, isolated sunspot with spectro-polarimeteric measurements that were acquired at the Fe I 6173 nm and Ca II 8542 nm lines by the spectropolarimeter IBIS/DST under excellent seeing conditions lasting more than three hours. Using the Non-LTE inversion code NICOLE, we inverted both line measurements simultaneously, to retrieve the three-dimensional magnetic and thermal structure of the penumbral region from the bottom of the photosphere to the middle chromosphere. Our analysis of data acquired at spectral ranges unexplored in previous studies shows clear spine and intra-spine structure of the penumbral magnetic field at chromopheric heights. Our investigation of the magnetic field gradient in the penumbra along the vertical and azimuthal directions confirms results reported in the literature from analysis of data taken at the spectral region of the He I 1083 nm triplet. [ABSTRACT FROM AUTHOR]

We report on multi-wavelength ultraviolet (UV) high-resolution observations taken with the IRIS satellite during the emergence phase of an emerging flux region embedded in the unipolar plage of active region NOAA 12529. These data are complemented by measurements taken with the spectropolarimeter aboard the Hinode satellite and by observations from SDO. In the photosphere, we observe the appearance of opposite emerging polarities, separating from each other, and cancellation with a pre-existing flux concentration of the plage. In the upper atmospheric layers, recurrent brightenings resembling UV bursts, with counterparts in all UV/EUV filtergrams, are identified in the EFR site. In addition, plasma ejections are observed at chromospheric level. Most important, we unravel a signature of plasma heated up to 1 MK detecting Fe XII emission in the core of the brightening sites. Comparing these findings with previous observations and numerical models, we suggest evidence of several long-lasting, small-scale magnetic reconnection episodes between the new bipolar EFR and the ambient field. [ABSTRACT FROM AUTHOR]