Miracle-dz/UniFAR-FTUs huggingface dataset:
Mindfulness in the Maintenance of Cognitive Capacities in Alzheimer's Disease: A Randomized Clinical Trial.

BACKGROUND The Canary Islands longitudinal study on non-pharmacological treatments showed the overall effectiveness of mindfulness in Alzheimer's disease (AD). However, no specific data on the maintenance of cognitive capacities were presented. OBJECTIVE To determine whether the practice of mindfulness modifies the course of cognitive impairment in AD. METHODS DESIGN Longitudinal, non-inferiority and equivalence, randomized clinical trial, repeated-measures design, with three experimental groups and one control group. PARTICIPANTS Patients with AD who voluntarily attended the Lidia García Foundation (n = 502). Only those who were treated with donepezil and MMSE ≥18 were included (n = 120). INTERVENTION Over a two-year period, each group carried out three weekly sessions of stimulation based on mindfulness, cognitive stimulation therapy, and progressive muscle relaxation. MEASURES Cognitive assessment CAMDEX-R (MMSE and CAMCOG). STATISTICAL ANALYSIS Repeated-measures ANOVA (p < 0.05) and the effect size Cohen's d were performed. RESULTS The mindfulness group showed significant scores compared with the control and muscle relaxation groups (p < 0.05), while mindfulness and cognitive stimulation therapy were equivalent (p≥0.05). Group cognitive stimulation evolved better than the control (p < 0.05) group but not better than the muscle relaxation group (p≥0.05). The effect size compared over two years was large for the mindfulness group (p≥0.80), moderate for the relaxation group (p≥0.50), and low for the cognitive stimulation group (p≥0.20). CONCLUSION The practice of mindfulness maintained cognitive function over a period of two years. This longitudinal study suggests that mindfulness can be used as a non-pharmacological treatment to slow cognitive impairment in AD.
Tracking of Blood Pressure From Childhood to Adulthood: A Systematic Review and Meta–Regression Analysis

Background— A large number of studies have examined the tracking of blood pressure (BP) from childhood to adulthood, but the reported findings are inconsistent and few systematic analyses have been conducted. Methods and Results— We conducted a systematic search of PubMed for studies that examined the tracking of BP from childhood to adulthood published between January 1970 and July 2006. From 301 retrieved papers, 50 cohort studies met our inclusion criteria and provided 617 data points (Pearson/Spearman correlation coefficients) for systolic BP (SBP) and 547 data points for diastolic BP (DBP) for our meta-analysis. Information on sample characteristics and BP measurement protocols was extracted. Fisher z transformation and random-effects meta–regression analysis were conducted. The reported BP tracking correlation coefficients varied from −0.12 to 0.80 for SBP and from −0.16 to 0.70 for DBP, with an average of 0.38 for SBP and 0.28 for DBP. BP tracking varied significantly by baseline age and length of follow-up. The strength of BP tracking increased with baseline age by 0.012 for SBP (P<0.001) and 0.009 for DBP (P<0.001) and decreased with follow-up length by 0.008 for SBP (P<0.001) and 0.005 for DBP (P<0.001). BP tracking did not vary markedly across the number of BP measurements or race/population groups. Conclusions— Data from diverse populations show that the evidence for BP tracking from childhood into adulthood is strong. Childhood BP is associated with BP in later life, and early intervention is important.
Local homogeneity of tonotopic organization in the primary auditory cortex of marmosets

Significance Marmoset is a New World monkey rich in social interaction and vocal communication. We used in vivo two-photon fluorescence calcium imaging of sound-evoked responses of large neuronal populations at single-neuron resolution in the primary auditory cortex (A1) of anesthetized marmosets. We found that the pure tone-evoked responses of marmoset A1 neurons are highly homogeneous in their frequency preference within local cortical regions, in sharp contrast to that found in rodents. Thus, there is species-specific local tonotopic organization in A1, which imposes distinct neural circuitry constraints for the cortical integration of auditory information. Marmoset has emerged as a useful nonhuman primate species for studying brain structure and function. Previous studies on the mouse primary auditory cortex (A1) showed that neurons with preferential frequency-tuning responses are mixed within local cortical regions, despite a large-scale tonotopic organization. Here we found that frequency-tuning properties of marmoset A1 neurons are highly uniform within local cortical regions. We first defined the tonotopic map of A1 using intrinsic optical imaging and then used in vivo two-photon calcium imaging of large neuronal populations to examine the tonotopic preference at the single-cell level. We found that tuning preferences of layer 2/3 neurons were highly homogeneous over hundreds of micrometers in both horizontal and vertical directions. Thus, marmoset A1 neurons are distributed in a tonotopic manner at both macro- and microscopic levels. Such organization is likely to be important for the organization of auditory circuits in the primate brain.
Low Prevalence of Mixed Dementia in a Cohort of 2,000 Elderly Patients in a Memory Clinic Setting.

BACKGROUND It is generally assumed that with increasing age, pathology in clinically diagnosed Alzheimer's disease (AD) becomes more mixed, i.e., co-existence of amyloid plaques and cerebrovascular pathology. OBJECTIVE To test the hypothesis of increasing prevalence of mixed dementia in late-onset clinically diagnosed Alzheimer's disease (AD) in a single-center memory clinic population. METHODS Patients included had diagnoses of AD (n = 832), subjective cognitive impairment (SCI, n = 333), mild cognitive impairment (MCI, n = 492), vascular dementia (VaD, n = 57), other dementia (n = 53), or other diagnosis (n = 233). Prevalence of severe white matter lesions (WML) was defined as a score of 2 or higher on the Fazekas-scale on brain computed tomography to classify AD patients as having mixed dementia. We examined the effect of age on WML using multiple linear regression analysis, and AD patients were compared to SCI to determine the effect of disease on WML. RESULTS Prevalence of severe WML was 33.6% in AD patients (mixed dementia), 11.4% in SCI, 22.7% in MCI, 75.4% in VaD, 3.8% in other dementia, and 15.5% in other diagnosis. With increasing age there was a significant and similar increase of WML scores in SCI, MCI, AD, other dementia, and other diagnosis, indicating no effect modification by AD. The difference between AD patients and SCI averaged 0.16 on the WML score and difference in percentage severe WML between AD and SCI patients was 15% across all ages. CONCLUSION We found a low prevalence of mixed dementia. Furthermore, severe WML in AD was largely explained by age rather than effect of disease.
Prognostic Impact of Aortic Valve Area in Conservatively Managed Patients With Asymptomatic Severe Aortic Stenosis With Preserved Ejection Fraction

Background Data are scarce on the role of aortic valve area (AVA) to identify those patients with asymptomatic severe aortic stenosis (AS) who are at high risk of adverse events. We sought to explore the prognostic impact of AVA in asymptomatic patients with severe AS in a large observational database. Methods and Results Among 3815 consecutive patients with severe AS enrolled in the CURRENT AS (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis) registry, the present study included 1309 conservatively managed asymptomatic patients with left ventricular ejection fraction ≥50%. The study patients were subdivided into 3 groups based on AVA (group 1: AVA >0.80 cm2, N=645; group 2: 0.8 cm2 ≥AVA >0.6 cm2, N=465; and group 3: AVA ≤0.6 cm2, N=199). The prevalence of very severe AS patients (peak aortic jet velocity ≥5 m/s or mean aortic pressure gradient ≥60 mm Hg) was 2.0%, 5.8%, and 26.1% in groups 1, 2, and 3, respectively. The cumulative 5‐year incidence of AVR was not different across the 3 groups (39.7%, 43.7%, and 39.9%; P=0.43). The cumulative 5‐year incidence of the primary outcome measure (a composite of aortic valve–related death or heart failure hospitalization) was incrementally higher with decreasing AVA (24.1%, 29.1%, and 48.1%; P<0.001). After adjusting for confounders, the excess risk of group 3 and group 2 relative to group 1 for the primary outcome measure remained significant (hazard ratio, 2.21, 95% CI, 1.56–3.11, P<0.001; and hazard ratio, 1.34, 95% CI, 1.01–1.78, P=0.04, respectively). Conclusions AVA ≤0.6 cm2 would be a useful marker to identify those high‐risk patients with asymptomatic severe AS, who might benefit from early AVR. Clinical Trial Registration URL: www.umin. ac.jp. Unique identifier: UMIN000012140.
Extranuclear DNA accumulates in aged cells and contributes to senescence and inflammation

Systemic inflammation is central to aging‐related conditions. However, the intrinsic factors that induce inflammation are not well understood. We previously identified a cell‐autonomous pathway through which damaged nuclear DNA is trafficked to the cytosol where it activates innate cytosolic DNA sensors that trigger inflammation. These results led us to hypothesize that DNA released after cumulative damage contributes to persistent inflammation in aging cells through a similar mechanism. Consistent with this notion, we found that older cells harbored higher levels of extranuclear DNA compared to younger cells. Extranuclear DNA was exported by a leptomycin B‐sensitive process, degraded through the autophagosome–lysosomal pathway and triggered innate immune responses through the DNA‐sensing cGAS‐STING pathway. Patient cells from the aging diseases ataxia and progeria also displayed extranuclear DNA accumulation, increased pIRF3 and pTBK1, and STING‐dependent p16 expression. Removing extranuclear DNA in old cells using DNASE2A reduced innate immune responses and senescence‐associated (SA) β‐gal enzyme activity. Cells and tissues of Dnase2a−/− mice with defective DNA degradation exhibited slower growth, higher activity of β‐gal, or increased expression of HP‐1β and p16 proteins, while Dnase2a−/−;Sting−/− cells and tissues were rescued from these phenotypes, supporting a role for extranuclear DNA in senescence. We hypothesize a direct role for excess DNA in aging‐related inflammation and in replicative senescence, and propose DNA degradation as a therapeutic approach to remove intrinsic DNA and revert inflammation associated with aging.
Post-hoc analysis from phase III trials of human papillomavirus vaccines: considerations on impact on non-vaccine types

ABSTRACT Background: Substantial heterogeneity has been reported in efficacy against high-grade cervical intraepithelial neoplasia (CIN) irrespective of HPV type in phase III results for bivalent and quadrivalent human papillomavirus virus (HPV) vaccines (AS04-HPV and qHPV). Real-world data recently confirmed a very high overall impact of AS04-HPV, supporting the validity of the observed heterogeneity. To explore the reasons for heterogeneous efficacy, we assessed vaccine impact on high-grade lesions not caused by vaccine types. Research methods: We extracted case counts of CIN lesions containing (1) at least one vaccine HPV type, (2) at least one vaccine HPV type and a high-risk non-vaccine type (co-infections) and (3) no vaccine types (non-vaccine or no high-risk HPV types). Based on these, Phase III cross-protective efficacies were estimated with exclusion (3) and with inclusion (2 and 3) of co-infections. Results: Cross-protective efficacy of AS04-HPV against CIN3 lesions ranges from 81.3% (95%CI: 34.7;96.5) (excluding co-infections) to 88.5% (95%CI:62.4;97.8) (including co-infections). For qHPV the efficacy ranges from −58.7% (95%CI: −180.5;8.5) (excluding co-infections) to 13.1% (95%CI: −39.0;45.9) (including co-infections). Conclusions: Heterogenous overall efficacy against CIN3 between AS04-HPV and qHPV is driven by differential efficacy against lesions that do not contain vaccine types, which may be related to the impact of different adjuvants on the immune response.
Resettled Bhutanese Refugees in Ottawa: What Coping Strategies Promote Psychological Well-Being?

Background Since 2008, Bhutanese refugees have been resettled in Canada, including Ottawa. This relocation and resettling process is associated with significant physical and psychological stress, as individuals acclimatize to a new country. Purpose To assess the relationship between coping strategies and psychological well-being of Bhutanese refugees resettled in Ottawa. Methods A cross-sectional survey utilizing a convenience sample of adults (n = 110) was conducted in the fall of 2015 in Ottawa. Two tools, Brief COPE and general well-being schedule were used. Results Bhutanese refugees were in moderate distress. Using multiple linear regression, age, education, and three coping strategies (positive reframing, self-blame, and venting) were identified as predictors of general well-being (F (11, 96) = 3.61, p < . 001, R2 = 21.2%). Higher levels of education and positive reframing were associated with greater general well-being scores, while self-blame and well-being between ages 41 and 50 years were inversely associated with general well-being. Conclusions Findings suggest that a broad intersectorial approach between nurses and partner agencies is needed to enhance the mental health of this population for better adjustment in the host country. Nurses could provide support and counseling to minimize the use of self-blame and venting and promote positive coping strategies.
In vivo effect of mutant ELOVL4 on the expression and function of wild-type ELOVL4.

PURPOSE Mutations in the elongation of very long chain fatty acids 4 (ELOVL4) gene cause human Stargardt's macular dystrophy 3 (STGD3), a juvenile onset dominant form of macular degeneration. To understand the role of the ELOVL4 protein in retinal function, several mouse models have been developed by using transgenic (TG), knock-in (Elovl4(+/mut)), and knockout (Elovl4(+/-)) approaches. Here we analyzed quantitatively the ELOVL4 protein and its enzymatic products (very long chain saturated fatty acid [VLC-FA] and VLC-polyunsaturated fatty acid [VLC-PUFA]) in the retinas of 8 to 10-week-old TG1(+), TG2(+), and Elovl4(+/mut) mice that harbor the mutant ELOVL4 and compared them to their wild-type littermates and Elovl4(+/-) that do not express the mutant protein. We also analyzed skin from these mice to gain insight into the pathogenesis resulting from the ELOVL4 mutation. METHODS ELOVL4 protein localization in the retina was determined by immunohistochemistry. Levels of wild-type ELOVL4 protein in skin and retinas were determined by Western blotting. Total lipids from skin and retinas were measured by gas chromatography-mass spectrometry (GC-MS). Retinal glycerophosphatidylcholines (PC) were analyzed by tandem mass spectrometry. RESULTS Immunohistochemical and Western analysis indicated that wild-type ELOVL4 protein was reduced in heterozygous Elovl4(+/mut) and Elovl4(+/-) retinas, but not in TG2(+) retinas. We found that VLC-FA was reduced by 50% in the skin of Elovl4(+/-) and by 60% to 65% in Elovl4(+/mut). We found VLC-PUFA levels at ∼ 50% in both the retinas, and wild-type levels of VLC-PUFA in TG2(+) retinas. CONCLUSIONS We conclude that the presence of the mutant ELOVL4 does not affect the function of wild-type ELOVL4 in the fully developed 8- to 10-week-old retinas.
Effect of Severe Aortic Stenosis on the Outcome in Elderly Patients Undergoing Repair of Hip Fracture

Background: The perioperative assessment and management of elderly patients with hip fracture and significant aortic stenosis (AS) is an increasingly common clinical problem with little data available to guide perioperative management. Objectives: It was the aim of this study to examine the incidence of perioperative events in an elderly population of patients with severe AS undergoing repair of hip fracture as compared with controls without severe AS. Methods: Patients over the age of 70 with an echocardiographic diagnosis of severe AS defined as an aortic valve area ≤1.0 cm2 who underwent surgery for hip fracture repair were retrospectively identified. An age-matched group of patients without a history of AS who underwent surgical repair of hip fracture was the control group. The primary outcome of the incidence of postoperative cardiac events defined as death, acute coronary syndrome or pulmonary edema within 30 days was compared. Results: Thirty-two patients with AS (median age 84.5 years, range 72–94; 27 females and 5 males) and 88 controls (median age 86 years, range 80–95; 67 females and 21 males) were entered into the study. There were no significant differences between the AS group and controls for 30-day mortality (6.2 vs. 6.8%) or for the total cardiac event rate (18.7 vs. 11.8%). Conclusions: Our results demonstrate that elderly patients with severe AS can safely undergo repair of hip fractures with a mortality and morbidity comparable with a control population. These patients should not be denied surgery on the basis of their aortic valve disease.
Effects of socio‐demographic characteristics, premorbid functioning, and insight on duration of untreated psychosis in first‐episode schizophrenia or schizophreniform disorder in Northern Malawi

Long duration of untreated psychosis (DUP) is prevalent and has been shown to be associated with poorer prognosis. Thus, knowledge of its determinants may help to target early interventions to reduce DUP on the needed population. Previous studies seeking to understand determinants of DUP have been inconclusive. Therefore, this study aimed to investigate the effects of socio‐demographic characteristics, premorbid functioning, and insight on DUP in patients with first‐episode schizophrenia or schizophreniform disorder.
Visuospatial neglect is more severe when stimulus density is large

ABSTRACT Patients with visuospatial neglect (VSN) suffer from an imbalance in visual attention between their left and right (egocentric or allocentric) hemispace. The view of VSN as an attentional imbalance between two hemispaces ignores the fact that—in our daily life—we are presented with varying levels of stimulus density, within but also across hemispaces. Therefore, we developed a novel experimental paradigm in which stroke patients (n = 207) were presented with a different number of simple objects in the left and right (egocentric) hemispaces and were asked to indicate whether there were more objects in the left or the right hemispace. We systematically varied the density of visual stimuli to investigate whether a high level of stimulus density impairs task performance of patients with VSN to a larger degree than it does for patients without VSN. Error rate increased when more objects were presented in the display, but this effect was most pronounced in patients with VSN, especially when more objects were presented in their contralesional than in their ipsilesional hemispace. Our findings reveal that deficits in early visual processing in patients with VSN become especially apparent when overall stimulus density is high. The degree of stimulus density should therefore be taken into account when considering the impact of attentional deficits on activities in daily life.
Lipid-Lowering Agents.

Several new or emerging drugs for dyslipidemia owe their existence, in part, to human genetic evidence, such as observations in families with rare genetic disorders or in Mendelian randomization studies. Much effort has been directed to agents that reduce LDL (low-density lipoprotein) cholesterol, triglyceride, and Lp[a] (lipoprotein[a]), with some sustained programs on agents to raise HDL (high-density lipoprotein) cholesterol. Lomitapide, mipomersen, AAV8.TBG. hLDLR, inclisiran, bempedoic acid, and gemcabene primarily target LDL cholesterol. Alipogene tiparvovec, pradigastat, and volanesorsen primarily target elevated triglycerides, whereas evinacumab and IONIS-ANGPTL3-LRx target both LDL cholesterol and triglyceride. IONIS-APO(a)-LRx targets Lp(a).
Differentiated Antiretroviral Therapy Delivery: Implementation Barriers and Enablers in South Africa

Abstract Scale-up of antiretroviral therapy (ART) for people living with HIV requires differentiated models of ART delivery to improve access and contribute to achieving viral suppression for 95% of people on ART. We examined barriers and enablers in South Africa via semistructured interviews with 33 respondents (program implementers, nurses, and other health care providers) from 11 organizations. The interviews were recorded, transcribed, and analyzed for emerging themes using NVivo 11 software. Major enablers of ART delivery included model flexibility, provision of standardized guidance, and an increased focus on person-centered care. Major barriers were related to financial, human, and space resources and the need for time to allow buy-in. Stigma emerged as both a barrier and an enabler. Findings suggest that creating and strengthening models that cater to client needs can achieve better health outcomes. South Africa's efforts can inform emerging models in other settings to achieve epidemic control.
Open and Endovascular Management of Aortic Aneurysms

Aneurysmal disease can affect any segment of the aorta, from the aortic root to the aortic bifurcation. The treatment of aortic aneurysms has evolved dramatically in the past 3 decades, with the introduction of endovascular aneurysm repair using stent grafts causing a major paradigm shift in the field of aortic aneurysm surgery. While the technical details of the management of aortic aneurysms vary greatly depending on the location of an aneurysm, the principles remain the same. Successful aortic aneurysm treatment depends on either open replacement or endovascular exclusion of the aneurysmal segment with healthy artery proximal and distal to the repair. Major aortic branches of the arch and visceral segment add additional technical complexity to aneurysms involving these regions. Even as endovascular repair becomes the primary treatment modality for most aortic aneurysms, open repair remains an essential treatment modality in many circumstances. Additionally, long-term results of endovascular repair suggest that younger patients with long life expectancy and low-perioperative risk may benefit more from open repair. Therefore, technical expertise in both endovascular and open treatment is necessary for a comprehensive aortic aneurysm surgery practice.