High life satisfaction reported among small-scale societies with low incomes.

Global polls have shown that people in high-income countries generally report being more satisfied with their lives than people in low-income countries. The persistence of this correlation, and its similarity to correlations between income and life satisfaction within countries, could lead to the impression that high levels of life satisfaction can only be achieved in wealthy societies. However, global polls have typically overlooked small-scale, nonindustrialized societies, which can provide an alternative test of the consistency of this relationship. Here, we present results from a survey of 2,966 members of Indigenous Peoples and local communities among 19 globally distributed sites. We find that high average levels of life satisfaction, comparable to those of wealthy countries, are reported for numerous populations that have very low monetary incomes. Our results are consistent with the notion that human societies can support very satisfying lives for their members without necessarily requiring high degrees of monetary wealth.

Biocultural vulnerability exposes threats of culturally important species.

There are growing calls for conservation frameworks that, rather than breaking the relations between people and other parts of nature, capture place-based relationships that have supported social-ecological systems over the long term. Biocultural approaches propose actions based on biological conservation priorities and cultural values aligned with local priorities, but mechanisms that allow their global uptake are missing. We propose a framework to globally assess the biocultural status of specific components of nature that matter to people and apply it to culturally important species (CIS). Drawing on a literature review and a survey, we identified 385 wild species, mostly plants, which are culturally important. CIS predominate among Indigenous peoples (57%) and ethnic groups (21%). CIS have a larger proportion of Data-Deficient species (41%) than the full set of International Union for Conservation of Nature (IUCN) species (12%), underscoring the disregard of cultural considerations in biological research. Combining information on CIS biological conservation status (IUCN threatened status) and cultural status (language vitality), we found that more CIS are culturally Vulnerable or Endangered than they are biologically and that there is a higher share of bioculturally Endangered or Vulnerable CIS than of either biologically or culturally Endangered CIS measured separately. Bioculturally Endangered or Vulnerable CIS are particularly predominant among Indigenous peoples, arguably because of the high levels of cultural loss among them. The deliberate connection between biological and cultural values, as developed in our "biocultural status" metric, provides an actionable way to guide decisions and operationalize global actions oriented to enhance place-based practices with demonstrated long-term sustainability.

Cardiac index-guided therapy to maintain optimised postinduction cardiac index in high-risk patients having major open abdominal surgery: the multicentre randomised iPEGASUS trial.

BACKGROUND: It is unclear whether optimising intraoperative cardiac index can reduce postoperative complications. We tested the hypothesis that maintaining optimised postinduction cardiac index during and for the first 8 h after surgery reduces the incidence of a composite outcome of complications within 28 days after surgery compared with routine care in high-risk patients having elective major open abdominal surgery. METHODS: In three German and two Spanish centres, high-risk patients having elective major open abdominal surgery were randomised to cardiac index-guided therapy to maintain optimised postinduction cardiac index (cardiac index at which pulse pressure variation was <12%) during and for the first 8 h after surgery using intravenous fluids and dobutamine or to routine care. The primary outcome was the incidence of a composite outcome of moderate or severe complications within 28 days after surgery. RESULTS: We analysed 318 of 380 enrolled subjects. The composite primary outcome occurred in 84 of 152 subjects (55%) assigned to cardiac index-guided therapy and in 77 of 166 subjects (46%) assigned to routine care (odds ratio: 1.87, 95% confidence interval: 1.03-3.39, P=0.038). Per-protocol analyses confirmed the results of the primary outcome analysis. CONCLUSIONS: Maintaining optimised postinduction cardiac index during and for the first 8 h after surgery did not reduce, and possibly increased, the incidence of a composite outcome of complications within 28 days after surgery compared with routine care in high-risk patients having elective major open abdominal surgery. Clinicians should not strive to maintain optimised postinduction cardiac index during and after surgery in expectation of reducing complications. CLINICAL TRIAL REGISTRATION: NCT03021525.

A Comparison of Early Complication Rates of Endoscopic Carpal Tunnel Release With and Without Resident Involvement.

PURPOSE: The purpose of this study was to compare the complication rates of endoscopic carpal tunnel release (ECTR) relative to orthopedic resident trainee involvement in the procedure. METHODS: All patients undergoing isolated, elective ECTR by two attending surgeons within a 59-month period were analyzed. Cases were categorized as the following according to the degree of resident involvement: ECTR performed by attending with either no resident or a resident as an assistant (group 1), resident performing a portion of the procedure (group 2), and resident performing the entire procedure (group 3). Early postoperative complications and/or intraoperative conversion to an open procedure were the outcomes of interest. We used a noninferiority design, hypothesizing that resident involvement would not be associated with inferior outcomes compared with cases without resident involvement. Multiple logistic regression models, adjusted for patient demographic and surgical characteristics, were fit to assess the relationship between resident involvement groups and complication/conversion outcomes. RESULTS: A total of 1,167 ECTR cases (895 patients) were performed and returned for postoperative follow-up for at least 2 weeks after surgery. Operative time was significantly shorter for group 1 cases versus group 2 and 3 cases. The early postoperative complication and conversion rates were 1.7% and 1.0%, respectively. Superficial infection (1.2%), deep infection (0.3%), and transient neuropraxia (0.3%) occurred infrequently and did not differ relative to resident involvement. No differences in the odds of complication and/or conversion relative to resident involvement were observed. CONCLUSIONS: The results of ECTR performed entirely or in part by attending-supervised resident trainees were not inferior to ECTR performed by an attending surgeon regarding the odds of experiencing complications or conversion to an open procedure. With appropriate supervision, ECTR can be performed safely by orthopedic and plastic surgery residents. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic II.

A Comparison of Tenosynovial and Transverse Carpal Ligament Biopsy for Amyloid Detection in Open Carpal Tunnel Release.

PURPOSE: Our purpose was to compare differences in the incidence of amyloid deposition in tenosynovium (TS) versus transverse carpal ligament (TCL) biopsies obtained during open carpal tunnel release. We hypothesized that the incidence of amyloid would be similar between TCL and TS when obtaining both specimens from the same patient. METHODS: All primary, elective open carpal tunnel release cases that underwent biopsy for amyloid between January 2022 and September 2023 were reviewed. Tenosynovial and TCL specimens were independently evaluated by a pathologist to assess for amyloid. Demographic data were collected, and incidence of amyloid deposition was compared between the two samples. Agreement statistics, sensitivity, and specificity were calculated for TCL, using TS as the reference standard. RESULTS: A total of 196 cases met either Tier 1 (n=180) or Tier 2 (n=16) biopsy criteria. Forty-eight cases were excluded for missed biopsies or laboratory processing errors, leaving 148 cases available for analysis. Amyloid deposition was present in 31 out of 148 (21%) TS specimens and 33 out of 148 (22%) TCL specimens. Overall, the results of the TS biopsy agreed with TCL biopsy in 138 out of 148 cases (93%). In the 10 cases for which the results of the TCL and TS biopsy differed, six cases had (+) TCL and (-) TS, and four cases had amyloid deposition in TS without evidence of deposition in the TCL. Sensitivity and specificity values for the TCL specimen were 87% and 95%, respectively. Positive and negative predictive values were 82% and 97%, respectively. CONCLUSIONS: For cases of open carpal tunnel release undergoing biopsy, amyloid deposition was noted in 21% of TS specimens and 22% of TCL specimens. Results of TS and TCL biopsies obtained from the same patient agreed in 93% of cases. Single-source biopsy for amyloid represents a reasonable diagnostic approach. Future cost analyses should be performed to determine whether the addition of two biopsy sources to improve diagnostic accuracy is justified. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

Sensitivity, Specificity, and Reliability of the CTS-6 for Carpal Tunnel Syndrome Administered by Medical Assistants.

PURPOSE: The CTS-6 can be used clinically to diagnose carpal tunnel syndrome (CTS) and has demonstrated high levels of interrater reliability when administered by nonexpert clinicians. Our purpose was to assess sensitivity (Sn), specificity (Sp), and interrater reliability of the CTS-6 when administered by medical assistants (MAs). METHODS: A series of patients presenting to an academic, upper-extremity surgery clinic were screened using CTS-6 between May and June of 2023. The CTS-6 was first administered by one of seven MAs and then by one of four fellowship-trained upper-extremity surgeons. In addition to recording baseline demographics, the results of each of the six history and examination components of the CTS-6 were recorded, as was the cumulative CTS-6 score (0-26). Surgeons were blinded to the scores obtained by the MAs. Interrater reliability (Cohen's kappa) was determined between the groups with respect to the diagnosis of CTS and the individual CTS-6 items. Sensitivity/specificity was calculated for the MA-administered CTS-6, using the score obtained by the surgeon as the reference standard. A CTS-6 score >12 was considered diagnostic of CTS. RESULTS: Two hundred eighteen patients were included, and 26% had a diagnosis of CTS. The MA group demonstrated a Sn/Sp of 84%/91% for the diagnosis of CTS. Interrater reliability was substantial (Cohen's kappa: 0.72, 95% confidence interval: 0.62-0.83) for MAs compared with hand surgeons for the diagnosis of CTS. For individual CTS-6 components, agreement was lowest for the assessment of two-point discrimination (fair) and highest for the assessment of subjective numbness (near perfect). CONCLUSIONS: The CTS-6 demonstrates substantial reliability and high Sn/Sp when administrated by MAs in an upper-extremity clinic. These data may be used to inform the development of CTS screening programs and future investigations in the primary care setting. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic II.

Surgeon Factors and Trends Associated With the Use of Subacromial Decompression at the Time of Rotator Cuff Repair.

PURPOSE: Subacromial decompression (SAD) has historically been described as an essential part of the surgical treatment of rotator cuff disorders. However, investigations throughout the 21st century have increasingly questioned the need for routine SAD during rotator cuff repair (RCR). Our purpose was to assess for changes in the incidence of SAD performed during RCR over a 12-year period. In addition, we aimed to characterize surgeon and practice factors associated with SAD use. METHODS: Records from two large tertiary referral systems in the United States from 2010 to 2021 were reviewed. All cases of RCR with and without SAD were identified. The outcome of interest was the proportion of SAD performed during RCR across years and by surgeon. Surgeon-specific characteristics included institution, fellowship training, surgical volume, academic practice, and years in practice. Yearly trends were assessed using binomial logistic regression modeling, with a random effect accounting for surgeon-specific variability. RESULTS: During the study period, 37,165 RCR surgeries were performed by 104 surgeons. Of these cases, 71% underwent SAD during RCR. SAD use decreased by 11%. The multivariable model found that surgeons in academic practice, those with lower surgical volume, and those with increasing years in practice were significantly associated with increased odds of performing SAD. Surgeons with fellowship training were significantly more likely to use SAD over time, with the greatest odds of SAD noted for sports medicine surgeons (odds ratio = 3.04). CONCLUSIONS: Although SAD use during RCR appears to be decreasing, multiple surgeon and practice factors (years in practice, fellowship training, volume, and academic practice) are associated with a change in SAD use. CLINICAL RELEVANCE: These data suggest that early-career surgeons entering practice are likely driving the trend of declining SAD. Despite evidence suggesting limited clinical benefits, SAD remains commonly performed; future studies should endeavor to determine factors associated with practice changes among surgeons.

A Comparison of Amyloid Deposition in Endoscopic and Open Carpal Tunnel Release.

PURPOSE: Previous investigations assessing the incidence of amyloidosis detected with biopsy during carpal tunnel release (CTR) have focused on open CTR (OCTR). Prior authors have suggested that biopsy may be more technically challenging during endoscopic carpal tunnel release (ECTR). Our purpose was to compare differences in the incidence of amyloid deposition detected during ECTR versus OCTR. METHODS: We reviewed all primary ECTR and OCTR during which a biopsy for amyloid was obtained between February 2022 and June 2023. All procedures were performed by five upper-extremity surgeons from a single institution. Congo red staining was used to determine the presence of amyloid deposition in either the transverse carpal ligament (TCL) or tenosynovium. All positive cases underwent subtype analysis and protein identification through liquid chromatography-tandem mass spectrometry. Baseline demographics were recorded for each case, and the incidence of positive biopsy was compared between ECTR and OCTR cases. RESULTS: A total of 282 cases were included for analysis (143 ECTR and 139 OCTR). The mean age was 67 years, and 45% of cases were women. Baseline demographics were similar except for a significantly higher incidence of diabetes in OCTR cases (13% vs 33%). Overall, 13% of CTR cases had a positive biopsy. There was a statistically significant difference in the incidence of amyloid deposition detected during biopsy in ECTR cases (3.5%) compared with OCTR cases (23%). CONCLUSIONS: Biopsy performed during ECTR may result in a lower incidence of amyloid detection. Future basic science investigation may be necessary to determine histologic differences between tenosynovium proximal and distal to the leading edge of the TCL. When surgeons plan a biopsy during surgical release of the carpal tunnel, an open approach may be advantageous. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

Increased glucose metabolism and impaired glutamate transport in human astrocytes are potential early triggers of abnormal extracellular glutamate accumulation in hiPSC-derived models of Alzheimer's disease.

Glutamate recycling between neurons and astrocytes is essential to maintain neurotransmitter homeostasis. Disturbances in glutamate homeostasis, resulting in excitotoxicity and neuronal death, have been described as a potential mechanism in Alzheimer's disease (AD) pathophysiology. However, glutamate neurotransmitter metabolism in different human brain cells, particularly astrocytes, has been poorly investigated at the early stages of AD. We sought to investigate glucose and glutamate metabolism in AD by employing human induced pluripotent stem cell (hiPSC)-derived astrocytes and neurons carrying mutations in the amyloid precursor protein (APP) or presenilin-1 (PSEN-1) gene as found in familial types of AD (fAD). Methods such as live-cell bioenergetics and metabolic mapping using [13 C]-enriched substrates were used to examine metabolism in the early stages of AD. Our results revealed greater glycolysis and glucose oxidative metabolism in astrocytes and neurons with APP or PSEN-1 mutations, accompanied by an elevated glutamate synthesis compared to control WT cells. Astrocytes with APP or PSEN-1 mutations exhibited reduced expression of the excitatory amino acid transporter 2 (EAAT2), and glutamine uptake increased in mutated neurons, with enhanced glutamate release specifically in neurons with a PSEN-1 mutation. These results demonstrate a hypermetabolic phenotype in astrocytes with fAD mutations possibly linked to toxic glutamate accumulation. Our findings further identify metabolic imbalances that may occur in the early phases of AD pathophysiology.

Fast profiling of primary, secondary, conjugated, and sulfated bile acids in human urine and murine feces samples.

Bile acids (BAs) are a complex class of metabolites that have been described as specific biomarkers of gut microbiota activity. The development of analytical methods allowing the quantification of an ample spectrum of BAs in different biological matrices is needed to enable a wider implementation of BAs as complementary measures in studies investigating the functional role of the gut microbiota. This work presents results from the validation of a targeted ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for the determination of 28 BAs and six sulfated BAs, covering primary, secondary, and conjugated BAs. The analysis of 73 urine and 20 feces samples was used to test the applicability of the method. Concentrations of BAs in human urine and murine feces were reported, ranging from 0.5 to 50 nmol/g creatinine and from 0.012 to 332 nmol/g, respectively. Seventy-nine percent of BAs present in human urine samples corresponded to secondary conjugated BAs, while 69% of BAs present in murine feces corresponded to primary conjugated BAs. Glycocholic acid sulfate (GCA-S) was the most abundant BA in human urine samples, while taurolithocholic acid was the lowest concentrated compound detected. In murine feces, the most abundant BAs were α-murocholic, deoxycholic, dehydrocholic, and ß-murocholic acids, while GCA-S was the lowest concentrated BA. The presented method is a non-invasive approach for the simultaneous assessment of BAs and sulfated BAs in urine and feces samples, and the results will serve as a knowledge base for future translational studies focusing on the role of the microbiota in health.

High-fat diet activates splenic NOD1 and enhances neutrophil recruitment and neutrophil extracellular traps release in the spleen of ApoE-deficient mice.

In the course of atherogenesis, the spleen plays an important role in the regulation of extramedullary hematopoiesis, and in the control of circulating immune cells, which contributes to plaque progression. Here, we have investigated the role of splenic nucleotide-binding oligomerization domain 1 (NOD1) in the recruitment of circulating immune cells, as well as the involvement of this immune organ in extramedullary hematopoiesis in mice fed on a high-fat high-cholesterol diet (HFD). Under HFD conditions, the absence of NOD1 enhances the mobilization of immune cells, mainly neutrophils, from the bone marrow to the blood. To determine the effect of NOD1-dependent mobilization of immune cells under pro-atherogenic conditions, Apoe-/- and Apoe-/-Nod1-/- mice fed on HFD for 4 weeks were used. Splenic NOD1 from Apoe-/- mice was activated after feeding HFD as inferred by the phosphorylation of the NOD1 downstream targets RIPK2 and TAK1. Moreover, this activation was accompanied by the release of neutrophil extracellular traps (NETs), as determined by the increase in the expression of peptidyl arginine deiminase 4, and the identification of citrullinated histone H3 in this organ. This formation of NETs was significantly reduced in Apoe-/-Nod1-/- mice. Indeed, the presence of Ly6G+ cells and the lipidic content in the spleen of mice deficient in Apoe and Nod1 was reduced when compared to the Apoe-/- counterparts, which suggests that the mobilization and activation of circulating immune cells are altered in the absence of NOD1. Furthermore, confirming previous studies, Apoe-/-Nod1-/- mice showed a reduced atherogenic disease, and diminished recruitment of neutrophils in the spleen, compared to Apoe-/- mice. However, splenic artery ligation reduced the atherogenic burden in Apoe-/- mice an effect that, unexpectedly was lost in Apoe-/-Nod1-/- mice. Together, these results suggest that neutrophil accumulation and activity in the spleen are driven in part by NOD1 activation in mice fed on HFD, contributing in this way to regulating atherogenic progression.

The Risk of Early Postoperative Complications Associated With Preoperative Immunosuppression in Patients Undergoing Total Elbow Arthroplasty.

PURPOSE: Patients considering total elbow arthroplasty (TEA) may be receiving immunosuppressive therapy; however, the relationship between immunosuppressive medications and postoperative complications is not well defined. Our purpose was to assess the relationship between preoperative immunosuppression and short-term complications following TEA. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was reviewed from 2005 to 2020 to identify patients undergoing TEA. Procedures indicated for malignancy or infection were excluded. Patients were grouped according to preoperative chronic immunosuppressive status. Demographic and operative characteristics were compared between groups. The 30-day incidence of complications and reoperations were compared between groups. Multiple logistic regression models, inverse-weighted by propensity scores, were used to calculate odds ratio (OR) of experiencing any complication or return to the operating room based on immunosuppression status and other demographic characteristics. RESULTS: A total of 769 patients undergoing TEA were included, of whom 142 (18.5%) received chronic immunosuppression. Distribution of age, sex, race, body mass index, diabetes, and American Society of Anesthesiologists classification differed significantly between groups. Most procedures were performed on an inpatient basis, and the median operative duration was 148 minutes. Most procedures were indicated for fracture in the nonimmunosuppressed group and rheumatoid arthritis in the immunosuppressed group. Overall complication rates were 7.0% for immunosuppressed patients and 10.2% for nonimmunosuppressed patients. The incidence of complications and reoperations did not significantly differ between groups. After controlling for confounding and adjusting for patient characteristics, immunosuppressed patients were 0.52 times less likely to experience a complication. Additionally, there was no association between immunosuppression status and odds of return to the operating room. CONCLUSION: Similar rates of complications were observed following TEA, regardless of preoperative immunosuppression status. Chronic immunosuppression does not appear to increase the rates of postoperative complications for patients undergoing TEA. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

Local reports of climate change impacts in Sierra Nevada, Spain: sociodemographic and geographical patterns.

While we know that climate change is having different impacts on various ecosystems and regions of the world, we know less how the perception of such impacts varies within a population. In this study, we examine patterns of individual variation in climate change impacts reports using data from a sample (n = 238) drawn from 33 mountainous municipalities of Sierra Nevada, Spain. Sierra Nevada inhabitants report multiple climate change impacts, being the most frequently reported changes in snowfall and snow cover, abundance of terrestrial fauna, freshwater availability, and extreme temperatures. Reports of climate change impacts vary according to informants' sociodemographic characteristics and geographical location. People with life-long bonds with the environment and higher connection and dependence upon ecosystem services report more climate change impacts than other informants, as do people with lower level of schooling. We also found that reports of climate change impacts vary according to geographic areas, which reinforces the idea that climate change generates differentiated impacts even at small geographical scales. Understanding intracultural variation in reports of climate change impacts not only gives an enriched picture of the human dimensions of climate change but might also help design more targeted mitigation and adaptation responses. Supplementary Information: The online version contains supplementary material available at 10.1007/s10113-022-01981-5.

Expulsion from Community Childcare Centers During the COVID-19 Pandemic: A Review of One State's Practices.

Expulsion has been a well-documented practice in early learning centers throughout the United States. The present study attempted to describe expulsion practices in one state's community childcare centers during the COVID-19 pandemic. Surveys from 161 childcare program administrators were analyzed and, overall, expulsion rates appeared to be lower than they were pre-pandemic. No association was found between whether a program closed and reopened or remained open; the presence of a waiting list; if a program readmitted all or some children; factors that influenced which teachers were rehired; training provided to teaching staff; perceived frequency and intensity of challenging behavior; and availability of support for children with challenging behaviors and expulsion decisions. Results of the current study are analyzed and discussed in this article along with the results and how they fit into the literature.

Unraveling the interplay between iron homeostasis, ferroptosis and extramedullary hematopoiesis.

Iron participates in myriad processes necessary to sustain life. During the past decades, great efforts have been made to understand iron regulation and function in health and disease. Indeed, iron is associated with both physiological (e.g., immune cell biology and function and hematopoiesis) and pathological (e.g., inflammatory and infectious diseases, ferroptosis and ferritinophagy) processes, yet few studies have addressed the potential functional link between iron, the aforementioned processes and extramedullary hematopoiesis, despite the obvious benefits that this could bring to clinical practice. Further investigation in this direction will shape the future development of individualized treatments for iron-linked diseases and chronic inflammatory disorders, including extramedullary hematopoiesis, metabolic syndrome, cardiovascular diseases and cancer.

Use of 11C-acetate PET imaging in the evaluation of advanced atherogenic lesions.

The use of 11C-acetate as a PET/CT tracer for atherosclerotic lesions preferentially labels anti-inflammatory/pro-resolution intra-plaque macrophages. An overview of the mechanisms involved in the selective uptake.

NOD1 in the interplay between microbiota and gastrointestinal immune adaptations.

Nucleotide-binding oligomerization domain 1 (NOD1), a pattern recognition receptor (PRR) that detects bacterial peptidoglycan fragments and other danger signals, has been linked to inflammatory pathologies. NOD1, which is expressed by immune and non-immune cells, is activated after recognizing microbe-associated molecular patterns (MAMPs). This recognition triggers host defense responses and both immune memory and tolerance can also be achieved during these processes. Since the gut microbiota is currently considered a master regulator of human physiology central in health and disease and the intestine metabolizes a wide range of nutrients, drugs and hormones, it is a fact that dysbiosis can alter tissues and organs homeostasis. These systemic alterations occur in response to gastrointestinal immune adaptations that are not yet fully understood. Even if previous evidence confirms the connection between the microbiota, the immune system and metabolic disorders, much remains to be discovered about the contribution of NOD1 to low-grade inflammatory pathologies such as obesity, diabetes and cardiovascular diseases. This review compiles the most recent findings in this area, while providing a dynamic and practical framework with future approaches for research and clinical applications on targeting NOD1. This knowledge can help to rate the consequences of the disease and to stratify the patients for therapeutic interventions.

[Gender equality and health equity: strategic lessons from country experiences of gender mainstreaming in healthIgualdade de gênero e equidade em saúde: lições estratégicas de experiências de país na integração do gênero na saúde]. / Igualdad de género y equidad en salud: lecciones estratégicas de las experiencias de los países en la incorporación de la perspectiva de género en la salud.

OBJECTIVES: To analyze progress in organizational structures, mechanisms, strategies, and enabling factors and barriers towards gender mainstreaming (GM) in health in Guatemala, Guyana, and Peru, given GM's role in addressing gender inequalities in health as a key structural driver of health equity. METHODS: Data was obtained through a grey literature review of laws, policies, and/or program documents and semi-structured qualitative interviews with 37 informants. Analysis was based on a theoretical framework including 7 categories considered essential to advance GM in the health sector. RESULTS: Despite significant efforts and accumulated experiences of GM in health, structural barriers include: wider societal challenges of transforming gender unequal power relations; health system complexity combined with the low technical, political, and financial capacity of institutional structures tasked with GM; and limited coordination with (often weak) National Women's Machineries (NWMs). In some contexts, barriers are compounded by limited understanding of basic concepts underlying GM (at times exacerbated by misunderstandings related to intersectionality and/or engagement with men) and the absence of indicators to measure GM's concrete results and impact. CONCLUSIONS: Successful GM requires a more strategic and transformational agenda, developed and implemented in coordination with NWMs and civil society and with reference to external bodies (e.g. Committee on the Elimination of Discrimination against Women) to go beyond process, with clearer distinction between gender sensitivity and gender transformation, and definition of expected results and indicators to measure advances. These then could be better documented and systematized, enabling GM to be more broadly understood and operationalized as a concrete instrument towards health equity.

OBJETIVOS: Analisar o progresso nas estruturas organizacionais, mecanismos, estratégias, e fatores habilitadores e barreiras para a integração do gênero (IG) na saúde na Guatemala, na Guiana e no Peru, dado o papel da IG na abordagem das desigualdades de gênero na saúde como um dos principais impulsionadores estruturais da equidade em saúde. MÉTODOS: Os dados foram obtidos por meio de uma análise das leis, políticas e/ou documentos de programa e entrevistas qualitativas semi-estruturadas junto a 37 informantes, extraídos da literatura cinza. A análise foi efetuada com base em uma estrutura teórica que incluiu 7 categorias consideradas essenciais para promover a IG no setor da saúde. RESULTADOS: Apesar dos esforços significativos e das experiências acumuladas na IG na saúde, as barreiras estruturais incluem: os desafios sociais mais amplos de transformar relacionamentos desiguais de poder; a complexidade dos sistemas de saúde associada à baixa capacidade técnica, política e financeira das instituições encarregadas pela IG; e a coordenação limitada (e muitas vezes fraca) com as Maquinarias Nacionais de Mulheres (NWM, na sigla em inglês). Em alguns contextos, as barreiras são exacerbadas pela compreensão limitada de conceitos básicos nas bases da IG (às vezes agravadas por mal entendidos relacionados à intersecção com homens e/ou o envolvimento deles); e a ausência de indicadores para medir resultados concretos da IG e seu impacto. CONCLUSÕES: Para que a IG ocorra de fato, é necessária uma pauta mais estratégica e transformadora, elaborada e implementada em coordenação com as NWM e a sociedade civil, e fazendo referência a organismos externos (por exemplo, Comitê sobre a Eliminação de todas as Formas de Discriminação contra a Mulher) para que a integração inclua não só o processo, mas que forneça, além disso, uma diferenciação mais clara entre a sensibilidade às questões de gênero e a transformação das relações de gênero, e defina os resultados esperados e os indicadores para medir os avanços. A partir de então, elas poderiam ser melhor documentadas e sistematizadas, permitindo um melhor entendimento sobre a IG e sua operacionalização como instrumento concreto rumo à equidade na saúde.

Relation between Alpha-Synuclein and Core CSF Biomarkers of Alzheimer's Disease.

Background: Alzheimer's disease (AD) is characterized by the presence of ß-amyloid plaques and neurofibrillary tangles, while Lewy body dementia (LBD) is characterized by α-synuclein (α-syn) inclusions. Some authors examine α-syn protein in the neurodegeneration process of AD and propose to consider cerebrospinal fluid (CSF) α-syn as a possible additional biomarker to the so-called "core" of AD. Objective: To determine whether there is a correlation between α-syn levels and "core" AD biomarkers in patients with mild cognitive impairment (MCI). Materials and methods: In total, 81 patients in the early stages of MCI were selected from the outpatient dementia consultation in Alicante General Hospital. Using a cross-sectional case-control design, patients were analyzed in four groups: stable MCI (MCIs; n = 25), MCI due to AD (MCI-AD; n = 32), MCI due to LBD (MCI-LBD; n = 24) and a control group of patients with acute or chronic headache (Ctrl; n = 18). Correlation between CSF protein levels in the different groups was assessed by the Rho Spearman test. Results: We found positive correlations between T-tau protein and α-syn (ρ = 0.418; p value < 0.05) and p-tau181p and α-syn (ρ = 0.571; p value < 0.05) exclusively in the MCI-AD group. Conclusion: The correlation found between α-syn and tau proteins in the first stages of AD support the involvement of α-syn in the pathogenesis of AD. This result may have clinical and diagnostic implications, as well as help to apply the new concept of "precision medicine" in patients with MCI.

Intranasal pregnenolone increases acetylcholine in frontal cortex, hippocampus, and amygdala-Preferentially in the hemisphere ipsilateral to the injected nostril.

This study determined the effects of intranasal pregnenolone (IN-PREG) on acetylcholine (ACh) levels in selected areas of the rat brain, using in vivo microdialysis. Previous studies showed that PREG rapidly reaches the rodent brain after intranasal administration and that direct infusion of PREG and PREG-S into the basal forebrain modulates ACh release in frontal cortex, amygdala, and hippocampus. In the present study, we investigated the effects of IN-PREG on the cholinergic system in the rat brain. In the first experiment, IN-PREG (5.6 and 11.2 mg/ml) or vehicle was applied bilaterally, and we hypothesized that IN-PREG would increase ACh levels in amygdala, hippocampus, and frontal cortex, relative to baseline and vehicle. Dialysate was collected for 100 min, based on pilot data of duration of effect. Bilateral IN-PREG (5.6 and 11.2 mg/ml) increased frontal cortex and hippocampal ACh relative to both baseline and vehicle. Moreover, 11.2 mg/ml PREG increased ACh in the amygdala relative to baseline, the lower dose, and vehicle. Therefore, in the second experiment, IN-PREG (11.2 mg/ml) was applied only into one nostril, with vehicle applied into the other nostril, in order to determine whether ACh is predominantly increased in the ipsilateral relative to the contralateral amygdala. Unilateral application of IN-PREG increased ACh in the ipsilateral amygdala, whereas no effect was observed on the contralateral side, suggesting that PREG was transported from the nostrils to the brain via the olfactory epithelial pathway, but not by circulation. The present data provide additional information on IN-PREG action in the cholinergic system of frontal cortex, amygdala, and hippocampus. This may be relevant for therapeutic IN application of PREG in neurogenerative and neuropsychiatric disorders.