ROP39 is an Irgb10-specific parasite effector that modulates acute Toxoplasma gondii virulence.

Toxoplasma gondii (T. gondii) is a zoonotic apicomplexan parasite that is an important cause of clinical disability in humans. On a global scale, one third of the human population is infected with T. gondii. Mice and other small rodents are believed to be responsible for transmission of T. gondii to the domestic cat, its definitive host. Interferon-inducible Immunity-Related GTPases (IRG proteins) are important for control of murine T. gondii infections. Virulence differences between T. gondii strains are linked to polymorphic rhoptry proteins (ROPs) that cooperate to inactivate individual IRG family members. In particular, the pseudokinase ROP5 isoform B is critically important in laboratory strains of mice. We identified T. gondii ROP39 in complex with ROP5B and demonstrate its contribution to acute T. gondii virulence. ROP39 directly targets Irgb10 and inhibits homodimer formation of the GTPase leading to an overall reduction of IRG protein loading onto the parasitophorous vacuolar membrane (PVM). Maintenance of PVM integrity rescues the parasite from IRG protein-mediated clearance in vitro and in vivo. This study identifies a novel T. gondii effector that is important for specific inactivation of the IRG resistance system. Our data reveal that yet unknown T. gondii effectors can emerge from identification of direct interaction partners of ROP5B.

Phylogenomics reveals Adeleorina are an ancient and distinct subgroup of Apicomplexa.

Apicomplexans are a diverse phylum of unicellular eukaryotes that share obligate relationships with terrestrial and aquatic animal hosts. Many well-studied apicomplexans are responsible for several deadly zoonotic and human diseases, most notably malaria caused by Plasmodium. Interest in the evolutionary origin of apicomplexans has also spurred recent work on other more deeply-branching lineages, especially gregarines and sister groups like squirmids and chrompodellids. But a full picture of apicomplexan evolution is still lacking several lineages, and one major, diverse lineage that is notably absent is the adeleorinids. Adeleorina apicomplexans comprises hundreds of described species that infect invertebrate and vertebrate hosts across the globe. Although historically considered coccidians, phylogenetic trees based on limited data have shown conflicting branch positions for this subgroup, leaving this question unresolved. Phylogenomic trees and large-scale analyses comparing cellular functions and metabolism between major subgroups of apicomplexans have not incorporated Adeleorina because only a handful of molecular markers and a couple organellar genomes are available, ultimately excluding this group from contributing to our understanding of apicomplexan evolution and biology. To address this gap, we have generated complete genomes from mitochondria and plastids, as well as multiple deep-coverage single-cell transcriptomes of nuclear genes from two Adeleorina species, Klossia helicina and Legerella nova, and inferred a 206-protein phylogenomic tree of Apicomplexa. We observed distinct structures reported in species descriptions as remnant host structures surrounding adeleorinid oocysts. Klossia helicina and L. nova branched, as expected, with monoxenous adeleorinids within the Adeleorina and their mitochondrial and plastid genomes exhibited similarity to published organellar adeleorinid genomes. We show with a phylogeneomic tree and subsequent phylogenomic analyses that Adeleorina are not closely related to any of the currently sampled apicomplexan subgroups, and instead fall as a sister to a large clade encompassing Coccidia, Protococcidia, Hematozoa, and Nephromycida, collectively. This resolves Adeleorina as a key independently-branching group, separate from coccidians, on the tree of Apicomplexa, which now has all known major lineages sampled.

Rhodococcus erythropolis ATCC 4277 behavior against different metals and its potential use in waste biomining.

Rhodococcus erythropolis bacterium is known for its remarkable resistance characteristics that can be useful in several biotechnological processes, such as bioremediation. However, there is scarce knowledge concerning the behavior of this strain against different metals. This study sought to investigate the behavior of R. erythropolis ATCC 4277 against the residue of chalcopyrite and e-waste to verify both resistive capacities to the metals present in these residues and their potential use for biomining processes. These tests were carried out in a stirred tank bioreactor for 48 h, at 24ºC, pH 7.0, using a total volume of 2.0 L containing 2.5% (v/v) of a bacterial pre-culture. The pulp density of chalcopyrite was 5% (w/w), and agitation and oxygen flow rates were set to 250 rpm and 1.5 LO2 min-1, respectively. On the other hand, we utilized a waste of computer printed circuit board (WPCB) with a pulp density of 10% (w/w), agitation at 400 rpm, and an oxygen flow rate of 3.0 LO2 min-1. Metal concentration analyses post-fermentation showed that R. erythropolis ATCC 4277 was able to leach about 38% of the Cu present in the chalcopyrite residue (in ~ 24 h), and 49.5% of Fe, 42.3% of Ni, 27.4% of Al, and 15% Cu present in WPCB (in ~ 24 h). In addition, the strain survived well in the environment containing such metals, demonstrating the potential of using this bacterium for waste biomining processes as well as in other processes with these metals.

Pentraxin 3 Inhibits Complement-driven Macrophage Activation to Restrain Granuloma Formation in Sarcoidosis.

Rationale: Sarcoidosis is a multisystemic inflammatory disease characterized by the formation of granulomas in response to persistent stimuli. The long pentraxin PTX3 (pentraxin 3) has emerged as a component of humoral innate immunity with essential functions in the resolution of inflammation, but its role during granuloma formation is unknown. Objectives: To evaluate PTX3 as a modulator of pathogenic signals involved in granuloma formation and inflammation in sarcoidosis. Methods: Peripheral blood mononuclear cells obtained from patients with sarcoidosis harboring loss-of-function genetic variants and gene-deleted mice were used to assess the role of PTX3 in experimental models of granuloma formation in vitro and in vivo. The identified mechanisms of granulomatous inflammation were further evaluated in tissue and BAL samples and correlated with the disease course. Measurements and Main Results: We have identified a molecular link between PTX3 deficiency and the pathogenic amplification of complement activation to promote granuloma formation. Mechanistically, PTX3 deficiency licensed the complement component C5a-mediated activation of the metabolic checkpoint kinase mTORC1 (mammalian target of rapamycin complex 1) and the reprogramming of macrophages toward increased glycolysis to foster their proliferation and aggregation. This process sustained the further recruitment of granuloma-promoting immune cells and the associated proinflammatory microenvironment and influenced the clinical course of the disease. Conclusions: Our results identify PTX3 as a pivotal molecule that regulates complement-mediated signaling cues in macrophages to restrain granulomatous inflammation and highlight the therapeutic potential of this signaling axis in targeting granuloma formation in sarcoidosis.

Advancing health equity: A qualitative study assessing barriers and facilitators of implementing hereditary breast and ovarian cancer risk screening tools in community-based organizations.

Genetic counseling and testing (GCT) inform cancer management for persons at risk for hereditary breast and ovarian cancer (HBOC). Community-based organizations (CBOs) may play a role in identifying at-risk Latinx individuals to connect them to GCT but data are lacking. Two academic centers and their four CBO partners planned to implement a validated questionnaire for HBOC risk screening ("HBOC risk screening tool"). This study aimed to assess CBO's preferences for HBOC risk screening tools, as well as the barriers and facilitators anticipated for future implementation. Pre-implementation focus groups were conducted with CBO's staff. Discussions centered on current practices to identify and refer at-risk patients. During the discussion, staff were asked to select one out of five validated HBOC risk screening tools to implement and to discuss anticipated barriers/facilitators for implementation. The four focus groups were coded and qualitative analyzed following the Consolidated Framework for Implementation Research (CFIR) and Health Equity domains. All CBOs chose the Family History Screen 7 (FHS-7). Participants (N = 35) highlighted how the FHS-7 was easy to adapt to better fit the target population and changing guidelines. They had positive attitudes toward implementing the screening tool, stressed how the culture of the organization positioned them to reach the target population, and noted barriers in different CFIR domains (e.g., low knowledge about HBOC and GCT referrals; scarce available resources). Participants pointed to barriers related to health equity domains including limited access to GCT and follow-up care for uninsured and underinsured populations, challenges obtaining accurate family history, and immigration-related barriers. CBOs highlighted the importance of partnering with other stakeholders to overcome barriers. Findings emphasize the need to develop multi-level implementation strategies to overcome barriers and leverage facilitators. This study can inform the development of implementation toolkits for CBOs to implement HBOC screening tools to advance health equity.

Preliminary evidence on cigarette nicotine reduction with concurrent access to an e-cigarette: Manipulating cigarette nicotine content, e-liquid nicotine content, and e-liquid flavor availability.

The reinforcing characteristics of e-cigarettes could moderate the impact of reducing cigarette nicotine content. In this study, people who smoke daily were recruited from North Carolina and Pennsylvania (US) in 2018 and 2019. Within a randomized 2 × 2 × 2 factorial design, participants received investigational cigarettes and an e-cigarette for 12 weeks. Cigarette nicotine content was very low (0.4 mg/g of tobacco; VLNC) or normal (15.8 mg/g; NNC). E-liquids were 0.3% ("low") or 1.8% ("moderate") freebase nicotine, and available in tobacco flavors or tobacco, fruit, dessert and mint flavors. Study recruitment concluded before reaching the planned sample size (N = 480). Fifty participants were randomized and 32 completed the study. We found that randomization to VLNC, relative to NNC cigarettes, reduced self-reported cigarettes per day (CPD; mean difference: -12.96; 95% CI: -21.51, -4.41; p = 0.005); whereas e-liquid nicotine content and flavor availability did not have significant effects. The effect of cigarette nicotine content was larger in the moderate vs. low nicotine e-liquid groups and in the all flavors versus tobacco flavors e-liquid groups; tests of the interaction between e-liquid characteristics and cigarette nicotine content were not significant. Biomarkers of smoke exposure at Week 12 did not differ across conditions, which may reflect variability in adherence to only using VLNC cigarettes. In conclusion this study offers preliminary evidence that the extent to which cigarette nicotine reduction decreases smoking may depend on the reinforcing characteristics of alternative products, including the available nicotine contents and flavors of e-cigarettes.

BRCA1/2 mutations and risk-reducing bilateral salpingo-oophorectomy among Latinas: The UPTAKE study.

Bilateral salpingo-oophorectomy (BSO) is a risk management approach with strong evidence of mortality reduction for women with germline mutations in the tumor suppressor genes BRCA1 and BRCA2 (BRCA1/2). Few studies to date have evaluated uptake of BSO in women from diverse racial and ethnic backgrounds who carry BRCA1/2 mutations. The objective of the UPTAKE study was to explore rates and predictors of risk-reducing BSO among Latinas affected and unaffected with breast cancer who had a deleterious BRCA1/2 mutation. We recruited 100 Latina women with deleterious BRCA1/2 mutations from community hospitals, academic health systems, community, and advocacy organizations. Women completed interviews in Spanish or English. We obtained copies of genetic test reports for participants who provided signed medical release. After performing threefold cross-validation LASSO for variable selection, we used multiple logistic regression to identify demographic and clinical predictors of BSO. Among 100 participants, 68 had undergone BSO at the time of interview. Of these 68, 35 were US-born (61% of all US-born participants) and 33 were not (77% of the non-US-born participants). Among Latinas with BRCA1/2 mutations, older age (p = 0.004), personal history of breast cancer (p = 0.003), higher income (p = 0.002), and not having a full-time job (p = 0.027) were identified as variables significantly associated with uptake of BSO. Results suggest a high rate of uptake of risk-reducing BSO among a sample of Latinas with BRCA1/2 mutations living in the US. We document factors associated with BSO uptake in a diverse sample of women. Relevant to genetic counseling, our findings identify possible targets for supporting Latinas' decision-making about BSO following receipt of a positive BRCA1/2 test.

Process evaluation of a culturally targeted video for Latinas at risk of hereditary breast and ovarian cancer.

This paper presents a process evaluation of a culturally targeted narrative video about hereditary breast and ovarian cancer (HBOC) for Latina women at risk for HBOC. Spanish-speaking Latina women at risk for HBOC participated in a single arm study (n = 40). Participants watched the video developed by the authors and responded to surveys. We used mixed methods to assess theoretical constructs that are hypothesized mediators of narrative interventions (i.e., transportation or engagement, identification with characters, emotions) and implementation outcomes (e.g., acceptability). Descriptive statistics summarized theoretical constructs and implementation outcomes. We conducted Mann-Whitney U tests to assess the differences in theoretical and implementation outcomes between participants who were affected versus. unaffected and participants with different levels of education and health literacy. We used the consensual qualitative research framework to analyze qualitative data. Participants' mean age was 47.1 years (SD = 9.48). Most participants were high school graduates or less (62.5%). Acceptability of the video was extremely high (Md = 10.0, IQR = 0.2, scale 1-10). Most (82.5%) suggested video dissemination be through social media. Participants were highly engaged (Md = 5.7, IQR = 1.5, scale 1-7), strongly identified with the main character (Md = 8.7, IQR = 2.6, scale 1-10), and reported experiencing mostly positive emotions (Md = 9.5, IQR = 2.8, scale 1-10). Participants with low health literacy and affected participants reported a significantly higher identification with the main character (p<.05). Qualitative data reinforced the quantitative findings. Women reported gaining knowledge, correcting misconceptions, and feeling empowered. Our culturally targeted video is highly acceptable and targets mechanisms of behavior change for narrative interventions. The video is easily disseminable and can be used as an education tool for patients including affected and unaffected women and patients with different education and health literacy levels. Future studies should test the impact of the video in enhancing genetic counseling and testing uptake.

Host Genetic Signatures of Susceptibility to Fungal Disease.

Our relative inability to predict the development of fungal disease and its clinical outcome raises fundamental questions about its actual pathogenesis. Several clinical risk factors are described to predispose to fungal disease, particularly in immunocompromised and severely ill patients. However, these alone do not entirely explain why, under comparable clinical conditions, only some patients develop infection. Recent clinical and epidemiological studies have reported an expanding number of monogenic defects and common polymorphisms associated with fungal disease. By directly implicating genetic variation in the functional regulation of immune mediators and interacting pathways, these studies have provided critical insights into the human immunobiology of fungal disease. Most of the common genetic defects reported were described or suggested to impair fungal recognition by the innate immune system. Here, we review common genetic variation in pattern recognition receptors and its impact on the immune response against the two major fungal pathogens Candida albicans and Aspergillus fumigatus. In addition, we discuss potential strategies and opportunities for the clinical translation of genetic information in the field of medical mycology. These approaches are expected to transfigure current clinical practice by unleashing an unprecedented ability to personalize prophylaxis, therapy and monitoring for fungal disease.

A Nondilated Main Pancreatic Duct Predicts Type 2 Autoimmune Pancreatitis: Comparative Study of Resected Pancreatic Head Masses.

BACKGROUND: Chronic pancreatitis (CP), pancreatic cancer (PCa), and autoimmune pancreatitis (AIP) often present as a pancreatic mass. Accurate diagnosis is not always possible; up to 8% of surgical procedures are performed in benign pancreatic masses presumed to be malignant. OBJECTIVES: We aimed to compare clinical and imaging characteristics of resected focal type 2 AIP, CP, and PCa and identify factors that could improve preoperative differential diagnosis. METHODS: Charts from patients that underwent pancreatic resection under suspicion of PCa between 2000 and 2014 were reviewed. Clinical and imaging data were recorded. Subjects were grouped as type 2 AIP, CP, and PCa. RESULTS: We included 79 cases; 41 men, mean age of 57.3 years/old ± 15.6 SD. Pathology report was type 2 AIP (20%), CP (10%), and PCa (70%). According to international consensus criteria for AIP 11 cases were deemed probable type 2 and 5 as unspecific pancreatic mass. A nondilated main pancreatic duct (MPD) was associated with AIP (OR 9.3; 95% CI 3.05-28.7), p < 0.001; obstructive jaundice (OR 28.5; 95% CI 8.18-79.5); and a dilated MPD (OR 5.21; 95% CI 1.9-14.6) suggested malignancy. CONCLUSIONS: In the setting of undetermined pancreatic focal mass, a nondilated MPD suggests the diagnosis of type 2 AIP.

Latinas' knowledge of and experiences with genetic cancer risk assessment: Barriers and facilitators.

Disparities in genetic cancer risk assessment (GCRA) uptake persist between Latinas and Non-Hispanic Whites. This study utilized a mental model approach to interview 20 Latinas (10 affected, 10 unaffected) at increased risk for hereditary breast and ovarian cancer (HBOC). Participants were asked about their knowledge and perceptions of GCRA, HBOC, risk, benefits, motivators, barriers, challenges, and experiences with GCRA. Using the Consensual Qualitative Analysis Framework, two authors independently coded the interviews and applied the final codes upon consensus. Additionally, interviews were coded to identify whether participants spontaneously brought up certain topics without a prompt. Findings identified multiple barriers and facilitators to GCRA uptake in this population, including patient level psychosocial/cultural factors (e.g., limited knowledge, worry about relatives' risk) and healthcare system factors (e.g., receiving no referrals). There were notable differences in awareness and knowledge between affected and unaffected women (e.g., genetic testing awareness), as well as knowledge gaps that were evident in both groups (e.g., age of diagnosis as a risk factor). To reduce disparities in GCRA uptake, interventions should address identified facilitators and barriers. Differences in knowledge and awareness between affected and unaffected women support the development of targeted interventions that address specific knowledge gaps. This study was registered in ClinicalTrials.gov (NCT03075540) by Alejandra Hurtado de Mendoza, Ph.D.

High blood pressure in Hispanics in the United States: a review.

PURPOSE OF REVIEW: To provide an overview of the available data on the prevalence of hypertension (HTN) in various groups and segments of the Hispanic population; prevalence of awareness, treatment and control of HTN among Hispanics; and HTN-related disparities, through disproportionate effects on the Hispanic elderly, women, and young adults. RECENT FINDINGS: Data on HTN in Hispanics has been lacking or aggregated and frequently not inclusive of certain groups of Hispanics but the available data do show a pattern of more prevalent HTN and HTN disparities among Hispanics compared with non-Hispanic whites. Hispanic adults have some of the highest prevalence of poorly controlled blood pressure compared with any other race-ethnic group in the United States. Further, the impact of the most recent iteration of the HTN guidelines among all segments of the Hispanic population has not been well studied. SUMMARY: The most recent HTN guidelines will likely only further illuminate worsening HTN-related disparities among Hispanics. These findings suggest significant screening and treatment disparities must be addressed to reduce HTN risk among the Hispanic population.

The Effects of Yoga on Patients with Mild Cognitive Impairment and Dementia: A Scoping Review.

Yoga is an ancient mind body practice. Although yoga has been used as a complementary health approach for enhancing wellness and addressing a variety of health issues, little is known about the impact of yoga on cognitive functioning in adults with mild cognitive impairment (MCI) and dementia. We conducted a literature review to examine the impact of yoga on persons with MCI and dementia. Eight studies were identified that reported on yoga as either the primary intervention or one component of a multi-component intervention in samples of persons with MCI or dementia. Results suggest that yoga may have beneficial effects on cognitive functioning, particularly on attention and verbal memory. Further, yoga may affect cognitive functioning through improved sleep, mood, and neural connectivity. There are a number of limitations of the existing studies, including a lack of intervention details, as well as variability in the frequency/duration and components of the yoga interventions. A further complicating issue is the role of various underlying etiologies of cognitive impairment. Despite these limitations, providers may consider recommending yoga to persons with MCI or dementia as a safe and potentially beneficial complementary health approach.

Correlation among fecal indicator bacteria and physicochemical parameters with the presence of Helicobacter pylori DNA in raw and drinking water from Bogotá, Colombia.

BACKGROUND: The quality of raw and drinking water is a matter of considerable concern due to the possibility of fecal contamination. To assess the quality and public health risk of different types of water, the fecal indicator bacteria (FIB) are used. However, some pathogens, such as Helicobacter pylori, may be present in water when FIB cannot be found. H pylori is recognized as the causative agent of chronic gastritis, peptic and duodenal ulcers, and gastric cancer. The aim of this study was to evaluate the relationships among physicochemical parameters, FIB concentrations, and the presence of H pylori DNA in raw and drinking water from Bogotá, Colombia. MATERIALS AND METHODS: A total of 310 water samples were collected 1 day per week from July 2015 to August 2016, and physicochemical parameters (pH, turbidity, conductivity, and residual free chlorine) were measured. Presence of H pylori DNA was determined and quantified by quantitative polymerase chain reaction (qPCR). Fecal indicator bacteria (total coliforms, Escherichia coli, and spores of sulfite-reducing Clostridia) were enumerated by using standard culture techniques. RESULTS: Thirty of 155 (31%) raw water samples and forty-eight of 155 (38.7%) drinking water samples were positive for the presence of H pylori. No statistically significant relationships were found between physicochemical parameters or FIB with the presence or absence of H pylori in any sample (P < 0.05). CONCLUSIONS: This study provides evidence of the presence of H pylori DNA in raw and drinking water in Bogotá, and shows that the detection and enumeration of FIB and physicochemical parameters in water do not correlate with the risk of contamination with H pylori.

Pharmacologic Treatment of Hypertensive Urgency in the Outpatient Setting: A Systematic Review.

BACKGROUND: Hypertensive urgency (HU), defined as acute severe uncontrolled hypertension without end-organ damage, is a common condition. Despite its association with long-term morbidity and mortality, guidance regarding immediate management is sparse. Our objective was to summarize the evidence examining the effects of antihypertensive medications to treat. METHODS: We searched the PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Database of Abstracts of Reviews of Effects (DARE), Cochrane Database of Systematic Reviews, Web of Science, Google Scholar, and Embase through May 2016. STUDY SELECTION: We evaluated prospective controlled clinical trials, case-control studies, and cohort studies of HU in emergency room (ER) or clinic settings. We initially identified 11,223 published articles. We reviewed 10,748 titles and abstracts and identified 538 eligible articles. We assessed the full text for eligibility and included 31 articles written in English that were clinical trials or cohort studies and provided blood pressure data within 48 h of treatment. Studies were appraised for risk of bias using components recommended by the Cochrane Collaboration. The main outcome measured was blood pressure change with antihypertensive medications. Since studies were too diverse both clinically and methodologically to combine in a meta-analysis, tabular data and a narrative synthesis of studies are presented. RESULTS: We identified only 20 double-blind randomized controlled trials and 12 cohort studies, with 262 participants in prospective controlled trials. However, we could not pool the results of studies. In addition, comorbidities and their potential contribution to long-term treatment of these subjects were not adequately addressed in any of the reviewed studies. CONCLUSIONS: Longitudinal studies are still needed to determine how best to lower blood pressure in patients with HU. Longer-term management of individuals who have experienced HU continues to be an area requiring further study, especially as applicable to care from the generalist.

Absorption of Carotenoids and Mechanisms Involved in Their Health-Related Properties.

Carotenoids participate in the normal metabolism and function of the human body. They are involved in the prevention of several diseases, especially those related to the inflammation syndrome. Their main mechanisms of action are associated to their potent antioxidant activity and capacity to regulate the expression of specific genes and proteins. Recent findings suggest that carotenoid metabolites may explain several processes where the participation of their parent carotenoids was unclear. The health benefits of carotenoids strongly depend on their absorption and transformation during gastrointestinal digestion. The estimation of the 'bioaccessibility' of carotenoids through in vitro models have made possible the evaluation of the effect of a large number of factors on key stages of carotenoid digestion and intestinal absorption. The bioaccessibility of these compounds allows us to have a clear idea of their potential bioavailability, a term that implicitly involves the biological activity of these compounds.

Microbial source markers assessment in the Bogotá River basin (Colombia).

The microbiological indicators traditionally used to assess fecal contamination are insufficient to identify the source. The aim of this study was to detect microbial markers to identify the source of fecal pollution in the Bogotá River (Colombia). For this, we determined non-discriminating indicators such as Escherichia coli, somatic coliphages and phages infecting strain RYC2056 of Bacteroides, and potential source tracking markers as phages infecting strains GA17, HB13, and CA8 of Bacteroides, sorbitol-fermenting bifidobacteria, and molecular markers of Bifidobacterium adolescentis, Bifiodobacterium dentium, and Bacteroidetes in raw municipal wastewaters, slaughterhouse wastewaters, and the Bogotá River. Bacteriophages infecting Bacteroides strain GA17 and the molecular markers identified the wastewater sources. In contrast, sorbitol-fermenting bifidobacteria failed regarding specificity. In the Bogotá River, phages infecting strain GA17 were detected in all samples downstream of Bogotá, whereas they should be concentrated from 1 l samples in upstream samples containing less than 10(3) E. coli/100 ml to be detected. In the river water, the fraction of positive detections of molecular markers was lower than that of phages infecting strain GA17. The ratio SOMCPH/GA17PH was shown also to be a good marker. These results provide information that will allow focusing measures for sanitation of the Bogotá River.

Efficacy and Safety of Intravenous Magnesium Sulfate in Spinal Surgery: A Systematic Review and Meta-Analysis.

Optimizing pain management in spinal surgery is crucial for preventing adverse events due to delayed mobilization. Magnesium sulfate has potential benefits in spinal surgery because of its analgesic properties and modulation of neurotransmitters and autonomic nervous system. Existing evidence regarding the use of magnesium sulfate is partial and controversial, necessitating a comprehensive meta-analysis to evaluate its efficacy and safety. The aim of this study was to conduct a comprehensive meta-analysis to evaluate the efficacy and safety of magnesium sulfate in spinal surgery compared to other available options. This meta-analysis adhered to the PRISMA guidelines. Patients undergoing spinal surgery were included, with the intervention group receiving intravenous magnesium sulfate (MS) at various doses or combinations, whereas the comparison group received other alternatives or a placebo. The efficacy and safety outcomes were assessed. Data were collected from multiple databases and analyzed using Review Manager version 5.4. Heterogeneity was assessed and fixed- or random-effects models were applied. The meta-analysis included eight studies (n = 541). Magnesium sulfate demonstrated significant reductions in pain at 24 h (MD -0.20, 95% CI: -0.39 to -0.02) and opioid consumption (SMD -0.66, 95% CI: -0.95 to -0.38) compared to placebo. Additionally, a decrease in the use of muscle relaxants (SMD -0.91, 95% CI: -1.65 to -0.17) and remifentanil (SMD -1.52, 95% CI: -1.98 to -1.05) was observed. In contrast, an increase in extubation time (MD 2.42, 95% CI: 1.14 to 3.71) and verbal response (MD 1.85, 95% CI: 1.13 to 2.58) was observed compared to dexmedetomidine. In conclusion, magnesium sulfate administration in spinal surgery reduced pain and opioid consumption, and prolonged orientation and verbal response. No significant differences in blood pressure or heart rate were observed between the groups.

Palliative Care in the Ageing European Population: A Cross-Country Comparison.

With Europe's ageing population and rising demand for palliative care, it is crucial to examine the use of palliative care among older adults during their last years of life and understand the factors influencing their access and end-of-life circumstances. This study employed a cohort of SHARE participants aged 65 years or older who had passed away between Wave 6 (2015) and Wave 7 (2017). Information on death circumstances, palliative care utilization, and associated variables were analysed. The study revealed that nearly 13.0% of individuals across these countries died under palliative care, with Slovenia having the lowest rate (0.3%) and France the highest (30.4%). Palliative care utilization in the last 30 days before death was observed in over 24.0% of participants, with the Czech Republic having the lowest rate (5.0%) and Greece the highest (48.8%). A higher risk of using or dying in palliative care was significantly associated with cognitive impairment (low verbal fluency), physical inactivity, and good to excellent self-perceived health. This work highlights the urgent need for enhanced global access to palliative care and advocates for the cross-country comparison of effective practices within Europe, tailored to the unique healthcare needs of older adults.