Gut microbiota and its relationship with early vascular ageing in a Spanish population (MIVAS study).

BACKGROUND: Gut microbiota and its by-products are increasingly recognized as having a decisive role in cardiovascular diseases. The aim is to study the relationship between gut microbiota and early vascular ageing (EVA). METHODS: A cross-sectional study was developed in Salamanca (Spain) in which 180 subjects aged 45-74 years were recruited. EVA was defined by the presence of at least one of the following: carotid-femoral pulse wave velocity (cf-PWV), cardio-ankle vascular index (CAVI) or brachial-ankle pulse wave velocity (ba-PWV) above the 90th percentile of the reference population. All other cases were considered normal vascular ageing (NVA). MEASUREMENTS: cf-PWV was measured by SphygmoCor® System; CAVI and ba-PWV were determined by Vasera 2000® device. Gut microbiome composition in faecal samples was determined by 16S rRNA Illumina sequencing. RESULTS: Mean age was 64.4 ± 6.9 in EVA group and 60.4 ± 7.6 years in NVA (p < .01). Women in EVA group were 41% and 53% in NVA. There were no differences in the overall composition of gut microbiota between the two groups when evaluating Firmicutes/Bacteriodetes ratio, alfa diversity (Shannon Index) and beta diversity (Bray-Curtis). Bilophila, Faecalibacterium sp.UBA1819 and Phocea, are increased in EVA group. While Cedecea, Lactococcus, Pseudomonas, Succiniclasticum and Dielma exist in lower abundance. In logistic regression analysis, Bilophila (OR: 1.71, 95% CI: 1.12-2.6, p = .013) remained significant. CONCLUSIONS: In the studied Spanish population, early vascular ageing is positively associated with gut microbiota abundance of the genus Bilophila. No relationship was found between phyla abundance and measures of diversity.

Assessing short-term and long-term security and efficacy of anterior nucleus of the thalamus deep brain stimulation for treating drug-resistant epilepsy: A systematic review and single-arm meta-analysis.

Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) is a widespread invasive procedure for treating drug-resistant epilepsy. Nonetheless, there is a persistent debate regarding the short-term and long-term efficacy and safety of ANT-DBS. Thus we conducted a systematic review and meta-analysis. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), we searched PubMed, Cochrane, Embase, and Web of Science for studies treating refractory epilepsy with ANT-DBS. Short-term analysis was considered for studies with a mean follow-up of 3 years or less. The following outcomes were assessed for data extraction: procedure responders and nonresponders, increased seizure frequency, complications, and procedure-related mortality. Of 650 studies, 25 fit our inclusion criteria, involving 427 patients. Previous surgical treatments have been reported in 214 patients (50.1%) and a median average baseline seizure frequency of 64.9 monthly seizures. In the short-term analysis, we observed a proportion of 67% (95% confidence interval [CI] 54%-79%) of responders and 33% (95% CI 21%-46%) of nonresponders. In addition, 4% (95% CI 0%-9%) of the patients presented increased seizure frequency. In the long-term analysis, we observed 72% (95% CI 66%-78%) responders and 27% (95% CI 21%-34%) nonresponders. Moreover, there was a 2% (95% CI 0%-5%) increase in seizure frequency. No procedure-related mortality was reported at any follow-up. ANT-DBS effectively treats refractory epilepsy, with lasting short-term and long-term benefits. It remains safe and efficient despite complications, showing no procedure-linked fatalities, high patient responsiveness, and minimal increased seizures. Consistent results over time and low morbidity/mortality rates emphasize its worth. Further research is necessary to diminish the discrepancy among results.

Inflammation Is a Histological Characteristic of Skeletal Muscle in Chronic Limb Threatening Ischemia.

BACKGROUND: The loss of skeletal muscle is a prognostic factor in several diseases including in patients with chronic limb threatening ischemia (CLTI). Patients with CLTI also have a lower skeletal mass and area when compared to those with claudication. However, there are no currently available data regarding the histological characteristics of core muscles in patients with CLTI. This study aims to determine the differences in core skeletal muscles between patients with claudication and those with CLTI. The second aim is to evaluate the differences in myokines, which are molecules secreted by skeletal muscle, between patients with claudication and those with CLTI. METHODS: An observational, prospective study was conducted from January 2018 to July 2022 involving consecutive patients with peripheral arterial disease (PAD). The clinical characteristics were registered. In PAD patients with surgical indication for common femoral artery approach, samples of sartorius skeletal muscle (and not from the limb muscles directly involved in the ischemic process) were collected. The samples were submitted to histological characterization on hematoxylin-eosin and to immunohistochemical analysis to detect CD45+ leukocytes and CD163+ macrophages. The extent of the inflammatory cells (leukocytes and macrophages) was semiquantitatively assessed using a 0-to-4 grade scale as follows: absent (0†), mild (†), moderate (††), severe (†††), and very severe (††††). Serum levels of myokines: irisin, myostatin, IL-8, and lL-6 were determined with multiplex bead-based immunoassay. RESULTS: 119 patients (mean age: 67.58 ± 9.60 years old, 79.80% males) 64 with claudication and 54 with CLTI were enrolled in the study. No differences were registered between patients with claudication and those with CLTI on age, gender, cardiovascular risk factors, and medication, except on smoking habits. There was a significantly higher prevalence of smokers and a higher smoking load in the claudication group. Samples of sartorius skeletal muscle from 40 patients (14 with claudication and 26 with CLTI) were submitted to histological analysis. No differences were found in skeletal muscle fibers preservation, trauma, or hemorrhage (on hematoxylin-eosin staining). However, in the immunohistochemistry study, we found more inflammatory cells CD45+ leukocytes in patients with CLTI when compared to those with claudication [CD45+ ≥ moderate (††): claudication (n = 14): 4; 28.57%; CLTI (n = 25): 16; 64.00%; P = 0.034]. Patients with CLTI also had higher tissue levels of CD163+ macrophages, but this difference was not significant [CD163+ ≥ moderate (††): claudication (n = 13): 7; 53.85%; CLTI (n = 27): 21; 77.78%; P = 0.122]. The serum levels of the myokines, irisin, and myostatin were below the lower limit of detection, in the majority of patients, so no valid results were obtained. However, patients with CLTI had a higher serum level of Interleukin (IL)-6 and IL-8. CONCLUSIONS: CLTI patients exhibit increased quantities of leukocytes in their sartorius muscle, as well as elevated serum levels of myokines IL-8 and IL-6. Inflamed skeletal muscle can contribute to the loss of muscle mass and account for the lower density of skeletal muscle observed in CLTI. Additionally, inflamed skeletal muscle may contribute to the development of systemic inflammation through the secretion of pro-inflammatory cytokines into the systemic circulation. Halting the inflammatory process could eventually improve the prognosis of CLTI patients.

Higher Levels of Cytokines in Patients with Chronic Limb-Threatening Ischemia.

BACKGROUND: Inflammation is a key element in the initiation and progression of peripheral arterial disease (PAD). Understanding the impact of inflammatory molecules, as cytokines in PAD could help us to improve the prognosis of these patients. The main goal of this study was to compare the serum level of cytokines between patients with claudication to those with chronic limb-threatening ischemia (CLTI). The second objective was to evaluate the relationship between the levels of cytokines and death or amputation rate. METHODS: An observational, single-center, and prospective study was conducted from January 2018 to July 2022. The study was approved by the ethical commission of the Local Hospital (75/2017). Patients with PAD, suggested by the clinical history and objective examination and confirmed with ankle-brachial index, attending vascular surgery consultations of the first author were included. The following exclusion criteria were applied: i) bedridden individuals or subjects who refused to participate in the protocol; ii) diseases responsible for body composition changes or proinflammatory state; iii) recent diet change, iv) active malignancy, v) autoimmune disease, vi) active infection, vii) chronic renal failure (glomerular filtration rate <30 mL/min/1.73 m2), or viii) heart failure in the past 3 months. This cohort was observed at admission, 3, 6, and 12 months. A panel of 27 cytokines was determined with ELISA, at baseline. RESULTS: We included 119 subjects (mean age: 67.58 ± 9.60 years old; 79.80% males), 65 patients with claudication and 54 with CLTI. From the 27 cytokines analyzed, patients with CLTI, when compared to those with claudication, had a higher serum level of 11 cytokines: IL1ra, IL-6, IL-8, IL12 p70, G-CSF, IP-10, MCP-1, MIP-1α, PDGF-ß, RANTES, and TNF-α. From the group of patients with CLTI those who underwent a major amputation had a higher serum level of FGF-basic [median = 49.04; interquartile range = 37.03-52.49; versus median = 33.04; interquartile range = 28.60-38.98; P = 0.001]. CONCLUSIONS: Patients with CLTI have higher serum level of inflammatory cytokines, which may have role in the prognosis of these patients.

Efficacy and safety of microvascular decompression with or without partial sensory rhizotomy: a comprehensive meta-analysis and systematic review in treating trigeminal neuralgia.

Classical trigeminal neuralgia (TN), caused by vascular compression of the nerve root, is a severe cause of pain with a considerable impact on a patient's quality of life. While microvascular decompression (MVD) has lower recurrence rates when compared with partial sensory rhizotomy (PSR) alone, refractoriness can still be as high as 47%. We aimed to assess the efficacy and safety profile of MVD + PSR when compared to standalone MVD for TN. We searched Medline, Embase, and Web of Science following PRISMA guidelines. Eligible studies included those with ≥ 4 patients, in English, published between January 1980 and December 2023, comparing MVD vs. MVD + PSR for TN. Endpoints were pain cure, immediate post-operative pain improvement, long-term effectiveness, long-term recurrence, and complications (facial numbness, hearing loss, and intracranial bleeding). We pooled odds ratios (OR) with 95% confidence intervals with a random-effects model. I2 was used to assess heterogeneity, and sensitivity and Baujat analysis were conducted to address high heterogeneity. Eight studies were included, comprising a total of 1,338 patients, of whom 1,011 were treated with MVD and 327 with MVD + PSR. Pain cure analysis revealed a lower likelihood of pain cure in patients treated with MVD when compared to patients treated with MVD + PSR (OR = 0.30, 95% CI: 0.13 to 0.72). Immediate postoperative pain improvement assessment revealed a lower likelihood of improvement in the MVD group when compared with the MVD + PSR group (OR = 0.31, 95% CI: 0.10 to 0.95). Facial numbness assessment revealed a lower likelihood of occurrence in MVD alone when compared to MVD + PSR (OR = 0.08, 95% CI: 0.04 to 0.15). Long-term effectiveness, long-term recurrence, hearing loss, and intracranial bleeding analyses revealed no difference between both approaches. Our meta-analysis identified that MVD + PSR was superior to MVD for pain cure and immediate postoperative pain improvement for treating TN. However, MVD + PSR demonstrated a higher likelihood of facial numbness complications. Furthermore, identified that hearing loss and intracranial bleeding complications appear comparable between the two treatments, and no difference between long-term effectiveness and recurrence.

Differentiation of glioblastoma stem cells promoted by miR-128 or miR-302a overexpression enhances senescence-associated cytotoxicity of axitinib.

Despite the intense global efforts towards an effective treatment of glioblastoma (GB), current therapeutic options are unsatisfactory with a median survival time of 12-15 months after diagnosis, which has not improved significantly over more than a decade. The high tumoral heterogeneity confers resistance to therapies, which has hindered a successful clinical outcome, GB remaining among the deadliest cancers. A hallmark of GB is its high recurrence rate, which has been attributed to the presence of a small subpopulation of tumor cells called GB stem-like cells (GSC). In the present work, the efficacy of a multimodal strategy combining microRNA (miRNA) modulation with new generation multitargeted tyrosine kinase inhibitors (imatinib and axitinib) was investigated aiming at tackling this subpopulation of GB cells. MiR-128 and miR-302a were selected as attractive therapeutic candidates on the basis of previous findings reporting that reestablishment of their decreased expression levels in GSC resulted in cell differentiation, which could represent a possible strategy to sensitize GSC to chemotherapy. Our results show that overexpression of miR-128 or miR-302a induced GSC differentiation, which enhanced senescence mediated by axitinib treatment, thus further impairing GSC proliferation. We also provided evidence for the capacity of GSC to efficiently internalize functionalized stable nucleic acid lipid particles, previously developed and successfully applied in our laboratory to target GB. Taken together, our findings will be important in the future design of a GB-targeted multimodal miRNA-based gene therapy, combining overexpression of miR-128 or miR-302a with axitinib treatment, endowed with the ability to overcome drug resistance.

Exotic Compact Objects and the Fate of the Light-Ring Instability.

Ultracompact objects with light rings (LRs) but without an event horizon could mimic black holes (BHs) in their strong gravity phenomenology. But are such objects dynamically viable? Stationary and axisymmetric ultracompact objects that can form from smooth, quasi-Minkowski initial data must have at least one stable LR, which has been argued to trigger a spacetime instability; but its development and fate have been unknown. Using fully nonlinear numerical evolutions of ultracompact bosonic stars free of any other known instabilities and introducing a novel adiabatic effective potential technique, we confirm the LRs triggered instability, identifying two possible fates: migration to nonultracompact configurations or collapse to BHs. In concrete examples we show that typical migration (collapse) timescales are not larger than ∼10^{3} light-crossing times, unless the stable LR potential well is very shallow. Our results show that the LR instability is effective in destroying horizonless ultracompact objects that could be plausible BH imitators.

Inflammation and Loss of Skeletal Muscle Mass in Chronic Limb Threatening Ischemia.

BACKGROUND: Lower extremity peripheral arterial disease (PAD) is an atherosclerotic disease of the lower extremities. Atherosclerosis, inflammation, and sarcopenia are independently associated and potentiate each other. Inflammation is deeply involved in the formation and progression of atherosclerosis and is also involved in the pathophysiology of sarcopenia. Sarcopenia is defined as low muscle mass, with low muscle strength. This study aims to determine the differences in skeletal muscle characteristics and in inflammatory parameters between patients with claudication and with chronic limb threatening ischemia (CLTI). METHODS: An observational, prospective study in patients with PAD was conducted from January 2018 to December 2020. The clinical characteristics and the cardiovascular risk factors were prospectively registered. The inflammatory parameters determined were: positive acute phase proteins (C-reactive Protein- CRP- and fibrinogen) and negative acute phase proteins albumin, total cholesterol and high-density lipoprotein (HDL). The skeletal muscle area and density were quantified with a computed topography (CT) scan. The strength was determined with a Jamar® hydraulic hand dynamometer. RESULTS: A total of 116 patients (mean age: 67.65 ± 9.53 years-old) 64% with claudication and 46% with CLTI were enrolled in the study. No differences were registered between patients with claudication and CLTI on age, cardiovascular risk factors (hypertension, dyslipidemia, diabetes mellitus, and smoking habits) and medication. There was a higher prevalence of men in the claudication group (88.89% vs. 71.70%, P = 0.019). Analyzing the inflammatory parameters, we noted that patients with CLTI had increased serum levels of positive acute phase proteins: CRP (37.53 ± 46.61 mg/L vs. 9.18 ± 26.12 mg/L, P = 0.000), and fibrinogen (466.18 ± 208.07 mg/dL vs. 317.37 ± 79.42 mg/dL, P = 0.000). CLTI patients had decreased negative acute phase proteins: albumin (3.53 ± 0.85 g/dL vs. 3.91 ± 0.72 g/dL, P = 0.001), total cholesterol (145.41 ± 38.59 mg/dL vs. 161.84 ± 34.94 mg/dL, P = 0.013) and HDL (38.70 ± 12.19 mg/dL vs. 51.31 ± 15.85 mg/dL, P = 0.000). We noted that patients with CLTI had lower skeletal muscle area and mass (14,349.77 ± 3,036.60 mm2 vs. 15,690.56 ± 3,183.97 mm2P = 0.013; 10.11 ± 17.03HU vs. 18.02 ± 13.63HU P = 0.013). After adjusting for the variable sex, the association between skeletal muscle density and CLTI persisted (r (97) = -0.232, P = 0.021). The groups did not differ in strength (patients with claudication: 25.39 ± 8.23 Kgf vs. CLTI: 25.17 ± 11.95 Kgf P = 0.910). CONCLUSIONS: CLTI patients have decreased skeletal muscle mass and a systemic inflammation status. Recognizing the deleterious triad of atherosclerosis, inflammation and loss of skeletal mass patients with CLTI is an opportunity to improve medical therapy and to perform a timely intervention to stop this vicious cycle.

Burst Transspinal Magnetic Stimulation Alleviates Nociceptive Pain in Parkinson Disease-A Pilot Phase II Double-Blind, Randomized Study.

BACKGROUND AND AIMS: Nociception is the most prevalent pain mechanism in Parkinson disease (PD). It negatively affects quality of life, and there is currently no evidence-based treatment for its control. Burst spinal cord stimulation has been used to control neuropathic pain and recently has been shown to relieve pain of nociceptive origin. In this study, we hypothesize that burst transspinal magnetic stimulation (bTsMS) reduces nociceptive pain in PD. MATERIALS AND METHODS: Twenty-six patients were included in a double-blind, sham-controlled, randomized parallel trial design, and the analgesic effect of lower-cervical bTsMS was assessed in patients with nociceptive pain in PD. Five daily induction sessions were followed by maintenance sessions delivered twice a week for seven weeks. The primary outcome was the number of responders (≥ 50% reduction of average pain intensity assessed on a numerical rating scale ranging from 0-10) during the eight weeks of treatment. Mood, quality of life, global impression of change, and adverse events were assessed throughout the study. RESULTS: Twenty-six patients (46.2% women) were included in the study. The number of responders during treatment was significantly higher after active than after sham bTsMS (p = 0.044), mainly owing to the effect of the first week of treatment, when eight patients (61.5%) responded to active and two (15.4%) responded to sham bTsMS (p = 0.006); the number needed to treat was 2.2 at week 1. Depression symptom scores were lower after active (4.0 ± 3.1) than after sham bTsMS (8.7 ± 5.3) (p = 0.011). Patients' global impressions of change were improved after active bTsMS (70.0%) compared with sham bTsMS (18.2%; p = 0.030). Minor adverse events were reported in both arms throughout treatment sessions. One major side effect unrelated to treatment occurred in the active arm (death due to pulmonary embolism). Blinding was effective. CONCLUSION: BTsMS provided significant pain relief and improved the global impression of change in PD in this phase-II trial. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT04546529.

Association of Skeletal Muscle and Cardiovascular Risk Factors in Patients with Lower Extremity Arterial Disease.

BACKGROUND: Sarcopenia is defined as low muscle mass, with low muscle strength or low physical performance. The skeletal muscle mass (or density) and strength are inversely associated with cardiovascular risk factors. We aim to determine the relationship between skeletal muscle characteristics (strength, mass, area), and cardiovascular risk factors in a population with lower extremity artery disease (LEAD). METHODS: An observational, prospective study including patients with LEAD was conducted from January 2018 to December 2020. The cardiovascular risk factors and anthropometric measurements were prospectively registered. The skeletal muscle characteristics (area, density/mass and strength) were analysed. The skeletal muscle area and density were quantified with a CT scan. The strength was determined with a Jamar® hydraulic hand dynamometer. RESULTS: A total of 96 patients with LEAD with 67.70 ± 10.11 years-old were enrolled in the study. The most prevalent cardiovascular risk factor was hypertension, followed by dyslipidemia and diabetes. Patients with diabetes had a lower handgrip strength and skeletal muscle density, when compared with patients without diabetes (strength: 19.67 ± 9.98 kgf vs. 26.79 ± 11.80 kgf, P = 0.002 and skeletal muscle density: 10.58 ± 17.61 HU vs. 18.17 ± 15.33 HU, P = 0.032). There was a trend for the association between the presence of cardiovascular risk factors (hypertension and dyslipidemia) and a decrease in skeletal muscle density and strength (density: hypertension: 13.46 ± 16.74 HU vs. 20.38 ± 11.63 HU P=0.055; dyslipidemia: 13.57 ± 17.16 HU vs. 17.74 ± 13.00 HU P= 0.315; strength- hypertension: 22.55 ± 10.08 kgf vs. 27.58 ± 15.11 P= 0.073; dyslipidemia: 22.80 ± 10.52 kgf vs. 25.28 ± 13.14 kgf P= 0.315). Interestingly, we found that smokers had a favorable skeletal muscle characteristic, which could be explained by the higher prevalence of diabetes in nonsmokers. CONCLUSIONS: The indicators of skeletal muscle dysfunction (strength and density) are associated to the presence of diabetes in patients with LEAD. Therapeutic strategies to improve the skeletal muscle characteristics could have a role in improving LEAD risk factors, particularly diabetes.

Single-molecule DNA sequencing of widely varying GC-content using nucleotide release, capture and detection in microdroplets.

Despite remarkable progress in DNA sequencing technologies there remains a trade-off between short-read platforms, having limited ability to sequence homopolymers, repeated motifs or long-range structural variation, and long-read platforms, which tend to have lower accuracy and/or throughput. Moreover, current methods do not allow direct readout of epigenetic modifications from a single read. With the aim of addressing these limitations, we have developed an optical electrowetting sequencing platform that uses step-wise nucleotide triphosphate (dNTP) release, capture and detection in microdroplets from single DNA molecules. Each microdroplet serves as a reaction vessel that identifies an individual dNTP based on a robust fluorescence signal, with the detection chemistry extended to enable detection of 5-methylcytosine. Our platform uses small reagent volumes and inexpensive equipment, paving the way to cost-effective single-molecule DNA sequencing, capable of handling widely varying GC-bias, and demonstrating direct detection of epigenetic modifications.

Identification of Glycycometus malaysiensis (for the first time in Brazil), Blomia tropicalis and Dermatophagoides pteronyssinus through multiplex PCR.

Blomia tropicalis and Dermatophagoides pteronyssinus play an important role in triggering allergy. Glycycometus malaysiensis causes IgE reaction in sensitive people, but is rarely reported in domestic dust, because it is morphologically similar to B. tropicalis making the identification of these species difficult. The identification of mites is mostly based on morphology, a time-consuming and ambiguous approach. Herein, we describe a multiplex polymerase chain reaction (mPCR) assay based on ribosomal DNA capable to identify mixed cultures of B. tropicalis, D. pteronyssinus and G. malaysiensis, and/or to identify these species from environmental dust. For this, the internal transcribed spacer 2 (ITS2) regions, flanked by partial sequences of the 5.8S and 28S genes, were PCR-amplified, cloned and sequenced. The sequences obtained were aligned with co-specific sequences available in the GenBank database for primer design and phylogenetic studies. Three pairs of primers were chosen to compose the mPCR assay, which was used to verify the frequency of different mites in house dust samples (n = 20) from homes of Salvador, Brazil. Blomia tropicalis was the most frequent, found in 95% of the samples, followed by G. malaysiensis (70%) and D. pteronyssinus (60%). Besides reporting for the first time the occurrence of G. malaysiensis in Brazil, our results confirm the good resolution of the ITS2 region for mite identification. Furthermore, the mPCR assay proved to be a fast and reliable tool for identifying these mites in mixed cultures and could be applied in future epidemiological studies, and for quality control of mite extract production for general use.

PARASITOLOGIC AND PATHOLOGIC STUDY OF FREE-RANGING SOUTH AMERICAN RATTLESNAKES (CROTALUS DURISSUS TERRIFICUS) IN BRAZIL.

This study assesses parasitism and pathologic manifestations in free-ranging Crotalus durissus terrificus. A total of 96 rattlesnakes from the State of Minas Gerais (southeast Brazil) were necropsied between September 2019 and February 2020. Granulomatous gastritis affected 48% (46 of 96) of the snakes evaluated, which were associated with the ascaridid nematodes Ophidascaris sp. and Hexametra sp. Other nematodes found included Kalicephalus costatus costatus and Kalicephalus inermis inermis (Diaphanocephalidae; 7%, 7 of 96) in the intestines, Serpentirhabdias sp. (Rhabdiasidae; 18%, 17 of 96) in the lungs, and Hastospiculum sp. (Diplotriaenidae; 2%, 2 of 96) encapsulated in the serosa of the mesentery. Larval cestodes, probably spargana of Spirometra sp. (Diphyllobothriidae; 2%, 2 of 96), were found in the skeletal muscle and unidentified acanthocephalan cystacanths (Oligacanthorhynchidae; 5%, 5 of 96) in the subcutis and coelomic cavity. The pentastome Porocephalus crotali (Porocephalidae; 2%, 2 of 96) was also found in the lungs. Microscopically, intestinal disease was caused by Sarcocystis sp. (7%, 7 of 96), Cryptosporidium sp. (1%, 1 of 96), and Entamoeba sp. (1%, 1 of 96) and fungi (7%, 7 of 96). In addition, hemoparasites such as Hepatozoon spp. (23%, 22 of 96) and Trypanosoma sp. (1%, 1 of 96) were observed in blood smears. This study expands the knowledge of diseases, parasites, and other infectious agents affecting free-ranging C. durissus terrificus in Brazil.

Glucosylceramide synthase silencing combined with the receptor tyrosine kinase inhibitor axitinib as a new multimodal strategy for glioblastoma.

A great deal of evidence revealing that lipid metabolism is drastically altered during tumorigenesis has been accumulated. In this work, glucosylceramide synthase (GCS) was targeted, using RNA interference technology (siRNAs), in U87 and DBTRG human glioblastoma (GBM) cells, as in both cell types GCS showed to be overexpressed with respect to normal human astrocytes. The efficacy of a combined therapy to tackle GBM, allying GCS silencing to the new generation chemotherapeutics sunitinib and axitinib, or to the alkylating drugs etoposide and temozolomide, is evaluated here for the first time. With this purpose, studies addressing GBM cell viability and proliferation, cell cycle and apoptosis were performed, which revealed that combination of GCS silencing with axitinib treatment represents a promising therapeutic approach. The reduction of cell viability induced by this combined therapy is proposed to be mediated by excessive production of reactive oxygen species. This work, identifying GCS as a key molecular target to increase GBM susceptibility to a new generation chemotherapeutic, opens windows to the development of innovative strategies to halt GBM recurrence after surgical resection.

Exhaled breath condensate pH determinants in school-aged children: A population-based study.

BACKGROUND: Exhaled breath condensate (EBC) pH is a promising biomarker of airway inflammation. Lack of method standardization and interstudy variability precludes its use in clinical practice. While endogenous determinants have been described, underlying mechanisms for variability are mostly unknown. Thus, we aimed to assess the association between asthma and EBC pH in children, while studying potential environmental factors for interstudy variability. METHODS: A cross-sectional analysis of exhaled breath condensates from 613 children, aged 7-12 years, was conducted. Assessments included lung function and airway reversibility, exhaled nitric oxide, allergic sensitization, and body mass index (BMI). Indoor air quality (IAQ) was assessed in children's classrooms during 5 school days. Post-deaeration EBC pH showed a bimodal distribution, and the sample was split into acidic and alkaline groups. Regression models were constructed to assess the effects of asthma and asthma adjusted to IAQ parameters on EBC pH. RESULTS: Following adjustment to gender and BMI, asthma was significantly associated with a lower EBC pH in the acidic group. The effect of asthma on EBC pH was independent of IAQ, in both groups. In the acidic group, EBC pH was significantly affected by temperature [ß = -0.09 (-0.15, -0.02)] and PM 2.5 concentration [ß = -0.16 (-0.32, -0.01)], and in the alkaline group by relative humidity [ß = 0.07 (0.02, 0.13)] and concentration of endotoxins [ß = -0.06 (-0.1, -0.01)]. CONCLUSION: Our study shows that in addition to individual determinants such as asthma, environmental factors may influence and should be taken into consideration when interpreting EBC pH level in children.

A cross-sectional study of the impact of school neighbourhood on children obesity and body composition.

Schools' neighbourhoods provide an important environmental context that may influence the risk of obesity among children. The aim of this study was to assess the effect of neighbourhood surrounding schools on obesity and body composition in schoolchildren. Data on 845 children aged 7 to 12 years old from 20 primary schools were considered. Anthropometric measurements and bioelectrical impedance analysis were performed to assess body mass index (BMI) and characterize body composition. Land use characteristics were quantified within a 500-m buffer zone around schools. Mixed-effect models measured the effects of school neighbourhood on obesity and body composition. The results showed a tendency between green urban areas around schools and lower values of BMI and better body composition parameters compared with built areas, being BMI z-scores CDC, and body fat percentage significantly higher in-built than in green urban areas (ß = 0.48, 95% CI 0.05; 0.90, and ß = 2.56, 95% CI 0.39; 4.73, respectively).Conclusion: Our findings suggest that the school neighbourhood has an effect on BMI and body fat percentage in schoolchildren. These results may contribute to the creation of healthier cities and help reduce health expenses by focusing on prevention programmes towards the expansion of green spaces. What is Known: • Living in greener areas has been associated with healthy weight outcomes and to the lower impact of obesogenic urban environments. • The school environment may be especially important for youth health outcomes. What is New: • Neighbourhoods around schools may affect child health, specifically the development of obesity. • The presence of urban green areas around school may promote a framework of lifestyle or behaviours conducive to achieving a healthy weight.

Sarcopenia as a Prognostic Factor in Peripheral Arterial Disease: Descriptive Review.

BACKGROUND: Determine the influence of sarcopenia on the prognosis of peripheral arterial disease (PAD). METHODS: A systematic search of the PubMed and Cochrane Library databases was performed with the keywords and medical subject heading (MesH): "muscle, skeletal", "sarcopenia", "prognosis", "duration of stay", "death", "mortality", "patient readmission", "length of stay", "peripheral arterial disease", "intermittent claudication" and "critical limb ischemia". Papers published from January 2010 to October 2020 in English, French, Spanish and Portuguese were eligible for inclusion. The primary outcome was overall survival. Secondary outcomes included post-operative complications, amputation, length of hospital stay and hospital readmission. RESULTS: Of 1071 papers, 8 articles and 1511 patients were included (68.96% male, mean age 71.83 years). Five papers found an inverse relationship between SM area and mortality. Matsubara (2015) found that the 5-year overall survival rates were lower for patients with sarcopenia (23.5% ± 0.18% vs 77.5% ± 0.09% P = 0.001). Matsubara (2016) registered 3-year cardiovascular event-free survival rates of 43.1% and 91.2% for patients with and without sarcopenia (P < 0.01). Juszczak (2018) found that survival was lower in patients with reduced total psoas area. Taniguchi (2019) found that 3-year overall survival rate was 60% for patients with sarcopenia and 87% for patients without sarcopenia (P < 0.05). Shimazoe (2019) concluded sarcopenia was a significant predictor of overall survival. Distinctly, Nyers (2017) concluded that higher ratio bilateral psoas area to L4 vertebral body was associated with an increased risk of death. Two other studies analyzed other characteristics of the SM (density and strength). McDermott (2012) and found that lower calf muscle density and strength were associated with an increase in mortality. Sugai (2019) concluded that patients with major cardiovascular and limb events had a lower SM density. CONCLUSIONS: Lower SM area and mass seem to be associated with a higher mortality in PAD patients.

Percutaneous Foramen Ovale Puncture: Usefulness of Intraoperative CT Control, in the Eventuality of a Narrow Foramen.

BACKGROUND: Balloon compression of the gasserian ganglion has been a well-established percutaneous treatment of trigeminal neuralgia since the 1980s. However, puncture of the foramen ovale by conventional single-plane fluoroscopy can be difficult in cases of local anatomic abnormalities. CASE PRESENTATION: We present the case of a 49-year-old woman diagnosed with idiopathic trigeminal neuralgia refractory to pharmacological treatment. After failure of puncture by conventional fluoroscopy for percutaneous gasserian ganglion balloon compression due to a narrow foramen ovale, the patient was submitted to puncture guided by computed tomography. CONCLUSION: Alternative imaging methods, such as computed tomography, should be considered when puncture of the foramen ovale by conventional single-plane fluoroscopy fails, to minimize the risk of potential complications triggered by frustrated puncture attempts.

Combined evaluation of fecal calprotectin and C-reactive protein as a therapeutic target in the management of patients with Crohn's disease.

OBJECTIVES: Proper management of the inflammatory process in Crohn's disease (CD) results in lower rates of complications. The objective of this study was to investigate the performance of isolated and combined use of fecal calprotectin (FC) and serum levels of C-reactive protein (CRP) as markers of inflammatory activity in CD and the possibility of their use as a therapeutic target. PATIENTS AND METHODS: Patients with CD and indication for colonoscopy were prospectively enrolled in the study and allocated according to the presence or absence of endoscopic inflammatory activity. The correlation between FC and CRP levels and the Simplified Endoscopic Score of Crohn's Disease (SES-CD) was performed, and the accuracy of these markers was evaluated for the diagnosis of inflammatory activity, when used alone or in series. RESULTS: Eighty colonoscopies were performed in patients with CD. The FC cut-off value of 155µg/g showed high sensitivity (96%) and accuracy (78%) for the diagnosis of endoscopic activity. For CRP, the value of 6.7mg/L demonstrated sensitivity of 75% and specificity of 67%. The sequential usage of these markers (FC+CRP) showed greater specificity (82%) when compared to the use of these markers alone. Depending on the probability of inflammatory activity, different scenarios were used to evaluate the performance of these markers and an algorithm is proposed. DISCUSSION: Combined analysis of FC and CRP, when performed consecutively, allows decisions to be made with a high degree of certainty and even eliminates the need for colonoscopy in many situations.

Stationary Black Holes and Light Rings.

The ringdown and shadow of the astrophysically significant Kerr black hole (BH) are both intimately connected to a special set of bound null orbits known as light rings (LRs). Does it hold that a generic equilibrium BH must possess such orbits? In this Letter we prove the following theorem. A stationary, axisymmetric, asymptotically flat black hole spacetime in 1+3 dimensions, with a nonextremal, topologically spherical, Killing horizon admits, at least, one standard LR outside the horizon for each rotation sense. The proof relies on a topological argument and assumes C^{2} smoothness and circularity, but makes no use of the field equations. The argument is also adapted to recover a previous theorem establishing that a horizonless ultracompact object must admit an even number of nondegenerate LRs, one of which is stable.