The impact of social determinants on health outcomes in a region in the North of England: a structural equation modelling analysis.

OBJECTIVES: The aim of this study was to identify the impact of social determinants of health on physical and mental health outcomes in a UK population. STUDY DESIGN: Structural equation modelling was used to hypothesise a model of relationships between health determinants and outcomes within a region in the North of England using large-scale population survey data (6208 responses). METHODS: We analysed responses from a population survey to assess the influence of a deprivation-based index at the environmental level, education and income on a behaviour index (smoking, alcohol consumption, physical activity, and dietary habits) and the influence of all these factors on self-reported physical health and the influence of the behaviour index and income on mental wellbeing. RESULTS: The proposed model was well supported by the data. Goodness-of-fit statistics, most notably a low value of the root mean square error of approximation (RMSEA), supported the validity of the proposed relationships (RMSEA = 0.054). The model revealed all examined paths to be statistically significant. Income and education were influential in determining an individual's behaviour index score, which, with income was the most important predictor of both the correlated outcomes of physical health and mental wellbeing (P < 0.001 in all cases). CONCLUSIONS: Findings challenge the traditional view of singular causal pathways, emphasising that interventions should consider the underlying influencing socio-economic conditions, which would influence behaviour and therefore physical and mental wellbeing. The extent to which the model is supported by the data, and the statistical significance of individual relationships accentuates the imperative for comprehensive public health strategies that integrate multiple socio-economic factors.

Noncompliance to iodine supplementation recommendation is a risk factor for iodine insufficiency in Portuguese pregnant women: results from the IoMum cohort.

PURPOSE: After a recommendation for iodine supplementation in pregnancy has been issued in 2013 in Portugal, there were no studies covering iodine status in pregnancy in the country. The aim of this study was to assess iodine status in pregnant women in Porto region and its association with iodine supplementation. METHODS: A cross-sectional study was conducted at Centro Hospitalar Universitário São João, Porto, from April 2018 to April 2019. Pregnant women attending the 1st trimester ultrasound scan were invited to participate. Exclusion criteria were levothyroxine use, gestational age < 10 and ≥ 14 weeks, non-evolutive pregnancy at recruitment and non-signing of informed consent. Urinary iodine concentration (UIC) was measured in random spot urine by inductively coupled plasma-mass spectrometry. RESULTS: Median UIC was 104 µg/L (IQR 62-189) in the overall population (n = 481) of which 19% had UIC < 50 µg/L. Forty three percent (n = 206) were not taking an iodine-containing supplement (ICS) and median UIC values were 146 µg/L (IQR 81-260) and 74 µg/L (IQR 42-113) in ICS users and non-users, respectively (p < 0.001). Not using an ICS was an independent risk factor for iodine insufficiency [adjusted OR (95% CI) = 6.00 (2.74, 13.16); p < 0.001]. Iodised salt use was associated with increased median iodine-to-creatinine ratio (p < 0.014). CONCLUSIONS: A low compliance to iodine supplementation recommendation in pregnancy accounted for a mild-to-moderately iodine deficiency. Our results evidence the need to support iodine supplementation among pregnant women in countries with low household coverage of iodised salt. Trial registration number NCT04010708, registered on the 8th July 2019.

Lymphocyte subsets and Langerhans cells in the skin of kidney transplant recipients under three different immunosuppressive regimens.

BACKGROUND: Renal transplant recipients (RTRs) are at increased risk of developing skin cancer; however, the role of immunosuppression is not yet fully understood. In this study, we evaluated the immunohistochemical changes in the skin of RTRs under three different immunosuppression regimens: mTOR inhibitors (mTORi), sirolimus or everolimus, mycophenolic acid (MPA) precursors such as mycophenolate sodium or mofetil, or azathioprine (AZA). METHODS: We evaluated biopsies of sun-exposed and sun-protected skin for immunohistochemical quantification of B lymphocytes (CD20+ ), T lymphocytes (CD3+ , CD4+ , and CD8+ ), and Langerhans cells (LCs) (CD1a+ ) in 30 RTRs and 10 healthy controls. The RTRs were divided into three groups: mTORi (n = 10), MPA (n = 10), and AZA (n = 10). RESULTS: No differences were observed in the number of B lymphocytes. However, a significant decrease in the number of T lymphocytes and LCs was observed in both sun-protected and sun-exposed skin in the AZA and MPA groups, although to a lesser degree in the latter group. The skin of the mTORi group did not differ from that of the control group in terms of the number of B and T lymphocytes and LCs. CONCLUSIONS: Patients treated with mTORi exhibit preserved cellular elements related to cutaneous immune surveillance. The use of AZA induced a greater degree of skin immunosuppression than in the control group, as demonstrated by the decrease in T lymphocytes and LCs.

Assessing the effects of PMM2 variants on protein stability.

Phosphomannomutase 2 deficiency, PMM2-CDG, is the most frequent disorder of protein N-glycosylation. It is an autosomal recessive disease with a broad clinical and biochemical phenotype. Trying to predict the impact of novel variants is often a challenge due to the high number of variants and the difficulty to establish solid genotype-phenotype correlations. A potential useful strategy is to use computational chemistry calculations as a tool from which relevant information on the structural impact of novel variants may be deduced. Here we present our analyses based on four well-known PMM2 deleterious variants (p.(Leu32Arg), p.(Asp65Tyr), p.(Phe119Leu), p.(Arg141His)) and the polymorphic p.(Glu197Ala) for which we have predicted the effect on protein stability. Our work predicts the effect of different amino acid residues on the conformation and stability of PMM2. These computational simulations are, therefore, an extremely useful methodology which, in combination with routinely used in silico methods of pathogenicity prediction, may help to reveal the structural impact of novel variants at the protein level, potentially leading to a better understanding of target biological molecules.

Antimycobacterial compound of chitosan and ethambutol: ultrastructural biological evaluation in vitro against Mycobacterium tuberculosis.

Chitosan (CS) is a promising biopolymer and has been tested as a complement to the action and compensation of toxicity presented by anti-tuberculosis drugs. The present work studied the adjuvant effect of CS with the drug ethambutol (EMB) as a compound (CS-EMB), to explore its antimicrobial and cytotoxic activity, using transmission electron microscopy (TEM), to examine ultracellular changes that represent possible antimycobacterial action of CS on Mycobacterium tuberculosis (Mtb). Antimycobacterial activities were tested against reference strains Mtb ATCC® H37Rv and multidrug resistant (MDR). In vitro cytotoxicity tests were performed on Raw 264.7. For the studied compounds, morphological, ultrastructural, and physical-chemical analyses were performed. Drug-polymer interactions that occur through the H bridges were confirmed by physical-chemical analyses. The CS-EMB compound is stable at pHs of 6.5-7.5, allowing its release at physiological pH. The antibacterial activity (minimum inhibitory concentration) of the CS-EMB compound was 50% greater than that of the EMB in the H37Rv and MDR strains and the ultrastructural changes in the bacilli observed by TEM proved that the CS-EMB compound has a bactericidal action, allowing it to break down the Mtb cell wall. The cytotoxicity of CS-EMB was higher than that of isolated EMB, IC50 279, and 176 µg/mL, respectively. It is concluded that CS-EMB forms a promising composite against strains Mtb H37Rv and multidrug resistant (MDR-TB).Key points• Our study will be the first to observe ultrastructurally the effects of the CS-EMB compound on Mtb cells.• CS-EMB antimicrobial activity in a multidrug-resistant clinical strain.• The CS-EMB compound has promising potential for the development of a new drug to fight tuberculosis.

Repurposing strategies for Chagas disease therapy: the effect of imatinib and derivatives against Trypanosoma cruzi.

Chagas disease (CD) is a neglected parasitic condition endemic in the Americas caused by Trypanosoma cruzi. Patients present an acute phase that may or not be symptomatic, followed by lifelong chronic stage, mostly indeterminate, or with cardiac and/or digestive progressive lesions. Benznidazole (BZ) and nifurtimox are the only drugs approved for treatment but not effective in the late chronic phase and many strains of the parasite are naturally resistant. New alternative therapy is required to address this serious public health issue. Repositioning and combination represent faster, and cheaper trial strategies encouraged for neglected diseases. The effect of imatinib (IMB), a tyrosine kinase inhibitor designed for use in neoplasias, was assessed in vitro on T. cruzi and mammalian host cells. In comparison with BZ, IMB was moderately active against different strains and forms of the parasite. The combination IMB + BZ in fixed-ratio proportions was additive. Novel 14 derivatives of IMB were screened and a 3,2-difluoro-2-phenylacetamide (3e) was as potent as BZ on T. cruzi but had low selectivity index. The results demonstrate the importance of phenotypic assays, encourage the improvement of IMB derivatives to reach selectivity and testify to the use of repurposing and combination in drug screening for CD.

Heteronuclear molecules from matrix isolation sublimation and atomic diffusion.

We demonstrate the production of cryogenic beams of heteronuclear molecules from the matrix isolation sublimation (MISu) technique. A sapphire mirror serves as a substrate whereupon a solid Ne matrix is grown. Atoms of Li, H, Ca, and C are implanted into the matrix via subsequent laser ablation of different solid precursors such as Ca, Li, LiH, and graphite. The matrix is sublimated into vacuum generating a cryogenic beam of Ne carrying the previously isolated neutral atomic and molecular species. A compact and low energy electron source and time-of-flight mass spectrometer was designed to fit this system at low temperature. With electron ionization time-of-flight mass spectrometry, we analyze the species coming from MISu and demonstrate the formation of heteronuclear molecules in the matrix. In this first study, we produced LiCa from the sequential implantation of Li and Ca into the matrix and some clusters of CnLim after Li and C ablation. Also from ablation of a single LiH pellet, we observed clusters of LinHm. This novel technique opens up the opportunity to generate cryogenic beams of different molecules for precision physics and chemistry studies. Laser or microwave high resolution spectroscopy of a molecular beam benefits from low translational and rovibrational temperatures and forward velocities, such as the ones produced in this technique. Toward the prospect of enhancing the molecular formation, we introduce a new method to study the atomic diffusion of Li and Ca in the Ne matrix via laser spectroscopy during sublimation. We estimate a small diffusion coefficient at 7 K, but a surprisingly linear atomic dispersion during sublimation. The method is extensive to other species and matrices.

Performance and bacterial diversity of bioreactors used for simultaneous removal of sulfide, solids and organic matter from UASB reactor effluents.

Two bioreactors were investigated as an alternative to post-treatment of effluent from an upflow anaerobic sludge blanket (UASB) reactor treating domestic sewage, with an aim of oxidizing sulfide into elemental sulfur, and removal of solid and organic material. The bioreactors were operated at different hydraulic retention times (HRTs) (6, 4, and 2 h) and in the presence or absence (control) of packing material (polypropylene rings). Greater sulfide removal efficiencies - 75% (control reactor) and 92% (packed reactor) - were achieved in both reactors for an HRT of 6 h. Higher organic matter (COD) and solid (TSS) removal levels were observed in the packed reactor, which produced effluent with low COD (100 mg CODL-1) and TSS concentrations (30 mg TSSL-1). Denaturing gradient gel electrophoresis results revealed that a metabolically diverse bacterial community was present in both bioreactors, with sequences related to heterotrophic bacteria, sulfur bacteria (Thiocapsa, Sulfurimonas sp., Chlorobaculum sp., Chromatiales and Sulfuricellales), phototrophic purple non-sulfur bacteria (Rhodopseudomonas, Rhodocyclus sp.) and cyanobacteria. The packed reactor presented higher extracellular sulfur formation and potential for elemental sulfur recovery was seen. Higher efficiencies related to the packed reactor were attributed to the presence of packing material and higher cell retention time. The studied bioreactors seemed to be a simple and low-cost alternative for the post-treatment of anaerobic effluent.

Inflammasome gene profile is modulated in septic patients, with a greater magnitude in non-survivors.

Inflammasome signalling induces the processing and secretion of interleukin (IL)-1ß and IL-18 which, coupled with pyroptosis, activate further the inflammatory response. In the present study we evaluated the expression of genes involved in inflammasome signalling pathways in septic patients, their interaction networks and the predicted functions modulated in survivors and non-survivors. Twenty-seven patients with sepsis secondary to community-acquired pneumonia admitted to intensive care units from three general hospitals in São Paulo were included into the study. We performed a polymerase chain reaction (PCR) array encompassing 35 genes related to the nucleotide-binding oligomerization domain and leucine-rich repeat-containing (NLR)-inflammasome in peripheral blood mononuclear cells obtained at admission and after 7 days of follow-up. Eleven healthy volunteers were used as the reference group. Increased NLRC4 and NLRP3 and decreased nucleotide-binding oligomerization domain (NOD1), and NLRP1 expression was observed in septic patients compared to healthy individuals; the IL-1ß and IL-18 expression levels were also high in the patients. The gene expression changes followed the same patterns in surviving and non-surviving patients, with higher magnitudes observed in non-survivors. Functional analyses revealed, however, that activation and inhibition intensity for representing functions were different in survivors and non-survivors, as for production of reactive oxygen species, synthesis of nitric oxide and for the control of bacterial infections. Our results showed that the genes involved in the activation of the NLR-inflammasome cascades were altered substantially in septic patients, with a higher number of altered genes and a higher intensity in the disturbance of gene expression found among patients dying of sepsis.

Neuro-ophthalmologic manifestations in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can affect different ocular structures, such as cornea, conjunctiva, episclera, sclera, uveal tract, retina, optic nerve and vessels. Neuro-ophthalmologic manifestations in SLE include different degrees of involvement of retina, choroid and optic nerve. Retinal changes are one of the most common ocular involvements and are frequently used as clinical criteria for activity, even if isolated. Studies show that up to 29% of patients with active SLE manifest retinal disease. The exact prevalence of choroidal disease is unknown, but is thought to be less common than retinopathy, due to under-diagnosis. Optic nerve disease, represented by optic neuritis and anterior/posterior ischaemic optic neuropathy, affects approximately 1% of SLE patients. These ocular manifestations have been associated with neurologic flares, antiphospholipid antibodies, nephropathy, and increased mortality. The aim of this paper is to review the different aspects of neuro-ophthalmologic involvement in SLE. Since these manifestations are frequent and potentially severe, a multi-professional team approach is needed to investigate properly and provide early aggressive treatment in order to avoid visual sequelae.

Single dose versus multiple dose of antibiotic prophylaxis in caesarean section: a systematic review and meta-analysis.

BACKGROUND: Prophylactic antibiotics are traditionally given as a single dose for caesarean section. However, inconsistent application of recommendations and recent evidence prompted a literature review. OBJECTIVES: To assess the optimal regimen for antibiotic prophylaxis in caesarean section by comparing single versus multiple doses of the same intervention. SEARCH STRATEGY: MEDLINE, Web of Knowledge, SCOPUS, CENTRAL and ongoing trials databases were searched. Reference lists were reviewed and international groups contacted. SELECTION CRITERIA: Randomised controlled trials (RCT) comparing single with multiple dose regimens of the same antibiotic prophylaxis. Quasi-RCT and abstracts were suitable for inclusion. DATA COLLECTION AND ANALYSIS: Reviewers independently extracted data and assessed quality of evidence. A random-effects model was used and results presented as risk ratio (RR) with 95% confidence intervals (CI). MAIN RESULTS: Sixteen studies were included, involving 2695 women. Nonsignificant differences were observed between single dose and multiple dose antibiotic prophylaxis in the incidence of postpartum infectious morbidity (RR 0.95, 95% CI 0.75-1.20, I2 = 25%), endometritis (RR 1.03, 95% CI 0.74-1.42, I2 = 0%) and wound infection (RR 1.22, 95% CI 0.72-2.08, I2 = 0%). A trend towards lower risk of urinary tract infection was seen with multiple dose (RR 0.65, 95% CI 0.34-1.24, I2 = 0%). CONCLUSIONS: There was insufficient evidence to determine whether there is a difference between single and multiple dose regimens in reducing the incidence of infectious morbidity after caesarean section. The quality of evidence was very low and well-designed RCTs are needed. TWEETABLE ABSTRACT: Insufficient evidence of difference between dosage regimens of antibiotic prophylaxis in caesarean section.

Physical fitness and academic performance in youth: A systematic review.

Physical fitness (PF) is a construct of health- and skill-related attributes which have been associated with academic performance (AP) in youth. This study aimed to review the scientific evidence on the association among components of PF and AP in children and adolescents. A systematic review of articles using databases PubMed/Medline, ERIC, LILACS, SciELO, and Web of Science was undertaken. Cross-sectional and longitudinal studies examining the association between at least one component of PF and AP in children and adolescents, published between 1990 and June 2016, were included. Independent extraction of articles was carried out by the two authors using predefined data fields. From a total of 45 studies included, 25 report a positive association between components of PF with AP and 20 describe a single association between cardiorespiratory fitness (CRF) and AP. According to the Strengthening the Reporting of Observational Studies in Epidemiology guidelines: 12 were classified as low, 32 as medium risk, and 1 as high risk of bias. Thirty-one studies reported a positive association between AP and CRF, six studies with muscular strength, three studies with flexibility, and seven studies reported a positive association between clustered of PF components and AP. The magnitude of the associations is weak to moderate (ß = 0.10-0.42 and odds = 1.01-4.14). There is strong evidence for a positive association between CRF and cluster of PF with AP in cross-sectional studies; and evidence from longitudinal studies for a positive association between cluster of PF and AP; the relationship between muscular strength and flexibility with AP remains uncertain.

Epidemiology of human papillomavirus on anogenital warts in Portugal - The HERCOLES study.

BACKGROUND: Anogenital warts (AGW) are one of the most prevalent sexually transmitted disease worldwide. Approximately, 90% of AGWs are related to infection by HPV 6 and 11. However, AGW have been associated with infection by multiple genotypes, including HR-HPV, which may be associated with a long-term increased risk of anogenital cancer. OBJECTIVE: This observational prospective epidemiological study aims to estimate the type-specific HPV distribution on incident AGWs in both genders, and additionally to assess the frequency of anal and oral HPV infection in patients with AGWs. METHODS: According to defined inclusion criteria, individuals with incident clinical diagnosis of AGWs were recruited in seven Portuguese Centres. HPV genotyping was performed using CLART HPV2 test. RESULTS: Between November 2012 and March 2014, 162 women and 400 men (mean age: 34 years), were enrolled. After exclusion of patients with unqualified AGW samples, HPV was detected in 95.3% (505/530) AGW patients, 96.8% males and 91.6% females. Among men who have sex with men, HPV was detected in 98.5% patients. HPV 6 and/or HPV 11 were the most frequent genotypes (87.5%), and HPV 16 the most common HR-HPV (9.2%). Infection with HPV 6/11 and any HR-HPV was observed in 35.8% patients. HPV prevalence on the anal canal and oral mucosa was 83.1% and 15.0%, respectively. CONCLUSION: Incident AGWs were more frequent in males than in females. LR-HPVs were more common among males and HR-HPVs among females. HPV 6 and 11 were the most common genotypes on both genders. However, there was also a high prevalence of HR-HPVs, particularly of HPV 16. AGWs represent a clinical marker of both anal and oral HPV infections, including anal HR-HPV infections in women and men who have sex with men. The HERCOLES study could be a clue to further investigations concerning HPV burden of disease by gender and sexual behaviour.

Novel endodontic sealers induce cell cytotoxicity and apoptosis in a dose-dependent behavior and favorable response in mice subcutaneous tissue.

OBJECTIVES: The objective of the present study is to evaluate the in vitro cytotoxicity and in vivo biocompatibility of two novel endodontic sealers: RealSeal XT1 and Sealapex Xpress on the subcutaneous connective tissue of mice. MATERIALS AND METHODS: The cytotoxicity was assessed by cell viability using the MTT assay (one-way ANOVA), trypan blue test (Mann-Whitney) and cell apoptosis by flow cytometer. For the subcutaneous study, polyethylene tubes filled with the sealers were implanted in 70 BALB/c mice: 6 experimental groups (n = 10/group) and 2 control groups with empty tubes (n = 5/group). At the end of experimental periods (7, 21, and 63 days), the tissue was removed and histotechnically processed. Angioblastic proliferation and edema (Fisher's exact test) were evaluated, besides thickness measurement (µm) of the reactionary granulomatous tissue and neutrophil counts (Kruskal-Wallis and Dunn's post test; Mann-Whitney) (α = 0.05). RESULTS: MTT assay, trypan blue, and analysis of apoptotic cells showed a dose-dependent direct effect: the more diluted the sealer, the less cytotoxic. Regarding the angioblastic proliferation and edema, difference between the sealers at 7 and 63 days occurred (p < 0.05). Both endodontic sealers initially promoted perimaterial tissue reaction as a foreign body granuloma and thus stimulated favorable tissue responses. CONCLUSIONS: Both sealers showed a dose-dependent effect and promoted satisfactory subcutaneous tissue response; the sealer Sealapex Xpress was less cytotoxic and more biocompatible than RealSeal XT. CLINICAL RELEVANCE: The step of root canal filling during endodontic treatment is highly important for the preservation of the periapical tissue integrity. Subcutaneous reaction to endodontic sealers enables scientific basis for clinical use.

Post-Exercise Neurovascular Control in Chronic Heart Failure Patients.

It remains unknown whether or not a reduction in muscle sympathetic nerve activity in heart failure patients is associated over time with the effects of long- or short-term repeated exercise. 10 chronic heart failure patients, age 49±3 years old, functional class I-III NYHA, ejection fraction <40% were randomly submitted to either an acute bout of moderate continuous exercise OR high-intensity interval exercise. Muscle sympathetic nerve activity (microneurography) and forearm blood flow (venous occlusion plethysmography) were evaluated pre- and post-exercise sessions. The moderate exercise consisted of cycle exercise at an intensity corresponding to anaerobic threshold. The interval exercise consisted of a 2-min cycle exercise at intensity corresponding to anaerobic threshold, followed by a 1-min exercise set at respiratory compensation point. Exercise capacity was evaluated by cardiopulmonary exercise test. The caloric expenditure in both sessions was 100 kcal. Baseline muscle sympathetic nerve activity and forearm blood flow levels were not different between sessions. Moderate or high-intensity exercise caused no significant changes in muscle sympathetic nerve activity and forearm blood flow. These findings suggest that the reduction in muscle sympathetic nerve activity and the increase in forearm blood flow provoked by exercise training in chronic heart failure patients are due to cumulative effects over time.

Vulnerability in elderly patients with gastrointestinal cancer--translation, cultural adaptation and validation of the European Portuguese version of the Vulnerable Elders Survey (VES-13).

BACKGROUND: "Vulnerable Elders Survey" (VES-13) is a questionnaire accurate in predicting functional decline and highly correlated with comprehensive geriatric assessment in identifying vulnerable elderly. The purpose of this study was to translate, cultural adapt and validate the first Portuguese cross-cultural version of VES-13 and to estimate the prevalence of vulnerability in Portuguese elderly gastrointestinal (GI) cancer patients. METHODS: VES-13 European Portuguese translation and cultural adaptation was developed according to internationally accepted guidelines. Test-retest reliability and internal consistency were assessed by calculating the Kappa statistic and by analyzing the inter-item and item-total correlation matrices and calculation of Cronbach's alpha coefficients, respectively. Construct and criterion validity was assessed by Spearman's correlation coefficient between VES-13 and each EQ-5D-5 L dimension, clinical judgment and performance status. RESULTS: The translated and culturally adapted version of VES-13 revealed high test-retest reliability (test-retest Kappa ≥ 0.612; p < 0.001) in the pilot study (n = 22). For the validation phase 206 patients with GI cancer were recruited (median age: 73 years; colo-rectal cancer: 63 %). Criterion validity was confirmed by adequate correlations between VES-13 and clinical judgment of vulnerability, ECOG and KPS scores. Construct validity was confirmed by moderate correlations with most of EQ-5D-5 L dimensions. Cronbach's alpha of the questionnaire was 0.848. The estimated prevalence of vulnerability is 50 % (CI95% 0.43-0.56). CONCLUSIONS: The European Portuguese version of VES-13 is a valid and reliable approach to screening elderly cancer patients for geriatric needs. In our setting, one in two elderly patients was likely to be vulnerable or frail which stresses the importance of their correct identification to better inform cancer management.

Flow cytometric analysis: Interdependence of healthy and infected udder quarters.

An important question about intramammary infections that is still debated in the literature is the independence or interdependence of the quarters of dairy cows. The present study sought to explore milk neutrophil function and the milk lymphocyte profile of uninfected quarters from uninfected and infected (one infected quarter per cow) udders to evaluate interdependence of the quarters. Thus, 32 (8 cows) and 18 (6 cows) uninfected quarters from uninfected and infected udders were used, respectively. Using flow cytometry, we evaluated the percentage of milk neutrophils and their expression of adhesion molecules L-selectin (CD62L), ß2-integrin (CD11b), and an endothelial-selectin ligand (CD44); levels of intracellular reactive oxygen species (ROS); phagocytosis of Staphylococcus aureus by milk neutrophils; and neutrophil viability. Furthermore, we assessed the percentage of B-cell (CD21(+)) and T-lymphocyte subsets (CD3(+)/CD4(+)/CD8(-), CD3(+)/CD8(+)/CD4(-), CD3(+)/CD4(+)/CD25(-), CD3(+)/CD4(+)/CD25(+), and CD3(+)/CD4(-)/CD25(-)) using flow cytometry with monoclonal antibodies. The infected quarter did not affect somatic cell count or the percentage of neutrophils in the neighboring uninfected quarters. Furthermore, the infected quarter did not influence neutrophil viability, intracellular reactive oxygen species production, or phagocytosis of S. aureus by milk neutrophils. Conversely, the expression of adhesion molecules CD11b, CD62L, and CD44 by milk neutrophils differed between uninfected quarters from infected versus uninfected udders. The lymphocyte subsets did not differ between groups, except for a higher percentage of B cells in uninfected quarters from infected udders than in those from uninfected udders. Thus, our study strongly supports the hypothesis of interdependence of quarters based on the influence of infection on both the percentage of B cells and the expression of adhesion molecules by milk neutrophils in the neighboring uninfected quarters.

Intensive care in patients with lung cancer: a multinational study.

BACKGROUND: Detailed information about lung cancer patients requiring admission to intensive care units (ICUs) is mostly restricted to single-center studies. Our aim was to evaluate the clinical characteristics and outcomes of lung cancer patients admitted to ICUs. PATIENTS AND METHODS: Prospective multicenter study in 449 patients with lung cancer (small cell, n = 55; non-small cell, n = 394) admitted to 22 ICUs in six countries in Europe and South America during 2011. Multivariate Cox proportional hazards frailty models were built to identify characteristics associated with 30-day and 6-month mortality. RESULTS: Most of the patients (71%) had newly diagnosed cancer. Cancer-related complications occurred in 56% of patients; the most common was tumoral airway involvement (26%). Ventilatory support was required in 53% of patients. Overall hospital, 30-day, and 6-month mortality rates were 39%, 41%, and 55%, respectively. After adjustment for type of admission and early treatment-limitation decisions, determinants of mortality were organ dysfunction severity, poor performance status (PS), recurrent/progressive cancer, and cancer-related complications. Mortality rates were far lower in the patient subset with nonrecurrent/progressive cancer and a good PS, even those with sepsis, multiple organ dysfunctions, and need for ventilatory support. Mortality was also lower in high-volume centers. Poor PS predicted failure to receive the initially planned cancer treatment after hospital discharge. CONCLUSIONS: ICU admission was associated with meaningful survival in lung cancer patients with good PS and non-recurrent/progressive disease. Conversely, mortality rates were very high in patients not fit for anticancer treatment and poor PS. In this subgroup, palliative care may be the best option.

Sport modality affects bradycardia level and its mechanisms of control in professional athletes.

We investigated the influence of sport modalities in resting bradycardia and its mechanisms of control in highly trained athletes. In addition, the relationships between bradycardia mechanisms and cardiac structural adaptations were tested. Professional male athletes (13 runners, 11 cyclists) were evaluated. Heart rate (HR) was recorded at rest on beat-to-beat basis (ECG). Selective pharmacological blockade was performed with atropine and esmolol. Vagal effect, intrinsic heart rate (IHR), parasympathetic (n) and sympathetic (m) modulations, autonomic influence (AI) and autonomic balance (Abal) were calculated. Plasmatic norepinephrine (high-pressure liquid chromatography) and cardiac structural adaptations (echocardiography) were evaluated. Runners presented lower resting HR, higher vagal effect, parasympathetic modulation (n), AI and IHR than cyclists (P<0.05). Abal, sympathetic modulation (m) and norepinephrine level were similar within athletes regardless of modality. The cardiac chambers were also similar between runners and cyclists (P=0.30). However, cyclists displayed higher septum and posterior wall thickness than runners (P=0.04). Further analysis showed a trend towards inverse correlation between IHR with septum wall thickness and posterior wall thickness (P=0.056). Type of sport influences the resting bradycardia level and its mechanisms of control in professional athletes. Resting bradycardia in runners is mainly dependent on an autonomic mechanism. In contrast, a cyclist's resting bradycardia relies on a non-autonomic mechanism probably associated with combined eccentric and concentric hypertrophy.

Effect of flow rate and temperature on transmembrane blood pressure drop in an extracorporeal artificial lung.

INTRODUCTION: Transmembrane pressure drop reflects the resistance of an artificial lung system to blood transit. Decreased resistance (low transmembrane pressure drop) enhances blood flow through the oxygenator, thereby, enhancing gas exchange efficiency. This study is part of a previous one where we observed the behaviour and the modulation of blood pressure drop during the passage of blood through artificial lung membranes. METHODS: Before and after the induction of multi-organ dysfunction, the animals were instrumented and analysed for venous-venous extracorporeal membrane oxygenation, using a pre-defined sequence of blood flows. RESULTS: Blood flow and revolutions per minute (RPM) of the centrifugal pump varied in a linear fashion. At a blood flow of 5.5 L/min, pre- and post-pump blood pressures reached -120 and 450 mmHg, respectively. Transmembrane pressures showed a significant spread, particularly at blood flows above 2 L/min; over the entire range of blood flow rates, there was a positive association of pressure drop with blood flow (0.005 mmHg/mL/minute of blood flow) and a negative association of pressure drop with temperature (-4.828 mmHg/(°Celsius). These associations were similar when blood flows of below and above 2000 mL/minute were examined. CONCLUSIONS: During its passage through the extracorporeal system, blood is exposed to pressure variations from -120 to 450 mmHg. At high blood flows (above 2 L/min), the drop in transmembrane pressure becomes unpredictable and highly variable. Over the entire range of blood flows investigated (0-5500 mL/min), the drop in transmembrane pressure was positively associated with blood flow and negatively associated with body temperature.