Neutrophils seeking new neighbors: radiotherapy affects the cellular framework and the spatial organization in a murine breast cancer model.

Neutrophils are known to contribute in many aspects of tumor progression and metastasis. The presence of neutrophils or neutrophil-derived mediators in the tumor microenvironment has been associated with poor prognosis in several types of solid tumors. However, the effects of classical cancer treatments such as radiation therapy on neutrophils are poorly understood. Furthermore, the cellular composition and distribution of immune cells in the tumor is of increasing interest in cancer research and new imaging technologies allow to perform more complex spatial analyses within tumor tissues. Therefore, we aim to offer novel insight into intra-tumoral formation of cellular neighborhoods and communities in murine breast cancer. To address this question, we performed image mass cytometry on tumors of the TS/A breast cancer tumor model, performed spatial neighborhood analyses of the tumor microenvironment and quantified neutrophil-extracellular trap degradation products in serum of the mice. We show that irradiation with 2 × 8 Gy significantly alters the cellular composition and spatial organization in the tumor, especially regarding neutrophils and other cells of the myeloid lineage. Locally applied radiotherapy further affects neutrophils in a systemic manner by decreasing the serum neutrophil extracellular trap concentrations which correlates positively with survival. In addition, the intercellular cohesion is maintained due to radiotherapy as shown by E-Cadherin expression. Radiotherapy, therefore, might affect the epithelial-mesenchymal plasticity in tumors and thus prevent metastasis. Our findings underscore the growing importance of the spatial organization of the tumor microenvironment, particularly with respect to radiotherapy, and provide insight into potential mechanisms by which radiotherapy affects epithelial-mesenchymal plasticity and tumor metastasis.

SARS-CoV-2 seroprevalence in workers from a Colombian University Hospital.

BACKGROUND: Antibody (Ab) tests for SARS-CoV-2 virus allows for the estimation of incidence, level of exposure and duration of immunity acquired by a previous infection. In health workers, the hospital setting might convey a greater risk of infection. AIMS: To describe the frequency of immunoglobulin G (IgG) Abs (IgG-Abs) to the SARS-CoV-2 virus among workers at a third-level university hospital in Colombia. METHODS: In this cross-sectional study, we included medical and non-medical personnel with at least one real-time polymerase chain reaction (RT-PCR)/antigen test between March 2020 and March 2021. In April 2021, an IgG-Ab test against SARS-CoV-2 was conducted for all participants and replicated 2 weeks later in a random sample (10%). The frequency of IgG-Abs is presented based on status (positive/negative) and time elapsed since RT-PCR/antigen test (<3 months, 3-6 months, >6 months). RESULTS: We included 1021 workers (80% women, median age 34 years (interquartile range 28-42), 73% medical personnel, 23% with previous positive RT-PCR/antigen). The overall seroprevalence was 35% (95% CI 31.6-37.4, 35% in medical and 33% in non-medical personnel). For those with a previous positive RT-PCR/antigen test, the seroprevalence was 90% (<3 months), 82% (3-6 months) and 48% (>6 months). In participants with a previous negative RT-PCR/antigen test, the seroprevalence was 17% (<3 months), 21% (3-6 months) and 29% (>6 months). CONCLUSIONS: High IgG-Ab positivity was found in hospital personnel, regardless of work activities. The prevalence of detectable Abs differed by previous RT-PCR/antigen status and time elapsed since the diagnostic test.

Hemophilia and non-accidental head trauma in two siblings: lessons and legal implications.

Non-accidental head trauma (NAHT) is a common cause of traumatic brain injury in childhood, origin of profound and disabling neurological sequalae, and in the most disgraceful cases, ultimately death.Subdural hematoma (SDH) is the most common intracranial finding in NAHT. On the other hand, congenital bleeding disorders are a minor but a significant cause of ICH in the neonate and toddler. Not uncommonly, intracranial bleeding is the first sign of a severe inherited coagulation disorder. In the presence of an unexpected intracranial bleeding after a minor trauma or without a clear history of the related events, physicians and caregivers may be confronted to the dilemma of a possible child abuse. It must be bear in mind that physical abuse and bleeding disorders can co-exist in the same child.We report here the case of two siblings in whom a diagnosis of hemophilia coexisted with the presumption of a non-accidental head trauma. Child abuses were inflicted in both children with a spare time of 2 years. A diagnosis of mild hemophilia was prompted in the first sibling after initial NAHT, while inflicted trauma was evident in the second sibling after neuroimaging findings and concomitant lesions. Lessons from this case in co-existing bleeding disorders and inflicted trauma and legal implications derived will be discussed thereafter.The possibility of a bleeding disorder should be considered in all children presenting with unexplained bleeding at a critical site in the setting of suspected physical maltreatment, particularly intracranial hemorrhage (ICH).

High fructose-containing drinking water-induced steatohepatitis in rats is prevented by the nicotinamide-mediated modulation of redox homeostasis and NADPH-producing enzymes.

An imbalance in the redox state, increased levels of lipid precursors and overactivation of de novo lipogenesis determine the development of fibrosis during nonalcoholic steatohepatitis (NASH). We evaluated the modulation of NADPH-producing enzymes associated with the antifibrotic, antioxidant and antilipemic effects of nicotinamide (NAM) in a model of NASH induced by excess fructose consumption. Male rats were provided drinking water containing 40% fructose for 16 weeks. During the last 12 weeks of fructose administration, water containing NAM was provided to some of the rats for 5 h/day. The biochemical profiles and the ghrelin, leptin, lipoperoxidation and TNF-α levels in serum and the glucose-6-phosphate dehydrogenase (G6PD), malic enzyme (ME) and NADP+-dependent isocitric dehydrogenase (IDP) levels, the reduced/oxidized glutathione (GSH/GSSG) and reduced/oxidized nicotinamide adenine dinucleotide (phosphate) (NAD(P)H/NAD(P)+) ratios, and the levels of various lipogenic and fibrotic markers in the liver were evaluated. The results showed that hepatic fibrosis induced by fructose consumption was associated with weight gain, hunger-satiety system dysregulation, hyperinsulinemia, dyslipidemia, lipoperoxidation and inflammation. Moreover, increased levels of hepatic G6PD and ME activity and expression, the NAD(P)H/NAD(P)+ ratios, and GSSG concentration and increased expression of lipogenic and fibrotic markers were detected, and these alterations were attenuated by NAM administration. Specifically, NAM diminished the activity and expression of G6PD and ME, and this effect was associated with a decrease in the NADPH/NADP+ ratios, increased GSH levels and decreased lipoperoxidation and inflammation, ameliorating fibrosis and NASH development. NAM reduces liver steatosis and fibrosis by regulating redox homeostasis through a G6PD- and ME-dependent mechanism.

Recommendations for the prevention and diagnosis of asthma in children: Evidence from international guidelines adapted for Mexico.

BACKGROUND: With the availability of high-quality asthma guidelines worldwide, one possible approach of developing a valid guideline, without re-working the evidence, already analysed by major guidelines, is the ADAPTE approach, as was used for the development of National Guidelines on asthma. METHODS: The guidelines development group (GDG) covered a broad range of experts from medical specialities, primary care physicians and methodologists. The core group of the GDG searched the literature for asthma guidelines 2005 onward, and analysed the 11 best guidelines with AGREE-II to select three mother guidelines. Key clinical questions were formulated covering each step of the asthma management. RESULTS: The selected mother guidelines are British Thoracic Society (BTS), GINA and GEMA 2015. Responses to the questions were formulated according to the evidence in the mother guidelines. Recommendations or suggestions were made for asthma treatment in Mexico by the core group, and adjusted during several rounds of a Delphi process, taking into account: 1. Evidence; 2. Safety; 3. Cost; 4. Patient preference - all these set against the background of the local reality. Here the detailed analysis of the evidence present in BTS/GINA/GEMA sections on prevention and diagnosis in paediatric asthma are presented for three age-groups: children with asthma ≤5 years, 6-11 years and ≥12 years. CONCLUSIONS: For the prevention and diagnosis sections, applying the AGREE-II method is useful to develop a scientifically-sustained document, adjusted to the local reality per country, as is the Mexican Guideline on Asthma.

meso-Acetoxymethyl BODIPY dyes for photodynamic therapy: improved photostability of singlet oxygen photosensitizers.

We report two BODIPY based photosensitizers (Br2BOAc and I2BOAc) featuring an acetoxymethyl substituent at the meso-position. These photosensitizers show improved photostability against singlet oxygen, when compared to a BODIPY photosensitizer lacking the acetoxymethyl group. Both compounds were evaluated for photodynamic therapy against HeLa cells and photodynamic inactivation against E. coli bacteria. We show that the compounds readily embed in the lipid membranes of HeLa cervical cancer cells and efficiently induced light-dependent apoptosis at nanomolar concentration. Also, both compounds showed a substantial degree of photoinactivation of E. coli bacteria when used at low micromolar concentrations.

Effects of periodontal non-surgical therapy plus azithromycin on glycemic control in patients with diabetes: a randomized clinical trial.

BACKGROUND AND OBJECTIVE: Periodontitis may alter the systemic condition in patients with diabetes and hence interfere with glycemic control. The objective of this study was to determine the quantifiable changes in glycated hemoglobin (HbA1C) after periodontal non-surgical therapy plus azithromycin in a mixed population of patients with poorly controlled diabetes. MATERIALS AND METHODS: One hundred and five patients were randomized to receive non-surgical therapy plus azythromycin (AZ-Sca =33), non-surgical therapy plus placebo (PB-Sca = 37) and supragingival prophylaxis plus azithromycin (AZ-Pro = 35). Glycated hemoglobin, glycemia and periodontal parameters were measured at baseline, 3, 6 and 9 mo after treatment. RESULTS: Periodontal parameters were improved in the AZ-Sca and PB-Sca groups as compared to the AZ-Pro group. A greater reduction in probing depth was observed in the AZ-Sca as compared to the PB-Sca group. Improvement in clinical attachment level was similar between AZ-Sca and PB-Sca groups. A reduction from 8.0% to 7.2% (∆0.8%; p < 0.05) in HbA1C was observed in the AZ-Sca at 9 mo as compared to the PB-Sca group in which the reduction was from 7.9% to 7.6% (∆0.3%). There was no decrease in HbA1C in the AZ-Pro group over time. Mean glycemia values decreased from 195 mg/dL to 159.2 mg/dL (∆35.8 mg/dL; p < 0.05) in the AZ-Sca group whereas a decrease from 194 mg/dL to 174.8 mg/dL (∆19.2 mg/dL) in the PB-Sca group at 9 mo was observed. There were no differences between the AZ-Sca and PB-Sca groups for glycemic parameters. No improvement in glycemic values in the AZ-Pro group was observed. CONCLUSIONS: A modest improvement in glycemic control was detected with a trend towards the use of non-surgical therapy plus AZ as compared to the placebo.

Needs and preferences for the prevention of intimate partner violence among Hispanics: a community's perspective.

Research suggest that Hispanics in the U.S. are disproportionately affected by the consequences of intimate partner violence. Nevertheless, few intimate partner violence prevention interventions have been developed to address the unique needs and preferences of this population. The Partnership for Domestic Violence Prevention is a community-based participatory research project that assessed the needs and preferences for prevention programs for Hispanics in Miami-Dade County. Nine focus groups with domestic violence service providers, victims and general community members were conducted (N = 76). Four major themes emerged from the focus groups. These included immigrants and teens as the highest priority groups to target in prevention efforts, culture as a double-edged sword, the system that helps and hurts the victim, and the need for wide-scale prevention programs that would reach Hispanics systematically. The results from this study have important implications for the development of intimate violence prevention interventions targeting Hispanics in the U.S.

Modulatory role of α-MSH in hippocampal-dependent memory impairment, synaptic plasticity changes, oxidative stress, and astrocyte reactivity induced by short-term high-fat diet intake.

High-fat diet (HFD) consumption is associated with cognitive deficits and neurodegenerative diseases. Since the hippocampus is extremely sensitive to pathophysiological changes, neuroinflammation and the concomitant oxidative stress induced by HFD can significantly interfere with hippocampal-dependent functions related to learning and memory. The neuropeptide alpha-melanocyte stimulating hormone (α-MSH) mediates neuroprotective actions in the central nervous system and can reverse the effects of neuroinflammation in cognitive functions that depend on the hippocampus. In this study, we used male Wistar rats to evaluate the effect of short-term HFD intake (5 days) plus a mild immune challenge, Lipopolysaccharide (LPS 10 µg/kg) on contextual fear, changes in structural plasticity, oxidative stress, and astrocyte reactivation in the hippocampus. We also determined the possible modulatory role of α-MSH. HFD consumption was associated with an increase in markers of oxidative stress (Advanced oxidation protein products and Malondialdehyde) in the dorsal hippocampus (DH). We also found changes in hippocampal structural synaptic plasticity, observing a decrease in total spine in the DH after HFD plus LPS. We observed astrocyte proliferation and a significant increase in the percentage of the area occupied by GFAP. Treatment with α-MSH (0.1 µg/0.25 µl) in the DH reversed the effect of short-term HFD plus LPS on contextual fear memory, oxidative stress, and spine density. α-MSH also reduced astrocyte proliferation. Our present results indicate that HFD consumption for a short period sensitizes the central nervous system (CNS) to a subsequent immune challenge and impairs contextual fear memory and that α-MSH could have a modulatory protective effect.

[Translated article] Evaluation of factors related to the occurrence of new fragility fractures: A case-control study.

INTRODUCTION: Fragility fractures (FF) are frequent in osteoporotic patients. There are a series of risk factors and clinical variables that could predict their appearance. MATERIAL AND METHOD: A retrospective observational study of cases and controls was carried out. Cases were defined by the presence of FF (326 participants) and controls by patients with similar characteristics without FF (629 participants). RESULTS: Certain factors increase the risk of FF, such as a previous diagnosis of type 2 DM (OR: 2.001), 1ng/mL elevations of CTX (OR: 1.88), having a parental history of hip fracture (OR: 1.667), 5-year increase in age (OR: 1.39), and 1kg/m2 increases in BMI (OR: 1.041). In contrast, other factors evaluated decreased this risk, such as maintaining 25(OH)D levels≥30ng/mL (OR: 0.686) and a T-score≥-2.5 (OR: 0.642). CONCLUSIONS: Levels of 25(OH)D≥30ng/mL and a T-score at the femoral neck≥-2.5 are protective factors for FF, while a previous diagnosis of type 2 DM, an elevated CTX, a parental history of hip fracture, an increase of 1kg/m2 in BMI and an increase in age by 5 years would be predisposing to FF.

Evaluation of factors related to the occurrence of new fragility fractures: A case-control study. / Evaluación de los factores relacionados con la aparición de nuevas fracturas por fragilidad: un estudio de casos y controles.

INTRODUCTION: Fragility fractures (FF) are frequent in osteoporotic patients. There are a series of risk factors and clinical variables that could predict their appearance. MATERIAL AND METHOD: A retrospective observational study of cases and controls was carried out. Cases were defined by the presence of FF (326 participants) and controls by patients with similar characteristics without FF (629 participants). RESULTS: Certain factors increase the risk of FF, such as a previous diagnosis of type 2 DM (OR: 2.001), 1ng/mL elevations of CTX (OR: 1.88), having a parental history of hip fracture (OR: 1.667), 5-year increase in age (OR: 1.39), and 1kg/m2 increases in BMI (OR: 1.041). In contrast, other factors evaluated decreased this risk, such as maintaining 25(OH)D levels≥30ng/mL (OR: 0.686) and a T-score≥-2.5 (OR: 0.642). CONCLUSIONS: Levels of 25(OH)D≥30ng/mL and a T-score at the femoral neck≥-2.5 are protective factors for FF, while a previous diagnosis of type 2 DM, an elevated CTX, a parental history of hip fracture, an increase of 1kg/m2 in BMI and an increase in age by 5 years would be predisposing to FF.

Culture-negative TB: clinical characteristics, risk factors and treatment outcomes.

BACKGROUND: Although culture remains the standard for TB diagnosis, 15-20% of patients diagnosed and treated for TB are culture-negative. We explored clinical characteristics, risk factors and treatment outcomes for culture-negative TB in a Peruvian cohort.METHODS: We recruited 4,500 index TB patients and 10,160 household contacts in Lima, Peru, and enrolled 692 secondary patients diagnosed with TB during follow-up of household contacts. We analyzed smear and culture status, sociodemographic factors, clinical characteristics and TB treatment outcomes to compare culture-negative and positive patients.RESULTS: Of the 4,880 adult patients, 915 (18.8%) were culture-negative. Culture-negative patients were less likely to report symptoms of TB disease and disease of longer duration. A multivariate analysis showed no statistically significant difference in loss to follow-up, treatment failure or recurrence between the culture-negative and -positive groups but a higher rate of death among culture-negative patients with an adjusted OR of 1.65 (95% CI 1.05-2.60). In a multivariate analysis of determinants of culture negativity, older age, substance use and being a secondary case were associated with culture status.CONCLUSIONS: More recognition and awareness of culture-negative TB is key for early and correct diagnosis to reduce transmission and improve treatment outcomes.

In vitro activity of N-benzenesulfonylbenzotriazole on Trypanosoma cruzi epimastigote and trypomastigote forms.

Chagas disease is still an important health problem in Central and South America. However, the only drugs currently available for specific treatment of this disease may induce toxic side effects in the host. The aim of this work was to determine the activity of N-benzenesulfonylbenzotriazole (BSBZT) against the protozoan parasite Trypanosoma cruzi. The effects of BSBZT and benzotriazole (BZT) were compared to those of benznidazole (BZL) on epimastigote and trypomastigote forms. BSBZT was found to have an in vitro growth inhibitory dose-dependent activity against epimastigotes, with flow cytometry analysis confirming that the treated parasites presented size reduction. BSBZT showed an IC(50) of 21.56 µg/mL (81.07 µM) against epimastigotes at 72 h of incubation, whereas BZT did not affect the growth of this parasite form. Furthermore, the toxic effect of BSBZT, was stronger and appeared earlier (at 24h) in trypomastigotes than in epimastigotes, with the LC(50) of this compound being 28.40 µg/mL (106.79 µM) against trypomastigotes. The concentrations of BSBZT used in this study presented low hemolytic activity and cytotoxicity. Consequently, at concentrations near IC(50) and LC(50) (25µg/mL), BSBZT caused only 2.4% hemolysis and 15% of RAW 264.7 cell cytotoxicity. These results reveal the potential of BSBZT as a prototype in drug design for developing new anti-T. cruzi compounds.

[Hospital based internal medicine: a review of 2011]. / Médecine interne hospitalière: l'année 2011 en revue.

Numerous prospective randomised trials recently demonstrated the importance of an aggressive approach towards controlling cardiovascular risk factors. New studies reinforce the plethora of available data and confirm that interventional revascularisation strategies for stable coronary heart disease or cerebral vascular disease offer few benefits as compared to medical treatment, and can even lead to worse outcomes. This selective review describes some recent studies in the areas of cardiovascular disease, pulmonary disease, such as chronic obstructive pulmonary disease or screening of lung cancer, and gastroenterology.

[Retrospective observational study of the persistence of SARS-CoV-2 infection in patients previously treated with rituximab]. / Estudio observacional retrospectivo de persistencia de infección por SARS-CoV-2 en pacientes tratados previamente con rituximab.

OBJECTIVE: Rituximab-induced immunosuppression could be a risk factor for mortality from COVID-19. The aim of the study was to describe the prevalence of SARS-CoV-2 infection in patients who have received rituximab and its association with a persistent viral infection. METHODS: Retrospective observational study of patients who received rituximab in the 6 months before to the onset of the pandemic. We analyzed the presence of infection and associated them with demographic variables, pathological history related to an increased risk of developing severe COVID-19, the doses of rituximab received, the type of ventilatory support, thromboembolic events, and the treatment received. A descriptive analysis of all the variables was carried out and infected and uninfected patients were compared. RESULTS: We screened a total of 68 patients who had received rituximab (median cumulative dose: 4,161mg (2,611-8,187.5)). 54.4% men, mean age 60.8 years (15.7; 25-87)). C + was confirmed for 22 patients. Of these, 45.5% had high blood pressure, 36.4% Diabetes Mellitus, 31.8% smokers/ex-smoker, 22.7% lung disease, 13.6% heart disease and 4.5% obesity. There were no statistically significant differences between C+ and C-. Only 2 patients developed immunity. For 10 patients (45.5%) did not have a negative CRP until the end of the follow-up. There was no association with cumulative dose of rituximab. The mortality rate was 22.7% in the C+. CONCLUSIONS: We observe that the persistence of the infection leads to a worse evolution of COVID-19. The use of alternatives should be considered during the pandemic, because of patients with decreased B-cell function may have high risk of fatal progression from COVID-19.

Implementing 3HP vs. IPT as TB preventive treatment in Pakistan.

BACKGROUND: We assessed treatment uptake and completion for 6 months of isoniazid (6H) and 3 months of isoniazid plus rifapentine weekly (3HP) in a programmatic setting in Pakistan.METHODS: All household contacts were clinically evaluated to rule out TB disease. 6H was used for TB preventive treatment (TPT) from October 2016 to April 2017; from May to September 2017, 3HP was used for contacts aged ≥2 years. We compared clinical evaluation, TPT uptake and completion rates between contacts aged ≥2 years in the 6H period and in the 3HP period.RESULTS: We identified 3,442 contacts for the 6H regimen. After clinical evaluation, 744/1,036 (72%) started treatment, while 46% completed treatment. In contrast, 3,722 contacts were identified for 3HP. After clinical evaluation, 990/1,366 (72%) started treatment, while 67% completed treatment. Uptake of TPT did not differ significantly between the 6H and 3HP groups (OR 1.03, 95%CI 0.86-1.24). However, people who initiated 3HP had 2.3 times greater odds (95% CI 1.9-2.8) of completing treatment than those who initiated 6H after adjusting for age and sex.CONCLUSION: In programmatic settings in a high-burden country, household contacts of all ages were more likely to complete TPT with shorter weekly regimens, although treatment uptake rate for the two regimens was similar.

A structured community engagement strategy to support uptake of TB active case-finding.

BACKGROUND: In Lima, Peru, a mobile TB screening program ("TB Móvil") was implemented in high TB prevalence districts to increase TB screening. Community engagement activities to promote TB Móvil were simultaneously conducted. OBJECTIVE: To describe a structured, theory-driven community engagement strategy to support the uptake of TB Móvil. METHODS: We adapted Popular Opinion Leader (POL), an evidence-based social networking intervention previously used in Peru to promote HIV testing, for TB Móvil. Community health workers, women who run soup kitchens, and motorcycle taxi drivers served as "popular opinion leaders" who disseminated information about TB Móvil in everyday conversations, aided by a multi-media campaign. Performance indicators of POL included the number/characteristics of persons screened; number of multimedia elements; and proportion of persons with abnormal radiographs hearing about TB Móvil before attending. RESULTS: Between February 2019 and January 2020, 63,899 people attended the TB Móvil program at 210 sites; 60.1% were female. The multimedia campaign included 36 videos, 16 audio vignettes, flyers, posters, community murals and "jingles." Among attendees receiving an abnormal chest X-ray suggestive of TB, 48% (6,935/14,563) reported hearing about TB Móvil before attending. CONCLUSIONS: POL promotes the uptake of TB Móvil and should be considered as a strategy for increasing TB screening uptake.

CONTEXTE: À Lima, Pérou, un programme mobile de dépistage de la TB (« TB Móvil ¼) a été mis en place dans les quartiers à forte prévalence de TB afin d'accroître le dépistage de la maladie. Des activités de mobilisation communautaire visant à promouvoir TB Móvil ont été menées en parallèle. L'objectif de ce rapport est de décrire une stratégie structurée de mobilisation communautaire, fondée sur des principes théoriques, afin de soutenir le recours au programme TB Móvil. MÉTHODES: Nous avons adapté à TB Móvil l'intervention factuelle de réseautage social appelée « Popular Opinion Leader (POL; leader d'opinion) ¼, précédemment utilisée au Pérou pour promouvoir le dépistage du VIH. Les agents de santé communautaires, les femmes responsables de la soupe populaire et les chauffeurs de mototaxis étaient des leaders d'opinion. Ils communiquaient des informations sur TB Móvil lors de leurs conversations quotidiennes, qui étaient étayées par une campagne multimédia. Les indicateurs de performance des POL comprenaient le nombre/les caractéristiques des personnes dépistées, le nombre d'éléments multimédias et le pourcentage de personnes avec cliché radiographique anormal qui avaient entendu parler de TB Móvil avant de se faire dépister. RÉSULTATS: Entre février 2019 et janvier 2020, 63 899 personnes ont pris part au programme TB Móvil dans 210 sites ; 60,1% étaient des femmes. La campagne multimédia reposait sur 36 vidéos, 16 vignettes audio, des prospectus, des posters, des peintures murales dans la communauté et des « jingles ¼. Parmi les personnes dont la radiographie pulmonaire était anormale et évocatrice de TB, 48% (6 935/14 563) ont rapporté avoir entendu parler de TB Móvil avant de venir consulter. CONCLUSIONS: L'intervention POL, qui semblait renforcer le recours au programme TB Móvil, peut donc servir d'une stratégie de promotion du dépistage de la TB.

Evaluation and management of emergencies in the patient with cirrhosis.

The approach to and management of critically ill patients is one of the most versatile themes in emergency medicine. Patients with cirrhosis of the liver have characteristics that are inherent to their disease that can condition modification in acute emergency treatment. Pathophysiologic changes that occur in cirrhosis merit the implementation of an analysis as to whether the overall management of a critically ill patient can generally be applied to patients with cirrhosis of the liver or if they should be treated in a special manner. Through a review of the medical literature, the available information was examined, and the evidence found on the special management required by those patients was narratively synthesized, selecting the most representative decompensations within chronic disease that require emergency treatment.

Comparative transcriptome analysis of yeast strains carrying slt2, rlm1, and pop2 deletions.

The function of the genes SLT2 (encoding the Mpk1 protein), RLM1, and POP2 have previously been related to several stress responses in yeasts. DNA arrays have been used to identify differences among the transcriptomes of a Saccharomyces cerevisiae wild type strain and its derivative Δslt2, Δrlm1, and Δpop2 mutants. Correspondence analyses indicate that the vast majority of genes that show lower expression in Δrlm1 also show lower expression in Δslt2. In contrast, there is little overlap between the results of the transcriptome analyses of the Δpop2 strain and the Δslt2 or Δrlm1 strains. The DNA array data were validated by reverse Northern blotting and chromatin immunoprecipitation (ChIp). ChIp assays demonstrate Rlm1p binding to specific regions of the promoters of two genes that show expression differences between the Δrlm1 mutant and wild type strains. Interestingly, RLM1 deletion decreases the transcription of SLT2, encoding the Mpk1p kinase that phosphorylates Rlm1p, suggesting a feedback control in the signal transduction pathway. Also, deletion of RLM1 causes a decrease in the mRNA level of KDX1, which is paralogous to SLT2. In contrast, deletion of POP2 is accompanied by an increase of both SLT2 and KDX1 levels. We show that SLT2 mRNA increase in the Δpop2 strain is due to a decrease in RNA turnover, consistent with the expected loss of RNA-deadenylase activity in this strain.

Rapid and effective photodynamic treatment of biofilm infections using low doses of amoxicillin-coated gold nanoparticles.

Bacterial biofilm are complex microbial communities covered by a matrix of extracellular polymeric substances, which develops when a community of microorganisms irreversibly adheres to a living or inert surface. This structure is considered an important virulence factor because it is difficult to eradicate and often responsible for treatment failures. This adherent community represents one of the greatest problems in public health due to the continued emergence of conventional antibiotic-therapy resistance. Photodynamic Antimicrobial Therapy (PACT) is a therapeutic alternative and promises to be an effective treatment against multiresistant bacteria biofilm, demonstrating a broad spectrum of action. This work demonstrates the reduction in biofilms of relevant clinical isolates (as Pseudomonas aeruginosa and Staphylococcus aureus) treated with PACT using low concentrations of amoxicillin-coated gold nanoparticles (amoxi@AuNP) as a photosensitizer. Moreover, the viability reduction of 60% in S. aureus biofilms and 70% in P. aeruginosa biofilms were obtained after three hours of irradiation with white light and amoxi@AuNP. Scanning electron microscopy analysis revealed that amoxi@AuNP could penetrate and cause damage to the biofilm matrix, and interact with bacteria cells. A strong biofilm production in P. aeruginosa was observed by confocal laser scanning microscopy using acridine orange as a probe, and a markedly decrease in live bacteria was appreciated when PACT was applied. The use of amoxi@AuNP for PACT allows the viability reduction of clinical Gram positive and Gram negative biofilms. This novel strategy needs shorter irradiation times and lower concentrations of nanoparticles than other reports described. This could be attributed to two major innovations: the selectivity for the bacterial wall given by the amoxicillin and the polydispersity of size and shapes with seems to contribute to the photo-antibacterial capacity.