A20 attenuates pyroptosis and apoptosis in nucleus pulposus cells via promoting mitophagy and stabilizing mitochondrial dynamics.

BACKGROUND: A20 is an anti-inflammatory molecule in nucleus pulposus (NP) cells. The anti-inflammatory properties of A20 are mainly attributed to its ability to suppress the NF-κB pathway. However, A20 can protect cells from death independently of NF-κB regulation. This study aimed to investigate the effects of A20 on pyroptosis and apoptosis of NP cells induced by lipopolysaccharide (LPS). METHODS: NP cells induced by LPS were used as an in vitro model of the inflammatory environment of the intervertebral disc. Pyroptosis, apoptosis, and mitophagy marker proteins were detected. Then, NP cells were transfected with A20 overexpressed lentivirus or A20-siRNA. Annexin V FITC/PI, Western blotting, and immunofluorescence assays were used to detect the apoptosis, pyroptosis, and mitophagy of NP cells. Furthermore, the expressions of A20, related proteins, and related inflammatory cytokines were detected by western blotting, and ELISA. RESULTS: Apoptosis and pyroptosis of NP cells increased gradually treated with LPS for 12 h, 24 h, and 48 h. Differently, the level of mitophagy increased first and then decreased, and was the highest at LPS treatment for 12 h. Overexpression or knockdown of A20 in NP cells revealed that A20 attenuated the pyroptosis, apoptosis, and production of inflammatory cytokines of NP cells induced by LPS, while A20 sponsored mitophagy, reduced ROS production and collapse of mitochondrial membrane potential (ΔΨm). Moreover, A20 also promoted mitochondrial dynamic homeostasis and attenuated LPS-induced excessive mitochondrial fission. Excitingly, inhibition of mitophagy attenuated the effect of A20 on the negative regulation of pyroptosis of NP cells induced by LPS. Pyroptosis was accompanied by a large release of inflammatory cytokines. Inhibition of pyroptosis also significantly reduced apoptosis of NP cells. Finally, The mitochondria-targeted active peptide SS-31 inhibited LPS-induced pyroptosis and ROS production in NP cells. CONCLUSIONS: To sum up, A20 attenuates pyroptosis and apoptosis of NP cells via promoting mitophagy and stabilizing mitochondrial dynamics. Besides, A20 reduces LPS-induced NP cell apoptosis by inhibiting NLRP3 inflammasome-mediated pyroptosis. It provides theoretical support for the reduction of functional NP cell loss in the intervertebral disc through the gene-targeted intervention of A20.

Maternal antibiotic prophylaxis affects Bifidobacterium spp. counts in the human milk, during the first week after delivery.

Human milk is an important source of microorganisms for infant gut colonisation. Although the maternal antibiotic prophylaxis is an important strategy to prevent maternal/neonatal sepsis, it has to be investigated how it may affect the human milk microbiota, especially the genus Bifidobacterium, which has been associated to health benefits. Here, we investigated the impact of the maternal antibiotic prophylaxis on the human milk Bifidobacterium spp. and total bacteria counts, in the first week (short-term) and first month (medium-term) after delivery. Human milk samples were collected from 55 healthy lactating women recruited from the University Hospital of the University of São Paulo at days 7±3 and 30±4 after vaginal delivery. Twenty one volunteers had received maternal antibiotic prophylaxis (MAP group) and 34 had not received MAP (no-MAP group) during or after labour. Total DNA was isolated from milk samples, and the bacterial counts were estimated by quantitative PCR (qPCR). We found lower levels of Bifidobacterium in the MAP group in the first week after delivery (median = 2.1 vs 2.4 log of equivalent cells/ml of human milk, for MAP and no-MAP groups, respectively; P=0.01), although there were no statistical differences in total bacteria count. However, no differences were found in Bifidobacterium counts between the groups at day 30±4 (median = 2.5 vs 2.2 log of equivalent cells/ml of human milk, for MAP and no-MAP groups, respectively; P=0.50). Our results suggest that MAP has a significant impact on Bifidobacterium counts in human milk, reducing this population in the first week after delivery. However, throughout the first month after delivery, the Bifidobacterium counts tend to recover, reaching similar counts to those found in no-MAP group at day 30±4 after delivery.

Efeitos do Programa Escola de Postura e Reeducação Postural Global sobre a amplitude de movimento e níveis de dor em pacientes com lombalgia crónica / Efectos de un Programa de Escuela de Postura y Reeducación Postural Global sobre rango de movimiento y niveles de dolor en pacientes con dolor lumbar crónico (AU) / Effects of School-based exercise Program of Posture and Global Postural Reeducation on the range of motion and pain levels in patients with chronic low back pain

Objetivo. Comparar os efeitos do programa escola de postura (PEP) e reeducação postural global (RPG) sobre níveis de dor e amplitude de movimento em pacientes com lombalgia crônica. Método. A amostra foi dividida em 3 grupos de 10 sujeitos: grupo submetido ao tratamento através do PEP (idade: 46.30 ± 8.50 anos); grupo submetido ao tratamento através da RPG (idade: 43.60 ± 10.93 anos) e grupo controle (idade: 44.30 ± 10.68 anos). As intervenções foram realizadas em 10 sessões. Para avaliação do quadro álgico foi utilizada a escala subjetiva de dor CR10 de Borg. Para a análise da amplitude de movimento empregou‐se o protocolo de goniometria LABIFIE para os movimentos de extensão coxofemoral (ECF) e flexão da coluna lombar (FCL). Resultados. O teste de Wilcoxon mostrou uma redução nos escores dos níveis de dor nos grupos PEP e RPG (p < 0.0001) do pré para o pós‐tratamento. As comparações intergrupos, através do teste de Kruskal‐Wallis, apresentaram diminuição dos níveis de dor para o PEP (p < 0.0001) e o RPG (p < 0.0001) quando comparados ao CG no pós‐tratamento. A ANOVA com medidas repetidas revelou um aumento na amplitude do movimento para o PEP (ECF: p = 0.006; FCL: p = 0.002) e RPG (ECF: p = 0.034; FCL: p = 0.011) do pré para o pós‐tratamento. As comparações intergrupos apresentaram maiores amplitudes de movimento para o PEP (ECF: p = 0.006; FCL: p = 0.018) e RPG (EQ: p = 0.019; FCL: p = 0.020) quando comparados ao CG no pós‐tratamento. Não houve diferenças significativas entre o PEP e RPG. Conclusão. Os tratamentos PEP e RPG se mostraram eficientes para redução da lombalgia crónica (AU)

Objetivo. Comparar los efectos de un programa de escuela de postura (PEP) y reeducación postural global (RPG) individual sobre niveles de dolor y rango de movimiento en pacientes con dolor lumbar crónico. Método. La muestra se dividió en 3 grupos de 10 sujetos: grupo tratado por PEP (edad: 46.30 ± 8.50 años), grupo tratado por RPG (edad: 43.60 ± 10.93 años) y grupo control (edad: 44.30 ± 10.68 años). Las intervenciones se llevaron a cabo en 10 sesiones. Para la evaluación del dolor se utilizó la escala subjetiva del dolor CR10 Borg. Para el análisis de rango de movimiento, se utilizó el protocolo de goniometría en los movimientos de extensión de la cadera (EC) y flexión de la columna lumbar (FCL). Resultados. La prueba de Wilcoxon mostró una reducción en los niveles de dolor en los grupos de PEP y RPG (p < 0.0001). Las comparaciones entre los grupos mediante el test de Kruskal‐Wallis mostró disminución de los niveles de dolor para el PEP (p < 0.0001) y RPG (p < 0.0001) en comparación con CG después del tratamiento. El ANOVA con medidas repetidas reveló un aumento en rango de movimiento para el PEP (EC: p = 0.006; FCL: p = 0.002) y RPG (EC: p = 0.034; FCL: p = 0.011). Las comparaciones entre los grupos mostraron un mayor rango de movimiento para el PEP (EC: p = 0.006; FCL: p = 0.018) y RPG (EC: p = 0.019; FCL: p = 0.020) en comparación con el GC después del tratamiento. No hubo diferencias significativas entre el PEP y RPG. Conclusión. Los tratamientos de PEP y RPG fueron eficaces para reducir el dolor lumbar crônico (AU)

Objective. To compare the effects of school‐based exercise program of posture (SPP) and global postural reeducation (GPR) on pain levels and range of motion in patients with chronic low back pain. Method. The sample was divided into three groups of 10 subjects: group treated by SPP (age: 46.30 ± 8.50 years) group subjected to treatment by GPR (age: 43.60 ± 10.93 years) and control group (age: 44.30 ± 10.68 years). The interventions were performed in 10 sessions. For assessment of pain was used pain subjective scale CR10‐Borg. For the analysis of range of motion, we used the protocol to goniometry LABIFIE in the movements of hip extension (HE) and flexion of the lumbar spine (FLS). Results. The Wilcoxon test showed a reduction in levels of pain scores in groups SPP and GPR (p < 0.0001) of pre to post‐treatment. Comparisons between groups by the Kruskal‐Wallis test showed decreased levels of pain for SPP (p < 0.0001) and GPR (p < 0.0001) when compared to CG post‐treatment. Repeated measures ANOVA revealed an increase in range of motion for the SPP (HE: p = 0.006; FLS: p = 0.002) and GPR (HE: p = 0.034; FLS: p = 0.011) of pre to post‐treatment. Comparisons between groups showed greater range of motion for the SPP (HE: p = 0.006; FLS: p = 0.018) and GPR (HE: p = 0.019; FLS: p = 0.020) when compared to CG post‐treatment. There were no significant differences between the SPP and GPR. Conclusions. SPP and GPR treatments were effective for reducing chronic low back pain (AU)

Systematic review of evidence and consensus on perianal fistula: an analysis of national and international guidelines.

AIM: Treatment of perianal fistula has evolved with the introduction of new techniques and biologicals in Crohn's disease (CD). Several guidelines are available worldwide, but many recommendations are controversial or lack high-quality evidence. The aim of this work was to provide an overview of the current available national and international guidelines for perianal fistula and to analyse areas of consensus and areas of conflicting recommendations, thereby identifying topics and questions for future research. METHOD: MEDLINE, EMBASE and PubMed were systematically searched for guidelines on perianal fistula. Inclusion was limited to papers in English less than 10 years old. The included topics were classified as having consensus (unanimous recommendations in at least two-thirds of the guidelines) or controversy (fewer than three guidelines commenting on the topic or no consensus) between guidelines. The highest level of evidence was scored as sufficient (level 3a or higher of the Oxford Centre for Evidence-based Medicine Levels of Evidence 2009, http://www.cebm.net/oxford-centre-evidence-based-medicine-levels-evidence-march-2009/) or insufficient. RESULTS: Twelve guidelines were included and topics with recommendations were compared. Overall, consensus was present in 15 topics, whereas six topics were rated as controversial. Evidence levels varied from strong to lack of evidence. CONCLUSION: Evidence on the diagnosis and treatment of perianal fistulae (cryptoglandular or related to CD) ranged from nonexistent to strong, regardless of consensus. The most relevant research questions were identified and proposed as topics for future research.

Further contributions to nitrogen removal modelling in waste stabilization ponds.

A large database from an experimental maturation pond system in Brazil was used to verify the agreement of field results with values predicted by some of the most widely accepted models to describe ammonium and total nitrogen (TN) removal in facultative and maturation ponds. The same database was used to derive a pH-independent linear model to predict ammonium removal in ponds, which was proved to be, essentially, a function of ammonium surface loading rate. In general, all these models made reasonable predictions of ammonium or TN removal but tended to overestimate low ammonium effluent concentrations while underestimating higher values of field data.

The impact of malnutrition on morbidity, mortality and length of hospital stay in trauma patients.

BACKGROUND AND AIM: To asses the nutritional status of hospitalised trauma patients and the repercussion on the clinical follow up. METHODS: In a prospective way 161 adult patients admitted to the units of Intensive Care (ICU), General Surgery, Maxillofacial Surgery and Orthopedics of the Centro de Emergencias Médicas in Asunción, Paraguay, from March 2002 to March 2004 were evaluated at admission by using the Subjective Global Assessment (SGA). Patients were followed to determine length of hospital stay, complications and in-hospital mortality. RESULTS: From the trauma patients median age was 27 (14-92) years and 94% were males. Most patients (74%) were from the countryside. The most frequent anatomic sites of trauma were: head 25%, thorax 16.6%, limbs 15.4%, abdomen 14%. The median Injury Severity Score (ISS) was 20 (1-39). From this population of patients, 40% were malnourished or at risk of malnutrition according to the SGA. Multivariate analysis identified as significant risk factors for mortality: malnutrition according to the SGA (p = 0.04, RR = 4 (1-15), and admission to the ICU (p = 0.0001, RR 53 (12-234). Risk factors for complications were malnutrition according to the SGA (p = 0.003, RR 2.9 (1.4-5.8) and ISS over 20 (p = 0.001, RR = 8.4 (2.3-29.9). The risk factors for length of stay were malnutrition according to the Subjective Global Assesment (p = 0.01, RR = 2.3 (1.2-4.7) and Injury Severity Score over 20, p = 0.03, RR = 2.8 (1-7.3). CONCLUSIONS: In the conditions of this study, malnutrition is frequent on admission in trauma patients, and is an independent risk factor for morbidity, mortality, and prolongs the length of hospitalisation. Efforts should be made to quickly assess the nutritional status of these patients and early start nutritional intervention.

Study of lobation and vascularization of the lungs of wild boar (Sus scrofa).

The purpose of this study was to describe the anatomy of the lungs of wild boars for comparison with those of domestic swine. It was found that the right lung of the wild boar is divided into four lobes: cranial, median, caudal and accessory, whereas the left lung is divided into two lobes: cranial and caudal. In 93.4% of the cases, right pulmonary artery separates into the ascendant, descendant, median, accessory and caudal branches. In 73.3% of the cases, left pulmonary artery separates most frequently to form three branches to the cranial lobe, whereas the median lobe is generally supplied by only one arterial branch. There is a single pattern of bronchial distribution: in the right lung a tracheal bronchus leads to the cranial lobe, where it separates into the cranial and caudal bronchi and there are also bronchi to the median, caudal and accessory lobes. In the left lung, the large bronchus separates to form two branches, one of which further separates to form two branches to the cranial lobe whereas the other forms a single branch to the caudal lobe.

[Importance of serum albumin values in nutritional assessment and inflammatory activity in patients with Crohn's disease]. / Importância da albumina sérica na avaliação nutricional e de atividade inflamatória em pacientes com doença de Crohn.

BACKGROUND: The serum albumin concentration has frequently been regarded as an indicator of nutritional status, although the hypoalbuminemia may reflect an acute phase protein response during inflammation mediated by cytokines. Both hypoalbuminemia and malnutrition are observed in Crohn's disease. OBJECTIVES: To correlate the serum albumin values to disease activity and also to nutritional status in patients with Crohn's disease. PATIENTS/METHODS: Thirty six patients were studied. Nutritional status was assessed by anthropometry measures and inflammatory activity determined by Harvey's simple clinical index and erythrocyte sedimentation rate. RESULTS: No correlation was found between malnutrition and hypoalbuminemia. The serum albumin levels correlated inversely with the disease activity. Hypoalbuminemia was 100% sensitive for detection of disease activity. CONCLUSION: This study suggests that serum albumin concentration is a very sensitive marker of inflammatory activity and not good indicator of the nutritional status in Crohn's disease. It is necessary a suitable laboratorial parameter for routine nutrition assessment in patients with this inflammatory bowel disease.

[Determination of the arm circumference in newborn infants as a method of verifying low birth weight]. / Avaliação do perímetro braquial em recém-nascidos, como método de verificação de baixo peso ao nascer.

The authors studied 1,024 newborns in Recife, Brazil, to determine the association between arm circumference and birth weight. A strong correlation between these two parameters was found (R = +0.78). Specificity and sensitivity of this measurement in detecting low birth weight were also high. The authors concluded that arm circumference can be used as an alternative method of detecting at-risk neonates in areas where birth weight cannot be measured accurately.

Evaluation of newborn arm circumference as an indicator of low birth weight.

A sample of 1,024 newborns in Recife, Brazil, was studied to help determine the precision with which arem circumference measurements could be used to indicate low birth weight. The results support the view that when birth weight data are unobtainable, arm circumference measurements may be of value in screening for newborns needing special care.

Spatial distribution of proportional infant mortality and certain socioeconomic variables in Salvador, Bahia, Brazil.

PIP: The spatial distribution of infant deaths in each zone of the city of Salvador, Brazil, in 1980 was examined and related to selected socioeconomic and health care variables. The spatial distribution of infant mortality (defined as the ratio of infant deaths to total deaths in Salvador) was uneven, ranging from 3.9% in a zone in the center of the old city near the water to 52.5% in an outlying area. There was a direct correlation between proportional infant mortality and low income. The proportion of low-income families was 23.1% in the quartile containing the lowest rates of infant mortality compared with 97.7% in the quartile containing the highest such rates. Also noted was an inverse relationship between proportional infant mortality and water consumption. Similarly, the percentage of substandard housing (shacks) was directly associated with infant mortality, rising from 2% in the 1st quartile (low infant mortality) to 43% in the 4th quartile. There was additionally an inverse correlation between the average number of physicians per inhabitant and proportional infant mortality, with a rate of 5.7/10,000 inhabitants in the 1st quartile compared with 1.8 in the 4th. Overall, analysis of the spatial distribution of infant deaths in Salvador reveals that an especially high proportion of those dying were infants residing in certain zones of the city, most notably outlying neighborhoods and slums. The results further point to an important association between certain socioeconomic and sanitation variables and infant mortality. The fact that the highest correlation coefficient found in the present study was between proportional infant mortality and the percentage of low-income families underscores the significant role that economic structure plays in infant mortality. There is a need both to redefine the urban development model prevailing in Latin America and to reorient the aims of the health sector.^ieng