Effects of heat waves on cardiovascular and respiratory mortality in Rio de Janeiro, Brazil.

BACKGROUND: Heat waves are becoming more intense and extreme as a consequence of global warming. Epidemiological evidence reveals the health impacts of heat waves in mortality and morbidity outcomes, however, few studies have been conducted in tropical regions, which are characterized by high population density, low income and low health resources, and susceptible to the impacts of extreme heat on health. The aim of this paper is to estimate the effects of heat waves on cardiovascular and respiratory mortality in the city of Rio de Janeiro, Brazil, according to sex, age, and heat wave intensity. METHODS: We carried out a time-stratified case-crossover study stratified by sex, age (0-64 and 65 or above), and by sex for the older group. Our analyses were restricted to the hot season. We included 42,926 participants, 29,442 of whom died from cardiovascular and 13,484 from respiratory disease, between 2012 and 2017. The death data were obtained from Rio de Janeiro's Municipal Health Department. We estimated individual-level exposure using the inverse distance weighted (IDW) method, with temperature and humidity data from 13 and 12 stations, respectively. We used five definitions of heat waves, based on temperature thresholds (90th, 92.5th, 95th, 97.5th, and 99th of individual daily mean temperature in the hot season over the study period) and a duration of two or more days. Conditional logistic regression combined with distributed lag non-linear models (DLNM) were used to estimate the short-term and delayed effects of heat waves on mortality over a lag period (5 days for cardiovascular and 10 for respiratory mortality). The models were controlled for daily mean absolute humidity and public holidays. RESULTS: The odds ratios (OR) increase as heat waves intensify, although some effect estimates are not statistically significant at 95% level when we applied the most stringent heat wave criteria. Although not statistically different, our central estimates suggest that the effects were greater for respiratory than cardiovascular mortality. Results stratified by sex and age were also not statistically different, but suggest that older people and women were more vulnerable to the effects of heat waves, although for some heat wave definitions, the OR for respiratory mortality were higher among the younger group. The results also indicate that older women are the most vulnerable to heat wave-related cardiovascular mortality. CONCLUSION: Our results show an increase in the risk of cardiovascular and respiratory mortality on heat wave days compared to non-heat wave ones. These effects increase with heat wave intensity, and evidence suggests that they were greater for respiratory mortality than cardiovascular mortality. Furthermore, the results also suggest that women and the elderly constitute the groups most vulnerable to heat waves.

A Comparative Investigation Applying Testicular Fine Needle Aspiration Cytology and Open Testicular Biopsy Histology for the Diagnosis of Azoospermia and Severe Oligospermia.

Open testicular biopsy histology and fine needle aspiration cytology (FNAC) are the most popular tests used to diagnose male infertility. This study aimed to assess the cytological characteristics of 186 infertile males aged 24-63 with testicular FNAC. Furthermore, the existing relationship between males with severe oligospermia (sperm count: 5 million/ml) and azoospermia was investigated via both cytological and histological diagnosis methods. With a 1.5-inch and 25-gauge needle, the testis was aspirated from three locations (the upper, middle, and lower poles). Papanicolaou stain or Giemsa stain was used to make smears on albumenized slides, which were then dried in the air and stained. A biopsy of the testicles was performed there, preserved in Bouins solution, processed as usual, and stained with hematoxylin and eosin stain. According to our findings, 66.7% of patients had secondary maturation arrest, whereas 18.3% and 15.1% of them had hypospermatogenesis and Sertoli cell only (SCO). Results of the comparison showed that both procedures were very similar. According to biopsy histological examinations, only 3 (1.6%) of the 28 normal FNAC instances had hypospermatogenesis with lymphocyte infiltration. The majority of SCO patients were over 50 years old. These findings revealed that FNAC is more effective than testicular histology for the assessment of male infertility.

Association of urban inequality and income segregation with COVID-19 mortality in Brazil.

Socioeconomic factors have exacerbated the impact of COVID-19 worldwide. Brazil, already marked by significant economic inequalities, is one of the most affected countries, with one of the highest mortality rates. Understanding how inequality and income segregation contribute to excess mortality by COVID-19 in Brazilian cities is essential for designing public health policies to mitigate the impact of the disease. This paper aims to fill in this gap by analyzing the effect of income inequality and income segregation on COVID-19 mortality in large urban centers in Brazil. We compiled weekly COVID-19 mortality rates from March 2020 to February 2021 in a longitudinal ecological design, aggregating data at the city level for 152 Brazilian cities. Mortality rates from COVID-19 were compared across weeks, cities and states using mixed linear models. We estimated the associations between COVID-19 mortality rates with income inequality and income segregation using mixed negative binomial models including city and week-level random intercepts. We measured income inequality using the Gini index and income segregation using the dissimilarity index using data from the 2010 Brazilian demographic census. We found that 88.2% of COVID-19 mortality rates variability was between weeks, 8.5% between cities, and 3.3% between states. Higher-income inequality and higher-income segregation values were associated with higher COVID-19 mortality rates before and after accounting for all adjustment factors. In our main adjusted model, rate ratios (RR) per 1 SD increases in income inequality and income segregation were associated with 17% (95% CI 9% to 26%) and 11% (95% CI 4% to 19%) higher mortality. Income inequality and income segregation are long-standing hallmarks of large Brazilian cities. Risk factors related to the socioeconomic context affected the course of the pandemic in the country and contributed to high mortality rates. Pre-existing social vulnerabilities were critical factors in the aggravation of COVID-19, as supported by the observed associations in this study.

Assessing the nationwide impact of COVID-19 mitigation policies on the transmission rate of SARS-CoV-2 in Brazil.

COVID-19 is now identified in almost all countries in the world, with poorer regions being particularly more disadvantaged to efficiently mitigate the impacts of the pandemic. In the absence of efficient therapeutics or large-scale vaccination, control strategies are currently based on non-pharmaceutical interventions, comprising changes in population behavior and governmental interventions, among which the prohibition of mass gatherings, closure of non-essential establishments, quarantine and movement restrictions. In this work we analyzed the effects of 707 governmental interventions published up to May 22, 2020, and population adherence thereof, on the dynamics of COVID-19 cases across all 27 Brazilian states, with emphasis on state capitals and remaining inland cities. A generalized SEIR (Susceptible, Exposed, Infected and Removed) model with a time-varying transmission rate (TR), that considers transmission by asymptomatic individuals, is presented. We analyze the effect of both the extent of enforced measures across Brazilian states and population movement on the changes in the TR and effective reproduction number. The social mobility reduction index, a measure of population movement, together with the stringency index, adapted to incorporate the degree of restrictions imposed by governmental regulations, were used in conjunction to quantify and compare the effects of varying degrees of policy strictness across Brazilian states. Our results show that population adherence to social distance recommendations plays an important role for the effectiveness of interventions and represents a major challenge to the control of COVID-19 in low- and middle-income countries.

In vitro study of the proliferation and growth of human fetal osteoblasts on Mg and Si co-substituted tricalcium phosphate ceramics.

The objective of this work was to study the feasibility of the solid state sintering, a conventional ceramic processing method, to obtain Mg and Si co-substituted tricalcium phosphate bioceramics and composites containing diopside. A series of new Ca3 (PO4 )2 based ceramics has been prepared from attrition milled mixtures of synthetic Ca3 (PO4 )2 and CaMg(SiO3 )2 powders, isostatically pressed and sintered at 1250-1300°C. Materials containing 0, 1, and 5 wt % of CaMg(SiO3 )2 were constituted by ß + α - Ca3 (PO4 )2 solid solutions while the material containing 60 wt % of CaMg(SiO3 )2 was a constituted by ß- Ca3 (PO4 )2 and CaMg(SiO3 )2 . The biological responses of the developed ceramics were studied in vitro using human fetal osteoblast cultures. Culture times ranged from 1 to 21 days. The new family of materials promotes the adhesion and proliferation of human osteoblasts cultured onto their surface forming a monolayer and showing a normal morphology. The results of the MTT and Alamar Blue assays showed that the soluble components extracted from the Mg/Si- co-substituted Ca3 (PO4 )2 and the Ca3 (PO4 )2 -CaMg(SiO3 )2 composite were noncytotoxic. The specimens with diopside exhibited a better in vitro behavior which is attributed to the release of Si and Mg ions to the culture medium, enhancing the activity of cells. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2266-2275, 2017.

Liver mitochondrial membrane fluidity at early development of diabetes and its correlation with the respiration.

The biological membranes are important in cell function but, during development of diseases such as diabetes, they are impaired. Consequently, membrane-associated biological processes are impaired as well. The mitochondria are important organelles where oxidative phosphorylation takes place, a process closely related with the membranes. In general, it is accepted that the development process of diabetes decreases membrane fluidity. However, in some cases, it has been found to increase membrane fluidity of mitochondria but to decrease the Respiratory Control (RC) index. In this study we found an increase of membrane fluidity and an increase of the RC at an early phase of the development of a type 2 diabetes model. We measured the lipoperoxidation, analyzed the fatty acids composition by gas chromatography, and assessed membrane fluidity using three fluorescent monitors located at different depths inside the bilayer, dipyrenilpropane (DPyP), diphenylhexatriene (DPH), and trimethylammonium diphenylhexatriene (TMA-DPH). Our findings indicate that in the initial stage of diabetes development, when lipoperoxidation still is not significant, the membrane fluidity of liver mitochondria increases because of the increment in the unsaturated to saturated fatty acids ratio (U/S), thus producing an increase of the RC. The membrane fluidity is not the same at all depths in the bilayer. Contrary to the results obtained in mitochondria, the diabetes induced a decrease in the U/S fatty acids ratio of liver total lipids, indicating that the mitochondria might have an independent mechanism for regulating its fatty acids composition.

Rate of Organ Space Infection Is Reduced with the Use of an Air Leak Test During Major Hepatectomies.

BACKGROUND: Organ/space surgical site infections (OSIs) constitute an important postoperative metric. We sought to assess the impact of a previously described air leak test (ALT) on the incidence of OSI following major hepatectomies. METHODS: A single-institution hepatobiliary database was queried for patients who underwent a major hepatectomy without biliary-enteric anastomosis between January 2009 and June 2015. Demographic, clinicopathologic, and intraoperative data-including application of ALT-were analyzed for associations with postoperative outcomes, including OSI, hospital length of stay (LOS), morbidity and mortality rates, and readmission rates. RESULTS: Three hundred eighteen patients were identified who met inclusion criteria, of whom 210 had an ALT. ALT and non-ALT patients did not differ in most disease and treatment characteristics, except for higher rates of trisegmentectomy among ALT patients (53 vs. 34 %, p = 0.002). ALT patients experienced lower rates of OSI and 90-day morbidity than non-ALT patients (5.2 vs. 13.0 %, p = 0.015 and 24.8 vs. 40.7 %, p = 0.003, respectively). In turn, OSI was the strongest independent predictor of longer LOS (OR = 4.89; 95 % CI, 2.80-6.97) and higher rates of 30- (OR = 32.0; 95 % CI, 10.9-93.8) and 45-day readmissions (OR = 29.4; 95 % CI, 10.2-84.6). CONCLUSIONS: The use of an intraoperative ALT significantly reduces the rate of OSI following major hepatectomy and may contribute to lower post-discharge readmission rates.

Biologic mesh spacer placement facilitates safe delivery of dose-intense radiation therapy: A novel treatment option for unresectable liver tumors.

INTRODUCTION: Patients with unresectable liver tumors who fail initial treatment modalities have a poor prognosis (<1 yr). Although effective, delivery of high dose radiation therapy to these tumors is limited by proximity of radiosensitive bowel. We have previously reported that placement of a biologic mesh spacer (BMS) can effectively displace the bowel allowing for dose-intense radiation to be delivered with low short-term toxicity. The purpose of this study was to assess and report the long-term safety and oncologic outcomes of this cohort. METHODS: From 2012 to 2014 seven patients with unresectable hepatic malignancy (6 IHCC, 1 CRLM) underwent BMS (acellular human dermis) placement (2 open, 5 MIS) prior to radiation therapy. Prospective registry data were reviewed for tumor and treatment details, progression, metastasis and survival. RTOG guidelines were used to define radiation toxicities. RESULTS: Mean patient age was 50.4 years (30-62 years) and 4 patients were male (57.1%). Prior to surgery, all patients had been treated for an average of 12.5 months with surgery, chemotherapy, radiation and/or TACE. After surgery, all patients recovered well and received a mean radiation dose of 76.1 Gy (58.1-100 Gy) over 13-25 fractions. 1 patient received SBRT; 4 fractions, 10 Gy each. Maximum dose delivered was 100 Gy (Biologic Equivalent Dose of 140 Gy, α/ß = 10). Mean time to initiation of radiation therapy was 24 days (12-48 days) from surgery. No significant GI toxicity was recorded, and no GI bleeding or ulcers were observed. Mean follow-up after XRT was 18.2 months (5.5-31 months). Three patients had no loco-regional progression of disease. 2 patients had infield progression of liver disease and another had progressive lymphadenopathy. 3 patients developed pulmonary metastasis, at a mean time to distant failure of 3 months. There are 4 survivors over 2-years from surgery. CONCLUSION: For patients with unresectable liver tumors, placement of a BMS enhances the safety and efficacy of high-dose radiotherapy, providing a survival benefit via delay in time to progression compared to traditional treatments with no significant short or long term GI toxicity.

Effect of Mg and Si co-substitution on microstructure and strength of tricalcium phosphate ceramics.

Magnesium and silicon co-doped tricalcium phosphate (TCP) ceramics with compositions corresponding to 0, 5 and 10wt% CaMg(SiO3)2 in the system Ca3(PO4)2-CaMg(SiO3)2 were obtained by conventional sintering of compacted mixtures of Ca3(PO4)2, MgO, SiO2 and CaCO3 powders at temperatures between 1100 and 1450°C. Microstructural analyses were performed by X-ray diffraction and field emission scanning electron microscopy with energy dispersive spectroscopy. Major phases in the obtained ceramics were ß- or α+ß-tricalcium phosphate containing Mg and Si in solid solution. Certain amounts of liquid were formed during sintering depending on composition and temperature. There were found significant differences in distributions of strength determined by the diametral compression of disc tests (DCDT). Failure strengths were controlled by microstructural defects associated with phase development. Mg and Si additions were found to be effective to improve densification and associated strength of TCP bioceramics due to the enhancement of sintering by the low viscosity liquids formed. The highest density and strength were obtained for the TCP ceramic containing 5wt% CaMg(SiO3)2 sintered at 1300°C. Cracking and porosity increased at higher temperatures due to grain growth and swelling.

Caracterización de un modelo de diabetes tipo 2 en ratas Wistar hembra / Characterization of a type 2 diabetes model in female Wistar rats

Objetivo. Caracterizar un modelo de diabetes mellitus tipo 2 (DM2) en ratas hembra. Materiales y métodos. Se utilizaron 20 ratas Wistar hembra de 48 horas de edad; a 10 se les administró estreptozotocina (STZ), [135 mg/kg de peso corporal] en 50 µl de amortiguador de citratos a pH de 4.5, vía intraperitoneal (inducidos) y a 10 se les administró 50 µl del amortiguador (testigo). Resultados. Los animales inducidos presentaron glicemias de 7.8±2 mmol/L (52.9% más que el testigo; p<0.005) y un peso de 334.4±12 g (51.6 g menor que el testigo; p<0.05) al final del estudio. La concentración de colesterol fue del doble en el grupo inducido. La concentración de triglicéridos no presentó diferencia entre grupos al primer mes de edad, pero al segundo fue 50% mayor en los animales inducidos (p<0.05). La concentración de hemoglobina glicada fue de 4.3% en los testigos y de 5.9% en animales inducidos (p<0.05). La curva de tolerancia mostró alteración en el grupo inducido con glicemias superiores a 7.4 mmol/L hasta los 240 min. Conclusiones. De acuerdo con los parámetros de las pruebas comúnmente utilizadas para el diagnóstico y control de la diabetes en humanos, los valores obtenidos en el presente estudio convalidan el desarrollo de un modelo de DM2 en ratas hembras mediante el uso de STZ.

Objective. Characterization of a type 2 diabetes mellitus (DM2) model in female rats. Materials and methods. 20, 48 hour-old wistar female rats were used; 10 were intraperitoneally injected with streptozotocin (STZ) [135 mg/kg body weight] in 50 µl citrate buffer pH 4.5 (induced group) and 10 were injected with 50 µl of citrate buffer (control group). Results. The induced group had average glycemias of 7.8±2 mmol/L (52.9%; p<0.005) and a body weight of 334.4±12 g (51.6 g lower than the control group; p<0.05) at the end of the treatment. The cholesterol concentration was two-fold higher in the induced group. Triglyceride concentration was not different during the first month, but it was 50% higher on the second month for the induced group (p<0.05). The concentration of glycated hemoglobin was 4.3% for the control group and 5.9% for the induced group (p<0.05). The glucose tolerance curve was altered in the induced group with blood glucose concentrations in diabetic animals over 7.4 mmol/L until 240 min. Conclusions. According to the parameters currently used for diagnostic and control of diabetes in humans, the results displayed in this study support the development of a DM2 model in female rats through the use of STZ.

Dietary avocado oil supplementation attenuates the alterations induced by type I diabetes and oxidative stress in electron transfer at the complex II-complex III segment of the electron transport chain in rat kidney mitochondria.

Impaired complex III activity and reactive oxygen species (ROS) generation in mitochondria have been identified as key events leading to renal damage during diabetes. Due to its high content of oleic acid and antioxidants, we aimed to test whether avocado oil may attenuate the alterations in electron transfer at complex III induced by diabetes by a mechanism related with increased resistance to lipid peroxidation. 90 days of avocado oil administration prevented the impairment in succinate-cytochrome c oxidoreductase activity caused by streptozotocin-induced diabetes in kidney mitochondria. This was associated with a protection against decreased electron transfer through high potential chain in complex III related to cytochromes c + c1 loss. During Fe(2+)-induced oxidative stress, avocado oil improved the activities of complexes II and III and enhanced the protection conferred by a lipophilic antioxidant against damage by Fe(2+). Avocado oil also decreased ROS generation in Fe(2+)-damaged mitochondria. Alterations in the ratio of C20:4/C18:2 fatty acids were observed in mitochondria from diabetic animals that not were corrected by avocado oil treatment, which yielded lower peroxidizability indexes only in diabetic mitochondria although avocado oil caused an augment in the total content of monounsaturated fatty acids. Moreover, a protective effect of avocado oil against lipid peroxidation was observed consistently only in control mitochondria. Since the beneficial effects of avocado oil in diabetic mitochondria were not related to increased resistance to lipid peroxidation, these effects were discussed in terms of the antioxidant activity of both C18:1 and the carotenoids reported to be contained in avocado oil.

Integrative molecular profiling reveals asparagine synthetase is a target in castration-resistant prostate cancer.

The identification of new and effective therapeutic targets for the lethal, castration-resistant stage of prostate cancer (CRPC) has been challenging because of both the paucity of adequate frozen tissues and a lack of integrated molecular analysis. Therefore, in this study, we performed a genome-wide analysis of DNA copy number alterations from 34 unique surgical CRPC specimens and 5 xenografts, with matched transcriptomic profiling of 25 specimens. An integrated analysis of these data revealed that the asparagine synthetase (ASNS) gene showed a gain in copy number and was overexpressed at the transcript level. The overexpression of ASNS was validated by analyzing other public CRPC data sets. ASNS protein expression, as detected by reverse-phase protein lysate array, was tightly correlated with gene copy number. In addition, ASNS protein expression, as determined by IHC analysis, was associated with progression to a therapy-resistant disease state in TMAs that included 77 castration-resistant and 40 untreated prostate cancer patient samples. Knockdown of ASNS by small-interfering RNAs in asparagine-deprived media led to growth inhibition in both androgen-responsive (ie, LNCaP) and castration-resistant (ie, C4-2B) prostate cancer cell lines and in cells isolated from a CRPC xenograft (ie, MDA PCa 180-30). Together, our results suggest that ASNS is up-regulated in cases of CRPC and that depletion of asparagine using ASNS inhibitors will be a novel strategy for targeting CRPC cells.

Analysis of the membrane fluidity of erythrocyte ghosts in diabetic, spontaneously hypertensive rats.

Diabetes and hypertension are closely related diseases associated with changes in membrane fluidity. Here, we measured the membrane fluidity of erythrocyte ghosts from spontaneously hypertensive rats (SHR), with or without streptozotocin (STZ)-induced diabetes, at the ages of 1, 3 and 6 months, by introducing the use of the intramolecular excimer forming dipyrenylpropane (DPyP) in this model. Type 2 diabetes mellitus (T2DM) was induced in 48-h-old, newborn male SHR by intraperitoneal injection of STZ. We found lower excimer to monomer (I (e)/I (m)) DPyP ratios in diabetic SHR than in control SHR at 3 and 6 months old, indicating a decrease in membrane fluidity. Simultaneously, the composition of fatty acids was determined and it was found that the unsaturated to saturated fatty acids ratio (U/S) was compatible with changes in membrane fluidity. These results suggest that the change in fatty acid composition of erythrocyte ghosts contributes significantly to the decreased membrane fluidity detected with DPyP in diabetic SHR.

PTEN genomic deletion is associated with p-Akt and AR signalling in poorer outcome, hormone refractory prostate cancer.

PTEN haploinsufficiency is common in hormone-sensitive prostate cancer, though the incidence of genomic deletion and its downstream effects have not been elucidated in clinical samples of hormone refractory prostate cancer (HRPC). Progression to androgen independence is pivotal in prostate cancer and mediated largely by the androgen receptor (AR). Since this process is distinct from metastatic progression, we examined alterations of the PTEN gene in locally advanced recurrent, non-metastatic human HRPC tissues. Retrospective analyses of PTEN deletion status were correlated with activated downstream phospho-Akt (p-Akt) pathway proteins and with the androgen receptor. The prevalence of PTEN genomic deletions in transurethral resection samples of 59 HRPC patients with known clinical outcome was assessed by four-colour FISH analyses. FISH was performed using six BAC clones spanning both flanking PTEN genomic regions and the PTEN gene locus, and a chromosome 10 centromeric probe. PTEN copy number was also evaluated in a subset of cases using single nucleotide polymorphism (SNP) arrays. In addition, the samples were immunostained with antibodies against p-Akt, p-mTOR, p-70S6, and AR. The PTEN gene was deleted in 77% of cases, with 25% showing homozygous deletions, 18% homozygous and hemizygous deletions, and 34% hemizygous deletions only. In a subset of the study group, SNP array analysis confirmed the FISH findings. PTEN genomic deletion was significantly correlated to the expression of downstream p-Akt (p < 0.0001), AR (p = 0.025), and to cancer-specific mortality (p = 0.039). PTEN deletion is common in HRPC, with bi-allelic loss correlating to disease-specific mortality and associated with Akt and AR deregulation.

[Comparison of annual risk for tuberculosis infection (1994-2001) in school children in Djibouti: methodological limitations and epidemiological value in a hyperendemic context]. / Comparaison du risque annuel d'infection tuberculeuse (1994-2001) auprès d'enfants scolarisés à Djibouti: limites méthodologiques et intérêt épidémiologique dans un contexte hyperendémique.

The purpose of this report was to describe a tuberculin survey conducted in 2001 to assess the trend in the annual risk for tuberculosis infection in Djibouti and compare resulting data with those obtained in a previous survey conducted in 1994. In 2001 cluster sampling allowed selection of 5599 school children between the ages of 6 and 10 years including 31.2% (1747/5599) without BCG vaccination scar. In this sample the annual risk of infection (ARI) estimated using cutoff points of 6 mm, 10 mm, and 14 mm corrected by a factor of 1/0.82 and a mode value (18 mm) determined according to the "mirror" method were 4.67%, 3.64%, 3.19% and 2.66% respectively. The distribution of positive tuberculin skin reaction size was significantly different from the normal law. In 1994 a total of 5257 children were selected using the same method. The distribution of positive reactions was not significantly different from the gaussian distribution and 28.6% (1505/5257) did not have a BCG scar. The ARI estimated using cutoff points of 6 mm, 10 mm, and 14 mm corrected by a factor of 1/0.82 and a mode value (17 mm) determined according to the "mirror" method were 2.68%, 2.52%, 2.75% and 3.32 respectively. Tuberculin skin reaction size among positive skin test reactors was correlated with the presence of a BCG scar, and its mean was significantly higher among children with BCG scar. The proportion of positive skin test reactors was also higher in the BCG scar group regardless of the cutoff point selected. Comparison of prevalence rates and ARI values did not allow any clear conclusion to be drawn, mainly because of a drastic difference in the positive reaction distribution profiles between the two studies. The distribution of the skin test reaction's size 1994 study could be modelized by a gaussian distribution while it could not in 2001. A partial explanation for the positive reaction distribution observed in the 2001 study might be the existence of cross-reactions with environmental mycobacteria.

Low nuclear ErbB3 predicts biochemical recurrence in patients with prostate cancer.

OBJECTIVE: To further evaluate the association between the cytoplasmic or nuclear localization of ErbB3 with biochemical recurrence (BCR) in patients with prostate cancer and positive surgical margins, as there is a greater risk of BCR for such patients after radical prostatectomy (RP). PATIENTS AND METHODS: We recently noted that ErbB3, which is normally associated with the plasma membrane, can translocate to the nucleus, an event which appears to be associated with disease progression. We evaluated ErbB3 expression and localization using immunohistochemistry on tissue samples from 55 patients with positive surgical margins after RP; 30 of these 55 (55%) had BCR after 3 years of follow-up. The relationship between ErbB3 nuclear localization and BCR (prostate-specific antigen, PSA, >0.3 ng/mL) after RP was analysed by Kaplan-Meier survival analysis and Cox regression models. RESULTS: The BCR-free survival probability at 3 years was 0.65 and 0.35 for positive and negative nuclear ErbB3, respectively (Kaplan-Meier, P = 0.029). Patients negative for nuclear ErbB3 had a 2.47-fold increase in BCR frequency in a univariate Cox model (P = 0.008) and it remained an independent prognostic marker when combined with clinical prognostic variables in a multivariate model (P = 0.023). CONCLUSION: Low nuclear localization of ErbB3 is a predictor of BCR in patients with prostate cancer and positive surgical margins after RP.

Synergistic effects of ethanol and hyperthermia on carotid artery vasoconstriction.

BACKGROUND: Heatstroke is a serious condition and clinical studies indicate that vascular stroke increases with excessive consumption of alcohol (ethanol). It was our objective to test the influence of ethanol on cerebral perfusion at normal and higher temperatures. METHODS: Recording of isometric tension in rabbit carotid artery strips in organ baths with different concentrations of ethanol at 37 degrees C and during hyperthermia (39-43 degrees C) and scintigraphic cerebral imaging of a radioactive isotope in the control situation and during hyperthermia. RESULTS: Stepwise heating induced reproducible reversible graded contraction, proportional to temperature. At high concentrations (toxic levels), ethanol induced an increase in tension and heating potentiated these responses. Extracellular Mg(2+) potentiated both heat-induced contraction and ethanol-induced contraction while extracellular Ca(2+) had no effect on these responses. During hyperthermia and ethanol scintigraphic isotope uptake was reduced in cortical and cerebellar regions. CONCLUSIONS: Carotid artery vasomotor tone is temperature dependent and heating induces vasoconstriction. Alcohol (ethanol) at 37 degrees C elicited carotid artery contraction at high concentrations (toxic levels) but at any concentration during elevated temperature (39-43 degrees C). Ethanol potentiated the effect of hyperthermia-induced vasoconstriction and reduced cerebral perfusion as shown by radionuclide imaging. The synergistic effect of ethanol and hyperthermia may induce heat stroke and brain damage.

Prevalence and trends of infection with Mycobacterium tuberculosis in Djibouti, testing an alternative method.

SETTING: Djibouti, 1994 and 2001. OBJECTIVE: To estimate the prevalence of tuberculosis (TB) and average annual risk of TB infection (ARTI) and trends, and to test a new method for calculations. METHODS: Tuberculin surveys among schoolchildren and sputum smear-positive TB patients. Prevalence of infection was calculated using cut-off points, the mirror image technique, mixture analysis, and a new method based on the operating characteristics of the tuberculin test. Test sensitivity was derived from tuberculin reactions among TB patients and test specificity from a comparison of reaction size distributions among children with and without a BCG scar. RESULTS: The ARTI was estimated to lie between 2.6% and 3.1%, with no significant changes between 1994 and 2001. The close match of the distributions between children tested in 1994 and patients justifies the utilisation of the latter to determine test sensitivity. This new method gave very consistent estimates of prevalence of infection for any induration for values between 15 and 20 mm. Specificity was successfully determined for 1994, but not for 2001. Mixture analysis confirmed the estimates obtained with the new method. CONCLUSION: Djibouti has a high ARTI, and no apparent change over the observation time was found. Using operating test characteristics to estimate prevalence of infection looks promising.

Hyperthermia-induced vasoconstriction of the carotid artery, a possible causative factor of heatstroke.

Clinical and experimental studies indicate that hyperthermia can cause heatstroke with cerebral ischemia and brain damage. However, no study has examined the direct effects of heating carotid artery smooth muscle and tested the hypothesis that hyperthermia induces arterial vasoconstriction and, thereby, decreases cerebral blood flow. We recorded isometric tension of rabbit carotid artery strips in organ baths during stepwise temperature elevation. The heating responses were tested at basal tone, in norepinephrine- and KCl-precontracted vessels, and after electrical field stimulation. Stepwise heating from 37 degrees C to 47 degrees C induced reproducible graded contraction proportional to temperature. The responses could be elicited at basal tone and in precontracted vessels. Heating decreased the contractile responses to norepinephrine and electrical field stimulation but increased contraction to KCl. These responses were not eliminated by pretreatment with the neuronal blocker tetrodotoxin. Our results demonstrate that heating carotid artery preparations above 37 degrees C (normothermia) induced a reversible graded vasoconstriction proportional to temperature. In vivo this reaction may lead to a decrease in cerebral blood flow and cerebral ischemia with brain damage as in heatstroke. The heating-induced contraction is not mediated by a neurogenic process but is due to altered transcellular Ca2+ transport. Cooling, in particular of the neck area, therefore, should be used in the treatment of heatstroke.