Clinical Profiles and Factors Associated with Death in Adults with Dengue Admitted to Intensive Care Units,Minas Gerais,Brazil

The purpose of our study was to describe the clinical profile of dengue-infected patients admitted to Brazilian intensive care units (ICU) and evaluate factors associated with death. A longitudinal, multicenter case series study was conducted with laboratory-confirmed dengue patients admitted to nine Brazilian ICUs situated in Minas Gerais state, southeastern Brazil from January 1, 2008, to December 31, 2013. Demographic, clinical and laboratory data; disease severity scores; and mortality were evaluated. A total of 97 patients were studied. The in-ICU and in-hospital mortality rates were 18.6% and 19.6%, respectively. Patients classified as having severe dengue according to current World Health Organization classifications showed an increased risk of death in a univariate analysis. Nonsurvivors were older, exhibited lower serum albumin concentrations and higher total leukocyte counts and serum creatinine levels. Other risk factors (vomiting, lethargy/restlessness, dyspnea/respiratory distress) were also associated with death in a univariate analysis. Multivariate analysis indicated that in-hospital mortality was significantly associated with Acute Physiology and Chronic Health Evaluation II and the Sequential Organ Failure Assessment score. The ICU and in-hospital mortality observed in this study were higher than values reported in similar studies. An increased frequency of ICU admission due to severe organ dysfunction, higher severity indices and scarcity of ICU beds may partially explain the higher mortality.     

Antagonistic factors control the unproductive splicing of SC35 terminal intron

Alternative splicing is regulated in part by variations in the relative concentrations of a variety of factors, including serine/arginine-rich (SR) proteins. The SR protein SC35 self-regulates its expression by stimulating unproductive splicing events in the 3′ untranslated region of its own pre-mRNA. Using various minigene constructs containing the terminal retained intron and flanking exons, we identified in the highly conserved last exon a number of exonic splicing enhancer elements responding specifically to SC35, and showed an inverse correlation between affinity of SC35 and enhancer strength. The enhancer region, which is included in a long stem loop, also contains repressor elements, and is recognized by other RNA-binding proteins, notably hnRNP H protein and TAR DNA binding protein (TDP-43). Finally, in vitro and in cellulo experiments indicated that hnRNP H and TDP-43 antagonize the binding of SC35 to the terminal exon and specifically repress the use of SC35 terminal 3′ splice site. Our study provides new information about the molecular mechanisms of SC35-mediated splicing activation. It also highlights the existence of a complex network of self- and cross-regulatory mechanisms between splicing regulators, which controls their homeostasis and offers many ways of modulating their concentration in response to the cellular environment.     

<Emphasis Type="Italic">In vitro</Emphasis> organogenesis of <Emphasis Type="Italic">Passiflora alata</Emphasis>

Passiflora alata in vitro organogenesis was studied based on explant type, culture medium composition, and incubation conditions. The results indicated that the morphogenic process occurred more efficiently when hypocotyl segment-derived explants were cultured in media supplemented with cytokinin and AgNO₃ incubated under a 16-h photoperiod. The shoot bud elongation and plant development were obtained by transferring the material to MSM culture medium supplemented with GA₃ and incubated in flasks with vented lids. Histological analyses of the process revealed that the difficulties in obtaining plants could be related to the development of protuberances and leaf primordia structures, which did not contain shoot apical meristem. Roots developed easily by transferring elongated shoots to 1/2 MSM culture medium. Plant acclimatization occurred successfully, and somaclonal variation was not visually detected. The efficiency of this organogenesis protocol will be evaluated for genetic transformation of this species to obtain transgenic plants expressing genes that can influence the resistance to Cowpea aphid borne mosaic virus.     

Accuracy of patient-reported height loss and risk factors for height loss among postmenopausal women

Background

Since loss of height may indicate vertebral fracture, the accuracy of the information on height is relevant for clinical practice. We undertook this study to compare reported and measured loss of height among post-menopausal women in a primary care setting. We also analyzed the determinants of this height loss.

Methods

In an observational study conducted between December 2007 and May 2008, we asked 1779 randomly selected general practitioners to recruit the first five female patients who were more than 60 years of age, regardless of the reason for the consultation. Using a questionnaire, physicians collected data on demographic and clinical variables, history of osteoporosis and current anti-osteoporotic treatment. We used three assessments of height: tallest height in early adulthood recalled by the patient, estimated current height reported by the patient at the visit and current measured height. We defined loss of height as the difference between the patient’s tallest recalled height and her current measured height.

Results

A total of 8610 patients were included in the analysis; the mean age was 70.9 (standard deviation [SD] 7.2) years. The mean loss of height was 4.5 cm. The mean current reported height was 2.1 (SD 2.5) cm lower than the tallest recalled height and 2.4 (SD 2.6) cm lower than the measured current height. The best predictors of a loss of height of 3 cm or more were age (odds ratio [OR] 1.09, 95% confidence interval [CI] 1.08–1.10), previous vertebral fracture (OR 1.49, 95% CI 1.16–1.91), previous nonvertebral fracture (OR 1.26, 95% CI 1.06–1.51), thoracic kyphosis (OR 2.07, 95% CI 1.69–2.55), scoliosis (OR 1.35, 95% CI 1.12–1.63), back pain (OR 1.22, 95% CI 1.07–1.39) and osteoporosis (OR 1.39, 95% CI 1.20–1.60).

Interpretation

Our study showed that the patients’ estimated current height was not correct, with a mean difference of −2.5 cm from the current measured height. The mean height loss was 4.5 cm. Previous vertebral fracture and thoracic kyphosis were strong determinants of the height loss.Loss of height is common with advancing age.^1,2 Causes include changes in curvature of the spine, narrowing of intervertebral discs and vertebral fractures. Height loss is associated with back pain and thoracic hyperkyphosis.^3,4 Two-thirds of adults have back pain at any time. Controversies exist about the need for radiographs of the spine: Does the benefit of detecting treatable disorders of the spine such as vertebral fracture outweigh the harm of unnecessary radiographs? Loss of height is usually recorded as one of the clinical signs to help identify postmenopausal women with vertebral fractures.⁵ The use of this parameter to decide whether radiography is needed depends on the threshold for height loss associated with a strong risk of vertebral fracture. The thresholds useful in clinical practice to detect prevalent vertebral fracture range from 3 cm to 6 cm,^6–9 with the risk of prevalent fracture increasing with the magnitude of the height loss. Thus, the accuracy of the information on height is relevant for clinical practice.We conducted this study to compare reported and measured loss of height in a large population of women more than 60 years old in a primary care setting and to analyze the determinants of this height loss.     

Urinary Excretion of Zinc and Metabolic Control of Patients with Diabetes Type 2

The objective of this study was to assess urinary excretion of zinc and evaluation parameters of metabolic control in type 2 diabetic patients. Thirty-one type 2 diabetic patients, of both genders, with 5.8 ± 5.6 years average time of the disease, age range 20–60 years, were selected. Evaluation of the nutritional status was performed using anthropometric measurements. To evaluate food consumption, the 3-day alimentary log method was used, and its analysis was performed using a software. Determination of urinary zinc was by atomic absorption spectrophotometry. From the obtained results, it was concluded that 51.6% of the patients were overweight. The mean of found waist circumference was 100.4 and 92.2 cm for men and women, respectively. Blood glucose and glycated hemoglobin values were higher than reference values, and plasma albumin concentration was adequate. The median of found urinary zinc excretion was 474.9 μg/24 h, within normal standards (300–600 μg/day). Regarding diet composition, calorie and protein concentration were above recommendation, while mean zinc concentration was adequate. This data allow the conclusion that the evaluated patients presented adequate urinary zinc excretion in comparison with reference values.     

Partitioning and inactivation of viruses by the caprylic acid precipitation followed by a terminal pasteurization in the manufacturing process of horse immunoglobulins

Caprylic acid (octanoic acid), has been used for over 50 years as a stabilizer of human albumin during pasteurization. In addition caprylic acid is of great interest, by providing the advantage of purifying mammalian immunoglobulins and clearing viruses infectivity in a single step. Exploiting these two properties, we sequentially used the caprylic acid precipitation and the pasteurization to purify horse hyperimmune globulins used in the manufacturing of Sérocytol. To evaluate the effectiveness of the process for the removal/inactivation of viruses, spiking studies were carried out for each dedicated step. Bovine viral diarrhoea virus (BVDV), pseudorabies virus (PRV), encephalomyocarditis virus (EMCV) and minute virus of mice (MVM) were used for the virological validation. Our data show that the treatment with caprylic acid 5% (v/v) can effectively be used as well to purify or to ensure viral safety of immunoglobulins. Caprylic acid precipitation was very efficient in removing and/or inactivating enveloped viruses (PRV, BVDV) and moderately efficient against non-enveloped viruses (MVM, ECMV). However the combination with the pasteurization ensured an efficient protection against both enveloped and non-enveloped viruses. So that viruses surviving to the caprylic acid precipitation will be neutralized by pasteurization. Significant log reduction were achieved > or =9 log(10) for enveloped viruses and 4 log(10) for non-enveloped viruses, providing the evidence of a margin of viral safety achieved by our manufacturing process. Its a simple and non-expensive manufacturing process of immunoglobulins easily validated that we have adapted to a large production scale with a programmable operating system.     

Alpha6beta1 integrin expressed by sperm is determinant in mouse fertilization

Background  

Based on inhibition tests, the alpha6beta1 integrin was suggested to be a sperm receptor, but further experiments using gene deletion techniques have shown that neither oocyte alpha6, nor beta1 integrin subunits were essential for mouse fertilization.     

Characterization of expressed sequence tags obtained by SSH during somatic embryogenesis in <Emphasis Type="Italic">Cichorium intybus</Emphasis> L

Background  

Somatic embryogenesis (SE) is an asexual propagation pathway requiring a somatic-to-embryonic transition of differentiated somatic cells toward embryogenic cells capable of producing embryos in a process resembling zygotic embryogenesis. In chicory, genetic variability with respect to the formation of somatic embryos was detected between plants from a population of Cichorium intybus L. landrace Koospol. Though all plants from this population were self incompatible, we managed by repeated selfing to obtain a few seeds from one highly embryogenic (E) plant, K59. Among the plants grown from these seeds, one plant, C15, was found to be non-embryogenic (NE) under our SE-inducing conditions. Being closely related, we decided to exploit the difference in SE capacity between K59 and its descendant C15 to study gene expression during the early stages of SE in chicory.