Expression profiles of neotropical termites reveal microbiota-associated, caste-biased genes and biotechnological targets.

Termites are well recognized by their complex development trajectories, involving dynamic differentiation process between non-reproductive castes, workers and soldiers. These insects are associated with endosymbiotic microorganisms, which help in lignocellulose digestion and nitrogen metabolism. Aiming to identify genes harbouring biotechnological potential, we analyzed workers and soldiers RNA-Seq data of three neotropical termites: Heterotermes tenuis (Isoptera: Rhinotermitidae), Velocitermes heteropterus (Isoptera: Termitidae) and Cornitermes cumulans (Isoptera: Termitidae). We observed differences in the microbiota associated with each termite family, and found protists' genes in both Termitidae species. We found an opposite pattern of caste-biased gene expression between H. tenuis and the termitids studied. Moreover, the two termitids are considerably different concerning the number of differentially expressed genes (DEGs). Functional annotation indicated considerable differences in caste-biased gene content between V. heteropterus and C. cumulans, even though they share similar diet and biological niche. Among the most DEGs, we highlighted those involved in caste differentiation and cellulose digestion, which are attractive targets for studying more efficient technologies for termite control, biomass digestion and other biotechnological applications.

Optimal duration of risperidone or olanzapine adjunctive therapy to mood stabilizer following remission of a manic episode: A CANMAT randomized double-blind trial.

Atypical antipsychotic adjunctive therapy to lithium or valproate is effective in treating acute mania. Although continuation of atypical antipsychotic adjunctive therapy after mania remission reduces relapse of mood episodes, the optimal duration is unknown. As many atypical antipsychotics cause weight gain and metabolic syndrome, they should not be continued unless the benefits outweigh the risks. This 52-week double-blind placebo-controlled trial recruited patients with bipolar I disorder (n=159) who recently remitted from a manic episode during treatment with risperidone or olanzapine adjunctive therapy to lithium or valproate. Patients were randomized to one of three conditions: discontinuation of risperidone or olanzapine and substitution with placebo at (i) entry ('0-weeks' group) or (ii) at 24 weeks after entry ('24-weeks' group) or (iii) continuation of risperidone or olanzapine for the full duration of the study ('52-weeks' group). The primary outcome measure was time to relapse of any mood episode. Compared with the 0-weeks group, the time to any mood episode was significantly longer in the 24-weeks group (hazard ratio (HR) 0.53; 95% confidence interval (CI): 0.33, 0.86) and nearly so in the 52-weeks group (HR: 0.63; 95% CI: 0.39, 1.02). The relapse rate was similar in the 52-weeks group compared with the 24-weeks group (HR: 1.18; 95% CI: 0.71, 1.99); however, sub-group analysis showed discordant results between the two antipsychotics (HR: 0.48, 95% CI: 0.17; 1.32 olanzapine patients; HR: 1.85, 95% CI: 1.00, 3.41 risperidone patients). Average weight gain was 3.2 kg in the 52-weeks group compared with a weight loss of 0.2 kg in the 0-weeks and 0.1 kg in the 24-weeks groups. These findings suggest that risperidone or olanzapine adjunctive therapy for 24 weeks is beneficial but continuation of risperidone beyond this period does not reduce the risk of relapse. Whether continuation of olanzapine beyond this period reduces relapse risk remains unclear but the potential benefit needs to be weighed against an increased risk of weight gain.

Bacterial extract (OM-85) with human-equivalent doses does not inhibit the development of asthma in a murine model.

BACKGROUND: OM-85 is an immunostimulant bacterial lysate, which has been proven effective in reducing the number of lower airways infections. We investigated the efficacy of the bacterial lysate OM-85 in the primary prevention of a murine model of asthma. METHODS: In the first phase of our study the animals received doses of 0.5µg, 5µg and 50µg of OM-85 through gavage for five days (days -10 to -6 of the protocol), 10 days prior to starting the sensitisation with ovalbumin (OVA), in order to evaluate the results of dose-response protocols. A single dose (5µg) was then chosen in order to verify in detail the effect of OM-85 on the pulmonary allergic response. Total/differential cells count and cytokine levels (IL-4, IL-5, IL-13 and IFN-γ) from bronchoalveolar lavage fluid (BALF), OVA-specific IgE levels from serum, lung function and lung histopathological analysis were evaluated. RESULTS: OM-85 did not reduce pulmonary eosinophilic response, regardless of the dose used. In the phase protocol using 5µg/animal of OM-85, no difference was shown among the groups studied, including total cell and eosinophil counts in BALF, serum OVA-specific IgE, lung histopathologic findings and lung resistance. However, OM-85 decreased IL-5 and IL-13 levels in BALF. CONCLUSIONS: OM-85, administered in early life in mice in human-equivalent doses, does not inhibit the development of allergic pulmonary response in mice.

Plasma concentrations of lidocaine in dogs following lidocaine patch application over an incision compared to intact skin.

The objective was to compare plasma lidocaine concentrations when a commercially available 5% lidocaine patch was placed on intact skin vs. an incision. Our hypothesis was that greater absorption of lidocaine would occur from the incision site compared to intact skin. Ten dogs were used in a crossover design. A patch was placed over an incision, and then after a washout period, a patch was placed over intact skin. Plasma lidocaine concentrations were measured at patch placement; 20, 40 and 60 min; and 2, 4, 6, 12, 24, 36, 48, 72 and 96 h after patch placement. After patch removal, the skin was graded using a subjective skin reaction system. No dogs required rescue analgesia, and no toxicity or skin reaction was noted. Mean ± SD AUC and CMAX were 3054.29 ± 1095.93 ng·h/mL and 54.1 ± 15.84 ng/mL in the Incision Group, and 2269.9 ± 1037.08 ng·h/mL and 44.5 ± 16.34 ng/mL in the No-Incision Group, respectively. The AUC was significantly higher in the Incision Group. The results of the study demonstrate that the actual body exposure to lidocaine was significantly higher when an incision was present compared to intact skin. No adverse effects were observed from either treatment. Efficacy was not evaluated.

Analysis of the workers head transcriptome of the Asian subterranean termite, Coptotermes gestroi.

The lower termite, Coptotermes gestroi (Isoptera: Rhinotermitidae), is originally from Southeast Asia and has become a pest in Brazil. The main goal of this study was to survey C. gestroi transcriptome composition. To accomplish this, we sequenced and analyzed 3003 expressed sequence tags (ESTs) isolated from libraries of worker heads. After assembly, 695 uniESTs were obtained from which 349 have similarity with known sequences. Comparison with insect genomes demonstrated similarity, primarily with genes from Apis mellifera (28%), Tribolium castaneum (28%) and Aedes aegypti (10%). Notably, we identified two endogenous cellulases in the sequences, which may be of interest for biotechnological applications. The results presented in this work represent the first genomic study of the Asian subterranean termite, Coptotermes gestroi.

Descriptive assessment of adverse events associated with midazolam-etomidate versus saline-etomidate in healthy hydromorphone premedicated dogs.

OBJECTIVES: To determine the frequency, severity and duration of adverse events including myoclonus, pain on injection, hypersalivation, regurgitation and apnoea after administration of midazolam or saline followed by etomidate in hydromorphone premedicated dogs. MATERIALS AND METHODS: Dogs undergoing elective dental prophylaxis or soft tissue surgeries were enrolled in this randomised trial. Dogs were premedicated with hydromorphone 0.1 mg/kg IV. Sixty seconds later, midazolam 0.3 mg/kg or saline at an equivalent volume was administered IV. Sixty seconds after that, etomidate 1.5 mg/kg IV was administered over 60 seconds. Additional doses of 0.5 mg/kg etomidate were administered until endotracheal intubation was successful. Observers were blinded to the treatment. Frequency, duration and a severity score of 0 to 3 were recorded for myoclonus, pain on injection, hypersalivation and regurgitation. Duration of apnoea and frequency of any additional complications was recorded. RESULTS: Forty variable breed healthy dogs were enrolled in the study. Myoclonus, pain on injection, regurgitation, hypersalivation, gagging, tachypnoea and pigmenturia occurred, respectively, in 10%, 40%, 0%, 15%, 35%, 25% and 5% of dogs in the saline group and 0%, 65%, 0%, 10%, 45%, 15% and 5% of dogs in the midazolam group. Apnoea occurred for 115 seconds (range 0 to 660 seconds) and 160 seconds (range 0 to 600 seconds) in the saline and midazolam groups, respectively. Two dogs developed pigmenturia. The trial was stopped early due to the occurrence of pigmenturia. CLINICAL SIGNIFICANCE: Due to early stopping of the trial, the predefined sample size was not reached. Further investigation is needed to determine if midazolam reduced the incidence of adverse events or improved the induction quality when combined with hydromorphone and etomidate.

Early-life stress affects behavioral and neurochemical parameters differently in male and female juvenile Wistar rats.

Neonatal handling is an early life stressor that leads to behavioral and neurochemical changes in adult rats in a sex-specific manner and possibly affects earlier stages of development. Here, we investigated the effects of neonatal handling (days 1-10 after birth) on juvenile rats focusing on biochemical parameters and olfactory memory after weaning. Male neonatal handled rats performed more crossings on the hole-board task, increased Na+ /K+ -ATPase activity in the olfactory bulb, and decreased acetylcholinesterase activity in the hippocampus versus non-handled males. Female neonatal handled animals increased the number of rearing and nose-pokes on the hole-board task, decreased glutathione peroxidase activity, and total thiol content in the hippocampus versus non-handled females. This study reinforces that early life stress affects behavioral and neurochemical parameters in a sex-specific manner even before the puberty onset.

Regulation of immunoreactive GAP-43 expression in rat cortical macroglia is cell type specific.

Growth-associated protein 43 (GAP-43) is an abundant, intensely investigated membrane phosphoprotein of the nervous system (Benowitz, L.I., and A. Routtenberg. 1987. Trends Neurosci. 10:527-532; Skene, J. H. P. 1989. Annu. Rev. Neurosci. 12:127-156), with a hitherto unknown function. We have previously demonstrated that astrocytes, brain macroglial cells, contain GAP-43 (Steisslinger, H. W., V. J. Aloyo, and L. Vitkovic, 1987. Brain Res. 415:375-379; Vitkovic, L., H. W. Steisslinger, V. J. Aloyo, and M. Mersel. 1988. Proc. Natl. Acad. Sci. USA. 85:8296-8300; Vitkovic L., and M. Mersel. 1989. Metab. Brain Dis. 4:47-53). Results from double immunofluorescent labeling experiments presented here show that oligodendrocytes also contain GAP-43 immunoreactivity (GAP-43ir). Thus, all three macroglial cell types of the central nervous system (type I and type 2 astrocytes and oligodendrocytes) contain GAP-43. Whereas immunoreactive GAP-43 is expressed by progenitors of all macroglial cell types, the developmental regulation of its expression is cell type specific. Immunoreactive GAP-43 is downregulated in type 1 astrocytes, and constitutively expressed in both type 2 astrocytes and oligodendrocytes. These results may be relevant to potential function(s) of GAP-43.

Production of antibodies to Little cherry virus 1 coat protein by DNA prime and protein boost immunization.

Little cherry, an economically important disease of cherry is caused by at least two different viruses. One of these is Little cherry virus 1 (LChV-1) for the detection of which no efficient serological tools are available, so that diagnosis is based on molecular methods. In this study, different immunization strategies for producing antibodies against the viral coat protein of LChV-1 were tried, using either purified virus preparations, or bacterially expressed protein, or a DNA vector that expressed the cloned coat protein (CP) gene in vivo. Effective induction of specific antibodies to LChV-1 CP was obtained using DNA intramuscular immunization followed by a single boost with the recombinant protein. The entire coat protein sequence was cloned in a mammalian expression vector and, after being coated by an amphiphilic non-toxic reagent was delivered into rabbit. A protein boost increased the specific immune response against the virus protein. The sensitivity of this antiserum is lower if compared with that of antisera raised conventionally against other viruses, thus it requires improvements for use for diagnostic purposes.

Season, weather and predictors of healthcare-associated Gram-negative bloodstream infections: a case-only study.

BACKGROUND: Recent studies reported seasonality in healthcare-associated infections (HCAI). The association of this phenomenon with other risk factors for HCAI is not clear. AIM: To analyse the interplay of season, weather and usual predictors of healthcare-associated bloodstream infections caused by Gram-negative bacilli (GNB-BSI). METHODS: A case-only study was conducted in a teaching hospital in Brazil. The study enrolled 446 subjects with GNB-BSI diagnosed from July 2012 to June 2016. Demographic data, comorbidities, invasive procedures and use of antimicrobials were reviewed in medical charts. The season in which GNB-BSI occurred, and weather parameters on the day of diagnosis were recorded. Factors associated with occurrence of GNB-BSI in different seasons (reference category: winter) and caused by different GNB (reference category: Escherichia coli) were analysed. Uni- and multi-variable models of multi-nomial logistic regression were used for analysis. FINDINGS: GNB-BSI diagnosed in summer was more likely to be caused by Klebsiella spp. [odds ratio (OR) 5.33; 95% confidence interval (CI) 2.04-13.96] or Acinetobacter baumannii (OR 2.69; 95% CI 1.04-6.96), and there was an association between Klebsiella spp. and spring (OR 2.86; 95% CI 1.14-7.18). Average temperature on the day of diagnosis was associated with Klebsiella spp. (OR 1.19; 95% CI 1.07-1.33) and A. baumannii (OR 1.20; 95% CI 1.07-1.34). CONCLUSION: Warm seasons and daily temperature impact on the aetiology of GNB-BSI, even in models adjusted for usual risk factors. One possible explanation for these findings is that seasonality of healthcare-associated pathogens is intrinsic to micro-organisms, and not associated with comorbidities, procedures or use of antimicrobials.

Efficacy of glutamine-supplemented parenteral nutrition on short-term survival following allo-SCT: a randomized study.

Fifty-three patients with hematological malignancies who underwent Allo-SCT from HLA-identical siblings were randomly assigned to receive glutamine-enriched parenteral nutrition-PN (GlPN, n=27) or standard PN (PN, n=26), in isonitrogenous solutions. Deaths (D+100 and D+180), infections, acute GVHD, length of stay, time of neutropenia and intestinal permeability (IP) were studied. Ages, gender, diagnosis, disease status and treatment variables were equally distributed between groups. Survival on D+180 was increased in GlPN (74%) vs PN (46%), P=0.03 (log-rank), as on D+100 (P=0.05). Most deaths occurred before D+100, especially in PN (10/26, 39%) vs GlPN (4/27, 15%). GVHD was the most frequent cause of death (8/21, 38%), especially in PN (n=6, five before D+100). Other outcomes were not affected. IP was affected on admission, was not affected by glutamine enrichment, but consistently worsened throughout the study. Results showed that GlPN was efficacious in increasing short-term survival after Allo-SCT. Benefits of glutamine seem to be independent of mucosal protection, as IP was not affected by its use. A trend to a lower incidence of GVHD deaths may suggest an immunomodulatory role of glutamine.

Amantadine and rimantadine for influenza A in children and the elderly.

BACKGROUND: Although amantadine (AMT) and rimantadine (RMT) are used to relieve or treat influenza A symptoms in healthy adults, little is known about the effectiveness and safety of these antivirals in preventing and treating influenza A in children and the elderly. OBJECTIVES: The aim of this review was to systematically consider evidence on the effectiveness and safety of AMT and RMT in preventing and treating influenza A in children and the elderly. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2007, issue 3); MEDLINE (1966 to July 2007) and EMBASE (1980 to July 2007). SELECTION CRITERIA: Randomised or quasi-randomised trials comparing AMT and/or RMT in children and the elderly with placebo, control, other antivirals or comparing different doses or schedules of AMT and/or RMT or no intervention. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion and assessed methodological quality. Disagreements were resolved by consensus. In all comparisons except for one, the trials in children and in the elderly were analysed separately. Data were analysed and reported using Cochrane Review Manager 4.2. software. MAIN RESULTS: In children, RMT was effective in the abatement of fever on day three of treatment. AMT showed a prophylactic effect against influenza A infection. AMT and RMT were not related to an increase in the occurrence of adverse effects. RMT also was considered to be well tolerated by the elderly, but showed no prophylactic effect. Different doses were comparable in the prophylaxis of influenza in the elderly, as well as in reporting adverse effects. Zanamivir prevented influenza A more effectively than RMT in the elderly. AUTHORS' CONCLUSIONS: AMT was effective in the prophylaxis of influenza A in children. As confounding matters might have affected our findings, caution should be taken when considering which patients should to be given this prophylactic. Our conclusions about effectiveness of both antivirals for the treatment of influenza A in children were limited to a proven benefit of RMT in the abatement of fever on day three of treatment. Due to the small number of available studies we could not reach a definitive conclusion on the safety of AMT or the effectiveness of RMT in preventing influenza in children and the elderly.

Vaccinia virus detection in dairy products made with milk from experimentally infected cows.

Vaccinia virus (VACV) is the agent of bovine vaccinia (BV), an emerging zoonosis that causes exanthematic lesions on the teats of dairy cows and on the hands of milkers. The virus has been detected in the milk of naturally infected cows. The objective of this study was to investigate and quantify VACV DNA as well as the presence of infectious virus particles in samples of cheese curd, cheese whey and pasteurized milk produced using milk from cows experimentally inoculated with VACV-GP2, a Brazilian isolate of VACV (VACV-BR). VACV DNA was detected in samples of cheese and pasteurized milk at different time points, even after the resolution of the typical lesions caused by VACV, which occurred after 22 days post-infection (dpi), on average. Moreover, it was possible to detect infectious viral particles in cheese samples on alternate days until 27 dpi. The presence of both VACV DNA and infectious viral particles in cheese samples throughout the clinical course of BV and even after the disappearance of the typical clinical signs of disease draws attention to the risk associated with consumption of the cheese. Furthermore, VACV-contaminated milk and cheese may represent an occupational risk to cheesemakers who often manipulate milk and cheese curd without wearing gloves.

The Hierarchy of Proinflammatory Cytokines in Ocular Inflammation.

PURPOSE: The concept of tissue-dependent cytokine hierarchy has been demonstrated in a number of diseases, but it has not been investigated in ophthalmic diseases. Here, we evaluated the functional hierarchy of interleukin-1ß (IL-1ß), IL-6, IL-17A, and tumor necrosis factor (TNF) in the induction of ocular inflammation. MATERIALS AND METHODS: We delivered adeno-associated virus (AAV) vectors expressing IL-1ß, IL-6, IL-17A, or TNF intravitreally in naïve C57/BL6 mice and compared and contrasted the inflammatory effects in the eye 5 weeks after AAV-mediated gene transfer. We also used an in vitro human system to test the effect of cytokines on barrier function. RESULTS: We found that IL-1ß had the highest ability to initiate ocular inflammation. The continuous overexpression of IL-1ß resulted in a significant upregulation of additional proinflammatory mediators in the eye. Using scanning laser ophthalmoscope and optical coherence tomography imaging techniques, we showed that a low dose of AAVIL-1ß was sufficient and was as pathogenic as a high dose of TNF in inducing vascular leakage, retinal degeneration, and cellular infiltration. Furthermore, only a marginal increase in IL-1ß was enough to cause cellular infiltration, thus confirming the highly pathogenic nature of IL-1ß in the eye. Contrary to our expectation, IL-6 or IL-17A had minimal or no effect in the eye. To examine the clinical relevance of our findings, we used an impedance assay to show that IL-1ß alone or TNF alone was able to cause primary human retinal endothelial cell barrier dysfunction in vitro. Again, IL-6 alone or IL-17A alone had no effect on barrier function; however, in the presence of IL-1ß or TNF, IL-17A but not IL-6 may provide additive proinflammatory effects. CONCLUSIONS: Our studies demonstrate the existence of a functional hierarchy of proinflammatory cytokines in the eye, and we show that IL-1ß is the most pathogenic when it is continuously expressed in the eye.

Trends in underweight, overweight and body mass index among elderly population of Brazil.

OBJECTIVE: To evaluate body mass index (BMI - kg/m2) trend of the elderly (superior 60 y) in the poorest (Northeast) and richest (Southeast) regions of Brazil. METHOD: Household surveys conducted in 1975, 1989 and 1997 measured weight and stature of a probabilistic sample of about 18,000 elderly people. Weighted prevalences were calculated and analysis took into account the sample design. RESULTS: In the entire period, the prevalence of overweight doubled reaching 37.4% for men and 50.6% for women in the most recent survey. Although there was an important reduction in the prevalence of underweight, these percentages were still high in the poorest region for both sexes in 1997 (13%). The increase in BMI in the period from 1975 to 1989 was significant for all subgroups, except for the men living in the rural area of the richest region, but this group was the only one that presented a significant increase in the BMI in the 1989--1997 period. CONCLUSIONS: Overweight has highly prevalent among the elderly. However there was no trend of increasing BMI in the last period, except for men living in the rural area of the richest region. Underweight is still an important nutritional problem in the poorest region.

Expression of iron-related proteins in feline and canine mammary gland reveals unexpected accumulation of iron.

Dysregulation of cellular iron homeostasis in human breast cancer is reflected by the altered expression of regulatory proteins. The expressions of iron-related proteins in the mammary glands of cats and dogs have not been assessed. We evaluated the expressions of ferritin, ferroportin, hepcidin and transferrin receptor 1 in benign and malignant mammary gland lesions in cats and dogs. Iron deposition was detected using Perls' Prussian blue staining. We found no major differences in the expression of iron-related proteins between benign and malignant mammary gland lesions in either cats or dogs; however, these species exhibited accumulation of iron in benign lesions. Our findings provide an explanation for the absence of higher iron requirements by tumor cells in these animals. Further investigation of local iron homeostasis in cats and dogs and differences in their physiology compared to human breast cancer is required.

Input respiratory impedance in mice: comparison between the flow-based and the wavetube method to perform the forced oscillation technique.

Objective and approach: In this study, we estimated the constant phase model (CPM) parameters from the respiratory impedance of male BALB/c mice by performing the forced oscillation technique (FOT) in a control group (n = 8) and in a murine model of asthma (OVA) (n = 10). Then, we compared the results obtained by two different methods, using a commercial equipment (flexiVent-flexiWare 7.X; SCIREQ, Montreal, Canada) (FXV) and a wavetube method equipment (Sly et al 2003 J. Appl. Physiol. 94 1460-6) (WVT). We believe that the results from different methods may not be comparable. First, we compared the results performing a two-way analysis of variance (ANOVA) for the resistance, elastance and tissue damping. MAIN RESULTS: We found statistically significant differences in all CPM parameters, except for resistance, when comparing Control and OVA groups. When comparing devices, we found statistically significant differences in resistance, while differences in elastance were not observed. For tissue damping, the results from WVT were observed to be higher than those from FXV. Finally, when comparing the relative variation between the CPM parameters of the Control and OVA groups in both devices, no significant differences were observed for all parameters. SIGNIFICANCE: We then conclude that this assessment can compensate the effect of using different cannulas. Furthermore, tissue damping differences between groups can be compensated, since bronchoconstrictors were not used. Therefore, we believe that relative variations in the results between groups can be a comparing parameter when using different equipment without bronchoconstrictor administration.

Tuberculosis treatment default among Brazilian children.

OBJECTIVES: To study the prevalence and time of tuberculosis (TB) treatment default among children and to compare defaulters with those who completed treatment. METHODS: Retrospective cohort study at the Hospital Municipal Jesus, Rio de Janeiro, Brazil, among TB patients aged <15 years followed from 1998 to 2002. The group that completed treatment was compared with those that defaulted. RESULTS: The records of 248 patients were studied. The default rate was 24.2% and was more frequent in the first 2 months of treatment (43.3%) and among those aged <1 year (42.4%). The following variables were associated with default: previous default (relative risk [RR] 1.99, 95%CI 1.12-3.54, P = 0.035), father not living with the child (RR 1.85, 95%CI 1.06-3.21, P = 0.030) and father using illicit drugs (RR 2.93, 95%CI 1.44-5.97, P = 0.002). CONCLUSIONS: Health professionals responsible for treating children with TB should pay special attention to children aged <1 year, those with a history of previous default, and those whose father is absent or an illicit drug user.