Insecticide resistance mediated by an exon skipping event.

Many genes increase coding capacity by alternate exon usage. The gene encoding the insect nicotinic acetylcholine receptor (nAChR) α6 subunit, target of the bio-insecticide spinosad, is one example of this and expands protein diversity via alternative splicing of mutually exclusive exons. Here, we show that spinosad resistance in the tomato leaf miner, Tuta absoluta is associated with aberrant regulation of splicing of Taα6 resulting in a novel form of insecticide resistance mediated by exon skipping. Sequencing of the α6 subunit cDNA from spinosad selected and unselected strains of T. absoluta revealed all Taα6 transcripts of the selected strain were devoid of exon 3, with comparison of genomic DNA and mRNA revealing this is a result of exon skipping. Exon skipping cosegregated with spinosad resistance in survival bioassays, and functional characterization of this alteration using modified human nAChR α7, a model of insect α6, demonstrated that exon 3 is essential for receptor function and hence spinosad sensitivity. DNA and RNA sequencing analyses suggested that exon skipping did not result from genetic alterations in intronic or exonic cis-regulatory elements, but rather was associated with a single epigenetic modification downstream of exon 3a, and quantitative changes in the expression of trans-acting proteins that have known roles in the regulation of alternative splicing. Our results demonstrate that the intrinsic capacity of the α6 gene to generate transcript diversity via alternative splicing can be readily exploited during the evolution of resistance and identifies exon skipping as a molecular alteration conferring insecticide resistance.

Mutation (G275E) of the nicotinic acetylcholine receptor α6 subunit is associated with high levels of resistance to spinosyns in Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae).

The tomato leafminer, Tuta absoluta, now a major pest of tomato crops worldwide, is primarily controlled using chemical insecticides. Recently, high levels of resistance to the insecticide spinosad have been described in T. absoluta populations in Brazil. Selection of a resistant field-collected strain led to very high levels of resistance to spinosad and cross-resistance to spinetoram, but not to other insecticides that target the nicotinic acetylcholine receptor (nAChR). In this study the mechanisms underlying resistance to spinosad were investigated using toxicological, biochemical and molecular approaches. Inhibition of metabolic enzymes using synergists and biochemical assessment of detoxification enzyme activity provided little evidence of metabolic resistance in the selected strain. Cloning and sequencing of the nAChR α6 subunit from T. absoluta, the spinosad target-site, from susceptible and spinosad-resistant strains were done to investigate the role of a target-site mechanism in resistance. A single nucleotide change was identified in exon 9 of the α6 subunit of the resistant strain, resulting in the replacement of the glycine (G) residue at position 275 observed in susceptible T. absoluta strains with a glutamic acid (E). A high-throughput DNA-based diagnostic assay was developed and used to assess the prevalence of the G275E mutation in 17 field populations collected from different geographical regions of Brazil. The resistant allele was found at low frequency, and in the heterozygous form, in seven of these populations but at much higher frequency and in the homozygous form in a population collected in the Iraquara municipality. The frequency of the mutation was significantly correlated with the mortality of these populations in discriminating dose bioassays. In summary our results provide evidence that the G275E mutation is an important mechanism of resistance to spinosyns in T. absoluta, and may be used as a marker for resistance monitoring in field populations.

Human papillomavirus and chlamydia trachomatis infections in rheumatoid arthritis under anti-TNF therapy: an observational study.

The objective of this study was to evaluate human papillomavirus (HPV) and Chlamydia trachomatis (CT) infections in RA patients pre- and post-TNF blocker. Fifty female RA patients (ACR criteria), who were eligible to anti-TNF therapy [n = 50 at baseline (BL) and n = 45 after 6 months of treatment (6 M)], and 50 age-matched healthy controls were prospectively enrolled. They were assessed for demographic data, gynecologic, sexual, cervical cytology and histological evaluations, disease parameters and current treatment. HPV DNA and CT DNA testing in cervical specimens were done using Hybrid Capture II assays. At BL, the median current age of RA patients and controls was 49 (18-74) versus 49 (18-74) years, p = 1.0. A trend of lower frequency of HPV infection was observed in AR patients pre-anti-TNF compared with controls (14 vs. 30%, p = 0.054). Further evaluation of AR patients with and without HPV infection before anti-TNF therapy showed that the former group had higher frequency of sexual intercourses (100 vs. 48%, p = 0.014), higher median number of sexual partners [1 (1-1) vs. 0 (0-1), p = 0.032] and higher frequency of abnormal cervical cytology (43 vs. 7%, p = 0.029). Current age, disease duration, disease parameters and treatments were alike in both groups (p > 0.05). At 6 M after TNF blockage, HPV infection remained unchanged in five patients, whereas two became negative and one additional patient turned out to be positive (p = 1.0). CT infection was uniformly negative in RA patients pre- and post-TNF blockage and in controls. Anti-TNF does not seem to increase short-term risk of exacerbation and/or progression of HPV and CT infections in RA patients.

Status of pyrethroid resistance and mechanisms in Brazilian populations of Tuta absoluta.

The tomato leafminer, Tuta absoluta, is a major pest of tomato crops worldwide. This study surveyed the resistance of T. absoluta populations from four regions in Brazil to pyrethroid insecticides, the frequencies of L1014F, T929I and M918T Na channel mutations, and the role of detoxification metabolism in the resistance. Resistance ratios varied from 1- to 11-times among populations and insecticides, but control failure likelihood assays showed that all pyrethroids assessed exhibited no efficacy at all (and thus, 98-100% control failure likelihood) against all T. absoluta populations. The activity of glutathione S-transferase and cytochrome P450-mediated N-demethylation in biochemical assays was significantly correlated with the level of resistance to deltamethrin and permethrin suggesting that these enzymes may play a role in resistance. TaqMan assays were used to screen for the presence of knockdown resistance (kdr) mutations and revealed that the L1014F kdr mutation was fixed in all populations and associated with two super-kdr mutations, M918T and particularly T929I, at high frequency. Altogether, results suggest that control failures are because of mutations in the domain II of the sodium channel, as a prevailing mechanism of resistance to pyrethroids in populations of T. absoluta in Brazil. But, enhanced cytochrome P450-dependent monooxygenases and GST activities also play an important role in the resistance of some populations, which reinforce that pyrethroids must not be used overall to control T. absoluta.

Hearing impairment and deafness among HIV infected children and adolescents in Harare, Zimbabwe.

Background: Among HIV-infected children ear infections are recurrent and chronic, which may lead to hearing loss. Objective: To determine the prevalence, cause and severity of hearing impairment among HIV-infected children aged 5-17 years attending for HIV care in Harare. Design and Setting: An analytical cross-sectional survey conducted at Newlands Clinic, an opportunistic infections clinic in Harare. Materials and Methods: Participants underwent a standardised otoscopic examination of the ear and Pure Tone Audiometry (PTA). Factors associated with hearing impairment were investigated using multivariate logistic regression. Results: Three hundred and eighty (380) participants (55% female and mean age 11 years (SD: 3.3 years)) were consecutively recruited. The vast majority of participants (n=338; 89% were taking antiretroviral therapy (ART) for a median of 3 (IQR: 2-5) years at recruitment, and the most recent median CD4 Count (i.e. CD4 count measured within 6 months of the study recruitment) was 725 (IQR: 497-1000) cells/µL, with no difference by ART status. 61% (n= 231) of participants had an abnormal ear examination. Of the 359 participants who underwent audiometry, the prevalence of hearing impairment was 32.3% (95%CI: 27.5%-37.4%) based on a PTA threshold ≥26Db. Hearing impairment was associated with a recent CD4 count <350cell/µL (OR 2.1, P<0.037). Conclusion: There is a high prevalence of hearing impairment among HIV-infected children and adolescents. Low CD4 count remains a risk factor even among those who are on ART. We recommend that HIV infected children and adolescents, particularly those with low CD4 counts, should have routine evaluation of hearing as part of HIV care.

Metabolomic Response throughout 16 Weeks of Combined Aerobic and Resistance Exercise Training in Older Women with Metabolic Syndrome.

Increases in longevity and obesity have led to a higher prevalence of Metabolic Syndrome (MetS) and several chronic conditions, such as hypertension. The prevalence of MetS and hypertension increases with advancing age and their detrimental effects on health can be attenuated by physical activity. Combined aerobic and resistance exercise training (CT) is recommended to maintain good health in older adults and is known to generate important metabolic adaptations. In this study we performed a metabolomics analysis, based on Hydrogen Nuclear Magnetic Resonance (1H NMR), to investigate the kinetics of changes in metabolism in non-physically active older women with MetS in response to 16 weeks of CT. A subset of women with MetS were selected from a larger randomized trial (that included men and women without MetS), with 12 participants on CT and 13 from the Control Group (CG). CT comprised walking/running at 63% of VO2max, three times/week, and resistance training (RT), consisting of 15 repetitions of seven exercises at moderate intensity, twice/week. Serum metabolomic profile was analysed at baseline (0W), 4 (4W), 8 (8W), 12 (12W) and 16 weeks (16W) for CT or CG. Cardiorespiratory fitness, RT load, blood pressure, body composition, lipid and glycaemic profile were also assessed. After 16 weeks CT increased cardiorespiratory fitness (13.1%, p < 0.05) and RT load (from 48% in the lat pulldown to 160% in the leg press, p < 0.05), but there were no changes in MetS parameters, such as body composition (Body Mass, Body Mass Index (BMI), body fat percentage and waist circumference), blood pressure, lipid and glycaemic profile. However, we identified potential higher substrate to the tricarboxylic acid cycle (increase in 2-Oxobutyrate from 0W (0.0029 ± 0.0009) to 4W (0.0038 ± 0.0011) and 8W (0.0041 ± 0.0015), p < 0.05), followed by alterations (different from 0W, p < 0.05) in the production of ketone bodies (3-Hydroxybutyrate, 0W (0.0717 ± 0.0377) to 16W (0.0397 ± 0.0331), and Acetoacetate, 0W (0.0441 ± 0.0240) to 16W (0.0239 ± 0.0141)), which together might explain the known improvement in fatty acid oxidation with exercise. There was also a late increase in ornithine at 16W of CT. Further studies are needed to investigate the association between these metabolic pathways and clinical outcomes in this population.

The effect of primary health care on tuberculosis in a nationwide cohort of 7·3 million Brazilian people: a quasi-experimental study.

BACKGROUND: Universal health coverage is one of the WHO End TB Strategy priority interventions and could be achieved-particularly in low-income and middle-income countries-through the expansion of primary health care. We evaluated the effects of one of the largest primary health-care programmes in the world, the Brazilian Family Health Strategy (FHS), on tuberculosis morbidity and mortality using a nationwide cohort of 7·3 million individuals over a 10-year study period. METHODS: We analysed individuals who entered the 100 Million Brazilians Cohort during the period Jan 1, 2004, to Dec 31, 2013, and compared residents in municipalities with no FHS coverage with residents in municipalities with full FHS coverage. We used a cohort design with multivariable Poisson regressions, adjusted for all relevant demographic and socioeconomic variables and weighted with inverse probability of treatment weighting, to estimate the effect of FHS on tuberculosis incidence, mortality, cure, and case fatality. We also performed a range of stratifications and sensitivity analyses. FINDINGS: FHS exposure was associated with lower tuberculosis incidence (rate ratio [RR] 0·78, 95% CI 0·72-0·84) and mortality (0·72, 0·55-0·94), and was positively associated with tuberculosis cure rates (1·04, 1·00-1·08). FHS was also associated with a decrease in tuberculosis case-fatality rates, although this was not statistically significant (RR 0·84, 95% CI 0·55-1·30). FHS associations were stronger among the poorest individuals for all the tuberculosis indicators. INTERPRETATION: Community-based primary health care could strongly reduce tuberculosis morbidity and mortality and decrease the unequal distribution of the tuberculosis burden in the most vulnerable populations. During the current marked rise in global poverty due to the COVID-19 pandemic, investments in primary health care could help protect against the expected increases in tuberculosis incidence worldwide and contribute to the attainment of the End TB Strategy goals. FUNDING: TB Modelling and Analysis Consortium (Bill & Melinda Gates Foundation), Wellcome Trust, and Brazilian Ministry of Health. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.

Comprehensive Time-Course Effects of Combined Training on Hypertensive Older Adults: A Randomized Control Trial.

The aim was to identify whether 16 weeks of combined training (Training) reduces blood pressure of hypertensive older adults and what the key fitness, hemodynamic, autonomic, inflammatory, oxidative, glucose and/or lipid mediators of this intervention would be. Fifty-two individuals were randomized to either 16 weeks of Training or control group who remained physically inactive (Control). Training included walking/running at 63% of V˙O2max, three times per week, and strength training, consisting of one set of fifteen repetitions (seven exercises) at moderate intensity, twice per week. Both groups underwent a comprehensive health assessment at baseline (W0) and every four weeks, for 16 weeks total. p-value ≤ 0.05 was set as significant. Training did not reduce blood pressure. It increased V˙O2max after eight weeks and again after 16 weeks (~18%), differently from the Control group. At 16 weeks, Training increased strength (~8%), slightly reduced body mass (~1%), and reduced the number of individuals with metabolic syndrome (~7%). No other changes were observed (heart rate, carotid compliance, body composition, glycemic and lipid profile, inflammatory markers and oxidative profile, vasoactive substances, heart rate variability indices). Although Training increased cardiorespiratory fitness and strength, Training was able to reduce neither blood pressure nor a wide range of mediators in hypertensive older adults, suggesting other exercise interventions might be necessary to improve overall health in this population. The novelty of this study was the time-course characterization of Training effects, surprisingly demonstrating stability among a comprehensive number of health outcomes in hypertensive older adults, including blood pressure.

Multifunctional Hybrid MoS2-PEGylated/Au Nanostructures with Potential Theranostic Applications in Biomedicine.

In this work, flower-like molybdenum disulfide (MoS2) microspheres were produced with polyethylene glycol (PEG) to form MoS2-PEG. Likewise, gold nanoparticles (AuNPs) were added to form MoS2-PEG/Au to investigate its potential application as a theranostic nanomaterial. These nanomaterials were fully characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), photoelectron X-ray spectroscopy (XPS), Fourier-transformed infrared spectroscopy (FTIR), cyclic voltammetry and impedance spectroscopy. The produced hierarchical MoS2-PEG/Au microstructures showed an average diameter of 400 nm containing distributed gold nanoparticles, with great cellular viability on tumoral and non-tumoral cells. This aspect makes them with multifunctional characteristics with potential application for cancer diagnosis and therapy. Through the complete morphological and physicochemical characterization, it was possible to observe that both MoS2-PEG and MoS2-PEG/Au showed good chemical stability and demonstrated noninterference in the pattern of the cell nucleus, as well. Thus, our results suggest the possible application of these hybrid nanomaterials can be immensely explored for theranostic proposals in biomedicine.

Measurement of low-derivative surface lenses by two-laser holography with Bi12TiO20 crystals.

Refractive and profilometric analyses of lenses with large radii of curvature and/or large focal distance were performed through photorefractive holography using a Bi12TiO20 crystal as the recording medium and two red diode lasers as light sources. Both lasers were properly aligned and tuned in order to provide submillimetric synthetic wavelengths providing real-time interferograms in a two-color holography experiment. The resulting contour interferogram describes the form of the wavefront after the beam traveled back and forth through the lens. The fringe quantitative evaluation was carried out through the four-stepping technique, and the resulting phase map and the branch-cut method were employed for phase unwrapping. Exact ray tracing calculation was performed in order to establish a relation between the output wavefront geometry and the lens parameters such as radii of curvature, thickness, and refractive index. By quantitatively comparing the theoretically calculated wavefront geometry with the experimental results, errors below 1% for both refractive index and focal length were obtained.

Hybrid MoS2/h-BN Nanofillers As Synergic Heat Dissipation and Reinforcement Additives in Epoxy Nanocomposites.

Two-dimensional (2D) nanomaterials as molybdenum disulfide (MoS2), hexagonal boron nitride (h-BN), and their hybrid (MoS2/h-BN) were employed as fillers to improve the physical properties of epoxy composites. Nanocomposites were produced in different concentrations and studied in their microstructure, mechanical and thermal properties. The hybrid 2D mixture imparted efficient reinforcement to the epoxy leading to increases of up to 95% in tensile strength, 60% in ultimate strain, and 58% in Young's modulus. Moreover, an enhancement of 203% in thermal conductivity was achieved for the hybrid composite as compared to the pure polymer. The incorporation of MoS2/h-BN mixture nanofillers in epoxy resulted in nanocomposites with multifunctional characteristics for applications that require high mechanical and thermal performance.

Ryanodine receptor point mutations confer diamide insecticide resistance in tomato leafminer, Tuta absoluta (Lepidoptera: Gelechiidae).

Insect ryanodine receptors (RyR) are the molecular target-site for the recently introduced diamide insecticides. Diamides are particularly active on Lepidoptera pests, including tomato leafminer, Tuta absoluta (Lepidoptera: Gelechiidae). High levels of diamide resistance were recently described in some European populations of T. absoluta, however, the mechanisms of resistance remained unknown. In this study the molecular basis of diamide resistance was investigated in a diamide resistant strain from Italy (IT-GELA-SD4), and additional resistant field populations collected in Greece, Spain and Brazil. The genetics of resistance was investigated by reciprocally crossing strain IT-GELA-SD4 with a susceptible strain and revealed an autosomal incompletely recessive mode of inheritance. To investigate the possible role of target-site mutations as known from diamondback moth (Plutella xylostella), we sequenced respective domains of the RyR gene of T. absoluta. Genotyping of individuals of IT-GELA-SD4 and field-collected strains showing different levels of diamide resistance revealed the presence of G4903E and I4746M RyR target-site mutations. These amino acid substitutions correspond to those recently described for diamide resistant diamondback moth, i.e. G4946E and I4790M. We also detected two novel mutations, G4903V and I4746T, in some of the resistant T. absoluta strains. Radioligand binding studies with thoracic membrane preparations of the IT-GELA-SD4 strain provided functional evidence that these mutations alter the affinity of the RyR to diamides. In combination with previous work on P. xylostella our study highlights the importance of position G4903 (G4946 in P. xylostella) of the insect RyR in defining sensitivity to diamides. The discovery of diamide resistance mutations in T. absoluta populations of diverse geographic origin has serious implications for the efficacy of diamides under applied conditions. The implementation of appropriate resistance management strategies is strongly advised to delay the further spread of resistance.

The liver X receptor agonist AZ876 protects against pathological cardiac hypertrophy and fibrosis without lipogenic side effects.

AIMS: Liver X receptors (LXRs) transcriptionally regulate inflammation, metabolism, and immunity. Synthetic LXR agonists have been evaluated for their efficacy in the cardiovascular system; however, they elicit prolipogenic side effects which substantially limit their therapeutic use. AZ876 is a novel high-affinity LXR agonist. Herein, we aimed to determine the cardioprotective potential of LXR activation with AZ876. METHODS AND RESULTS: Cardiac hypertrophy was induced in C57Bl6/J mice via transverse aortic constriction (TAC) for 6 weeks. During this period, mice received chow supplemented or not with AZ876 (20 µmol/kg/day). In murine hearts, LXRα protein expression was up-regulated ∼7-fold in response to TAC. LXR activation with AZ876 attenuated this increase, and significantly reduced TAC-induced increases in heart weight, myocardial fibrosis, and cardiac dysfunction without affecting blood pressure. At the molecular level, AZ876 suppressed up-regulation of hypertrophy- and fibrosis-related genes, and further inhibited prohypertrophic and profibrotic transforming growth factor ß (TGFß)-Smad2/3 signalling. In isolated cardiac myocytes and fibroblasts, immunocytochemistry confirmed nuclear expression of LXRα in both these cell types. In cardiomyocytes, phenylephrine-stimulated cellular hypertrophy was significantly decreased in AZ876-treated cells. In cardiac fibroblasts, AZ876 prevented TGFß- and angiotensin II-induced fibroblast collagen synthesis, and inhibited up-regulation of the myofibroblastic marker, α-smooth muscle actin. Plasma triglycerides and liver weight were unaltered following AZ876 treatment. CONCLUSION: AZ876 activation of LXR protects from adverse cardiac remodelling in pathological pressure overload, independently of blood pressure. LXR may thus represent a putative molecular target for antihypertrophic and antifibrotic therapies in heart failure prevention.

Susceptibility of Tuta absoluta (Lepidoptera: Gelechiidae) Brazilian populations to ryanodine receptor modulators.

BACKGROUND: Phthalic and anthranilic diamides comprise a new insecticide class recently registered in Brazil to control Lepidoptera such as Tuta absoluta (Meyrick). Therefore, the baseline of susceptibility was determined for eight representative field populations of this species to establish a resistance monitoring programme. The potential for cross-resistance as well as detoxification metabolism was assessed in order to fine-tune the resistance management programme. RESULTS: Brazilian populations were very susceptible to chlorantraniliprole (LC50 values varied from 3.17 to 29.64 µg AI L(-1) ), cyantraniliprole (LC50 values varied from 8.61 to 28.95 µg AI L(-1) ) and flubendiamide (LC50 values varied from 94 to 230 µg AI L(-1) ), with respective resistance ratios of 9.33-, 3.36- and 2.45-fold between most susceptible and tolerant populations. Anthranilic diamides showed significant correlations between log LC50 values among themselves, suggesting a high risk of cross-resistance. However, the log LC50 values of T. absoluta to phthalic diamide did not show any correlation with anthranilic diamides. Cytochrome- P450-dependent monooxygenase activity showed a weak correlation with log LC50 values of T. absoluta populations to anthranilic diamides, which suggests a potential route for evolving resistance to anthranilic diamides. CONCLUSION: The diamides were highly effective against T. absoluta, with populations showing a homogeneous response to them. Cross-resistance is very likely between anthranilic diamides in T. absoluta. Populations of this pest may evolve resistance by increasing cytochrome- P450-dependent monooxygenases.

Stanford Health Partners: rationale and early experiences in establishing physician group visits and chronic disease self-management workshops.

Chronic disease is a major public health problem. The day-to-day management of a chronic illness requires accurate patient reporting and timely medical response. Patient group visits with the primary care physician and lay-led patient education workshops improve the provider-physician relationship, promote patient self-efficacy and self-management of chronic diseases, and facilitate positive health care outcomes. This article describes how group visits are being integrated into the clinical routine of a health care system.

Reference values for glucose tolerance test in the urban Zimbabwean pregnant woman.

A 50 g oral glucose tolerance test (OGTT) was performed on normal pregnant urban Zimbabwean women at 26-28 weeks (n = 65) and 36-40 weeks (n = 72) gestation. Women with factors predisposing to impaired glucose tolerance were excluded. The fasting, one hour and two hours values were compared to the North American standards as proposed by O'Sullivan and Mahan which are currently in use. The mean fasting levels were significantly higher and those at one and two hours significantly lower than the standards. The study also failed to demonstrate impairment of glucose tolerance with advancing gestation. These may have implications in the screening for impaired glucose tolerance in our African population.

Antimicrobial susceptibilities of Shigella dysenteriae type 1 isolated in Zimbabwe--implications for the management of dysentery.

Shigella dysenteriae type 1 was cultured from 56/170 (33 pc) rectal swab specimens collected from patients presenting to hospitals in Harare, Zimbabwe with dysentery. All of the isolates were resistant in vitro to trimethoprim-sulfamethoxazole, with MICs > 32 mg/l, and all except one were resistant to ampicillin, most with an MIC > 256 mg/l. One isolate was resistant to nalidixic acid (MIC > 256 mg/l), but all of the others were sensitive, most with an MIC of 2 mg/l or less. Using antibiotic disks, 96 pc isolates were resistant to chloromphenicol and 94 pc to tetracycline. All isolates were sensitive in vitro to gentamicin. On the basis of these findings, we suggest that commonly available antibiotics including ampicillin, cotrimoxazole, chloramphenicol or tetracycline should not be used for the treatment of dysentery. The most appropriate antimicrobial agent at the present time would be nalidixic acid. Resistance to this is, however, likely to emerge and data on susceptibilities to fluoroquinolones as well as to cephalosporins should be obtained so that further recommendations can be given timeously.

Predictors of mortality in children hospitalized with dysentery in Harare, Zimbabwe.

OBJECTIVES: To document the pattern of complications and identify risk factors for subsequent mortality in a hospitalized paediatric population during a Shigella dysenteriae type 1 epidemic. DESIGN: Hospital based prognostic study. SETTING: Paediatric wards in Harare and Parirenyatwa tertiary referral hospitals. SUBJECTS: All children aged one month to 12 years admitted to the wards with a history of bloody diarrhoea between January 1993 to June 30 1994 were included in the study (n = 312). MAIN OUTCOME MEASURES: Patterns of complications and predictors of mortality. RESULTS: The peak age group of the patients was 12 to 23 months. Ninety five children died giving an overall case fatality rate (CFR) of 30.4% (95% CI, 25.3 to 35.6). One third (n = 107) had haemolytic uraemic syndrome (HUS), among whom the CFR was 43%. Other complications included altered consciousness (35%), seizures (12%), coma (4.5%), severe dehydration (14%), abdominal distention (17%), rectal prolapse (5%) and ileus (6%). In a multivariate analysis, temperature < 36 degrees C (OR 2.12; 95% CI, 1.33 to 3.39), severe dehydration (OR, 1.70; 95% CI, 1.15 to 2.53), hyperkalemia (> 5.5 mmol/L) (OR, 1.74; 95% CI, 1.01 to 1.97), hyponatremia (< 120 mmol/L) (OR, 1.57; 95% CI, 1.17 to 2.11), urea (> 8 mmol/L) (OR, 1.74; 95% CI, 1.29 to 2.36), and abdominal distention (OR, 1.67; 95% CI, 1.16 to 2.41) were found to be predictors of mortality. CONCLUSION: Some of the major clinical and laboratory features allowing the early identification of children at increased risk of dying during dysentery outbreaks have been delineated. The high fatality associated with complicated dysentery highlights the need for preventive strategies which are sustainable in the region.

[Proposal of a questionnaire for the characterization of the prevalence of digestive symptoms in connective tissue diseases]. / Proposta de questionário para caracterização da prevalência de sintomas digestivos nas doenças difusas do tecido conjuntivo.

BACKGROUND: Connective tissue diseases may damage multiple organic systems, including digestive system. In this one, the degree of injury vary according to the associated disease. Despite the significant frequency of gastrointestinal involvement, there are few studies characterizing the prevalence of digestive symptoms in connective tissue diseases. Furthermore, most of the studies available are less detailed and based in personal experiences or reviews of records. AIM: To establish a reliable list of gastrointestinal symptoms found in the progressive systemic sclerosis, rheumatoid arthritis, polymyositis/dermatomyositis, mixed connective tissue disease and systemic lupus erythematosus, through a medical interview and a predefined questionnaire of symptoms. PATIENTS AND METHODS: There were studied 99 patients, 90% females, mean age 45 years. The whole group were composed of 35 rheumatoid arthritis, 26 progressive systemic sclerosis, 21 systemic lupus erythematosus, 12 polymyositis/dermatomyositis and 5 mixed connective tissue disease. Each patient was submitted to an interview with a well trained doctor and answered a structured questionnaire, containing 17 questions. RESULTS: It was found a high prevalence of digestive symptoms in all five connective tissue diseases searched. Many of them were present in more than 50% of the patients. Called special attention the detection of some manifestations neglected by the literature like, for example, fecal incontinence. Also, disagreeing with other authors, was the finding of multiple gastrointestinal manifestations associated with rheumatoid arthritis. It was particularly surprising the occurrence of dysphagia in one third of the rheumatoid arthritis group. CONCLUSIONS: The connective tissue diseases are usual causes of many gastrointestinal complaints. The use of an interview plus predefined questionnaire seems a very effective way to identify and characterize symptoms and is even sometimes able to uncover features unknown before. Finally, the lack of studies, specially updated studies, did not allow more comprehensive comparisons.