Impact of Tdap vaccine during pregnancy on the incidence of pertussis in children under one year in Brazil – A time series analysis

Pertussis is a globally distributed infectious disease that is a significant cause of morbidity and mortality, especially in infants who are too young to be immunized. This disease is common in childhood, and when it occurs during the first few months of life, it leads to hospitalization and, sometimes, death. Brazil has adopted the strategy of maternal immunization against pertussis in late 2014. This study aims to analyze public data on the disease to determine whether there was an impact on the disease burden following the introduction of the vaccine Tdap in pregnant women and its magnitude. We performed a time-series analysis of the incidence of pertussis between October 2010 and January 2019. We stratified the population of interest into three groups: infants aged less than two months old, infants aged two to six months, and infants aged six months to one year, according to Brazil's vaccination schedule. We found a protective effect of maternal vaccination in all age groups, more prominent on the first group. Before the intervention, infants under two months had a higher risk of getting pertussis in comparison with infants two to six months old (HR 1.15, CI 95%: 1.11–1.19). After the intervention, age under two months is a protective factor compared with two to six months (HR 0.90, CI 95%: 0.82–0.98). The pertussis incidence reduced in all age groups and all Brazil's Regions.     

Exposure to psychosocial work strain and changes in smoking behavior during pregnancy – a longitudinal study within the Danish National Birth Cohort

Objective:Knowledge of the relationship between psychosocial strain in the work environment and smoking during pregnancy is scarce. This study aimed to examine the association between psychosocial job strain and change in smoking behavior during pregnancy.Methods:The cohort included 65 645 pregnancies from the Danish National Birth Cohort (1996–2002), where pregnant women were interviewed on job factors and lifestyle during the first and third trimesters. Smoking was categorized into non-, non-daily, and daily smoking at each interview. Psychosocial job strain was categorized into four groups based on the concept of Karasek’s demand–control model: low strain (reference), passive, active and high strain. Associations between psychosocial strain and change in smoking status between the first and second interviews were analyzed by multinomial logistic regression, separately for each smoking category at first interview.Results:Non-smoking women exposed to high strain work were more likely to become daily smokers [adjusted odds ratio (OR_adj) 1.41, (95% confidence interval (CI) 1.08–1.83)] compared to non-smoking women exposed to low strain work. Non-smoking women exposed to passive work were more likely to become both non-daily and daily smokers [OR_adj 1.59 (95% CI 1.21–2.08) and OR_adj 1.32 (95% CI 1.03–1.70), respectively]. Daily smoking women exposed to high strain work were less likely to decrease their smoking [OR_adj 0.57 (95% CI 0.32–0.99)] compared to daily smoking women exposed to low strain work.Conclusions:Psychosocial strain influenced the women’s smoking behavior during pregnancy, especially in job types with low control.     

Working conditions and health behavior as causes of educational inequalities in self-rated health: an inverse odds weighting approach

Objective:Using a novel mediation method that presents unbiased results even in the presence of exposure–mediator interactions, this study estimated the extent to which working conditions and health behaviors contribute to educational inequalities in self-rated health in the workforce.Methods:Respondents of the longitudinal Survey of Health, Ageing, and Retirement in Europe (SHARE) in 16 countries were selected, aged 50–64 years, in paid employment at baseline and with information on education and self-rated health (N=15 028). Education, health behaviors [including body mass index (BMI)] and working conditions were measured at baseline and self-rated health at baseline and two-year follow-up. Causal mediation analysis with inverse odds weighting was used to estimate the total effect of education on self-rated health, decomposed into a natural direct effect (NDE) and natural indirect effect (NIE).Results:Lower educated workers were more likely to perceive their health as poor than higher educated workers [relative risk (RR) 1.48, 95% confidence interval (CI) 1.37–1.60]. They were also more likely to have unfavorable working conditions and unhealthy behaviors, except for alcohol consumption. When all working conditions were included, the remaining NDE was RR 1.30 (95% CI 1.15–1.44). When BMI and health behaviors were included, the remaining NDE was RR 1.40 (95% CI 1.27–1.54). Working conditions explained 38% and health behaviors and BMI explained 16% of educational inequalities in health. Including all mediators explained 64% of educational inequalities in self-rated health.Conclusions:Working conditions and health behaviors explain over half of the educational inequalities in self-rated health. To reduce health inequalities, improving working conditions seems to be more important than introducing health promotion programs in the workforce.     

Molecular characterization and genetic variation of the VP7 gene of human rotaviruses isolated in Paraguay

Rotavirus is the main cause of acute diarrhea in infants and young children worldwide. In Paraguay, acute diarrhea ranks fourth among the causes of mortality in children under 4 years of age. Rotavirus was detected in 93 out of 410 patients admitted to three main hospitals in Asunción, Paraguay from August 1998 to August 2000. Samples from 64 patients were analyzed by RT-PCR for G and P typing. G4P[8] (46.9%; 30/64) was the most common strain detected, followed by G9P[8] (17.2%; 11/64) and G1P[8] (10,9%; 7/64). Since G4 was predominant during the epidemiological peaks of 1998 and 1999, four samples were sequenced and all grouped into sublineage Ic. This sublineage was reported for the first time in 1998 in Argentina, southern border of Paraguay, and it was shown to be responsible for the increased prevalence of G4 during the epidemiological season of 1998 in that country. In addition, Paraguayan G1 strains grouped in different lineages (I and II). However, G9 was predominant during the rotavirus epidemiological peak of 2000, and phylogenetic analysis of five samples grouped into a common emergent/reemergent lineage that circulates worldwide. Since vaccination could reduce the severity and the number of cases of rotavirus disease, this study suggests that a vaccine containing recently isolated variants of the most prevalent types (G1-G4) together with the emerging G9 type, might be sufficient to elicit a protective immune response against the rotavirus types circulating currently in Paraguay.     

Cdc7 kinase is required for postnatal brain development

The evolutionally conserved Cdc7 kinase plays crucial roles in initiation of DNA replication as well as in other chromosomal events. To examine the roles of Cdc7 in brain development, we have generated mice carrying Cdc7 knockout in neural stem cells by using Nestin-Cre. The Cdc7^Fl/Fl Nestin^Cre mice were born, but exhibited severe growth retardation and impaired postnatal brain development. These mice exhibited motor dysfunction within 9 days after birth and did not survive for more than 19 days. The cerebral cortical layer formation was impaired, although the cortical cell numbers were not altered in the mutant. In the cerebellum undergoing hypoplasia, granule cells (CGC) decreased in number in Cdc7^{Fl/F l}Nestin^Cre mice compared to the control at E15-18, suggesting that Cdc7 is required for DNA replication and cell proliferation of CGC at mid embryonic stage (before embryonic day 15). On the other hand, the Purkinje cell numbers were not altered but its layer formation was impaired in the mutant. These results indicate differential roles of Cdc7 in DNA replication/cell proliferation in brain. Furthermore, the defects of layer formation suggest a possibility that Cdc7 may play an additional role in cell migration during neural development.     

Trophic effect of angiotensin II in neonatal rat cardiomyocytes: role of endothelin-1 and non-myocyte cells

1. Angiotensin II (AII) and the endothelins (ET) are known to be potent trophic stimuli in various cells including cardiomyocytes. In order to characterize further these effects we studied, in neonatal rat ventricular cardiomyocytes, the effects of several endothelin-receptor antagonists and the AT₁-receptor antagonist losartan on AII- and endothelin-induced inositol phosphate (IP)-formation (assessed as accumulation of total [³H]-IPs in myo-[³H]-inositol prelabelled cells) and increase in rate of protein synthesis (assessed as [³H]-phenylalanine incorporation).
2. Endothelin (10 pM–1 μM) concentration-dependently increased IP-formation (max. increase at 100 nM ET-1: 130±14% above basal, n=25) and [³H]-phenylalanine incorporation (max. increase at 1 μM: 52±4% above basal, n=16) with an order of potency: ET-1>>ET-3. Both effects were antagonized by the ET_A/ET_B-receptor antagonist bosentan and the ET_A-receptor antagonist BQ-123, but not affected by the ET_B-receptor antagonist IRL 1038 and the AT₁-receptor antagonist losartan.
3. Pretreatment of the cells with 500 ng ml⁻¹ pertussis toxin (PTX) overnight that completely inactivated PTX-sensitive G-proteins did not attenuate but rather enhance ET-1-induced IP-formation. On the other hand, in PTX-pretreated cardiomyocytes ET-1-induced [³H]-phenylalanine incorporation was decreased by 39±5% (n=5).
4. AII (1 nM–1 μM) concentration-dependently increased IP-formation (max. increase at 1 μM: 42±7% above basal, n=16) and [³H]-phenylalanine incorporation (max. increase at 1 μM: 29±2%, n=9). These effects were antagonized by losartan, but they were also antagonized by bosentan and BQ-123.
5. In well-defined cultures of cardiomyocytes (not contaminated with non-myocyte cells) AII failed to increase [³H]-phenylalanine incorporation; addition of non-myocyte cells to the cardiomyocytes restored AII-induced increase in [³H]-phenylalanine incorporation.
6. We conclude that, in rat neonatal ventricular cardiomyocytes, (a) the ET-1-induced increase in rate of protein synthesis (through ET_A-receptor stimulation) involves at least two signalling pathways: one via a PTX-insensitive G-protein coupled to IP-formation, and the other one via a PTX-sensitive G-protein, and (b) the trophic effects of AII are brought about via local ET-1 secretion upon AT₁-receptor stimulation in neonatal rat ventricular non-myocyte cells.

     

The role of radiation therapy in the treatment of anal carcinoma: Techniques and current recommendations

Background: In view of the results of surgery for anal cancer the treatment of choice is radiation therapy with or without chemotherapy. Methods: From 1987 until 1990 a total of 14 patients have undergone primarily conservative treatment at the University Clinic of Radiology in Graz. 10 patients were treated with a split-course technique of external beam and interstitial radiation over a period of 7 weeks. In 4 patients a similar radiation protocol, omitting the second implantation, was combined with 2 courses of 5-Fluorouracil (5-FU) and Mitomycin C (MMC). Results: Permanent tumor control was achieved in 8/10 cases after radiotherapy only, with sphincter preservation in 7 patients. Combined chemo-radiotherapy yielded complete remission in 3/4 patients. All failures of therapy occurred in T3 tumors. Conclusions: At present the best results in terms of tumor response and toxicity are achieved by 5-FU and MMC given synchronously with radiotherapy. Radiation is preferably applied according to a split-course protocol, as established by Papillon.     

Activation of 5-HT1B receptors in the nucleus accumbens reduces amphetamine-induced enhancement of responding for conditioned reward

Previously, we have demonstrated that 5-hydroxytryptamine (5-HT) injected into the nucleus accumbens attenuates the potentiating effects of d-amphetamine on responding for conditioned reward (CR). The present studies examined the 5-HT receptor involved in this effect by investigating the effects of 5-HT agonists with differing affinities for 5-HT₁ and 5-HT₂ receptors on d-amphetamine-induced potentiation of responding for CR. Rats were trained to associate a light/tone stimulus (subsequently the CR) with water delivery. In a test phase, they were allowed access to a lever delivering the CR, and an inactive (NCR) lever. Responding on the CR lever was greater than responding on the NCR lever, indicating that the light/tone stimulus functioned as a CR. Responding for the CR was selectively potentiated by injections of d-amphetamine (10 μg) into the nucleus accumbens. This effect was reduced by injections into the nucleus accumbens of 5-CT (0.5 and 1 μg), RU24969 (10 μg), CP93,129 (1.25 and 2.5 μg) but not by DOI (10 μg) or 8-OH-DPAT (5 μg). The lower doses of 5-CT and CP93,129 did not reduce baseline responding for CR, or responding for water in a separate group of animals, indicating that the effects of these drugs were behaviourally selective. The higher doses abolished the CR effect, and in the case of 5-CT and RU24969 also reduced responding for water. All of the effective drugs share in common the ability to stimulate 5-HT_1B receptors, albeit with differing selectivities. The effect of CP93,129, the most selective of the 5-HT_1B agonists, to inhibit the response-potentiating effect of d-amphetamine was reversed by the5-HT_1B/1D antagonist GR127935 (3 mg/kg). The results indicate that activation of 5-HT_1B receptors within the nucleus accumbens attenuates the effects of a dopamine-dependent behaviour, and that activation of these receptors can oppose the behavioural effects of elevated mesolimbic dopamine transmission. Received: 22 April 1998/Final version: 28 July 1998     

Automatic decomposition electromyography in idiopathic inflammatory myopathies

Automatic decomposition electromyography (ADEMG) is a commercially available software package with installed reference values that enables the objective measurement of motor unit action potentials (MUAPs). To assess the diagnostic yield of this package in idiopathic inflammatory myopathies (IIM) we performed biceps brachii ADEMG in 17 patients with polymyositis, dermatomyositis and inclusion body myositis. Results were compared with those in 12 controls, and with the results of conventional EMG of the biceps and other muscles. Decreased mean values for MUAP duration occurred significantly more frequently in IIM patients than in controls; other MUAP characteristics did not differ. In IIM patients, decreased mean amplitude and increased mean number of turns occurred significantly less frequently on ADEMG than did corresponding abnormalities on conventional biceps EMG. Decreased mean values for duration and amplitude, and increased mean values for number of turns were seen significantly less often on ADEMG than corresponding abnormalities on conventional EMG of four different, individually chosen muscles. Overall evaluation of ADEMG resulted in a diagnosis of possible myopathy in 1 and probable myopathy in 8 patients, whereas overall evaluation of conventional EMG led to a diagnosis suggestive of IIM in 13 patients. We conclude that, although measurement of mean MUAP duration might be valuable in IIM diagnosis, our results do not favour the use of biceps brachii ADEMG and the installed reference values for the diagnosis of IIM. We suggest modifications to improve ADEMG's applicability.