Amoxicillin-Resistant Streptococci Carriage in the Mouths of Children: A Systematic Review and Meta-Analysis.

Streptococcal bacteremia that occurs during invasive dental procedures can lead to infective endocarditis (IE) in children with certain heart diseases. Prior to such procedures, antibiotic prophylaxis (AP) with amoxicillin (AMPC) is recommended. However, the detection of amoxicillin-resistant strains (AMPC-RS) in the mouths of children with heart diseases raises the concern that they would be uncovered by the action of standard AP. This work carried out a systematic review and meta-analysis regarding AMPC-RS carriage in the mouths of children. We consulted databases covering studies between the years 2000 and 2021, following the PRISMA declaration. A meta-analysis was carried out to assess the prevalence of children carrying AMPC-RS in the mouths. The antimicrobial tests were carried out by microdilution (46.2% of articles), disk diffusion (38.3%), and the E-test (15.4%). Streptococcus mitis and S. sanguinis were bacteria with the most found resistance phenotype, with MIC reaching values of 128 µg/mL. Of the 13 selected articles, only 6 presented results that made it possible to calculate the prevalence of children carrying AMPC-RS in their mouths, ranging from 5.5% to 86.3%. Most of the studies were classified as high quality, and the collected data demonstrate the presence of streptococcal strains with different levels of resistance in the collected samples, such as the dental plaque. The meta-analysis pointed to evidence of AMPC-RS being carried, with a prevalence of 21.3% (I² = 0%, p = 0.705). There is an important prevalence of AMPC-RS carriage in the mouths of children. Specific attention should be directed to AP in those susceptible to IE.

Anthelmintic, Antibacterial and Cytotoxicity Activity of Imidazole Alkaloids from Pilocarpus microphyllus Leaves.

Pilocarpus microphyllus Stapf ex Wardlew (Rutaceae), popularly known as jaborandi, is a plant native to the northern and northeastern macroregions of Brazil. Several alkaloids from this species have been isolated. There are few reports of antibacterial and anthelmintic activities for these compounds. In this work, we report the antibacterial and anthelmintic activity of five alkaloids found in P. microphyllus leaves, namely, pilosine, epiisopilosine, isopilosine, epiisopiloturine and macaubine. Of these, only anthelmintic activity of one of the compounds has been previously reported. Nuclear magnetic resonance, HPLC and mass spectrometry were combined and used to identify and confirm the structure of the five compounds. As regards the anthelmintic activity, the alkaloids were studied using in vitro assays to evaluate survival time and damaged teguments for Schistosoma mansoni adult worms. We found epiisopilosine to have anthelmintic activity at very low concentrations (3.125 µg mL-1 ); at this concentration, it prevented mating, oviposition, reducing motor activity and altered the tegument of these worms. In contrast, none of the alkaloids showed antibacterial activity. Additionally, alkaloids displayed no cytotoxic effect on vero cells. The potent anthelmintic activity of epiisopilosine indicates the potential of this natural compound as an antiparasitic agent. Copyright © 2017 John Wiley & Sons, Ltd.

The role of perfectionism in postpartum depression and symptomatology.

The role of perfectionism as a correlate and as a predictor of perinatal depressive symptomatology and disorder was examined. Three-hundred and eighty-six pregnant women (mean age = 30.08 years; SD = 4.205; range = 19-44) completed the Portuguese versions of the Multidimensional Perfectionism Scale, Beck Depression Inventory-II/BDI-II and three questions evaluating anxiety trait, life stress and social support perception. Diagnoses of depression were obtained using the Portuguese version of the Diagnostic Interview for Genetic Studies/OPCRIT system. Women who were depressed in pregnancy (ICD-10/DSM-IV) were excluded from the analyses. Self-Oriented Perfectionism and Socially Prescribed Perfectionism subcomponents (Conditional Acceptance and Others' High Standards) were significant correlates of depressive symptomatology/BDI-II in pregnancy. Others' High Standards was a significant predictor of postpartum depressive symptomatology/BDI-II, after controlling the other independent variables (depressive symptomatology and trait anxiety in pregnancy, life stress and social support perception in postpartum). None of the perfectionism subscales predicted postpartum depressive disorder (ICD-10/DSM-IV). Self-Oriented Perfectionism was an important correlate of depressive symptomatology in pregnancy and Others' High Standards and Conditional Acceptance were significant correlates of perinatal depressive symptomatology. Others' High Standards accounted for 0.8 % of the depressive symptomatology variance in postpartum after controlling the effect for other depressive symptomatology correlates. Perfectionism was not a risk factor for postpartum depressive disorder. Our findings improve the knowledge regarding the risk factors implicated in the development of postpartum depressive symptomatology/disorder, which is of utmost importance to develop adequate prevention and intervention strategies.

Affective state dependence and relative trait stability of perfectionism in sleep disturbances.

OBJECTIVE: To evaluate the degree of absolute change, relative stability and state dependence of trait perfectionism in sleep disturbances in a sample of university students. METHOD: Participants completed the Multidimensional Perfectionism Scale and two items concerning sleep difficulties. The mean age at T0 (baseline) was 19.59 years (SD = 1.61, range = 17-25) and 62.5% of the sample were female. RESULTS: Absolute changes in self-oriented and socially-prescribed perfectionism were found. Relative stability was found for all perfectionism dimensions. Prior and concurrent sleep disturbances explained a significant amount of variance in perfectionism. Controlling for the effects of sleep measures, prior self-oriented perfectionism and other-oriented perfectionism were the only significant predictors of subsequent self-oriented perfectionism and other-oriented perfectionism, at T1 and T2. Difficulties falling asleep at T1 and socially-prescribed perfectionism at T0 were significant predictors of socially-prescribed perfectionism at T1. CONCLUSION: Despite significant changes in perfectionism mean scores over the follow-up, the correlation analyses demonstrated that participants remained quite stable in regard to their relative levels of perfectionism. As concurrent difficulties initiating sleep also predicted concurrent socially-prescribed perfectionism, this seems to be one dimension of perfectionism with trait-state characteristics.

Affective state dependence and relative trait stability of perfectionism in sleep disturbances / Dependência do estado afetivo e estabilidade relativa do traço do perfeccionismo nas perturbações de sono

OBJECTIVE: To evaluate the degree of absolute change, relative stability and state dependence of trait perfectionism in sleep disturbances in a sample of university students. METHOD: Participants completed the Multidimensional Perfectionism Scale and two items concerning sleep difficulties. The mean age at T0 (baseline) was 19.59 years (SD = 1.61, range = 17-25) and 62.5 percent of the sample were female. RESULTS: Absolute changes in self-oriented and socially-prescribed perfectionism were found. Relative stability was found for all perfectionism dimensions. Prior and concurrent sleep disturbances explained a significant amount of variance in perfectionism. Controlling for the effects of sleep measures, prior self-oriented perfectionism and other-oriented perfectionism were the only significant predictors of subsequent self-oriented perfectionism and other-oriented perfectionism, at T1 and T2. Difficulties falling asleep at T1 and socially-prescribed perfectionism at T0 were significant predictors of socially-prescribed perfectionism at T1. CONCLUSION: Despite significant changes in perfectionism mean scores over the follow-up, the correlation analyses demonstrated that participants remained quite stable in regard to their relative levels of perfectionism. As concurrent difficulties initiating sleep also predicted concurrent socially-prescribed perfectionism, this seems to be one dimension of perfectionism with trait-state characteristics.

OBJETIVOS: Avaliar o grau de mudança absoluta, de estabilidade relativa e dependência do estado do perfeccionismo nas perturbações de sono numa amostra de estudantes universitários. MÉTODO: Os sujeitos completaram a Escala Multidimensional do Perfeccionismo e dois itens sobre dificuldades em dormir. Os dados foram recolhidos em três momentos de avaliação, separados por um intervalo de um ano acadêmico. A idade média dos sujeitos no T0 era de 19,59 anos (DP = 1,61, variação = 17-25); 62,5 por cento eram mulheres. RESULTADOS: Foram encontradas ao longo do follow-up mudanças absolutas para o perfeccionismo auto-orientado e para o perfeccionismo socialmente prescrito. Foi encontrada estabilidade relativa para todas as dimensões do perfeccionismo. As dificuldades de sono prévias e concorrentes explicaram significativamente a variância do perfeccionismo. Controlando o efeito das dificuldades em dormir, o perfeccionismo auto-orientado e o perfeccionismo orientado para o outro prévios foram os únicos preditores significativos de perfeccionismo auto-orientado e perfeccionismo orientado para o outro (T1 e T2). As dificuldades em iniciar o sono no T1 e o perfeccionismo socialmente prescrito prévio (T0) revelaram-se preditores significativos de perfeccionismo socialmente prescrito no T1. CONCLUSÃO: Apesar das mudanças significativas nas pontuações médias de perfeccionismo ao longo do follow-up, as análises de correlação demonstraram que os participantes permaneceram relativamente estáveis nos seus níveis de perfeccionismo. Uma vez que as dificuldades em iniciar o sono concorrentes se revelaram um preditor significativo de perfeccionismo socialmente prescrito, esta é a dimensão do perfeccionismo que possui características traço-estado.

Sleep disturbances, body mass index and eating behaviour in undergraduate students.

This study investigates the association between sleep disturbances, body mass index (BMI) and eating behaviour in a sample of undergraduate students. The sample comprises 870 medicine and dentistry students from Coimbra University (62.5% females), aged between 17 and 25 years. The Eating Attitudes Test-40 was used to measure eating behaviour, and two questions were applied addressing difficulties of initiating sleep (DIS) and difficulties of maintaining sleep (DMS). A sleep disturbance index (SDI) was calculated from the sum of DIS and DMS scores. Body mass index (BMI) was determined from self-reported weight and height. The correlation analyses generally indicated that global eating disturbance, bulimic behaviour dimension and social pressure to eat were associated particularly with sleep difficulties. An association between diet concerns and sleep difficulties was less consistent. Regression analyses showed that bulimic behaviour (BB) and social pressure to eat (SPE) dimensions were associated significantly with sleep difficulties (DIS, DMS, SDI) in the total sample (BB: from P<0.01 to P<0.001; SPE: P<0.05) and in males (BB: from P<0.05 to P<0.001; SPE: P<0.05) and with insomnia symptoms (P<0.01). In females, bulimic behaviour was the only factor associated significantly with sleep difficulties (SDI, DIS; P<0.01) and with insomnia symptoms (P<0.05). Although BMI was correlated negatively with sleep difficulties (P<0.05), regression analyses indicated that it was not associated significantly with them. Our findings support an association between eating behaviour and sleep disturbances in both genders, which may have treatment implications.

Feasibility of differential diagnosis of kidney tumors by comparative genomic hybridization of fine needle aspiration biopsies.

The association of a genetic analysis that could improve the diagnostic accuracy of renal cell tumors in biopsy samples would allow better-informed therapeutic decisions. We performed comparative genomic hybridization (CGH) on an ex vivo fine-needle aspiration (FNA) biopsy and a tumor fragment obtained from 75 patients consecutively diagnosed with renal tumors and subjected to radical nephrectomy. The pattern of genomic changes by CGH was used blindly to classify the renal tumors and the genetic findings were subsequently compared with the histopathologic diagnosis. In particular cases, including in two carcinomas with morphologically distinct tumor areas, we performed FISH with several locus-specific probes, and looked for VHL point mutations, exonic rearrangements, or promoter methylation. CGH was successful in 82.7% FNA biopsies and in 96% tumor fragments, with the former allowing genetic diagnosis in 75% of renal cell tumors. The genetic and the initial histological classification differed in two renal neoplasias, but the genetic diagnosis was confirmed after review. The genetic pattern correctly diagnosed 93.5% of clear cell renal cell carcinomas (RCC), 61.5% of chromophobe RCC, 100% of papillary RCC, and 14.3% of oncocytomas, with the negative predictive value being 93.9, 90.7, 100, and 90.2%, respectively. The positive predictive value and specificity of copy number profiles was 100%. We demonstrate that genetic diagnosis by CGH on FNA biopsies can improve differential diagnosis in patients with kidney tumors.

CSF1R copy number changes, point mutations, and RNA and protein overexpression in renal cell carcinomas.

Renal cell carcinomas comprise a heterogeneous group of tumors. Of these, 80% are clear cell renal cell carcinomas, which are characterized by loss of 3p, often with concomitant gain of 5q22qter. Although VHL is considered the main target gene of the 3p deletions, none has been identified as the relevant target gene for the 5q gain. We have studied 75 consecutive kidney tumors and paired normal kidney samples to evaluate at the genomic and expression levels the tyrosine kinase genes CSF1R and PDGFRB as potential targets in this region. Our findings show that RNA expression of CSF1R, but not of PDGFRB, was significantly higher in clear cell renal cell carcinomas than in normal tissue samples, something that was corroborated at the protein level by immunohistochemistry. The CSF1R staining pattern in clear cell renal cell carcinomas was clearly different from that observed in other renal cell carcinomas, suggesting its potential usefulness in differential diagnosis. FISH analysis demonstrated whole chromosomal gain and relative CSF1R/PDGFRB copy number gain in clear cell renal cell carcinomas, which might contribute to CSF1R overexpression. Finally, one polymorphism and two novel mutations were identified in CSF1R in clear cell renal cell carcinoma patients. Our data allow us to conclude that CSF1R plays a relevant role in clear cell renal cell carcinoma carcinogenesis and raise the possibility that CSF1R may represent a future valuable therapeutic target in these patients.

Overexpression of the mitotic checkpoint genes BUB1 and BUBR1 is associated with genomic complexity in clear cell kidney carcinomas.

BACKGROUND: A defective mitotic checkpoint has been proposed to contribute to chromosomal instability (CIN). We have previously shown that expression changes of the mitotic arrest deficiency (MAD) gene family plays a role in renal cell cancer (RCC) characterized by numerical chromosomal changes, namely papillary and chromophobe carcinomas, but nothing is known about the expression of mitotic checkpoint genes in the clear cell histotype (ccRCC). METHODS: We analyzed the mRNA expression levels of the major mitotic checkpoint genes of the budding uninhibited by benzimidazole family (BUB1, BUBR1, BUB3) and of the MAD gene family (MAD1, MAD2L1, MAD2L2) by real-time quantitative PCR in 39 ccRCC and in 36 normal kidney tissue samples. We have additionally analyzed these tumors by comparative genomic hybridization (CGH) in order to evaluate the relationship between mitotic checkpoint defects and the pattern of chromosome changes in this subset of RCC. RESULTS: BUB1, BUBR1, MAD1 and MAD2L1 showed significant expression differences in tumor tissue compared to controls (BUB1, BUBR1 and MAD2L1 were overexpressed, whereas MAD1 was underexpressed). Overexpression of BUB1 and BUBR1 was significantly correlated with the number of genomic copy number changes (p<0.001 for both genes) and with Furhman grade of the tumors (p=0.006 and p=0.005, respectively). CONCLUSIONS: We conclude that BUB1 and BUBR1 overexpression plays a role in cytogenetic and morphologic progression of ccRCC.

Association of the gene encoding neurogranin with schizophrenia in males.

The neurogranin (NRGN) gene produces a postsynaptic brain-specific protein that regulates calmodulin-Ca(2+) availability in neurons. Acting downstream of the NMDA receptor and upstream of calcineurin and other proteins implicated in schizophrenia, NRGN is a good candidate for association studies in schizophrenia. NRGN expression is regulated during development and is modulated by thyroid hormones and retinoids, molecules essential for the proper development of the central nervous system. Given the genetic complexity of schizophrenia and the potential genetic heterogeneity in different populations, we studied a possible association of NRGN with schizophrenia in 73 Azorean proband-parent triads and in two independent case-control samples from the Portuguese-mainland (244 schizophrenic and 210 controls) and Brazil (69 schizophrenic and 85 mentally healthy individuals). Genotype distribution showed association of the rs7113041 SNP with schizophrenia in males of Portuguese origin, which was confirmed by the analysis of the proband-parent triads. This evidence, implicating NRGN in schizophrenia, introduces another player into the glutamatergic hypothesis of schizophrenia.

Expression changes of the MAD mitotic checkpoint gene family in renal cell carcinomas characterized by numerical chromosome changes.

Papillary and chromophobe renal cell carcinomas are characterized by multiple trisomies and monosomies, respectively, but the molecular mechanisms behind the acquisition of these numerical chromosome changes are unknown. To evaluate the role of mitotic checkpoint defects for the karyotypic patterns characteristic of these two renal cell cancer subtypes, we analyzed the messenger RNA expression levels of the major mitotic checkpoint genes of the budding uninhibited by benzimidazole family (BUB1, BUBR1, BUB3) and of the mitotic arrest deficiency family (MAD1, MAD2L1, MAD2L2) by real-time quantitative polymerase chain reaction in 30 renal cell cancer samples (11 chromophobe and 19 papillary) and 36 normal kidney tissue samples. MAD1, MAD2L1, and MAD2L2 showed significant expression differences in tumor tissue compared to controls. Chromophobe tumors presented underexpression of MAD1, and MAD2L2, whereas papillary tumors showed overexpression of MAD2L1. The expression level of the BUB gene family did not differ significantly from that of normal kidney. We conclude that expression changes in mitotic arrest deficiency genes (MAD1, MAD2L1, and MAD2L2) play a role in renal carcinogenesis characterized by multiple numerical chromosome abnormalities.

Transthyretin: no association between serum levels or gene variants and schizophrenia.

It has been proposed that schizophrenia results from an environmental insult in genetically predisposed individuals. Environmental factors capable of modulating transcriptional activity and their carriers could link the genetic and environmental components of schizophrenia. Among these is transthyretin (TTR), a major carrier of thyroid hormones and retinol-binding protein (RBP). Retinoids and thyroid hormones regulate the expression of several genes, both during development and in the adult brain. Decreased TTR levels have been reported in the cerebrospinal fluid of patients with depression and Alzheimer's disease, and the absence of TTR influences behavior in mice. DNA variants capable of altering TTR ability to carry its ligands, either due to reduced transcription of the gene or to structural modifications of the protein, may influence development of the central nervous system and behavior. In the present study we searched for variants in the regulatory and coding regions of the TTR gene, and measured circulating levels of TTR and RBP. We found a novel single nucleotide polymorphism (SNP), ss46566417, 18 bp upstream of exon 4. Neither this SNP nor the previously described rs1800458 were found associated with schizophrenia. In addition, serum TTR and RBP levels did not differ between mentally healthy and schizophrenic individuals. In conclusion, our data does not support an involvement of the TTR gene in the pathophysiology of schizophrenia.

Lack of association or linkage disequilibrium between schizophrenia and polymorphisms in the 5-HT1Dalpha and 5-HT1Dbeta autoreceptor genes: family-based association study.

Genetic factors play a major role in the etiology of schizophrenia and disturbances of serotonergic pathways have been implicated in this disorder. The aim of the present study was to examine genetic association between schizophrenia and polymorphisms in the 5-HT1Dalpha (TaqI) and 5-HT1Dbeta (T261G and G861C) autoreceptor genes in ninety trios from Portugal. No association or linkage disequilibrium was obtained between schizophrenia and 5-HT1Dalpha and 5-HT1Dbeta autoreceptor genes with both haplotype relative risk (HRR) and transmission disequilibrium test (TDT). Concerning 5-HT1Dbeta autoreceptor gene, also negative results was obtained in the analysis of the haplotypes with transmit. Thus, our data provide no support for the hypothesis that polymorphisms at 5-HT1Dalpha (TaqI) and 5-HT1Dbeta (T261G and G861C) genes contributes to susceptibility to schizophrenia in the Portuguese population.

Nonparametric linkage analysis between schizophrenia and candidate genes of dopaminergic and serotonergic systems.

BACKGROUND: Alterations in dopaminergic and serotonergic systems have been implicated in the pathophysiology of schizophrenia for many years. This study was performed to assess the possible involvement of the dopamine receptor genes D2 (DRD2), D3, D4, serotonin receptor genes 1Da, 1Db, and 2A in the etiology of schizophrenia. METHODS: We examined 33 multiplex schizophrenic families from Portugal. RESULTS: Linkage analysis performed by GENEHUNTER showed nonsignificant linkage for these genes. A maximum nonparametric linkage score of 1.635 (P=.032) at DRD2 gene was observed, and this finding suggests DRD2 gene for further studies. CONCLUSION: the polymorphisms studied at dopamine receptor genes D3, D4, serotonin receptor genes 1Da, 1Db, and 2A do not have a major effect in susceptibility to schizophrenia in a Portuguese population.

No evidence of association or linkage disequilibrium between polymorphisms in the 5' upstream and coding regions of the dopamine D4 receptor gene and schizophrenia in a Portuguese population.

Alterations in dopaminergic system have been implicated in the pathophysiology of this disease for many years, and this study was performed to assess the possible involvement of the dopamine D4 receptor (DRD4) gene polymorphisms either in the 5' upstream or in the coding regions, in the etiology of schizophrenia. The approach included an association study with 90 Portuguese trios by doing the analysis of the individual alleles and the haplotypes. For the polymorphisms in the 5' upstream region (-C616G and -C521T) and in the coding region (48 bp repeat) of the DRD4 gene, negative results were obtained with both haplotype relative risk (HRR) and transmission disequilibrium test (TDT), as well as transmit. These data suggest that polymorphisms (-C616G, -C521T, and 48 bp repeat) at the DRD4 gene do not have a minor effect in the susceptibility to schizophrenia in our sample.

Analysis of different molecular methods for typing methicillin-resistant Staphylococcus aureus isolates belonging to the Brazilian epidemic clone.

The extensive geographic spread of MRSA isolates belonging to the Brazilian epidemic clone (BEC) limited the value of pulsed-field gel electrophoresis (PFGE) in epidemiological studies of outbreaks caused by these strains. Thus, the discriminatory power of eight different molecular methods was evaluated in an attempt to establish a methodology for genotyping BEC isolates involved in intra-hospital outbreaks. BEC isolates from five hospitals in Teresina City, Piaui State were genotyped by conventional electrophoresis or PFGE of Cla I- or Sma I-digested genomic DNA hybridised with specific labelled mecA, Tn554, IS257 and IS256 probes. The combination of PFGE with Cla I/mecA, Cla I/Tn554, Cla I/IS257, Sma I/mecA and Sma I/IS257 probe-fingerprinting techniques provided a very poor discriminatory power for BEC strains. Although Cla I/IS256 fingerprinting discriminated 17 different polymorphisms among the isolates displaying PFGE A1 pattern, this strategy was not reproducible. In contrast, the combination of PFGE and Sma I/IS256 polymorphisms differentiated BEC isolates into nine stable polymorphisms. Thus combination of PFGE and hybridisation with IS256 probe may be recommended as a useful means of typing BEC strains involved in intra-hospital infections.