Fungicides as a risk factor for the development of neurological diseases and disorders in humans: a systematic review.

Although studies show that pesticides, especially insecticides, may be toxic to humans, publications on the neurological effects of fungicides are scarce. As fungicides are used widely in Brazil, it is necessary to gather evidence to support actions aimed at safely using of these chemicals. We investigated through a systematic review of publications on the use of fungicides and consequences of exposure related to nervous system diseases or neurological disorders in humans. The protocol review was registered on PROSPERO and followed the guidelines of the PRISMA-Statement. As far as it is known, there is no apparent systematic review in the literature on this topic. The search was comprised of the following databases: PubMed; Web of Science; Scopus and EMBASE, using groups of Mesh terms and strategies specific to each database. Thirteen articles were selected for this review. Regarding the substances analyzed in the studies, some reported the use of fungicides in general, without separating them by type, while others summarized the categories of all pesticides by their function (insecticides, herbicides, fungicides, etc.) or chemical class (dithiocarbamate, dicarboximide, inorganic, etc.). However, most of the articles referred to fungicides that contain the metal manganese (Mn) in their composition. As for neurological disorders, articles addressed Parkinson's disease (PD), neurodevelopmental outcomes, extrapyramidal syndrome resembling PD, cognitive disorders, depression, neural tube defects, motor neurone disease, and amyotrophic lateral sclerosis. Most investigations pointed to exposure to fungicides, mainly maneb and mancozeb, leading to the development of at least one neurological disease, which suggests the need for further multicentric clinical trials and prospective studies for greater clarity of the research problem.

Evolution of research funding for neglected tropical diseases in Brazil, 2004-2020.

Neglected tropical diseases are a global public health problem. Although Brazil is largely responsible for their occurrence in Latin America, research funding on the subject does not meet the population's health needs. The present study analyzed the evolution of research funding for neglected tropical diseases by the Ministry of Health and its partners in Brazil, from 2004 to 2020. This is a retrospective study of data from investigations registered on Health Research (Pesquisa Saúde in Portuguese), a public repository for research funded by the Ministry of Health's Department of Science and Technology. The temporal trend of funding and the influence of federal government changes on funding were analyzed using Prais-Winster generalized linear regression. From 2004 to 2020, 1,158 studies were financed (purchasing power parity (PPP$) 230.9 million), with most funding aimed at biomedical research (81.6%) and topics involving dengue, leishmaniasis and tuberculosis (60.2%). Funding was stationary (annual percent change of -5.7%; 95%CI -54.0 to 45.0) and influenced by changes to the federal government. Research funding was lacking for chikungunya, Chagas disease, schistosomiasis, malaria and taeniasis/cysticercosis, diseases with a high prevalence, burden or mortality rates in Brazil. Although the Ministry of Health had several budgetary partners, it was the main funder, with 69.8% of investments. The study revealed that research funding for neglected tropical diseases has stagnated over the years and that diseases with a high prevalence, burden and mortality rate receive little funding. These findings demonstrate the need to strengthen the health research system by providing sustainable funding for research on neglected tropical diseases that is consistent with the population's health needs.

Fracture resistance of weakened roots restored with relined or milled CAD-CAM glass fiber posts.

This in vitro study compared the fracture resistance of weakened roots restored with milled or relined glass fiber post (GFP). Seventy bovine incisors were divided into seven groups, according to the weakening protocol (none: control; medium-weakened: MW; highly-weakened: HW) and post anatomization technique (non-relined, relined with Bulk Fill or Z350 resin; milled GFP: M). Roots were thermomechanical cycled and submitted to compression. Frequencies and groups were compared by the chi-square test and two-factor ANOVA, Tukey's, and t-test (α=5%). The HW-M obtained the lowest values, showing significant differences compared to all groups (p<0.001). The highest value was HW-Bulk fill, with significant difference compared to MW-M (p=0.037) and HW-M (p<0.001). The frequency of repairable fractures was 100% in the control, 87%, and 63% in the MW and HW, respectively. Relined or milled GFPs can be considered to rehabilitate weakened teeth since failure patterns were predominantly repairable in all groups.

Fracture resistance and stress distribution of weakened teeth reinforced with a bundled glass fiber-reinforced resin post.

OBJECTIVES: To make an in vitro assessment of fracture resistance of weakened and non-weakened teeth receiving intraradicular reinforcement using Rebilda bundled glass fiber-reinforced composite posts (GT), Rebilda conventional glass fiber posts (RP), or both systems combined (GT + RP). MATERIALS AND METHODS: Eighty sound bovine incisors were prepared and divided randomly into eight groups as follows: (a) nWnR: without simulating weakness, and without intraradicular reinforcement; (b) WnR: simulating weakness, but without intraradicular reinforcement; (c) nWGT: without simulating weakness, but with GT; (d) WGT: simulating weakness, and with GT; (e) nWRP: without simulating weakness, but with RP; (f) WRP: simulating weakness, and with RP; (g) nWGTRP: without simulating weakness, but with GT + RP; (h) WGTRP: simulating weakness, and with GT + RP. The specimens were subjected to the load-to-fracture test using the DL-2000MF universal testing machine. The finite element method assessed the mechanical behavior and stress distribution in endodontically treated teeth. RESULTS: The groups nWGTRP and WGTRP presented the best results in the load-to-fracture test, with the former being better than the latter, but with no statistically significant difference (P > 0.05). However, there was a significant difference between these and the other groups (P < 0.05), except for nWRP. Stress distribution inside the canal wall was different among the groups, with promising mechanical behavior for nWGTRP and nWRP. CONCLUSIONS: The Rebilda conventional fiber post (RP), combined with the Rebilda bundled glass fiber-reinforced composite post (GT) improves the resistance and stress distribution of immature teeth. CLINICAL RELEVANCE: Longitudinal fracture is less frequent in teeth restored with GT and RP posts.

Efeitos sinérgicos antimicrobianos da combinação dos extratos de sálvia e alcaçuz sobre cepas clínicas de Enterococcus faecalis e Enterococcus faecium / Synergistic antimicrobial effects of the combination of sage and licorice extracts on clinical strains of Enterococcus faecalis and Enterococcus faecium

A crescente busca pelo conhecimento do potencial biológico presente nas plantas medicinais tem estimulado pesquisas, principalmente no que diz respeito ao potencial antimicrobiano dos extratos de plantas. Entretanto, mais estudos sobre os efeitos sinérgicos da combinação desses extratos são fundamentais para sua maior aplicação clínica. O objetivo desse estudo foi avaliar in vitro os efeitos sinérgicos antimicrobianos das associações dos extratos naturais de Salvia officinalis (S. officinalis) e Glycyrrhiza glabra (G. glabra). Foi realizada a análise antimicrobiana sobre três cepas clínicas de Enterococcus faecalis (E. faecalis), duas cepas clínicas de Enterococcus faecium (E. faecium) e uma cepa padrão de cada espécie. Foram determinadas as Concentração Inibitória Mínima (CIM) e Concentração Microbicida Mínima (CMM) por microdiluição em caldo com semeadura, e Índice de Concentração Inibitória Fracionada (ICIF) pela técnica checkerboard. Para avaliar o efeito combinado dos extratos sobre biofilme foram utilizadas duas combinações dos extratos sobre biofilme formado de E. faecalis e sobre biofilme formado de E. faecium, por dois períodos diferentes: 5 minutos e 24 h, e foram avaliados os valores médios de unidades formadoras de colônias por mililitro (UFC/mL). A análise estatística foi feita aplicando método ANOVA e teste de Tukey ou Kruskall-Wallis e Dunn (significância de 5%). Os extratos de S. officinalis e G. glabra apresentaram concentração microbicida para as cepas avaliadas. A combinação dos extratos apresentou valores indiferentes (ICIF ˃ 0,5 e ≤ 4) para as cepas de E. faecium, e valores indiferentes e sinérgicos (ICIF ≤0,5) para cepas de E. faecalis. Sobre biofilme as duas combinações apresentaram reduções estatisticamente significantes do grupo controle negativo (p < 0,05). Dessa forma concluiu-se que a combinação dos extratos de S. officinalis e G. glabra possui feito sinérgico antimicrobiano contra E. faecalis e atividade antibiofilme contra E. faecalis e E. faecium (AU)

The growing search for knowledge of the biological potential present in medicinal plants has stimulated research, especially with regard to the effective antimicrobial potential of plant extracts, however, further studies on the synergistic effects of the combination of these extracts is essential for their greater clinical application. The aim of this study was to evaluate in vitro the synergistic antimicrobial effects of the association of natural extracts of Salvia officinalis (S. officinalis) and Glycyrrhiza glabra (G. glabra). Antimicrobial analysis was performed on three clinical strains of Enterococcus faecalis (E. faecalis), two clinical strains of Enterococcus faecium (E. faecium) and one standard strain of each species. The Minimum Inhibitory Concentration (MIC) and Minimum Microbicidal Concentration (MMC) were determined by microdilution in broth with seeding, and Fractional Inhibitory Concentration Index by the checkerboard technique. To evaluate the combined effect of extracts on biofilm, two combinations of extracts on biofilm formed by E. faecalis and on biofilm formed by E. faecium were used, for two different periods: 5 min and 24 h, and the mean values of units were evaluated. colony forming agents per milliliter (CFU/mL). Statistical analysis was performed using the ANOVA method and Tukey's or Kruskall-Wallis and Dunn's test (5% significance). The extracts of S. officinalis and G. glabra showed microbicidal concentration for the strains evaluated. The combination of extracts showed indifferent values (FICI ˃ 0.5 and ≤ 4) for E. faecium strains, and indifferent and synergistic values FICI ≤0.5) for E. faecalis strains. On biofilm, the two combinations showed statistically significant reductions compared to the negative control group (p < 0.05). Thus, it is concluded that the combination of extracts of S. officinalis and G. glabra has synergistic antimicrobial effect against E. faecalis and antibiofilm activity against E. faecalis and E. faecium (AU)

Padrão prescritivo de medicamentos para hipertensão arterial sistêmica na atenção primária em saúde: revisão sistemática e meta-análise / Pattern prescription drugs for systemic hypertension in primary health care: systematic review and meta-analysis

Investigamos publicações científicas sobre o padrão prescritivo de medicamentos para hipertensão arterial sistêmica e uso de diretrizes na atenção primária em saúde por revisão sistemática e meta-análise. Os artigos foram selecionados nas bases de dados PubMed, Web of Science e LILACS, de acordo com as declarações PRISMA, de 2004 a 2020. A revisão sistemática mostrou um padrão de prescrição superior para terapia combinada (52,9%). A metanálise confirmou a superioridade para a terapia combinada (OR 1,76; IC 1,29 - 2,41). Foi observada maior prevalência de monoterapia no estudo Sueco (98%) e terapia combinada no Nigeriano (98%). Maior frequência prescritiva de inibidores da enzima de conversão da angiotensina em Trinidade (64%); diuréticos (64%), betabloqueadores (63%) e bloqueadores dos canais de cálcio (53%) na Nigéria; e bloqueadores dos receptores da angiotensina (43%) em Portugal. Quanto ao uso das diretrizes, 53% dos estudos relataram a sua utilização na prescrição de anti-hipertensivos na atenção primária em saúde.

We investigated scientific publications on the prescription pattern of systemic hypertension drugs and use of guidelines in primary health care by systematic review and meta-analysis. Articles were selected in the PubMed, Web of Science and LILACS databases, according to the PRISMA statements, from 2004 to 2020. The systematic review showed a higher prescription pattern for combination therapy (52,9%). The meta-analysis confirmed the superiority of prescription for combination therapy (OR 1.76, CI 1.29 - 2.41). Was observed higher monotherapy prevalence in the Swedish study (98%) and combined therapy in Nigerian (98%). Higher frequency prescriptive of angiotensin-converting enzyme inhibitors in Trinidad (64%); diuretics (64%), beta blockers (63%), and calcium channel blockers (53%) in Nigeria; and angiotensin-receptor blockers (43%) in Portugal. Regarding the use of guidelines, 50% the studies reported their use for the prescription of antihypertensive in primary health care.

Bond strength of cemented fiber posts to teeth with simulated internal root resorption.

BACKGROUND: Teeth with internal root resorption (IRR) have guarded prognosis, considering that IRR defect could influence on the post bond strength. The aim of this study was to evaluate the bond strength and the bond interface between different glass fiber-reinforced posts (FRP) after cementation in teeth with simulated internal root resorption (IRR). MATERIAL AND METHODS: Forty-five (45) human premolar roots with simulated IRR were embedded in acrylic resin blocks and cross-sectioned into two segments, enabling them to be re-approximated by screws. Intracanal medication was inserted for 15-days, removed by passive ultrasonic irrigation (PUI) and examined by stereomicroscopy. The push-out bond strength of two fiber reinforced composite posts (Rebilda Post - RP) and Rebilda Post GT - GT, (VOCO) were evaluated at the cervical and IRR regions (n = 20). And, the bonded interface between resin cement and root dentine was analysed by scanning electron microscopy (SEM). RESULTS: 62.5% of IRR were not completely cleaned by PUI. Bond strength values at the cervical region (9.8 and 14.6 MPa) were higher than the IRR region (6.3 and 4.2 MPa). Micrographies showed bubbles in the cement and spaces in the bonded interface. CONCLUSIONS: RP post showed better bond strength at the cervical region while GT had better bond strength at the IRR region. Key words:Endodontics, root canal filling materials, root resorption, X-Ray microtomography.

Minimum Bactericidal Concentration Techniques in Mycobacterium tuberculosis: A Systematic Review.

Minimum bactericidal concentration (MBC) assay is an accepted parameter for evaluating new antimicrobial agents, and it is frequently used as a research tool to provide a prediction of bacterial eradication. To the best of our knowledge, there is no standardization among researchers regarding the technique used to detect a drug's MBC in Mycobacterium tuberculosis. Thus, the aim of this systematic review is to discuss the available literature in determining a drug's MBC in M. tuberculosis, to find the most commonly used technique and standardize the process. A broad and rigorous literature search of three electronic databases (PubMed, Web of Knowledge, and LILACS) was performed according to the PRISMA statement. We considered studies that were published from January 1, 1990 to February 19, 2019. Google Scholar was also searched to increase the number of publications. We searched for articles using the MeSH terms "microbiological techniques," "Mycobacterium," "antibacterial agents." In addition, free terms were used in the search. The search yielded 6,674 publications. After filter application, 5,348 publications remained. Of these, we evaluated the full text of 187 publications. By applying the inclusion criteria, 69 studies were included in the present systematic review. In the literature analyzed, a great variety in the techniques used to determine a drug's MBC in M. tuberculosis was observed. The most common variability is related to the culture media used, culture incubation time, and the percentage of bacterial death for the drug to be considered as bactericidal. The most commonly used technique for drug's MBC determination was carried out using the drug's minimum inhibitory concentration (MIC) assay. Aliquots from prior MIC values were subcultured in Middlebrook agar and incubated for 4 weeks at 35°C for determining the colony forming unit (CFU) with relevance to detect 99.9% bacilli killed or reduction in 3 log10 viable bacilli.

The impact of KIR/HLA genes on the risk of developing multibacillary leprosy.

BACKGROUND: Killer-cell immunoglobulin-like receptors (KIRs) are a group of regulatory molecules able to activate or inhibit natural killer cells upon interaction with human leukocyte antigen (HLA) class I molecules. Combinations of KIR and HLA may contribute to the occurrence of different immunological and clinical responses to infectious diseases. Leprosy is a chronic neglected disease, both disabling and disfiguring, caused mainly by Mycobacterium leprae. In this case-control study, we examined the influence of KIRs and HLA ligands on the development of multibacillary leprosy. METHODOLOGY/PRINCIPAL FINDINGS: Genotyping of KIR and HLA genes was performed in 264 multibacillary leprosy patients and 518 healthy unrelated controls (238 healthy household contacts and 280 healthy subjects). These are unprecedented results in which KIR2DL2/KIR2DL2/C1/C2 and KIR2DL3/2DL3/C1/C1 indicated a risk for developing lepromatous and borderline leprosy, respectively. Concerning to 3DL2/A3/A11+, our study demonstrated that independent of control group (contacts or healthy subjects), this KIR receptor and its ligand act as a risk factor for the borderline clinical form. CONCLUSIONS/SIGNIFICANCE: Our finding suggests that synergetic associations of activating and inhibitory KIR genes may alter the balance between these receptors and thus interfere in the progression of multibacillary leprosy.

Association of TNF, IL12, and IL23 gene polymorphisms and psoriatic arthritis: meta-analysis.

BACKGROUND: Psoriatic arthritis (PsA) is a chronic skin and joint condition that considerably affects patient quality of life. Several studies have demonstrated different associations of genetic polymorphisms in the pathogenic process of PsA. Therefore, we conducted a meta-analysis to estimate the effect of polymorphisms in the cytokines TNF, IL12B, IL23A, and IL23R on PsA risk. METHODS: We screened 1,097 abstracts and identified 14 relevant studies published between January 2007 and December 2017. A systematic search was conducted in PubMed, Web of Knowledge and Scopus databases. Meta-analyses were performed for the comparisons of alleles and multiple genetic models. RESULTS: Among the cytokines studied, we found 17 polymorphisms that were the most investigated. The association to PsA was observed in the presence of polymorphisms: TNF-238 G > A (rs361525), -308 G > A (rs1800629), and -857 C > T (rs1799724); IL12B C > G (rs6887695) and A > C (rs3212227); IL23A A > G (rs2066808) and IL23R G > A (rs11209026). CONCLUSION: Our findings suggest that these variant cytokine genes may strongly influence the immunological response of PsA.

Resistência à fratura de dentes fragilizados utilizando reforço intra-radicular com pino de fibra de vidro: Rebilda Post e Rebilda Post GT / Fracture resistance in fragile teeth using root reinforcements with glass fiber posts: Rebilda Post and Rebilda Post GT

O objetivo deste trabalho foi avaliar, in vitro, pelo teste de compressão, a resistência à fratura de dentes fragilizados que receberam como reforço intra-radicular sistema de pino de fibra de vidro. Foram utilizados 80 dentes bovinos divididos de acordo com o tipo de reforço intra-radicular e com a presença ou não de preparos para simular fragilidade radicular (n=10): SF/SR - sem fragilização e sem reforço intra- radicular; F/SR - com fragilização e sem reforço intra-radicular; SF/GT - sem fragilização e com reforço intra-radicular Rebilda Post GT; F/GT ­ com fragilização e com reforço intraradicular Rebilda Post GT; SF/RP - sem fragilização e com reforço intra-radicular Rebilda Post; F/RP ­ com fragilização e com reforço intra-radicular Rebilda Post; SF/GT+RP - sem fragilização e com reforço intra-radicular Rebilda Post GT + Rebilda Post; e F/GT+RP ­ com fragilização e com reforço intra-radicular Rebilda Post GT + Rebilda Post. Todos os espécimes tiveram suas coroas seccionadas, comprimento radicular padronizado em 16 mm e canais radiculares preparados endodonticamente. Para os espécimes com fragilização simulada, o desgaste radicular foi realizado até 9 mm no interior do canal e a espessura do remanescente radicular obtida foi de aproximadamente 2 mm. Exceto para o SF/SR, todos os canais radiculares foram obturados. O material obturador foi removido dos terços cervical e médio, permanecendo apenas 4 mm no terço apical. A cimentação dos pinos foi realizada seguindo o protocolo do fabricante. Apenas para os espécimes dos grupos SF/GT+RP e F/GT+RP, após a inserção do pino Rebilda Post GT e antes da polimerização final, foi inserido no centro do conjunto o pino Rebilda Post. Os espécimes foram submetidos ao teste de compressão à 45º. Os valores de resistência à fratura encontrados para os grupos, em ordem decrescente, foram: F/SR ­ 5,045 kgf, SF/SR ­ 9,157 kgf, SF/GT ­ 14,032 kgf, F/RP ­ 27,727 kgf, F/GT ­ 28,303 kgf, SF/RP ­ 29,986 kgf, F/GT+RP ­ 38,650 kgf e SF/GT+RP ­ 39,783 kgf. Os resultados obtidos foram submetidos à análise estatística (ANOVA e Tukey) que demonstrou diferença estatisticamente significativa (p<0,05). Dessa forma observouse que o pino único, Rebilda Post, proporcionou maior resistência à fratura que o sistema Rebilda Post GT e os grupos sem reforço intra-radicular, SF/SR e F/SR; e que a associação dos sistemas produziu os maiores valores de resistência à fratura do que os demais(AU)

The objective of this work was to evaluate, in vitro, by the compression test, the fracture strength of fragile teeth that received a fiberglass pin system as intra- radicular reinforcement. It was used 80 bovine teeth divided according to the type of intraradicular reinforcement and with the presence or not of preparations to simulate root fragility (n = 10): SF / SR - without embrittlement and without intra-radicular reinforcement; F / SR - with embrittlement and without intra-radicular reinforcement; SF / GT - without embrittlement and with intra-radicular reinforcement Rebilda Post GT; F / GT - with embrittlement and intra-radicular reinforcement Rebilda Post GT; SF / RP - without embrittlement and with intra-radicular reinforcement Rebilda Post; F / RP - with embrittlement and intra-radicular reinforcement Rebilda Post; SF / GT + RP - without embrittlement and with intra-radicular reinforcement Rebilda Post GT + Rebilda Post; and F / GT + RP - with embrittlement and with intra-radicular reinforcement Rebilda Post GT + Rebilda Post. All specimens had their crowns sectioned, root length standardized at 16 mm and root canals prepared endodontically. For specimens with simulated embrittlement, root wear was performed up to 9 mm inside the canal and the thickness of the root remainder obtained was approximately 2 mm. Except for SF / SR, all root canals were filled. The obturator material was removed from the cervical and middle thirds, remaining only 4 mm in the apical third. Pin cementation was performed following the manufacturer's protocol. Only for the specimens of the groups SF / GT + RP and F / GT + RP, after the insertion of the Rebilda Post GT pin and before the final polymerization, the Rebilda Post pin was inserted in the center of the set. The specimens were submitted to the 45º compression test. The values of fracture resistance found for the groups, in descending order, were: F / SR - 5,045 kgf, SF / SR - 9,157 kgf, SF / GT - 14,032 kgf, F / RP - 27,727 kgf, F / GT - 28,303 kgf, SF / RP-29.986 kgf, F / GT + RP-38.650 kgf and SF / GT + RP-39.783 kgf. The results were submitted to statistical analysis (ANOVA and Tukey), which showed a statistically significant difference (p< 0,05). In this way, it was observed that the single post, Rebilda Post, provided greater resistance to fracture than the Rebilda Post GT system and the non-reinforced groups, SF / SR and F / SR; and that the association of the systems produced the highest values of fracture resistance than the others(AU)

Pregnancy Complications Associated With Maternal Hypothyroidism: A Systematic Review.

IMPORTANCE: Hypothyroidism is one of the most prevalent diseases in pregnancy, but there is no consensus about its management in pregnant women. OBJECTIVE: In this systematic review, we evaluated the association between pregnancy complications and treated or untreated maternal hypothyroidism. EVIDENCE ACQUISITION: PubMed and reference lists were searched for the Medical Subject Headings terms "pregnancy complications" and "hypothyroidism." The eligibility criteria for inclusion in the study were an original study published between 2002 and 2013. Six reviewers independently selected the studies, and 3 extracted the data. Two reviewers assessed the risk of bias and quality of the studies. RESULTS: Eighteen studies were included in the systematic review. The most prevalent complications associated with maternal hypothyroidism were abortion, intrauterine fetal death, preterm delivery, and preeclampsia. The pregnancy outcome depended on the treatment that was received by the patient. CONCLUSIONS: Strong evidence indicates that maternal hypothyroidism is associated with maternal-fetal complications, but no consensus was found among the studies reviewed herein. The dose of levothyroxine that is required to maintain euthyroidism is still questioned, but studies have suggested that levothyroxine should be adjusted according to the gestational period and laboratory profile.

Antiphospholipid syndrome and recurrent miscarriage: A systematic review and meta-analysis.

Antiphospholipid syndrome (APS) is an autoimmune condition that is associated with thrombosis and morbidity in pregnancy. The exact mechanisms by which these associations occur appear to be heterogeneous and are not yet well understood. The aim of this study was to identify and analyze publications in recent years to better understand the diagnosis and its contribution to monitoring APS among women with recurrent miscarriage (RM). This systematic review and meta-analysis was conducted using the PubMed and Web of Knowledge databases, with articles published between 2010 and 2014, according to the PRISMA statement. Of the 85 identified studies, nine were selected. Most of the studies reported an association between recurrent miscarriage and specific antiphospholipid antibodies, as anticardiolipin antibodies (aCL), lupus anticoagulant (LA), anti-ß2-glycoprotein I antibodies (aß2GPI) and antiphosphatidylserine (aPS), which showed a relationship with RM. The main result of the meta-analysis revealed association between antiphospholipid antibodies (aPLs) and/or APS compared to the patients with RM (OR: 0.279; 95% CI: 0.212-0.366) and APS cases compared to the patients with RM (OR: 0.083; 95% CI: 0.036-0.189). High heterogeneity among these studies (I2=100.0%, p <0.001) was observed. In addition, there was no significant publication bias across studies according to Begg's test (p=0.230), although Egger's test (p=0.037) suggests significant publication bias. The funnel plot was slightly asymmetrical. Systematic review and meta-analysis demonstrated a positive association between antiphospholipid antibodies and/or antiphospholipid syndrome in patients with recurrent miscarriage.

Simvastatin and artesunate impact the structural organization of adult Schistosoma mansoni in hypercholesterolemic mice.

Experimental data have shown that simvastatin and artesunate possess activity against Schistosoma mansoni worms in mice fed standard chow. However, little is known regarding the roles of these drugs in mice fed high-fat chow. We have extended past studies by measuring the effects of these drugs on the structural organization of adult schistosomes in hypercholesterolemic mice. For this purpose, mice were gavaged with either simvastatin or artesunate at nine weeks post-infection and were euthanized by cervical dislocation at two weeks post-treatment. Adult worms were then collected and examined by conventional light microscopy, morphometry and confocal laser scanning microscopy. Plasma total cholesterol and worm reduction rates were significantly increased in mice fed high-fat chow compared with their respective control groups. Simvastatin and artesunate caused changes in the tegument, tubercles, and reproductive system (testicular lobes, vitelline glands and ovarian cells), particularly when administered to mice fed high-fat chow. In particular, the tegument and tubercles were significantly thinner in artesunate-treated worms in mice fed high-fat chow compared with mice fed standard chow. This study thus demonstrated that simvastatin and artesunate have several novel effects on the structural organization of adult worms. Together, these results show, for the first time, that simvastatin and artesunate display antischistosomal activity in hypercholesterolemic mice.