Antibacterial and immunological properties of piperine evidenced by preclinical studies: a systematic review.

Aim: To review in vitro, in vivo, and in silico studies examining the antibacterial and immunomodulatory properties of piperine (PPN). Methods: This systematic review followed PRISMA guidelines, and five databases were searched. Results: A total of 40 articles were included in this study. Six aspects of PPN activity were identified, including antibacterial spectrum, association with antibiotics, efflux pump inhibition, biofilm effects, protein target binding, and modulation of immune functions/virulence factors. Most studies focused on Mycobacterium spp. and Staphylococcus aureus. Cell lineages and in vivo models were employed to study PPN antibacterial effects. Conclusion: We highlight PPN as a potential adjuvant in the treatment of bacterial infections. PPN possesses several antibacterial properties that need further exploration to determine the mechanisms behind its pharmacological activity.

Prevalence of ictal injuries in functional (psychogenic nonepileptic) seizures: A systematic review and meta-analysis.

OBJECTIVE: Ictal injuries have long been considered typical signs of epileptic seizures. However, studies have shown that patients with functional seizures (FS)-also named psychogenic nonepileptic seizures-can also present these signs, misleading physicians and delaying a correct diagnosis. This systematic review aimed to assess the prevalence of injuries from FS. METHODS: A literature search was performed in PubMed, Embase, LILACS (Latin American and Caribbean Health Sciences Literature), Scopus, Web of Science, PsycINFO, Google Scholar, OpenGrey, and ProQuest. Observational studies were included. The risk of bias was assessed using the Joanna Briggs Institute (JBI) checklist for studies reporting prevalence data. RStudio was used for meta-analyses. Cumulative evidence was evaluated according to Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria. RESULTS: From the 2607 identified records, 41 studies were included in the qualitative synthesis, and 28 were included in meta-analyses. A meta-analysis of 13 studies, including 1673 individuals, resulted in an overall lifetime prevalence of injuries due to FS per person of 25% (95% confidence interval [CI] = 19%-32%, I2 = 88%). Considering a limited period (video-electroencephalographic [VEEG] monitoring days), a meta-analysis of 13 studies, including 848 individuals, resulted in an injury prevalence due to FS per person of .7% (95% CI = 0%-3%, I2 = 73%). Also, a meta-analysis of eight studies, including 1000 individuals, resulted in a prevalence of injuries per FS of .1% (95% CI = 0%-.98%, I2 = 49%). The certainty in cumulative evidence assessed by GRADE was rated "very low" for lifetime prevalence of injuries per person, "low" for prevalence per person during VEEG monitoring, and "moderate" for prevalence per number of FS. SIGNIFICANCE: Overall pooled lifetime prevalence of injuries due to FS per person was 25%. In comparison, the prevalence of injuries per person during VEEG monitoring and per functional seizure was .7% and .1%, respectively. [Correction added on 07 October 2023, after first online publication: In the preceding sentence, 'consecutively' was corrected to 'respectively'.] The evidence of the occurrence of injuries due to FS breaks the paradigm that epileptic seizures can cause injuries but FS cannot.

Inflammatory biomarkers on an LPS-induced RAW 264.7 cell model: a systematic review and meta-analysis.

INTRODUCTION: Several experimental models have been designed to promote the development of new anti-inflammatory drugs. The in vitro model using RAW 264.7 cells has been widely used. However, there is still no consensus on which inflammatory mediators should initially be measured to screen for possible anti-inflammatory effects. To determine the rationality of measuring inflammatory mediators together with NO, such as the levels of tumor necrosis factor (TNF)-α, and interleukins (IL) 1ß and 6, we carried out this systematic review (SR) and meta-analysis (MA). METHODOLOGY: We conducted this SR and MA in accordance with the Preferred Reporting of Systematic Reviews and Meta-Analysis and the Cochrane Handbook for Systematic Reviews of Intervention. This review was registered in the Open Science Framework ( https://doi.org/10.17605/OSF.IO/8C3HT ). RESULTS: LPS-induced cells produced high NO levels compared to non-LPS induced, and this production was not related to cell density. TNF-α, IL-1ß, and IL-6, also showed high levels after cells had been stimulated with LPS. Though with some restrictions, all studies were reliable, as the risk of bias was detected in the test compounds and systems. CONCLUSION: Measurement of NO levels may be sufficient to screen for possible anti-inflammatory action in the context of LPS-induced RAW 264.7 cells.

A standardized intraperitoneal Glucantime™ for experimental treatment of cutaneous leishmaniasis caused by Leishmania amazonensis in BALB/c mice.

Glucantime™ is the pentavalent antimony (Sb+5) recommended as the first choice for treating cutaneous leishmaniasis (CL). It has been used as treatment control in animal studies to investigate new anti-Leishmania compounds. However, these studies have a range of Glucantime™ doses, different treatment times and routes of administration, and differing results. Our goal was to standardize intraperitoneal Glucantime™ treatment for CL in BALB/c mice infected with L. amazonensis. BALB/c mice were divided into six groups, with eight animals per group. The animals were infected with L. amazonensis and intraperitoneally treated with different doses of Sb+5 (20, 100 and 200 mg/kg/day) for 30 consecutive days. Healthy animals were used as negative infection and treatment control. Infected and untreated animals were used as positive infection control. Animals infected and treated with Ampho B were used as treatment control. Biochemical and histological analysis was performed to assess renal and liver toxicity. The parasite load in the popliteal lymph node, spleen and liver was determined by limiting dilution. Histological and collagen fiber analyses were performed on the lesions. Animals treated with Sb+5 100 and 200 mg/kg/day showed a decreased paw measurements, associated with a reduction in the parasite load, with a clinical cure rate of 50% and 37.5%, respectively. These groups of animals also showed tissue regeneration and reduced inflammation. Animals treated with 100 mg/kg/day had collagen fiber parameters similar to those of the negative infection control. There were no biochemical signs of renal or liver toxicity in any of the groups. We found that Sb+5 100 mg/kg/day was the lowest dose that showed effectiveness in treating CL in mice, and it may be a good model of treatment control in studies evaluating new treatments for CL in BALB/c mice.

The anti-Leishmania potential of bioactive compounds derived from naphthoquinones and their possible applications. A systematic review of animal studies.

Leishmaniasis affects millions of people worldwide, and available treatments have severe limitations. Natural and derivative products are significant sources of innovative therapeutic agents. Naphthoquinones are natural or synthetic chemical compounds with broad biological activity. This systematic review aimed to evaluate the potential anti-Leishmania activity of bioactive compounds derived from naphthoquinones in animal models. Conducted in accordance with PRISMA guidelines, two blocks of MeSH terms were assembled: group I, Leishmania OR Leishmaniasis; group II, Atovaquone OR Lapachol OR Beta lapachone OR Naphthoquinones. The search was performed on PubMed, Web of Science, SCOPUS, EMBASE, and Lilacs databases. Twenty-four articles were retrieved and submitted for quality assessment using the SYRCLE critical appraisal tool. The in vivo anti-Leishmania potential of naphthoquinones was evaluated in visceral and cutaneous leishmaniasis using several measurement parameters. Analyzed compounds varied in structure, association with reference drugs, and encapsulation using a drug delivery system. The study design, including treatment protocol, differed between studies. The findings of the studies in this systematic review indicate the anti-Leishmania potential of naphthoquinones in vivo, with different treatment regimens directed against different Leishmania species. The employed drug delivery systems improve the results concerning selectivity, distribution, and required therapeutic dose. The immunomodulatory action was shown to be beneficial to the host, favoring an adequate immune response against infection by Leishmania parasites since it favored Th1 responses. All studies presented a moderate to high risk of bias. These findings suggest that more studies are needed to assess the overall effectiveness and safety of these treatments.

Evidence of Lactobacillus reuteri to reduce colic in breastfed babies: Systematic review and meta-analysis.

OBJECTIVE: To investigate evidence for the treatment of childhood colic by supplementing Lactobacillus reuteri in infants breastfed with breast milk. METHODS: The study was conducted according to the PRISMA protocol. The databases used for acquiring data were PubMed and Web of Science, applying MeSH terms and free terms. Meta-analysis was conducted using Stata ™ 12.0. The risk of bias was evaluated by the Review Manager (RevMan) 5.3 tool, and the strength of evidence was assessed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: Ten clinical trials were included in the review. The administration of L. reuteri (DSM 17938 or ATCC55730) was tested in infants (n = 248) versus the control/placebo group (n = 229). Eight articles were included in the meta-analysis. There was a significant response in reducing crying time (minutes/day) and treatment effectiveness (reduction ≥ 50% in average daily crying time) in the first week (p = 0.001 and p = 0.003, respectively). These results were similar in the second, third weeks (p < 0.001 for both outcomes) and fourth weeks (p<0.001 and p = 0.002, respectively). The risk of bias was low for the majority of the studies. Confidence in evidence was considered very low for crying time and low for effectiveness treatment. CONCLUSIONS: The evidence shows that the administration of Lactobacillus reuteri to babies fed with breast milk reduces the crying time in babies diagnosed with colic. But our confidence in the effect estimate is limited.

In vivo efficacy of meglumine antimoniate-loaded nanoparticles for cutaneous leishmaniasis: a systematic review.

Background: Nanotechnology is a promising strategy to improve existing antileishmanial agents. Objective: To explore the evidence of encapsulated meglumine antimoniate for cutaneous leishmaniasis treatment in animal models. Materials & methods: The studies were recovered from PubMed, Scopus, EMBASE, LILACS, WoS and Google according to eligibility criteria following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the Population, Intervention, Comparison, Outcomes and Study design (PICOS) strategy. Study appraisal was assessed using the Animal Research Reporting of In Vivo Experiments, SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) and Grading of Recommendations Assessment, Development and Evaluation (GRADE) recommendations. Results: Five studies were included. Liposomes, metallic and polymeric nanoparticles were tested in BALB/c mice against Leishmania major, L. tropica or L. amazonensis. Limitations: Few studies were found to meet the eligibility criteria. Conclusion: All formulations had a significant efficacy, similar to the meglumine antimoniate reference treatment concerning the lesion size and parasite burden. The studies had a high and moderate risk of bias, and the confidence in cumulative evidence was considered low. Therefore, we encourage the development of high-quality preclinical studies. Registration: PROSPERO register CRD42020170191.

Genetic variations in the human immune system influence susceptibility to tegumentary leishmaniasis: a systematic review and meta-analysis.

OBJECTIVES: The outcomes of tegumentary leishmaniasis (TL) rely on a complex interaction between the host immune system and the parasite. This study assessed the influence of polymorphisms in immune-related genes on TL. METHODS: Web of Science, Scopus, PubMed, and Embase databases were searched systemically. The meta-analysis used a retrospective model in examining alleles, heterozygotes, and homozygotes. A quality assessment and an analysis of cumulative evidence were performed. RESULTS: A total of 29 genes (encoding for cytokines, chemokines, and other immune receptors) and 84 polymorphisms were analyzed. The IL-1ß_rs16944 (OR = 1.341, p = 0.003), TNF-α_rs1800629 (OR = 3.804, p = 0.004), MIF_rs755622 (OR = 3.357, p = 0.001), and INF- γ_rs243056 (OR = 1.670, p = 0.028) polymorphisms were speculated as risk factor for TL. They decrease the expression of the corresponding genes crucial for TL control. The quality assessment score was approximately 50%, suggesting the need for a clear method and polymorphism characterization for further comparison. The relevant risk of bias and other considerations resulted in low and moderate cumulative evidence confidence. CONCLUSIONS: IL-1ß_rs16944, TNF-α_rs1800629, MIF_rs755622, and INF-γ_rs2430561 polymorphisms were speculated as risk factor for TL, corroborating that IL-1ß, TNF-α, INF-γ, and MIF are involved in the TL pathogenesis.

Screening of six medicinal plant species for antileishmanial activity.

This study is aimed to investigate the in vitro anti-leishmanial activity of ethanolic, aqueous or dichloromethane extracts of leaves, flowers, fruits or roots, of six medicinal plant species, namely, Nectandra megapotamica, Brunfelsia uniflora, Myrcianthes pungens, Anona muricata, Hymenaea stigonocarpa and Piper corcovandesis. After isolation and analysis of chemical components by ultra-high performance liquid chromatography-high-resolution tandem mass spectrometry (UHPLC-HRMS/MS), the extracts were also tested for toxicity in J774.A1 macrophages and human erythrocytes. Phenolic acids, flavonoids, acetogenins, alkaloids and lignans were identified in these extracts. Grow inhibition of promastigotes forms of Leishmania amazonensis and Leishmania braziliensis and the cytotoxicity in J774.A1 macrophages were estimated by the XTT method. The most promising results for L. amazonensis and L. braziliensis were shown by the ethanolic extract of the fruits of Hymenaea stigonocarpa and dichloromethane extract of the roots of Piper corcovadensis, with IC 50 of 160 and 150 µg mL-1, resp. Ethanolic extracts of A. muricata (leaf), B. uniflora (flower and leaf), M. pungens (fruit and leaf), N. megapotamica (leaf), and aqueous extract of H. stigonocarpa (fruit) showed IC 50 > 170 µg mL-1 for L. amazonensis and > 200 µg mL-1 for L. braziliensis. The extracts exhibited low cytotoxicity towards J774.A1 macrophages with CC 50 > 1000 µg mL-1 and hemolytic activity from 0 to 46.1 %.

Campomanesia xanthocarpa (Mart.) O. Berg essential oil induces antileishmanial activity and remodeling of the cytoplasm organelles.

Leishmaniasis is a neglected disease that affects millions of people worldwide. This study aimed to analyze antileishmanial activity of Campomanesia xanthocarpa leaf essential oil (EO) on promastigote and amastigote forms of Leishmania amazonensis, cytotoxicity in murine macrophages and sheep erythrocytes. The essential oil (EO) was analyzed by gas chromatography/mass spectrophotometry. The main and most abundant compounds were sesquiterpene hydrocarbons (71.22%) such as trans-caryophyllene (7.87%), bicyclogermacrene (11.28%), and δ-cadinene (8.34%). The IC50 for promastigote and amastigote forms of L. amazonensis was 70 µg mL-1 and 6 µg mL-1, respectively. C. xanthocarpa EO was not cytotoxic for murine macrophages (CC50 1860 µg mL-1) and sheep erythrocytes (1.5%), presenting high selectivity index for protozoan (310). C. xanthocarpa EO induced effects on the morphology and ultrastructure of this parasite. The high activity for intracellular amastigote forms, low toxicity to murine macrophages, and erythrocytes, suggest that C. xanthocarpa EO is promising for the treatment of leishmaniasis.

PCR primers designed for new world Leishmania: A systematic review.

Studies of the primers that were designed to detect New World Leishmania were systematically reviewed to report the characteristics of each target, detection limit, specificity of the primers designed and diagnostic sensibility. The papers identified in the databases PubMed and Web of Science involved 50 studies. Minicircle is the most applied target in molecular research for diagnosis, due to its high sensitivity in detecting Leishmania in different clinical samples, a characteristic that can be partially attributed to the higher number of copies of the minicircle per cell. The other molecular targets shown in this review were less sensitive to diagnostic use because of the lower number of copies of the target gene per cell, but more specific for identification of the subgenus and/or species. The choice of the best target is an important step towards the result of the research. The target allows the design of primers that are specific to the genus, subgenus or a particular species and also imparts sensitivity to the method for diagnosis. The findings of this systematic review provide the advantages and disadvantages of the main molecular targets and primers designed for New World Leishmania, offering information so that the researcher can choose the PCR system best suited to their research need. This is a timely and extremely thorough review of the primers designed for New World Leishmania.

6,7-Dehydroroyleanone diterpene derived from Tetradenia riparia essential oil modulates IL-4/IL-12 release by macrophages that are infected with Leishmania amazonensis.

The treatment of cutaneous leishmaniasis in associated with several adverse effects and therapeutic failure, resulting in patients' abandonment of treatment. Research on new drugs with leishmanicidal potential from medicinal plants is essential. The anti-Leishmania activity of Tetradenia riparia essential oil (TrEO) and its derivatives, such as the diterpene 6,7-dehydroroyleanone (TrROY), and the immunomodulatory effects of TrEO have been reported. However, few studies have investigated the effects of TrROY. The present study evaluated the modulation of cytokine production by murine macrophages that were infected with Leishmania amazonensis (6 parasites/macrophage) and treated with TrROY (0.1, 1, and 100 µg/ml). Cytokine levels were measured by flow cytometry. The results were analyzed using Student's t test at a 95% confidence interval. Microscopic counting was performed to evaluate the inhibitory effects of TrROY on intracellular infection. TrROY modulated the production of cytokines that are essential for the immune defense response to Leishmania, with a decrease in interleukin-4 (IL-4) levels and an increase in IL-12 levels. A TrROY concentration of 0.1 µg/ml was chosen for the subsequent experiments. This dose was chosen because it modulated IL-4/IL-12 release by murine macrophages that were infected with Leishmania and because it presented no cytotoxic effects. TrROY (0.1 µg/ml) induced a 31% reduction of the rate of infection in murine macrophages compared with untreated cells. TrROY may be a promising leishmanicidal agent. Further in vitro and in vivo studies should be conducted to evaluate the anti-Leishmania and immunomodulatory activity of TrROY.

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.

The role of metalloproteases in Leishmania species infection in the New World: a systematic review.

This is a systematic review on the role of metalloproteases in the pathogenicity of the American tegumentary leishmaniasis (ATL) caused by New World Leishmania species. The review followed the PRISMA method, searching for articles in PubMed, EMBASE, LILACS and ISI Web of Science, by employing the following terms: 'leishmaniasis', 'cutaneous leishmaniasis', 'mucocutaneous leishmaniasis', 'diffuse cutaneous leishmaniasis', 'Leishmania' and 'metalloproteases'. GP63 of New World Leishmania species is a parasite metalloproteases involved in the degradation and cleavage of many biological molecules as kappa-B nuclear factor, fibronectin, tyrosine phosphatases. GP63 is capable of inhibiting the activity of the complement system and reduces the host's immune functions, allowing the survival of the parasite and its dissemination. High serological/tissue levels of host matrix metalloproteases (MMP)-9 have been associated with tissue damage during the infection, while high transcriptional levels of MMP-2 related with a satisfactory response to treatment. Host MMPs serological and tissue levels have been investigated using Western Blot, zymography, and Real Time polymerase chain reaction. GP63 detection characterizes species and virulence in promastigotes isolated from lesions samples using techniques mentioned previously. The monitoring of host MMPs levels and GP63 in Leishmania isolated from host samples could be used on the laboratory routine to predict the prognostic and treatment efficacy of ATL.

Contribution of photodynamic therapy in wound healing: A systematic review.

OBJECTIVE: We researched articles that used photodynamic therapy (PDT) for skin wound healing in humans. METHODS: The systematic review was conducted through scientific articles that investigated the action of PDT on wound healing in humans, published from July 2005 to March 2017, in the data bases PubMed and LILACS. RESULTS: The main types of wound described in selected articles in this review were chronic ulcer and non-melanoma skin cancer. For accomplishing the PDT, second generation of photosensitizing agents with laser or light emitting diode were used. The studies demonstrated that PDT contribute in several ways to the wound healing process: leading to cellular death; reducing or increasing inflammation; stimulating fibroblasts proliferation and, consequently, of collagen and elastin; raising transforming growth factor beta and metalloproteinases. Based on this, PDT provided good results in wound healing process, acting in several steps and accelerating tissue repair. CONCLUSIONS: PDT improved healing in many wound models in humans, revealing itself as a promising therapeutic modality for stimulating wound healing and remodelling.

Pentavalent Antimonials Combined with Other Therapeutic Alternatives for the Treatment of Cutaneous and Mucocutaneous Leishmaniasis: A Systematic Review.

The first choice drugs for the treatment of cutaneous and mucocutaneous leishmaniasis are pentavalent antimonials, sodium stibogluconate, or meglumine antimoniate. However, the treatment with these drugs is expensive, can cause serious adverse effects, and is not always effective. The combination of two drugs by different routes or the combination of an alternative therapy with systemic therapy can increase the efficacy and decrease the collateral effects caused by the reference drugs. In this systematic review we investigated publications that described a combination of nonconventional treatment for cutaneous and mucocutaneous with pentavalent antimonials. A literature review was performed in the databases Web of Knowledge and PubMed in the period from 01st of December 2004 to 01st of June 2017, according to Prisma statement. Only clinical trials involving the treatment for cutaneous or mucocutaneous leishmaniasis, in English, and with available abstract were added. Other types of publications, such as reviews, case reports, comments to the editor, letters, interviews, guidelines, and errata, were excluded. Sixteen articles were selected and the pentavalent antimonials were administered in combination with pentoxifylline, granulocyte macrophage colony-stimulating factor, imiquimod, intralesional sodium stibogluconate, ketoconazole, silver-containing polyester dressing, lyophilized LEISH-F1 protein, cryotherapy, topical honey, and omeprazole. In general, the combined therapy resulted in high rates of clinical cure and when relapse or recurrence was reported, it was higher in the groups treated with pentavalent antimonials alone. The majority of the articles included in this review showed that cure rate ranged from 70 to 100% in patients treated with the combinations. Serious adverse effects were not observed in patients treated with drugs combination. The combination of other drugs or treatment modalities with pentavalent antimonials has proved to be effective for cutaneous and mucocutaneous leishmaniasis and for most seemed to be safe. However, new randomized, controlled, and multicentric clinical trials with more robust samples should be performed, especially the combination with immunomodulators.

Percepção e conscientização de universitários sobre o sistema único de saúde / Perception and conscience-raising of undergraduates on the brazilian health care system

O objetivo desse estudo foi avaliar a percepção dos acadêmicos participantes do Programa de Educação Tutorial (PET) da Universidade Estadual de Maringá (UEM) sobre o Sistema Único de Saúde (SUS) e elucidá-los sobre os serviços disponibilizados pelo sistema, bem como seus direitos e deveres enquanto usuários. Um questionário semiestruturado foi aplicado e simultaneamente desenvolveu-se um processo de conscientização dos acadêmicos sobre a importância e funções do sistema para o Brasil por meio de dinâmicas e debates. Ao final do processo de conscientização, 97,97% dos petianos afirmaram ser usuário do SUS, comparado aos 72,97% que inicialmente declararam fazer uso do sistema. O conhecimento dos acadêmicos do PET-UEM sobre o SUS, embora satisfatório, é ainda limitado e carece de informações a respeito dos direitos e deveres enquanto usuários, sendo influenciado pela perspectiva midiática.

The perception of undergraduates participating in the Program for Tutorial Education (PET) of the State University of Maringá on the Brazilian Health Care System (SUS) was evaluated. The discussion also includes information on services available and on the rights and duties of clients. A half-structured questionnaire was applied and a conscience-raising process was developed with undergraduates on the system´s importance and functions through several discussions and debates. At the end of the process, 97.97% of the participants stated they were SUS clients when compared with 72.97% who initially stated they used the system. Knowledge on SUS by PET-UEM undergraduates, although satisfactory, is still limited and lacks information on clients´ rights and duties, influenced by social media.

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.

Safety and efficacy of current alternatives in the topical treatment of cutaneous leishmaniasis: a systematic review.

Studies of topical treatments for leishmaniasis were systematically reviewed, to evaluate the therapeutic efficacy, safety and any adverse effects of these treatments. The papers identified in the databases PubMed and Web of Knowledge involved eight studies with a total of 1744 patients. The majority of trials was from Iran (4/8), covered a period of 8 years (2003-2011), and included patients 4-85 years of age. The most frequent Leishmania species in the studies were L. tropica (4/8) and L. major (2/8). The treatments administered were thermotherapy, paromomycin and combinations, CO2 laser, 5-aminolevulinic acid hydrochloride (10%) plus visible red light (633 nm) and cryotherapy. Six articles reported cure rates over 80·0%. Six studies reported on failure rates, three of them reporting rates lower than 10%. Four studies did not report relapses or recurrences, while the other studies reported low rates (1·8-6·3%). The most common adverse effects of the topical treatments were redness/erythema, pain, pruritus burning, oedema, vesicles and hyper- or hypopigmentation. The results provide strong evidence that the treatments topical evaluated showed high cure rates, safety and effectiveness, with low side-effects, relapse and recurrence rates, except for cryotherapy, which showed a moderate cure rate.