Antiseptics and disinfectants for the treatment of vaginal discharge in non-pregnant women (Protocol)

Q1Q1Paciente femeninoThis is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the safety and effectiveness of antiseptics and disinfectants for the treatment of vaginal discharge in non‐pregnant women. Description of the condition A normal and healthy vaginal ecosystem is defined by an acidic environment (pH less than 4.5), which is inhospitable for most bacteria and viruses. This acidic environment is associated with the presence of lactobacilli and hydrogen peroxide (H2O2); a decrease of these buffer agents is linked with vaginal infections (Verstraelen 2009). Vaginal discharge syndrome represents a group of vaginal infections that are characterized by abnormal vaginal secretion, irritation, vulvar itching and sometimes vaginal odour (CDC 2017). In most cases, it is diagnosed by clinical signs (Gaitán‐Duarte 2013). The most common vaginal infections with vaginal discharge as the main clinical symptom are: bacterial vaginosis (BV), vulvovaginal candidiasis (VC), and trichomoniasis (TV), which is a sexually transmitted infection (Gaitán‐Duarte 2013; Sherrard 2011). Prevalence varies from 40% for BV, to 12% for VC and less than 1% for trichomoniasis (Angel 2012). Bacterial vaginosis is an infection characterized by a change in the vaginal flora due to the decrease of lactobacilli, an increase in vaginal pH and anaerobic bacteria such as Gardnerella vaginalis, genital mycoplasma, anaerobic Gram‐negative rods, Gram‐positive cocci (Beigi 2004; Petersen 2002; Verstraelen 2012). Symptomatic patients are evidenced by foul‐smelling, profuse vaginal discharge (which is thin, white and homogenous, and coats the walls of the vagina and vestibule) and no signs of vulvar or vaginal inflammation (Verstraelen 2009). BV is not a sexual infection, though it is associated with sexual intercourse (Amaya‐Guio 2016). It can remit spontaneously or it can be persistent or recurrent, especially when the woman engages in vaginal douching or frequent sexual activity (which can cause changes in vaginal pH and lead to the decrease or lack of lactobacilli), or when lactobacilli are attacked by specific viruses and are subsequently unable to recolonize the vagina due to the overgrowth of anaerobic bacteria (Sherrard 2011). Bacterial vaginosis is a significant genital tract infection; published studies have found it to be associated with pelvic inflammatory disease, intrauterine infections, post‐procedural gynaecological infections, and predisposition to an increased risk of sexually transmitted diseases, such as trichomoniasis, gonorrhea, chlamydia and the human immunodeficiency virus (HIV) (Verstraelen 2009). Vulvovaginal candidiasis is caused by an overgrowth of Candida albicans (90%), C. glabrata,C. tropicalis, and other species (Sherrard 2011). This infection has inflammatory symptoms such as edema, erythema, vulvar excoriation, fissure formation, pruritus, superficial dyspareunia, dysuria, irritation, curdy vaginal discharge and soreness (Molteni 2004). Trichomoniasis is the most common non‐viral sexually transmitted infection, caused by an anaerobic protozoan called Trichomonas vaginalis (humans are the only known hosts). The symptoms include dysuria, itching, vulvar irritation, "strawberry" cervix visible to naked eye (2%), and occasionally, abdominal pain and greenish‐yellow, foamy, foul‐smelling vaginal discharge (KIissinger 2015; Jeffery 2017). The diagnosis of VB as the other two infections (VC and TV) in the vaginal discharge syndrome is by manly clinical symptoms. Treatment for vaginal discharge syndrome mainly includes antimicrobials, such as imidazoles (metronidazole or tinidazole) for VB and TV, or used as antifungal agents (clotrimazole or fluconazole) and lincosamines (clindamycin) for VB.Revista Nacional - Indexad

Estado periodontal y microbiota subgingival en mujeres preeclámpticas.

Objetivos: Describir el estado periodontal y la microbiota subgingival de mujeres gestantes con diagnostico de preeclampsia en el Hospital Universitario del Valle (HUV) de Cali-Colombia. Metodología: Participaron 81 mujeres con diagnóstico de preeclampsia, internadas en el Hospital Universitario del Valle, a quienes se les colectaron datos médicos y periodontales tales como profundidad al sondeo, nivel de inserción clínica, índice gingival y periodontal, con el fin de realizar el diagnóstico clínico periodontal teniendo en cuenta los parámetros de la Academia Americana de Periodoncia (AAP 1999); además se tomaron muestras microbiológicas subgingivales para cultivo e identificación de bacterias periodontopatógenas. Resultados: El 63 de la gestantes presentó preeclampsia leve y el 27.2 preeclampsia severa. Un 91.4 (n=74) de las pacientes presentó afección en el estado de salud periodontal dentro del cual el 59.3 (n=48) presentó un diagnóstico de periodontitis crónica y solo el 8.6 de las gestantes presentó un buen estado de salud periodontal. Los microorganismos periodontopáticos más frecuentes en las mujeres con preeclampsia fueron Fusobacterium ssp 80.2 (n=65), Porphyromonas gingivalis 59.3 (n = 48) y Prevotella intermedian/nigrescens 51.9 (n=42). Conclusiones: Se encontró que una alta proporción de las mujeres con preeclampsia tuvo afección en el estado periodontal con predominio de un diagnostico clínico de periodontitis crónica y presencia de una microbiota periodontopática. Solo un bajo porcentaje de las gestantes presentaron un estado de salud periodontal

Methylation-state-specific recognition of histones by the MBT repeat protein L3MBTL2.

The MBT repeat has been recently identified as a key domain capable of methyl-lysine histone recognition. Functional work has pointed to a role for MBT domain-containing proteins in transcriptional repression of developmental control genes such as Hox genes. In this study, L3MBTL2, a human homolog of Drosophila Sfmbt critical for Hox gene silencing, is demonstrated to preferentially recognize lower methylation states of several histone-derived peptides through its fourth MBT repeat. High-resolution crystallographic analysis of the four MBT repeats of this protein reveals its unique asymmetric rhomboid architecture, as well as binding mechanism, which preclude the interaction of the first three MBT repeats with methylated peptides. Structural elucidation of an L3MBTL2-H4K20me1 complex and comparison with other MBT-histone peptide complexes also suggests that an absence of distinct surface contours surrounding the methyl-lysine-binding pocket may underlie the lack of sequence specificity observed for members of this protein family

Characterizing the involvement of FaMADS9 in the regulation of strawberry fruit receptacle development

FaMADS9 is the strawberry (Fragaria x ananassa) gene that exhibits the highest homology to the tomato (Solanum lycopersicum) RIN gene. Transgenic lines were obtained in which FaMADS9 was silenced. The fruits of these lines did not show differences in basic parameters, such as fruit firmness or colour, but exhibited lower Brix values in three of the four independent lines. The gene ontology MapMan category that was most enriched among the differentially expressed genes in the receptacles at the white stage corresponded to the regulation of transcription, including a high percentage of transcription factors and regulatory proteins associated with auxin action. In contrast, the most enriched categories at the red stage were transport, lipid metabolism and cell wall. Metabolomic analysis of the receptacles of the transformed fruits identified significant changes in the content of maltose, galactonic acid-1,4-lactone, proanthocyanidins and flavonols at the green/white stage, while isomaltose, anthocyanins and cuticular wax metabolism were the most affected at the red stage. Among the regulatory genes that were differentially expressed in the transgenic receptacles were several genes previously linked to flavonoid metabolism, such as MYB10, DIV, ZFN1, ZFN2, GT2, and GT5, or associated with the action of hormones, such as abscisic acid, SHP, ASR, GTE7 and SnRK2.7. The inference of a gene regulatory network, based on a dynamic Bayesian approach, among the genes differentially expressed in the transgenic receptacles at the white and red stages, identified the genes KAN1, DIV, ZFN2 and GTE7 as putative targets of FaMADS9. A MADS9-specific CArG box was identified in the promoters of these genes

Genome of the Avirulent Human-Infective Trypanosome—Trypanosoma rangeli

Background: Trypanosoma rangeli is a hemoflagellate protozoan parasite infecting humans and other wild and domestic mammals across Central and South America. It does not cause human disease, but it can be mistaken for the etiologic agent of Chagas disease, Trypanosoma cruzi. We have sequenced the T. rangeli genome to provide new tools for elucidating the distinct and intriguing biology of this species and the key pathways related to interaction with its arthropod and mammalian hosts.  Methodology/Principal Findings: The T. rangeli haploid genome is ,24 Mb in length, and is the smallest and least repetitive trypanosomatid genome sequenced thus far. This parasite genome has shorter subtelomeric sequences compared to those of T. cruzi and T. brucei; displays intraspecific karyotype variability and lacks minichromosomes. Of the predicted 7,613 protein coding sequences, functional annotations could be determined for 2,415, while 5,043 are hypothetical proteins, some with evidence of protein expression. 7,101 genes (93%) are shared with other trypanosomatids that infect humans. An ortholog of the dcl2 gene involved in the T. brucei RNAi pathway was found in T. rangeli, but the RNAi machinery is non-functional since the other genes in this pathway are pseudogenized. T. rangeli is highly susceptible to oxidative stress, a phenotype that may be explained by a smaller number of anti-oxidant defense enzymes and heatshock proteins.  Conclusions/Significance: Phylogenetic comparison of nuclear and mitochondrial genes indicates that T. rangeli and T. cruzi are equidistant from T. brucei. In addition to revealing new aspects of trypanosome co-evolution within the vertebrate and invertebrate hosts, comparative genomic analysis with pathogenic trypanosomatids provides valuable new information that can be further explored with the aim of developing better diagnostic tools and/or therapeutic targets

Structural Studies of a Four-MBT Repeat Protein MBTD1

The Polycomb group (PcG) of proteins is a family of important developmental regulators. The respective members function as large protein complexes involved in establishment and maintenance of transcriptional repression of developmental control genes. MBTD1, Malignant Brain Tumor domain-containing protein 1, is one such PcG protein. MBTD1 contains four MBT repeats.We have determined the crystal structure of MBTD1 (residues 130-566aa covering the 4 MBT repeats) at 2.5 A resolution by X-ray crystallography. The crystal structure of MBTD1 reveals its similarity to another four-MBT-repeat protein L3MBTL2, which binds lower methylated lysine histones. Fluorescence polarization experiments confirmed that MBTD1 preferentially binds mono- and di-methyllysine histone peptides, like L3MBTL1 and L3MBTL2. All known MBT-peptide complex structures characterized to date do not exhibit strong histone peptide sequence selectivity, and use a "cavity insertion recognition mode" to recognize the methylated lysine with the deeply buried methyl-lysine forming extensive interactions with the protein while the peptide residues flanking methyl-lysine forming very few contacts [1]. Nevertheless, our mutagenesis data based on L3MBTL1 suggested that the histone peptides could not bind to MBT repeats in any orientation.The four MBT repeats in MBTD1 exhibits an asymmetric rhomboid architecture. Like other MBT repeat proteins characterized so far, MBTD1 binds mono- or dimethylated lysine histones through one of its four MBT repeats utilizing a semi-aromatic cage.This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S1

The Genetic Landscape and Epidemiology of Phenylketonuria

Phenylketonuria (PKU), caused by variants in the phenylalanine hydroxylase (PAH) gene, is the most common autosomal-recessive Mendelian phenotype of amino acid metabolism. We estimated that globally 0.45 million individuals have PKU, with global prevalence 1:23,930 live births (range 1:4,500 [Italy]-1:125,000 [Japan]). Comparing genotypes and metabolic phenotypes from 16,092 affected subjects revealed differences in disease severity in 51 countries from 17 world regions, with the global phenotype distribution of 62% classic PKU, 22% mild PKU, and 16% mild hyperphenylalaninemia. A gradient in genotype and phenotype distribution exists across Europe, from classic PKU in the east to mild PKU in the southwest and mild hyperphenylalaninemia in the south. The c.1241A gt G (p.Tyr414Cys)-associated genotype can be traced from Northern to Western Europe, from Sweden via Norway, to Denmark, to the Netherlands. The frequency of classic PKU increases from Europe (56%) via Middle East (71%) to Australia (80%). Of 758 PAH variants, c.1222C gt T (p.Arg408Trp) (22.2%), c.1066-11G gt A (IVS10-11G gt A) (6.4%), and c.782G gt A (p.Arg261Gln) (5.5%) were most common and responsible for two prevalent genotypes: p.[Arg408Trp];[Arg408Trp] (11.4%) and c.[1066-11G gt A];[1066-11G gt A] (2.6%). Most genotypes (73%) were compound heterozygous, 27% were homozygous, and 55% of 3,659 different genotypes occurred in only a single individual. PAH variants were scored using an allelic phenotype value and correlated with pre-treatment blood phenylalanine concentrations (n = 6,115) and tetrahydrobiopterin loading test results (n = 4,381), enabling prediction of both a genotype-based phenotype (88%) and tetrahydrobiopterin responsiveness (83%). This study shows that large genotype databases enable accurate phenotype prediction, allowing appropriate targeting of therapies to optimize clinical outcome

Cannabinoid Agonists Inhibit Neuropathic Pain Induced by Brachial Plexus Avulsion in Mice by Affecting Glial Cells and MAP Kinases

Many studies have shown the antinociceptive effects of cannabinoid (CB) agonists in different models of pain. Herein, we have investigated their relevance in neuropathic pain induced by brachial plexus avulsion (BPA) in mice.Mice underwent BPA or sham surgery. The mRNA levels and protein expression of CB(1) and CB(2) receptors were assessed by RT-PCR and immunohistochemistry, respectively. The activation of glial cells, MAP kinases and transcription factors were evaluated by immunohistochemistry. The antinociceptive properties induced by cannabinoid agonists were assessed on the 5(th) and 30(th) days after surgery. We observed a marked increase in CB(1) and CB(2) receptor mRNA and protein expression in the spinal cord and dorsal root ganglion, either at the 5(th) or 30(th) day after surgery. BPA also induced a marked activation of p38 and JNK MAP kinases (on the 30(th) day), glial cells, such as microglia and astrocytes, and the transcription factors CREB and NF-κB (at the 5(th) and 30(th) days) in the spinal cord. Systemic treatment with cannabinoid agonists reduced mechanical allodynia on both the 5(th) and 30(th) days after surgery, but the greatest results were observed by using central routes of administration, especially at the 30(th) day. Treatment with WIN 55,212-2 prevented the activation of both glial cells and MAP kinases, associated with an enhancement of CREB and NF-κB activation.Our results indicate a relevant role for cannabinoid agonists in BPA, reinforcing their potential therapeutic relevance for the management of chronic pain states