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Background Bacterial vaginosis (BV) affects 30–50% of women at some time in their lives and is an embarrassing and distressing condition which can be associated with potentially serious comorbidities. Current antibiotic treatments such as metronidazole are effective but can result in side effects, and recurrence is common. This trial aims to investigate whether lactic acid gel is clinically effective and cost effective in the treatment of recurrent BV compared with metronidazole. Methods VITA is an open-label, multicentre, parallel group randomised controlled trial for women with a clinical diagnosis of BV and at least one previous BV episode in the past 2 years. Participants will be randomised 1:1 to intravaginal lactic acid gel 5 ml once daily for 7 days or oral metronidazole tablets 400 mg twice daily for 7 days. All participants will be followed up for 6 months to assess health status and healthcare costs. A subgroup will be interviewed to further explore adherence, tolerability and acceptability of treatment. The estimated sample size is 1900 participants to detect a 6% absolute increase in response rate to 86% in those receiving lactic acid gel. The primary outcome is participant-reported resolution of BV at Week 2. Discussion Results from this trial will help inform UK treatment guidelines for BV and may provide an alternative effective treatment for recurrent episodes of this condition which avoids repeated exposure to antibiotics. Trial registration ISRCTN, ISRCTN14161293 . Registered on 8 September 2017.

PurposeThe main objective of this open, prospective, multicentre, observational study is to investigate the relapse rate and tolerability of lactic acid gels in adult female patients with recurrent urinary tract infections during routine practice.MethodsData were collected from patients undergoing intermittent short courses of intravaginal treatment with lactic acid gel for prevention of recurrent urinary tract infections. The observation period for individual patients was 4 months, aimed at covering four short courses of intravaginal treatment. Data on UTI relapses, tolerability, handling and satisfaction with the treatment were collected via patient diaries and physician assessments and comprised any adverse events (AEs).ResultsIn total, 72 patients were treated. During the last 12 months prior to the study, patients had on average 4.0 UTIs. In the 4 months after commencing treatment, 63.5% of patients had no recurrence of UTI symptoms. Overall efficacy was rated by physicians as ‘excellent/good’ for 96.7% of patients. The patients’ overall acceptance of local treatment was high with 94.1% being ‘(very) satisfied’. Similarly, handling was rated as ‘(very) easy’ by 94.2% of patients. The tolerability was assessed as ‘highly tolerable/tolerable’ by over 98% of patients and physicians alike. Safety analyses reported six AEs of mild intensity, all of which had resolved by the end of the study.ConclusionTreatment with lactic acid gel may increase resilience against uropathogens, possibly preventing the need for antibiotic prevention of recurrent urinary tract infections. Treatment was positively assessed by the patients. The physician assessments corroborate these findings.Trial registration number and date of registrationDRKS00016760, 18.02.2019.

Bacterial vaginosis (BV) is associated with an elevated vaginal pH and the presence of abnormal offensive discharge. It is common, often recurrent, and the most effective treatment regimen is unknown. 'Metronidazole Versus lactic acId for Treating bacterial vAginosis' (VITA) is a UK-based randomised controlled trial assessing clinical and cost-effectiveness of topical lactic acid gel compared to oral metronidazole antibiotic for treating second and subsequent BV episodes. Few BV trials report on women's preferences for treatment in the context of their own experiences. This qualitative study investigated the acceptability and tolerability of the two treatments. During the trial, semi-structured telephone interviews were undertaken between January-May 2018. A total of 33 women diagnosed with BV were consecutively sampled then interviewed from six sites across England. Thematic analysis was guided by the acceptability of health interventions framework. Potential causes of BV and its impact on women's lives were explored in addition to women's treatment preference and perceived treatment effectiveness. Although women felt antibiotics treat BV effectively, and were associated with longer time periods between episodes, they generally preferred using the lactic acid gel because of ease of use, once daily application and less side-effects. Women would recommend the lactic acid gel to others for mild cases of BV but to take antibiotics when more severe. The risk of antibiotic drug resistance was a common concern. Self-help medicating or self-decision to not treat was also evident due to prior experience of poor outcomes from treatment. Triggers of BV were attributed to personal hygiene habits-soaps used to wash the vagina and sexual practices such as unprotected sex. Acceptability and preference for topical lactic acid gel or oral metronidazole tablets in the treatment of recurrent BV was affected by personal choice relating to affective attitude, burden, ethicality, intervention coherence, opportunity costs, and self-efficacy. These differed depending on ease of use, tolerability and past experiences, but not necessarily based on perceived drug effectiveness. Knowledge of a patient preference for topical lactic acid gel therapy despite lower perceived effectiveness may be useful for clinicians when making treatment decisions.

The microbiota of pre-ensiled crop and silage were examined using denaturing gradient gel electrophoresis (DGGE) and next-generation sequencing (NGS). Wilted Italian ryegrass (IR), whole crop corn (WC), and wilted alfalfa (AL) silages stored for 2 months were examined. All silages contained lactic acid as a predominant fermentation product. Across the three crop species, DGGE detected 36 and 28 bands, and NGS identified 253 and 259 genera in the pre-ensiled crops and silages, respectively. The NGS demonstrated that, although lactic acid bacteria (LAB) became prevalent in all silages after 2 months of storage, the major groups were different between crops: Leuconostoc spp. and Pediococcus spp. for IR silage, Lactobacillus spp. for WC silage, and Enterococcus spp. for AL silage. The predominant silage LAB genera were also detected by DGGE, but the presence of diverse non-LAB species in pre-ensiled crops was far better detected by NGS. Likewise, good survival of Agrobacterium spp., Methylobacterium spp., and Sphingomonas spp. in IR and AL silages was demonstrated by NGS. The diversity of the microbiota described by principal coordinate analysis was similar between DGGE and NGS. Our finding that analysis of pre-ensiled crop microbiota did not help predict silage microbiota was true for both DGGE and NGS.

This paper presents a study of biodegradation, in soil, of samples of poly(butylene adipate-co-terephthalate)(PBAT), poly(lactic acid) (PLA) and blends of these materials prepared in torque rheometer with the addition of a chain extender. Film samples of these materials were buried in soil under controlled laboratory conditions. The degraded samples were regularly taken from soil and analyzed by visual inspection, size exclusion chromatography, differential scanning calorimetry and infrared spectroscopy. Respirometry biodegradation tests were conducted to assess samples mineralization degree. Blends showed higher degree of crystallinity compared to pure polymers. Crystallinity degree enhanced during the biodegradation process in all samples, being able to causing the samples to degrade slowly. The study showed the great complexity of the biodegradation process of PLA and PBAT blends when compatibilized with a chain extender. The biodegradation rate showed different results depending on the characteristic applied to evaluate it: visual, molecular weight or mineralization. The chain extender had strong influence in PBAT and blends degradation, slowing the process as observed by the variation of molecular weight and carbonyl index. Blends showed an intermediate behavior compared to the original polymers.

The intestinal microbiota and morphology of tilapia (Oreochromis niloticus) were investigated after the application of a multi-species probiotic containing Lactobacillus reuteri, Bacillus subtilis, Enterococcus faecium and Pediococcus acidilactici (AquaStar® Growout). Tilapia (55.03 ± 0.44 g) were fed either a control diet or a probiotic diet (control diet supplemented with AquaStar® Growout at 5 g kg⁻¹). After four and eight weeks, culture-dependent analysis showed higher levels of lactic acid bacteria (LAB), enterococci and Bacillus spp. in the mucosa and digesta of fish fed AquaStar® Growout. At week four, polymerase chain reaction denaturing gradient gel electrophoresis (PCR-DGGE) revealed a higher similarity within the probiotic fed replicates than replicates of the control group; after eight weeks, the compositional dissimilarity of the microbiome profiles between the groups was greater than the dissimilarities within each group (P < 0.05). High-throughput sequencing revealed that the probiotic treatment significantly reduced the number of operational taxonomic units and species richness in the digesta. Significantly higher proportions of reads belonging to Proteobacteria and Cyanobacteria were detected in the control group whereas the probiotic-fed fish displayed a significantly higher abundance of reads assigned to the Firmicutes (which accounted for >99 % of reads). Bacillus, Cetobacterium and Mycobacterium were the dominant genera in the digesta of control fish whereas Bacillus, Enterococcus and Pediococcus were the largest constituents in probiotic-fed fish. The addition of AquaStar® Growout to tilapia diets led to increased populations of intraepithelial leucocytes, a higher absorptive surface area index and higher microvilli density in the intestine. These data suggest that AquaStar® Growout can modulate both the intestinal microbiota and morphology of tilapia.

The presence of an abnormal vaginal microflora in early pregnancy is a risk factor for preterm delivery. There is no investigation on vaginal flora dominated by lactic acid bacteria and possible association with preterm delivery. We assessed the dominant vaginal Lactobacillus species in healthy pregnant women in early pregnancy in relation to pregnancy outcome. We observed 111 low risk pregnant women with a normal vaginal microflora 11 + 0 to 14 + 0 weeks of pregnancy without subjective complaints. Vaginal smears were taken for the identification of lactobacilli using denaturing gradient gel electrophoresis (DGGE). Pregnancy outcome was recorded as term or preterm delivery (limit 36 + 6 weeks of gestation). The diversity of Lactobacillus species in term vs. preterm was the main outcome measure. L. iners alone was detected in 11 from 13 (85%) women who delivered preterm. By contrast, L. iners alone was detected in only 16 from 98 (16%) women who delivered at term (p < 0.001). Fifty six percent women that delivered at term and 8% women that delivered preterm had two or more vaginal Lactobacillus spp. at the same time. This study suggests that dominating L. iners alone detected in vaginal smears of healthy women in early pregnancy might be associated with preterm delivery.

The aim of this study was to investigate the lactic acid bacteria (LAB) and yeast community from home-made sauerkraut collected from Southwest China through culture-dependent and culture-independent technology. Forty-eight samples of home-made sauerkraut were collected from households at three different locations in Southwest China. The pH, total acidity and salt contents among these fermented vegetables were 3.69 ± 0.42, 0.86 ± 0.43 g/100 ml, and 3.86 ± 2.55 g/100 ml, respectively. The number of lactic acid bacteria (LAB) and yeasts were 7.25 ± 1.05 log10 colony-forming units (CFU)/ml and 3.74 ± 1.01 log CFU/ml, respectively. A total of 182 LAB and 81 yeast isolates were identified. The dominant isolates were Lactobacillus plantarum, L. brevis, Pediococcus ethanolidurans, Pichia membranifaciens, P. fermentans and Kazachstania bulderi. Denaturing gradient gel electrophoresis (DGGE) showed that L. plantarum, uncultured Lactobacillus sp, P. ethanolidurans, and K. exigua were the predominant microflora. Our studies demonstrated that the DGGE technique combined with a culture-dependent method is very effective for studying the LAB and yeast community in Chinese traditional fermentation vegetables. The results will give us an understanding of LAB and yeast community of Chinese sauerkraut and improve the knowledge of LAB and yeast community of Chinese sauerkraut.

Oral Topiramate therapy is associated with systemic adverse effects including paresthesia,abdominal pain, and fluctuations in plasma levels. The purpose of this research was to develop an intranasal in situ  gel based system comprising Topiramate polymeric nanoparticles and evaluate its potential both in vitro and in vivo . Poly (lactic-co-glycolic acid) (PLGA)nanoparticles prepared by nanoprecipitation method were added into the in situ gelling system of Poloxamer 407 and HPMC K4M. Selected formulation (TG5) was evaluated for physicochemical properties, nasal permeation and in vivo pharmacokinetics in rats. PLGAnanoparticles (O1) exhibited low particle size (~ 144.4 nm), good polydispersity index (0.202), negative zeta potential (-12.7 mV), and adequate entrapment efficiency (64.7%). Developed in situ gel showed ideal pH (6.5), good gelling time (35 s), gelling temperature(37℃), suitable viscosity (1335 cP)and drug content of 96.2%. In vitro drug release conformedto Higuchi release kinetics, exhibiting a biphasic pattern of initial burst release and sustained release for 24 h. Oral administration of the drug to Sprague–Dawley rats (G3) showed higher plasma C max (504 ng/ml, p  < 0.0001) when compared to nasal delivery of in situ gel (G4) or solution (G5). Additionally, AUC 0-α of G3 (8786.82 ng/ml*h) was considerably higher than othergroups. Brain uptake data indicates a higher drug level with G4 (112.47 ng /ml) at 12 h when compared to G3. Histopathological examination of groups; G1 (intranasal saline), G2(intranasal placebo), G3, G4, and G5 did not show any lesions of pathological significance. Overall, the experimental results observed were promising and substantiated the potential of developed in situ gel for intranasal delivery. Graphical Abstract

Salmonella is a serious foodborne pathogen responsible for more than 90 million cases of gastroenteritis worldwide annually. Due to the gradual increase in antibiotic-resistant Salmonella strains, the identification of natural antibacterial substances is urgently needed. Herein, we purified natural l-phenyl lactic acid (L-PLA) from Lactobacillus plantarum ZJ316 and revealed its antimicrobial mode against Salmonella enterica subsp. enterica ATCC 14028. L-PLA (98.14% pure) was obtained using the macroporous resin XAD-16, solid-phase extraction (SPE), reverse-phase high-performance liquid chromatography (RP-HPLC), and chiral chromatography. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) results showed that the cell morphology was severely compromised. Transmembrane electrical potential (ΔΨ), transmembrane pH gradient (ΔpH), intracellular ATP level, extracellular electrical conductivity (EC), and genomic DNA analyses were employed to evaluate the antibacterial mode of action of L-PLA. The proton motive force (PMF) and ATP of Salmonella cells rapidly dissipated, and the EC markedly increased. The gel retardation assay demonstrated that L-PLA could bind to genomic DNA and intercalate into the nucleic acids. The anti-Salmonella mode of action of L-PLA was attributed to the destruction of the cell membrane and genomic DNA binding. This research suggests that L-PLA has potential applications as an antimicrobial agent in food, medicine, and other fields.Key Points• Natural L-PLA was purified from L. plantarum ZJ316 with a purity of 98.14%.• L-PLA effectively inhibited Salmonella strains by antibacterial activities and MICs.• Membrane destruction and binding with DNA are the anti-Salmonella modes of L-PLA.