First Steps towards the Pharmaceutical Development of Ovules Containing Lactobacillus Strains: Viability and Antimicrobial Activity as Basic First Parameters in Vaginal Formulations.

In the majority of Latin-American countries, including Argentina, there is a limited availability of vaginal bioproducts containing probiotics in the market. In addition, the conventional treatments of genital tract infections in women represent a high cost to the public health systems. The future development of this type of bioproducts that employ specific lactobacilli strains would not only have a meaningful impact on women's health but would also represent a significant challenge to the pharmaceutical industry. The aims of the work described in this paper were (i) to study different pharmaceutical formulations of vaginal ovules containing Lactobacillus fermentum L23 and L. rhamnosus L60, to determine in which formulation lactobacilli viability was sustained for longer time and (ii) to evaluate if probiotic strains maintained both the antimicrobial activity and biofilm-producing ability after being recovered from the ovules. In this study, we developed and characterized three pharmaceutical formulations containing different glycerol amounts and specific lactobacilli strains. Three relevant parameters, cell viability, antimicrobial activity, and biofilm production, by lactobacilli recovered from the ovules were tested. Although the viability of L23 and L60 strains was mainly influenced by high ovule's glycerol proportion, they survived at 4 °C during the 180 days. Both lactobacilli's antimicrobial activity and biofilm-producing ability were maintained for all treatments. In conclusion, employing a much reduced number of components, we were able to select the most suitable pharmaceutical formulation which maintained not only lactobacilli viability for a long period of time but also their antimicrobial activity and biofilm-producing ability.

Consensus statement on the treatment of multiple sclerosis by the Spanish Society of Neurology in 2016. / Consenso para el tratamiento de la esclerosis múltiple 2016. Sociedad Española de Neurología.

With the advent of new disease-modifying drugs, the treatment of multiple sclerosis is becoming increasingly complex. Using consensus statements is therefore advisable. The present consensus statement, which was drawn up by the Spanish Society of Neurology's study group for demyelinating diseases, updates previous consensus statements on the disease. The present study lists the medications currently approved for multiple sclerosis and their official indications, and analyses such treatment-related aspects as activity, early treatment, maintenance, follow-up, treatment failure, changes in medication, and special therapeutic situations. This consensus statement includes treatment recommendations for a wide range of demyelinating diseases, from isolated demyelinating syndromes to the different forms of multiple sclerosis, as well as recommendations for initial therapy and changes in drug medication, and additional comments on induction and combined therapy and practical aspects of the use of these drugs.

Effect of two probiotic strains of Lactobacillus on in vitro adherence of Listeria monocytogenes, Streptococcus agalactiae, and Staphylococcus aureus to vaginal epithelial cells.

The lactobacilli probiotics maintain a normal vaginal biota and prevent disease recurrence. This microorganisms form a pellicle on the vaginal epithelium that acts as a biologic barrier against colonization by pathogenic bacteria. In this paper were realized assays of exclusion, competition, and displacement. For these test, vaginal epithelial cells, two strains of lactobacilli and pathogenic bacteria (Staphylococcus aureus, Streptococcus agalactiae and Listeria monocytogenes) were used. The lactobacilli strains showed a great capacity of adherence, with a mean of 83.5 ± 26.67 Lactobacillus fermentum cells and 56.2 ± 20.87 Lactobacillus rhamnosus cells per vaginal epithelial cells. L. fermentum and L. rhamnosus were able to reduce the adherence of S. aureus, S. agalactiae and L. monocytogenes in a significant level in this assay (P < 0.01). The lactobacilli used in this study protect the vaginal epithelium through a series of barriers and interference mechanisms. The aim of present study was to assess the ability of vaginal Lactobacillus strains, selected for their probiotic properties, to block the adherence of pathogenic microorganisms in vitro by displacement, competition, and exclusion mechanisms.

Curative effect of the probiotic strain Lactobacillus fermentum L23 in a murine model of vaginal infection by Gardnerella vaginalis.

UNLABELLED: Bacterial vaginosis is a common vaginal infection characterized by changes in the vaginal microbiota. The objective of this work was to evaluate the colonization ability and curative effect of Lactobacillus fermentum L23 after vaginal administration in female BALB/c mice infected with Gardnerella vaginalis. One dose of Lact. fermentum L23 containing 10(9 ) CFU ml(-1) was administered locally in a murine vaginal model. L23 colonized the vaginal tract of BALB-c mice after one inoculation. The infection by G. vaginalis in a murine model was induced by vaginal administration of a 1 × 10(6 ) CFU ml(-1) suspension. Infection with the pathogen was observed in the vaginal tract for 4 days. At 144 h after inoculation, levels of 4 log10 CFU ml(-1) were observed. The curative effect of L23 was evaluated with one administration at 1 × 10(9 ) CFU ml(-1) 72 h after the inoculation with G. vaginalis. Lactobacillus fermentum L23 inhibited the growth of G. vaginalis. The results of suppression of G. vaginalis using different concentrations of L23 were favourable due that these concentrations are normally used in commercial formulas. The obtained results indicate that Lact. fermentum L23 inhibited the growth of G. vaginalis. Therefore, L23 might be used as a potential biotherapeutic agent for the elimination of this bacterium. SIGNIFICANCE AND IMPACT OF THE STUDY: The use of the probiotic strain Lactobacillus fermentum L23 as a biotherapeutic agent can be expected to prevent and treat genital infections, particularly recurrent bacterial vaginosis, with similar concentrations to those normally used in commercial formulas. It is likely that the use of this probiotic strain for the treatment of bacterial vaginosis will provide a natural and nontoxic treatment modality.

Consensus statement of the Spanish Society of Neurology on the treatment of multiple sclerosis and holistic patient management in 2023.

The last consensus statement of the Spanish Society of Neurology's Demyelinating Diseases Study Group on the treatment of multiple sclerosis (MS) was issued in 2016. Although many of the positions taken remain valid, there have been significant changes in the management and treatment of MS, both due to the approval of new drugs with different action mechanisms and due to the evolution of previously fixed concepts. This has enabled new approaches to specific situations such as pregnancy and vaccination, and the inclusion of new variables in clinical decision-making, such as the early use of high-efficacy disease-modifying therapies (DMT), consideration of the patient's perspective, and the use of such novel technologies as remote monitoring. In the light of these changes, this updated consensus statement, developed according to the Delphi method, seeks to reflect the new paradigm in the management of patients with MS, based on the available scientific evidence and the clinical expertise of the participants. The most significant recommendations are that immunomodulatory DMT be started in patients with radiologically isolated syndrome with persistent radiological activity, that patient perspectives be considered, and that the term "lines of therapy" no longer be used in the classification of DMTs (> 90% consensus). Following diagnosis of MS, the first DMT should be selected according to the presence/absence of factors of poor prognosis (whether epidemiological, clinical, radiological, or biomarkers) for the occurrence of new relapses or progression of disability; high-efficacy DMTs may be considered from disease onset.

Early prophylactic treatment in pregnant women during the 2009-2010 H1N1 pandemic: obstetric and neonatal outcomes.

The aim of the study was to estimate the risk factors associated with the 2009 H1N1 influenza infection, during pregnancy; to describe complications and obstetric and perinatal outcomes of pregnancies during the H1N1 pandemic in 2009; to identify if there is teratogenicity at birth after antiviral treatment. Medical records of 168 pregnant women treated in Reina Sofia University Hospital (Cordoba, Spain) for suspected influenza A H1N1 from September 2009 to February 2010 were analysed. Using the PCR test, 76 pregnant women were diagnosed with H1N1 + infection, and infection was ruled out in the remaining 92. To manage the pandemic, recommendations of the Centres for Disease Control and Prevention were followed. Results showed that the majority of pregnant women were attended at the hospital between October and December 2009 (91.27%). Most of them were in the third-quarter of pregnancy (42.9%). In our sample, being aged between 29 and 37 years reduces the risk of acquiring infection (odds ratio, OR 0.379, 95% confidence interval, CI 0.188-0.763). However, in pregnant women who have required hospitalisation, the risk of infection increased five-fold (OR = 4.999; 95% CI = 1.178-21.212). No differences were found between obstetric and perinatal outcomes of both affected and unaffected or treated and untreated cohorts. No teratogenicity was observed at birth. It was concluded that maternal age and 3rd trimester pregnancy were found related to the risk of acquiring H1N1. No differences in obstetric outcomes or worse perinatal outcomes were found in patients affected by the pandemic. Early prophylactic treatment may be related to better maternal-fetal results.

Real life experience following combined excimer laser trabeculostomy and phacoemulsification in eyes with ocular hypertension or mild glaucoma and cataract.

OBJECTIVES: To assess the efficacy and safety of combined phacoemulsification and excimer laser trabeculostomy (ELT) in eyes with cataract and mild controlled glaucoma or ocular hypertension (OHT). METHODS: Single-centre analysis of eyes that underwent phacoemulsification and ELT between 2017 and 2021. Change in intraocular pressure (IOP), glaucoma medication requirements, corrected distance visual acuity (CDVA), complications and re-interventions were evaluated. Success was defined as a reduction ≥20% from preoperative IOP, an IOP ≤ 14 mmHg or a reduction in glaucoma medication requirements with an IOP equal or lower than the preoperative IOP. RESULTS: Mean follow-up was 658 ± 64 days. Mean preoperative IOP was 17.76 ± 4.88 mmHg, it decreased to 15.35 ± 3.10 mmHg at 1 year (n = 37) (p = 0.006) and to 14.00 ± 3.78 at 3 years (n = 8) (p = 0.074). Mean number of glaucoma medication requirements decreased from 2.02 ± 1.0 preoperatively to 1.02 ± 0.96 at 1 year (n = 37) (p < 0.001) and to 1.63 ± 0.92 at 3 years (n = 8) (p = 0.197). Complete success was achieved in 17.7% of eyes and qualified success in 54.8%. Two eyes of 2 patients had early postoperative hyphema. Two eyes of 1 patient underwent filtering surgery 2 months after the procedure, and 2 eyes of 1 patient underwent laser trabeculoplasty 3.8 years after the procedure due to uncontrolled IOP. CONCLUSIONS: Combined phacoemulsification and ELT is effective and safe in eyes with mild glaucoma or OHT and cataract. It significantly reduced IOP and glaucoma medication requirements 1 year after surgery.

Ureaplasma urealyticum and Mycoplasma hominis sensitivity to bacteriocins produced by two Lactobacilli strains.

The purpose of the present study was to determine the inhibitory activities of two bacteriocins, produced by lactobacilli, against genital mycoplasmas. In this study, infections produced by genital mycoplasmas were studied; of these, 1.3% were caused by Mycoplasma hominis, 10.7% by Ureaplasma urealyticum and 5.6% by U. urealyticum + M. hominis. U. urealyticum was isolated from 75 out of 123 patients with genital mycoplasmas, while M. hominis was isolated from 9 patients (7.3%) and both U. urealyticum and M. hominis from 39 patients (31.7%). Bacteriocins, L23 and L60, produced by Lactobacillus fermentum and L. rhamnosus, respectively, appear to be two novel inhibitors of bacterial infection with potential antibacterial activity. Both bacteriocins proved to be active against 100% of strains tested; MICs of bacteriocin L23 ranged between 320 and 160 UA ml(-1) for 78% of the M. hominis strains and between 320 and 80 UA ml(-1) for 95% of the U. urealyticum strains. In addition, bacteriocin L60 was still active at 160 UA ml(-1) for a high percentage (56%) of M. hominis strains, and at 80 UA ml(-1) for 53% of the U. urealyticum strains. Interestingly, these antimicrobial substances produced by lactobacilli showed an inhibitory activity against genital mycoplasmas even when diluted. Altogether, our study indicates that the bacteriocins, L23 and L60, are good candidates for the treatment or prevention of genital infections in women.

Solar photocatalytic degradation of pesticides over TiO2-rGO nanocomposites at pilot plant scale.

Two TiO2-rGO nanocomposites were prepared by hydrothermal method from commercial TiO2 (P25 and Hombikat UV100, HBK). In both cases TiO2 nanoparticles appeared intimate and homogeneously distributed on rGO surface, but forming a dense network in P25-rGO nanocomposite, and a more open structure in HBK-rGO. Zeta potential and particle size distribution favored the ease of HBK-rGO nanocomposite to form stable suspensions. A comparative analysis of these two photocatalysts was performed on the pilot plant scale solar assisted photodegradation of a 200 µg·L-1 or 5 mg·L-1 mixture of persistent and biorecalcitrant pollutants in deionized water (methomyl, pyrimethanil, isoproturon and alachlor, all used as pesticides). Complete removal of pesticides was achieved, though faster with P25-rGO when O2 was the oxidant. However, the use of hydrogen peroxide (H2O2) dosage as oxidant speeded up pesticides removal, but HBK-rGO performance resulted much improved. Finally, at realistic very low concentrations of 200 µgeach pesticide·L-1, the complete removal of pesticides was achieved at very short times (<25 min), showing the efficiency of the synthetized TiO2-rGO nanocomposites in this pilot-plat scale solar process to mitigate refractory and biorecalcitrant contaminants on effluents as a sustainable and efficient process.

Convolutional Neural Network-Based Automated Segmentation of the Spinal Cord and Contusion Injury: Deep Learning Biomarker Correlates of Motor Impairment in Acute Spinal Cord Injury.

BACKGROUND AND PURPOSE: Our aim was to use 2D convolutional neural networks for automatic segmentation of the spinal cord and traumatic contusion injury from axial T2-weighted MR imaging in a cohort of patients with acute spinal cord injury. MATERIALS AND METHODS: Forty-seven patients who underwent 3T MR imaging within 24 hours of spinal cord injury were included. We developed an image-analysis pipeline integrating 2D convolutional neural networks for whole spinal cord and intramedullary spinal cord lesion segmentation. Linear mixed modeling was used to compare test segmentation results between our spinal cord injury convolutional neural network (Brain and Spinal Cord Injury Center segmentation) and current state-of-the-art methods. Volumes of segmented lesions were then used in a linear regression analysis to determine associations with motor scores. RESULTS: Compared with manual labeling, the average test set Dice coefficient for the Brain and Spinal Cord Injury Center segmentation model was 0.93 for spinal cord segmentation versus 0.80 for PropSeg and 0.90 for DeepSeg (both components of the Spinal Cord Toolbox). Linear mixed modeling showed a significant difference between Brain and Spinal Cord Injury Center segmentation compared with PropSeg (P < .001) and DeepSeg (P < .05). Brain and Spinal Cord Injury Center segmentation showed significantly better adaptability to damaged areas compared with PropSeg (P < .001) and DeepSeg (P < .02). The contusion injury volumes based on automated segmentation were significantly associated with motor scores at admission (P = .002) and discharge (P = .009). CONCLUSIONS: Brain and Spinal Cord Injury Center segmentation of the spinal cord compares favorably with available segmentation tools in a population with acute spinal cord injury. Volumes of injury derived from automated lesion segmentation with Brain and Spinal Cord Injury Center segmentation correlate with measures of motor impairment in the acute phase. Targeted convolutional neural network training in acute spinal cord injury enhances algorithm performance for this patient population and provides clinically relevant metrics of cord injury.

[Sinus syndrome, an uncommon cause of enophthalmos]. / Síndrome del seno silente, una causa infrecuente de enoftalmos.

CLINICAL CASE: A 29-year-old woman presented with a subjective sensation of ocular asymmetry from several months beforehand. Ophthalmological exam showed 3,5 mm right enophthalmos and light hypoglobus. CT (Computerized Tomography) scan showed a collapsed maxillar sinus, and a thinned inferior orbital wall. The diagnosis of silent sinus syndrome was made. An endoscopic maxillary antrostomy with uncinectomy was made with an excellent surgical outcome. DISCUSSION: Clinical features of silent sinus syndrome are described, including diagnosis, differential diagnosis and treatment.

[Agreement between pneumotachograph and PiKo-1 measurements of PEF and FEV1]. / Estudio de la concordancia de 2 aparatos para la medida del PEF y FEV1: neumotacógrafo y PiKo-1.

OBJECTIVE: To assess how well values for peak expiratory flow (PEF) and forced expiratory volume in 1 second (FEV1) agree when measured with the PiKo-1 device and with a conventional pneumotachograph. PATIENTS AND METHODS: This randomized, single-blind study included 40 patients who attended the clinic for lung function testing. The 2 measurement devices were the Masterlab pneumotachograph and the PiKo-1. A correction factor estimated by the manufacturer was applied to the measurements taken with the PiKo-1. RESULTS: The values obtained with the 2 devices differed by a mean of 5.8218 L/min for PEF (95% confidence interval [CI], -9.4809 to 21.1387) and 0.001 L for FEV1 (95% CI, -0.0616 to 0.0636). The intraclass correlation coefficient was 0.9652 (95% CI, 0.9336-0.9819) for PEF and 0.9876 (95% CI, 0.9761-0.9936) for FEV1. CONCLUSIONS: The PiKo-1 is a simple and easy-to-use device that can be very useful for monitoring and assessing the severity of obstructive pulmonary diseases. The results must be corrected for altitude and the estimated correction factor should be applied.

Impact of mode of delivery on the milk microbiota composition of healthy women.

Breast milk constitutes one of the most important sources of postnatal microbes. However, the influence of perinatal factors on the milk microbiome is still poorly understood. The aim of our study was to assess the impact of mode of delivery on the microbiome composition and diversity present in breast milk of healthy mothers. Mature milk samples (n=10) were taken from mothers after 1 month of exclusively breastfeeding. Microbiomes from milk samples were analyzed with 16S ribosomal RNA gene pyrosequencing and targeted quantitative polymerase chain reaction (PCR). Despite inter-individual variability in bacterial composition, The Principal Coordinates Analysis clearly separated milk microbiome from mothers with vaginal delivery (n=6) from those who undergo C-section (n=4). In addition, higher bacterial diversity and richness was found in milk samples from vaginal deliveries. Quantitative PCR data showed that higher levels of Bifidobacterium spp. were related significantly to lower levels of Staphylococcus spp. Despite the low sample size, our data suggest that mode of delivery has an important impact on milk microbiome composition. Further studies with larger sample sizes are needed to confirm these results and to understand the biological effects of C-section associated microbes on infant's health.

Differential influence of LDL cholesterol and triglycerides on lipoprotein(a) concentrations in diabetic patients.

OBJECTIVE: To evaluate the relationship between plasma lipid profiles and lipoprotein(a) [Lp(a)] concentrations in diabetic patients, taking into account the Lp(a) phenotype. RESEARCH DESIGN AND METHODS: We included 191 consecutive diabetic outpatients (69 type 1 and 122 type 2 diabetic patients) in a cross-sectional study Serum Lp(a) was determined by enzyme-linked immunosorbent assay, and Lp(a) phenotypes were assessed by SDS-PAGE followed by immunoblotting. The statistical methods included a stepwise multiple regression analysis using the Lp(a) serum concentration as the dependent variable. The lipid profile consisted of total cholesterol, HDL cholesterol, LDL cholesterol, corrected LDL cholesterol, triglycerides, and apolipoproteins AI and B. RESULTS: In the multiple regression analysis, LDL cholesterol (positively) and triglycerides (negatively) were independently related to the Lp(a) concentration, and they explained the 6.6 and 7.8% of the Lp(a) variation, respectively. After correcting LDL cholesterol, the two variables explained 3.8 and 6.4% of the Lp(a) variation, respectively. In addition, we observed that serum Lp(a) concentrations were significantly lower in patients with type IV hyperlipidemia (mean 1.0 mg/dl [range 0.5-17], n = 16) than in normolipidemic patients (6.5 mg/dl [0.5-33.5], n = 117) and in type II hyperlipidemic patients (IIa 15.5 mg/dl [3.5-75], n = 13; IIb 9 mg/dl [1-80], n = 45); P < 0.001 by analysis of variance. CONCLUSIONS: Lp(a) concentrations were directly correlated with LDL cholesterol and negatively correlated with triglyceride levels in diabetic patients. Therefore, our results suggest that the treatment of diabetic dyslipemia may indirectly affect Lp(a) concentrations.