Interspecies interactions in mixed-species biofilms formed by Enterococcus faecalis and gram-negative bacteria isolated from polymicrobial diabetic foot ulcers.

Diabetic foot ulcers (DFU) are exacerbated by bacterial colonisation. Here, a high prevalence of Enterococcus faecalis was observed in DFU patients from an Argentinean hospital. E. faecalis was frequently co-isolated with Escherichia coli, Morganella morganii, and Pseudomonas aeruginosa. The effect of interspecies interactions on bacterial growth was investigated in mixed-species macrocolony biofilms developed in Lubbock-Glc-agar. Similar cell counts were found for E. faecalis and M. morganii growing in mixed and single-species biofilms. An E. faecalis strain showed 1 Log higher cell counts in mixed biofilms with E. coli. Remarkably, E. faecalis strains showed 2 to 4 Log higher cell counts in mixed biofilms with P. aeruginosa. This effect was not observed in planktonic growth or biofilms developed in tryptic soy agar. The present findings reveal bacterial interactions that benefit E. faecalis in mixed-species biofilms, mainly with P. aeruginosa, in a medium that partially mimics the nutrients found in DFU.

Assessment of cognitive impairment and depressive signs in patients with type 2 diabetes treated with metformin from Southeast Mexico: A cross-sectional study.

Multiple factors associate diabetes with cognitive impairment and depression. Antidiabetic drugs have reported antidepressant and pro-cognitive effects in diabetic and non-diabetic subjects. Antidepressant and pro-cognitive effects of metformin are reported in various studies; however, these effects are not consistent among researches. We designed a cross-sectional study. We recruited patients with T2D diagnosis from the Diabetes Clinic of the Regional Hospital of High Specialty "Dr. Gustavo A. Rovirosa Pérez" from January 2019 to May 2022. We included 431 subjects with T2D, 374 patients with metformin treatment and 57 subjects without metformin. These patients were on intensive therapies and had not a previous diagnosis of cognitive impairment or depression. We applied Mini-Mental State Examination (MMSE) to evaluate cognitive impairment, and Hamilton Depression Rating Scale (HAM-D) to assess depressive signs. Our sample had a mean age of 53.77 ± 13.43 years. Metformin users were 374 individuals, and 57 subjects didn't use metformin. MMSE found cognitive impairment in 8.3% (n = 31) of metformin users, and 14.8% (n = 8) of patients without metformin. HAM-D scale showed that 39.5% (n = 147) of patients with metformin had depression signs, subjects without metformin and depressive signs were 44.6% (n = 25). We found no differences between groups for cognitive impairment and depression grades. We did not find associations between metformin treatment, cognitive impairment measures and depression sign measures. However, chronic metformin treatment, insulin use, glycemic control and age could influence our results.

Identification and phenotypic characterization of patients with LADA in a population of southeast Mexico.

Latent autoimmune diabetes in adults (LADA) has clinical and metabolic features of type 1 and type 2 diabetes. LADA does not have specific features for its diagnosis apart from autoantibody detection; however, these tests are not affordable in clinical settings. In this cross-sectional study, we analyzed clinical criteria, metabolic control, pharmacological treatment, and diabetic complications in two groups of patients with diabetes -LADA and T2D- in order to identify specific characteristic of these clinical entities. Finally, we evaluated if the estimated glucose disposal rate (eGDR) and age at diagnosis of diabetes could be used as a diagnostic criterion for LADA. Demographic, biochemical, clinical and treatment were measured in 377 individuals with diabetes. The diagnostics of LADA were determined using Glutamic acid decarboxylase autoantibodies levels. Chi-square test or t-Student test were used to establish differences between groups. To identify factors associated with LADA, a logistic regression analysis was used. Finally, a ROC curve was plotted to assess the possible variables as diagnostic criteria for LADA. The 377 patients with diabetes were separated into 59 patients with LADA and 318 patients with T2D. Patients with LADA showed lower fasting glucose values, fewer diabetic complications, younger age at diagnosis of diabetes, higher insulin use, and higher eGDR in comparison to patients with T2D. Both groups had a mean BMI classified as overweight. The ROC evaluated the sensitivity and specificity, this analysis indicated that an age younger than 40.5 years and an eGDR value higher than 9.75 mg/kg/min correlated better with LADA. These parameters could be useful to identify patients suspected to have LADA at the first level of medical care in the population of southeastern Mexico and refer them to a second level of care.

Association between the HTR1A rs6295 gene polymorphism and suicidal behavior: an updated meta-analysis.

Several association studies have indicated that the HTR1A gene is associated with suicidal behavior (SB). Thus, a systematic assessment of the association of HTR1A was performed based on a literature review and pooled analysis. Four electronic databases were comprehensively searched to find and pinpoint all case-control articles related to this study. When analyzing the genetic association with SB, data were divided into: (A) SB cases vs. healthy controls and (B) SB cases vs. psychiatric controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were assessed as measures of association. Heterogeneity among included studies was analyzed using sensitivity test and Q statistics. Publication bias was also explored by Egger and rank correlation test. Thirteen case-control studies were selected in this meta-analysis, involving 2817 SB patients, 2563 healthy controls and 545 psychiatric controls. In the overall comparison between SB cases and healthy controls, result showed that the rs6295 polymorphisms of HTR1A gene was associated with SB, but only when using the recessive model (OR = 2.21, 95% CI = 1.80-2.71, P < 0.001). In the smaller sample size comparison between SB and psychiatric controls, no significant association was detected with rs6295 in any of the five genetics models tested. The present meta-analysis suggests that rs6295 polymorphism of HTR1A gene could increase the risk for SB. Well-designed studies with more patients will be required to validate these results.

Effect of risperidone on serum IL-6 levels in individuals with schizophrenia: a systematic review and meta-analysis.

BACKGROUND: Risperidone has been significant correlated with a direct effect of interleukin-6 (IL-6) levels in patients with schizophrenia. This fact allows the opportunity to link the probable immunomodulatory effect of antipsychotic medication. Specially, a proper functioning of IL-6 pathway plays a potential role in the treatment or development of schizophrenia. OBJECTIVE: Our primary aim was to perform a systematic review and meta-analysis to determine the effect of risperidone on IL-6 levels in individuals with schizophrenia. METHODS: Studies were identified through a systematic search using PubMed, Scopus, and Web of Science databases. The articles found were subjected to the inclusion and exclusion criteria; then, the mean and standardised differences were extracted to calculate the standardised mean differences using the CMA software. RESULTS: IL-6 levels in individuals with schizophrenia were compared before and after receiving risperidone as treatment. Increased levels of IL-6 levels were observed in individuals with schizophrenia who received risperidone (point estimate 0.249, lower limit 0.042, upper limit 0.455, p-value 0.018). In the Asian population sub-analysis, no statistically significant differences were observed (point estimate 0.103, lower limit -0.187, upper limit 0.215, p value 0.890). When we compared individuals with schizophrenia to the control groups, a significant increase of IL-6 levels was observed in the group with schizophrenia (point estimate 0.248, lower limit 0.024, upper limit 0.472, p-value 0.30). CONCLUSIONS: Risperidone appears to play an important role in IL-6 levels in schizophrenia. Potential implications of increased IL-6 levels in people with schizophrenia should be considered in future studies.KEY POINTSIncreased levels of IL-6 levels were observed in individuals with schizophrenia who received risperidone.Risperidone appears to play an important role in IL-6 levels in schizophrenia.This study could serve for future research focussed on IL-6.

Pediatric Mental Health Emergency Visits During the COVID-19 Pandemic.

Introduction: Paediatric and adult psychiatric emergency department (ED) visits decreased during the initial COVID-19 outbreak. Long-term consequences of the COVID-19 pandemic will include increases in mental healthcare needs, especially among vulnerable groups such as children and adolescents. Aim: This study examined changes in the number of overall and diagnosis-specific mental health ED visits among patients aged <18 years following the onset of the COVID-19 pandemic in Madrid, Spain. Methods: Using clinical records from all psychiatric ED visits at a major teaching hospital between October 2018 and April 2021, we conducted interrupted time-series analyses and compared trends before and after the day of the first ED COVID-19 case (1st March 2020). Results: A total of 663 patients were included. In March 2020, there was a marked initial decrease of -12.8 (95% CI -21.9, - 7.9) less monthly mental health ED visits. After April 2020, there was a subsequent increasing trend of 3.4 (95% CI 2.6, 4.2) additional monthly mental health ED visits. Conclusion: After the onset of the COVID-19 pandemic, there was an increase in paediatric psychiatric ED visits, especially due to suicide-related reasons. These data reinforce the crucial role of the ED in the management of acute mental health problems among youth and highlight the need for renovated efforts to enhance access to care outside of and during acute crises during the pandemic and its aftermath.

Proteus mirabilis outcompetes Klebsiella pneumoniae in artificial urine medium through secretion of ammonia and other volatile compounds.

Klebsiella pneumoniae and Proteus mirabilis form mixed biofilms in catheter-associated urinary tract infections. However, co-inoculation of P. mirabilis with K. pneumoniae in artificial urine medium (AUM) resulted in a drastic reduction of K. pneumoniae cells in both biofilm and planktonic growth. Here, the mechanism behind this competitive interaction was studied. Both pH and aqueous ammonia (NH3aq) increased in mixed cultures (to 9.3 and 150 mM, respectively), while K. pneumoniae viable cells dramatically diminished over time (>6-log reduction, p < 0.05). Mixed cultures developed in either 2-(N-morpholino) ethanesulfonic acid (MES)-buffered AUM (pH 6.5) or AUM without urea did not show bacterial competition, evidencing that the increase in pH and/or NH3aq concentration play a role in the competitive interaction. Viability of K. pneumoniae single-species cultures decreased 1.5-log in alkaline AUM containing 150 mM NH3aq after 24 h inoculation, suggesting that ammonia is involved in this inter-species competition. Besides NH3aq, additional antimicrobials should be present to get the whole competitive effect. Supernatants from P. mirabilis-containing cultures significantly diminished K. pneumoniae viability in planktonic cultures and affected biofilm biomass (p < 0.05). When subjected to evaporation, these supernatants lost their antimicrobial activity suggesting the volatile nature of the antimicrobial compounds. Exposure of K. pneumoniae to volatile compounds released by P. mirabilis significantly decreased cell viability in both planktonic and biofilm cultures (p < 0.05). The current investigation also evidenced a similar bactericidal effect of P. mirabilis volatiles over Escherichia coli and Morganella morganii. Altogether, these results evidence the secretion of ammonia and other volatile compounds by P. mirabilis, with antimicrobial activity against gram-negative uropathogens including K. pneumoniae. This investigation provides novel insight into competitive inter-species interactions that are mediated by production of volatile molecules.

Role of nutrient limitation in the competition between uropathogenic strains of Klebsiella pneumoniae and Escherichia coli in mixed biofilms.

Klebsiella pneumoniae and Escherichia coli form mixed species biofilms in catheter-associated urinary tract infections. Recently, a detrimental effect of K. pneumoniae over E. coli was observed in mixed species biofilms grown in an artificial urine medium. The mechanism behind this competitive interaction was studied. K. pneumoniae partially outcompeted E. coli in early-stage batch-fed biofilms, whereas both microorganisms co-exist at longer times (K. pneumoniae:E. coli ratio, 55:1), as shown by cell counts and confocal microscopy. E. coli cells were scattered along the K. pneumoniae biofilm. Biofilm supernatants did not appear to contain either antimicrobial or anti-biofilm activities against E. coli. Biofilms grown under continuous flow prevented interspecies competition. K. pneumoniae showed both increased siderophore production and better growth in iron-limited media compared to E. coli. In summary, these results indicate the importance of nutrient (particularly iron) competition in the modulation of the bacterial composition of mixed species biofilms formed by uropathogenic K. pneumoniae and E. coli.

Soluble factors from Lactobacillus reuteri CRL1098 have anti-inflammatory effects in acute lung injury induced by lipopolysaccharide in mice.

We have previously demonstrated that Lactobacillus reuteri CRL1098 soluble factors were able to reduce TNF-α production by human peripheral blood mononuclear cells. The aims of this study were to determine whether L. reuteri CRL1098 soluble factors were able to modulate in vitro the inflammatory response triggered by LPS in murine macrophages, to gain insight into the molecular mechanisms involved in the immunoregulatory effect, and to evaluate in vivo its capacity to exert anti-inflammatory actions in acute lung injury induced by LPS in mice. In vitro assays demonstrated that L. reuteri CRL1098 soluble factors significantly reduced the production of pro-inflammatory mediators (NO, COX-2, and Hsp70) and pro-inflammatory cytokines (TNF-α, and IL-6) caused by the stimulation of macrophages with LPS. NF-kB and PI3K inhibition by L. reuteri CRL1098 soluble factors contributed to these inhibitory effects. Inhibition of PI3K/Akt pathway and the diminished expression of CD14 could be involved in the immunoregulatory effect. In addition, our in vivo data proved that the LPS-induced secretion of the pro-inflammatory cytokines, inflammatory cells recruitment to the airways and inflammatory lung tissue damage were reduced in L. reuteri CRL1098 soluble factors treated mice, providing a new way to reduce excessive pulmonary inflammation.

Lactobacillus reuteri CRL 1098 and Lactobacillus acidophilus CRL 1014 differently reduce in vitro immunotoxic effect induced by Ochratoxin A.

Ochratoxin A (OTA) is a widespread mycotoxin contaminating several food products which causes detrimental health effects. The ability of Lactobacillus reuteri CRL 1098 and Lactobacillus acidophilus CRL 1014 to prevent OTA effects on TNF-α and IL-10 production and apoptosis induction in human peripheral blood mononuclear cells (PBMC) was investigated. Membrane rafts participation in these responses was also evaluated. L. reuteri reduced by 29% the OTA inhibition of TNF-α production whereas L. acidophilus increased 8 times the TNF-α production by OTA treated-PBMC. Also, both bacteria reversed apoptosis induced by OTA by 32%. However, neither of the bacteria reversed the OTA inhibition on IL-10 production. On the other hand, the lactobacilli were less effective to reverse OTA effects on disrupted-rafts PBMC. This study shows that two lactobacilli strains can reduce some negative OTA effects, being membrane rafts integrity necessary to obtain better results. Also, the results highlight the potential capacity of some lactobacilli strains usually included in natural dietary components in milk-derived products and cereals feed, to reduce OTA toxicity once ingested by humans or animals.