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Neutrophils play a crucial role in eliminating bacteria that invade the human body; however, cathepsin G can induce biofilm formation in a non-biofilm-forming Staphylococcus epidermidis 1457 strain, suggesting that neutrophil proteases may be involved in biofilm formation. Cathepsin G, cathepsin B, proteinase-3, and metalloproteinase-9 (MMP-9) from neutrophils were tested on the biofilm induction in commensal (skin isolated) and clinical non-biofilm-forming S. epidermidis isolates. From 81 isolates, 53 (74%) were aap+, icaA−, icaD− genotype, and without the capacity of biofilm formation under conditions of 1% glucose, 4% ethanol or 4% NaCl, but these 53 non-biofilm-forming isolates induced biofilm by the use of different neutrophil proteases. Of these, 62.3% induced biofilm with proteinase-3, 15% with cathepsin G, 10% with cathepsin B and 5% with MMP -9, where most of the protease-induced biofilm isolates were commensal strains (skin). In the biofilm formation kinetics analysis, the addition of phenylmethylsulfonyl fluoride (PMSF; a proteinase-3 inhibitor) showed that proteinase-3 participates in the cell aggregation stage of biofilm formation. A biofilm induced with proteinase-3 and DNAse-treated significantly reduced biofilm formation at an early time (initial adhesion stage of biofilm formation) compared to untreated proteinase-3-induced biofilm (p < 0.05). A catheter inoculated with a commensal (skin) non-biofilm-forming S. epidermidis isolate treated with proteinase-3 and another one without the enzyme were inserted into the back of a mouse. After 7 days of incubation period, the catheters were recovered and the number of grown bacteria was quantified, finding a higher amount of adhered proteinase-3-treated bacteria in the catheter than non-proteinase-3-treated bacteria (p < 0.05). Commensal non-biofilm-forming S. epidermidis in the presence of neutrophil cells significantly induced the biofilm formation when multiplicity of infection (MOI) 1:0.01 (neutrophil:bacteria) was used, but the addition of a cocktail of protease inhibitors impeded biofilm formation. A neutrophil:bacteria assay did not induce neutrophil extracellular traps (NETs). Our results suggest that neutrophils, in the presence of commensal non-biofilm-forming S. epidermidis, do not generate NETs formation. The effect of neutrophils is the production of proteases, and proteinase-3 releases bacterial DNA at the initial adhesion, favoring cell aggregation and subsequently leading to biofilm formation.

Marine obligate actinobacteria produce a wide variety of secondary metabolites with biological activity, notably those with antibiotic activity urgently needed against multi-drug-resistant bacteria. Seventy-five marine actinobacteria were isolated from a marine sediment sample collected in Punta Arena de La Ventana, Baja California Sur, Mexico. The 16S rRNA gene identification, Multi Locus Sequence Analysis, and the marine salt requirement for growth assigned seventy-one isolates as members of the genus Salinispora, grouped apart but related to the main Salinispora arenicola species clade. The ability of salinisporae to inhibit bacterial growth of Staphylococcus epidermidis, Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacer baumannii, Pseudomonas aeruginosa, and Enterobacter spp. was evaluated by cross-streaking plate and supernatant inhibition tests. Ten supernatants inhibited the growth of eight strains of S. epidermidis from patients suffering from ocular infections, two out of the eight showed growth inhibition on ten S. epidermidis strains from prosthetic joint infections. Also, it inhibited the growth of the remaining six multi-drug-resistant bacteria tested. These results showed that some Salinispora strains could produce antibacterial compounds to combat bacteria of clinical importance and prove that studying different geographical sites uncovers untapped microorganisms with metabolic potential.

PURPOSE To assess the effects of aerobic exercise (AE) on patients with migraine in terms of pain intensity, frequency and duration of migraine, and quality of life. METHODS A systematic review and meta-analysis of randomized controlled trials were conducted. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were calculated for relevant outcomes and were pooled in a meta-analysis using the random-effects model. RESULTS A total of 10 articles from 1950 to 2019 were included, involving 508 patients. The meta-analysis showed statistically significant differences in the decrease in pain intensity (five studies, n = 166; SMD = 1.25; 95% CI 0.47-2.04), frequency (six studies, n = 214; SMD = 0.76; 95% CI 0.32-1.2) and duration of migraine (four studies, n = 106; SMD = 0.41; 95% CI 0.03-0.8), in the short-term. In addition, the meta-analysis showed statistically significant differences in the increase in quality of life (four studies, n = 150; SMD = 2.7; 95% CI 1.17-4.24), even though the Egger's test suggested significant evidence of publication bias for the analysis of quality of life (intercept = 5.81; t = 6.97; P = .02). CONCLUSIONS There is low- and moderate-quality evidence that in patients with migraine AE can decrease the pain intensity, frequency and duration of migraine and can also increase quality of life.

Currently, the treatment of infections by Staphylococcus epidermidis (S. epidermidis) represents a challenge because some strains have multidrug-resistance to antimicrobial products (antibiotic and biocides) and can produce biofilms. These biofilms protect bacterial cells from both antimicrobials and the host immune response. Therefore, it is crucial to encourage research on the development of new treatments. One method is immunotherapy, targeting components of S. epidermidis, such as S. epidermidis surface (Ses) proteins. Ses is expressed constitutively in most strains, and they participate in biofilm formation. This review is an update on Ses, regarding their structure, biological function, their relationship with S. epidermidis biofilm formation, and its possible role as therapeutic targets to develop immunotherapeutic treatments to prevent infections by S. epidermidis.

The Staphylococcus aureus’ SdrG protein is glycosylated by SdgA and SdgB for their protection against its degradation by the neutrophil’s cathepsin G. So far, there is not information about the role of Staphylococcus epidermidis’ SdgA nor SdgB in the production of biofilm, therefore the main of this work was to determine the distribution and expression of sdrG, sdgA and sdgB genes in S. epidermidis in conditions of biofilm. The frequency of the genes sdrG, sdgA and sdgB were evaluated by PCR in a collection of 75 isolates. The isolates were grown in dynamic conditions (in agitation) or static conditions (biofilm productor: planktonic or sessile cells). The expression of sdrG, sdgA and sdgB were determined by RT-qPCR in cells grown under dynamic conditions (CGDC), as well as planktonic and sessile cells, and in cells adhered to a catheter (in vivo). The genes sdrG and sdgB were detected in 100% of isolates, meanwhile the gene sdgA was detected in 71% of the samples (psdrG, sdgA and sdgB mRNAs. The planktonic and sessile cells expressed sdrG and sdgB, and the same was seen in cells adhered to the catheter. In particular, one isolate, able to induce biofilm under cathepsin G treatment, expressed sdrG and sdgB in planktonic, sessile and in cells adhered to the catheter. This suggests that the state of cells adherence is an important factor for the transcription of sdgA, sdgB and sdrG.

The Staphylococcus aureus SdrG protein is glycosylated by SdgA and SdgB for protection against its degradation by the neutrophil cathepsin G. So far, there is no information about the role of Staphylococcus epidermidis SdgA or SdgB in biofilm-forming; therefore, the focus of this work was to determine the distribution and expression of the sdrG, sdgA and sdgB genes in S. epidermidis under in vitro and in vivo biofilm conditions. The frequencies of the sdrG, sdgA and sdgB genes were evaluated by PCR in a collection of 75 isolates. Isolates were grown in dynamic (non-biofilm-forming) or static (biofilm-forming) conditions. The expression of sdrG, sdgA and sdgB was determined by RT-qPCR in cells grown under dynamic conditions (CGDC), as well as in planktonic and sessile cells from a biofilm and cells adhered to a catheter implanted in Balb/c mice. The sdrG and sdgB genes were detected in 100% of isolates, while the sdgA gene was detected in 71% of the sample (p 0.001). CGDC did not express sdrG, sdgA and sdgB mRNAs. Planktonic and sessile cells expressed sdrG and sdgB, and the same was observed in cells adhered to the catheter. In particular, one isolate, capable of inducing a biofilm under treatment with cathepsin G, expressed sdrG and sdgB in planktonic and sessile cells and cells adhering to the catheter. This suggests that bacteria require biofilm conditions as an important factor for the transcription of the sdgA, sdgB and sdrG genes.

The three-component apsXRS system senses and responds to cationic antimicrobial peptides (CAMPs), which induces the expression of the dlt operon and the genes mprF and vrafG, modifying the surface net charge in Staphylococcus epidermidis, resulting in the repulsion of CAMPs. The apsXRS system has been only studied in the S. epidermidis 1457 strain, and there are no studies of prevalence and level of expression of apsXRS in commensal and clinical isolates. From 60 isolates, those selected from commensal healthy skin (n = 20), commensal healthy conjunctive (n = 10), and clinical ocular infection (n = 30) presented the apsX, apsR, and apsS genes in their genomes. Constitutive expression of apsX, apsR, and apsS genes was determined by RT-qPCR in all isolates. It was found that expression of apsX, apsR, and apsS was 3.3–5.9-fold higher in commensal isolates stimulated with LL-37 (15 µg/mL) than in clinical isolates. Similarly, expression of the dlt operon and the genes mprF, and vraFG was 8–10-fold higher in commensal isolates than in clinical. However, LL-37 did not increase the addition of lysine in the phospholipids of the cytoplasmic membrane in any of the isolates. Mutations in the apsS loop region, apsR, and their promoter sequence were not found. These results demonstrated that apsXRS system is essential in all isolates for its constitutive expression; however, LL-37 caused an increase of apsXRS expression in commensal isolates, suggesting that S. epidermidis isolates do not respond in the same way to the presence of LL-37.

Staphylococci have quorum-sensing (QS) systems that enable cell-to-cell communication, as well as the regulation of numerous colonization and virulence factors. The accessory gene regulator (Agr) operon is one of the Staphylococcus genus QS systems. Three groups (I, II, and III) are present in Staphylococcus epidermidis Agr operon. To date, it is unknown whether Agr groups can interact symbiotically during biofilm development. This study analyzed a symbiotic association among Agr groups during biofilm formation in clinical and commensal isolates. Different combinations among Agr group isolates was used to study biofilm formation in vitro and in vivo (using a mouse catheter-infection model). The analysis of Agr groups were also performed from samples of human skin (head, armpits, and nostrils). Different predominant coexistence was found within biofilms, suggesting symbiosis type. In vitro, Agr I had a competition with Agr II and Agr III. Agr II had a competition with Agr III, and Agr II was an antagonist to Agr I and III when the three strains were combined. In vivo, Agr II had a competition to Agr I, but Agr I and II were antagonists to Agr III. The associations found in vitro and in vivo were also found in different sites of the skin. Besides, other associations were observed: Agr III antagonized Agr I and II, and Agr III competed with Agr I and Agr II. These results suggest that, in S. epidermidis, a symbiotic association of competition and antagonism occurs among different Agr groups during biofilm formation.

Objective To assess the effectiveness of cervical manual therapy (MT) on patients with temporomandibular disorders (TMDs) and to compare cervico-craniomandibular MT vs cervical MT. Design Systematic review and meta-analysis (MA). Methods A search in PubMed, EMBASE, PEDro, and Google Scholar was conducted with an end date of February 2019. Two independent reviewers performed the data analysis, assessing the relevance of the randomized clinical trials regarding the studies’ objectives. The qualitative analysis was based on classifying the results into levels of evidence according to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE). Results Regarding cervical MT, MA included three studies and showed statistically significant differences in pain intensity reduction and an increase in masseter pressure pain thresholds (PPTs), with a large clinical effect. In addition, the results showed an increase in temporalis PPT, with a moderate clinical effect. MA included two studies on cervical MT vs cervico-craniomandibular MT interventions and showed statistically significant differences in pain intensity reduction and pain-free maximal mouth opening, with a large clinical effect. Conclusions Cervical MT treatment is more effective in decreasing pain intensity than placebo MT or minimal intervention, with moderate evidence. Cervico-craniomandibular interventions achieved greater short-term reductions in pain intensity and increased pain-free MMO over cervical intervention alone in TMD and headache, with low evidence.

Objectives The objective was to explore whether action observation (AO) and motor imagery (MI) of aerobic and isometric exercise could induce hypoalgesic responses in asymptomatic individuals compared with placebo observation (PO). Methods A randomized controlled pilot trial was designed. Twenty-four healthy participants (mean age = 21.9 ± 2.1 years) were randomized into three groups: AO+MI (N = 8), AO, (N = 8), and PO (N = 8). All participants performed an actual aerobic running exercise (three series of 90 seconds at 85% of their VO2max and 30 seconds at 65% of their VO2max) and an isometric exercise protocol (isometric squats). A day later, they all performed the mental intervention, observing or imagining exercise execution performed the day before, according to their allocated group. Pressure pain thresholds (PPTs) of the quadriceps and epicondyle regions were assessed at baseline, postintervention, and 15 minutes postintervention. Results Analysis of variance revealed statistically significant differences in the group*time interaction for PPT in the quadriceps. The AO group showed a statistically significant increase at postintervention and at 15 minutes postintervention. The AO+MI group obtained a statistically significant increase in the two PPT regions compared with the PO group at Δpre–post. The AO group obtained a greater increase in the PPT in the quadriceps femoris than the PO group at Δpre–post and Δpre–post 15 minutes. Conclusions AO and MI induce hypoalgesic responses compared with PO. AO isolated training showed pain modulation responses in the PPTs of the quadriceps region in young physically active adults. These findings highlight the potential role of brain training in pain management.

Epidemiological studies comparing clinical and commensal Staphylococcus epidermidis isolates suggest that biofilm formation is a discriminant biomarker. A study showed that four non‐biofilm‐forming clinical S. epidermidis isolates could form an induced biofilm by trypsin treatment, suggesting that S. epidermidis can form biofilms in a protease‐independent way and in a trypsin‐induced way. In this study, the trypsin capacity to induce biofilm formation was evaluated in non‐biofilm‐forming S. epidermidis isolates (n = 133) in order to support this mechanism and to establish the importance of total biofilms (meaning the sum of protease‐independent biofilm and trypsin‐induced biofilm). Staphylococcus epidermidis isolates from ocular infections (OI; n = 24), prosthetic joint infections (PJI; n = 64), and healthy skin (HS‐1; n = 100) were screened for protease‐independent biofilm formation according to Christensen's method. The result was that there are significant differences (p, Epidemiological studies comparing clinical and commensal Staphylococcus epidermidis isolates suggest that biofilm formation is a discriminant biomarker. In this study, the capacity of trypsin to induce biofilm formation was evaluated in non‐biofilm‐forming S. epidermidis isolates. Trypsin is capable to induce biofilm production in non‐biofilm‐forming commensal S. epidermidis isolates with the icaA −/aap+ genotype

The three-component apsXRS system senses and responds to cationic antimicrobial peptides (CAMPs), which induces the expression of the dlt operon and the genes mprF and vrafG, modifying the surface net charge in Staphylococcus epidermidis, resulting in the repulsion of CAMPs. The apsXRS system has been only studied in the S. epidermidis 1457 strain, and there are no studies of prevalence and level of expression of apsXRS in commensal and clinical isolates. From 60 isolates, those selected from commensal healthy skin (n = 20), commensal healthy conjunctive (n = 10), and clinical ocular infection (n = 30) presented the apsX, apsR, and apsS genes in their genomes. Constitutive expression of apsX, apsR, and apsS genes was determined by RT-qPCR in all isolates. It was found that expression of apsX, apsR, and apsS was 3.3–5.9-fold higher in commensal isolates stimulated with LL-37 (15 µg/mL) than in clinical isolates. Similarly, expression of the dlt operon and the genes mprF, and vraFG was 8–10-fold higher in commensal isolates than in clinical. However, LL-37 did not increase the addition of lysine in the phospholipids of the cytoplasmic membrane in any of the isolates. Mutations in the apsS loop region, apsR, and their promoter sequence were not found. These results demonstrated that apsXRS system is essential in all isolates for its constitutive expression; however, LL-37 caused an increase of apsXRS expression in commensal isolates, suggesting that S. epidermidis isolates do not respond in the same way to the presence of LL-37.

Previous studies have shown that biofilm-forming bacteria are deficient in tricarboxylic acid (TCA) cycle metabolites, suggesting a relationship between these cellular processes. In this work, we compared the proteomes of planktonic vs biofilm cells from a clinical strain of Staphylococcus epidermidis using LC-MS/MS. A total of 168 proteins were identified from both growth conditions. The biofilm cells showed enrichment of proteins participating in glycolysis for the formation of pyruvate; however, the absence of TCA cycle proteins and the presence of lactate dehydrogenase, formate acetyltransferase, and acetoin reductase suggested that pyruvate was catabolized to their respective products: lactate, formate and acetoin. On the other hand, planktonic cells showed proteins participating in glycolysis and the TCA cycle, the pentose phosphate pathway , gluconeogenesis , ATP generation and the oxidative stress response. Functional networks with higher interconnection were predicted for planktonic proteins. We propose that in S. epidermidis , the relative absence of TCA cycle proteins is associated with the formation of biofilms and that lactate, formate and acetoin are the end products of partial glucose metabolism .

Staphylococci produce a large number of extracellular proteases, some of which are considered as potential virulence factors. Staphylococcus epidermidis is a causative agent of nosocomial infections in medical devices by the formation of biofilms. It has been proposed that proteases contribute to the different stages of biofilm formation. S. epidermidis secretes a small number of extracellular proteases, such as serine protease Esp, cysteine protease EcpA, and metalloprotease SepA that have a relatively low substrate specificity. Recent findings indicate a significant contribution of extracellular proteases in biofilm formation through the proteolytic inactivation of adhesion molecules. The objective of this work is to provide an overview of the current knowledge of S. epidermidis' extracellular proteases during pathogenicity, especially in the different stages of biofilm formation.

Background The Edinburgh postnatal depression scale (EPDS) has been validated and used successfully in detecting postnatal depression in several language versions in a number of countries. However, there is not any Mexican version of the EPDS that had been validated. Therefore, we sought to validate a Spanish translated Mexican version of the EPDS in a population of puerperal Mexican women. Methods One hundred puerperal women within their three month postpartum period attending routine postnatal consultations in a public hospital in Durango City, Mexico participated in the study. The participants were divided into two groups: one group included 49 women with less than 4 weeks of postpartum, and the other group included 51 women within 4 to 13 weeks of postpartum. All participants submitted a Spanish translated Mexican version of the EPDS and were interviewed by a psychiatrist to assess major and minor depression by using DSM-IV criteria. Results Out of the 49 women with less than 4 weeks of postpartum, 4 were found as suffering from major depression and none from minor depression by using the DSM-IV criteria. In this group of women we found that the best EPDS score for screening depression was 11/12. This threshold showed a sensitivity of 75% (95% CI: 63.8–86.2), a specificity of 93% (95% CI: 84.6–100), a positive predictive value of 50%, a negative predictive value of 97.6%, and an area under the curve of 0.84. While in the 51 women within 4 to 13 weeks of postpartum, 7 were found as suffering from major depression and 1 from minor depression by using the DSM-IV criteria. In this group we found that the best EPDS score for screening depression was 7/8. This threshold showed a sensitivity of 75% (95% CI: 66.1–83.9), a specificity of 84% (95% CI: 76.1–91.9), a positive predictive value of 46.2%, a negative predictive value of 94.7% and an area under the curve of 0.80. Conclusion The Mexican version of the EPDS can be considered for screening depression in puerperal Mexican women whenever cut-off scores of 11/12 and 7/8 in women with less than 4 weeks and within 4 to 13 weeks of postpartum are used, respectively.