HIV gp120 in the lungs of antiretroviral therapy–treated Individuals impairs alveolar macrophage responses to pneumococci

Rationale People living with HIV (PLWH) are at significantly increased risk of invasive pneumococcal disease, despite long-term antiretroviral therapy (ART). The mechanism explaining this observation remains undefined. Objectives We hypothesized apoptosis-associated microbicidal mechanisms, required to clear intracellular pneumococci that survive initial phagolysosomal killing, are perturbed. Methods Alveolar macrophages (AM) were obtained by bronchoalveolar lavage (BAL) from healthy donors or HIV-1-seropositive donors on long-term ART with undetectable plasma viral load. Monocyte-derived macrophages (MDM) were obtained from healthy donors and infected with HIV-1BaL or treated with gp120. Macrophages were challenged with opsonized serotype 2 Streptococcus pneumoniae and assessed for apoptosis, bactericidal activity, protein expression and mitochondrial reactive oxygen species (mROS). AM phenotyping, ultra-sensitive HIV-1 RNA quantification and gp120 measurement were also performed in BAL. Measurements and Main Results HIV-1BaL infection impaired apoptosis, induction of mROS and pneumococcal killing by MDM. Apoptosis-associated pneumococcal killing was also reduced in AM from ART treated HIV-1-seropositive donors. BAL fluid from these individuals demonstrated persistent lung CD8+ T-cell lymphocytosis, and gp120 or HIV-1 RNA was also detected. Despite this, transcriptional activity in AM freshly isolated from PLWH was broadly similar to healthy volunteers. Instead, gp120 phenocopied the defect in pneumococcal killing in healthy MDM through post-translational modification of Mcl-1, preventing apoptosis induction, caspase activation and increased mROS generation. Moreover gp120 also inhibited mROS dependent pneumococcal killing in MDM. Conclusions. Despite ART, HIV-1, via gp120, drives persisting innate immune defects in AM microbicidal mechanisms, enhancing susceptibility to pneumococcal disease

Impaired Mitochondrial Microbicidal Responses in Chronic Obstructive Pulmonary Disease Macrophages

RATIONALE: Chronic obstructive pulmonary disease (COPD) is characterized by impaired clearance of pulmonary bacteria. OBJECTIVES: The effect of COPD on alveolar macrophage (AM) microbicidal responses was investigated. METHODS: Alveolar macrophages (AMs) were obtained from bronchoalveolar lavage from healthy donors or COPD patients and challenged with opsonized serotype 14 Streptococcus pneumoniae. Cells were assessed for apoptosis, bactericidal activity and mitochondrial reactive oxygen species (mROS) production. A transgenic mouse line, in which the CD68 promoter ensures macrophage specific expression of human Mcl-1 (CD68.hMcl-1), was used to model the molecular aspects of COPD. MEASUREMENTS AND MAIN RESULTS: COPD AM had elevated levels of Mcl-1, an anti-apoptotic Bcl-2 family member, with selective reduction of delayed intracellular bacterial killing. CD68.hMcl-1 AM phenocopied the microbicidal defect since transgenic mice demonstrated impaired clearance of pulmonary bacteria and increased neutrophilic inflammation. Murine bone marrow-derived macrophages (BMDM) and human monocyte-derived macrophages (MDM) generated mitochondrial reactive oxygen species (mROS) in response to pneumococci, which co-localized with bacteria and phagolysosomes to enhance bacterial killing. The Mcl-1 transgene increased oxygen consumption rates and mROS expression in mock-infected BMDM but reduced caspase-dependent mROS production after pneumococcal challenge. COPD AM also increased basal mROS expression, but failed to increase production after pneumococcal challenge, in keeping with reduced intracellular bacterial killing. The defect in COPD AM intracellular killing was associated with a reduced ratio of mROS /superoxide dismutase 2. CONCLUSIONS: Upregulation of Mcl-1 and chronic adaption to oxidative stress alters mitochondrial metabolism and microbicidal function, reducing the delayed phase of intracellular bacterial clearance in COPD

The role of physiotherapy interventions in the management of temporomandibular joint ankylosis: a systematic review and meta-analysis

Abstract Background The main aim of this systematic review and meta-analysis was to identify peer-reviewed scholarly journal articles reporting the significance of physiotherapy interventions in managing TMJ ankylosis. In addition, this study aimed to critically appraise the existing evidence on the prevalence and clinical presentation, physiotherapy intervention approaches, efficacy of physiotherapy interventions, adverse effects, and safety of physiotherapy interventions in TMJ ankylosis management. Methods An all-inclusive literature search was conducted using the PubMed, Google Scholar, and Scopus electronic databases. The researchers screened the potential articles and assessed for eligibility based on the reported inclusion and exclusion criteria. The quality evaluation tool for observational cohort and cross-sectional studies developed by the National Institutes of Health (NIH) and the Cochrane Collaboration's Risk of Bias Tool were used to assess the quality of the included studies. Researchers also comprehensively analyzed the data, reported the results, and discussed them according to the predominant themes. Results The primary electronic database search yielded 409 articles, of which 25 were included in this review. A secondary search was conducted from citations of the included studies, yielding 74 articles, of which six were included in the study. A significantly higher prevalence of bony ankylosis than fibrous ankylosis, with an overall effect size of p < 0.00001. In addition, there were significantly more unilateral than bilateral presentations with an overall effect size of p < 0.00001. Moreover, there were 78 reported complications out of 245 subjects according to five included studies demonstrating a significant effect size with p = 0.001 following the treatment protocols. Conclusion This study highlighted the prevalence of bony ankylosis in temporomandibular joint ankylosis, emphasizing its impact on patients' well-being. On the other hand, the results show that physiotherapy is essential to optimize postoperative outcomes and minimize adverse events such as re-ankylosis. Practitioners and healthcare professionals must monitor postoperative recovery and ensure strict adherence to physiotherapy protocols for optimal outcomes

Co-exposure of chromium or cadmium and a low concentration of amoxicillin are responsible to emerge amoxicillin resistant Staphylococcus aureus

ABSTRACT: Background: Heavy metals and antimicrobials co-exist in many environmental settings. The co-exposure of heavy metals and antimicrobials can drive emergence of antimicrobial resistant (AMR) Enterobacteriaceae. We hypothesized that co-exposure to heavy metals and a low concentration of antibiotic might alter antimicrobial susceptibility patterns, which facilitate emergence of AMR Staphylococcus aureus. Methods: The growth kinetics of antimicrobial susceptible S. aureus was carried out in the presence of chromium or cadmium salt and a low concentration of antibiotics. Subsequently, the antimicrobial susceptibility pattern was determined by the Kirby-Bauer disc diffusion method. Moreover, the mRNA copy number was determined by reverse transcription polymerase chain reaction. Results: The antimicrobial susceptibility profile revealed that the zone of inhibition (ZOI) for ampicillin, amoxicillin, ciprofloxacin and doxycycline was significantly decreased in chromium pre-exposed S. aureus compared to unexposed bacteria, whereas cadmium pre-exposed bacteria only showed significant decreased in ZOI for amoxicillin. Moreover, the MIC of amoxicillin for S. aureus was increased by 8-fold in chromium and 32-fold in cadmium when bacteria were co-exposed with low concentrations of amoxicillin. The mRNA expression of femX, mepA and norA also significantly increased in S. aureus after exposure to chromium and a low concentration of amoxicillin. Conclusion: Cultivation of S. aureus at the minimum levels of chromium or cadmium and a low concentration of amoxicillin increased the inhibitory concentration of amoxicillin through inducing bacterial efflux pumps and antibiotic resistant genes. However, it is warranted to assess the whole transcriptome to find out all responsible factors behind this de novo amoxicillin resistant S. aureus

Spectrophotometric Analysis of Dental Enamel Staining to Antiseptic and Dietary Agents: In Vitro Study

Background/Objectives. Use of antiseptics as an adjunct to a traditional mechanical tooth brushing method has limited their application for long duration because of their side effects such as staining and calculus formation. The objective of this in vitro study is to analyse the staining effects of antiseptic mouthwashes on dental enamel and compare it with those containing nanoparticles, dietary agents, and distilled water (control). Material and Methods. 105 intact premolars extracted for orthodontic reasons and without any caries or anatomical defects were selected for analysis. The samples were randomly divided into 7 different groups of fifteen teeth each for different solutions. A spectrophotometer was used to assess the colorimeter analysis of buccal dental enamel surface at R1 (baseline examination), R2 (24 hours after immersion in different solutions), and R3 (after brushing). Statistical analysis was done using the Kolmogorov–Smirnov test and Levene’s test (p<0.05), respectively. One-way ANOVA was used to compare the difference in color (∆E) between the readings, R1, R2, and R3. Results. The mouthwash containing titanium dioxide (TiO2) nanoparticles produced the greater enamel discoloration compared to that of chlorhexidine. Brushing had little effect on removal of stains induced by all mouthwashes except for dietary solutions (lemon with sodium bicarbonate and olive with laurel) and distilled water (control). Conclusion. The results from this study show that mouthwashes containing TiO2 nanoparticles and other antiseptic mouthwashes cause change in color of the teeth and lead to poor esthetic appearance when compared to dietary and control solutions. Thus, future in vivo studies have to be conducted to confirm these findings as in vitro studies may not provide a reliable simulation of the clinical situations