The cellular architecture of the antimicrobial response network in human leprosy granulomas.

Granulomas are complex cellular structures composed predominantly of macrophages and lymphocytes that function to contain and kill invading pathogens. Here, we investigated the single-cell phenotypes associated with antimicrobial responses in human leprosy granulomas by applying single-cell and spatial sequencing to leprosy biopsy specimens. We focused on reversal reactions (RRs), a dynamic process whereby some patients with disseminated lepromatous leprosy (L-lep) transition toward self-limiting tuberculoid leprosy (T-lep), mounting effective antimicrobial responses. We identified a set of genes encoding proteins involved in antimicrobial responses that are differentially expressed in RR versus L-lep lesions and regulated by interferon-γ and interleukin-1ß. By integrating the spatial coordinates of the key cell types and antimicrobial gene expression in RR and T-lep lesions, we constructed a map revealing the organized architecture of granulomas depicting compositional and functional layers by which macrophages, T cells, keratinocytes and fibroblasts can each contribute to the antimicrobial response.

Second-Strand Synthesis-Based Massively Parallel scRNA-Seq Reveals Cellular States and Molecular Features of Human Inflammatory Skin Pathologies.

High-throughput single-cell RNA-sequencing (scRNA-seq) methodologies enable characterization of complex biological samples by increasing the number of cells that can be profiled contemporaneously. Nevertheless, these approaches recover less information per cell than low-throughput strategies. To accurately report the expression of key phenotypic features of cells, scRNA-seq platforms are needed that are both high fidelity and high throughput. To address this need, we created Seq-Well S3 ("Second-Strand Synthesis"), a massively parallel scRNA-seq protocol that uses a randomly primed second-strand synthesis to recover complementary DNA (cDNA) molecules that were successfully reverse transcribed but to which a second oligonucleotide handle, necessary for subsequent whole transcriptome amplification, was not appended due to inefficient template switching. Seq-Well S3 increased the efficiency of transcript capture and gene detection compared with that of previous iterations by up to 10- and 5-fold, respectively. We used Seq-Well S3 to chart the transcriptional landscape of five human inflammatory skin diseases, thus providing a resource for the further study of human skin inflammation.

Effects of pasture management and supplementation on the productive performance of recently lambed ewes.

The hypothesis was tested that the performance of lactating ewes is affected by the supplementation level and pasture management. Two supplementation levels (0.5 and 1.0% of body weight, BW) and two pasture managements (mowed and non-mowed) were tested. Forty adult ewes (2 years old) with an average weight at lambing of 62.97 ± 7.0 kg (day 0) and an average the body condition score of 2.5 points (day 0) were evaluated. Verminosis was monitored with periodic deworming. The number of eggs per gram of feces (EPG) of ewes at lambing was used as a covariate for performance assessments. Ewes lost an average of 7.5 kg over the 90 days post-partum (12% BW). The weaning rate was 53%. The body condition of the ewes was influenced by the post-partum period. The ewes mobilized their body reserves in the first 30 days of lactation. Mowing management negatively affected the nutritive value of the forage. Supplementation with 0.5% BW was sufficient for nutritional management post-partum. Pasture management (mowed vs. not mowed) cannot prevent post-partum weight loss. Supplementation levels and pasture management altered the morphological and chemical components of the pasture.

Antioxidant action of yerba mate on carcass and meat characteristics and fatty acid profile in meat and fat of lambs finished in tropical pastures.

The objective was to evaluate the effect of the supplementation with natural antioxidants from Yerba mate (Ilex paraguariensis St. Hil.) on the performance, carcass and meat characteristics, and fatty acid profile in meat and fat of Texel × Ile de France lambs kept in Brachiaria-grass pasture. Twenty lambs with a mean age of 90 days and 26.3 kg of BW were distributed in a completely randomized design in two treatments with 10 replicates/treatment: Control-protein-energy supplement based on corn and soybean meal (150 g/kg DM of crude protein) without the addition of natural antioxidant yerba mate and Yerba Mate - energy protein supplement with the addition of yerba mate (110 g/kg DM). There was no treatment effect on animal performance and carcass characteristics. The subcutaneous fat thickness was significantly higher for lambs treated without yerba mate. There was no effect of nutritional treatments on the oxidative markers of lamb meat. The muscle of the animals treated with yerba mate showed a higher concentration of unsaturated and polyunsaturated fatty acids elaidic, linolenic, thymnodonic, docosadienoic, and ceorvonic. The fat of the animals treated with yerba mate showed a higher concentration of palmitoleic acid, linoelaidic acid, heneicosanoic acid, dihomo-γ-linolenic acid, and arachidonic acid. The concentration of polyunsaturated fatty acids was significantly higher in meat and fat of lambs treated with yerba mate. Including yerba mate in the diet of lambs kept on Brachiaria pastures improves the lipid profile of polyunsaturated fatty acids in meat and fat, without altering the performance of the animals.

Mathematical models to predict the lamb weight at birth and at weaning reared in the tropical warm-climate pasture.

Our objective was to evaluate the productive parameters of ewes and their lambs in relation to ewe age and to develop models for predicting lamb weight at birth and weaning in a tropical warm-climate pasture. Individual data were collected from 273 ewes and 273 lambs, between 2013 and 2021. During this period all animals were kept on pastures of Brachiaria brizantha cv. Marandu All lambs in the experiments were supplemented in creep-feeding. A descriptive statistical analysis was performed using the PROC SUMMARY procedure in SAS (SAS University Edition, SAS Institute Inc. Cary, CA, USA). Pearson correlation coefficients between variables were estimated using the PROC CORR procedure in SAS (SAS University Edition, SAS Institute Inc. Cary, CA, USA). Model adjustments and variable selection were performed using PROC REG in SAS (SAS University Edition, SAS Institute Inc. Cary, CA, USA). The STEPWISE option and Mallow's C(p) were used to select the variables included in the equations. Outliers were identified by evaluating the studentized residuals based on the predicted values from the equations. Residual analysis was predicted by regression minus observed values and those that fell outside the range of -2.5 to 2.5 were removed. Several statistics were used to assess the predictability of the equations, including the coefficients of determination (r2) and mean standard error (RMSE). The average ewe age at lambing was 3.4 ± 1.7 years, with an average weight of 56.9 ± 8,9 kg and average body condition score (BCS) of 2,4 ± 0.8 points. The average ewe age at weaning was 51.1 ± 7.9, with average BCS of 1.8 ± 0.8 points. The average lamb at birthing was 3.9 ± 0.9 kg. The average lamb at weaning was 21.0 ± 4.9, with daily gain of 0.2 ± 0.1 kg/day and total gain of 17.1 ± 4.7 kg birth to weaning. The lamb produced by ewe at lambing was 5.3 ± 1.7 kg/ewe. The lamb weaned by ewe at weaning was 28.7 ± 10.8 kg/ewe. The ratios of lamb produced per ewe at birth and at weaning were 0.1 ± 0.03 and 0.6 ± 0.2, respectively. The lamb's birth weight showed a positive linear relationship with the age of the ewe, increasing by 115 g per year of age. The regression equations adjusted for ewe age had maximum points ranging from 4.2 to 5.2, occurring at average age of 4,7 years. The other characteristics showed a quadratic tendency. The results suggest the culling of ewes at five years of age to generate lambs with ideal weight at birth and at weaning raised in warm tropical pastures.

Collagen V α1 Chain Decrease in Papillary Dermis from Early Systemic Sclerosis: A New Proposal in Cutaneous Fibrosis Molecular Structure.

Cutaneous fibrosis is one of the main features of systemic sclerosis (SSc). Recent findings correlated abnormal collagen V (Col V) deposition in dermis with skin thickening and disease activity in SSc. Considering that Col V is an important regulator of collagen fibrillogenesis, understanding the role of Col V in the first two years of the skin fibrosis in SSc (early SSc) can help to determine new targets for future treatments. In this study, we analyzed the morphological, ultrastructural and molecular features of α1(V) and α2(V) chains and the expression of their coding genes COL5A1 and COL5A2 in collagen fibrillogenesis in early-SSc. Skin biopsies were obtained from seven consecutive treatment-naïve patients with SSc-related fibrosis and four healthy controls. Our data showed increased α1(V) and α2(V) chain expression in the reticular dermis of early-SSc patients; however, immunofluorescence and ultrastructural immunogold staining determined a significant decreased expression of the α1(V) chain along the dermoepidermal junction in the papillary dermis from early-SSc-patients in relation to the control (12.77 ± 1.34 vs. 66.84 ± 3.36; p < 0.0001). The immunoblot confirmed the decreased expression of the α1(V) chain by the cutaneous fibroblasts of early-SSc, despite the increased COL5A1 and COL5A2 gene expression. In contrast, the α2(V) chain was overexpressed in the small vessels (63.18 ± 3.56 vs. 12.16 ± 0.81; p < 0.0001) and capillaries (60.88 ± 5.82 vs. 15.11 ± 3.80; p < 0.0001) in the reticular dermis of early-SSc patients. Furthermore, COLVA2 siRNA in SSc cutaneous fibroblasts resulted in a decreased α1(V) chain expression. These results highlight an intense decrease in the α1(V) chain along the dermoepidermal junction, suggesting an altered molecular histoarchitecture in the SSc papillary dermis, with a possible decrease in the expression of the α1(V)3 homotrimeric isoform, which could interfere with the thickening and cutaneous fibrosis related to SSc.

Yerba mate (Ilex paraguariensis) as a source of antioxidants with soybean grain in supplementation of lactating ewes reared in tropical pastures.

The hypothesis tested is that the association of soybean grain and yerba mate as an antioxidant source can increase the concentration of polyunsaturated fatty acids (PUFA) with lower oxidation of milk from lactating ewes reared in tropical pastures. Sixteen ewes were randomly distributed in a 2x2 factorial scheme (with or without yerba mate at 110 g / kg of dry matter (DM); with or without soybean grain at 210 g/kg of DM). Yerba mate intake reduced DM intake, and concentrations of ether extract (EE), protein, lactose, defatted dry extract, density, omega-3 concentrations, and the ratio between saturated/monounsaturated fatty acids (FA), but increased the concentration of monounsaturated FA and the sequestering power of free radicals by DPPH without altering the concentrations of conjugated dienes and the concentrations of substances reactive to thiobarbituric acid in milk. Supplementation with soybean grain decreased the birth weight of the lambs and increased the concentrations of conjugated linoleic acid (CLA), PUFA, omega - 6, omega ratio - 6/omega - 3, and total blood cholesterol. The addition of yerba mate did not influence the oxidative profile of milk. Supplementation with soybean grain improved the FA profile of milk, increasing the concentrations of CLA and PUFA. The results suggest that the association of yerba mate and soybean grain helps to improve the fat quality of milk from ewes raised in tropical pastures, as shown by the enhanced antioxidant activity, although it does not help prevent oxidation of milk rich in PUFA.

Autophagy Is an Innate Mechanism Associated with Leprosy Polarization.

Leprosy is a chronic infectious disease that may present different clinical forms according to the immune response of the host. Levels of IFN-γ are significantly raised in paucibacillary tuberculoid (T-lep) when compared with multibacillary lepromatous (L-lep) patients. IFN-γ primes macrophages for inflammatory activation and induces the autophagy antimicrobial mechanism. The involvement of autophagy in the immune response against Mycobacterium leprae remains unexplored. Here, we demonstrated by different autophagic assays that LC3-positive autophagosomes were predominantly observed in T-lep when compared with L-lep lesions and skin-derived macrophages. Accumulation of the autophagic receptors SQSTM1/p62 and NBR1, expression of lysosomal antimicrobial peptides and colocalization analysis of autolysosomes revealed an impairment of the autophagic flux in L-lep cells, which was restored by IFN-γ or rapamycin treatment. Autophagy PCR array gene-expression analysis revealed a significantly upregulation of autophagy genes (BECN1, GPSM3, ATG14, APOL1, and TPR) in T-lep cells. Furthermore, an upregulation of autophagy genes (TPR, GFI1B and GNAI3) as well as LC3 levels was observed in cells of L-lep patients that developed type 1 reaction (T1R) episodes, an acute inflammatory condition associated with increased IFN-γ levels. Finally, we observed increased BCL2 expression in L-lep cells that could be responsible for the blockage of BECN1-mediated autophagy. In addition, in vitro studies demonstrated that dead, but not live M. leprae can induce autophagy in primary and lineage human monocytes, and that live mycobacteria can reduce the autophagy activation triggered by dead mycobacteria, suggesting that M. leprae may hamper the autophagic machinery as an immune escape mechanism. Together, these results indicate that autophagy is an important innate mechanism associated with the M. leprae control in skin macrophages.

Chemical composition and evaluation of antileishmanial and cytotoxic activities of the essential oil from leaves of Cryptocarya aschersoniana Mez. (Lauraceae Juss.).

Leishmaniasis is an endemic disease caused by protozoa of the genus Leishmania, which affects around two million people worldwide. One major drawback in the treatment of leishmaniasis is the emergence of resistance to current chemotherapeutics. Medicinal and aromatic plants constitute a major source of natural organic compounds. In this study, the leaf essential oil of Cryptocarya aschersoniana was obtained by hydrodistillation in a Clevenger-type apparatus, and the chemical composition was analyzed by GC-MS and GC-FID. The essential oil of these species was predominantly constituted by monoterpene hydrocarbons (48.8%). Limonene (42.3%), linalool (9.7%) and nerolidol (8.6%) were the main constituents in the oil of C. aschersoniana. The in vitro activity of the oil was evaluated against the promastigote forms of Leishmania amazonensis, the causative agent of cutaneous leishmaniasis in humans. The essential oil of C. aschersoniana showed high activity against L. amazonensis promastigote forms (IC50 = 4.46 µg/mL), however, it also demonstrated a relatively high cytotoxicity on mouse peritoneal macrophages (CC50 = 7.71 µg/mL). This is the first report of the chemical composition and the leishmanicidal and cytotoxic activities of the leaf essential oil of C. aschersoniana.

Photodynamic therapy decrease immune-inflammatory mediators levels during periodontal maintenance.

Antimicrobial photodynamic therapy (aPDT) was introduced as a promising adjuvant therapy on the periodontal treatment. The aim of this study was to evaluate the effect of aPDT on inflammatory mediator levels in residual periodontal pockets of patients with severe chronic periodontitis under periodontal maintenance, during 12 months follow-up. A randomized controlled trial study was conducted in 28 patients with severe chronic periodontitis. After non-surgical periodontal treatment, patients with at least four teeth with residual pocket probing depth (PPD) ≥4 mm were randomly assigned to either aPDT or control group. The aPDT (low power laser: 660 nm, 40 mW, 90 J/cm2, methylene blue 0.01 %) was performed at baseline and 3, 6, and 9 months. Clinical parameters were collected before and 3 and 12 months after the intervention, and gingival crevicular fluid was collected in the same times, including 1 week after the intervention. Immunological evaluation was carried out using the Luminex assay which quantified the expression of ten cytokines: interleukin (IL)-1α, IL-1ß, IL-8, IL-1ra, fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF), interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-4, and IL-10. All clinical variables showed significant improvement for both groups, but there was no statistical difference between groups with no clinical benefits. IL-1α, IL-1ß, IL-8, and VEGF showed significant differences (p < 0.05) between groups, whereas IL-1ra mediators, IFN-γ, and IL-10 demonstrated a statistical difference (p < 0.01) over time in the same group. At any time, FGF, IL-4, and TNF-α showed no statistical difference between groups (p > 0.05). aPDT therapy can improve the benefits on inflammation control during the periodontal maintenance.

Antimicrobial photodynamic effect to treat residual pockets in periodontal patients: a randomized controlled clinical trial.

AIM: A randomized controlled clinical trial was designed to evaluate the efficacy of the photodynamic therapy (PDT) in the treatment of residual pockets of chronic periodontitis patients. MATERIAL AND METHODS: Thirty-four patients with at least four residual periodontal pockets undergoing maintenance care were included and randomly assigned to test group (PDT, n = 18) or control group (sham procedure, n = 16). The intervention was performed at baseline, 3, 6 and 12 months. Clinical parameters such as pocket probing depth (PPD), clinical attachment level (CAL), bleeding on probing (BoP) and plaque index (PI) were measured before intervention and after 3, 6 and 12 months. Subgingival samples were obtained at baseline, and after 7 days, 3, 6 and 12 months to quantify Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia by real-time polimerase chain reaction (PCR). RESULTS: All clinical variables showed significant improvement during the study, but there was no significant difference between test and control groups. The microbiological analyses showed no differences between groups at any time during the study. CONCLUSION: Within the limits of this clinical trial and considering the laser and photosensitizer protocol used, PDT failed to demonstrate additional clinical and bacteriological benefits in residual pockets treatment.

Effect of apoptotic cell recognition on macrophage polarization and mycobacterial persistence.

Intracellular Mycobacterium leprae infection modifies host macrophage programming, creating a protective niche for bacterial survival. The milieu regulating cellular apoptosis in the tissue plays an important role in defining susceptible and/or resistant phenotypes. A higher density of apoptotic cells has been demonstrated in paucibacillary leprosy lesions than in multibacillary ones. However, the effect of apoptotic cell removal on M. leprae-stimulated cells has yet to be fully elucidated. In this study, we investigated whether apoptotic cell removal (efferocytosis) induces different phenotypes in proinflammatory (Mϕ1) and anti-inflammatory (Mϕ2) macrophages in the presence of M. leprae. We stimulated Mϕ1 and Mϕ2 cells with M. leprae in the presence or absence of apoptotic cells and subsequently evaluated the M. leprae uptake, cell phenotype, and cytokine pattern in the supernatants. In the presence of M. leprae and apoptotic cells, Mϕ1 macrophages changed their phenotype to resemble the Mϕ2 phenotype, displaying increased CD163 and SRA-I expression as well as higher phagocytic capacity. Efferocytosis increased M. leprae survival in Mϕ1 cells, accompanied by reduced interleukin-15 (IL-15) and IL-6 levels and increased transforming growth factor beta (TGF-ß) and IL-10 secretion. Mϕ1 cells primed with M. leprae in the presence of apoptotic cells induced the secretion of Th2 cytokines IL-4 and IL-13 in autologous T cells compared with cultures stimulated with M. leprae or apoptotic cells alone. Efferocytosis did not alter the Mϕ2 cell phenotype or cytokine secretion profile, except for TGF-ß. Based on these data, we suggest that, in paucibacillary leprosy patients, efferocytosis contributes to mycobacterial persistence by increasing the Mϕ2 population and sustaining the infection.

CD163 favors Mycobacterium leprae survival and persistence by promoting anti-inflammatory pathways in lepromatous macrophages.

Lepromatous macrophages possess a regulatory phenotype that contributes to the immunosuppression observed in leprosy. CD163, a scavenger receptor that recognizes hemoglobin-haptoglobin complexes, is expressed at higher levels in lepromatous cells, although its functional role in leprosy is not yet established. We herein demonstrate that human lepromatous lesions are microenvironments rich in IDO⁺CD163⁺. Cells isolated from these lesions were CD68⁺IDO⁺CD163⁺ while higher levels of sCD163 in lepromatous sera positively correlated with IL-10 levels and IDO activity. Different Myco-bacterium leprae (ML) concentrations in healthy monocytes likewise revealed a positive correlation between increased concentrations of the mycobacteria and IDO, CD209, and CD163 expression. The regulatory phenotype in ML-stimulated monocytes was accompanied by increased TNF, IL-10, and TGF-ß levels whereas IL-10 blockade reduced ML-induced CD163 expression. The CD163 blockade reduced ML uptake in human monocytes. ML uptake was higher in HEK293 cells transfected with the cDNA for CD163 than in untransfected cells. Simultaneously, increased CD163 expression in lepromatous cells seemed to be dependent on ML uptake, and contributed to augmented iron storage in lepromatous macrophages. Altogether, these results suggest that ML-induced CD163 expression modulates the host cell phenotype to create a favorable environment for myco-bacterial entry and survival.

Pericapsular Nerve Group (PENG) block versus fascia iliaca compartment (FI) block for hip surgery: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: This study compares Fascia Iliaca compartment (FI) block and Pericapsular Nerve Group (PENG) block for hip surgery. METHODS: Pubmed, Embase and Cochrane were systematically searched in April 2022. Inclusion criteria were: Randomized Controlled Trials (RCTs); comparing PENG block versus FI block for hip surgery; patients over 18 years of age; and reporting outcomes immediately postoperative. We excluded studies with overlapped populations and without a head-to-head comparison of the PENG block vs. FI block. Mean-Difference (MD) with 95% Confidence Intervals (CI) were pooled. Trial Sequential Analyses (TSA) were performed to assess inconsistency. Quality assessment and risk of bias were performed according to Cochrane recommendations. RESULTS: Eight RCTs comprising 384 patients were included, of whom 196 (51%) underwent PENG block. After hip surgery, PENG block reduced static pain score at 12h post-surgery (MD = 0.61 mm; 95% CI 1.12 to -0.09; p = 0.02) and cumulative postoperative oral morphine consumption in the first 24h (MD = -6.93 mg; 95% CI -13.60 to -0.25; p = 0.04) compared with the FI group. However, no differences were found between the two techniques regarding dynamic and static pain scores at 6 h or 24 h post-surgery, or in the time to the first analgesic rescue after surgery. CONCLUSION: The findings suggest that PENG block reduced opioid consumption in the first 24 h after surgery and reduced pain scores at rest at 12 h post-surgery. Further research is needed to fully understand the effects of the PENG block and its potential benefits compared to FI block. PROSPERO REGISTRATION: CRD42022339628 PROSPERO REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=339628.

Spirituality, religiosity, and their representations for people living with HIV: daily life and its experiences.

OBJECTIVE: To describe the process of living with HIV/AIDS in the daily life of people living with HIV in its interface with the social representations of spirituality and religiosity. METHOD: Qualitative research, supported by the theory of social representations. A semi-structured interview was carried out with 32 people undergoing treatment for HIV in an outpatient clinic specialized in HIV/AIDS. Analysis carried out with the support of software IRAMUTEQ. RESULTS: Participants were mostly men, aged over 51 years, Catholic, and living with the virus for more than 10 years. IRAMUTEQ generated three classes, in which the influence of spirituality and religiosity as a promoter of strength to face the infection and the difficulties in the process of coping with the diagnosis was observed, as well as the importance of the support network, and the naturalization of HIV/AIDS. CONCLUSION: The participants make associations between spirituality and the transcendent and divine; religiosity was anchored to religion and its experience, with both being a source of support and strength. Therefore, it is important to make room for the patient to talk about their spiritual/religious needs.

IFN-γ-mediated control of SARS-CoV-2 infection through nitric oxide.

Introduction: The COVID-19 pandemic has highlighted the need to identify mechanisms of antiviral host defense against SARS-CoV-2. One such mediator is interferon-g (IFN-γ), which, when administered to infected patients, is reported to result in viral clearance and resolution of pulmonary symptoms. IFN-γ treatment of a human lung epithelial cell line triggered an antiviral activity against SARS-CoV-2, yet the mechanism for this antiviral response was not identified. Methods: Given that IFN-γ has been shown to trigger antiviral activity via the generation of nitric oxide (NO), we investigated whether IFN-γ induction of antiviral activity against SARS-CoV-2 infection is dependent upon the generation of NO in human pulmonary epithelial cells. We treated the simian epithelial cell line Vero E6 and human pulmonary epithelial cell lines, including A549-ACE2, and Calu-3, with IFN-γ and observed the resulting induction of NO and its effects on SARS-CoV-2 replication. Pharmacological inhibition of inducible nitric oxide synthase (iNOS) was employed to assess the dependency on NO production. Additionally, the study examined the effect of interleukin-1b (IL-1ß) on the IFN-g-induced NO production and its antiviral efficacy. Results: Treatment of Vero E6 cells with IFN-γ resulted in a dose-responsive induction of NO and an inhibitory effect on SARS-CoV-2 replication. This antiviral activity was blocked by pharmacologic inhibition of iNOS. IFN-γ also triggered a NO-mediated antiviral activity in SARS-CoV-2 infected human lung epithelial cell lines A549-ACE2 and Calu-3. IL-1ß enhanced IFN-γ induction of NO, but it had little effect on antiviral activity. Discussion: Given that IFN-g has been shown to be produced by CD8+ T cells in the early response to SARS-CoV-2, our findings in human lung epithelial cell lines, of an IFN-γ-triggered, NO-dependent, links the adaptive immune response to an innate antiviral pathway in host defense against SARS-CoV-2. These results underscore the importance of IFN-γ and NO in the antiviral response and provide insights into potential therapeutic strategies for COVID-19.

Clinical nursing care protocol for convalescent plasma transfusion in patients with COVID-19.

Introduction: The treatment of COVID-19 is still challenge. So convalescent plasma can be an important alternative of treatment. Protocols with nursing care during infusion is very important to guide an effective and safety care. Objective: to analyze the evidence in the literature on the action of convalescent plasma, of the use of protocols with nursing care to use convalescent plasma and build a nursing care protocol for transfusion in patients with COVID-19. Methods: Methodological study carried out in two stages: scoping review. The search was done using the descriptors: convalescent plasma transfusion, convalescent plasma, and acute respiratory syndromes or COVID-19, to found protocols and effectiveness of convalescent plasm. Beside was done a specialist panel to build the protocol. Results: Low-evidence studies have shown improvement in the clinical signs of COVID-19 using Convalescent Plasma, reduction or elimination of viral load, benefits in the production of lymphocytes, decreases C-reactive protein, increases titers of anti-SARS-CoV-2 antibodies, positive evolution in lung involvement identified by X-rays, decrease in hospitalization. No studies were found in the databases on the protocol for clinical nursing care in plasma transfusion. Therefore, a protocol was developed with the description of clinical nursing care to be performed before, during and after the transfusion by plasma: checking of vital signs and indicative signs of transfusion reaction, measurement of oxygen saturation, assessment of venous access and checking of the level of consciousness. Conclusion: There are no evidence studies to support the use of plasma, nor anything related to bundles.

Microbiological identification and resistance profile of microorganisms in pressure injuries after the use of polyhexamethylene biguanide: a series of fourteen cases.

INTRODUCTION: Colonization of a pressure injury with microorganisms can negatively affect wound healing. Thus, it is necessary to evaluate which products best facilitate wound healing. OBJECTIVE: This case series evaluated the effectiveness of the antimicrobial polyhexamethylene biguanide (PHMB) on microorganisms in pressure injuries. MATERIALS AND METHODS: Fourteen patients (14 wounds) were treated with PHMB in the hospital setting after collection of a wound swab sample for microbiological analysis and determination of the risk profile using the disk diffusion method. RESULTS: Thirteen lesions (92.9%) were positive for 1 or more bacterial strains, the most prevalent of which were Staphylococcus aureus and Pseudomonas aeruginosa. Two strains of methicillin-resistant S aureus (MRSA) were also identified. Klebsiella pneumoniae demonstrated 100% resistance to the tested antibiotics, with Acinetobacter demonstrating 90% resistance, P aeruginosa 88.9%, Citrobacter freundii 87.5%, S aureus 66.7%, and MRSA 57.1%. Only Serratia marcescens demonstrated no resistance to any antibiotic tested. Polyhexamethylene biguanide was effective only against strains of S marcescens, which were not present in the second wound swab sample collected (after the application of PHMB); other microorganisms were present in the second wound swab sample collected. CONCLUSIONS: Polyhexamethylene biguanide has an immediate antimicrobial effect on S marcescens. However, it had no qualitative effect on the other microorganisms. Studies with larger populations and randomized clinical trial methodologies are necessary to elucidate additional findings concerning the effectiveness of PHMB in managing microorganisms in pressure injuries.

TREM2 macrophages induced by human lipids drive inflammation in acne lesions.

Acne affects 1 in 10 people globally, often resulting in disfigurement. The disease involves excess production of lipids, particularly squalene, increased growth of Cutibacterium acnes, and a host inflammatory response with foamy macrophages. By combining single-cell and spatial RNA sequencing as well as ultrahigh-resolution Seq-Scope analyses of early acne lesions on back skin, we identified TREM2 macrophages expressing lipid metabolism and proinflammatory gene programs in proximity to hair follicle epithelium expressing squalene epoxidase. We established that the addition of squalene induced differentiation of TREM2 macrophages in vitro, which were unable to kill C. acnes. The addition of squalene to macrophages inhibited induction of oxidative enzymes and scavenged oxygen free radicals, providing an explanation for the efficacy of topical benzoyl peroxide in the clinical treatment of acne. The present work has elucidated the mechanisms by which TREM2 macrophages and unsaturated lipids, similar to their involvement in atherosclerosis, may contribute to the pathogenesis of acne.

Interaction between Work and Metabolic Syndrome: A Population-Based Cross-Sectional Study.

Metabolic syndrome (MS) is a clinical condition and a relevant risk factor in the development of cardiovascular diseases; it occurs as a result of lifestyle factors, e.g., work. The aim of this research was to estimate the interaction between work and MS among primary health care (PHC) nursing professionals in the state of Bahia, Brazil. A sectional multicentered study carried out in 43 municipalities in Bahia, whose study population consisted of nursing professionals. The exposure variables were occupation, professional exhaustion, and working time, and the outcome variable was MS. Interaction measures based on the additivity criteria were verified by calculating the excess risks due to the interactions and according to the proportion of cases attributed to the interactions and the synergy index. The global MS prevalence is 24.4%. There was a greater magnitude in the exposure group regarding the three investigated factors (average level occupation, professional exhaustion, and working time in PHC for more than 5 years), reaching an occurrence of 44.9% when compared to the prevalence of 13.1% in the non-exposure group (academic education, without professional burnout, and working time in PHC for up to 5 years). The study's findings showed a synergistic interaction of work aspects for MS occurrence among PHC nursing professionals.