Full Robotic Whole Graft Liver Transplantation: A Step Into The Future.

OBJECTIVE: To report the first European series of full robotic whole liver transplantation (RLT) with technical details and future perspectives. SUMMARY BACKGROUND DATA: Few cases of liver transplantation with a minimally invasive approach using partial grafts have been reported so far, and no cases of robotic whole liver transplantation have been reported in the scientific literature. METHODS: The adopted technique was full robotic liver hepatectomy, followed by robotic implantation after graft introduction through a small midline incision. Patients presenting with Hepatocellular Carcinoma (HCC) in liver cirrhosis with a small caudate lobe, low degree of portal hypertension, no porto-mesenteric thrombosis, as well as low MELD patients have been considered ideal candidates. RESULTS: Six patients underwent RLT between February and March 2024 at Lisbon and Modena University Liver Transplant Centers. Warm ischemia time during RLT ranged between 55 and 90 min, with a total surgery duration between 440 and 710 min. The median total operative time was 595 (±111,3) minutes. Only one recipient had prolonged hyperbilirubinemia, which was safely treated. The median in-hospital stay was 7.5 days, (±4.8 days). CONCLUSIONS: RLT is a promising technique to further reduce the impact of liver transplantation thanks to smaller incision, gentle tissue manipulation, high magnification and precision for vascular and biliary anastomosis, and reduced postoperative pain. This is the first step toward the demonstration of the feasibility of minimally invasive surgery in liver transplantation, although further selection and technical refinements are needed to improve reproducibility.

Synthetic Colors in Food: A Warning for Children's Health.

This study addressed the harmful effects of artificial colors in pediatric populations, including children diagnosed with Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD), as well as those without behavioral disorders. There is a consensus that synthetic food colorings have several impacts on consumers, especially pediatrics, due to their influence on sensory appeal, which can encourage preference for certain foods. The results revealed that these color additives are directly linked to a series of health problems, with a greater impact on children, including a predisposition to pathological conditions such as carcinogenic, allergenic, mutagenic, cytotoxic, and clastogenic activities, as well as gastrointestinal and respiratory problems, in addition to behavioral changes in children with and without diagnosed disorders. The harms of synthetic dyes in children with or without comorbidities are worrying and require a careful and proactive approach from parents, caregivers and public authorities.

Unusual presentation of pancreatitis: Inguinoscrotal edema mimicking an incarcerated hernia - a case report.

INTRODUCTION: In rare instances, pancreatitis can manifest as inguinal edema without typical abdominal symptoms, posing diagnostic challenges. CASE PRESENTATION: We report a case of a man in his 40s, with alcohol addiction, who presented with left inguinal pain and swelling but no other abdominal complaints. Physical examination revealed inguinal tenderness and edema, with no hernia signs. Laboratory results showed leukocytosis and elevated C-reactive protein, inconsistent with the patient's symptoms. Abdominopelvic CT scan revealed peripancreatic fat densification and retroperitoneal fluid extending into the inguinal area. No hernia was evident. Extended analysis revealed elevated amylase and lipase levels, sustaining the diagnosis of pancreatitis. The patient responded well to supportive care and was discharged symptom-free. DISCUSSION: Acute pancreatitis emerging as an inguinoscrotal swelling, in the absence of any abdominal symptoms or signs, is extremely rare and can mimic more common causes of inguinoscrotal swellings, such as incarcerated hernias. This case highlights the ability of leaking pancreatic juice to track widely in the retroperitoneal tissues, particularly on the left side. A high level of suspicion, in combination with a CT scan, is essential for achieving an accurate diagnosis and determining the disease's extent. Failure to diagnose correctly could lead to unnecessary surgical procedures and inappropriate/delayed medical care. CONCLUSION: Inguinal edema as the sole presentation of acute pancreatitis is extremely rare. Therefore, it is essential to maintain a high index of suspicion, especially in patients with a history of alcohol consumption, in order to proceed with prompt treatment and avoid unnecessary surgery.

Exercise-based physiotherapeutic interventions in frailty syndrome: A systematic review and meta-analysis.

OBJECTIVE: To identify the effect of exercise interventions on physical frailty in community-dwelling older adults. METHODS: Relevant articles were searched in MEDLINE, LILACS, Scielo, Embase, and PEDro in November 2022, based on a protocol registered in PROSPERO and according to items prescribed in Report for Systematic Reviews and Meta-Analyses, using Health Sciences Descriptors (DeCS) and free terms for search strategy, with no language restrictions. The studies were considered if they had been published between January 2010 and November 2022, and were randomized clinical trials in which pre-frail and frail older community-dwelling adults had undergone exercise-based physical therapy. RESULTS: The systematic review found 5360 citations; after screening, abstract, and full-text screening for eligibility, seven studies were included, involving 1304 participants overall. The exercise modalities differed substantially between studies. The meta-analysis identified a statistically significant difference in frailty between older adults who exercised compared with those who exercised with no or minimal intervention. No heterogeneity between articles was observed, and the risk of bias was considered low according to funnel plot visual inspection. CONCLUSIONS: The results of this review suggest that physical therapy programs are effective in decreasing levels of physical frailty in community-dwelling older adults.

Does the intensity of pain and disability affect health-related quality of life of older adults with back pain? Multilevel analysis between Brazil and Netherlands: a cross-sectional study of the BACE consortium.

BACKGROUND: The prognosis of back pain (BP) in the older adults is less favorable than in younger adults and progress to adverse outcomes and consequent worsening of health-related quality of life (HRQoL). The present study aimed to verify the association between BP intensity, disability and HRQoL in older adults residents in Brazil and Netherlands, and to evaluate whether the country of residence influences the associations. METHODS: Data were collected from 602 Brazilian and 675 Dutch participants with a new episode of BP from the Back Complaints in Elders (BACE) consortium. For the present study, a cross section was used. Pain intensity and disability were assessed using the Numerical Rating Scale (NRS) and the Roland-Morris Disability Questionnaire (RMDQ), respectively. HRQoL was assessed using the Short Form Health Survey (SF-36) quality of life questionnaire. Age, sex, and education were descriptive variables. Pain intensity (NPS score) and country were the independent variables and quality of life assessed by each SF domain - 36 was the dependent variable. Analysis of models at the individual level was performed to verify the association between pain and disability, also HRQoL in Netherlands and Brazil in the total sample. The multilevel model was used to verify whether the older adults person's country of residence influenced this relationship. RESULTS: The average age of the participants was 67.00 (7.33) years. In the total sample, linear regression analysis adjusted for sex and age showed a significant association between BP intensity scores and HRQoL, for all domains. There was no association between disability and HRQoL. In the multilevel analysis, there was an association between BP intensity and HRQoL in all domains and an association between the country of residence and HRQoL, influencing the effect of pain, in all domains, except for the physical functioning. CONCLUSION: Socioeconomic and cultural aspects of different countries can affect the perception of the elderly about their HRQoL in the presence of BP. Pain and disability in Brazilian and Dutch older adults ones are experienced differently in relation to their HRQoL.

Changes in splenic tissue and immune response profile of Schistosoma mansoni infected mice submitted to chronic ethanol intake.

In Schistosoma mansoni infection, the spleen is one of the organs affected, causing its enlargement (splenomegaly). Intake of ethanol through alcoholic beverages can cause spleen atrophy and interfere with immune activity. To gain knowledge of this association on the spleen and on the immune response profile, male mice were used as an experimental model. These animals were divided into four groups: C. control; EC. uninfected/ethanol gavage; I. infected; and IE. infected/ethanol gavage. Groups I and IE were infected with about 100 cercariae (BH strain) of S. mansoni and in the fifth week of infection, gavage 200 µL/day/animal of 18 % ethanol was started for 28 consecutive days. At the end of the gavage (9th week of infection) all animals were euthanized. The spleen was removed and longitudinally divided in two parts. After histological processing, the sections were stained with H&E and Gomori's Reticulin for histopathological and stereological analyses, white pulp morphometry and quantification of megakaryocytes. The other fragment was macerated (in laminar flow) and the cell suspension, after adjusting the concentration (2 × 106), was plated to obtain cytokines produced by spleen cells that were measured by flow cytometry (Citometric Bead Array). Histopathological and quantitative analyzes in the spleen of the IE group showed an increase in the number of trabeculae and megakaryocytes, a decrease in reticular fibers, as well as important organizational changes in the white pulp and red pulp. Due to the decrease in the levels of cytokines measured and the result of the calculation of the ratio between the IFN-y and IL-10 cytokines (p = 0.0079) of the infected groups, we suggest that ethanol decreased the inflammatory and anti-inflammatory response generated by the infection (group IE, the production of cytokines was significantly decreased (p < 0.01). These changes demonstrate that ethanol ingestion interferes with some parameters of experimental S. mansoni infection, such as changes in splenic tissue and in the pattern of cytokine production.

Identification of Chromoblastomycosis and Phaeohyphomycosis Agents through ITS-RFLP.

Chromoblastomycosis (CBM) and phaeohyphomycosis (FEO) are infections caused by melanized filamentous fungal agents, primarily found in tropical and subtropical regions. Both infections pose significant challenges for the correct identification of the causative agent due to their morphological similarity, making conventional methods of morphological analysis highly subjective. Therefore, molecular techniques are necessary for the precise determination of these species. In this regard, this study aimed to contribute to a new methodology based on PCR-RFLP for the identification of agents causing CBM and FEO. Sequences from the Internal Transcribed Spacer (ITS) region were used to identify potential restriction enzyme sites in silico, followed by in vitro validation using the selected restriction enzymes. The obtained results were compared with species identification through morphological analyses and sequencing. The results demonstrated that the PCR-RFLP applied in this study accurately identified two major agents of chromoblastomycosis, Fonsecaea pedrosoi and Fonsecaea monophora, as well as Cladophialophora bantiana and Exophiala dermatitidis, both causative agents of phaeohyphomycosis. In this context, the proposed assay can complement current methods for identifying these species, aiding in diagnosis, and contributing to the proper management of these infections.

Influence of CK2 protein kinase activity on the interaction between Trypanosoma cruzi and its vertebrate and invertebrate hosts.

Chagas disease, endemic from Latin America, is caused by Trypanosoma cruzi and is transmitted by triatomine feces. This parasite undergoes complex morphological changes through its life cycle, promoted by significant changes in signal transduction pathways. The activity of protein kinase CK2 has been described in trypanosomatids. Using a specific peptide and radioactive ATP, we identified CK2 activity on the cellular surface and the cytoplasmic content in Trypanosoma cruzi, apart from the secreted form. Dephosphorylated casein promoted an increase of 48% in the secreted CK2 activity. Total extract of peritoneal macrophages from BALB/c and inactivated human serum promoted an increase of 67% and 36%, respectively, in this activity. The protein secreted by parasites was purified by HPLC and had shown compatibility with the catalytic subunit of mammalian CK2. Incubation of the parasites with CK2 inhibitors, added to the culture medium, prevented their growth. The opposite was observed when CK2 activators were used. Results of interaction between Trypanosoma cruzi and the gut of the vector have revealed that, in the presence of CK2 inhibitors, there is a reduction in the association rate. A similar inhibition profile was seen in the Trypanosoma cruzi-macrophages interaction, confirming the importance of this enzyme in the life cycle of this protozoan.

R3-Walk and R6-Walk, Simple Clinical Equations to Accurately Predict Independent Walking at 3 and 6 Months After Stroke: A Prospective, Cohort Study.

OBJECTIVE: To investigate if independent walking at 3 and 6 months poststroke can be accurately predicted within the first 72 hours, based on simple clinical bedside tests. DESIGN: Prospective observational cohort study with 3-time measurements: immediately after stroke, and 3 and 6 months poststroke. SETTING: Public hospital. PARTICIPANTS: Adults with first-ever stroke evaluated at 3 (N=263) and 6 (N=212) months poststroke. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: The outcome of interest was independent walking at 3 and 6 months after stroke. Predictors were age, walking ability, lower limb strength, motor recovery, spatial neglect, continence, and independence in activities of daily living. RESULTS: The equation for predicting walking 3 months poststroke was 3.040 + (0.283 × FAC baseline) + (0.021 × Modified Barthel Index), and for predicting walking 6 months poststroke was 3.644 + (-0.014 × age) + (0.014 × Modified Barthel Index). For walking ability 3 months after stroke, sensitivity was classified as high (91%; 95% CI: 81-96), specificity was moderate (57%; 95% CI: 45-69), positive predictive value was high (76%; 95% CI: 64-86), and negative predictive value was high (80%; 95% CI: 60-93). For walking ability 6 months after stroke, sensitivity was classified as moderate (54%; 95% CI: 47-61), specificity was high (81%; 95% CI: 61-92), positive predictive value was high (87%; 95% CI: 70-96), and negative predictive value was low (42%; 95% CI: 50-73). CONCLUSIONS: This study provided 2 simple equations that predict walking ability 3 and 6 months after stroke. This represents an important step to accurately identify individuals, who are at high risk of walking dependence early after stroke.

Effect of aquatic exercise programs according to the International Classification of Functionality, Disability and Health domains in individuals with Parkinson's disease: a systematic review and meta-analysis with GRADE quality assessment.

PURPOSE: To investigate the effects of aquatic exercise programs (AEP) in body structure and function, activity, and participation outcomes in individuals with Parkinson's disease (PD) with mild to moderate disability levels. METHODS: Six databases were searched from inception until November 2022. Randomized clinical trials that used AEP alone, AEP combined and/or compared two types of AEP were included. The quality of evidence was assessed by the GRADE approach and the standardized mean differences (SMD) were calculated the meta-analysis. RESULTS: Twelve studies (n = 380) were included. AEP alone was superior to active control in improving body structure and function outcome: postural balance (low evidence, SMD = 0.47, p = 0.02). No statistically significant differences were found for the other body structure and function outcomes: lower limb muscle strength (p = 0.14) and depressive symptoms (p = 0.79), activity outcomes: mobility (p = 0.32) and participation outcomes: quality of life (p = 0.05). AEP combined showed no statistically significant difference for the outcomes of body structure and function: postural balance (p = 0.11) and activity: mobility (p = 0.21) when compared to active control. CONCLUSION: AEP showed positive effects on body structure and function outcome (postural balance) in individuals with PD with mild to moderate disability levels while, no significant improvements were noticed for activity and participation outcomes.IMPLICATIONS FOR REHABILITATIONOur findings indicate that aquatic exercise programs (AEP) lead to significant improvements on body structure and function (i.e., postural balance) in individuals with Parkinson's disease (PD).The AEP evaluated in this study implemented postural balance, gait, single and double training, as well as aerobic exercises, trunk mobility exercises, and Ai Chi.The average duration, frequency, and total time implemented were 50 minutes, three times a week, for seven weeks, respectively.Considering the potential benefits identified in this study, AEP can be recommended as an adjunct treatment strategy for individuals with PD.Additionally, the use of the International Classification of Functionality, Disability and Health on the development of rehabilitation treatment plans is advised.

Localized APP expression results in progressive network dysfunction by disorganizing spike timing.

Progressive cognitive decline in Alzheimer's disease could either be caused by a spreading molecular pathology or by an initially focal pathology that causes aberrant neuronal activity in a larger network. To distinguish between these possibilities, we generated a mouse model with expression of mutant human amyloid precursor protein (APP) in only hippocampal CA3 cells. We found that performance in a hippocampus-dependent memory task was impaired in young adult and aged mutant mice. In both age groups, we then recorded from the CA1 region, which receives inputs from APP-expressing CA3 cells. We observed that theta oscillation frequency in CA1 was reduced along with disrupted relative timing of principal cells. Highly localized pathology limited to the presynaptic CA3 cells is thus sufficient to cause aberrant firing patterns in postsynaptic neuronal networks, which indicates that disease progression is not only from spreading pathology but also mediated by progressively advancing physiological dysfunction.

Are assessment measures for components of the International Classification of Functioning, Disability and Health reproducible for use on pre-frail and frail older adults? A systematic review.

OBJECTIVE: To analyze the internal consistency, reliability and measurement error of assessment measures for body structure and function (postural balance, muscle strength, cardiorespiratory function and physical fitness), activity (walking and mobility) and participation (quality of life and social reintegration) outcomes for use on pre-frail and frail older adults. METHODS: Searches were performed in six databases (Medline, Embase, ScienceDirect, Web of Science, The Cochrane Library and Lilacs) and reproducibility studies were included. Cronbach's alpha and the classification proposed by Terwee et al. (2007) were used for the interpretation of internal consistency. The intraclass correlation coefficient (ICC) and the Munro classification were used for the determination of reliability. The standard error of measurement (SEM), minimal detectable change (MDC) as well as percentages of error (SEM%) and change (MDC%) were calculated. Methodological quality of the studies was appraised using Boxes 4, 6 and 7 of the COSMIN Risk of Bias checklist. RESULTS: Six studies were included in the present systematic review, with a total of 835 (82.4 years; 582 women and 253 men) pre-frail and frail older adults analyzed. Seven measures were identified for the assessment of body structure and function, activity and participation outcomes (Hierarchical Assessment of Balance and Mobility, Self-Assessment of Physical Fitness, Sarcopenia Quality of Life, Reintegration to Normal Living Index, Two-Minute Walking test, Six-Minute Walking test and Ten-Meter Walking test). The following measurement properties were identified: internal consistency = 0.84 (mean Cronbach's alpha); reliability = 0.87 (mean ICC); SEM range = 0.06 to 10.10; MDC range = 0.13 to 28.10; SEM% range = 5.2 % to 9.5 %; and MDC% range = 10.7 % to 28.5 %. CONCLUSION: The present systematic review found adequate internal consistency, high reliability and an acceptable measurement error for assessment measures of body structure and function, activity and participation outcomes for use on pre-frail and frail older adults.

Exploring the chemical composition, in vitro and in silico study of the anticandidal properties of annonaceae species essential oils from the Amazon.

Chemical composition of the essential oils (EOs) from the leaves of five Annonaceae species found in the amazon region was analyzed by Gas chromatography coupled to mass spectrometry. The antifungal activity of theses EOs was tested against Candida albicans, Candida auris, Candida famata, Candida krusei and Candida tropicalis. In addition, an in silico study of the molecular interactions was performed using molecular modeling approaches. Spathulenol (29.88%), α-pinene (15.73%), germacra-4(15),5,10(14)-trien-1-α-ol (6.65%), and caryophylene oxide (6.28%) where the major constitents from the EO of Anaxagorea dolichocarpa. The EO of Duguetia echinophora was characterized by ß-phellanderene (24.55%), cryptone (12.43%), spathulenol (12.30%), and sabinene (7.54%). The major compounds of the EO of Guatteria scandens where ß-pinene (46.71%), α-pinene (9.14%), bicyclogermacrene (9.33%), and E-caryophyllene (8.98%). The EO of Xylopia frutescens was characterized by α-pinene (40.12%) and ß-pinene (36.46%). Spathulenol (13.8%), allo-aromadendrene epoxide (8.99%), thujopsan-2-α-ol (7.74%), and muurola-4,10(14)-dien-1-ß-ol (7.14%) were the main chemical constituents reported in Xylopia emarginata EO. All EOs were active against the strains tested and the lowest inhibitory concentrations were observed for the EOs of D. echinophora, X. emarginata, and X. frutescens against C. famata the Minimum Inhibitory Concentration values of 0.07, 0.019 and 0.62 µL.mL-1, respectively. The fungicidal action was based on results of minimum fungicidal concentration and showed that the EOs showed fungicide activity against C. tropicalis (2.5 µL.mL-1), C. krusei (2.5 µL.mL-1) and C. auris (5 µL.mL-1), respectively. The computer simulation results indicated that the major compounds of the EOs can interact with molecular targets of Candida spp.

Validity and reliability of the short form brief pain inventory in older adults with nociceptive, neuropathic and nociplastic pain.

OBJECTIVE: The aim of this study was to evaluate the validity and reliability of the Short Form Brief Pain Inventory (SF-BPI) for community-dwelling Brazilian older adults with chronic neuropathic, nociceptive and nociplastic pain. METHODS: Cross-sectional psychometric testing was conducted in a convenience sample, n=114 (66.5 ± 4.9 years). RESULTS: The 2-factor structure of the SF-BPI was ratified by confirmatory factor analysis. Convergent validity was found between the SF-BPI and the Present Pain Intensity (PPI). There was good overall internal consistency (Cronbach's α: 0.87). Test-retest reliability was excellent for pain intensity and interference scores of the SF-BPI (ICC: 0.90 and 0.96, respectively), as well as inter-rater reliability for both dimensions (ICC: 0.77). CONCLUSION: The findings support the validity and reliability of the SF-BPI for community-dwelling older adults with chronic pain and may contribute to health professionals having a brief multidimensional assessment for more effective therapeutic approaches in this population.

Brazilian guide to nutrition in bariatric and metabolic surgery.

PURPOSE: Brazilian nutrition recommendations for bariatric and metabolic surgery aim to provide knowledge, based on scientific evidence, on nutritional practices related to different surgical techniques in the surgical treatment of obesity and metabolic diseases. MATERIALS AND METHODS: A systematic literature search was carried out with the appropriate MeSH terms using Medline/Pubmed/LiLACS and the Cochrane database, with the established criteria being based on the inclusion of articles according to the degree of recommendation and strength of evidence of the Classification of Recommendations, Evaluation, Development, and Evaluation System (GRADE). RESULTS: The recommendations that make up this guide were gathered to assist in the individualized clinical practice of nutritionists in the nutritional management of patients with obesity, including nutritional management in the intragastric balloon; pre and postoperative nutritional treatment and supplementation in bariatric and metabolic surgeries (adolescents, adults, elderly, pregnant women, and vegetarians); hypoglycemia and reactive hyperinsulinemia; and recurrence of obesity, gut microbiota, and inflammatory bowel diseases. CONCLUSION: We believe that this guide of recommendations will play a decisive role in the clinical practice of nutritionists who work in bariatric and metabolic surgery, with its implementation in health services, thus promoting quality and safety in the treatment of patients with obesity. The concept of precision nutrition is expected to change the way we understand and treat these patients.

High levels of pro-inflammatory SARS-CoV-2-specific biomarkers revealed by in vitro whole blood cytokine release assay (CRA) in recovered and long-COVID-19 patients.

BACKGROUND: Cytokines induced by SARS-CoV-2 infection play a crucial role in the pathophysiology of COVID-19 and hyperinflammatory responses have been associated with poor clinical outcomes, with progression to severe conditions or long-term subacute complications named as long-COVID-19. METHODS: In this cross-sectional study, we aimed to evaluate a set of antigen-specific inflammatory cytokines in blood from recovered COVID-19 individuals or who suffered a post-acute phase of SARS-CoV-2 infection compared to healthy individuals with no history of COVID-19 exposition or infection. Interferon-gamma (IFN-γ), IFN-γ-induced protein 10 (IP-10), tumor necrosis factor (TNF), IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, and IL-17A were quantified by multiplex cytometric bead assay and enzyme-linked immunosorbent assay after stimulation of whole blood with recombinant Spike protein from SARS-CoV-2. Additionally, all participants have evaluated for anti-(S) protein-specific IgG antibodies. Clinical specimens were collected within two months of COVID-19 diagnosis. RESULTS: A total of 47 individuals were enrolled in the study, a median age of 43 years (IQR = 14.5), grouped into healthy individuals with no history of infection or exposure to SARS-CoV-2 (unexposed group; N = 21); and patients from the Health Complex of the Rio de Janeiro State University (UERJ), Brazil, who were SARS-CoV-2 positive by RT-PCR (COVID-19 group)-categorized as recovered COVID-19 (N = 11) or long-COVID-19 (N = 15). All COVID-19 patients presented at least one signal or symptom during the first two weeks of infection. Six patients were hospitalized and required invasive mechanical ventilation. Our results showed that COVID-19 patients had significantly higher levels of IFN-γ, TNF, IL-1ß, IL-2, IL-6, IL-8, and IP-10 than the unexposed group. The long-COVID-19 group has presented significantly high levels of IL-1ß and IL-6 compared to unexposed individuals, but not from recovered COVID-19. A principal-component analysis demonstrated 84.3% of the total variance of inflammatory-SARS-CoV-2 response in the first two components, and it was possible to stratify IL-6, TNF, IL-1ß, IL-10, and IL-2 as the top-five cytokines which are candidates to discriminate COVID-19 group (including long-COVID-19 subgroup) and healthy unexposed individuals. CONCLUSION: We revealed important S protein-specific differential biomarkers in individuals affected by COVID-19, bringing new insights into the inflammatory status or SARS-CoV-2 exposition determination.

Genus Streptomyces: Recent advances for biotechnological purposes.

Actinomycetes are a distinct group of filamentous bacteria. The Streptomyces genus within this group has been extensively studied over the years, with substantial contributions to society and science. This genus is known for its antimicrobial production, as well as antitumor, biopesticide, and immunomodulatory properties. Therefore, the extraordinary plasticity of the Streptomyces genus has inspired new research techniques. The newest way of exploring Streptomyces has comprised the discovery of new natural metabolites and the application of emerging tools such as CRISPR technology in drug discovery. In this narrative review, we explore relevant published literature concerning the ongoing novelties of the Streptomyces genus.

Low doses of 3-phenyl-lawsone or meglumine antimoniate delivery by tattooing route are successful in reducing parasite load in cutaneous lesions of Leishmania (Viannia) braziliensis-infected hamsters.

Current therapeutic ways adopted for the treatment of leishmaniasis are toxic and expensive including parasite resistance is a growing problem. Given this scenario, it is urgent to explore treatment alternatives for leishmaniasis. The aim of this study was to evaluate the effect of 3-phenyl-lawsone (3-PL) naphthoquinone on Leishmania (Viannia) braziliensis infection, both in vitro and in vivo, using two local routes of administration: subcutaneous (higher dose) and tattoo (lower dose). In vitro 3-PL showed low toxicity for macrophages (CC50 >3200 µM/48h) and activity against intracellular amastigotes (IC50 = 193 ± 19 µM/48h) and promastigotes (IC50 = 116 ± 26 µM/72h), in which induced increased ROS generation. Additionally, 3-PL up-regulated the production of cytokines such as tumor necrosis factor alpha (TNF-α), monocyte chemotactic protein 1 (MCP-1), interleukin-6 (IL-6) and IL-10 in infected macrophages. However, the anti-amastigote action was independent of nitric oxide production. Treatment of hamsters infected with L. (V.) braziliensis from one week after infection with 3-PL by subcutaneous (25 µg/Kg) or tattooing (2.5 µg/Kg) route, during 3 weeks (3 times/week) or 2 weeks (2 times/week) significantly decreased the parasite load (p<0.001) in the lesion. The reduction of parasite load by 3-PL treatment was comparable to reference drug meglumine antimoniate administered by the same routes (subcutaneous 1mg/Kg and tattoo 0.1mg/Kg). In addition, treatment started from five weeks after infection with 3-PL per tattoo also decreased the parasite load. These results show the anti-leishmanial effect of 3-PL against L. (V.) braziliensis and its efficacy by subcutaneous (higher dose) and tattoo (lower dose) routes. In addition, this study shows that drug delivery by tattooing the lesion allows the use of lower doses than the conventional subcutaneous route, which may support the development of a new therapeutic strategy that can be adopted for leishmaniasis.

The impact of low back pain and disability on frailty levels in older women: longitudinal data from the BACE-Brazil cohort.

METHODS: This is a longitudinal observational study with a convenience subsample from the international Back Complaints in the Elders (BACE)-Brazil. Frailty was assessed by researchers at baseline, 6 and 12 months according to the Frailty Phenotype. Pain was assessed using a Numerical Pain Scale (NPS). Disability was assessed using the Roland Morris Disability Questionnaire. RESULTS: A total of 155 older women (70.4 ± 5.4 years) participated. Follow-up for 6 and 12 months in this study was associated with a change of older women to worse frailty levels (OR = 2.83, 95% CI 1.98-4.67; p < 0.01). A significant association was observed between greater pain intensity and the transition of the older women through the frailty levels (ß = - 0.73; p < 0.01) when inserting the pain variable at baseline of the statistical model. Older women who reported greater pain intensity worsened their frailty level. The same happened when the disability variable was inserted in the model (ß = - 0.74; p < 0.01). The criteria proposed by Fried et al. were able to identify frailty throughout the follow-up and no prevalence of any item. CONCLUSIONS: In older women, relevant factors such as pain and disability are closely linked to the frailty phenomenon. Thus, the frailty syndrome must be assessed, monitored and treated in relation to the individualities of older adults, as those with back pain and greater disabilities are more susceptible to frailty.