RANKL signaling drives skeletal muscle into the oxidative profile.

The bone-muscle unit refers to the reciprocal regulation between bone and muscle by mechanical interaction and tissue communication via soluble factors. The receptor activator of NF-κB ligand (RANKL) stimulation induces mitochondrial biogenesis and increases the oxidative capacity in osteoclasts and adipocytes. RANKL may bind to the membrane bound receptor activator of NF-κB (RANK) or to osteoprotegerin (OPG), a decoy receptor that inhibits RANK-RANKL activation. RANK is highly expressed in skeletal muscle, but the contribution of RANKL to healthy skeletal muscle fiber remains elusive. Here we show that RANKL stimulation in C2C12-derived myotubes induced activation of mitochondrial biogenesis pathways as detected by RNA-seq and western blot. RANKL expanded the mitochondrial reticulum, as shown by mitochondrial DNA quantification and MitoTracker staining, and boosted the spare respiratory capacity. Using MEK and MAPK inhibitors, we found that RANKL signals via ERK and p38 to induce mitochondrial biogenesis. The soleus from OPG-/- and OPG+/- mice showed higher respiratory rates compared to C57BL6/J wild-type (WT) mice, which correlates with high serum RANKL levels. RANKL infusion using a mini-osmotic pump in WT mice increased the number of mitochondria, boosted the respiratory rate, increased succinate dehydrogenase (SDH) activity in skeletal muscle, and improved the fatigue resistance of gastrocnemius. Therefore, our findings reveal a new role of RANKL as an osteokine-like protein that impacts muscle fiber metabolism.

Bone modeling and remodeling are processes intricately related to bone health regulated by the RANKL system. The RANKL (receptor activator of NF-κB ligand) is a protein essential for bone resorption. RANKL activates RANK (receptor activator of NFκB) in the cell membrane of osteoclasts and can also bind to OPG (osteoprotegerin), which acts as a soluble decoy receptor. Therefore, the levels of RANKL and OPG determine the degree of osteoclast activation and bone resorption. Bone and muscle mechanically interact for movement as bone is a lever for skeletal muscle to exert force. They also communicate via soluble factors that reciprocally regulate their function. Skeletal muscle fibers express RANK, but the role of RANKL signaling in healthy myotubes was still unknown. Here, we propose that RANKL regulates muscle metabolism by inducing mitochondrial biogenesis. We show that RANKL increases mitochondrial area in myotubes and the expression of mitochondrial markers, boosting the spare respiratory capacity. In mice knockout for OPG, which shows high levels of RANKL and unopposed RANK-RANKL stimulation, we found higher respiratory rates than in the wild-type mice. We also infused a low dose of RANKL in wild-type mice, which is around ten times lower than the dose to induce osteoporosis, and found increased mitochondrial number and higher respiratory rates in soleus. In the gastrocnemius, we also observed increased phosphorylative respiration and improved resistance to fatigue compared to mice treated with the vehicle solution. Our findings indicate that RANKL regulates both bone and muscle under physiological conditions by inducing mitochondrial biogenesis and oxidative metabolism in skeletal muscle fibers.

Consensus of the Brazilian Association of Hematology, Hemotherapy and Cellular Therapy (ABHH) and the Brazilian Ministry of Health - General management of blood and blood products on the tests necessary for the release of exceptional medicines for sickle cell disease.

To date, hydroxyurea is the only effective and safe drug that significantly reduces morbidity and mortality of individuals with Sickle cell disease. Twenty years of real-life experience has demonstrated that hydroxyurea reduces pain attacks, vaso-occlusive events, including acute chest syndrome, the number and duration of hospitalizations and the need for transfusion. The therapeutic success of hydroxyurea is directly linked to access to the drug, the dose used and adherence to treatment which, in part, is correlated to the availability of hydroxyurea. This consensus aims to reduce the number of mandatory exams needed to access the drug, prioritizing the requesting physician's report, without affecting patient safety.

A stronger antibody response in increased disease severity of SARS-CoV-2.

BACKGROUND: An assessment of the factors that interfere with serum levels and the persistence of anti-SARs-CoV-2 IgG antibodies is essential in order to estimate the risk of reinfection and to plan vaccination. We analyzed the impact of the severity of coronavirus disease 2019 (COVID-19) and the clinical and biological factors regarding the persistence of SARs-CoV-2 anti-spike protein (IgG-S) antibodies at 12 months. METHODS: This was an observational, longitudinal study with individuals who had recovered from COVID-19 between August 2020 and June 2021. Peripheral blood samples were collected from volunteers who were hospitalized (SERIOUS COVID-19) and those who required no hospitalization (COVID-19 LIGHT). Samples were grouped according to days after symptom onset: up to 90, between 91 and 180, ≥ 180 days after symptom onset. A semiquantitative test for IgG anti-spike protein S1(IgG-S1) was used. RESULTS: We analyzed 238 individuals who had recovered from COVID-19, of whom 87 had been hospitalized and 151 had not. They provided 148 and 220 samples, respectively. Among those hospitalized, males (65.5%), volunteers aged over 60 years (41.1%), comorbidities such as arterial hypertension (67.8%) and diabetes mellitus (37.9%) were most frequent. We observed higher median serum IgG-S1 titers among those who had recovered from COVID-19 and had been hospitalized, at all collection time intervals (p < 0.001). We observed a weak correlation of increasing age with humoral IgG-S1 response (Spearman correlation = 0.298). There was a greater probability of IgG-S1 antibody persistence over time among samples from hospitalized individuals compared to samples from non-hospitalized participants (p = 0.001). CONCLUSION: This study has revealed higher titers and a higher probability of the persistence of IgG-S1 in severe cases after SARs-CoV-2 primary infection in unvaccinated recovered patients. Thus, in this study, the severe clinical presentation of COVID-19 was the main factor influencing serum levels and the persistence of IgG-S1 antibodies in COVID-19.

What is the significance of the chloroform stabilizer C5H10 and its association with MeOH in concentration-dependent polymeric solutions?

The understanding of excitonic transitions associated with polymeric aggregates is fundamental, as such transitions have implications on coherence lengths, coherence numbers and inter- and intra-chain binding parameters. In this context, the investigation of efficient solvents and other ways to control polymer aggregate formation is key for their consolidation as materials for new technologies. In this manuscript, we use Poly(3-hexothiophene) (P3HT) as a probe to investigate the significance of amylene (C5H10) and its association with methanol (MeOH) in both pure and C5H10-stabilized chloroform (CHCl3)-based polymeric solutions. Using the intensity ratio between the first and second vibronic transitions of the P3HT H-aggregates formed, values for their exciton bandwidths and interchain interactions are obtained and correlated with the presence of C5H10 and MeOH as agents determining the CHCl3 quality.

Chlorella vulgaris extract and Imiquimod as new therapeutic targets for leishmaniasis: An immunological approach.

The therapeutic regimen for the treatment of American Tegumentary Leishmaniasis (ATL) is targeted at the death of the parasite; therefore, it is essential to develop a treatment that can act on the parasite, combined with the modulation of the inflammatory profile. Thus, the aim of this study was to make an in vitro evaluation of the therapeutic potential of Chlorella vulgaris extract (CV) and Imiquimod for ATL. Selectivity indices (SI) were determined by inhibitory concentration assays (IC50) in L. braziliensis cells and cytotoxic concentrations (CC50) were measured in human cells using the MTT method, based on the CV microalgae extract (IC50 concentrations of 15.63 to 500 µg/mL; CC50 concentrations of 62.5-1000 µg/mL) in comparison with the reference drugs and Imiquimod. The immune response was evaluated in healthy human cells by gene expression (RT-qPCR) and cytokine production (Flow Cytometry). The CV extract (SI = 6.89) indicated promising results by showing higher SI than meglumine antimoniate (SI = 3.44) (reference drug). In all analyses, CV presented a protective profile by stimulating the production of Th1 profile cytokines to a larger extent than the reference drugs. Imiquimod showed a high expression for Tbx21, GATA3, RORc and Foxp3 genes, with increased production only of the TNF cytokine. Therefore, the data highlight the natural extract and Imiquimod as strong therapeutic or adjuvant candidates against ATL, owing to modulation of immune response profiles, low toxicity in human cells and toxic action on the parasite.

Levels of soluble TNF receptors (sTNFR1 and sTNFR2) increase with clinical worsening of patients and are related to COVID-19 mortality.

The present study aimed to inspect the serum levels of the soluble receptors, sTNFR1 and sTNFR2, in patients with COVID-19. The large production of inflammatory cytokines is an essential process in the pathogenesis of COVID-19. TNF is a multifaceted proinflammatory cytokine which has soluble and membrane receptors. Thus, knowing the role of these receptors will help better understand this disease's immunopathogenesis. We included 131 patients confirmed for SARS-CoV-2, separated into three groups: ward patients without O2 support, group A (n = 14); ward patients with O2 support, group B (n = 85), and patients in an intensive care unit (ICU), group C (n = 32), making up the receptors dosed by flow cytometry. The results showed that sTNFR1 and sTNFR2 are associated with disease severity, being higher in group C when compared to group A. As for the levels of receptors and their relationship with the degree of lung involvement, we found higher values of sTNFR1 in patients in group 1 (pulmonary involvement < 25%), suggesting that inflammatory processes related to TNF are not necessarily associated with the primary site of infection. When we analysed the patients who passed away compared to those who recovered, both receptors significantly increased the mortality numbers. These findings suggest a relevant influence of soluble receptors in the inflammatory processes involved in the pathogenesis of COVID-19. Wherefore, we suggest using these receptors as biomarkers of severity and mortality of the disease.

Strength and endurance training in cytokine and body composition of people with hiv/aids / Entrenamiento de fuerza y resistencia en citoquinas y composición corporal de personas con vih/sida / Treinamento de força e resistência em citocinas e composição corporal de pessoas com hiv/aids

ABSTRACT Introduction: HIV/AIDS is considered one of the great cases of public health, but it is seen that patients who use antiretroviral therapy (ART) and practice strength training promote a promotion of their health. Objectives: Assess the impact of strength and resistance training on cytokines and body composition in people living with HIV/AIDS. Methods: Randomized clinical trial, the sample consisted of 12 patients, 7 from the Strength Group (GF) and 5 from Group 2, Muscular Resistance (MGR). We compared the levels of IL-2, IL-4, IL-6, IL-10 and TNF-α cytokines and body composition in the first and last sessions. The patients completed 36 strength and resistance training sessions over 12 weeks. Results: After 36 sessions of GRM resistance training, there was a significant increase from 4,734 pg/mL to 5,050 pg/mL of IL-10 (p=0.002). Regarding the GFR, no significant results were found. For body composition, there were significant differences in GFR due to the increase in lean mass of the arms from 6,441g to 7,014g (p=0.04), legs from 16,379g to 17,281g (p=0.02) and whole body of 45,640g to 47,343g (p=0.01). In G2 there was a significant decrease in the percentage of fat in the arms from 23,160% to 20,750% (p = 0.04). To assess quality of life, the WHOQOL-HIV-Bref questionnaire was used, where significant improvement was found in all domains, except for the level of independence domain. Conclusion: We conclude that muscular resistance training is effective in increasing IL-10 and decreasing the percentage of fat in the arms, whereas strength training increases lean mass in arms, legs, and the whole body. Level of Evidence I; Randomized Clinical Trial.

RESUMEN Introducción: El VIH/SIDA es considerado uno de los grandes casos de salud pública, sin embargo, está comprobado que pacientes que hacen uso de la terapia antirretroviral (TARV) y practican entrenamiento de fuerza provoca una promoción de su salud. Objetivos: Evaluar el impacto del entrenamiento de fuerza en la resistencia a las citoquinas y en la composición corporal de las personas que viven con VIH/SIDA. Métodos: Ensayo clínico aleatorizado, la muestra estuvo compuesta por 12 pacientes, siete del Grupo de Fuerza (TFG) y cinco del Grupo de Resistencia Muscular (GRM). Se compararon los niveles de las citocinas IL-2, IL-4, IL-6, IL-10 y TNF-α y la composición corporal en la primera y la última sesión. Los pacientes completaron 36 sesiones de entrenamiento de fuerza y resistencia durante 12 semanas. Resultados: Tras 36 sesiones de entrenamiento de resistencia GRM, se produjo un aumento significativo de 4.734 pg/mL a 5.050 pg/mL de IL-10 (p=0,002). En cuanto a la TFG, no se encontraron resultados significativos. En cuanto a la composición corporal, hubo diferencias significativas en la TFG debido al aumento de la masa magra en brazos de 6.441g a 7.014g (p=0,04), piernas de 16.379g a 17.281g (p=0,02) y cuerpo entero de 45.640g a 47.343g (p=0,01). En el GRM hubo una disminución significativa del porcentaje de grasa en los brazos de 23.160% a 20.750% (p = 0,04). Para la evaluación de la calidad de vida se utilizó el cuestionario WHOQOL-HIV-Bref, donde se encontró una mejoría significativa en todos los dominios, excepto en el dominio nivel de independencia. Conclusión: Concluimos que el entrenamiento de resistencia muscular es eficaz para aumentar la IL-10 y disminuir el porcentaje de grasa en los brazos, mientras que el entrenamiento de fuerza aumenta la masa magra total. Nivel de Evidencia I; Ensayo clínico aleatorizado.

RESUMO Introdução: O HIV/AIDS é considerado um dos grandes casos de saúde pública, porém verifica-se que pacientes que fazem uso de terapia antirretroviral (TARV) e praticam treinamento de força provocam uma promoção de sua saúde. Objetivos: Avaliar o impacto do treinamento de força sobre a resistência nas citocinas e a composição corporal de pessoas vivendo com HIV/AIDS. Métodos: Ensaio clínico randomizado, a amostra foi composta por 12 pacientes, sendo sete do Grupo Força (TFG) e cinco do Grupo Resistência Muscular (GRM). Comparou-se os níveis das citocinas IL-2, IL-4, IL-6, IL-10 e TNF-α e a composição corporal na primeira e na última sessão. Os pacientes completaram 36 sessões de treinamento de força e resistência ao longo de 12 semanas. Resultados: Após 36 sessões de treinamento resistido GRM, houve um aumento significativo de 4.734 pg/mL para 5.050 pg/mL de IL-10 (p=0,002). Em relação à TFG, não foram encontrados resultados significativos. Para composição corporal, houve diferenças significativas na TFG devido ao aumento da massa magra dos braços de 6.441g para 7.014g (p=0,04), pernas de 16.379g para 17.281g (p=0,02) e corpo inteiro de 45.640g para 47.343g (p=0,01). No GRM houve diminuição significativa do percentual de gordura nos braços de 23.160% para 20.750% (p = 0,04). Para avaliação da qualidade de vida foi utilizado o questionário WHOQOL-HIV-Bref, onde foi encontrada uma melhora significativa em todos os domínios, exceto no domínio nível de independência. Conclusão: Conclui-se que o treinamento de resistência muscular é eficaz em aumentar a IL-10 e diminuir o percentual de gordura nos braços, enquanto o treinamento de força aumenta a massa magra geral. Nível de Evidência I; Ensaio Clínico Randomizado.

Troubleshooting spectral artifacts from biplate retarders for reliable Stokes spectropolarimetry.

Polarimetry is generally used to determine the polarization state of light beams in various research fields, such as biomedicine, astronomy, and materials science. In particular, the rotating quarter-wave plate polarimeter is an inexpensive and versatile option used in several single-wavelength applications to determine the four Stokes parameters. Extending this technique to broadband spectroscopic measurements is of great scientific interest since the information on light polarization is highly sensitive to anisotropic phenomena. However, the need for achromatic polarizing elements, especially quarter-wave plates, requires special attention in their modeling. In this study, we implemented a rotating retarder spectropolarimeter for broadband measurements using a commercially available quasi-achromatic biplate retarder over the visible range. Here, we present a comprehensive approach for troubleshooting this type of spectropolarimeter through the observation of artifacts stemming from the standard single-plate retarder model. Then, we derive a more suitable model for a quasi-achromatic retarder consisting of a biplate junction. This new biplate model requires knowledge of the intrinsic dispersive properties of the biplate, namely the equivalent retardance, fast axis tilt, and rotatory angle. Hence, in this study, we also show a self-consistent methodology to determine these biplate properties using the same polarimeter apparatus so that accurate Stokes parameters can be determined independently. Finally, the comparison of data generated with the standard single-plate and new biplate models shows a significant improvement in the measurement precision of the investigated polarization states, which confirms that remodeling the retarder for reliable spectropolarimetry is necessary.

Improving Riparin-A Dissolution through a Laponite Based Nanohybrid.

(1) Background: Riparin-A presents several pharmacological activities already elucidated, such as antimicrobial modulator, antileishmania, anxiolytic, anti-inflammatory, antinociceptive, and antioxidant. Even with important bioactive effects, the applicability of Riparin-A is limited due to its low solubility in water, impairing its dissolution in biological fluids. Thus, the objective of this study was to develop a nanohybrid based on Riparin-A and Laponite to obtain a better dissolution profile and evaluate its cytotoxic potential. (2) Methods: The formation of a hybrid system was highlighted by X-ray powder diffraction, infrared spectroscopy, and thermal analysis. Solubility, dissolution, and cytotoxicity studies were performed; (3) Results: An increase in the solubility and aqueous dissolution rate of Riparin-A was observed in the presence of clay. Diffractometric analysis of the hybrid system suggests the amorphization of Riparin-A, and thermal analyses indicated attenuation of decomposition and melting of the Riparin-A after interaction with clay. Furthermore, the nanosystem did not exhibit cytotoxic activity on normal and tumorigenic lines. (4) Conclusions: These results are promising for the development of the Riparin-A/Laponite nanosystem for therapeutic purposes, suggesting an increase in the range of possible routes of administration and bioavailability of this bioactive compound.

ANTEROMEDIAL OR CENTRAL ANATOMIC ACL RECONSTRUCTION? A CADAVERIC HIP-TO-TOE STUDY.

Objective: To compare anatomic anterior cruciate ligament (ACL) reconstruction between two tunnel positions in knees with isolated ligament tears. Methods: Anatomic ACL reconstruction was performed, from hip-to-toe, on 15 fresh cadaveric specimens. No associated lesions were created to enhance knee instability. The protocol was conducted in three states: (1) complete isolated ACL deficiency; (2) anatomic femoral and tibial anteromedial ACL reconstruction (AM REC); and (3) anatomic femoral and tibial central ACL reconstruction (Central REC). The reconstruction protocols were randomly assigned. The continuous mechanized pivot-shift test was recorded dynamically with a tracking system. Results: The Central REC group showed a smaller degree of internal rotation (0.6° ± 0.3° vs. 1.8° ± 0.3°, respectively, P < 0.05) and no difference in anterior translation (4.7 mm ± 0.4 mm vs. 4.5 mm ± 0.4 mm, respectively, P > 0.05) in the pivot-shift test, compared with the AM REC group. Conclusion: The central anatomic ACL reconstruction resulted in greater restriction of internal rotation than the anteromedial anatomic ACL reconstruction. Experimental Study on Cadaver.

Objetivo: Comparar a reconstrução anatômica do ligamento cruzado anterior (LCA) entre duas posições de túnel em joelhos com lesões isoladas do ligamento. Métodos: A reconstrução anatômica do LCA foi realizada, do quadril aos pés, em 15 peças anatômicas de cadáveres frescos. Não foram criadas lesões associadas para intensificar a instabilidade do joelho. O protocolo foi realizado em três estados: (1) deficiência isolada completa do LCA; (2) reconstrução anatômica femoral e anteromedial tibial do LCA (AM REC); e (3) reconstrução anatômica femoral e central tibial do LCA (Central REC). Os protocolos de reconstrução foram atribuídos aleatoriamente. O teste de pivot-shift mecanizado contínuo foi registrado dinamicamente com um sistema de rastreamento. Resultados: O grupo Central REC apresentou menor grau de rotação interna (0,6° ± 0,3° vs. 1,8° ± 0,3°, respectivamente, p < 0,05) e nenhuma diferença na translação anterior (4,7 mm ± 0,4 mm vs. 4,5 mm ± 0,4 mm, respectivamente, p > 0,05) no teste de pivot-shift, comparado ao grupo AM REC. Conclusão: A reconstrução anatômica central tibial do LCA resultou em maior restrição da rotação interna do que a reconstrução anteromedial tibial do LCA. Estudo em Cadáver Experimental.

Cutaneous Tuberculosis in Heart Transplant.

Tuberculosis is a disease with a significant global burden in terms of morbidity and mortality. It usually presents as a pulmonary disease but can occasionally have extrapulmonary presentations. Immunosuppressed people are at an increased risk of tuberculosis and more frequently have atypical manifestations of the disease. Cutaneous involvement is estimated to occur in only 2% of extrapulmonary presentations. We report a case of a heart transplant recipient with disseminated tuberculosis who initially presented with cutaneous manifestations in the form of multiple abscesses that were mistaken for a community-acquired bacterial infection. The diagnosis was made after positive nucleic acid amplification testing and cultures for Mycobacterium tuberculosis from the drainage of the abscesses. After initiating antituberculous treatment, the patient had 2 instances of immune reconstitution inflammatory syndrome. A combination of diminished immunosuppression due to discontinuation of mycophenolate mofetil in the setting of acute infection, rifampin drug interactions with cyclosporine, and the beginning of treatment of tuberculosis all contributed to this paradoxical worsening. The patient responded favorably to increased glucocorticoid therapy and showed no signs of treatment failure after 6 months of antituberculous therapy.

Clinical and Epidemiological Characteristics of Neurocryptococcosis Associated with HIV in Northeastern Brazil.

Cryptococcal meningitis is a serious infection of the central nervous system that is predominant in developing countries, caused by fungi of the genus Cryptococcus, and which affects immunosuppressed patients, especially those with HIV. Here, we aim to diagnose and characterize the clinical-epidemiological profile of cryptococcosis in patients admitted to two tertiary public hospitals in northeastern Brazil. The study is divided into three moments: (1) the isolation of fungus and diagnosis from biological samples collected between 2017 and 2019, (2) a description of the clinical and epidemiological characteristics of the patients, and (3) the experimental tests related to an in vitro susceptibility antifungal profile. The species were identified by MALDI-TOF/MS. Among the 100 patients evaluated, 24 (24.5%) were diagnosed with cryptococcosis based on positive culture. Clinical-epidemiological analysis showed a slightly higher prevalence in men between 30 and 39 years. When comparing the date of HIV diagnosis and the development of cryptococcosis, it was observed that 50% received the diagnosis of infection by cryptococcosis after or equal to a period of 12 months from being diagnosed with HIV; the other 50% received it within the first 30 days of the HIV diagnosis. Neurocryptococcosis was the most prevalent clinical form, and, at the time of hospital admission, the most common clinical signs were high fever (75%), intense headache (62.50%), and neck stiffness (33.33%). The cerebrospinal fluid showed 100% sensitivity and positivity for direct examination by India ink, and fungal culture. The mortality rate in this study was 46% (11/24), a lower rate than in the other literature. An antifungigram showed that 20 (83.33%) isolates were susceptible to amphotericin B and 15 (62.5%) to fluconazole. Mass spectrometry identified 100% of the isolates as Cryptococcus neoformans. In Brazil, this infection is not mandatory notifiable. Therefore, although there is little information on the subject, it is obsolete and does not express the reality of the facts, mainly in the northeast region, where this information is insufficient. The data obtained in this research contribute to the epidemiological knowledge of this mycosis in Brazil and will serve as a basis for future globally comparative epidemiological studies.

An Unexpected Cause of Acute Abdomen Late After Heart Transplantation-A Case Report.

Cytomegalovirus (CMV) infection is a frequent complication after a solid organ transplant, and in 86% of the cases, CMV disease occurred during the first 6 months after transplantation. Invasive CMV infections may be present as ulcerative infections of the upper gastrointestinal tract with esophagitis, gastritis, and ulcerations of the duodenum and the small bowel; however, CMV infections of the pancreatobiliary system, especially papillitis, are rarely observed. We present a case report of a man who underwent a heart transplant 6 years before, with a clinical picture of duodenitis and a simultaneous pseudotumor of major duodenal papilla who developed signs of acute abdomen caused by gastrointestinal CMV infection, successfully treated with medical therapy with valganciclovir. There is an urgent need for developments in CMV and solid organ transplantation to stratify the risk of late-onset CMV disease.

Comparison of Retinal Structure Using Optical Coherence Tomography Angiography between Persons with and without HIV Infection.

HIV retinal microangiopathy is an important predictor for increased risk of mortality. Optical coherence tomography angiography (OCTA) can investigate microvascular changes resulting from retinal diseases. Study included 25 persons with HIV and 25 healthy persons. OCTA evaluated the vascularization of retinal layers, choriocapillary, and optic disk. HIV group had lower vessel flow density (VFD) in superficial plexus. No difference was observed in the deep plexus. VFD of the optic disk and peripapillary region showed no difference between the groups. HIV group showed a thinner retinal nerve fiber layer and smaller area of the optic disk rim. HIV infection is associated with VFD reduction in superficial retinal plexus, neural rim area reduction, and retinal nerve fiber layer thinning in individuals without microangiopathic alterations on fundus examination. Therefore, OCTA can find retinal changes before clinical evidence of retinopathy.

Risk factors associated with surgical site infection in patients with musculoskeletal cancer / Fatores de risco associados à infecção de sítio cirúrgico em portadores de câncer musculoesquelético / Factores de riesgo asociados a la infección del sitio quirúrgico en pacientes con cáncer musculoesquelético

Background and objectives: surgical site infections (SSI) continue to be a major concern in orthopedic oncology and pose as great a challenge as cancer recurrence, despite the preventive potential of surgery. SSI can be avoided if evidence-based measures are taken. The objective was to assess the frequency of infections in oncological orthopedic surgeries and associated risk factors and inflammatory markers in a reference hospital in the state of Pernambuco. Methods: the frequency of SSI, the identification of isolated microorganisms, the risk factors and the profile of Th1 and Th2 inflammatory markers (IL-2, IL-4, IL-6, IL-10, TNF and IFN-Ƴ) in patients with musculoskeletal cancer were analyzed. Results: SSI were found in 9.1% of patients undergoing orthopedic surgery. Bivariate analysis revealed that a surgical team comprising more than five members (p=0.041) and the need for intraoperative transfusion (p=0.012) were correlated with a higher risk of SSI. The measurement of ultrasensitive C-reactive protein levels to assess the inflammatory response after SSI showed results that were superior to the reference values for each sample, ranging from >5 to >200mg/dl by the immunoturbidimetric method. Of the IL-2, INFγ and TNF (Th1) and IL-4, IL-6, IL-10 (Th2) levels, only interleukin 6 showed high levels, between 6.68 and 58.76 pg/mL. Conclusion: the study found that surgical team with five or more members and blood transfusion were factors associated with the development of SSI in orthopedic surgery in patients with musculoskeletal cancer. Among the inflammatory markers, interleukin 6 (IL-6) showed the highest correlation with the outcome.(AU)

Justificativa e objetivos: as infecções do sítio cirúrgico (ISC) continuam sendo uma grande preocupação na oncologia ortopédica e representam um desafio tão grande quanto a recorrência do câncer, apesar do potencial preventivo da cirurgia. As ISC podem ser evitadas se forem tomadas medidas baseadas em evidências. O objetivo foi avaliar a frequência de infecções em cirurgias ortopédicas oncológicas e os fatores de risco e marcadores inflamatórios associados em um hospital de referência no estado de Pernambuco. Métodos: foram analisados a frequência de ISC, a identificação de microrganismos isolados, os fatores de risco e o perfil de marcadores inflamatórios Th1 e Th2 (IL-2, IL-4, IL-6, IL-10, TNF e IFN-Ƴ) em pacientes portadores de câncer musculoesquelético. Resultados: as ISC foram encontradas em 9,1% dos pacientes submetidos à cirurgia ortopédica. A análise bivariada revelou que uma equipe cirúrgica composta por mais de cinco membros (p=0,041) e a necessidade de transfusão intraoperatória (p=0,012) foram correlacionadas com maior risco de ISC. A dosagem dos níveis de proteína C reativa ultrassensível para avaliação da resposta inflamatória após ISC apresentou resultados superiores aos valores de referência para cada amostra, variando de >5 a >200mg/dl pelo método imunoturbidimétrico. Dos níveis de IL-2, INFγ e TNF (Th1) e IL-4, IL-6, IL-10 (Th2), apenas a interleucina 6 apresentou níveis elevados, entre 6,68 e 58,76 pg/mL. Conclusão: o estudo constatou que equipe cirúrgica com cinco ou mais membros e transfusão sanguínea foram fatores associados ao desenvolvimento de ISC em cirurgia ortopédica em pacientes com câncer musculoesquelético. Entre os marcadores inflamatórios, interleucina 6 (IL-6) apresentou maior correlação com o desfecho.(AU)

Justificación y objetivos: las infecciones del sitio quirúrgico (ISQ) siguen siendo una preocupación importante en la oncología ortopédica y representan un desafío tan grande como la recurrencia del cáncer, a pesar del potencial preventivo de la cirugía. Las ISQ se pueden prevenir si se toman medidas basadas en la evidencia. El objetivo fue evaluar la frecuencia de infecciones en cirugías ortopédicas oncológicas y los factores de riesgo y marcadores inflamatorios asociados en un hospital de referencia en el estado de Pernambuco. Métodos: se analizaron la frecuencia de ISQ, la identificación de microorganismos aislados, los factores de riesgo y el perfil de marcadores inflamatorios Th1 y Th2 (IL-2, IL-4, IL-6, IL-10, TNF e IFN-Ƴ) en pacientes con cáncer musculoesquelético. Resultados: se encontraron ISQ en el 9,1% de los pacientes sometidos a cirugía ortopédica. El análisis bivariado reveló que un equipo quirúrgico compuesto por más de cinco miembros (p=0,041) y la necesidad de transfusión intraoperatoria (p=0,012) se correlacionaron con un mayor riesgo de ISQ. La medición de los niveles de proteína C reactiva ultrasensible para evaluar la respuesta inflamatoria después de la ISQ presentó resultados superiores a los valores de referencia para cada muestra, variando de >5 a >200 mg/dl por el método inmunoturbidimétrico. De los niveles de IL-2, INFγ y TNF (Th1) e IL-4, IL-6, IL-10 (Th2), solo la interleucina 6 mostró niveles elevados, entre 6,68 y 58,76 pg/mL. Conclusión: el estudio encontró que el equipo quirúrgico con cinco o más miembros y la transfusión el estudio encontró que un equipo quirúrgico con cinco o más miembros y transfusión de sangre fueron factores asociados con el desarrollo de ISQ en cirugía ortopédica en pacientes con cáncer musculoesquelético. Entre los marcadores inflamatorios, la interleucina 6 (IL-6) mostró la mayor correlación con el resultado.(AU)

Acute myocardial infarction during late COVID-19 era: patient characteristics, presentation and outcomes.

COVID-19 pandemic has unquestionably influenced care of acute myocardial infarction (AMI). Still, its impact on patients (pts) characteristics, presentation, treatment, and outcomes remains not well established in late pandemic times. To address this issue, we performed a prospective study of type-1 AMI patients admitted in a tertiary care hospital. Pts were enrolled during 6-months in 2019 [n=122; pre-COVID-19 (PC) group] and in 2021 [n=196; late-COVID-19 (C) group]. Data was based on pts interview and review of medical records. Age and gender distribution, as well as ST/non-ST-elevation myocardial infarction (STEMI/NSTEMI) proportion and access to coronariography and revascularization were similar between groups. Group C patients presented more pre-existing established cardiovascular disease (CVD) (43% vs 30%; p=0.03); more frequent description of typical chest pain (94% vs 84%; p=0,002); higher levels of pain intensity, in a 0-10 scale (8±2 vs 7±2; p=0.02); higher frequencies of AMI complications (27% vs 15%; p=0.01) and worse Killip (K) class evolution (K≥2 in 22% C vs13% PC patients; p=0.05). In conclusion, late pandemic AMI patients presented worse in-hospital outcomes in our study, though pre-hospital and hospital care were comparable to pre-pandemic times. COVID patients had a higher burden of pre-existing established CVD and a more typical and intense symptom presentation. Therefore, it can be hypothesized that "sicker" patients continued to look for help when presenting AMI symptoms, while "less sick" patients and the ones with less typical and intense symptoms possibly avoided contact with health care services during late pandemic period.

Efeitos de 16 semanas de exercícios multimodais na capacidade funcional e cognitiva em idosos / Effects of 16 weeks of multimodal exercise on functional and cognitive capacity in the elderly / Efectos de 16 semanas de ejercicios multimodales sobre la capacidad funcional y cognitiva de los ancianos

O presente estudo buscou verificar o efeito de 16 semanas de exercícios multimodais na capacidade funcional e cognitiva em idosos comunitários do município de Tocantinópolis-TO. A pesquisa teve caráter descritivo, longitudinal e quase- experimental. Participaram deste estudo 44 idosos, sendo 20 do sexo masculino, com média de idade de 69 ± 7,3 anos e 24 do sexo feminino, com média de idade de 66 ± 7,6 anos. A seleção dos participantes foi realizada por meio da técnica de amostragem por conveniência em utentes da Academia da Melhor Idade (AMI), em Tocantinópolis-TO. Antes e após as 16 semanas de intervenção com exercícios multimodais, foram aplicadas: a bateria Senior fitness test de Rikli & Jones (2013) e avaliação do estado cognitivo com o Mini Exame de Estado Mental (MEEM). Em relação às variáveis da capacidade funcional, apenas o teste de "Caminhada de 6 minutos" apresentou diferença significativa nos participantes do sexo masculino (C6Min pré = 516,2 metros vs. pós = 545,8 metros; p < 0,05). Nas mulheres foram observadas diferenças significativas nas variáveis "Levantar e Sentar da Cadeira" (LSC pré = 12,5 repetições vs. Pós = 14,1 repetições; p < 0,05), "Sentado, Caminhar 2,44 m e sentar" (SCS pré = 7,3 segundos vs. pós = 6,8 segundos; p < 0,05) e "Caminhada de 6 minutos" (C6Min pré = 483,1 m vs. pós = 514,1 m; p < 0,05). O nível de cognição apresentou diferença significativa após 16 semanas de intervenção em relação aos valores verificados no baseline, tanto para os homens (MEEM pré = 21,2 vs. pós = 23,9; p < 0,05), quanto para as mulheres (MEEM pré = 23,9 pontos vs. pós = 25,1 pontos; p < 0,05). Conclui-se que os exercícios multimodais foram efetivos na melhora da cognição em e em determinadas variáveis relacionadas à capacidade funcional nos idosos após 16 semanas de intervenção.

The present study sought to verify the effect of 16 weeks of multimodal exercises on functional and cognitive capacity in community elderly of the municipality of Tocantinópolis-TO. The research had a descriptive, longitudinal and quasi- experimental character. This study included 44 elderly subjects, 20 of whom were male, with mean age of 69 ± 7.3 years, and 24 of whom were female, with mean age of 66 ± 7.6 years. The selection of the participants was carried out by means of the technique of sampling for convenience in users of the Academy of the Best Age (AMI), in Tocantinópolis-TO. Before and after the 16 weeks of intervention with multimodal exercises, we applied: the Rikli & Jones Senior fitness test (2013) and cognitive status assessment with the Mini Mental State Examination (MEEM). Regarding the functional capacity variables, only the "6-minute walk" test showed a significant difference in the male participants (C6Min pre = 516.2 meters vs. post = 545.8 meters; p < 0.05). In women, significant differences were observed in the variables "Lift and Sit of the Chair" (LSC pre = 12.5 repetitions vs. Post = 14.1 repetitions; p < 0.05), "Sit, Walk 2.44 m and sit" (SCS pre = 7.3 seconds vs. post = 6.8 seconds; p < 0.05) and "Walk of 6 minutes" (C6Min pre = 483.1 m vs. post = 514.1 m; p < 0.05). The level of cognition was significantly different after 16 weeks of intervention from baseline values for both men (pre-MSE = 21.2 vs. post = 23.9; p < 0.05) and women (pre-MSE = 23.9 points vs. post = 25.1 points; p < 0.05). It is concluded that multimodal exercises were effective in improving cognition in and in certain variables related to functional capacity in the elderly after 16 weeks of intervention.

Este estudio buscó verificar el efecto de 16 semanas de ejercicio multimodal sobre la capacidad funcional y cognitiva de las personas mayores en el municipio de Tocantinópolis-TO. La investigación tenía un carácter descriptivo, longitudinal y casi experimental. Este estudio incluyó 44 sujetos de edad avanzada, 20 de los cuales eran hombres, de una edad media de 69 ± 7,3 años y 24 eran mujeres, con una edad media de 66 ± 7,6 años. La selección de los participantes se realizó mediante una técnica de muestreo para la conveniencia de los usuarios de la Academia de la Mejor Edad (AMI), en Tocantinópolis-TO. Antes y después de 16 semanas de intervención con ejercicios multimodales, se aplicó la Senior fitness test de Rikli & Jones (2013) y la evaluación del estado cognitivo con el Mini Examen de Estado Mental (MEEM). Para las variables de capacidad funcional, sólo el test de "caminata de 6 minutos" mostró una diferencia significativa en los participantes masculinos (C6Min pre = 516,2 metros vs. post = 545,8 metros; p < 0,05). En las mujeres se observaron diferencias significativas en las variables "Levantamiento y siéntate desde la silla" (pre = 12,5 repeticiones vs. Post = 14,1 repeticiones; p < 0,05), "Sitting, Walk 2,44 m y Sit" (pre-SCS = 7,3 segundos vs. Post = 6,8 segundos; p < 0,05) y "6 minutos de sentido" (C6S) Mínimo pre = 483,1 m vs. post = 514,1 m; p < 0,05). El nivel de cognición fue significativamente diferente después de 16 semanas de intervención respecto al valor baseline para ambos hombres (MEEM pre= 21,2 vs. post = 23,9; p < 0,05) y mujeres (MEEM pre= 23,9 puntos vs. post = 25,1 puntos; p < 0,05). Se concluye que los ejercicios multimodales fueron eficaces para mejorar la cognición en y sobre determinadas variables relacionadas con la capacidad funcional en las personas mayores después de 16 semanas de intervención.

Anteromedial or central anatomic acl reconstruction? a cadaveric hip-to-toe study / Reconstrução anatômica anteromedial ou central do lca? estudo em cadáver completo

ABSTRACT Objective: To compare anatomic anterior cruciate ligament (ACL) reconstruction between two tunnel positions in knees with isolated ligament tears. Methods: Anatomic ACL reconstruction was performed, from hip-to-toe, on 15 fresh cadaveric specimens. No associated lesions were created to enhance knee instability. The protocol was conducted in three states: (1) complete isolated ACL deficiency; (2) anatomic femoral and tibial anteromedial ACL reconstruction (AM REC); and (3) anatomic femoral and tibial central ACL reconstruction (Central REC). The reconstruction protocols were randomly assigned. The continuous mechanized pivot-shift test was recorded dynamically with a tracking system. Results: The Central REC group showed a smaller degree of internal rotation (0.6° ± 0.3° vs. 1.8° ± 0.3°, respectively, P < 0.05) and no difference in anterior translation (4.7 mm ± 0.4 mm vs. 4.5 mm ± 0.4 mm, respectively, P > 0.05) in the pivot-shift test, compared with the AM REC group. Conclusion: The central anatomic ACL reconstruction resulted in greater restriction of internal rotation than the anteromedial anatomic ACL reconstruction. Experimental Study on Cadaver.

RESUMO Objetivo: Comparar a reconstrução anatômica do ligamento cruzado anterior (LCA) entre duas posições de túnel em joelhos com lesões isoladas do ligamento. Métodos: A reconstrução anatômica do LCA foi realizada, do quadril aos pés, em 15 peças anatômicas de cadáveres frescos. Não foram criadas lesões associadas para intensificar a instabilidade do joelho. O protocolo foi realizado em três estados: (1) deficiência isolada completa do LCA; (2) reconstrução anatômica femoral e anteromedial tibial do LCA (AM REC); e (3) reconstrução anatômica femoral e central tibial do LCA (Central REC). Os protocolos de reconstrução foram atribuídos aleatoriamente. O teste de pivot-shift mecanizado contínuo foi registrado dinamicamente com um sistema de rastreamento. Resultados: O grupo Central REC apresentou menor grau de rotação interna (0,6° ± 0,3° vs. 1,8° ± 0,3°, respectivamente, p < 0,05) e nenhuma diferença na translação anterior (4,7 mm ± 0,4 mm vs. 4,5 mm ± 0,4 mm, respectivamente, p > 0,05) no teste de pivot-shift, comparado ao grupo AM REC. Conclusão: A reconstrução anatômica central tibial do LCA resultou em maior restrição da rotação interna do que a reconstrução anteromedial tibial do LCA. Estudo em Cadáver Experimental.

Proximal tubular dysfunction related to tenofovir in people living with HIV/AIDS: a pharmacogenetic study.

OBJECTIVES: The purpose of this case-control study was to verify the association between single nucleotide polymorphisms (SNPs) in genes encoding drug transporters related to tenofovir disoproxil fumarate (TDF) and proximal renal tubular dysfunction (PRTD), and the association between PRTD and clinical characteristics. METHODS: The 'cases' met the diagnostic criteria for PRTD, determined by the presence of two or more of the following abnormalities: non-diabetic glycosuria, metabolic acidosis, increased uric acid and phosphorus excretion, decreased tubular phosphorus reabsorption and ß2-microglobulinuria. We analyzed eight SNPs in ABCC2, ABCC4, ABCC10 and SLC28A2 genes. Genotyping was performed using real-time PCR. RESULTS: Of the 204 people living with HIV, 38 (18.6%) met the criteria for diagnosis of PRTD and 131 were male (64.2%), with a mean age of 49 years and a history of previous antiretroviral therapy for an average of 5 years. In the multivariate analysis, older individuals, TDF use, protease inhibitor, antihypertensives and anticonvulsants were associated with a risk of developing PRTD. Increased excretion of ß2microglobulin was associated with the A/G genotype of rsCC8187710 from ABCC2 ( P = 0.003) and the following genotypes of ABCC4 SNPs: A/G from rs1059751 ( P = 0.023), G/G from rs1059751 ( P = 0.030) and C/C of rs3742106 ( P = 0.041). The increase in the fraction of excreted phosphorus was associated with the C/T genotype of SNCC rsP40037 from ABCC2 ( P = 0.0041). CONCLUSIONS: The results indicate an important relationship between SNPs associated with these markers and changes in proximal renal tubule function, and thus support their use as biomarkers for the early detection of PRTD risk.

Hyperkalemia as a limiting factor of neurohormonal blockade/modulation in everyday clinical practice.

INTRODUCTION AND OBJECTIVES: Neurohormonal blockade (NB)/modulation is the combination of two renin-angiotensin-aldosterone system inhibitors (RAASi) with a beta blocker. It is the core therapy for heart failure with reduced ejection fraction (HFrEF). While improving long term prognosis, it also induces hyperkalemia (serum K+ >5.0 mEq/L) due to RAASi effects. This may cause lethal arrhythmias and increase mortality in the short term. Thus, hyperkalemia frequently leads to withholding or reducing the intensity of neurohormonal blockade/modulation, which is associated with worsening long term prognosis. We assessed the relevance of hyperkalemia as a limiting factor of neurohormonal blockade/modulation in real life clinical conditions. METHODS: We reviewed the medical records of HFrEF patients attending a HF clinic at a tertiary Portuguese hospital during 2018 (n=240). The number of patients not tolerating maximal neurohormonal blockade/modulation due to hyperkalemia was determined. The incidence and characteristics of hyperkalemia episodes were also assessed. RESULTS: Only six patients (3%) achieved maximal doses of neurohormonal blockade/modulation. Hyperkalemia was the limiting factor in 48 (20%) patients. A total of 185 hyperkalemia episodes occurred in 100 (42%) patients. Forty-five (24%) episodes were moderate or severe (serum K+ >5.5 mEq/L). In these HFrEF patients, the co-existence of hypertension, diabetes or renal failure was associated with the occurrence of hyperkalemia. CONCLUSIONS: In daily clinical practice, hyperkalemia is frequent and limits neurohormonal blockade/modulation by leading to the withholding or reducing of the intensity of RAAS inhibition. Considering the negative prognostic impact associated with sub-optimal neurohormonal blockade/modulation, addressing hyperkalemia is an important issue when treating HFrEF patients.