[Persistent Polyclonal B-Cell Lymphocytosis (PPBL): An Entity That Is Not What it Seems]. / Linfocitose Policlonal Persistente de Células B (LPPB): Uma Entidade que Não É o que Parece.

Persistent polyclonal B-cell lymphocytosis is a rare disease with chronic lymphocytosis of polyclonal origin, which is more frequent in mostly asymptomatic middle-aged female smokers. The hallmark of this entity is the presence of bilobed/binucleated B lymphocytes, which are polyclonal as demonstrated by immunophenotyping; an elevated IgM level is common. This disease shows, in most cases, an indolent course over many years and, although controversial, it may rarely convert to malignant lymphoma. In addition to smoking, a genetic predisposition for persistent polyclonal B-cell lymphocytosis is likely. Recurrent genetic aberrations have been described. The differential diagnosis includes non-Hodgkin's lymphoma and a clear distinction between both entities is of the utmost importance because treatment is generally not indicated in the former: instead, regular follow-up is recommended. The authors describe the case of a 46-year-old female smoker, who presented with chronic lymphocytosis, elevated IgM and circulating binucleated lymphocytes. Excluding lymphoma was important considering the unusual presentation with constitutional symptoms and splenomegaly.

A linfocitose policlonal persistente de células B é uma doença rara, caracterizada por linfocitose crónica policlonal, que ocorre mais frequentemente em mulheres fumadoras de meia-idade, que se apresentam assintomáticas ou com sintomas inespecíficos. A presença de linfócitos B binucleados é considerada a assinatura citomorfológica desta entidade. A imunofenotipagem comprova a sua origem policlonal, observando-se muitas vezes uma elevação da IgM sérica. É controverso se existe um risco aumentado de desenvolvimento de linfoma. A predisposição genética é também um fator de risco, além do tabagismo. Apesar da sua natureza policlonal, alterações genéticas recorrentes estão descritas. Na linfocitose policlonal persistente de células B a abordagem terapêutica consiste habitualmente numa vigilância regular, o que reforça a importância do seu reconhecimento. Os autores descrevem o caso de uma mulher de 46 anos, fumadora, com linfocitose crónica, IgM elevada e linfócitos binucleados. O diagnóstico diferencial com linfoma assumiu particular importância, considerando os sintomas constitucionais e esplenomegalia que apresentava.

Dietary supplementation with live or autolyzed yeast: Effects on performance, nutrient digestibility, and ruminal fermentation in dairy cows.

This study was conducted to evaluate the effects of live or autolyzed yeast supplementation on dairy cow performance and ruminal fermentation. Two experiments were conducted to evaluate performance, feed sorting, total-tract apparent digestibility of nutrients, purine derivatives excretion, N utilization, ruminal fermentation, and abundance of specific bacterial groups in the rumen. In Exp. 1, 39 Holstein cows (171 ± 40 d in milk and 32.6 ± 5.4 kg/d milk yield) were blocked according to parity, days in milk, and milk yield and randomly assigned to the following treatments: Control (CON); autolyzed yeast (AY) fed at 0.625 g/kg DM (Levabon, dsm-firmenich); or live yeast (LY) fed at 0.125 g/kg DM (Vistacell, AB Vista). Cows were submitted to a 2-wk adaptation period followed by a 9-wk trial. In Exp. 2, 8 ruminal cannulated Holstein cows (28.4 ± 4.0 kg/d milk yield and 216 ± 30 d in milk), of which 4 multiparous and 4 primiparous, were blocked according to parity and enrolled into a 4 × 4 Latin square experiment with 21 d-periods (the last 7 d for sampling). Cows within block were randomly assigned to treatments sequences: control (CON2); live yeast (LY) using the same product and dietary concentration as described in Exp. 1; or autolyzed yeast fed at 0.625 g/kg DM (AY) or 0.834 g/kg DM (AY2). In Exp. 1 and 2, nutrient intake and total-tract apparent digestibility were not affected by treatments. Sorting for long feed particles (>19 mm) tended to be greater in cows fed yeast supplements than CON in Exp.1. Efficiency of N conversion into milk N was increased when feeding yeast supplements in Exp. 1. 3.5% Fat-corrected milk yield tended to be greater in cows fed yeast supplements than CON. Feed efficiency was increased when yeast supplements were fed to cows in relation to CON in Exp. 1. In Exp. 2, yield of fat-corrected milk and fat were greater in cows fed yeast supplements compared with CON2. Uric acid concentration and output in urine were increased when feeding yeast supplements when compared with CON2. Neither ruminal pH nor total volatile fatty acids were influenced by treatments. The current study did not reveal treatment differences in ruminal abundance of Anaerovibrio lipolytica, genus Butyrivibrio, Fibrobacter succinogenes, Butyrivibrio proteoclasticus, or Streptococcus bovis. Yeast supplementation can increase feed efficiency without affecting nutrient intake and digestibility, ruminal volatile fatty acid concentration, or ruminal abundance of specific bacterial groups. Supplementing live or autolyzed yeast, regardless of the dose, resulted in similar performance.

International validation of a health-related quality-of-life questionnaire for Hodgkin lymphoma: the EORTC QLQ-HL27.

Hodgkin lymphoma (HL) has become 1 of the most curable cancers. Therefore, rigorous assessment of health-related quality of life (HRQoL) and symptom burden of these patients is essential to support informed clinical decisions. The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Group previously developed the EORTC Quality of Life Questionnaire (QLQ) Hodgkin Lymphoma 27. This paper reports the final results of an international study by the EORTC group to develop a HRQoL disease-specific measure for these patients: the EORTC QLQ-HL27. Patients with a confirmed diagnosis of HL (N = 381) were enrolled from 12 countries and completed the EORTC QLQ-C30, QLQ-HL27, and a debriefing questionnaire at baseline (any time after diagnosis). A subset completed a retest (n = 126) or responsiveness-to-change analyses (RCA) second measurement (n = 98). Psychometrics were evaluated. Confirmatory factor analysis showed an acceptable fit of the 27 items of the QLQ-HL27 on its 4 scales (symptom burden, physical condition/fatigue, emotional impact, and worries about health/functioning). Test-retest reliability, convergent validity, known-group comparisons, and RCA find satisfactory results. Symptom burden and fatigue was higher among patients on treatment (with 36%-83% reporting at least a few problems) compared with those who had completed treatment (19%-61% reporting at least a few problems). Prevalence of worries about health and functioning (reporting at least some worry) was similar for patients on treatment (51%-81%) vs those who had completed treatment (52%-78%). Implementation of the EORTC QLQ-HL27 in research and clinical applications will increase sensitivity of HRQoL assessment in patients with HL. High quality data generated through use of this questionnaire are expected to facilitate clinical decision making in the HL setting.

International validation of two EORTC questionnaires for assessment of health-related quality of life for patients with high-grade non-Hodgkin lymphoma (QLQ-NHL-HG29) and low-grade non-Hodgkin lymphoma (QLQ-NHL-LG20).

BACKGROUND: Health-related quality of life (HRQOL) is a critical aspect to consider when making treatment decisions for patients with non-Hodgkin-lymphoma (NHL). This international study by the European Organisation for Research and Treatment of Cancer (EORTC) tested the psychometric properties of two newly developed measures for patients with high-grade (HG)- and low-grade (LG)-NHL: the EORTC QLQ-NHL-HG29 and the EORTC QLQ-NHL-LG20 to supplement the core questionnaire (EORTC QLQ-C30). METHODS: Overall, 768 patients with HG-NHL (N = 423) and LG-NHL (N = 345) from 12 countries completed the QLQ-C30, QLQ-NHL-HG29/QLQ-NHL-LG20 and a debriefing questionnaire at baseline, and a subset at follow-up for either retest (N = 125/124) or responsiveness to change (RCA; N = 98/49). RESULTS: Confirmatory factor analysis showed an acceptable to good fit of the 29 items of the QLQ-NHL-HG29 on its five scales (symptom burden [SB], neuropathy, physical condition/fatigue [PF], emotional impact [EI], and worries about health/functioning [WH]), and of the 20 items of the QLQ-NHL-LG20 on its four scales (SB, PF, EI, and WH). Completion took on average 10 minutes. Test-retest reliability, convergent validity, known-group comparisons, and RCA find satisfactory results of both measures. A total of 31%-78% of patients with HG-NHL and 22%-73% of patients with LG-NHL reported symptoms and/or worries (e.g., tingling in hands/feet, lack of energy, and worries about recurrence). Patients reporting symptoms/worries had substantially lower HRQOL compared to those without. DISCUSSION: The use of the EORTC QLQ-NHL-HG29 and QLQ-NHL-LG20 questionnaires in clinical research and practice will provide clinically relevant data to better inform treatment decision-making. PLAIN LANGUAGE SUMMARY: The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Group developed two questionnaires. These questionnaires measure health-related quality of life. The questionnaires are for patients with high-grade or low-grade non-Hodgkin lymphoma. They are called the EORTC QLQ-NHL-HG29 and QLQ-NHL-LG20. The questionnaires are now internationally validated. This study demonstrates that the questionnaires are reliably and valid, which are important aspects of a questionnaire. The questionnaires can now be used in clinical trials and practice. With the information gathered from the questionnaires, patients and clinicians can better evaluate treatments and discuss the best choice for a patient.

Extramedullary T-lymphoblastic Crisis in a Myelodysplastic/Myeloproliferative Neoplasm with a t(12;22)/MN1::ETV6 Translocation.

Myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are not a single disease, but rather a heterogenous group of entities which are increasingly subclassified according to recurrent genetic abnormalities. Chromosomal translocations involving meningioma 1 (MN1) and ETS variant 6 (ETV6) genes are extremely rare, but recurrent in myeloid neoplasms. We describe the case of a patient with a myelodysplastic/myeloproliferative neoplasm with neutrophilia, who developed an extramedullary T-lymphoblastic crisis with the t(12;22)(p13;q12) translocation as the only cytogenetic abnormality. This case shares several clinical and molecular features with myeloid/lymphoid neoplasms with eosinophilia. The treatment of this patient was challenging, as the disease proved to be highly refractory to chemotherapy, with allogenic stem cell transplantation as the only curative option. This clinical presentation has not been reported in association with these genetic alterations and supports the concept of a hematopoietic neoplasm originating in an early uncommitted precursor cell. Additionally, it stresses the importance of molecular characterization in the classification and prognostic stratification of these entities.

Acesso a um serviço de saúde público especializado: experiência no centro de referência de doença trofoblástica gestacional do Hospital São Paulo / Accessing a specialized public health service: the São Paulo Hospital reference center for gestational trophoblastic diseases

Objetivo: Analisar a trajetória das mulheres com doença trofoblástica gestacional (DTG) até o Centro de Referência de Doença Trofoblástica Gestacional do Hospital São Paulo (CRDTG-HSP), identificando as portas de entrada ao serviço e as dificuldades que elas enfrentaram desde o diagnóstico. Métodos: Estudo de caso transversal exploratório, descritivo-analítico, com abordagem quali-quantitativa, que incluiu pacientes atendidas no período de 2015 a 2018. A coleta dos dados se deu por meio de um questionário on-line e de uma entrevista com roteiro semiestruturado. Resultados: Entre 96 pacientes, 40,63% (n = 39) tiveram acesso ao CRDTG-HSP por encaminhamento entre médicos, 31,25% (n = 30), pela página do Facebook da Associação Brasileira de Doença Trofoblástica Gestacional e 10,42% (n = 10), por meio da central de regulação de vagas do estado de São Paulo (CROSS), das quais 28,2%, 73% e 30%, respectivamente, possuíam assistência privada, na qual receberam tratamento inicial. As 12 entrevistadas relataram dificuldades, tais como a percepção da falta de preparo médico no manejo e comunicação da doença, o desconhecimento da sua situação de saúde mesmo após procedimentos cirúrgicos, a exposição a conversas inapropriadas entre médicos sobre o seu caso e o recebimento de encaminhamento sem explicação esclarecedora sobre seu quadro clínico. Por fim, as pacientes avaliaram positivamente a utilização de e-mail e WhatsApp como facilitadores no atendimento no CRDTG-HSP. Conclusão: O acesso ao CRDTG-HSP ocorreu minoritariamente pela CROSS e, mesmo tendo assistência privada, pacientes migraram para atendimento no centro especializado. Além disso, as pacientes tiveram percepção de falta de preparo médico no atendimento da DTG fora do CRDTG.(AU)

Objective: To understand and elaborate the trajectories of women with gestational trophoblastic disease from the initial entry to the healthcare system to follow-up at a public tertiary reference center. Methods: This exploratory, descriptive-analytical, cross-sectional case study included patients from 2015 to 2018. The data collected through online questionnaires and semi-structured interviews were analyzed via quantitative and qualitative approaches. Statistical analysis was performed using Pearson's chi-square test at 5% significance using software R version 4.0.2. The test power for the sample was calculated using G*power software version 3.1.9.6. Results: Overall, 96 patients completed the questionnaire. Only 10(10.42%) patients reached the reference center through the official channel, Sao Paulo State Vacancy Regulation Center, while 39(40.63%) patients through referral from physicians, and 30(31.25%) patients through the Brazilian Association of Gestational Trophoblastic Disease's Facebook fan page. Overall, 36 patients (37.5%) had private insurance and 73% of patients who reached the reference center via Facebook had private insurance. Twelve participants were interviewed and reported barriers, such as difficulties in understanding their health issues prior to arrival at the reference center, lack of professional knowledge about the disease, poor communication, and exposure to inappropriate conversations. They positively evaluated the reference center, the interaction was facilitated using email and WhatsApp. Conclusion: Although appropriate public care for these women exists, the flow from the diagnosis to specialized treatment remains unclear for both professionals and patients. The participants perceived that communication and physicians' expertise were inadequate.(AU)

Eye diseases associated with psoriatic arthritis in the Amazon / Achados oftalmológicos em pacientes com artrite psoriásica na região Amazônica

ABSTRACT Purpose: Ocular disorders are among the most frequent manifestations of psoriatic arthritis. The incidence, type, and severity of these disorders may be influenced by genetics, local environmental factors, and access to ophthalmic treatment. Here we describe the ocular manifestations of psoriatic arthritis among denizens of the Amazon region of Para, Brazil, treated by the rheumatology service of Universidade do Estado do Pará. Methods: This cross-sectional study examined 23 psoriatic arthritis patients (median age 47.78 years, no sex predominance) diagnosed according to Caspar's criteria. Disease activity was evaluated according to the Clinical Disease Activity Index for Psoriatic Arthritis. Ophthalmological examinations performed included visual acuity with distance correction, biomicroscopy, applanation tonometry, fundoscopy, Schirmer test I, tear breakup time, fluorescein staining, and lissamine green staining. Patients also completed The Ocular Surface Disease Index questionnaire. Results: The most common ophthalmic disorders were dry eye (60.9%), cataracts (56.5%), blepharitis (47.8%), keratitis (43.5%), meibomitis (30.4%), pterygium (26, 1%), and pinguecula (13%). More than half of all patients demonstrated recent onset (>5 years), the peripheral disease type, and severe symptoms according to Clinical Disease Activity Index for Psoriatic Arthritis. Conclusion: The ocular manifestations of psoriatic arthritis are varied and mainly affect the ocular surface. Regular ophthalmological follow-up is recommended for patients in the early stage with high disease activity.

RESUMO Objetivo: Descrever as manifestações oftalmológicas observadas em pacientes com artrite psoriásica atendidos no Serviço de Reumatologia da Universidade do Estado do Pará. Métodos: Estudo transversal. A amostra foi composta por 23 pacientes com artrite psoriásica, segundo os critérios de Caspar, atendidos no ambulatório de reumatologia da Universidade do Estado do Pará. Para avaliação da atividade de doença foi aplicado o Clinical Disease Activity index for Psoriatic Arthritis e, posteriormente, foi realizado o exame oftalmológico (acuidade visual com correção para distância, biomicroscopia, tonometria de aplanação de Goldmann, fundoscopia, teste de Schirmer I, tempo de ruptura do filme lacrimal, lissamina verde e questionário The Ocular Surface Disease Index). Resultados: Nesta pesquisa não houve predomínio entre os sexos e a população tinha uma mediana de idade de 47,78 anos. As manifestações mais comuns foram olho seco (60,9%), catarata (56,5%), blefarite (47,8%), ceratite (43,5%), meibomite (30,4%) e pterígio (26,1%). Conclusão: As manifestações oculares encontradas em pacientes com artrite psoriásica são variadas e afetam sobretudo a superfície ocular; no entanto, são clinicamente subestimadas; por isso recomenda-se o acompanhamento oftalmológico regular e periódico para pacientes com artrite psoriásica.

Telemedicine in post-molar follow-up: is it a useful tool?

BACKGROUND: Telemonitoring is an alternative to in-person appointments and overcomes geographic distance barriers. OBJECTIVE: The primary objective of this study was to evaluate adherence to post-molar follow-up using both WhatsApp and in-person appointments compared with standard care. The secondary objective was to evaluate the rate of completion of post-molar follow-up of complete moles, considering 6 and 3 months of duration. METHODS: This retrospective cohort study was conducted at the Gestational Trophoblastic Disease Center, São Paulo Hospital. Patients with complete or partial mole treatment between January 1, 2009 and December 31, 2018 were included in two groups: group 1 (patients from 2009 to 2013) and group 2 (from 2014 to 2018), before and after telemonitoring implementation, respectively. Complete follow-up was considered if after the first normal human chorionic gonadotropin (hCG) level (<5 mIU/mL), the patient was followed up for an additional 30 days (partial mole) or 180 days (complete mole). Loss to post-molar follow-up with positive hCG was also evaluated. Statistical analysis was performed using Pearson's Χ2 test, 5% significance level (p=0.05), and R version 4.0.2. RESULTS: A total of 308 patients were included in the study, 92 of them were assessed in group 1 and 216 patients in group 2. There was no difference between the rates of complete follow-up after telemonitoring implementation (complete mole: 42/72=58.3% group 1 vs 85/163=52.1% group 2; p=0.38; partial mole: 16/20=80% group 1 vs 37/53=69.8 group 2; p=0.3), and no increase of loss to post-molar follow-up with positive hCG (8/92=8.7% group 1 vs 14/216=6.5% group 2; p=0.49). The shortening of follow-up of complete moles to 90 days increased the rate of complete post-molar follow-up (from 127/235=54.0% to 189/235=80.4%, p<0.001). CONCLUSIONS: The association of telemonitoring with in-person appointments could have had an advantage in post-molar follow-up since it did not reduce adherence to hormonal surveillance. Shortening post-molar follow-up after complete mole to 90 days after the first normal hCG level increased the rate of complete post-molar follow-up.

Eye diseases associated with psoriatic arthritis in the Amazon.

PURPOSE: Ocular disorders are among the most frequent manifestations of psoriatic arthritis. The incidence, type, and severity of these disorders may be influenced by genetics, local environmental factors, and access to ophthalmic treatment. Here we describe the ocular manifestations of psoriatic arthritis among denizens of the Amazon region of Para, Brazil, treated by the rheumatology service of Universidade do Estado do Pará. METHODS: This cross-sectional study examined 23 psoriatic arthritis patients (median age 47.78 years, no sex predominance) diagnosed according to Caspar's criteria. Disease activity was evaluated according to the Clinical Disease Activity Index for Psoriatic Arthritis. Ophthalmological examinations performed included visual acuity with distance correction, biomicroscopy, applanation tonometry, fundoscopy, Schirmer test I, tear breakup time, fluorescein staining, and lissamine green staining. Patients also completed The Ocular Surface Disease Index questionnaire. RESULTS: The most common ophthalmic disorders were dry eye (60.9%), cataracts (56.5%), blepharitis (47.8%), keratitis (43.5%), meibomitis (30.4%), pterygium (26, 1%), and pinguecula (13%). More than half of all patients demonstrated recent onset (>5 years), the peripheral disease type, and severe symptoms according to Clinical Disease Activity Index for Psoriatic Arthritis. CONCLUSION: The ocular manifestations of psoriatic arthritis are varied and mainly affect the ocular surface. Regular ophthalmological follow-up is recommended for patients in the early stage with high disease activity.

End of treatment FDG-PET in primary mediastinal B-cell lymphoma treated with R-chemotherapy: Prognostic indicator and implications for consolidation radiotherapy.

The ideal therapeutic regimen in primary mediastinal B-cell lymphoma (PMBCL) is controversial and may include consolidation radiotherapy (RT). An adequate strategy is essential in a population where long-term effects of RT are significant. We evaluated the prognostic value of end-of-treatment (EOT) FDG-PET in 50 patients receiving rituximab and anthracycline-containing chemotherapy and its implications for consolidative RT. Thirty patients (60%) obtained complete metabolic response (CMR), five received consolidation RT. The remaining patients had partial response (14) and progression (6). Of these, 12 received mediastinal RT, six salvage chemotherapy, and two no further treatment. Five-year progression free survival was 100% and 48% (95% CI 30%-77%) in patients with negative and positive EOT FDG-PET, respectively (P < .001). Five-year overall survival for negative and positive EOT FDG-PET was 100% and 67% (95% CI 48%-93%) respectively (P = .001). Within positive EOT FDG-PET cases, an association was found between Deauville score and survival. The negative predictive value (NPV) of EOT FDG-PET for disease relapse/progression was 100% (95% CI 0.88-1.00); the positive predictive value was 47% (95% CI 0.24-0.71). This study demonstrates the importance of metabolic assessment in PMBCL and is relevant for its high NPV. Our data favor the use of EOT FDG-PET for decisions concerning RT.

Rare Association Between Idiopathic Multicentric Castleman Disease, Nephrotic Syndrome and Polyneuropathy in an Immunocompetent Patient.

Multicentric Castleman disease (MCD) represents a group of poorly understood lymphoproliferative disorders related to proinflammatory hypercytokinaemia. In immunocompetent patients the aetiology is still unknown, hence the designation of idiopathic MCD (iMCD). To successfully diagnose iMCD, diagnostic criteria must be fulfilled and a large array of alternative diagnoses excluded. Peripheral neuropathy and nephropathy are relatively common findings in cases associated with POEMS syndrome, but very rarely reported in iMCD. We present the case of a 64-year-old man with iMCD (HIV- and HHV-8-negative) with nephrotic syndrome and severe motor polyneuropathy. Alternative diagnoses were excluded. The patient was treated with intravenous glucocorticoid followed by rituximab. Complete clinical and laboratory remission was achieved and maintained at the 2-year follow-up. LEARNING POINTS: iMCD is a lymphoproliferative disease in immunocompetent patients with no known cause.To diagnose iMCD major and minor criteria must be fulfilled, and alternative diagnoses must be excluded.Nephrotic syndrome and motor polyneuropathy are rare in iMCD and all alternative diagnoses must be excluded before relating all of these.

A laboratory-based analysis of rapidly growing mycobacteria in Northwest Paulista, Sao Paulo, Brazil.

Background: Rapidly growing mycobacteria (RGM) are a group of nontuberculous mycobacteria (NTM) implicated in difficult-to-treat pulmonary and extrapulmonary diseases, possibly associated with invasive procedures and failures in sterilization of materials and equipment. Methods: We report our experience with the laboratory identification of RGM in a routine work and give an overview of the RGM isolated in our setting. Laboratorial data from all RGM mycobacterial isolates received at Adolfo Lutz Institute of São José do Rio Preto were analyzed from January 2000 to December 2015. Results: Five hundred and seventy-nine isolates were identified with NTM, of which 193 were RGM, which affected 113 patients. Among the 113 patients, the female gender was more frequent (55%) and the average age was 50 years. Pulmonary samples were the most frequent (79%), and 54.9% of the cases were isolated from sputum. Twelve different species were found and the most identified were group Mycobacterium abscessus and Mycobacterium fortuitum, making up 77.9% of all identified RGM. The most frequent comorbidities were smoking (n = 21), alcoholism (n = 12), and human immunodeficiency virus (n = 16). Drug susceptibility test was performed for nine patients and all showed susceptibility to amikacin and seven resistances to doxycycline. Conclusions: This study showed the experience of mycobacterial diagnosis in a routine laboratory, revealing that failure to meet the bacteriological criteria generates losses in the establishment of cases of RGM and consequently its correct treatment.

International Patent Survey of Products and Processes Concerning Homeopathy.

BACKGROUND: Homeopathy is a complementary medicine characterized by the use of diluted and potentized medicines. Innovations in this area are constantly being proposed in the relevant literature, such as scientific articles and patents. The objective of this study was to carry out a patent survey of homeopathic products and processes. METHODS: A free and international patent database, Espacenet, was used. The search was carried out using the keyword homeop*, with two approaches: (1) no date restrictions for the search and (2) a date limit for the publication years 2008 to 2018. The patents from the limited period were organized as depositor countries, ownerships and groups, including homeopathic formulations, equipment, packaging, production procedures, and analytical methods. RESULTS: Without date restriction, 601 patents were identified in the survey. Of these, 174 were related to homeopathy and published in the period 2008 to 2018. Technologies come mainly from the following countries: United States (55 patents), Russia (24), Germany (15), France (13), India (12), Ukraine (11), Brazil (6), and China (6). Among the ownerships, 69% of patent applications were by independent depositors, 23% by companies, 7.5% by universities, and 0.5% by company/university partnerships. New formulations represented 75.9% of technologies, whilst the others comprised 14.3% for equipment, 3.8% for drugs packaging, 3.8% for production procedures, and 2.2% for analytical methods. CONCLUSIONS: The present review helps visualize the homeopathy-related patents published in recent years, as well as the main countries and researchers investing in the field of homeopathy.

Insights on 3D Structures of Potential Drug-targeting Proteins of SARS-CoV-2: Application of Cavity Search and Molecular Docking.

The emergence of the COVID-19 has caused public health problems worldwide and there is no effective pharmacological treatment for this disease. Research on 3D models of proteins and the search for active molecular sites are important tools to assist in the discovery of effective antiviral drugs to combat COVID-19. To address this problem, the 3D protein structures of SARS-CoV 2 were analyzed and submitted to cavities research, evaluation of their druggabillity and liganbility, and applied to molecular docking studies with potential ligand candidates actually assayed against COVID-19. Eight druggable potential cavity sites were determined in model structures' PDB code, 6W4B, 6VWW, 6W01, 6M3M, and 6VYO, and these are the good alternatives to be characterized as targets for antiviral compounds. The good cavity model of the protease 3D structure was used in molecular docking, and this allowed verifying the theoric interactions of this protein and lopinavir and ritonavir antiviral drugs. These results may assist in the use of 3D protein models in drug design studies aiming to develop drugs against the COVID-19 pandemic.

Acidente com autoinjetor de adrenalina / Accidental use of an adrenaline autoinjector

A anafilaxia é uma reação alérgica potencialmente fatal. Autoinjetor pode ser prescrito para tratamento precoce nesses casos. Relatamos o caso de uma criança que fez uso acidental de adrenalina autoinjetora que ao exame de imagem evidenciou falange distal com fratura. Objetivamos alertar a importância de orientar o paciente e seus familiares acerca do uso correto desse dispositivo.

Anaphylaxis is a potentially fatal allergic reaction. Autoinjection can be prescribed for early treatment in these cases. We report the case of a child who accidentally used an adrenaline autoinjector and then had a distal phalanx fracture on imaging examination. We aim to draw attention to the importance of carefully guiding patients and their families about the correct use of this device.

Pellucidin A promotes antinociceptive activity by peripheral mechanisms inhibiting COX-2 and NOS: In vivo and in silico study.

Peperomia pellucida (PP) belongs to the Peperomia genus, which has a pantropic distribution. PP is used to treat a wide range of symptoms and diseases, such as pain, inflammation, and hypertension. Intriguingly, PP extract is used by different tropical countries for its anti-inflammatory and antinociceptive effects. In fact, these outcomes have been shown in animal models, though the exact bioactive products of PP that exert such results are yet to be discovered. To determine and elucidate the mechanism of action of one of these compounds, we evaluated the antinociceptive effect of the novel dimeric ArC2 compound, Pellucidin A by using in vivo and in silico models. Animals were then subjected to chemical, biphasic and thermal models of pain. Pellucidin A induced an antinociceptive effect against chemical-induced pain in mice, demonstrated by the decrease of the number of writhes, reaching a reduction of 43% and 65% in animals treated with 1 and 5 mg/kg of Pellucidin A, respectively. In the biphasic response (central and peripheral), animals treated with Pellucidin A showed a significant reduction of the licking time exclusively during the second phase (inflammatory phase). In the hot-plate test, Pellucidin A did not have any impact on the latency time of the treated animals. Moreover, in vivo and in silico results show that Pellucidin A's mechanism of action in the inflammatory pain occurs most likely through interaction with the nitric oxide (NO) pathway. Our results demonstrate that the antinociceptive activities of Pellucidin A operate under mechanism(s) of peripheral action, involving inflammatory mediators. This work provides insightful novel evidence of the biological properties of Pellucidin A, and leads to a better understanding of its mechanism of action, pointing to potential pharmacological use.

The effects of genetic group and sex on residual feed intake, performance, morphometric, testicular, and carcass traits' in lambs.

The aim of this study was to analyze the effects of genetic group and sex on residual feed intake, performance, testicular size, carcass and morphometric traits in Santa Ines purebred and Dorper ´ Santa Ines crossbred lambs. A total of 32 lambs, with initial body weight of 18±3.7 kg were used. Analysis of variance, considering the interaction between sex and genetic group of all the traits were performed. Crossbred females (-0.018±0.06) and purebred males (-0.018±0.05) were more efficient (p<0.001) in residual feed intake than crossbred males (0.018±0.04) or purebred females (0.018±0.04). The most efficient animal in residual feed intake consumed 37.9% less feed (1.179 kg/day) than the least efficient animal (1.899 kg/day). Crossbred, when compared to purebred, showed higher values for body weight, average daily gain, testicle size, carcass traits; had greater muscle accumulation, were more compact and with more aptitude to beef. Purebred were taller, but with lower body length and thoracic perimeter than crossbred. Males had greater muscle accumulation, were more compact and with more aptitude to meat. Crossing of native (Santa Ines) with exotic breed (Dorper) is an alternative to align efficiency in feed use, testicular size, compactness, aptitude for meat and ability for muscle accumulation.

Efeito da realidade virtual no recrutamento de fibras musculares e força muscular respiratória em pacientes com doença de Parkinson - estudo piloto / Effect of virtual reality on recruitment of muscle fibers and respiratory muscle strength in patients with Parkinson's disease - pilot study

Introdução: A Doença de Parkinson compromete a mobilidade da caixa torácica, acarretando limitação progressiva da ventilação, devido ao padrão de flexão e rigidez e fraqueza muscular. A realidade virtual propicia interação em tempo real com atividades e ambientes tridimensionais. Objetivo: Avaliar o efeito da realidade virtual no recrutamento de fibras e forças musculares respiratória e postural em pacientes com doença de Parkinson. Métodos: Estudo clínico, piloto, prospectivo, com alocação por conveniência. Dez indivíduos foram selecionados e alocados em grupo estudo (GE n=5) constituídos por idosos com DP e grupo controle (GC n=5) formado por idosos na mesma faixa etária, sem condições clínicas neurológicas e respiratórias. As variáveis mensuradas foram: independência funcional, desempenho motor, força muscular respiratória, recrutamento de fibras musculares respiratórias e posturais, e qualidade de vida. Foram realizadas 16 sessões com realidade virtual. Resultados: As Pressões Inspiratória máxima (PImáx) e Expiratória máxima (PEmáx) melhoraram em alguns momentos da intervenção. O recrutamento de fibras musculares em esternocleidomastóideo diminuiu e o recrutamento de fibras musculares no diafragma aumentou. Conclusão: A PImáx e a PEmáx melhoraram em alguns momentos do tratamento, e houve diminuição do recrutamento de fibras musculares dos músculos respiratórios acessórios nos pacientes com DP. (AU)

Introduction: Parkinson's disease commits the mobility of the rib cage, causing progressive ventilation limitation due to bending and stiffness. Virtual reality provides real-time interaction with activities and three-dimensional environments. Objective: To evaluate the effect of virtual reality on the recruitment of muscle fibers and respiratory and postural muscle strength in patients with Parkinson's disease. Methods: Clinical, pilot, prospective study, with allocation by convenience. Ten individuals were selected and allocated to a study group (EG n = 5) consisting of elderly people with Parkinson and a control group (CG n = 5) formed by elderly people in the same age group, without neurological and respiratory conditions. The measured variables were functional independence, motor performance, respiratory muscle strength, recruitment of respiratory and postural muscle fibers, and quality of life. 16 sessions were held with virtual reality. Results: The maximum inspiratory pressures (MIP) and maximum expiratory pressures (MEP) improved in some moments of the intervention. The recruitment of muscle fibers in the sternocleidomastoid decreased and the recruitment of muscle fibers in the diaphragm increased. Conclusion: MIP and MEP improved in some moments of treatment, and there was a decrease in the recruitment of muscle fibers from accessory respiratory muscles in patients with PD. (AU)

Genetic diversity in oocyte donors used in in vitro bovine embryo production programs in Brazil / Diversidad genética en donadoras de ovocitos utilizadas en programas de producción de embriones bovinos in vitro en Brasil / Diversidade genética em doadoras de oócitos utilizadas em programas de produção de embriões bovinos in vitro no Brasil

Abstract Background: Current reproductive management of bovine elite populations involves the use of assisted reproductive technologies (ARTs), aiming to obtain the greatest genetic gain. However, inadequate use of ARTs may lead to loss of genetic diversity in the offspring. Objective: To assess the genetic diversity in elite female cattle populations used in commercial in vitro embryo production. Methods: Using genetic and ecological approaches for the study of populations based on microsatellite markers, we assessed the genetic diversity between and within populations of cows used in commercial in vitro embryo production programs in Brazil. Results: Endogamy within populations varied from zero to 9.1%, while heterozygosity between populations (FST) was <0.05 in the different population interactions. AMOVA showed 1% variation between populations, 8% between individuals and 91% within individuals. The dimensionality reduction method utilized indicated a lack of structure in the populations analyzed, identifying two main clusters in the three populations. Conclusions: Low genetic diversity between cow populations associated with commercial programs of in vitro embryo production in Brazil was evidenced. Variable levels of endogamy within the populations were observed. Approaches of population genetics as well as ecological diversity can be implemented to more thoroughly estimate genetic diversity in livestock populations.

Resumen Antecedentes: El actual manejo reproductivo en poblaciones de bovinos de élite incluye la utilización de tecnologías de reproducción asistida (ARTs) con el fin de obtener mayor ganancia genética. Sin embargo, el uso inadecuado de las ART puede llevar a la pérdida de diversidad genética en los descendientes. Objetivo: Evaluar la diversidad genética en poblaciones de vacas de élite utilizadas en la producción comercial de embriones bovinos in vitro. Métodos: Utilizando abordajes de la genética y ecología de poblaciones basados en marcadores microsatélites, evaluamos la diversidad genética entre y dentro de poblaciones de vacas participantes de programas comerciales de producción de embriones in vitro en Brasil. Resultados: La endogamia dentro de las poblaciones varió de cero a 9,1%, mientras que la heterocigosidad entre poblaciones (FST) fue <0,05 en las diferentes interacciones de la población. El AMOVA mostró variación del 1% entre poblaciones, 8% entre individuos y 91% dentro de individuos. El método de reducción de dimensionalidad utilizado indicó una falta de estructura en las poblaciones analizadas, identificando dos grupos principales en las tres poblaciones. Conclusiones: Se evidenció una baja diversidad genética entre las poblaciones de vacas asociadas a programas comerciales de producción de embriones in vitro en Brasil. Se evidenciaron niveles variables de endogamia entre las poblaciones. Abordajes de la genética poblacional, así como de diversidad ecológica pueden ser implementados para estimar de manera más amplia la diversidad genética en poblaciones animales de interés pecuario.

Resumo Antecedentes: O atual manejo reprodutivo das populações de elite em bovinos envolve o uso de tecnologias de reprodução assistida (ARTs), visando obter o maior ganho genético. No entanto, o uso inadequado de ARTs pode levar à perda de diversidade genética na prole. Objetivo: Avaliar a diversidade genética em populações de vacas de elite utilizadas na produção comercial de embriões bovinos in vitro. Métodos: Utilizando abordagens da genética e ecologia de populações baseadas em marcadores microssatélites, foi avaliada a diversidade genética entre e dentro das populações de vacas participantes de programas comercias de produção in vitro de embriões. Resultados: A endogamia dentro das populações variou de zero a 9,1%, enquanto a heterozigosidade entre populações (FST) foi <0,05 nas diferentes interações populacionais. AMOVA mostrou variação de 1% entre populações, 8% entre indivíduos e 91% dentro de indivíduos. O método de redução de dimensionalidade utilizado indicou uma falta de estrutura nas populações analisadas, identificando dois clusters principais nas três populações. Conclusões: Baixa diversidade genética entre populações de vacas associadas a programas de produção in vitro de embriões foi evidenciada. Níveis de endogamia variáveis dentro das populações foram observados. Abordagens da genética populacional assim como de diversidade ecológica podem ser implementadas na tentativa de estimar de maneira mais abrangente a diversidade genética em populações animais de interesse pecuário.

Fatores intervenientes na qualidade de vida do estudante de enfermagem / Intervening factors in the quality of life of nursing student

Objetivo: avaliar o grau de qualidade de vida dos estudantes concluintes do curso de enfermagem de uma universidade privada acerca dos fatores considerados estressantes. Método: trata-se de estudo quantitativo em que participaram 60 graduandos do curso de enfermagem e que utilizou como instrumento de coleta a Escala de Qualidade de Vida de Flanagan. Resultados: observou-se que a maioria entrevistada é do sexo feminino, com idade entre 23 e 27 anos. Constatou-se que a QV destes alunos conforme as dimensões do questionário foi classificada como média a baixa. Conclusão: os níveis de QV desses alunos são considerados preocupantes, uma vez que a QV implica diretamente no desempenho acadêmico e emocional do indivíduo, ocasionando problemas na sua saúde mental. Esses achados podem contribuir para o desenvolvimento de medidas que diminuam o estresse provocado neste ambiente e, assim, promover a melhora da QV de universitários.(AU)