People With Patellofemoral Pain Have Bilateral Deficits in Physical Performance Regardless of Pain Laterality.

CONTEXT: People with patellofemoral pain (PFP) may have lower performance during the forward step-down and single-leg hop with their painful (unilateral complaints) or most painful (bilateral complaints) limb when compared to pain-free controls. Yet, no study has investigated the appropriateness of using the pain-free/less painful limb as a reference standard in clinical practice or whether deficits might be present depending on the laterality of pain. OBJECTIVE: To compare performance scores and proportion of side-to-side limb symmetry during the forward step-down and single-leg hop tests among people with unilateral and bilateral PFP, and pain-free controls. DESIGN: Cross-sectional study. SETTING: Laboratory. PATIENTS OR OTHER PARTICIPANTS: Fifty-two young adults (18-35 years old) with unilateral PFP, 72 with bilateral PFP, and 76 controls. MAIN OUTCOME MEASURE(S): Group-by-limb interactions on the performance during the step- down (repetitions) and hop test (distance [cm] normalized by the limb length) were investigated using a repeated-measures analysis of covariance controlling for sex. Pairwise comparisons were interpreted using effect sizes. A Chi-square test was used to compare the proportion of symmetry/asymmetry (cutoff point of ≥ 90% for symmetries indices) across groups and tests. RESULTS: Main effects for groups (small-to-medium effects) but not limbs indicated lower performance of both limbs of individuals with unilateral and bilateral PFP compared to controls during forward step-downs and single-leg hop tests. No significant differences for the proportion of symmetry/asymmetry were identified across groups (p ≥ 0.05), which further suggests an impaired physical performance of the contralateral limb. CONCLUSIONS: Our results indicate bilateral deficits in the physical performance of people with unilateral and bilateral PFP when compared to pain-free controls during the forward step-down and single-leg hop tests. Limb symmetries indices greater than 90% should be interpreted with caution, as they may overstate the physical performance by not assuming bilateral deficits.

Amlodipine and lufenuron as repurposing drugs against Sporothrix brasiliensis.

Background: Sporotrichosis caused by Sporothrix brasiliensis is a globally emerging infectious disease with limited therapeutic options. Thus, we aimed to evaluate the in vitro activity of amlodipine (AML) and lufenuron (LUF) alone and their interaction with itraconazole (ITZ), the first-choice drug against S. brasiliensis. Methods: Twenty clinical isolates of S. brasiliensis from two hyperendemic regions were tested through a microdilution assay to evaluate the minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) of AML and LUF. Checkerboard assay was performed with 10 isolates for both drug interactions with ITZ. Results: AML showed inhibitory and fungicidal activity against all isolates included, with MIC values ranging from 32 to 256 µg/mL, and MFC from 64 to 256 µg/mL. However, none of the S. brasiliensis isolates were inhibited by the highest soluble concentration of LUF (MIC >64 µg/mL for all strains). Synergic interaction of AML and LUF with ITZ occurred in 50% and 40% of the isolates tested, without any antagonistic effects. Conclusion: Both repurposing drugs evaluated in our study showed a promising in vitro activity, especially in synergy with ITZ against S. brasiliensis, warranting future in vivo investigations regarding its activity.

Cytotoxicity, mutagenicity and acute oral toxicity of aqueous Ocotea minarum leaf extracts.

Ocotea minarum (Nees & Mart.) Mez., a native species of Brazil, is used in the treatment of infections and oxidative stress; however, there is no scientific evidence of its toxicological characteristics. We assessed the cytotoxicity, mutagenic activity, and acute oral toxicity of the aqueous extract isolated from O. minarum leaves. The cytotoxicity of this extract was evaluated in tumour and non-tumour cell lines, while the Ames test with a Salmonella Typhimurium was used to determine the mutagenic activity. Wistar rats received a single 2 g/kg dose as part of an LD50 toxicity assessment. Our results showed that the aqueous extract of O. minarum leaves did not present cytotoxic and mutagenic properties and was not toxic, with an LD50 greater than 2 g/kg. Therefore, the O. minarum extracts are pharmacologically safe and can continue to be investigated for the development of new drugs and herbal medicines.

Smell tests to distinguish Parkinson's disease from other neurological disorders: a systematic review and meta-analysis.

Introduction: Olfactory impairment has been considered for differential diagnosis in Parkinson's disease (PD) patients. The authors aimed to identify the tests used to assess the olfactory function in PD patients and examine these tests' ability to distinguish them from other neurological disorders.Areas covered: Cross-sectional studies published until May 2020 comparing the olfactory function of PD patients to other neurological disorders were searched on PubMed, PsycInfo, Cinahl, and Web of Science databases using search terms related to PD, olfactory function, and assessment. Five thousand three hundred and four studies were screened, and 35 were included in the systematic review. Six smell tests that evaluated a total of 1,544 PD patients were identified. Data of 1,144 patients included in the meta-analyses revealed worse smell performance than individuals with other neurological disorders, such as progressive supranuclear palsy and essential tremor, but not with idiopathic rapid eye movement sleep behavior disorder.Expert opinion: The University of Pennsylvania Smell Identification Test was the most used test to assess the olfactory function of PD. Smell loss was worse in PD than in some neurological disorders. The smell tests' ability in differentiating PD from other neurological disorders still deserves more attention in future studies. Protocol register (PROSPERO/2018-CRD42018107009).

Anti-dengue Vaccines: From Development to Clinical Trials.

Dengue Virus (DENV) is an arbovirus (arthropod-borne virus). Four serotypes of DENV are responsible for the infectious disease called dengue that annually affects nearly 400 million people worldwide. Although there is only one vaccine formulation licensed for use in humans, there are other vaccine formulations under development that apply different strategies. In this review, we present information about anti-dengue vaccine formulations regarding development, pre-clinical tests, and clinical trials. The improvement in vaccine development against dengue is much needed, but it should be considered that the correlate of protection is still uncertain. Neutralizing antibodies have been proposed as a correlate of protection, but this ignores the key role of T-cell mediated immunity in controlling DENV infection. It is important to confirm the accurate correlate of protection against DENV infection, and also to have other anti-dengue vaccine formulations licensed for use.

Controvérsias em torno do uso experimental da cloroquina / hidroxicloroquina contra a Covid-19: "no magic bullet" / Controversies about the experimental use of chloroquine / hydroxychloroquine against Covid-19: "no magic bullet"

Resumo O artigo apresenta um panorama dos testes clínicos conduzidos em 2020, que visam produzir evidências sobre a eficácia de dois medicamentos utilizados experimentalmente contra a Covid-19 - hidroxicloroquina e cloroquina -, desde que se passou a cogitar eficácia de seu uso, seja no tratamento de doentes graves, de infectados sem quadro clínico importante, ou mesmo como agente preventivo. Foram utilizados dados secundários - bancos de dados de testes clínicos, material da mídia e literatura especializada. Em meio à urgência de tratamentos para contenção da pandemia, o uso experimental gerou controvérsias inicialmente no meio científico, mas que acabaram por ser fortemente capturadas politicamente. Líderes como Trump e Bolsonaro, em discursos mal fundamentados, têm se declarado altamente favoráveis ao uso desses medicamentos, gerando uma minimização da gravidade da epidemia e, simultaneamente, negligenciando a necessidade de elevação importante de gastos públicos em saúde. Face às frágeis evidências científicas produzidas, a euforia social em torno desses medicamentos e sua promoção suscitou exageros e comportamentos irracionais, como automedicação. Esperar-se-ia de governantes e gestores de nações democráticas, muito mais cautela e responsabilidade, que contribuíssem na construção de respostas cientificamente embasadas, racionais e eficazes ao controle da pandemia, protegendo a saúde de suas populações, pressuposto do poder de Estado.

Abstract The article presents an overview of clinical tests conducted in 2020, which aim to produce evidence on the efficacy of two drugs used experimentally against Covid-19 - hydroxychloroquine and chloroquine -, since the effectiveness of their use, whether in the treatment of seriously ill, infected with no significant clinical condition, or even as a preventive agent. Secondary data were used - clinical test databases, media material and specialized literature. Considering the urgency of treatments to contain the pandemic, the experimental use generated controversies initially in the scientific environment, but which ended up being strongly captured politically. Leaders like Trump and Bolsonaro, in ill-founded speeches, have declared themselves highly favorable to the use of these drugs, generating a minimization of the severity of the epidemic and, simultaneously, neglecting the need for significant increase in public spending on health. In view of the fragile scientific evidence produced, the social euphoria surrounding these drugs and their promotion led to exaggerations and irrational behaviors, such as self-medication. It would be expected from governments and managers of democratic nations, much more caution and responsibility, to contribute to the construction of scientifically based, rational and effective responses to the control of the pandemic, protecting the health of their populations, an assumption of state power.

Repeatability and comparison of clinical tests in children with spastic diplegia and with typical development, / Repetibilidade e comparação de testes clínicos para crianças diparéticas e com desenvolvimento típico

Objective The aims of this study were to evaluate the reliability of three range of motion tests (Straight Leg Raise, Modified Thomas, and Duncan-Ely) using photographic measurements in children with spastic diplegic cerebral palsy (SD) and with typical development (TD). Methods A cross-sectional test-retest design was applied to compare muscle-tendon unit shortening tests between groups. Results The tests showed reliability that ranged from good to excellent (ICC > 0.8), except for the Thomas Test for the bi-articular hip flexor muscle-tendon unit of the TD group (ICC = 0.7). Differences between groups were found in all tests (p < 0.05), except when the range of motion of the bi-articular hip flexor muscles was assessed using the Thomas test (p > 0.05). Conclusion Children with SD presents a smaller range of motion than the TD group. However, the Thomas Test for the bi-articular hip flexor muscles was unable to determine differences between children with spastic diplegic cerebral palsy from that with typical development. .

Objetivo O objetivo do estudo foi avaliar a repetibilidade de três testes de amplitude de movimento (Elevação da perna reta, Thomas Modificado e Duncan-Ely) usando medidas realizadas por fotografia em crianças com paralisia cerebral do tipo diparesia espástica (SD) e com desenvolvimento típico (TD). Métodos O estudo teve design transversal do tipo teste-reteste para comparar o comprimento musculotendíneo entre os grupos. Resultados Os testes mostraram repetibilidade de boa a excelente (ICC > 0,8), com exceção do teste de Thomas para os flexores biarticulares do quadril para o grupo TD (ICC = 0,7). Diferenças entre os grupos foram encontradas em todos os testes (p < 0,05), à exceção da amplitude de movimento dos flexores biarticulares do quadril ao se utilizar o teste de Thomas (p > 0,05). Crianças com SD apresentam menores amplitudes de movimento que as crianças do grupo TD. Entretanto, o teste de Thomas para os flexores biarticulares do quadril não foi capaz de determinar diferenças entre as crianças com diparesia espástica e as crianças com desenvolvimento típico. .