Validating an inertial measurement unit for cricket fast bowling: a first step in assessing the feasibility of diagnosing back injury risk in cricket fast bowlers during a tele-sport-and-exercise medicine consultation

This study aimed to validate an array-based inertial measurement unit to measure cricket fast bowling kinematics as a first step in assessing feasibility for tele-sport-and-exercise medicine. We concurrently captured shoulder girdle relative to the pelvis, trunk lateral flexion, and knee flexion angles at front foot contact of eight cricket medium-fast bowlers using inertial measurement unit and optical motion capture. We used one sample t-tests and 95% limits of agreement (LOA) to determine the mean difference between the two systems and Smallest Worth-while Change statistic to determine whether any differences were meaningful. A statistically significant (p < 0.001) but small mean difference of −4.7° ± 8.6° (95% Confidence Interval (CI) [−3.1° to −6.4°], LOA [−22.2 to 12.7], SWC 3.9°) in shoulder girdle relative to the pelvis angle was found between the systems. There were no statistically significant differences between the two systems in trunk lateral flexion and knee flexion with the mean differences being 0.1° ± 10.8° (95% CI [−1.9° to 2.2°], LOA [−22.5 to 22.7], SWC 1.2°) and 1.6° ± 10.1° (95% CI [−0.2° to 3.3°], LOA [−19.2 to 22.3], SWC 1.9°) respectively. The inertial measurement unit-based system tested allows for accurate measurement of specific cricket fast bowling kinematics and could be used in determining injury risk in the context of tele-sport-and-exercise-medicine

Ethnic differences in cancer symptom awareness and barriers to seeking medical help in England

Background: Ethnic differences in cancer symptom awareness and barriers to seeking medical help in the English population are not fully understood. We aimed to quantify these differences, to help develop more effective health campaigns, tailored to the needs of different ethnic groups. Methods: Using a large national data set (n=38492) of cross-sectional surveys that used the Cancer Research UK Cancer Awareness Measure, we examined how cancer symptom awareness and barriers varied by ethnicity, controlling for socio-economic position, age and gender. Data were analysed using multivariable logistic regression. Results: Awareness of cancer symptoms was lower in minority ethnic groups than White participants, with the lowest awareness observed among Bangladeshis and Black Africans. Ethnic minorities were more likely than White British to report barriers to helpseeking. South Asians reported the highest emotional barriers, such as lack of confidence to talk to the doctor, and practical barriers, such as worry about many other things. The Irish were more likely than the White British to report practical barriers, such as being too busy to visit a doctor. White British participants were more likely than any other ethnic group to report that they would feel worried about wasting the doctor’s time. Overall, Black Africans had the lowest barriers. All differences were statistically significant (P<0.01 level), after controlling for confounders. Conclusions: Our findings suggest the need for culturally sensitive and targeted health campaigns, focused on improving recognition of cancer symptoms among ethnic minorities. Campaigns should tackle the specific barriers prevalent in each ethnic group

SARS-CoV-2 antibody dynamics in blood donors and COVID-19 epidemiology in eight Brazilian state capitals: A serial cross-sectional study

BACKGROUND: The COVID-19 situation in Brazil is complex due to large differences in the shape and size of regional epidemics. Understanding these patterns is crucial to understand future outbreaks of SARS-CoV-2 or other respiratory pathogens in the country. METHODS: We tested 97,950 blood donation samples for IgG antibodies from March 2020 to March 2021 in 8 of Brazil's most populous cities. Residential postal codes were used to obtain representative samples. Weekly age- and sex-specific seroprevalence were estimated by correcting the crude seroprevalence by test sensitivity, specificity, and antibody waning. RESULTS: The inferred attack rate of SARS-CoV-2 in December 2020, before the Gamma variant of concern (VOC) was dominant, ranged from 19.3% (95% credible interval [CrI] 17.5-21.2%) in Curitiba to 75.0% (95% CrI 70.8-80.3%) in Manaus. Seroprevalence was consistently smaller in women and donors older than 55 years. The age-specific infection fatality rate (IFR) differed between cities and consistently increased with age. The infection hospitalisation rate increased significantly during the Gamma-dominated second wave in Manaus, suggesting increased morbidity of the Gamma VOC compared to previous variants circulating in Manaus. The higher disease penetrance associated with the health system's collapse increased the overall IFR by a minimum factor of 2.91 (95% CrI 2.43-3.53). CONCLUSIONS: These results highlight the utility of blood donor serosurveillance to track epidemic maturity and demonstrate demographic and spatial heterogeneity in SARS-CoV-2 spread. FUNDING: This work was supported by Itaú Unibanco 'Todos pela Saude' program; FAPESP (grants 18/14389-0, 2019/21585-0); Wellcome Trust and Royal Society Sir Henry Dale Fellowship 204311/Z/16/Z; the Gates Foundation (INV- 034540 and INV-034652); REDS-IV-P (grant HHSN268201100007I); the UK Medical Research Council (MR/S0195/1, MR/V038109/1); CAPES; CNPq (304714/2018-6); Fundação Faculdade de Medicina; Programa Inova Fiocruz-CE/Funcap - Edital 01/2020 Number: FIO-0167-00065.01.00/20 SPU N°06531047/2020; JBS - Fazer o bem faz bem

Efficacious and Safe Tissue-Selective Controlled Gene Therapy Approaches for the Cornea

Untargeted and uncontrolled gene delivery is a major cause of gene therapy failure. This study aimed to define efficient and safe tissue-selective targeted gene therapy approaches for delivering genes into keratocytes of the cornea in vivo using a normal or diseased rabbit model. New Zealand White rabbits, adeno-associated virus serotype 5 (AAV5), and a minimally invasive hair-dryer based vector-delivery technique were used. Fifty microliters of AAV5 titer (6.5×1012 vg/ml) expressing green fluorescent protein gene (GFP) was topically applied onto normal or diseased (fibrotic or neovascularized) rabbit corneas for 2-minutes with a custom vector-delivery technique. Corneal fibrosis and neovascularization in rabbit eyes were induced with photorefractive keratectomy using excimer laser and VEGF (630 ng) using micropocket assay, respectively. Slit-lamp biomicroscopy and immunocytochemistry were used to confirm fibrosis and neovascularization in rabbit corneas. The levels, location and duration of delivered-GFP gene expression in the rabbit stroma were measured with immunocytochemistry and/or western blotting. Slot-blot measured delivered-GFP gene copy number. Confocal microscopy performed in whole-mounts of cornea and thick corneal sections determined geometric and spatial localization of delivered-GFP in three-dimensional arrangement. AAV5 toxicity and safety were evaluated with clinical eye exam, stereomicroscopy, slit-lamp biomicroscopy, and H&E staining. A single 2-minute AAV5 topical application via custom delivery-technique efficiently and selectively transduced keratocytes in the anterior stroma of normal and diseased rabbit corneas as evident from immunocytochemistry and confocal microscopy. Transgene expression was first detected at day 3, peaked at day 7, and was maintained up to 16 weeks (longest tested time point). Clinical and slit-lamp eye examination in live rabbits and H&E staining did not reveal any significant changes between AAV5-treated and untreated control corneas. These findings suggest that defined gene therapy approaches are safe for delivering genes into keratocytes in vivo and has potential for treating corneal disorders in human patients

BluePort: A Platform to Study the Eosinophilic Response of Mice to the Bite of a Vector of Leishmania Parasites, Lutzomyia longipalpis Sand Flies

transmission in residents of endemic areas has been attributed to the acquisition of immunity to sand fly salivary proteins. One theoretical way to accelerate the acquisition of this immunity is to increase the density of antigen-presenting cells at the sand fly bite site. Here we describe a novel tissue platform that can be used for this purpose. sand flies. Results presented indicate that a shift in the inflammatory response, from neutrophilic to eosinophilic, is the main histopathological feature associated with the immunity acquired through repeated exposure to the bite of sand flies, and that the BluePort tissue compartment could be used to accelerate this process. In addition, changes observed inside the BluePort parenchyma indicate that it could be used to study complex immunobiological processes, and to develop ectopic secondary lymphoid structures.Understanding the characteristics of the dermal response to the bite of sand flies is a critical element of strategies to control leishmaniasis using vaccines that target salivary proteins. Finding that dermal eosinophilia is such a prominent component of the anti-salivary immunity induced by repeated exposure to sand fly bites raises one important consideration: how to avoid the immunological conflict derived from a protective Th2-driven immunity directed to sand fly saliva with a protective Th1-driven immunity directed to the parasite. The BluePort platform is an ideal tool to address experimentally this conundrum

Resistance of Leishmania (Leishmania) amazonensis and Leishmania (Viannia) braziliensis to nitric oxide correlates with disease severity in Tegumentary Leishmaniasis

BACKGROUND: Nitric oxide (NO(•)) plays a pivotal role as a leishmanicidal agent in mouse macrophages. NO(• )resistant Escherichia coli and Mycobacterium tuberculosis have been associated with a severe outcome of these diseases. METHODS: In this study we evaluated the in vitro toxicity of nitric oxide for the promastigote stages of Leishmania (Viannia) braziliensis and Leishmania (Leishmania) amazonensis parasites, and the infectivity of the amastigote stage for human macrophages. Parasites were isolated from patients with cutaneous, mucosal or disseminated leishmaniasis, and NO(• )resistance was correlated with clinical presentation. RESULTS: Seventeen isolates of L. (L.) amazonensis or L. (V.) braziliensis promastigotes were killed by up to 8 mM of more of NaNO(2 )(pH 5.0) and therefore were defined as nitric oxide-susceptible. In contrast, eleven isolates that survived exposure to 16 mM NaNO(2 )were defined as nitric oxide-resistant. Patients infected with nitric oxide-resistant Leishmania had significantly larger lesions than patients infected with nitric oxide-susceptible isolates. Furthermore, nitric oxide-resistant L. (L.) amazonensis and L. (V.) braziliensis multiplied significantly better in human macrophages than nitric oxide-susceptible isolates. CONCLUSION: These data suggest that nitric oxide-resistance of Leishmania isolates confers a survival benefit for the parasites inside the macrophage, and possibly exacerbates the clinical course of human leishmaniasis