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Background: A knee injury in an athlete leads to periods of forced exercise interruption. Myocardial work (MW) assessed by echocardiographic and cardiopulmonary exercise testing (CPET) are two essential methods for evaluating athletes during the period following injury. However, compared to pre-surgery evaluations, the variations in cardiovascular parameters and functional capacity assessed by these methods after surgery remain unclear. Methods: We evaluated 22 non-professional athletes aged 18–52, involved in prevalently aerobic or alternate aerobic/anaerobic sports activities, who were affected by a knee pathology requiring surgical treatment. The evaluation was performed at rest using transthoracic echocardiography, including MW assessment, and during exercise using CPET. Each athlete underwent the following two evaluations: the first before surgery and the second after surgery (specifically at the end of the deconditioning period). Results: Resting heart rate (HR) increased significantly (from 63.3 ± 10.85 to 71.2 ± 12.52 beats per minute, p = 0.041), while resting diastolic and systolic blood pressure, forced vital capacity, and forced expiratory volume in the first second did not show significant changes. Regarding the echocardiographic data, global longitudinal strain decreased from −18.9 ± 1.8 to −19.3 ± 1.75; however, this reduction was not statistically significant (p = 0.161). However, the global work efficiency (GWE) increased significantly (from 93.0% ± 2.9 to 94.8% ± 2.6, p = 0.006) and global wasted work (GWW) reduced significantly (from 141.4 ± 74.07 to 98.0 ± 50.9, p = 0.007). Additionally, the patients were able to perform maximal CPET at both pre- and post-surgery evaluations, as demonstrated by the peak respiratory exchange ratio and HR. However, the improved myocardial contractility (increased GWE and decreased GWW) observed at rest did not translate into significant changes in exercise parameters, such as peak oxygen consumption and the mean ventilation/carbon dioxide slope. Conclusions: After surgery, the athletes were more deconditioned (as indicated by a higher resting HR) but exhibited better resting myocardial contractility (increased GWE and reduced GWW). Interestingly, no significant changes in exercise capacity parameters, as evaluated by CPET, were found after surgery, suggesting that the improved myocardial contractility was offset by a greater degree of muscular deconditioning.

Sulforaphane (SFN) has shown potential as an antioxidant and anti-inflammatory agent. To improve its druggability, we developed new analgesic formulations with sulforaphane-loaded hyaluronic acid (HA)-poloxamer (PL) hydrogel. This study evaluated the pre-clinical safety and effectiveness of these formulations. Effectiveness was tested on Wistar rats divided into groups (n = 15) receiving (IM, 10 mg/kg) SFN formulations or control groups (without SFN). This study used a hind paw incision postoperative pain model to evaluate mechanical hypersensitivity with von Frey filaments. TNF-α, IL-1β, substance P, and CGRP levels verified anti-inflammatory activity in the hind paw tissue. Histopathology of tissues surrounding the injection site was assessed after 2 and 7 days post-treatment. To corroborate drug safety, cell viability of 3T3 and RAW 264.7 cultures was assessed. Additionally, RAW 264.7 cultures primed with carrageenan evaluated nitric oxide (NO) levels. All animals exhibited post-incisional hypersensitivity, and F2 (PL 407/338 (18/2%) + HA 1% + SFN 0.1%) showed a longer analgesic effect (p < 0.05). F2 reduced TNF-α, IL-1β, and CGRP levels (p < 0.05). Histopathological evaluation showed mild to moderate inflammatory reactions after the formulations’ injections. F2 produced no significant difference in cell viability (p > 0.05) but reduced NO production (p < 0.05). Thus, our results highlight the biocompatibility and effectiveness of F2.

Pycnodysostosis is a skeletal dysplasia characterized by short stature, generalized osteosclerosis, acro-osteolysis, and recognizable facial features. Oral manifestations are commonly described and include a high-arched palate with dental crowding and malocclusion, hypoplastic enamel, and retained deciduous teeth with impacted permanent teeth, and there is an increased risk of developing osteomyelitis of the jaw. We report here the history of a 9-year-old male with the typical facial and skeletal phenotype of pycnodysostosis but novel oral features. He presented with bilateral progressive facial swelling, which caused functional impairment with chewing and contributed to his severe obstructive sleep apnea (OSA). The severity of his OSA required surgical intervention, and the lesions were resected. Extensive bone remodeling and replacement by fibrous tissue were noted on submucosal dissection, and bilateral subtotal maxillectomies were required. The histopathology of the biopsied lesion was consistent with a giant cell-rich lesion. Genetic testing identified a pathogenic homozygous variant in the CTSK gene, c.953G > A, p. (Cys318Tyr). The proband had a good postsurgical response with sustained improvement in his sleep OSA. We present here the history and clinical characteristics of a patient with typical features of pycnodysostosis and an unusual presentation and histopathology of gnathic bone lesions. This report adds to the body of literature on this rare condition and also highlights the finding of giant cell-rich lesions of the gnathic bones. Giant cell-rich lesions in pycnodysostosis have previously been reported in two cases in the literature. While there is not enough evidence to support a certain association with pycnodysostosis, it is prudent to consider regular oral dental reviews in affected individuals to identify pathology early and avoid such life-threatening complications.

The third Sustainable Development Goal (SDG), to ensure healthy lives and promote well-being for all at all ages, has particular relevance and implementation challenges amongst people living with rare diseases such as cystic fibrosis (CF). Although the treatment and projected outcome of CF has significantly improved with the advent of CF transmembrane conductance regulator protein modulator (CFTRm) therapy, there remains significant global inequality with regards to access to these life-saving and life-altering drugs. Elexacaftor, tezacaftor, and ivacaftor (ETI) triple combination therapy, first licensed in the United States in 2019, has rapidly become the standard of care for children aged 6 years and older in most high-income countries for individuals with CFTR variants responsive to ETI. Negotiated agreements for access to ETI are currently in place in North America,Europe, Israel ,Australia and New Zealand. However, less priority has been given to negotiate agreements for access to CFTRm in low-middle income countries(LMIC) with significant CF populations such as Central and South America, India, the Middle East, and Southern Africa. These countries and individuals living with CF are therefore effectively being left behind, in direct conflict with the stated principle of the 2030 SDGs. In this review, we highlight the current global inequity in access to CFTRm drugs and its impact on widening disparities between high-income countries and LMIC in CF outcomes and survival. We further discuss the reasons for this inequity and explore the ethical- and human rights-based principles and dilemmas that clinicians, families, governments, and healthcare funders must consider when prioritizing fair and affordable access to expensive CFTRm drugs. Lastly, we propose possible solutions to overcoming the barriers to accessing affordable CFTRm drugs in LMIC and illustrate with examples how access to drug therapies for other conditions have been successfully negotiated in LMIC through innovative partnerships between governments and pharmaceutical industries.

Background: A knee injury in an athlete leads to periods of forced exercise interruption. Myocardial work (MW) assessed by echocardiographic and cardiopulmonary exercise testing (CPET) are two essential methods for evaluating athletes during the period following injury. However, compared to pre-surgery evaluations, the variations in cardiovascular parameters and functional capacity assessed by these methods after surgery remain unclear. Methods: We evaluated 22 non-professional athletes aged 18–52, involved in prevalently aerobic or alternate aerobic/anaerobic sports activities, who were affected by a knee pathology requiring surgical treatment. The evaluation was performed at rest using transthoracic echocardiography, including MW assessment, and during exercise using CPET. Each athlete underwent the following two evaluations: the first before surgery and the second after surgery (specifically at the end of the deconditioning period). Results: Resting heart rate (HR) increased significantly (from 63.3 ± 10.85 to 71.2 ± 12.52 beats per minute, p = 0.041), while resting diastolic and systolic blood pressure, forced vital capacity, and forced expiratory volume in the first second did not show significant changes. Regarding the echocardiographic data, global longitudinal strain decreased from −18.9 ± 1.8 to −19.3 ± 1.75; however, this reduction was not statistically significant (p = 0.161). However, the global work efficiency (GWE) increased significantly (from 93.0% ± 2.9 to 94.8% ± 2.6, p = 0.006) and global wasted work (GWW) reduced significantly (from 141.4 ± 74.07 to 98.0 ± 50.9, p = 0.007). Additionally, the patients were able to perform maximal CPET at both pre- and post-surgery evaluations, as demonstrated by the peak respiratory exchange ratio and HR. However, the improved myocardial contractility (increased GWE and decreased GWW) observed at rest did not translate into significant changes in exercise parameters, such as peak oxygen consumption and the mean ventilation/carbon dioxide slope. Conclusions: After surgery, the athletes were more deconditioned (as indicated by a higher resting HR) but exhibited better resting myocardial contractility (increased GWE and reduced GWW). Interestingly, no significant changes in exercise capacity parameters, as evaluated by CPET, were found after surgery, suggesting that the improved myocardial contractility was offset by a greater degree of muscular deconditioning. [ABSTRACT FROM AUTHOR]

This brief contribution aims to complement a study of well-posedness started by the same authors in 2020, showing—for that same mathematical model—the existence of a domain of influence of external data. The object of investigation, we recall, is a linear thermoelastic model with a porous matrix modeled on the basis of the Cowin–Nunziato theory, and for which the heat exchange phenomena are intended to obey a time-differential heat transfer law with three delay times. We therefore consider, without reporting it explicitly, the (suitably adapted) initial-boundary value problem formulated at that time, as well as some analytical techniques employed to handle it in order to address the uniqueness and continuous dependence questions. Here, a domain of influence theorem is proven, showing the spatial behavior of the solution in a cylindrical domain, by activating the hypotheses that make the model thermodynamically consistent. The theorem, in detail, demonstrates that for a finite time t>0, the assigned external (thermomechanical) actions generate no disturbance outside a bounded domain contained within the cylindrical region of interest. The length of the work is deliberately kept to a minimum, having opted where possible for bibliographic citations in favor of greater reading fluency.

Mycobacterium abscessus is a nontuberculous mycobacterium (NTM) of particular concern in individuals with obstructive lung diseases such as cystic fibrosis (CF). Treatment requires multiple drugs and is characterised by high rates of relapse; thus, new strategies to limit infection are urgently required. This study sought to determine how Bacille Calmette-Guérin (BCG) vaccination may impact NTM infection, using a murine model of Mycobacterium abscessus infection and observational data from a non-BCG vaccinated CF cohort in Sydney, Australia and a BCG-vaccinated CF cohort in Cape Town, South Africa. In mice, BCG vaccination induced multifunctional antigen-specific CD4+ T cells circulating in the blood and was protective against dissemination of bacteria to the spleen. Prior infection with M. abscessus afforded the highest level of protection against M. abscessus challenge in the lung, and immunity was characterised by a greater frequency of pulmonary cytokine-secreting CD4+ T cells compared to BCG vaccination. In the clinical CF cohorts, the overall rates of NTM sampling during a three-year period were equivalent; however, rates of NTM colonisation were significantly lower in the BCG-vaccinated (Cape Town) cohort, which was most apparent for M. abscessus. This study provides evidence that routine BCG vaccination may reduce M. abscessus colonisation in individuals with CF, which correlates with the ability of BCG to induce multifunctional CD4+ T cells recognising M. abscessus in a murine model. Further research is needed to determine the optimal strategies for limiting NTM infections in individuals with CF.

Childhood mucoepidermoid carcinomas (MEC) of the bronchus are rare. They present with non-specific symptoms and signs making diagnosis delayed. We present two children with bronchial MEC managed in a tertiary children's hospital in Cape Town, South Africa. The first was a 11-year male with recurrent haemoptysis and the second child was a 6-year female with recurrent unifocal pneumonia. Chest CT scan and bronchoscopy with biopsy confirmed the diagnosis. Both patients underwent treatment, including surgery and are doing well. It is important to exclude endobronchial lesions when children present with recurrent respiratory symptoms, since early diagnosis will enable lung-sparing treatment.

Objective: to understand the experience of mothers after the diagnosis of congenital malformation and the expectations of care from the health and social network. Methods: qualitative research based on Social Phenomenology, with the participation of six mothers living in border towns, by means of semi-structured interviews. Results: the reports brought information about the diagnosis of congenital malformation, the experience of pregnancy, becoming a mother of a child with malformation and the expectations of health and social care. Conclusion: the social group studied experienced the diagnosis of malformation with suffering, emotional repercussions and changes in their daily lives. Contributions to practice: communication by the health team contributes to understanding and facing the malformation. The importance of the family and social network support was highlighted. It is necessary to develop professional skills related to communication and to make more investments in training and working conditions that allow more time for the care of this public.

Sulforaphane (SFN) has shown potential as an antioxidant and anti-inflammatory agent. To improve its druggability, we developed new analgesic formulations with sulforaphane-loaded hyaluronic acid (HA)-poloxamer (PL) hydrogel. This study evaluated the pre-clinical safety and effectiveness of these formulations. Effectiveness was tested on Wistar rats divided into groups (n = 15) receiving (IM, 10 mg/kg) SFN formulations or control groups (without SFN). This study used a hind paw incision postoperative pain model to evaluate mechanical hypersensitivity with von Frey filaments. TNF-α, IL-1β, substance P, and CGRP levels verified anti-inflammatory activity in the hind paw tissue. Histopathology of tissues surrounding the injection site was assessed after 2 and 7 days post-treatment. To corroborate drug safety, cell viability of 3T3 and RAW 264.7 cultures was assessed. Additionally, RAW 264.7 cultures primed with carrageenan evaluated nitric oxide (NO) levels. All animals exhibited post-incisional hypersensitivity, and F2 (PL 407/338 (18/2%) + HA 1% + SFN 0.1%) showed a longer analgesic effect (p < 0.05). F2 reduced TNF-α, IL-1β, and CGRP levels (p < 0.05). Histopathological evaluation showed mild to moderate inflammatory reactions after the formulations' injections. F2 produced no significant difference in cell viability (p > 0.05) but reduced NO production (p < 0.05). Thus, our results highlight the biocompatibility and effectiveness of F2. [ABSTRACT FROM AUTHOR]

This article explores the challenges faced by cystic fibrosis (CF) patients in low- to middle-income countries in accessing the triple combination therapy of elexacaftor, tezacaftor, and ivacaftor (ETI). The therapy is currently expensive and not widely available due to regulatory approval and cost issues. The authors propose a strategy using pharmacokinetic enhancement to reduce the cost of treatment, which involves the use of boosting agents like ritonavir. They also suggest the potential use of generic ETI formulations. Preliminary data from South Africa shows promising results, but further clinical trials are needed to evaluate the effectiveness, safety, and cost-effectiveness of this approach. [Extracted from the article]

A prescrição e a utilização do metilfenidato consistem em aumentar a produtividade escolar e a motivação do usuário, pois amplia as habilidades cognitivas e diminui a fadiga. Este estudo tem como objetivo discutir, à luz das evidências disponíveis na literatura, a assistência de enfermagem prestada ao usuário de metilfenidato na atenção primária à saúde, ancorada no referencial teórico dos atributos essenciais da atenção primária. Trata-se de revisão integrativa de literatura utilizando os descritores: Methylphenidate and Primary Health e Methylphenidate and Nursing Care. O recrutamento dos artigos completos ocorreu no mês de janeiro de 2022, na Biblioteca Virtual em Saúde, nos idiomas espanhol, inglês e português, desde as primeiras publicações registradas nas bases de dados, período de 1975 até 2021. Resultado: nenhum artigo recrutado retratava a assistência de enfermagem prestada ao usuário de metilfenidato na atenção primária à saúde pelos profissionais enfermeiros. Conclusão: a ausência de literatura sobre a referida temática requer uma reflexão sobre os atributos da atenção primária no que se refere à organização da atenção primária e ao cuidado prestado aos usuários de metilfenidato, uma vez que eles existem. Dessa maneira, são necessárias respostas de como eles são acompanhados dentro da atenção primária à saúde.

Introduction Little is known about cystic fibrosis (CF) in low- to middle-income settings. This study aimed to describe the spectrum and outcomes of CF in South Africa (SA) from the recently established SA CF registry (SACFR). Methods Demographic, diagnosis and clinical data were extracted from the SACFR. Cross-sectional univariable and multivariable regression analysis of best forced expiratory volume in 1 s (FEV1; age≥6 years) and nutrition (all ages) in 2018 was conducted to investigate factors associated with severe lung disease (SLD; FEV1 ≤3.0 z-score) and undernutrition. Results By December 2018, ancestry of 447 individuals included in the SACFR was Caucasian (315; 70%), mixed (87; 19%) and black African (41; 9%). Median diagnosis age was 7.6 months (IQR 2.7–37.1). Genotype was p.Phe508del homozygous (220; 49%); p.Phe508del heterozygous (144; 32%) and neither p.Phe508del or unknown Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) variant in 83 (19%); the second most frequent CFTR variant was 3120+1G>A, common in black Africans. Median age of patients in 2018 was 14.7 years (IQR 7.4–24.4). SLD was independently associated with chronic methicillin-resistant Staphylococcus aureus (MRSA) (adjusted odds ratio( aOR) 16.75; 95% CI 1.74–161.50), undernutrition (aOR 5.20; 95% CI 2.23–12.13) and age (aOR 2.23 per 10 years; 95% CI 1.50–3.31). Undernutrition was associated in univariable analysis with low weight at diagnosis, non-Caucasian ancestry, chronic P. aeruginosa infection and lower socioeconomic status. Conclusion Interventions targeting MRSA infection and nutrition are needed to improve CF outcomes in SA. Most people with CF in SA are eligible for highly effective CFTR modulator therapy.

ABSTRACT: On-farm culturing is a technology booming in Brazil. It is based on the microbiological diagnosis of milk samples collected from clinical cases of bovine mastitis, on the farm where the animals are handled, quickly, simply, and at an affordable cost. With this resource, after 24 h of incubation, the isolated microorganisms are classified as gram positive or gram negative, helping to make decisions regarding the therapy of the animals. Considering the relevance of the Midwestern region of Santa Catarina State in the national dairy production scenario, the objectives of the study were: 1) to promote the technical training of the farmers in three dairy farms located in Treze Tílias-SC, 2) to assist in the implementation and evaluation of on-farm culturing as technological resource viewing the reduced use of antimicrobials in herds. In addition to the rapid acceptance by the farmers and their efficient training, with the use of the technology, there was a 45-50% reduction in the use of antimicrobials in dairy herds. This result demonstrated a significant effect on animal health, and determines an important cost reduction for farmers, as presented in detail in this manuscript.

The present paper is dedicated to the structural stability of the linear model of a mixture of two porous solids. It is shown that the variation of the characteristic coefficients that describe the coupling of the various mechanical effects involved in the model in concern does not destroy its structure. This means that any small variation of these coefficients leads to small variations in the corresponding solutions of the associated initial boundary value problems. For this purpose, more mathematical estimates are presented describing precisely the continuous dependence of the solutions with respect to all external given data of the initial boundary value problem, as well as with respect to appropriate measures of the set of coupling parameters. This allows the conclusion that the model of the mixture of porous materials is consistent. In particular, it is believed that the estimates obtained in terms of structural stability are particularly meaningful with regard to the materials used in building contexts and the related decay phenomena. [ABSTRACT FROM AUTHOR]