Chemical reversion of age-related oocyte dysfunction fails to enhance embryo development in a bovine model of postovulatory aging.

PURPOSE: There are no clinical treatments to prevent/revert age-related alterations associated with oocyte competence decline in the context of advanced maternal age. Those alterations have been attributed to oxidative stress and mitochondrial dysfunction. Our study aimed to test the hypothesis that in vitro maturation (IVM) medium supplementation with antioxidants (resveratrol or phloretin) may revert age-related oocyte competence decline. METHODS: Bovine immature oocytes were matured in vitro for 23 h (young) and 30 h (aged). Postovulatory aged oocytes (control group) and embryos obtained after fertilization were examined and compared with oocytes supplemented with either 2 µM of resveratrol or 6 µM phloretin (treatment groups) during IVM. RESULTS: Aged oocytes had a significantly lower mitochondrial mass and proportion of mitochondrial clustered pattern, lower ooplasmic volume, higher ROS, lower sirtuin-1 protein level, and a lower blastocyst rate in comparison to young oocytes, indicating that postovulatory oocytes have a lower quality and developmental competence, thus validating our experimental model. Supplementation of IVM medium with antioxidants prevented the generation of ROS and restored the active mitochondrial mass and pattern characteristic of younger oocytes. Moreover, sirtuin-1 protein levels were also restored but only following incubation with resveratrol. Despite these findings, the blastocyst rate of treatment groups was not significantly different from the control group, indicating that resveratrol and phloretin could not restore the oocyte competence of postovulatory aged oocytes. CONCLUSION: Resveratrol and phloretin can both revert the age-related oxidative stress and mitochondrial dysfunction during postovulatory aging but were insufficient to enhance embryo developmental rates under our experimental conditions.

Case report: Myelitis and ganglionitis, an atypical presentation of Hansen's disease.

Hansen's disease, or leprosy, is a disease characterized by dermatological and neurological disorders. A neural form also exists, in which peripheral neuropathy occurs in the absence of skin lesions. However, cases of leprosy that involve the central nervous system and proximal nerves are rare in the literature. We describe the case of an oligosymptomatic patient diagnosed with the neural form of leprosy with involvement of peripheral nerves, dorsal root ganglion, and cervical spinal cord in an atypical presentation of the disease. Through complementary examinations and nerve biopsies, the bacillus was identified, and treatment was subsequently initiated. This case highlights the importance of investigating the suspicion of leprosy, even in cases with atypical manifestations, as early diagnosis and treatment can reduce neurological damage and deformities.

Biomechanical gait analysis in sheep: kinematic parameters.

Animals have been used as models to help to better understand biological and anatomical systems, and pathologies in both humans and non-human species, and sheep are often used as an in vivo experimental model for orthopedic research. Gait analysis has been shown to be an important tool in biomechanics research with clinical applications. The purpose of this study was to perform a kinematic analysis using a tridimensional (3D) reconstruction of the sheep hindlimb. Seven healthy sheep were evaluated for natural overground walking, and motion capture of the right hindlimb was collected with an optoelectronic system while the animals walked in a track. The analysis addressed gait spatiotemporal variables, hip, knee and ankle angle and intralimb joint angle coordination measures during the entire walking cycle. This study is the first that describes the spatiotemporal parameters from the hip, knee and ankle joints in a tridimensional way: flexion/extension; abduction/adduction and inter/external rotation. The results of this assessment can be used as an outcome indicator to guide treatment and the efficacy of different therapies for orthopedic and neurological conditions involving the locomotor system of the sheep animal model.

Granulomatous meningoencephalitis and blindness associated with Mycobacterium tuberculosis complex infection in a senile female chimpanzee (Pan troglodytes).

A 40-year old female chimpanzee (Pan troglodytes) developed hyporexia, weight loss, followed by progressive and complete blindness. Tomography demonstrated an intracranial mass in the rostroventral brain involving the optic chiasm, with a presumptive diagnosis of neoplasm. However, histopathology revealed a granulomatous meningoencephalitis, and tissue samples tested positive for Mycobacterium tuberculosis.

Regular source of primary care and health services utilisation among Brazilian elderly with mental-physical multimorbidity.

BACKGROUND: In ageing populations, multimorbidity is a complex challenge to health systems, especially when the individuals have both mental and physical morbidities. Although a regular source of primary care (RSPC) is associated with better health outcomes, its relation with health service utilisation in elderly patients with mental-physical multimorbidity (MP-MM) is scarce. OBJECTIVE: This study explored the relations among health service utilisation, presence of RSPC and MP-MM among elderly Brazilians. METHODS: A national cross-sectional study performed with data from national representative samples from the Brazilian National Health Research (PNS, in Portuguese; Pesquisa Nacional de Saúde) carried out in 2013 with 11,177 elderly Brazilian people. MP-MM was defined as the presence of two or more morbidities, including at least one mental morbidity, and was evaluated using a list of 16 physical and mental morbidities. The RSPC was analysed by the presence of regular font of care in primary care and health service utilisation according to the demand for health services ≤ 15 days, medical consultation ≤ 12 months, and hospitalisation ≤ 1 year. Frequency description of variables and bivariate association were performed using Stata v.15.2 software. RESULTS: The majority of individuals was female (56.4%), and their mean age was 69.8 years. The observed prevalence of MP-MM was 12.2%. Individuals with MP-MM had higher utilisation of health services when compared to those without MP-MM. RSPC was present at 36.5% and was higher in women (37.8% vs. 34.9%). There was a lower occurrence of hospitalisation ≤ 1 year among MP-MM individuals with RSPC and without a private plan of health. CONCLUSION: Our findings demonstrate that RSPC can be an important component of care in elderly individuals with MP-MM because it was associated with lower occurrence of hospitalisation, mainly in those that have not a private plan of health. Longitudinal studies are necessary to confirm these findings.

[Penicillin: from discovery to patenting the large-scale production process]. / Penicilina: da descoberta ao patenteamento do processo de produção em larga escala.

This article examines discoveries, inventions, and innovations related to penicillin by sampling activities to solve technological problems which can be traced by the distribution of scientific articles, government reports, innovations, and patents between 1929 and 1945, and proposes reflection on the importance of scientific progress for national security. The analysis highlights the technological trajectory and outcomes in the area of intellectual property, considering US policy implemented to catalyze innovation and provide institutional conditions to meet national defense needs as an important factor, although this did not necessarily imply a unique solution in other contexts.

A partir de pesquisa sobre a descoberta, a invenção e a inovação relacionadas à penicilina, por amostra de atividades de resolução de problemas tecnológicos rastreada pela distribuição, no período de 1929 a 1945, de trabalhos científicos, relatórios de governo, inovações e patentes, o artigo propõe uma reflexão sobre a importância do progresso científico para a segurança nacional. A análise destaca a trajetória tecnológica e os resultados na área de propriedade intelectual, considerando um fator importante a política implementada nos EUA para catalisar processos de inovação e oferecer condições institucionais para atender às demandas de defesa nacional, o que não significa necessariamente unicidade de solução em outros contextos.

Equine Musculoskeletal Pathologies: Clinical Approaches and Therapeutical Perspectives-A Review.

Musculoskeletal injuries such as equine osteoarthritis, osteoarticular defects, tendonitis/desmitis, and muscular disorders are prevalent among sport horses, with a fair prognosis for returning to exercise or previous performance levels. The field of equine medicine has witnessed rapid and fruitful development, resulting in a diverse range of therapeutic options for musculoskeletal problems. Staying abreast of these advancements can be challenging, prompting the need for a comprehensive review of commonly used and recent treatments. The aim is to compile current therapeutic options for managing these injuries, spanning from simple to complex physiotherapy techniques, conservative treatments including steroidal and non-steroidal anti-inflammatory drugs, hyaluronic acid, polysulfated glycosaminoglycans, pentosan polysulfate, and polyacrylamides, to promising regenerative therapies such as hemoderivatives and stem cell-based therapies. Each therapeutic modality is scrutinized for its benefits, limitations, and potential synergistic actions to facilitate their most effective application for the intended healing/regeneration of the injured tissue/organ and subsequent patient recovery. While stem cell-based therapies have emerged as particularly promising for equine musculoskeletal injuries, a multidisciplinary approach is underscored throughout the discussion, emphasizing the importance of considering various therapeutic modalities in tandem.

Corrigendum: Evaluation of PIK3CA mutations in advanced ER+/HER2-breast cancer in Portugal - U-PIK Project.

[This corrects the article DOI: 10.3389/fmolb.2023.1082915.].

Shape-Versatile Fixed Cellular Materials for Multiple Target Immunomodulation.

Therapeutic cells are usually administered as living agents, despite the risks of undesired cell migration and acquisition of unpredictable phenotypes. Additionally, most cell-based therapies rely on the administration of single cells, often associated with rapid in vivo clearance. 3D cellular materials may be useful to prolong the effect of cellular therapies and offer the possibility of creating structural volumetric constructs. Here, the manufacturing of shape-versatile fixed cell-based materials with immunomodulatory properties is reported. Living cell aggregates with different shapes (spheres and centimeter-long fibers) are fixed using a method compatible with maintenance of structural integrity, robustness, and flexibility of 3D constructs. The biological properties of living cells can be modulated before fixation, rendering an in vitro anti-inflammatory effect toward human macrophages, in line with a decreased activation of the nuclear factor kappa B (NF-κB) pathway that preponderantly correlated with the surface area of the materials. These findings are further corroborated in vivo in mouse skin wounds. Contact with fixed materials also reduces the proliferation of activated primary T lymphocytes, while promoting regulatory populations. The fixation of cellular constructs is proposed as a versatile phenotypic stabilization method that can be easily implemented to prepare immunomodulatory materials with therapeutic potential.

Long-term suppression of turfgrass insect pests with native persistent entomopathogenic nematodes.

Entomopathogenic nematodes (EPNs) can control several important turfgrass insect pests including white grubs, weevils, cutworms, and sod webworms. But most of the research has focused on inundative releases in a biopesticide strategy using EPN strains that may have lost some of their ability to persist effectively over years of lab maintenance and / or selection for virulence and efficient mass-production. Our study examined the potential of fresh field isolate mixes of endemic EPNs to provide multi-year suppression of turfgrass insect pests. In early June 2020, we applied isolate mixes from golf courses of the EPNs Steinernema carpocapsae, Heterorhabditis bacteriophora, and their combination to plots straddling fairway and rough on two golf courses in central New Jersey, USA. Populations of EPNs and insect pests were sampled on the fairway and rough side of the plots from just before EPN application until October 2022. EPN populations increased initially in plots treated with the respective species. Steinernema carpocapsae densities stayed high for most of the experiment. Heterorhabditis bacteriophora densities decreased after 6 months and stabilized at lower levels. Several insect pests were reduced across the entire experimental period. In the fairway, the combination treatment reduced annual bluegrass weevil larvae (59 % reduction) and adults (74 %); S. carpocapsae reduced only adults (42 %). White grubs were reduced by H. bacteriophora (67 %) and the combination (63 %). Black turfgrass ataenius adults were reduced in all EPN treatments (43-62 %) in rough and fairway. Sod webworm larvae were reduced by S. carpocapsae in the fairway (75 %) and the rough (100 %) and by H. bacteriophora in the rough (75 %). Cutworm larvae were reduced in the fairway by S. carpocapsae (88 %) and the combination (75 %). Overall, our observations suggest that inoculative applications of fresh field isolate mixes of endemic EPNs may be a feasible approach to long-term suppression of insect pests in turfgrass but may require periodic reapplications.

Preliminary outcomes of the Cervical Cancer Screening Program of Northern Portugal: A snapshot.

BACKGROUND: Cervical cancer screening remains an essential preventive tool worldwide. First line high-risk Human Papillomavirus (HrHPV) genotyping became gold standard for cervical cancer screening, and has been adopted by several countries, including Portugal. Herein, we aimed to assess the early outcomes of the regional Cervical Cancer Screening Program of Northern Portugal. METHODS: The analysis of a representative set of cases evaluated during a one-month period (January 2020), with adequate follow-up was performed. Descriptive analysis was performed. RESULTS: Overall, 7278 samples were received, of which 15.2% were HrHPV positive, most of these disclosing a negative result in subsequent liquid-based cytology. Nearly half of the HrHPV-positive women were referred to colposcopy. Within this group, HPV16/18+ cases depicted the higher frequency of high-grade squamous intraepithelial lesion (HSIL) or worse, compared with abnormal cytology or persistent HrHPV infection. Among women with non-HPV16/18 HrHPV infection and negative cytology, which are eligible for repeat sampling in one year, 65% were re-tested. Importantly, nearly half of these cleared HrHPV infection. Furthermore, referral to colposcopy due to HPV16/18 infection and/or abnormal cytology results were associated with > 40% risk for HSIL or worse lesion. CONCLUSIONS: Our study confirmed the reliability and effectiveness of first line HrHPV genotyping in the Cervical Cancer Screening Program of Northern Portugal. Nonetheless, it also raised concerns about excessive referral to colposcopy, with the inherent human and financial costs. Thus, further improvement and optimization are key to ensure the sustainability of the program.

Relevance of individual bronchial symptoms for asthma diagnosis and control in patients with rhinitis: A MASK-air study.

RATIONALE: It is unclear how each individual asthma symptom is associated with asthma diagnosis or control. OBJECTIVES: To assess the performance of individual asthma symptoms in the identification of patients with asthma and their association with asthma control. METHODS: In this cross-sectional study, we assessed real-world data using the MASK-air® app. We compared the frequency of occurrence of five asthma symptoms (dyspnea, wheezing, chest tightness, fatigue and night symptoms, as assessed by the Control of Allergic Rhinitis and Asthma Test [CARAT] questionnaire) in patients with probable, possible or no current asthma. We calculated the sensitivity, specificity and predictive values of each symptom, and assessed the association between each symptom and asthma control (measured using the e-DASTHMA score). Results were validated in a sample of patients with a physician-established diagnosis of asthma. MEASUREMENT AND MAIN RESULTS: We included 951 patients (2153 CARAT assessments), with 468 having probable asthma, 166 possible asthma and 317 no evidence of asthma. Wheezing displayed the highest specificity (90.5%) and positive predictive value (90.8%). In patients with probable asthma, dyspnea and chest tightness were more strongly associated with asthma control than other symptoms. Dyspnea was the symptom with the highest sensitivity (76.1%) and the one consistently associated with the control of asthma as assessed by e-DASTHMA. Consistent results were observed when assessing patients with a physician-made diagnosis of asthma. CONCLUSIONS: Wheezing and chest tightness were the asthma symptoms with the highest specificity for asthma diagnosis, while dyspnea displayed the highest sensitivity and strongest association with asthma control.

Current State of Canine Heartworm in Portugal.

The favourable geo-climatic conditions in Portugal have made it highly conducive to the development of Dirofilaria immitis in dogs, leading to its identification as an endemic region. This nematode is rapidly spreading across Europe, particularly in northeastern countries. The objective of this study was to provide an updated assessment of the prevalence of this disease in Portuguese dogs, analysing the results in relation to epidemiological and geo-environmental factors, and to identify potential risk factors. A total of 1367 dogs from all continental and insular districts were included in the study and tested for D. immitis antigens. The overall prevalence was found to be 5.9%. It was observed that the disease is spreading northward, with previously unaffected districts now reporting cases, and that the prevalence in coastal districts exceeded that of inland ones. Notably, the Aveiro district exhibited a significant increase in D. immitis prevalence, while in certain districts such as Setúbal, Santarém, Madeira, or Faro, a stabilisation or decrease in prevalence was noted. Furthermore, outdoor and older dogs were found to be at a higher risk of infection. No positive cases were detected in the Azores. Most of the infected dogs were located in areas of high and medium risk of infection. This study underscores the importance of implementing pharmacological prophylaxis, vector control strategies, and public awareness programs to control the spread of this zoonotic disease.

Measurement properties of patient-reported outcome measures for women with dysmenorrhea: A systematic review.

BACKGROUND: Dysmenorrhea, or menstrual pain, is a subjective experience, and can only be assessed by patient-reported outcomes. These instruments should be reliable, valid and responsive. AIM: To identify and critically appraise the available evidence for the measurement properties of specific patient-reported outcome measures used for dysmenorrhea. METHODS: The PRISMA statement was used to report this systematic review. Databases searched were PubMed, SCOPUS, CINAHL, Web of Science, ScienceDirect and Google Scholar (April 2021; updated on February 2023). Original studies with primary data collection, with no restriction on language and publication date that reported psychometric properties of one or more dysmenorrhea-related patient-reported outcome measure. The literature searches, selection of studies, data extraction and assessment of the risk of bias were performed independently by two reviewers and followed the COSMIN guidelines. RESULTS: Thirty studies were analysed in this review, and 19 patient-reported outcome measures were evaluated. The instruments varied in relation to the measured construct and measurement properties (validity, reliability and responsiveness). The methodological quality of the studies and the quality of evidence of the patient-reported outcome measures were variable. Among the 13 studies that reported the development of patient-reported outcome measures, most had inadequate methodological quality, and the overall rating was insufficient or inconsistent. CONCLUSIONS: The Dysmenorrhea Symptom Interference (DSI) scale was the only identified patient-reported outcome measure that has the potential to be recommended because of its sufficient rating combined with moderate quality of evidence for content validity. Future studies should further evaluate the measurement properties of the existing patient-reported outcome measures, or develop new patient-reported outcome measures following the COSMIN methodology. PATIENT OR PUBLIC CONTRIBUTION: Not applicable as this is a systematic review. TRIAL REGISTRATION: PROSPERO protocol: CRD42021244410. Registration on April 22, 2021.

Assessing the risk of transfusion-transmitted variant Creutzfeldt-Jakob disease: a European perspective.

Several countries have recently reassessed the international risk of variant Creutzfeldt-Jakob disease (vCJD) transmission through transfusion of blood and blood components (red blood cells, platelets and plasma) and relaxed donor deferrals based on geographic and transfusion exposure in countries formerly considered to be high risk, such as the UK. In this regard, the European Blood Alliance organised a consensus meeting of experts and involved professionals to discuss current knowledge, epidemiological data, prevention and various methods for assessing the risk of transfusion-transmitted vCJD, as well as to develop an appropriate position on possible approaches to address these challenges in Europe. Participants reached a consensus that the current risk of transfusion-transmitted vCJD associated with blood donors who either travelled to or received transfusions in the UK during the vCJD outbreak is minimal. In addressing such risks, it would be pragmatic that assessments and guidelines are developed by European expert bodies, rather than individual assessments by Member States. Regardless of the approach used, European or national, a qualitative risk assessment based on a review and analysis of available data, considering all the uncertainties and experiences of other countries, would provide crucial information to reassess blood donation strategies regarding the transfusion-associated vCJD risk.

Enhancement of the Inner Foveal Response of Young Adults with Extended-Depth-of-Focus Contact Lens for Myopia Management.

BACKGROUND: Myopia management contact lenses have been shown to successfully decrease the rate of eye elongation in children by changing the peripheral refractive profile of the retina. Despite the efforts of the scientific community, the retinal response mechanism to defocus is still unknown. The purpose of this study was to evaluate the local electrophysiological response of the retina with a myopia control contact lens (CL) compared to a single-vision CL of the same material. METHODS: The retinal electrical activity and peripheral refraction of 16 eyes (16 subjects, 27.5 ± 5.7 years, 13 females and 3 males) with myopia between -0.75 D and -6.00 D (astigmatism < 1.00 D) were assessed with two CLs (Filcon 5B): a single-vision (SV) CL and an extended-depth-of-focus (EDOF) CL used for myopia management. The peripheral refraction was assessed with an open-field WAM-5500 auto-refractometer/keratometer in four meridians separated by 45° at 2.50 m distance. The global-flash multifocal electroretinogram (gf-mfERG) was recorded with the Reti-port/scan21 (Roland Consult) using a stimulus of 61 hexagons. The implicit time (in milliseconds) and response density (RD, in nV/deg2) of the direct (DC) and induced (IC) components were used for comparison between lenses in physiological pupil conditions. RESULTS: Although the EDOF decreased both the HCVA and the LCVA (one and two lines, respectively; p < 0.003), it still allowed a good VA. The EDOF lens induced a myopic shift in most retinal areas, with a higher and statistically significant effect on the nasal retina. No differences in the implicit times of the DC and IC components were observed between SV and EDOF. Compared with the SV, the EDOF lens showed a higher RD in the IC component in the foveal region (p = 0.032). In the remaining retinal areas, the EDOF evoked lower, non-statistically significant RD in both the DC and IC components. CONCLUSIONS: The EDOF myopia control CL enhanced the response of the inner layers of the fovea. This might suggest that, besides other mechanisms potentially involved, the central foveal retinal activity might be involved in the mechanism of myopia control with these lenses.