Introduction: Informal caregivers provide a significant part of the total care needed by dependent older people poststroke. Although informal care is often the preferred option of those who provide and those who receive informal care, informal caregivers often report lack of preparation to take care of older dependent people. This article outlines the development and psychometric testing of informal caregivers’ skills when providing care to older people after a stroke – ECPICID-AVC. Design: Prospective psychometric instrument validation study. Methods: Eleven experts participated in a focus group in order to delineate, develop and validate the instrument. Data were gathered among adult informal caregivers (n = 186) living in the community in Northern Portugal from August 2013 to January 2014. Results: The 32-item scale describes several aspects of informal caregiver’s skills. The scale has eight factors: skill to feed/hydrate by nasogastric feeding, skill to assist the person in personal hygiene, skill to assist the person for transferring, skill to assist the person for positioning, skill to provide technical aids, skill to assist the person to use the toilet, skill to feed/hydrate and skill to provide technical aids for dressing/undressing. Analysis demonstrated adequate internal consistency (Cronbach’s alpha = 0.83) and good temporal stability 0.988 (0.984–0.991). Conclusion: The psychometric properties of the measurement tool showed acceptable results allowing its implementation in clinical practice by the nursing community staff for evaluating practical skills in informal caregivers when providing care to older stroke survivors living at home.

Click chemistry has revolutionized the field of peptide and antibody drug development by enabling highly selective and efficient bioconjugation strategies. This chapter explores the latest advancements in click chemistry applications for peptide-based therapeutic platforms and antibody-drug conjugates, emphasizing its role in enhancing stability, bioavailability, and target specificity. The discussion includes key click reactions such as copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC), strain-promoted azide-alkyne cycloaddition (SPAAC), thiol-norbornene photoclick chemistry (TNPC), among several others, which have been instrumental in improving pharmacokinetics, promoting site-specific modifications of biomolecules and developing novel functional biomaterials. Recent studies highlight the impact of click chemistry on homogeneity, therapeutic efficacy, and reduced off-target toxicity of diverse peptide-based constructs and antibody-drug conjugates. Furthermore, the integration of click chemistry into peptide drug design has facilitated the development of novel scaffolds that mimic natural peptides or peptide-based scaffolds while improving their properties. This chapter provides a comprehensive overview of the transformative potential of click chemistry in the context of peptide therapeutics and antibody-drug conjugates in modern drug development, with a focus on recent years.

Pentraxin 3 (PTX3) is a fluid-phase pattern recognition receptor of the humoral innate immune system with ancestral antibody-like properties but unknown antibody-inducing function. In this study, we found binding of PTX3 to splenic marginal zone (MZ) B cells, an innate-like subset of antibody-producing lymphocytes strategically positioned at the interface between the circulation and the adaptive immune system. PTX3 was released by a subset of neutrophils that surrounded the splenic MZ and expressed an immune activation–related gene signature distinct from that of circulating neutrophils. Binding of PTX3 promoted homeostatic production of IgM and class-switched IgG antibodies to microbial capsular polysaccharides, which decreased in PTX3-deficient mice and humans. In addition, PTX3 increased IgM and IgG production after infection with blood-borne encapsulated bacteria or immunization with bacterial carbohydrates. This immunogenic effect stemmed from the activation of MZ B cells through a neutrophil-regulated pathway that elicited class switching and plasmablast expansion via a combination of T cell–independent and T cell–dependent signals. Thus, PTX3 may bridge the humoral arms of the innate and adaptive immune systems by serving as an endogenous adjuvant for MZ B cells. This property could be harnessed to develop more effective vaccines against encapsulated pathogens.

Diagnosis of prostate cancer via PCA3 biomarker detection is promising to be much more efficient than with the prostatic specific antigens currently used. In this study, we present the first electrochemical and impedance-based biosensors that are capable of detecting PCA3 down to 0.128 nmol/L. The biosensors were made with a layer of PCA3-complementary single-stranded DNA (ssDNA) probe, immobilized on a layer-by-layer (LbL) film of chitosan (CHT) and carbon nanotubes (MWCNT). They are highly selective to PCA3, which was confirmed in impedance measurements and with polarization-modulated infrared reflection absorption spectroscopy (PM-IRRAS). Using information visualization methods, we could also distinguish between cell lines expressing the endogenous PCA3 long noncoding RNA (lncRNA) from cells that did not contain detectable levels of this biomarker. Since the methods involved in fabrication the biosensors are potentially low cost, one may hope to deploy PCA3 tests in any laboratory of clinical analyses and even for point-of-care diagnostics.

Mutation testing of the key genes involved in melanoma oncogenesis is now mandatory for the application of targeted therapeutics. However, knowledge of the mutational profile of melanoma remains largely unknown in Brazil. PURPOSE Mutation testing of the key genes involved in melanoma oncogenesis is now mandatory for the application of targeted therapeutics. However, knowledge of the mutational profile of melanoma remains largely unknown in Brazil. PATIENTS AND METHODS In this study, we assessed the mutation status of melanoma driver genes BRAF, NRAS, TERT, KIT, and PDGFRA in a cohort of 459 patients attended at Barretos Cancer Hospital between 2001 and 2012. We used polymerase chain reaction followed by Sanger sequencing to analyze the hot spot mutations of BRAF exon 15 (V600E), NRAS (codons 12/13 and 61), TERT (promoter region), KIT (exons 9, 11, 13, and 17), and PDGFRA (exons 12, 14, and 18) in tumors. The mutational profile was investigated for associations with demographic, histopathologic, and clinical features of the disease. RESULTS The nodular subtype was most frequent (38.9%) followed by the superficial spreading subtype (34.4%). The most frequent tumor location was in the limbs (50.0%). The mutation rates were 34.3% for TERT and 34.1% for BRAF followed by NRAS (7.9%), KIT (6.2%), and PDGFRA (2.9%). The BRAF (P = .014) and TERT (P = .006) mutations were associated with younger patients and with different anatomic locations, particularly in the trunk, for the superficial spreading and nodular subtypes, respectively (P = .0001 for both). PDGFRA mutations were associated with black skin color (P = .023) and TERT promoter mutations with an absence of ulceration (P = .037) and lower levels of lactate dehydrogenase. There was no association between patient survival rates and mutational status. CONCLUSION The similar mutational profile we observe in melanomas in Brazil compared with other populations will help to guide precision medicine in this country.

As the brain ages, it suffers several neurochemical, structural and functional changes. These deficits are primarily reflected on daily memory tasks. In the present work, we use the Wisconsin Card Sorting Task (WCST) task to assess P300 component of the event-related potential (ERP) as a marker for aging. Considering age-related effects, WCST was applied to young, middle-aged and elder participants. Early-late trial analysis tested the attentional set shifting and working memory updating hypothesis for the mechanisms behind WCST. The results suggest that, as people age, P3b peak latency highly correlates with age on both early and late trials, increasing as people gets older. P3b peak amplitude significantly distinguished between early and late trials regardless the subjects' age, while there were no differences on P300 peak latency

A Good Practice is a practice that works well, produces good results, and is recommended as a model. MACVIA-ARIA Sentinel Network (MASK), the new Allergic Rhinitis and its Impact on Asthma (ARIA) initiative, is an example of a Good Practice focusing on the implementation of multi-sectoral care pathways using emerging technologies with real life data in rhinitis and asthma multi-morbidity. The European Union Joint Action on Chronic Diseases and Promoting Healthy Ageing across the Life Cycle (JA-CHRODIS) has developed a checklist of 28 items for the evaluation of Good Practices. SUNFRAIL (Reference Sites Network for Prevention and Care of Frailty and Chronic Conditions in community dwelling persons of EU Countries), a European Union project, assessed whether MASK is in line with the 28 items of JA-CHRODIS. A short summary was proposed for each item and 18 experts, all members of ARIA and SUNFRAIL from 12 countries, assessed the 28 items using a Survey Monkey-based questionnaire. A visual analogue scale (VAS) from 0 (strongly disagree) to 100 (strongly agree) was used. Agreement equal or over 75% was observed for 14 items (50%). MASK is following the JA-CHRODIS recommendations for the evaluation of Good Practices.

BASIGIN/CD147/EMMPRIN is a multifunctional transmembrane glycoprotein strongly expressed in tumours. BASIGIN controls tumour metabolism, particularly glycolysis by facilitating lactic acid export through the two monocarboxylate transporters MCT1 and hypoxia-inducible MCT4. However, before being recognized as a co-carrier of MCTs, BASIGIN was described as an inducer of extracellular matrix metalloproteases (MMPs). Early on, a model emerged in which, tumour cells use the extracellular domain of BASIGIN to recognize and stimulate neighbouring fibroblasts to produce MMPs. However, this model has remained hypothetical since a direct link between BASIGIN and MMPs production has not yet been clearly established. To validate the BASIGIN/MMP hypothesis, we developed BASIGIN knockouts in three human tumour cell lines derived from glioma, colon, and lung adenocarcinoma. By using co-culture experiments of either human or mouse fibroblasts and tumour cell lines we showed, contrary to what has been abundantly published, that the disruption of BASIGIN in tumour cells and in MEFs has no action on the production of MMPs. Our findings do not support the notion that the pro-tumoural action of BASIGIN is mediated via induction of MMPs. Therefore, we propose that to date, the strongest pro-tumoural action of BASIGIN is mediated through the control of fermentative glycolysis.

[Excerpt] The Global Initiative for chronic Obstructive Lung disease (GOLD)guideline of 2018 describes COPD as‘the result of a complexinterplay of long-term cumulative exposure to noxious gases andparticles, combined with a variety of host factors includinggenetics, airway hyper-responsiveness and poor lung growthduring childhood’.1Tobacco smoking is traditionally viewed as themain contributing factor to the development of COPD. However,COPD also occurs among non-smokers, especially in low-incomeand middle-income countries (LMICs).2,3Notably, more than 90%of COPD-related deaths occur in LMICs.4For these countries, otherrisk factors, such as ambient, occupational and household airpollution play a significant role in the development of COPD.1,2,5–7Does COPD in these settings have a different pathophysiologicaltrajectory compared to COPD in high-income countries, and if so:what does this imply?In normal lung development, airway branching is completed bythe 17th week of gestation, after which airways increase in volumeuntil young adulthood. Alveoli are present at birth and developfurther during childhood. Lung volume and airflow continue toincrease as the thorax grows, influenced by age, sex, and ethnicity,reaching a peak at young adulthood. Lung function then remainsconstant for about 10 years (the plateau phase), after which itgradually declines.8In the‘classic’COPD patient, the decline inlung function is more rapid than in healthy individuals. However,in a considerable proportion of COPD patients, lung function doesnot decline rapidly, but reaches a lower plateau phase in earlyadulthood instead. For these patients, a completely differentpathophysiological trajectory seems to lead to the diagnosis ofCOPD: the decline in lung function follows a normal pattern, yetthey seem to have a‘false start’by attaining a lower maximumlung function. [...]

The development of molecular diagnostics that detect both the presence of Mycobacterium tuberculosis in clinical samples and drug resistance-conferring mutations promises to revolutionize patient care and interrupt transmission by ensuring early diagnosis. However, these tools require the identification of genetic determinants of resistance to the full range of antituberculosis drugs.