Background iSupport is an online program developed by the World Health Organization to provide education, skills training, and social support to informal carers of persons with dementia. This pilot study examines the feasibility of the protocol for a main effectiveness trial of iSupport-Portugal and explores how the intervention and control arms compare over time on well-being outcomes. Methods A mixed-methods experimental parallel between-group design with two arms is followed. Participants were recruited nationwide, by referral or advertising, through the National Alzheimer’s Association. Inclusion criteria are being Portuguese adults, providing e-consent, providing unpaid care to someone with dementia for at least 6 months, experiencing relevant scores on burden (≥ 21 on ZBI) or depression or anxiety (≥ 8 on HADS), and using webpages autonomously. Participants were consecutively randomized to receive iSupport-Portugal or an education-only e-book and were not blinded to group assignment. Data were collected online with self-administered instruments, at baseline, 3 and 6 months after. Outcomes comprise caregiver burden, depression, anxiety, QoL, positive aspects of caregiving, and self-efficacy. Generalized estimating equations were used to estimate group, time, and group-by-time effects. Intervention engagement data were extracted from iSupport’s platform. Semi-structured interviews were conducted. Results Forty-two participants were allocated to the intervention (N = 21) and control (N = 21) arms. Participation (78.1%) and retention rates (73.8%) were fair. More carers in the control arm completed the study (N = 20, 95.2%) than in the intervention arm (N = 11; 52.4%) (χ2 = 9.98, p = .002). Non-completers were younger, spent less time caring, and scored higher on anxiety. Among carers in the intervention arm, the average attendance rate was of 53.7%. At post-test 38.9% of participants still used iSupport; the remainder participants interrupted use within 2 weeks (Mdn). For per-protocol analyses, significant group-by-time interaction effects favouring the intervention were found for anxiety (Wald χ2 = 6.17, p = .046) and for environmental QoL (Wald χ2 = 7.06, p = .029). Those effects were not observed in intention-to-treat analyses adjusted for age. Interviewees from the intervention arm (N = 12) reported positive results of iSupport on knowledge and on experiencing positive feelings. No adverse effects were reported. Conclusions This study provides information for a forthcoming full-scale effectiveness trial, as on the acceptability and potential results of iSupport-Portugal. iSupport is suggested as a relevant resource for Portuguese carers. Trial registration ClinicalTrials.gov, NCT04104568. 26/09/2019.

Bovine tuberculosis has been tackled for decades by costly eradication programs in most developed countries, involving the laboratory testing of tissue samples from allegedly infected animals for detection of Mycobacterium tuberculosis complex (MTC) members, namely Mycobacterium bovis. Definitive diagnosis is usually achieved by bacteriological culture, which may take up to 6–12 weeks, during which the suspect animal carcass and herd are under sanitary arrest. In this work, a user-friendly DNA extraction protocol adapted for tissues was coupled with an IS6110-targeted semi-nested duplex real-time PCR assay to enhance the direct detection of MTC bacteria in animal specimens, reducing the time to achieve a diagnosis and, thus, potentially limiting the herd restriction period. The duplex use of a novel β-actin gene targeted probe, with complementary targets in most mammals, allowed the assessment of amplification inhibitors in the tissue samples. The assay was evaluated with a group of 128 fresh tissue specimens collected from bovines, wild boars, deer and foxes. Mycobacterium bovis was cultured from 57 of these samples. Overall, the full test performance corresponds to a diagnostic sensitivity and specificity of 98.2% (CIP95% 89.4–99.9%) and 88.7% (CIP95% 78.5–94.7%), respectively. An observed kappa coefficient was estimated in 0.859 (CIP95% 0.771–0.948) for the overall agreement between the semi-nested PCR assay and the bacteriological culture. Considering only bovine samples (n = 69), the diagnostic sensitivity and specificity were estimated in 100% (CIP95% 84.0–100%) and 97.7% (CIP95% 86.2–99.9%), respectively. Eight negative culture samples exhibiting TB-like lesions were detected by the semi-nested real-time PCR, thus emphasizing the increased potential of this molecular approach to detect MTC-infected animal tissues. This novel IS6110-targeted assay allows the fast detection of tuberculous mycobacteria in animal specimens with very high sensitivity and specificity, being amenable and cost effective for use in the routine veterinary diagnostic laboratory with further automation possibilities.

Although drugs currently used for the various types of diseases (e.g., antiparasitic, antiviral, antibacterial, etc.) are effective, they present several undesirable pharmacological and pharmaceutical properties. Most of the drugs have low bioavailability, lack of sensitivity, and do not target only the damaged cells, thus also affecting normal cells. Moreover, there is the risk of developing resistance against drugs upon chronic treatment. Consequently, their potential clinical applications might be limited and therefore, it is mandatory to find strategies that improve those properties of therapeutic agents. The development of prodrugs using amino acids as moieties has resulted in improvements in several properties, namely increased bioavailability, decreased toxicity of the parent drug, accurate delivery to target tissues or organs, and prevention of fast metabolism. Herein, we provide an overview of models currently in use of prodrug design with amino acids. Furthermore, we review the challenges related to the permeability of poorly absorbed drugs and transport and deliver on target organs.