A web step-based digital solution's impact on physical, cognitive and psychosocial functioning of community-dwelling older adults: A mixed methods randomized and controlled trial.

Background: As the population ages, innovative responses are urgently needed to promote physical activity at scale. Thus, this study investigated whether a step-based activity mediated by a digital solution impacts the physical functioning of community-dwelling older adults. The secondary aims were to assess whether the same activity impacts cognitive and psychosocial functioning and explore participants' views towards the activity. Methods: A mixed method, randomized, and controlled study with one group performing a step-based activity using DanceMove (recommended dosage: twice a week for 20 to 30 min for eight weeks) and the other their usual activities. DanceMove was used at the individuals' homes without any direct supervision. Clinical tests and questionnaires administered in person were used to assess participants at baseline, post-intervention, and three-month follow-up. The primary outcome of interest was gait velocity. Secondary outcomes were balance, pain intensity, cognitive functioning, self-efficacy, social support, loneliness, and quality of life. Also, at the end of the intervention, a semi-structured individual interview was conducted with participants in the experimental group. Results: Seventy participants were randomized to the control (n = 37) and experimental (n = 33) groups. Of the 33 participants in the experimental group, four did not use the DanceMove at all and two used it for only 3 min. The remaining 26 participants used it for a total time over the eight weeks that varied between 15 and 991 min (mean ± SD = 306.55 ± 258.83 min). The step-based activity was not more effective than usual activities for any of the variables assessed (P > .05). Difficulties, positive and negative aspects regarding the digital solution, and reasons for not using it were identified in the interviews. Conclusions: Eight weeks of a step-based activity mediated by a digital solution did not impact the physical, cognitive, and psychosocial functioning of community-dwelling healthy older adults. However, the activity was enjoyable and safe to be performed at home without direct supervision. Further studies are needed to explore aspects that could modulate the impact of this type of technology-mediated activity. Trial registration: The study was registered at clinialtrials.gov (NCT05460039) before the enrolment of the first participant.

SAR Study of 4,8-Disubstituted Pyrimido[5,4-d]pyrimidines Exhibiting Antitrypanosomal and Antileishmanial Activity.

A set of new derivatives of 4,8-disubstituted pyrimido[5,4-d]pyrimidines were efficiently synthesized and in vitro evaluated against Trypanosoma brucei and Leishmania infantum promastigotes and intramacrophage amastigotes. The in vitro cytotoxicity was determined using the THP-1 cell line, and early in vitro ADME-Tox was carried out using in vitro assays for cytotoxicity (A549 and HEK293 cell lines) and CYP3A4 and hERG cardiotoxicity liabilities. All the new compounds were active against T. brucei (0.11 µM ≤ IC50 ≤ 8.72 µM; 1 ≤ selectivity index (SI) ≤ 877), but only eight were active against L. infantum promastigotes (0.20 µM ≤ IC50 ≤ 14.88 µM; 1 ≤ SI < 502) with three also active against L. infantum intramacrophage amastigotes (3.00 µM ≤ IC50 ≤ 8.51 µM). Compounds 4a, 4c, and 4n were identified as the hit compounds to further develop as antitrypanosomal and antileishmanial agents.

An exploration of available methods and tools to improve the efficiency of systematic review production: a scoping review.

BACKGROUND: Systematic reviews (SRs) are time-consuming and labor-intensive to perform. With the growing number of scientific publications, the SR development process becomes even more laborious. This is problematic because timely SR evidence is essential for decision-making in evidence-based healthcare and policymaking. Numerous methods and tools that accelerate SR development have recently emerged. To date, no scoping review has been conducted to provide a comprehensive summary of methods and ready-to-use tools to improve efficiency in SR production. OBJECTIVE: To present an overview of primary studies that evaluated the use of ready-to-use applications of tools or review methods to improve efficiency in the review process. METHODS: We conducted a scoping review. An information specialist performed a systematic literature search in four databases, supplemented with citation-based and grey literature searching. We included studies reporting the performance of methods and ready-to-use tools for improving efficiency when producing or updating a SR in the health field. We performed dual, independent title and abstract screening, full-text selection, and data extraction. The results were analyzed descriptively and presented narratively. RESULTS: We included 103 studies: 51 studies reported on methods, 54 studies on tools, and 2 studies reported on both methods and tools to make SR production more efficient. A total of 72 studies evaluated the validity (n = 69) or usability (n = 3) of one method (n = 33) or tool (n = 39), and 31 studies performed comparative analyses of different methods (n = 15) or tools (n = 16). 20 studies conducted prospective evaluations in real-time workflows. Most studies evaluated methods or tools that aimed at screening titles and abstracts (n = 42) and literature searching (n = 24), while for other steps of the SR process, only a few studies were found. Regarding the outcomes included, most studies reported on validity outcomes (n = 84), while outcomes such as impact on results (n = 23), time-saving (n = 24), usability (n = 13), and cost-saving (n = 3) were less often evaluated. CONCLUSION: For title and abstract screening and literature searching, various evaluated methods and tools are available that aim at improving the efficiency of SR production. However, only few studies have addressed the influence of these methods and tools in real-world workflows. Few studies exist that evaluate methods or tools supporting the remaining tasks. Additionally, while validity outcomes are frequently reported, there is a lack of evaluation regarding other outcomes.

Veterinary perspectives on the urbanization of leishmaniosis in Morocco.

BACKGROUND: Leishmaniosis caused by Leishmania infantum, L. major and L. tropica is endemic in Morocco. Growing evidence of both human and canine Leishmania infections in urban centres has been reported. Since many forms of the disease are zoonotic, veterinarians play an important role in leishmaniosis control by intervening at the parasite host level. This study aimed to bring together One Health principles to connect canine and feline leishmaniosis epidemiology within urban centres of Morocco (Rabat and Fez) and assess the level of awareness of Moroccan veterinarians about facing this threat. METHODS: A molecular survey was conducted for Leishmania DNA detection in canine (n = 155) and feline (n = 32) whole-blood samples. Three conventional polymerase chain reaction (PCR) protocols were implemented. The first PCR aimed at identifying infected animals by targeting Leishmania spp. kinetoplast minicircle DNA (kDNA). The second and third PCR targeted the Leishmania internal transcribed spacer region (ITS-1) and the Leishmania small subunit ribosomal RNA (SSUrRNA) gene, respectively, aiming at identification of the infecting species after Sanger sequencing-positive amplicons. Total immunoglobulin G (IgG) against Leishmania spp. was evaluated in 125 dogs by enzyme-linked immunosorbent assays (ELISA) using an in-house protocol, including three Leishmania-specific antigens (SPLA, rKDDR and LicTXNPx). Sera from 25 cats were screened for total IgG to Leishmania spp. by an indirect immunofluorescence antibody test (IFAT). An online questionnaire was presented to Moroccan veterinarians addressing their knowledge and practices towards animal leishmaniosis. RESULTS: Overall, 19.4% of the dogs tested positive for Leishmania kDNA and ITS-1 and sequencing revealed infection with L. infantum among PCR-positive dogs. These animals presented a wide range of ELISA seropositivity results (16.7%, 34.9% and 51.6%) according to the tested antigens (rKDDR, SPLA and LicTXNPx, respectively). Use of kDNA-PCR revealed 12.5% cats positive to Leishmania spp. otherwise found to be seronegative by IFAT. CONCLUSIONS: A considerable prevalence of infection was identified in dogs from urban centres of Morocco. Additionally, this is the first report of feline infection with Leishmania spp. in this country and in urban settings. Moroccan veterinarians are aware that animal leishmaniosis is endemic in Morocco, representing a public health threat, and are knowledgeable about canine leishmaniosis diagnosis and treatment.

Identification of Innovative Folate Inhibitors Leveraging the Amino Dihydrotriazine Motif from Cycloguanil for Their Potential as Anti-Trypanosoma brucei Agents.

Folate enzymes, namely, dihydrofolate reductase (DHFR) and pteridine reductase (PTR1) are acknowledged targets for the development of antiparasitic agents against Trypanosomiasis and Leishmaniasis. Based on the amino dihydrotriazine motif of the drug Cycloguanil (Cyc), a known inhibitor of both folate enzymes, we have identified two novel series of inhibitors, the 2-amino triazino benzimidazoles (1) and 2-guanidino benzimidazoles (2), as their open ring analogues. Enzymatic screening was carried out against PTR1, DHFR, and thymidylate synthase (TS). The crystal structures of TbDHFR and TbPTR1 in complex with selected compounds experienced in both cases a substrate-like binding mode and allowed the rationalization of the main chemical features supporting the inhibitor ability to target folate enzymes. Biological evaluation of both series was performed against T. brucei and L. infantum and the toxicity against THP-1 human macrophages. Notably, the 5,6-dimethyl-2-guanidinobenzimidazole 2g resulted to be the most potent (Ki = 9 nM) and highly selective TbDHFR inhibitor, 6000-fold over TbPTR1 and 394-fold over hDHFR. The 5,6-dimethyl tricyclic analogue 1g, despite showing a lower potency and selectivity profile than 2g, shared a comparable antiparasitic activity against T. brucei in the low micromolar domain. The dichloro-substituted 2-guanidino benzimidazoles 2c and 2d revealed their potent and broad-spectrum antitrypanosomatid activity affecting the growth of T. brucei and L. infantum parasites. Therefore, both chemotypes could represent promising templates that could be valorized for further drug development.

Tactile acuity and active joint repositioning sense in individuals with and without chronic low back pain: a cross-sectional study.

BACKGROUND: Sensorimotor dysfunction, as measured by tactile acuity and active joint repositioning, has been identified as a contributing factor of chronic low back pain (CLBP). Existing research suggests that further research is necessary to improve the characterization of sensorimotor perception in patients with CLBP. OBJECTIVES: The main aim is to investigate whether tactile acuity and repositioning errors differ between individuals with CLBP and controls without CLBP. A secondary aim was to investigate the association between age, body mass index (BMI) and physical activity, and tactile acuity and repositioning sense. METHODS: Cross-sectional study. Sixty-eight participants (36 with, 32 without CLBP) were examined. Two-Point Discrimination (TPD) test (four measures: horizontal and vertical run, left and right side) and Active Joint Reposition Sense (AJRS) test (2 directions: to flexion and to extension) were used. RESULTS: No differences were found for TPD (right horizontal run: p = .069; left horizontal run: p = .066; right vertical run: p = .933; left vertical run: p = .285) or AJRS (flexion: p = .792; extension: p = .956) between participants with and without CLBP. Older subjects had significantly worse tactile acuity (3 sites, p = .018, p = .004, p = .041) and worse repositioning sense (2 directions, p = .026, p = .040,) than younger subjects. Individuals with BMI ≥ 25 had significantly worse TPD compared to individuals with normal weight (2 sites, p = .028, p = .020). CONCLUSIONS: Individuals with CLBP did not have impaired tactile and repositioning accuracy when compared to controls without CLBP. Future studies comparing sensorimotor performance should consider age and BMI as potential confounding factors.

A Practice Guide for Physical Therapists Prescribing Physical Exercise for Older Adults.

INTRODUCTION: Physical activity and exercise are protective factors for physical and cognitive decline in older adults, but recent studies reveal that a large percentage of this population do not practice exercise at the levels recommended by international guidelines. The frequency, intensity, type, time, volume, and progression (FITT-VP) principles are a widely used method for prescribing physical exercise, allowing the development of a personalized exercise program that meets the needs of each individual. OBJECTIVES: This masterclass is intended to serve as a professional application tool for physical therapists who prescribe physical exercise for older adults. We present a section for each FITT-VP principle to facilitate handling these principles individually when prescribing exercise for this population. METHODS: Review of the scientific literature and international guidelines on the prescription of physical exercises for older adults. RESULTS: Aerobic, mobility, resistance, balance, and flexibility exercises, as well as functional training, should be included in an exercise program for older adults, which should be progressed using different methods for each of the exercise modalities. CONCLUSIONS: An exercise program for older adults should integrate different exercise modalities. Exercise progression should be performed following the FITT-VP principles and some specific progression factors recommended for each exercise modality. SIGNIFICANCE: Considering the challenge faced by clinicians in designing a viable exercise program for older adults that responds to international recommendations, with this masterclass we hope to help physical therapists to plan an exercise program that is feasible and at the same time, responds to the expected needs of this population.

Exploring hydrophilic 2,2-di(indol-3-yl)ethanamine derivatives against Leishmania infantum.

Herein we report the design and the synthesis of a library of new and more hydrophilic bisindole analogues based on our previously identified antileishmanial compound URB1483 that failed the preliminary in vivo test. The novel bisindoles were phenotypically screened for efficacy against Leishmania infantum promastigotes and simultaneously for toxicity on human macrophage-like THP-1 cells. Among the less toxic compounds, eight bisindoles showed IC50 below 10 µM. The most selective compound 1h (selectivity index = 10.1, comparable to miltefosine) and the most potent compound 2c (IC50 = 2.7 µM) were tested for their efficacy on L. infantum intracellular amastigotes. The compounds also demonstrated their efficacy in the in vitro infection model, showing IC50 of 11.1 and 6.8 µM for 1h and 2c, respectively. Moreover, 1h showed a better toxicity profile than the commercial drug miltefosine. For all these reasons, 1h could be a possible new starting point for hydrophilic antileishmanial agents with low cytotoxicity on human macrophage-like cells.

Associations between pain intensity, pain sensitivity, demographics, psychological factors, disability, physical activity, pain phenotype and COVID-19 history in low back pain: An observational study.

BACKGROUND AND PURPOSE: Knowledge of the factors affecting pain intensity and pain sensitivity can inform treatment targets and strategies aimed at personalizing the intervention, conceivably increasing its positive impact on patients. Therefore, this study aimed to investigate the association between demographic factors (sex and age), body mass index (BMI), psychological factors (anxiety and depression, kinesiophobia and catastrophizing), self-reported physical activity, pain phenotype (symptoms of central sensitization, and nociceptive or neuropathic pain), history of COVID-19 and pain intensity and sensitivity in patients with chronic non-specific low back pain (LBP). METHODS: This was a cross-sectional secondary analysis with 83 participants with chronic non-specific LBP recruited from the community between August 2021 and April 2022. BMI, pain intensity (Visual Analog Scale), pain sensitivity at the lower back and at a distant point [pressure pain threshold], catastrophizing (Pain Catastrophizing Scale), kinesiophobia (Tampa Scale for Kinesiophobia), anxiety and depression (Hospital Anxiety and Depression Scale), pain phenotype (Central Sensitization Inventory and PainDetect Questionnaire), physical activity (International Physical Activity Questionnaire), and disability (Roland Morris Disability Questionnaire) were assessed. Multiple linear regression analyses with pain intensity and sensitivity as the dependent variables were used. RESULTS: The model for pain intensity explained 34% of its variance (Adjusted R2 = -0.343, p < 0.001), with depression and anxiety (p = 0.008) and disability (p = 0.035) reaching statistical significance. The model for pain sensitivity at the lower back, also explained 34% of its variance (Adjusted R2 = 0.344, p < 0.001) at the lower back with sex, BMI, and kinesiophobia reaching statistical significance (p < 0.05) and 15% of the variance at a distant body site (Adjusted R2 = 0.148, p = 0.018) with sex and BMI reaching statistical significance (p < 0.05). DISCUSSION: This study found that different factors are associated with pain intensity and pain sensitivity in individuals with LBP. Increased pain intensity was associated with higher levels of anxiety and depression and disability and increased pain sensitivity was associated with being a female, higher kinesiophobia, and lower BMI.

Discovery of 1,3,4-Oxadiazole Derivatives as Broad-Spectrum Antiparasitic Agents.

Vector-borne parasitic diseases (VBPDs) pose a significant threat to public health on a global scale. Collectively, Human African Trypanosomiasis (HAT), Leishmaniasis, and Malaria threaten millions of people, particularly in developing countries. Climate change might alter the transmission and spread of VBPDs, leading to a global burden of these diseases. Thus, novel agents are urgently needed to expand therapeutic options and limit the spread of drug-resistant parasites. Herein, we report the development of broad-spectrum antiparasitic agents by screening a known library of antileishmanial and antimalarial compounds toward Trypanosoma brucei (T. brucei) and identifying a 1,3,4-oxadiazole derivative (19) as anti-T. brucei hit with predicted blood-brain barrier permeability. Subsequently, extensive structure-activity-relationship studies around the lipophilic tail of 19 led to a potent antitrypanosomal and antimalarial compound (27), with moderate potency also toward Leishmania infantum (L. infantum) and Leishmania tropica. In addition, we discovered a pan-active antiparasitic molecule (24), showing low-micromolar IC50s toward T. brucei and Leishmania spp. promastigotes and amastigotes, and nanomolar IC50 against Plasmodium falciparum, together with high selectivity for the parasites over mammalian cells (THP-1). Early ADME-toxicity assays were used to assess the safety profile of the compounds. Overall, we characterized 24 and 27, bearing the 1,3,4-oxadiazole privileged scaffold, as broad-spectrum low-toxicity agents for the treatment of VBPDs. An alkyne-substituted chemical probe (30) was synthesized and will be utilized in proteomics experiments aimed at deconvoluting the mechanism of action in the T. brucei parasite.

Leishmania and HIV co-infection: first naturally Leishmania strain presenting decreased susceptibility to miltefosine, recovered from a patient in Portugal.

BACKGROUND: In Europe, up to 70% of visceral leishmaniasis (VL) cases occurring in adults living with HIV. People living with HIV with VL co-infection often display persistent parasitemia, requiring chronic intermittent anti-Leishmania therapies. Consequently, frequent VL relapses and higher mortality rates are common in these individuals. As such, it is of paramount importance to understand the reasons for parasite persistence to improve infection management. METHODS: To outline possible causes for treatment failure in the context of HIV-VL, we followed a person living with HIV-VL co-infection for nine years in a 12-month period. We characterized: HIV-related clinicopathological alterations (CD4+ T counts and viremia) and Leishmania-specific seroreactivity, parasitemia, quantification of pro-inflammatory cytokines upon stimulation and studied a Leishmania clinical isolate recovered during this period. RESULTS: The subject presented controlled viremia and low CD4+ counts. The subject remained PCR positive for Leishmania and also seropositive. The cellular response to parasite antigens was erratic. The isolate was identified as the first Leishmania infantum case with evidence of decreased miltefosine susceptibility in Portugal. CONCLUSION: Treatment failure is a multifactorial process driven by host and parasite determinants. Still, the real-time determination of drug susceptibility profiles in clinical isolates is an unexplored resource in the monitoring of VL.

Predictors of improvement in community adolescents with chronic neck pain: A secondary analysis using different improvement criteria.

BACKGROUND: Interventions based on pain neuroscience education and exercise have emerged as effective in the management of chronic neck pain in adolescents. No studies have explored factors that might be associated with recovery in adolescents with neck pain. OBJECTIVE: To explore predictors of improvement after an intervention based on exercise and pain neuroscience education. DESIGN: Secondary analysis of a randomized trial. SETTING: Community. PARTICIPANTS: 127 community adolescents with neck pain. INTERVENTIONS: Blended-learning intervention based on exercise and pain neuroscience education. MAIN OUTCOME MEASURES: A set of variables including sociodemographic data, pain characteristics, physical activity, disability, sleep, catastrophizing, fear of movement, self-efficacy, symptoms of central sensitization, knowledge of pain neuroscience, pressure pain thresholds, and neck muscles endurance were used to predict a clinical response at 1 week after intervention and at 6-month follow-up. RESULTS: Different predictors of improvement and non-improvement to intervention were found, but common predictors were not found for all the improvement criteria explored and time points. CONCLUSIONS: These findings suggest that using different criteria to characterize adolescents with neck pain as improved and non-improved after pain neuroscience education and exercise have an effect on the variables associated with a response to the intervention.

The discovery of aryl-2-nitroethyl triamino pyrimidines as anti-Trypanosoma brucei agents.

Pteridine reductase 1 (PTR1) is a catalytic protein belonging to the folate metabolic pathway in Trypanosmatidic parasites. PTR1 is a known target for the medicinal chemistry development of antiparasitic agents against Trypanosomiasis and Leishmaniasis. In previous studies, new nitro derivatives were elaborated as PTR1 inhibitors. The compounds showing a diamino-pyrimidine core structure were previously developed but they showed limited efficacy. Therefore, a new class of phenyl-, heteroaryl- and benzyloxy-nitro derivatives based on the 2-nitroethyl-2,4,6-triaminopyrimidine scaffold were designed and tested. The compounds were assayed for their ability to inhibit T. brucei and L. major PTR1 enzymes and for their antiparasitic activity towards T. brucei and L. infantum parasites. To understand the structure-activity relationships of the compounds against TbPTR1, the X-ray crystallographic structure of the 2,4,6-triaminopyrimidine (TAP) was obtained and molecular modelling studies were performed. As a next step, only the most effective compounds against T. brucei were then tested against the amastigote cellular stage of T. cruzi, searching for a broad-spectrum antiprotozoal agent. An early ADME-Tox profile evaluation was performed. The early toxicity profile of this class of compounds was investigated by measuring their inhibition of hERG and five cytochrome P450 isoforms (CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4), cytotoxicity towards A549 cells and mitochondrial toxicity. Pharmacokinetic studies (SNAP-PK) were performed on selected compounds using hydroxypropyl-ß-cyclodextrins (50 % w/v) to preliminarily study their plasma concentration when administered per os at a dose of 20 mg/kg. Compound 1p, showed the best pharmacodynamic and pharmacokinetic properties, can be considered a good candidate for further bioavailability and efficacy studies.

Impact of different CRPS phenotypes and diagnostic criteria on quantitative sensory testing outcomes: systematic review and meta-analysis.

OBJECTIVES: This review and meta-analysis evaluated the impact of diagnostic criteria and clinical phenotypes on quantitative sensory testing (QST) outcomes in patients with complex regional pain syndrome (CRPS). METHODS: Eight databases were searched based on a previously published protocol. Forty studies comparing QST outcomes between CRPS-I vs II, warm vs cold CRPS, upper vs lower limb CRPS, males vs females, or using Budapest vs older IASP criteria were included. RESULTS: Studies investigating QST differences between CRPS-I vs II (n = 4), between males vs females (n = 2), and between upper and lower limb CRPS (n = 2) showed no significant differences. Four studies compared QST outcomes in warm vs cold CRPS, showing heat hyperalgesia in warm CRPS, with thermal and mechanical sensory loss in cold CRPS. Although CRPS diagnosed using the Budapest criteria (24 studies) vs 1994 IASP criteria (13 studies) showed similar sensory profiles, there was significant heterogeneity and low quality of evidence in the latter. CONCLUSIONS: Based on the findings of this review, classifying CRPS according to presence or absence of nerve lesion into CRPS-I and II, location (upper or lower limb) or according to sex might not be clinically relevant as all appear to have comparable sensory profiles that might suggest similar underlying mechanisms. In contrast, warm vs cold phenotypes exhibited clear differences in their associated QST sensory profiles. To the extent that differences in underlying mechanisms might lead to differential treatment responsiveness, it appears unlikely that CRPS-I vs II, CRPS location, or patient sex would prove useful in guiding clinical management.

Effectiveness of Neural Mobilisation on Pain Intensity, Functional Status, and Physical Performance in Adults with Musculoskeletal Pain - A Systematic Review with Meta-Analysis.

OBJECTIVE: To investigate up-to-date evidence of the effectiveness of neural mobilisation techniques compared with any type of comparator in improving pain, function, and physical performance in people with musculoskeletal pain. DATA SOURCES: The following sources were consulted: PubMed, Web of Science, CENTRAL, CINAHL, Scopus, and PEDro databases; scientific repositories; and clinical trial registers. The last search was performed on 01/06/2023. METHODS: Two reviewers independently assessed the studies for inclusion. We included randomised, quasi-randomised, and crossover trials on musculoskeletal pain in which at least one group received neural mobilisation (alone or as part of multimodal interventions). Meta-analyses were performed where possible. The RoB 2 and the Grading of Recommendations Assessment, Development and Evaluation tools were used to assess risk of bias and to rate the certainty of evidence, respectively. RESULTS: Thirty-nine trials were identified. There was a significant effect favouring neural mobilisation for pain and function in people with low back pain, but not for flexibility. For neck pain, there was a significant effect favouring neural mobilisation as part of multimodal interventions for pain, but not for function and range of motion. Regarding other musculoskeletal conditions, it was not possible to conclude whether neural mobilisation is effective in improving pain and function. There was very low confidence for all effect estimates. CONCLUSIONS: Neural mobilisation as part of multimodal interventions appears to have a positive effect on pain for patients with low back pain and neck pain and on function in people with low back pain. For the other musculoskeletal conditions, results are inconclusive.

A single session of action observation therapy versus observing a natural landscape in adults with chronic neck pain - a randomized controlled trial.

BACKGROUND: Action observation (AO) has emerged as a potential neurorehabilitation therapy for patients with neck pain (NP), but evidence of its effectiveness is scarce. This study aims to assess the effect of a single session of AO when compared to observing a natural landscape on NP intensity, fear of movement, fear-avoidance beliefs, neck muscles' strength, pressure pain threshold, and tactile acuity. METHODS: Sixty participants with NP were randomly allocated to the AO group (n = 30) or control group (n = 30). Both groups watched an 11-minute video: the AO group watched a video of a person matched for age and sex performing neck exercises, while the control group watched a video of natural landscapes. Neck pain intensity, fear of movement, fear-avoidance beliefs, tactile acuity, pressure pain thresholds, and neck muscle strength were assessed both at baseline and post-intervention. General linear models of repeated measures (ANCOVA of two factors) were used to explore between-group differences at post-intervention. RESULTS: There was a significant main effect of time for pain intensity (p = 0.02; η2p = 0.09; within-group mean change and 95% CI: AO=-1.44 (-2.28, -0.59); control=-1.90 (-2.74, -1.06), but no time versus group interaction (p = 0.46). A time versus group significant interaction was found for one out of the six measurement sites of two-point discrimination and the neck flexors strength (p < 0.05) favoring the control group. No other statistically significant differences were found for the remaining variables). CONCLUSIONS: Results suggest a similar acute benefit for both a single session of AO and observing natural landscapes for promoting hypoalgesia, but no impact on kinesiophobia, fear-avoidance beliefs, or pressure pain thresholds. Also, AO had no positive effect on two-point discrimination and muscle strength. Further research is needed, with longer interventions. TRIAL REGISTRATION: Clinialtrials.gov (NCT05078489).

Efficacy of ultrasound-guided infiltration with levobupivacaine and triamcinolone for myofascial pain syndrome of the quadratus lumborum: a retrospective observational study

Abstract Introduction and objectives: Myofascial Pain Syndrome (MPS) of the Quadratus Lumborum muscle (QL) is a frequent cause of chronic low back pain. With this study, we aimed to assess the efficacy of ultrasound-guided infiltration with 0.25% levobupivacaine and 40 mg triamcinolone for MPS of the QL. Methods: Observational and retrospective study of participants submitted to ultrasound-guided infiltration of the QL muscle from January 1, 2015 to June 31, 2019. Pain intensity was assessed using the five-point pain Numeric Rating Scale (NRS): pre-intervention, at 72 hours, 1 month, 3 months and 6 months post-intervention. Additional data collected were demographic characteristics, opioid consumption, and adverse effects. Results: We assessed 90 participants with mean age of 55.2 years. Sixty-eight percent of participants were female. Compared to the pre-intervention assessment, there was an improvement in pain at 72 hours (Mean Difference [MD = 3.085]; 95% CI: 2.200-3.970, p < 0.05), at the 1st month (MD = 2.644; 95% CI: 1.667-3.621, p < 0.05), at the 3rdmonth (MD = 2.017; 95% CI: 0.202-2.729, p < 0.05) and at the 6th month (MD = 1.339; 95% CI 0.378-2.300, p < 0.05), post-intervention. No statistically significant differences in opioid consumption were observed. No adverse effects associated with the technique were reported. Conclusions: Ultrasound-guided infiltration of the QL muscle is a safe and effective procedure for the treatment of pain in the QL MPS within 6 months post-intervention.

High-Throughput Phenotypic Screening and Machine Learning Methods Enabled the Selection of Broad-Spectrum Low-Toxicity Antitrypanosomatidic Agents.

Broad-spectrum anti-infective chemotherapy agents with activity against Trypanosomes, Leishmania, and Mycobacterium tuberculosis species were identified from a high-throughput phenotypic screening program of the 456 compounds belonging to the Ty-Box, an in-house industry database. Compound characterization using machine learning approaches enabled the identification and synthesis of 44 compounds with broad-spectrum antiparasitic activity and minimal toxicity against Trypanosoma brucei, Leishmania Infantum, and Trypanosoma cruzi. In vitro studies confirmed the predictive models identified in compound 40 which emerged as a new lead, featured by an innovative N-(5-pyrimidinyl)benzenesulfonamide scaffold and promising low micromolar activity against two parasites and low toxicity. Given the volume and complexity of data generated by the diverse high-throughput screening assays performed on the compounds of the Ty-Box library, the chemoinformatic and machine learning tools enabled the selection of compounds eligible for further evaluation of their biological and toxicological activities and aided in the decision-making process toward the design and optimization of the identified lead.

Synthesis and Evaluation of Marine-Inspired Compounds Result in Hybrids with Antitrypanosomal and Antileishmanial Activities.

Natural products are a very rich source for obtaining new compounds with therapeutic potential. In the search for new antiparasitic and antimicrobial agents, molecular hybrids were designed based on the structures of antimicrobial marine quinazolinones and eugenol, a natural phenolic compound. Following reports of the therapeutic potential of quinazolinones and eugenol derivatives, it was expected that the union of these pharmacophores could generate biologically relevant substances. The designed compounds were obtained by classical synthetic procedures and were characterized by routine spectrometric techniques. Nine intermediates and final products were then evaluated in vitro against Trypanosoma brucei and Leishmania infantum. Antifungal and antibacterial activity were also evaluated. Six compounds (9b, 9c, 9d, 10b, 10c, and 14) showed mild activity against T. brucei with IC50 in the range of 11.17-31.68 µM. Additionally, intermediate 9c showed anti-Leishmania activity (IC50 7.54 µM) and was six times less cytotoxic against THP-1 cells. In conclusion, novel derivatives with a simple quinazolinone scaffold showing selectivity against parasites without antibacterial and antifungal activities were disclosed, paving the way for new antitrypanosomal agents.