Semi-supervised mixture multi-source exchangeability model for leveraging real-world data in clinical trials.

The traditional trial paradigm is often criticized as being slow, inefficient, and costly. Statistical approaches that leverage external trial data have emerged to make trials more efficient by augmenting the sample size. However, these approaches assume that external data are from previously conducted trials, leaving a rich source of untapped real-world data (RWD) that cannot yet be effectively leveraged. We propose a semi-supervised mixture (SS-MIX) multisource exchangeability model (MEM); a flexible, two-step Bayesian approach for incorporating RWD into randomized controlled trial analyses. The first step is a SS-MIX model on a modified propensity score and the second step is a MEM. The first step targets a representative subgroup of individuals from the trial population and the second step avoids borrowing when there are substantial differences in outcomes among the trial sample and the representative observational sample. When comparing the proposed approach to competing borrowing approaches in a simulation study, we find that our approach borrows efficiently when the trial and RWD are consistent, while mitigating bias when the trial and external data differ on either measured or unmeasured covariates. We illustrate the proposed approach with an application to a randomized controlled trial investigating intravenous hyperimmune immunoglobulin in hospitalized patients with influenza, while leveraging data from an external observational study to supplement a subgroup analysis by influenza subtype.

A Stratified Approach for Managing Patients With Low Back Pain in Primary Care (SPLIT Program): A Before-and-After Study.

PURPOSE: To determine the effects of stratified primary care for low back pain (SPLIT program) in decreasing back-related disability for patients with low back pain (LBP) in primary care. METHODS: We conducted a before-and-after study. We compared health-related outcomes for 2 sequential, independent cohorts of patients with LBP recruited at 7 primary care units in Portugal. The first prospective cohort study characterized usual care (UC) and collected data from February to September 2018. The second was performed when the SPLIT program was implemented and collected data from November 2018 to October 2021. Between cohorts, physical therapists were trained in the implementation of the SPLIT program, which used the STarT Back Screening Tool to categorize patients for matched treatment. We compared back-related disability (Roland-Morris Disability Questionnaire, 0-24 points), pain (Numeric Pain Rating Scale, 0-10 points), perceived effect of treatment (Global Perceived Effect Scale, -5 to +5 points), and health-related quality of life (EuroQoL 5 dimensions 3 levels index, 0-1 points). RESULTS: We enrolled a total of 447 patients: 115 in the UC cohort (mostly treated with pharmacologic treatment) and 332 in the SPLIT cohort (all referred for a physical therapy intervention program). Over the study period of 6 months, patients in the SPLIT program showed significantly greater improvements in back-related disability (ß, -2.94; 95% CI, -3.63 to -2.24; P ≤ .001), pain (ß, -0.88; 95% CI, -1.18 to -0.57; P ≤ .001), perceived effect of treatment (ß, 1.40; 95% CI, 0.97 to 1.82; P ≤ .001), and health-related quality of life (ß, 0.11; 95% CI, 0.08 to 0.14; P ≤ .001) compared with UC. CONCLUSIONS: Patients in the SPLIT program for LBP showed greater benefits regarding health-related outcomes than those receiving UC.

Recurrent and metastatic cellular cutaneous fibrous histiocytoma: A case report and literature review.

Cutaneous fibrous histiocytoma (FH) is considered a benign dermal tumor. The cellular variant is rare and poorly documented. Besides presenting a high risk of local recurrence, it has a low but serious metastatic potential. We present a case of metastatic cellular FH and also review the literature on this tumor, given its unusual metastatic development. A 47-year-old male patient presented with a lesion in the anterior surface of the right thigh, which has been present since adolescence but had grown during last year. Anatomopathological evaluation revealed a cellular FH, and the lesion was completely removed. Six months later, tumor recurrence with multiple compartment muscle involvement and pulmonary metastasis were detected. Both lesions were completely resected and after 3 years of follow-up, the patient is asymptomatic and free of the disease. We conclude that FH should be carefully sampled to detect variants with high local recurrence rates or with some metastatic risk such as the cellular one. We recommend wide surgical resection and a close follow-up including chest x-rays or thorax computed tomography (CT) in all cellular FH cases with local recurrence.

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.

MyBack - effectiveness and implementation of a behavior change informed exercise programme to prevent low back pain recurrences: a hybrid effectiveness-implementation randomized controlled study protocol.

BACKGROUND: Low back pain (LBP) is a common health condition and the leading cause of years lived with disability worldwide. Most LBP episodes have a favourable prognosis, but recurrences within a year are common. Despite the individual and societal impact related to LBP recurrences, there is limited evidence on effective strategies for secondary prevention of LBP and successful implementation of intervention programmes in a real-world context. The aim of this study is to analyse the effectiveness of a tailored exercise and behavioural change programme (MyBack programme) in the secondary prevention of LBP; and evaluate acceptability, feasibility and determinants of implementation by the different stakeholders, as well as the implementation strategy of the MyBack programme in real context. METHODS: This protocol describes a hybrid type I, randomized controlled trial to evaluate the effectiveness and implementation of MyBack programme in the context of primary health care. The Behaviour Change Wheel framework and FITT-VP principles will inform the development of the behaviour change and exercise component of MyBack programme, respectively. Patients who have recently recovered from an episode of non-specific LBP will be randomly assigned to MyBack and usual care group or usual care group. The primary outcome will be the risk of LBP recurrence. The secondary outcomes will include disability, pain intensity, musculoskeletal health, and health-related quality of life. Participants will be followed monthly for 1 year. Costs data related to health care use and the MyBack programme will be also collected. Implementation outcomes will be assessed in parallel with the effectiveness study using qualitative methods (focus groups with participants and health providers) and quantitative data (study enrolment and participation data; participants adherence). DISCUSSION: To our knowledge, this is the first study assessing the effectiveness and implementation of a tailored exercise and behaviour change programme for prevention of LBP recurrences. Despite challenges related to hybrid design, it is expected that data on the effectiveness, cost-effectiveness, and implementation of the MyBack programme may contribute to improve health care in patients at risk of LBP recurrences, contributing to direct and indirect costs reduction for patients and the health system. TRIAL REGISTRATION NUMBER: NCT05841732.

Complete tumor necrosis after neoadjuvant chemotherapy defines good responders in patients with Ewing sarcoma.

BACKGROUND: Survival in patients who have Ewing sarcoma is correlated with postchemotherapy response (tumor necrosis). This treatment response has been categorized as the response rate, similar to what has been used in osteosarcoma. There is controversy regarding whether this is appropriate or whether it should be a dichotomy of complete versus incomplete response, given how important a complete response is for in overall survival of patients with Ewing sarcoma. The purpose of this study was to evaluate the impact that the amount of chemotherapy-induced necrosis has on (1) overall survival, (2) local recurrence-free survival, (3) metastasis-free survival, and (4) event-free survival in patients with Ewing sarcoma. METHODS: In total, 427 patients who had Ewing sarcoma or tumors in the Ewing sarcoma family and received treatment with preoperative chemotherapy and surgery at 10 international institutions were included. Multivariate Cox proportional-hazards analyses were used to assess the associations between tumor necrosis and all four outcomes while controlling for clinical factors identified in bivariate analysis, including age, tumor volume, location, surgical margins, metastatic disease at presentation, and preoperative radiotherapy. RESULTS: Patients who had a complete (100%) tumor response to chemotherapy had increased overall survival (hazard ratio [HR], 0.26; 95% CI, 0.14-0.48; p < .01), recurrence-free survival (HR, 0.40; 95% CI, 0.20-0.82; p = .01), metastasis-free survival (HR, 0.27; 95% CI, 0.15-0.46; p ≤ .01), and event-free survival (HR, 0.26; 95% CI, 0.16-0.41; p ≤ .01) compared with patients who had a partial (0%-99%) response. CONCLUSIONS: Complete tumor necrosis should be the index parameter to grade response to treatment as satisfactory in patients with Ewing sarcoma. Any viable tumor in these patients after neoadjuvant treatment should be of oncologic concern. These findings can affect the design of new clinical trials and the risk-stratified application of conventional or novel treatments.

Cxcr3 constrains pancreatic cancer dissemination through instructing T cell fate.

Pancreatic ductal adenocarcinoma (PDA) is a lethal and metastatic malignancy resistant to therapy. Elucidating how pancreatic tumor-specific T cells differentiate and are maintained in vivo could inform novel therapeutic avenues to promote T cell antitumor activity. Here, we show that the spleen is a critical site harboring tumor-specific CD8 T cells that functionally segregate based on differential Cxcr3 and Klrg1 expression. Cxcr3+ Klrg1- T cells express the memory stem cell marker Tcf1, whereas Cxcr3-Klrg1 + T cells express GzmB consistent with terminal differentiation. We identify a Cxcr3+ Klrg1+ intermediate T cell subpopulation in the spleen that is highly enriched for tumor specificity. However, tumor-specific T cells infiltrating primary tumors progressively downregulate both Cxcr3 and Klrg1 while upregulating exhaustion markers PD-1 and Lag-3. We show that antigen-specific T cell infiltration into PDA is Cxcr3 independent. Further, Cxcr3-deficiency results in enhanced antigen-specific T cell IFNγ production in primary tumors, suggesting that Cxcr3 promotes loss of effector function. Ultimately, however, Cxcr3 was critical for mitigating cancer cell dissemination following immunotherapy with CD40 agonist + anti-PD-L1 or T cell receptor engineered T cell therapy targeting mesothelin. In the absence of Cxcr3, splenic Klrg1 + GzmB + antitumor T cells wain while pancreatic cancer disseminates suggesting a role for these cells in eliminating circulating metastatic tumor cells. Intratumoral myeloid cells are poised to produce Cxcl10, whereas splenic DC subsets produce Cxcl9 following immunotherapy supporting differential roles for these chemokines on T cell differentiation. Together, our study supports that Cxcr3 mitigates tumor cell dissemination by impacting peripheral T cell fate rather than intratumoral T cell trafficking.

Vaccines for preventing herpes zoster in older adults.

BACKGROUND: Herpes zoster, commonly known as shingles, is a neurocutaneous disease caused by the reactivation of the virus that causes varicella (chickenpox). After resolution of the varicella episode, the virus can remain latent in the sensitive dorsal ganglia of the spine. Years later, with declining immunity, the varicella zoster virus (VZV) can reactivate and cause herpes zoster, an extremely painful condition that can last many weeks or months and significantly compromise the quality of life of the affected person. The natural process of ageing is associated with a reduction in cellular immunity, and this predisposes older adults to herpes zoster. Vaccination with an attenuated form of the VZV activates specific T-cell production avoiding viral reactivation. Two types of herpes zoster vaccines are currently available. One of them is the single-dose live attenuated zoster vaccine (LZV), which contains the same live attenuated virus used in the chickenpox vaccine, but it has over 14-fold more plaque-forming units of the attenuated virus per dose. The other is the recombinant zoster vaccine (RZV) which does not contain the live attenuated virus, but rather a small fraction of the virus that cannot replicate but can boost immunogenicity. The recommended schedule for the RZV is two doses two months apart. This is an update of a Cochrane Review first published in 2010, and updated in 2012, 2016, and 2019. OBJECTIVES: To evaluate the effectiveness and safety of vaccination for preventing herpes zoster in older adults. SEARCH METHODS: For this 2022 update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL 2022, Issue 10), MEDLINE (1948 to October 2022), Embase (2010 to October 2022), CINAHL (1981 to October 2022), LILACS (1982 to October 2022), and three trial registries. SELECTION CRITERIA: We included studies involving healthy older adults (mean age 60 years or older). We included randomised controlled trials (RCTs) or quasi-RCTs comparing zoster vaccine (any dose and potency) versus any other type of intervention (e.g. varicella vaccine, antiviral medication), placebo, or no intervention (no vaccine). Outcomes were cumulative incidence of herpes zoster, adverse events (death, serious adverse events, systemic reactions, or local reaction occurring at any time after vaccination), and dropouts. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. MAIN RESULTS: We included two new studies involving 1736 participants in this update. The review now includes a total of 26 studies involving 90,259 healthy older adults with a mean age of 63.7 years. Only three studies assessed the cumulative incidence of herpes zoster in groups that received vaccines versus placebo. Most studies were conducted in high-income countries in Europe and North America and included healthy Caucasians (understood to be white participants) aged 60 years or over with no immunosuppressive comorbidities. Two studies were conducted in Japan and one study was conducted in the Republic of Korea. Sixteen studies used LZV. Ten studies tested an RZV. The overall certainty of the evidence was moderate, which indicates that the intervention probably works. Most data for the primary outcome (cumulative incidence of herpes zoster) and secondary outcomes (adverse events and dropouts) came from studies that had a low risk of bias and included a large number of participants. The cumulative incidence of herpes zoster at up to three years of follow-up was lower in participants who received the LZV (one dose subcutaneously) than in those who received placebo (risk ratio (RR) 0.49, 95% confidence interval (CI) 0.43 to 0.56; risk difference (RD) 2%; number needed to treat for an additional beneficial outcome (NNTB) 50; moderate-certainty evidence) in the largest study, which included 38,546 participants. There were no differences between the vaccinated and placebo groups for serious adverse events (RR 1.08, 95% CI 0.95 to 1.21) or deaths (RR 1.01, 95% CI 0.92 to 1.11; moderate-certainty evidence). The vaccinated group had a higher cumulative incidence of one or more adverse events (RR 1.71, 95% CI 1.38 to 2.11; RD 23%; number needed to treat for an additional harmful outcome (NNTH) 4.3) and injection site adverse events (RR 3.73, 95% CI 1.93 to 7.21; RD 28%; NNTH 3.6; moderate-certainty evidence) of mild to moderate intensity. These data came from four studies with 6980 participants aged 60 years or older. Two studies (29,311 participants for safety evaluation and 22,022 participants for efficacy evaluation) compared RZV (two doses intramuscularly, two months apart) versus placebo. Participants who received the new vaccine had a lower cumulative incidence of herpes zoster at 3.2 years follow-up (RR 0.08, 95% CI 0.03 to 0.23; RD 3%; NNTB 33; moderate-certainty evidence), probably indicating a favourable profile of the intervention. There were no differences between the vaccinated and placebo groups in cumulative incidence of serious adverse events (RR 0.97, 95% CI 0.91 to 1.03) or deaths (RR 0.94, 95% CI 0.84 to 1.04; moderate-certainty evidence). The vaccinated group had a higher cumulative incidence of adverse events, any systemic symptom (RR 2.23, 95% CI 2.12 to 2.34; RD 33%; NNTH 3.0), and any local symptom (RR 6.89, 95% CI 6.37 to 7.45; RD 67%; NNTH 1.5). Although most participants reported that their symptoms were of mild to moderate intensity, the risk of dropouts (participants not returning for the second dose, two months after the first dose) was higher in the vaccine group than in the placebo group (RR 1.25, 95% CI 1.13 to 1.39; RD 1%; NNTH 100, moderate-certainty evidence). Only one study reported funding from a non-commercial source (a university research foundation). All other included studies received funding from pharmaceutical companies. We did not conduct subgroup and sensitivity analyses AUTHORS' CONCLUSIONS: LZV (single dose) and RZV (two doses) are probably effective in preventing shingles disease for at least three years. To date, there are no data to recommend revaccination after receiving the basic schedule for each type of vaccine. Both vaccines produce systemic and injection site adverse events of mild to moderate intensity. The conclusions did not change in relation to the previous version of the systematic review.

Evolution and molecular interactions of major histocompatibility complex (MHC)-G, -E and -F genes.

Classical HLA (Human Leukocyte Antigen) is the Major Histocompatibility Complex (MHC) in man. HLA genes and disease association has been studied at least since 1967 and no firm pathogenic mechanisms have been established yet. HLA-G immune modulation gene (and also -E and -F) are starting the same arduous way: statistics and allele association are the trending subjects with the same few results obtained by HLA classical genes, i.e., no pathogenesis may be discovered after many years of a great amount of researchers' effort. Thus, we believe that it is necessary to follow different research methodologies: (1) to approach this problem, based on how evolution has worked maintaining together a cluster of immune-related genes (the MHC) in a relatively short chromosome area since amniotes to human at least, i.e., immune regulatory genes (MHC-G, -E and -F), adaptive immune classical class I and II genes, non-adaptive immune genes like (C2, C4 and Bf) (2); in addition to using new in vitro models which explain pathogenetics of HLA and disease associations. In fact, this evolution may be quite reliably studied during about 40 million years by analyzing the evolution of MHC-G, -E, -F, and their receptors (KIR-killer-cell immunoglobulin-like receptor, NKG2-natural killer group 2-, or TCR-T-cell receptor-among others) in the primate evolutionary lineage, where orthology of these molecules is apparently established, although cladistic studies show that MHC-G and MHC-B genes are the ancestral class I genes, and that New World apes MHC-G is paralogous and not orthologous to all other apes and man MHC-G genes. In the present review, we outline past and possible future research topics: co-evolution of adaptive MHC classical (class I and II), non-adaptive (i.e., complement) and modulation (i.e., non-classical class I) immune genes may imply that the study of full or part of MHC haplotypes involving several loci/alleles instead of single alleles is important for uncovering HLA and disease pathogenesis. It would mainly apply to starting research on HLA-G extended haplotypes and disease association and not only using single HLA-G genetic markers.

Trajectories of physical function and quality of life in people with osteoarthritis: results from a 10-year population-based cohort.

OBJECTIVE: To identify long-term trajectories of physical function and health-related quality of life (HRQoL) among people with hip and/or knee osteoarthritis (HKOA) and the sociodemographic, lifestyle, and clinical factors associated with different trajectories. METHODS: Participants with HKOA from the EpiDoC study, a 10-year follow-up (2011-2021) population-based cohort, were considered. Sociodemographic, lifestyle, and clinical variables were collected at baseline in a structured interview and clinical appointment. Physical function and HRQoL were evaluated with the Health Assessment Questionnaire (HAQ) and EuroQoL, respectively, at baseline and the three follow-ups. Group-based trajectory modeling identified physical function and HRQoL trajectories. Multinomial logistic regression analyzed the associations between the covariates of interest and trajectory assignment (p < 0.05). RESULTS: We included 983 participants with HKOA. We identified three trajectories for each outcome: "consistently low disability" (32.0%), "slightly worsening moderate disability" (47.0%), and "consistently high disability" (21.0%) for physical function; "consistently high HRQoL" (18.3%), "consistently moderate HRQoL" (48.4%) and "consistently low HRQoL" (33.4%) for HRQoL. Age ≥ 75 years, female sex, multimorbidity, and high baseline clinical severity were associated with higher risk of assignment to poorer physical function and HRQoL trajectories. Participants with high education level and with regular physical activity had a lower risk of assignment to a poor trajectory. Unmanageable pain levels increased the risk of assignment to the "consistently moderate HRQoL" trajectory. CONCLUSION: Although the trajectories of physical function and HRQoL remained stable over 10 years, approximately 70% of people with HKOA maintained moderate or low physical function and HRQoL over this period. Modifiable risk factors like physical activity, multimorbidity and clinical severity were associated with poorer physical function and HRQoL trajectories. These risk factors may be considered in tailored healthcare interventions.

Prevalence of and factors associated with unmanageable pain levels in people with knee or hip osteoarthritis: a cross-sectional population-based study.

BACKGROUND: Pain due to knee and / or hip osteoarthritis (HKOA) is the most common symptom for seeking healthcare. Pain interferes on daily activities, social and occupational participation in people with HKOA. The goal of this study is to estimate the prevalence of unmanageable pain levels (UPL) among people with HKOA), characterize this population and identify factors associated with UPL, and compare therapeutic strategies used by people with UPL versus manageable pain levels (MPL). METHODS: We analysed data from the EpiReumaPt study (n = 10,661), that included a representative sample of the Portuguese population. Among these, 1081 participants had a validated diagnosis of HKOA by a rheumatologist.. Sociodemographic, lifestyle and health-related data were collected in a structured interview. Pain intensity (NPRS) data were collected in a medical appointment. Painmedication (last month), physiotherapy and surgery were considered as therapies for pain management. UPL was defined as a mean pain intensity in the previous week of ≥5 points on 11-point numeric pain rating scale. The factors associated with UPL were analyzed with logistic regression (p < 0.05, 95%CI). The effect of unmanageable pain levels was assessed by the HOOS/KOOS activities of daily living and quality of life subscales. Symptoms of anxiety and depression were assessed by the Hospital Anxiety and Depression Scale (HADS). Analysis was completed with linear and logistic regression. All analysis were weighted. RESULTS: The estimated prevalence of UPL among people with HKOA was 68.8%. UPL was associated with being female (odds ratio (OR) = 2.36, p < 0.001), being overweight (OR = 1.84, p = 0.035) or obese (OR = 2.26, p = 0.006), and having multimorbidity (OR = 2.08, p = 0.002). People with UPL reported worse performance in activities of daily living and lower quality of life (ß = - 21.28, p < 0.001 and ß = - 21.19, p < 0.001, respectively) than people with MPL. People with UPL consumed more NSAIDs (22.0%, p = 0.003), opioids (4.8%, p = 0.008), paracetamol (2.7%, p = 0.033), and overall analgesics (7.3%, p = 0.013) than people with MPL. A higher proportion of people with UPL underwent physiotherapy (17.5%, p = 0.002) than people with MPL. CONCLUSION: Two-thirds of people with HKOA in Portugal have poor management of their pain levels. Clinical and lifestyle factors, that are highly presented in individuals with HKOA, are associated with unmanageable pain. Our results highlighting the need for further research and implementation of effective interventions to improve pain, function and quality of life in people with HKOA.

Differences in Trapezius Muscle H-Reflex between Asymptomatic Subjects and Symptomatic Shoulder Pain Subjects.

In chronic shoulder pain, adaptations in the nervous system such as in motoneuron excitability, could contribute to impairments in scapular muscles, perpetuation and recurrence of pain and reduced improvements during rehabilitation. The present cross-sectional study aims to compare trapezius neural excitability between symptomatic and asymptomatic subjects. In 12 participants with chronic shoulder pain (symptomatic group) and 12 without shoulder pain (asymptomatic group), the H reflex was evoked in all trapezius muscle parts, through C3/4 nerve stimulation, and the M-wave through accessory nerve stimulation. The current intensity to evoke the maximum H reflex, the latency and the maximum peak-to-peak amplitude of both the H reflex and M-wave, as well as the ratio between these two variables, were calculated. The percentage of responses was considered. Overall, M-waves were elicited in most participants, while the H reflex was elicited only in 58-75% or in 42-58% of the asymptomatic and symptomatic participants, respectively. A comparison between groups revealed that the symptomatic group presented a smaller maximum H reflex as a percentage of M-wave from upper trapezius and longer maximal H reflex latency from the lower trapezius (p < 0.05). Subjects with chronic shoulder pain present changes in trapezius H reflex parameters, highlighting the need to consider trapezius neuromuscular control in these individuals' rehabilitation.

The European Portuguese Version of the Composite Physical Function Scale: Cross-Cultural Adaptation and Validation in Community-Dwelling Older Adults.

This study aims to perform the cross-cultural adaptation to European Portuguese of the Composite Physical Function Scale and to assess its validity and reliability in a sample of community-dwelling older adults. The scale was translated into European Portuguese, back translated, and piloted in a sample of 16 representative individuals. Its validity and reliability were tested in an independent sample of 114 community-dwelling older adults (52 were tested twice to assess test-retest reliability). The results showed that the scale had good internal consistency (α = .90), construct validity (ρ = .71) and measurement error (78.8% agreement), and excellent test-retest reliability (κ = .98). However, a ceiling effect was found as 28% of the participants achieved the highest possible score. Although the scale has good measurement properties, the presence of ceiling effects is indicative that this tool is not able to distinguish higher levels of intrinsic capacity within community-dwelling older adults.

Prospects and Advances in Adoptive Natural Killer Cell Therapy for Unmet Therapeutic Needs in Pediatric Bone Sarcomas.

Malignant bone tumors are aggressive tumors, with a high tendency to metastasize, that are observed most frequently in adolescents during rapid growth spurts. Pediatric patients with malignant bone sarcomas, Ewing sarcoma and osteosarcoma, who present with progressive disease have dire survival rates despite aggressive therapy. These therapies can have long-term effects on bone growth, such as decreased bone mineral density and reduced longitudinal growth. New therapeutic approaches are therefore urgently needed for targeting pediatric malignant bone tumors. Harnessing the power of the immune system against cancer has improved the survival rates dramatically in certain cancer types. Natural killer (NK) cells are a heterogeneous group of innate effector cells that possess numerous antitumor effects, such as cytolysis and cytokine production. Pediatric sarcoma cells have been shown to be especially susceptible to NK-cell-mediated killing. NK-cell adoptive therapy confers numerous advantages over T-cell adoptive therapy, including a good safety profile and a lack of major histocompatibility complex restriction. NK-cell immunotherapy has the potential to be a new therapy for pediatric malignant bone tumors. In this manuscript, we review the general characteristics of osteosarcoma and Ewing sarcoma, discuss the long-term effects of sarcoma treatment on bones, and the barriers to effective immunotherapy in bone sarcomas. We then present the laboratory and clinical studies on NK-cell immunotherapy for pediatric malignant bone tumors. We discuss the various donor sources and NK-cell types, the engineering of NK cells and combinatorial treatment approaches that are being studied to overcome the current challenges in adoptive NK-cell therapy, while suggesting approaches for future studies on NK-cell immunotherapy in pediatric bone tumors.

Gene expression in cell lines from human ameloblastoma immortalized using hTERT and HPV16-E6/E7.

OBJECTIVE: The aim of this study was to evaluate and compare alterations in gene expression using two distinct immortalization methods (hTERT and HPV16-E6/E7) in ameloblastoma cell lines. MATERIALS AND METHODS: A primary cell culture derived from human ameloblastoma (AME-1) was established and immortalized by two different methods using a transfection processes to hTERT and HPV-E6/E7. The RNA-seq was used to verify which immortalization method had less influence on gene expression. It was performed in four steps: extraction and collection of mRNA, PCR amplification, comparison with the human reference genome, and analysis of differential expression. The genes with differentiated expression were identified and mapped. RESULTS: RNA-seq revealed genetic alterations in ameloblastoma cell lines after the immortalization process, including increased expression of tumor genes like MYC, E2F1, BRAF, HRAS, and HTERT, and a decrease in tumor suppressor genes like P53, P21, and Rb. CONCLUSIONS: It is possible to affirm that cell immortalization is not an inert method regarding gene regulation mechanisms and the hTERT method (AME-TERT) presented fewer changes in gene expression levels.

Scapular Dynamic Muscular Stiffness Assessed through Myotonometry: A Narrative Review.

Several tools have been used to assess muscular stiffness. Myotonometry stands out as an accessible, handheld, and easy to use tool. The purpose of this review was to summarize the psychometric properties and methodological considerations of myotonometry and its applicability in assessing scapular muscles. Myotonometry seems to be a reliable method to assess several muscles stiffness, as trapezius. This method has been demonstrated fair to moderate correlation with passive stiffness measured by shear wave elastography for several muscles, as well as with level of muscle contraction, pinch and muscle strength, Action Research Arm Test score and muscle or subcutaneous thickness. Myotonometry can detect scapular muscles stiffness differences between pre- and post-intervention in painful conditions and, sometimes, between symptomatic and asymptomatic subjects.

The positive relationship between Indigenous language use and community-based well-being in four Nahua ethnic groups in Mexico.

OBJECTIVE: In this article, we examine the relationship between Indigenous language use and community-based well-being among four Nahua ethnic groups in Mexico, taking into account the role of positive emotions related to speaking the heritage language as a mediator of the influence of its use in the family domain on community-based well-being. METHOD: We employ an emic community-based well-being scale, a second scale measuring the use of Nahuatl and Spanish across different domains of social life, and a third scale measuring positive emotions related to the use of Nahuatl in order to examine the relationship between Nahuatl use and community-based well-being, in a sample (N = 552) of Indigenous Nahua participants (55.4% female, Mage = 37.9, SD = 18.3) coming from four different regions of Mexico. RESULTS: Results from the mediation analysis revealed that the relation between the frequency of Nahuatl use and community-based well-being in the total sample is partially mediated by experiencing positive emotions related with Nahuatl use. Furthermore, the relation between Nahuatl use and community-based well-being was also found to be moderated by group membership. CONCLUSIONS: Our study confirms that the role of heritage language use for Nahua communities in Mexico is beneficial and that this effect is also significant in communities strongly affected by language loss and assimilation. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Self-image, self-esteem and depression in children and adolescents with and without obesity.

INTRODUCTION: In Mexico, the prevalence of childhood obesity is 35%, and it continues to increase. OBJECTIVE: To determine the correlation between self-image, self-esteem and depression in children aged 8 to 14 years with and without obesity. METHODS: Cross-sectional, comparative study of 295 children: 116 with overweight/obesity (group 1) and 179 with normal weight (group 2). Body mass index, scholarship, school achievement, school problems, socioeconomic status, self-image (current, desired), satisfaction, self-esteem and presence of depression were recorded. Descriptive statistics, Spearman's rho and Mann-Whitney's U-test were used; a p-value ≤ 0.05 was considered significant. RESULTS: In group 1, 53.4% perceived themselves as with normal weight, and in 77.6%, the desired self-image was normal weight; 67.2% wanted to be slimmer; in 53.4%, self-esteem was high, and 75.9% had no depression. In group 2, current self-image was normal weight in 79.3%, and the desired self-image was normal weight in 85.5%; 35.2% wanted to be slimmer; self-esteem was high in 49.7% and 77.1% had no depression. Significant correlations were observed for self-esteem-depression (r = 0.228) and self-esteem-socioeconomic status (r = 0.130). CONCLUSIONS: Current self-image and body satisfaction are different with and without obesity. The relationship between self-esteem and depressive symptoms begins at school age.

INTRODUCCIÓN: La obesidad infantil es un problema de salud pública mundial. En México, la prevalencia es de 35 % y continúa ascendiendo. OBJETIVO: Determinar la correlación entre autoimagen, autoestima y depresión en niños de ocho a 14 años con y sin obesidad. MÉTODOS: Estudio transversal comparativo de 295 niños: 116 niños con sobrepeso u obesidad (grupo 1) y 179 sin obesidad (grupo 2). Se registró índice de masa corporal, escolaridad, aprovechamiento escolar, conflictos escolares, nivel socioeconómico, autoimagen (actual, deseada), satisfacción, autoestima y presencia de depresión. Se utilizó estadística descriptiva, rho de Spearman y U de Mann-Whitney; p ≤ 0.05 se consideró significativa. RESULTADOS: En el grupo 1, 53.4 % de los niños se autopercibió con normopeso y en 77.6 % la autoimagen deseada era normopeso; 67.2 % deseaba ser más delgado; en 53.4 % la autoestima era elevada; 75.9 % se observó sin depresión. En el grupo 2, en 79.3 % la autoimagen actual era normopeso y la autoimagen deseada en 85.5 % fue normopeso; 35.2 % deseaba ser más delgado; la autoestima era elevada en 49.7 % y 77.1 % no presentaba depresión. Se identificaron correlaciones significativas en autoestima-depresión (r = 0.228) y autoestima-nivel socioeconómico (r = 0.130). CONCLUSIONES: La autoimagen actual y la satisfacción corporal son diferentes en niños y adolescentes con y sin obesidad. La relación de la autoestima y síntomas depresivos inicia desde la edad escolar.

Radiological and histopathological assessment of bone infiltration in soft tissue sarcomas.

BACKGROUND: Deep soft tissue sarcomas are frequently in contact with bone. The therapeutic decision of a composite resection strategy may be challenging, which is usually based on clinical and radiological criteria. The aims of the study were to evaluate the overall frequency of bone and periosteal infiltration in these patients in whom composite resection was indicated, and evaluate the role of magnetic resonance imaging and bone scintigraphy in this scenario. METHODS: Forty-nine patients with a composite surgical resection (soft tissue sarcoma and bone), treated at a single institution between 2006 and 2018, were retrospectively included. Presurgical planning of the resection limits was based on clinical and imaging findings (magnetic resonance imaging and bone scintigraphy). Magnetic resonance imaging was performed in all patients (100%) and bone scintigraphy in 41 (83.7% of the cases). According to magnetic resonance imaging results, patients were divided into two groups: Group A, in which the tumor is adjacent to the bone without evidence of infiltration (n = 24, 48,9%), and Group B, patients with evidence of bone involvement by magnetic resonance imaging (n = 25, 51,1%). BS showed a pathological deposit in 28 patients (68.3%). Histological analysis of the resection specimen was preceded to identify bone and periosteal infiltration. For the analysis of the diagnostic validity of imaging tests, histological diagnosis was considered as the gold standard in the evaluation of STS bone infiltration. RESULTS: Histological bone infiltration was identified in 49% of patients and isolated periosteal infiltration in 14.3%. In terms of diagnostic accuracy, magnetic resonance imaging and bone scintigraphy sensitivity values were 92% and 90%, and their specificity values were 91.7% and 52.4%, respectively. CONCLUSIONS: The incidence of bone and periosteal infiltration of soft tissue sarcomas in contact with bone is high. Presurgical bone assessment by MRI has proven to be a sensitive and specific tool in the diagnosis of bone infiltration. Due to its high negative predictive value, BS is a useful test to rule out it. In those cases, in which there is suspicion of bone infiltration not confirmed by MRI, new diagnostic protocols should be established in order to avoid inappropriate resections.

Eribulin activity in soft tissue sarcoma monolayer and three-dimensional cell line models: could the combination with other drugs improve its antitumoral effect?

BACKGROUND: Eribulin has shown antitumour activity in some soft tissue sarcomas (STSs), but it has only been approved for advanced liposarcoma (LPS). METHODS: In this study, we evaluated the effect of eribulin on proliferation, migration and invasion capabilities in LPS, leiomyosarcoma (LMS) and fibrosarcoma (FS) models, using both monolayer (2D) and three-dimensional (3D) spheroid cell cultures. Additionally, we explored combinations of eribulin with other drugs commonly used in the treatment of STS with the aim of increasing its antitumour activity. RESULTS: Eribulin showed activity inhibiting proliferation, 2D and 3D migration and invasion in most of the cell line models. Furthermore, we provide data that suggest, for the first time, a synergistic effect with ifosfamide in all models, and with pazopanib in LMS as well as in myxoid and pleomorphic LPS. CONCLUSIONS: Our results support the effect of eribulin on LPS, LMS and FS cell line models. The combination of eribulin with ifosfamide or pazopanib has shown in vitro synergy, which warrants further clinical research.