SETD8 inhibition targets cancer cells with increased rates of ribosome biogenesis.

SETD8 is a methyltransferase that is overexpressed in several cancers, which monomethylates H4K20 as well as other non-histone targets such as PCNA or p53. We here report novel SETD8 inhibitors, which were discovered while trying to identify chemicals that prevent 53BP1 foci formation, an event mediated by H4K20 methylation. Consistent with previous reports, SETD8 inhibitors induce p53 expression, although they are equally toxic for p53 proficient or deficient cells. Thermal stability proteomics revealed that the compounds had a particular impact on nucleoli, which was confirmed by fluorescent and electron microscopy. Similarly, Setd8 deletion generated nucleolar stress and impaired ribosome biogenesis, supporting that this was an on-target effect of SETD8 inhibitors. Furthermore, a genome-wide CRISPR screen identified an enrichment of nucleolar factors among those modulating the toxicity of SETD8 inhibitors. Accordingly, the toxicity of SETD8 inhibition correlated with MYC or mTOR activity, key regulators of ribosome biogenesis. Together, our study provides a new class of SETD8 inhibitors and a novel biomarker to identify tumors most likely to respond to this therapy.

Influence of the kinesiophobia and its pain intensity relationship in subjects with onychocryptosis.

Background: Onychocryptosis is a nail deformity that occurs when the side of the nail grows into soft tissue, which causes pain, sepsis and the formation of granulation. The aim of the study was to evaluate and compare different levels of kinesiophobia in subjects with onychocryptosis before and after surgery to eliminate this condition. Methods: A descriptive and observational study was conducted with a total sample size of 25 subjects with a mean age of 40.96 ± 18.25 years. The pretest sample was composed of the 25 subjects before the surgical treatment of onychocryptosis and the posttest sample was composed of the same 25 subjects after the surgical treatment of onychocryptosis. Kinesiophobia levels and total scores were self-reported using the Spanish version of the Tampa Scale for Kinesiophobia (TSK-11). Results: The Wilcoxon test for related samples and the Mann-Whitney U test for independent samples were used to compare the results before and after the surgical treatment. It was observed that in all the items as well as in the total score, there were significant changes in the levels of kinesiophobia, after the surgical intervention for onychocryptosis (P < 0.05) compared to the levels before surgery, except for items 4 and 11 in which there were no significant differences (P > 0.05). Before surgery, 0% of the subjects with onychocryptosis reported not being afraid of movement, 16% reported mild fear of movement, 8% reported moderate fear of movement and 76% of the subjects with onychocryptosis reported severe and maximum fear of movement. On the other hand, 100% of the subjects did not report kinesiophobia after surgical treatment (P < 0.01). Conclusions: The levels of kinesiophobia were higher in the subjects with onychocryptosis compared to the subjects after having undergone surgery to eliminate onychocryptosis.

Use of an age-simulation suit as an empathy-building method for dental students: a pre-post study.

Background: The aging of the population highlights the need to establish empathetic connections with older adults. To achieve this, age simulation suits have been designed, allowing users to experience the physical limitations associated with aging. This study aimed to evaluate the experience of dental students with these devices, using psychometric tools to measure the impact on their understanding and empathy. Methods: A pre/post-test study was conducted with the participation of 63 dental students from Rey Juan Carlos University who were fitted with an age simulation suit and asked to perform different tasks. Psychometric tools were used to assess specific parameters. Empathy was measured using the Jefferson Empathy Scale, emotional intelligence was assessed with the Trait Meta-Mood Scale-24 (TMMS-24), and the emotional attention dimension was analyzed using the Positive and Negative Affect Schedule (PANAS). Results: The scores on the Jefferson Empathy Scale significantly improved from 88.44 ± 6.8 to 91.06 ± 10.11 after using the simulation suit (P < 0.026). Pearson's product moment correlation analysis showed no significant positive association or correlation between age and scores from the three questionnaires. In the rest, a positive and significant correlation was observed (P < 0.0001). Conclusions: Age simulation activities effectively enhance empathy among dental students. However, more studies are needed to foster positive attitudes toward aging and prevent negative stereotypes.

Investigating the Role of Fat Mass and Obesity-Associated (FTO) Single Nucleotide Polymorphisms and Methylation in Breast Cancer.

Background Fat mass and obesity-associated (FTO) protein is an mRNA demethylase enzyme essential for active genome regulation. The FTO gene codes for a protein that is part of the methylosome complex and has a regulatory role in cancer development. Some studies have shown a relationship between FTO and cancer, where single nucleotide polymorphisms (SNPs) may have some impact on cancer risk. The present study aimed to evaluate the risk of FTO polymorphisms rs9939609, rs1477196, and rs9930506; analyze the methylation status of FTO promoters among Mexican women with breast cancer (BC); and investigate by in silico analysis the methylation status in the region near these polymorphisms. Methods A total of 157 BC patients and 137 healthy controls were genotyped for rs9939609, rs1477196, and rs9930506 FTO polymorphisms by TaqMan SNP Genotyping Assays. Promoter methylation was analyzed by sodium bisulfite and methylation-specific polymerase chain reaction (MSP) for 78 tissue samples. An in silico analysis using The Cancer Genome Atlas Program (TCGA) database was employed to investigate the methylation state in promoter and near polymorphism locations and its relation to survival. Results The AG genotype of FTO rs9930506 was associated with BC protection (P= 0.0025; adjusted OR, 0.27; 95% CI: 0.10-0.70). rs9939609 and rs1477196, according to the results of the present study, had no relation to BC. Promoter methylation status assays by MSP revealed no changes in methylation in BC or healthy tissues. Trying to know more about the methylation in promoters and near polymorphisms' relation to survival, we performed an in silico analysis. Bioinformatics analysis showed a correlation between poor survival and methylation near polymorphisms but not with methylation in the promoter region. Conclusions The AG genotype rs9930506 has a protective function against BC. Whereas high methylation near polymorphisms was related to lower survival, the hypomethylated promoter region does not impact survival.

Effectiveness of simultaneous bilateral visual diaphragm biofeedback under low back pain: influence of age and sex.

Introduction: The aim of the present study was to determine the effectiveness of simultaneous bilateral visual diaphragm biofeedback (BFB) from ultrasonography in conjunction with inspiratory muscle training (IMT) on diaphragmatic thickness during normal breathing and respiratory and clinical outcomes in patients with non-specific low back pain (NSLBP) and determine the influence of age and sex. Methods: A single-blind randomized clinical trial was carried out (NCT04582812). A total sample of 96 patients with NSLBP was recruited and randomized by sex-based stratification into IMT (n = 48) and BFB + IMT (n = 48) interventions over 8 weeks. Bilateral diaphragmatic thickness at maximum inspiration (Tins) and expiration (Texp), respiratory pressures, lung function, pain intensity, bilateral pressure pain threshold (PPT), disability, and quality of life were measured at baseline and after 8 weeks. Results: The BFB + IMT group showed significant differences (p < 0.05) with increased left hemidiaphragm thickness at Tins and Tins-exp (d = 0.38-053), and right and left PPT (d = 0.71-0.74) versus the IMT group. The interaction with sex was statistically significant (p = 0.007; F(1,81) = 7.756; ηp 2 = 0.087) and higher left hemidiaphragm thickness at Tins was predicted by the BFB + IMT group (R 2 = 0.099; ß = 0.050; F(1,82) = 8.997; p = 0.004) and male sex (R 2 = 0.079; ß = 0.045; F(1,81) = 7.756;p = 0.007). Furthermore, greater left hemidiaphragm thickness at Tins-exp was predicted by younger age (R 2 = 0.052; ß = -0.001; F(1,82) = 4.540; p = 0.036). Discussion: The simultaneous bilateral visual diaphragm biofeedback by ultrasonography in conjunction with IMT was effective in both increasing the left diaphragmatic thickness during inspiration, which was positively influenced and predicted by male sex and younger age, and increasing the bilateral PPT of the paraspinal muscles in patients with NSLBP.

Impact of SARS-CoV-2 infection on the cognitive functioning of patients institutionalized in nursing homes.

BACKGROUND: COVID-19 disease affected the cognitive level of institutionalized patients in nursing homes, especially in the older subjects regardless of gender. This study aims to assess cognitive impairment using the Mini-Mental State Examination (MMSE) before and after COVID-19 infection, and to determine whether these changes varied based on gender. METHODS: A pre- and post-COVID-19 study was conducted, involving 68 geriatric patients (34 men and 34 women) from two nursing homes. Cognitive impairment was assessed using the MMSE. RESULTS: COVID-19 infection had a notable impact on the cognitive health of older adults residing in nursing homes, primarily attributed to the social isolation they experienced. This effect was more pronounced in older individuals. A comparison of the MMSE results by gender before and after contracting COVID-19 revealed significant differences in attention and calculation, with women obtaining the worst score before the virus. However, following their recovery from the virus, men demonstrated significantly lower scores in time and space orientation and evocation. CONCLUSION: COVID-19 has led to a decline in cognitive functioning, significantly worsening the mental state of older individuals, even after recovery from the virus. Consequently, it is crucial to implement proactive measures to prevent isolation and safeguard the cognitive well-being of this vulnerable population.

Impact of Lymphedema on Foot-Health-Related Quality of Life: A Case-Control Investigation.

OBJECTIVE: To evaluate the foot-health-related quality of life in individuals with versus without lower-limb lymphedema. METHODS: A case-control study was carried out in an academic clinic in Lisbon, Portugal. Eighty participants (40 controls and 40 with lymphedema) were included in the study. The researchers examined sociodemographic and clinical data and foot-health-related quality of life in both groups. In the group with lymphedema, lower-limb lymphedema was also characterized. RESULTS: Individuals with lower-limb lymphedema had significantly lower scores on all dimensions of the Foot Health Status Questionnaire in comparison with the control group. CONCLUSIONS: Individuals with lower-limb lymphedema appear to have a poorer foot-health-related quality of life than the general population.

Moral Distress Healthcare Providers in Spain: Observational Study.

Objective: To evaluate the moral distress (MD)in health professionals of pediatric and adult units to show how the complexity of care in the pediatric field causes the professionals who carry out their activity in these units to present a higher level of moral distress and a worse climate ethical. Design: Observational study with health professionals who currently work in Spanish Hospitals. Methods: A 58-item questionnaire was electronically distributed which included sociodemographic and employment characteristics, the Spanish version of the Measure of Moral Unrest for Healthcare Professionals (MMD-HP-SPA) and the Hospital Ethical Climate Survey (HECS). Results: A total of 169 health professionals completed the questionnaire. The moral distress was significantly higher among nurses than among physicians and nursing assistant care technicians. Focusing on the type of unit, moral distress it was only significantly higher for those physicians treating adult patients compared to those treating pediatric patients. Regarding the total score of the HECS survey, the medical group shows higher scores compared to the nursing group. Conclusion: Statistically significant differences have been found only in the medical group that treats adult patients, presenting a higher level of moral unrests than the pediatrician group. The MMD-HP-SPA questionnaire is a valid and useful instrument to detect MD in our hospital units in order to be able to implement strategies/interventions that improve the ethical climate and other factors that can mitigate and prevent this MD.

A Secondary Analysis of Gender Respiratory Features for Ultrasonography Bilateral Diaphragm Thickness, Respiratory Pressures, and Pulmonary Function in Low Back Pain.

The aim of the present study was to determine the gender respiratory differences of bilateral diaphragm thickness, respiratory pressures, and pulmonary function in patients with low back pain (LBP). A sample of 90 participants with nonspecific LBP was recruited and matched paired by sex (45 women and 45 men). Respiratory outcomes included bilateral diaphragm thickness by ultrasonography, respiratory muscle strength by maximum inspiratory (MIP) and expiratory (MEP) pressures, and pulmonary function by forced expiratory volume during 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC spirometry parameters. The comparison of respiratory outcomes presented significant differences (p < 0.001), with a large effect size (d = 1.26-1.58) showing means differences (95% CI) for MIP of -32.26 (-42.99, -21.53) cm H2O, MEP of -50.66 (-64.08, -37.25) cm H2O, FEV1 of -0.92 (-1.18, -0.65) L, and FVC of -1.00 (-1.32, -0.69) L, with lower values for females versus males. Gender-based respiratory differences were presented for maximum respiratory pressures and pulmonary function in patients with nonspecific LBP. Women presented greater inspiratory and expiratory muscle weakness as well as worse lung function, although these differences were not linked to diaphragm thickness during normal breathing.

Reliability and validity of the Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5) test for post-traumatic stress disorder in mental health nurses in Spain.

BACKGROUND: Here we report the reliability and test/re-test validity of a Castillan version of the PCL-5 (PCL5-C) in mental health nurses. METHODS: A sample of 52 consecutive nurses was recruited from two psychiatric hospitals and four psychiatrists units of general hospitals in Madrid, Spain. RESULTS: We detected high internal consistency for the study questionnaire at the test assessment (n = 52) and at retest 0.929 and 0.935, respectively, by total Cronbach's α. All of the items at test and re-test correlated with the total score. CONCLUSIONS: Reproducibility analysis showed excellent test/re-test reliability for the total score and each item. Based on our findings, we conclude that the PCL5-C is a valid and reliable questionnaire when applied among Spanish mental health nurses population.

Impact of ankylosing spondylitis on foot health and quality of life: an observational case-control study.

Background: Ankylosing spondylitis (AS) is a chronic, inflammatory, and autoimmune disease. This condition primarily affects the axial skeleton and presents direct foot involvement, such as Achilles enthesitis or plantar fascia involvement. Objective: This study aimed to investigate the impact of foot health on the quality of life of individuals with AS compared to a control group without AS. Materials and methods: A sample of 112 subjects was recruited, with a mean age of 46.80 ± 10.49 years, divided into two groups: 56 individuals with AS (cases) and 56 individuals without AS (controls). Demographic data were collected, and the scores obtained in the Foot Health Status Questionnaire domains were recorded. Results: Of the participants, 27.79% (N = 30) were men and 73.21% (N = 82) were women. The mean age in the group was 46.80 ± 10.49. Significant differences (p < 0.05) were found in the domains of foot function, foot pain, footwear, overall foot health, general health-related physical activity, and social capacity between the AS group and the control group. Conclusion: Individuals with AS exhibited a decreased quality of life, as indicated by their Foot Health Status Questionnaire scores.

Resilience and psychological factors among dentistry students who received face-to-face lectures during the COVID-19 pandemic.

BACKGROUND: This research evaluated whether the relationships between factors of resilience, self-esteem, depression, and anxiety in dental students with changes in teaching and learning methods. We also studied the psychological impact of face-to-face lectures during the COVID-19 pandemic. METHODS: This cross-sectional descriptive study used Google Forms to collect data with the Rosenberg Self-Esteem Scale (RSE), Connor-Davidson Risk Resilience Scale (CD-RISC), Beck Anxiety Inventory (BAI), and Beck Depression Inventory (BDI and BDI-II). An open-ended question was also asked about important learning difficulties. RESULTS: The analysis revealed very high levels of resilience (30.23 ± 5.84), self-esteem in the normal range (29.08 ± 4.03), minimal depression levels (12.32 ± 8.05), and low anxiety levels (17.20 ± 12.41). There were no significant differences between sociodemographic variables ranges in regard to all psychological questionnaires. No high levels of depression and anxiety were found. CONCLUSIONS: The levels were low compared to other studies in which online teaching was used, which is explained by the fact that the students retained adequate resilience and self-esteem thanks to being able to contact teachers and, above all, their own peers.

Respiratory syncytial virus incidence and typing in the last six seasons in the north of Spain (Asturias). Genetic characterization during the SARS-CoV-2 pandemic.

Respiratory syncytial virus is associated with lower respiratory tract infections. As several types and genotypes can circulate at the same time, genomic characterization is important for timely epidemiological control and treatment measures. In the last 6 seasons (2017-2023), 191 236 nasopharyngeal swabs were processed for respiratory viruses to determine the etiology of acute respiratory infections, describe the incidence and distribution of RSV types and enrich the data of epidemiological molecular studies on RSV in Spain. The incidence of RSV reached 7% in the pre-pandemic season. RSV was most frequent in children under 5 years of age (12.6%), but was also significant in those over 70 years of age (5.63%). The measures taken to control SARS-CoV-2 infection were useful for RSV control and the incidence decreased to 1.8%, but caused a change in the types. Pre-pandemic, the majority circulating types were RSV-B/RSV-B/RSV-A and in the pandemic it was RSV-B/RSV-B. In the last season, RSV-B and RSV-A were detected in the same proportion. Genetic characterization showed three new clades. This has been taken into account to understand the epidemiology as well as the development of therapeutic and preventive strategies.

The relationship of kinesiophobia in patients with lymphedema: a case-control investigation.

Introduction: Kinesiophobia and lymphedema appear to be related conditions, and it is important to understand this relationship, as many of the symptoms and comorbidities presented by individuals with lower limb lymphedema are prevented and treated through movement, thus constituting kinesiophobia as a barrier to intervention. The objective of this study is, therefore, to evaluate and analyze the kinesiophobic beliefs reported by individuals with and without lower limb lymphedema, regarding the agreement, severity and differences found, and to establish levels of kinesiophobia. Methods: A case-control study with a total sample of 80 participants (40 with lower limb lymphedema and 40 without) was performed. Both groups (with and without lymphedema) were characterized anthropologically, sociodemographically, and clinically. In the case group, lymphedema was evaluated. Participants in both groups completed the Tampa Scale for Kinesiophobia - 13 items (TSK-13). Results: Individuals with lower limb lymphedema had higher TSK-13 scores than their matched group without lymphedema. The items belonging to the activity avoidance subscale had the highest agreement and score in both groups. Differences between groups were mainly established for items belonging to the somatic focus subscale, showing that individuals with lower limb lymphedema have kinesiophobic beliefs related to the perceived severity of their lymphedema. The prevalence of kinesiophobia was increased in both groups, but the severity was mild. Conclusions: Considering the apparent tendency of people with lower limb lymphedema to present kinesiophobia and movement-limiting beliefs regarding the condition, greater attention should be paid to its assessment, prevention and treatment from a multidisciplinary and multimodal perspective, which takes into account the multiplicity of factors inherent to kinesiophobia and lymphedema and thus reduce their impact on the management of lymphedema.

Influence of quality of life related to perceived foot health between in a rural an urban population: A case-control research.

Foot problems are very common in the community. Studies indicate that between 18% and 63% of people have foot pain or stiffness and that foot problems have a large impact on people's functional decline and a significant detrimental impact on measures of quality of life related to health. The general objective of this research was to compare foot health in people from the rural population compared to people from the urban population and its relationship with quality of life. A case-control descriptive study was developed with a sample of 304 patients, 152 patients from the rural population and 152 patients from the urban population. Quality of life was measured through the SF-36 Health Questionnaire in its Spanish version. The rural population group had a mean age of 46.67 ± 13.69 and the urban population group 49.02 ± 18.29. Regarding the score of the lowest levels of quality of life related to foot problems, the rural population group compared to the urban population group showed: for body pain (52.21 ± 30.71 vs. 67.80 ± 25.28, p < 0.001); and for mental health (69.58 ± 18.98 vs. 64.60 ± 14.88, p < 0.006). Differences between groups were analysed using Student's t-test for independent samples, which showed statistical significance (p < 0.05). This research offers evidence that the rural population presents better levels of mental health and lower levels of bodily pain in the domains of the SF-36 Health Questionnaire comparing with the urban population.

Mesenchymal Stromal Cells Derived from Dental Tissues: Immunomodulatory Properties and Clinical Potential.

Mesenchymal stem/stromal cells (MSCs) are multipotent cells located in different areas of the human body. The oral cavity is considered a potential source of MSCs because they have been identified in several dental tissues (D-MSCs). Clinical trials in which cells from these sources were used have shown that they are effective and safe as treatments for tissue regeneration. Importantly, immunoregulatory capacity has been observed in all of these populations; however, this function may vary among the different types of MSCs. Since this property is of clinical interest for cell therapy protocols, it is relevant to analyze the differences in immunoregulatory capacity, as well as the mechanisms used by each type of MSC. Interestingly, D-MSCs are the most suitable source for regenerating mineralized tissues in the oral region. Furthermore, the clinical potential of D-MSCs is supported due to their adequate capacity for proliferation, migration, and differentiation. There is also evidence for their potential application in protocols against autoimmune diseases and other inflammatory conditions due to their immunosuppressive capacity. Therefore, in this review, the immunoregulatory mechanisms identified at the preclinical level in combination with the different types of MSCs found in dental tissues are described, in addition to a description of the clinical trials in which MSCs from these sources have been applied.

Family adaptation in families of individuals with Down syndrome from 12 countries.

Our current understanding of adaptation in families of individuals with Down syndrome (DS) is based primarily on findings from studies focused on participants from a single country. Guided by the Resiliency Model of Family Stress, Adjustment, and Adaptation, the purpose of this cross-country investigation, which is part of a larger, mixed methods study, was twofold: (1) to compare family adaptation in 12 countries, and (2) to examine the relationships between family variables and family adaptation. The focus of this study is data collected in the 12 countries where at least 30 parents completed the survey. Descriptive statistics were generated, and mean family adaptation was modeled in terms of each predictor independently, controlling for an effect on covariates. A parsimonious composite model for mean family adaptation was adaptively generated. While there were cross-country differences, standardized family adaptation mean scores fell within the average range for all 12 countries. Key components of the guiding framework (i.e., family demands, family appraisal, family resources, and family problem-solving communication) were important predictors of family adaptation. More cross-country studies, as well as longitudinal studies, are needed to fully understand how culture and social determinants of health influence family adaptation in families of individuals with DS.

Uncovering the relationship between community participation and socio-political control among the migrant population.

Prior research on psychological empowerment has found that community participation is associated with socio-political control, which takes place when people perceive control in their socio-political contexts. However, the process by which this relationship occurs remains an understudied area for migrants. This study aims to: (a) analyze the differences in socio-political control, critical thinking, and ethnic identity according to membership in migrant community-based organizations; and (b) propose a predictive model of socio-political control. A total of 239 first-generation migrants living in northern Italy completed a questionnaire (48.4% belonged to a migrant community-based organization). Members were found to have higher levels than nonmembers in all the variables. A moderated mediation model was proposed, whereby ethnic identity was a mediator between community participation and socio-political control, and critical thinking was a negative moderator between ethnic identity and socio-political control. Practical implications for enhancing socio-political control among migrants in receiving societies are discussed.

Orthopaedic Simulation of a Morton's Extension to Test the Effect on Plantar Pressures of Each Metatarsal Head in Patients without Deformity: A Pre-Post-Test Study.

BACKGROUND: the area beneath the metatarsal heads is a common location of foot pain, which is often associated with high plantar pressures. The aim of this study was to determine the effect of the application of a Morton's extension on the pressure in the metatarsal bones of the foot using a pressure platform. METHODS: twenty-five subjects without musculoskeletal pathology were selected for this study, and an experiment was conducted with them as the subjects, before and after application of a Morton's extension. The foot regions were divided into the forefoot (transversely subdivided into six areas corresponding to the first, second, third, fourth, and fifth metatarsal heads, and the hallux), midfoot, and rearfoot, and then the maximum and average pressures exerted at each region were measured before and after placing a Morton's extension. MAIN FINDINGS: we found a pressure reduction, with a p-value less than (p < 0.05), in the head of the second and third metatarsals in statics and dynamics. CONCLUSIONS: we can conclude that the Morton's extension produces a variation in plantar pressures on the lesser metatarsals. The application of a Morton's extension may be beneficial for the management of forefoot pathology. This study will help clinicians consider various tools to treat forefoot disorders. NCT05879094 (ClinicalTrial.gov (accessed on 18 May 2023)).