Engaging and following physical injury survivors at risk for developing posttraumatic stress disorder symptoms: A 25 site US national study.

INTRODUCTION: Early intervention for patients at risk for Posttraumatic Stress Disorder (PTSD) relies upon the ability to engage and follow trauma-exposed patients. Recent requirements by the American College of Surgeons Committee on Trauma (College) have mandated screening and referral for patients with high levels of risk for the development of PTSD or depression. Investigations that assess factors associated with engaging and following physically injured patients may be essential in assessing outcomes related to screening, intervention, and referral. METHODS: This investigation was a secondary analysis of data collected as part of a United States level I trauma center site randomized clinical trial. All 635 patients were ages ≥18 and had high PTSD symptom levels (i.e., DSM-IV PTSD Checklist score ≥35) at the time of the baseline trauma center admission. Baseline technology use, demographic, and injury characteristics were collected for patients who were followed up with over the course of the year after physical injury. Regression analyses were used to assess the associations between technology use, demographic and injury characteristics, and the attainment of follow-up outcome assessments. RESULTS: Thirty-one percent of participants were missing one or more 3-, 6- or 12-month follow-up outcome assessments. Increased risk of missing one or more outcome assessments was associated with younger age (18-30 versus ≥55 Relative Risks [RR] = 1.78, 95 % Confidence Interval [CI] = 1.09, 2.91), lack of cell phone (RR = 1.32, 95 % CI = 1.01, 1.72), no internet access (RR = 1.47, 95 % CI = 1.01, 2.16), public versus private insurance (RR = 1.47, 95 % CI = 1.12, 1.92), having no chronic medical comorbidities (≥4 versus none, RR = 0.28, 95 % CI = 0.20, 0.39), and worse pre-injury mental health function (RR = 0.99, 95 % CI = 0.98, 0.99). CONCLUSIONS: This multisite investigation suggests that younger and publicly insured and/or uninsured patients with barriers to cell phone and internet access may be particularly vulnerable to lapses in trauma center follow-up. Clinical research informing trauma center-based screening, intervention, and referral procedures could productively explore strategies for patients at risk for not engaging and adhering to follow-up care and outcome assessments.

Can stepped collaborative care interventions improve post-traumatic stress disorder symptoms for racial and ethnic minority injury survivors?

Objectives: No large-scale randomized clinical trial investigations have evaluated the potential differential effectiveness of early interventions for post-traumatic stress disorder (PTSD) among injured patients from racial and ethnic minority backgrounds. The current investigation assessed whether a stepped collaborative care intervention trial conducted at 25 level I trauma centers differentially improved PTSD symptoms for racial and ethnic minority injury survivors. Methods: The investigation was a secondary analysis of a stepped wedge cluster randomized clinical trial. Patients endorsing high levels of distress on the PTSD Checklist (PCL-C) were randomized to enhanced usual care control or intervention conditions. Three hundred and fifty patients of the 635 randomized (55%) were from non-white and/or Hispanic backgrounds. The intervention included care management, cognitive behavioral therapy elements and, psychopharmacology addressing PTSD symptoms. The primary study outcome was PTSD symptoms assessed with the PCL-C at 3, 6, and 12 months postinjury. Mixed model regression analyses compared treatment effects for intervention and control group patients from non-white/Hispanic versus white/non-Hispanic backgrounds. Results: The investigation attained between 75% and 80% 3-month to 12-month follow-up. The intervention, on average, required 122 min (SD=132 min). Mixed model regression analyses revealed significant changes in PCL-C scores for non-white/Hispanic intervention patients at 6 months (adjusted difference -3.72 (95% CI -7.33 to -0.10) Effect Size =0.25, p<0.05) after the injury event. No significant differences were observed for white/non-Hispanic patients at the 6-month time point (adjusted difference -1.29 (95% CI -4.89 to 2.31) ES=0.10, p=ns). Conclusion: In this secondary analysis, a brief stepped collaborative care intervention was associated with greater 6-month reductions in PTSD symptoms for non-white/Hispanic patients when compared with white/non-Hispanic patients. If replicated, these findings could serve to inform future American College of Surgeon Committee on Trauma requirements for screening, intervention, and referral for PTSD and comorbidities. Level of evidence: Level II, secondary analysis of randomized clinical trial data reporting a significant difference. Trial registration number: NCT02655354.

The Application of Shear Wave Elastography to Determine the Elasticity of the Levator Ani Muscle and Vaginal Tissue in Patients With Pelvic Organ Prolapse.

OBJECTIVES: The changes of the extracellular matrix of the connective tissue have significantly contributed to the incidence of pelvic organ prolapse (POP). It seems reasonable that sonoelastography could be a useful tool to evaluate the elasticity of pelvic floor tissue in patients with POP and compare it to those without POP. The main aim of this pilot study was to determine if there are differences in the elasticity of the levator ani muscle (LAM) and vaginal tissue between patients with and without POP. METHODS: Prospective observation study, including 60 patients (30 with POP and 30 without POP). Sonoelastography was performed to evaluate the elasticity (in kilopascals, kPa) of the following regions of interest: vagina at the level of middle third of the urethra; vagina at the level of the bladder trigone; vagina in the anterior and posterior fornix; vagina at the level of middle third of the anorectal canal; posterior third of the LAM. RESULTS: A total of 60 patients completed the study (30 with POP, 30 without POP). In the POP group, 18/30 (60%) had an anterior vaginal wall prolapse, 3/30 (10%) a uterine prolapse, 15/30 (50%) a rectocele, and 6/30 (20%) a enterocele. Patients with POP had higher elasticity in all anatomical study areas, with statistically significant differences in the anterior fornix (13.6 vs 11.2 kPa; P: .012). A multiple regression (controlling age, menopausal stage, and parity) allowed to detect statistically significant differences in the elasticity of the middle third of the urethra (P: .03) and the middle third of the anorectal canal (P: .019). CONCLUSION: It is possible to evaluate the elasticity of the LAM and vaginal tissue using sonoelastography, detecting a higher elasticity in patients with POP than in those without POP.

Stepped collaborative care versus American College of Surgeons Committee on Trauma required screening and referral for posttraumatic stress disorder: Clinical trial protocol.

BACKGROUND: Each year in the US, approximately 1.5-2.5 million individuals are so severely injured that they require inpatient hospital admissions. The American College of Surgeons Committee on Trauma (College) now requires that trauma centers have in place protocols to identify and refer hospitalized patients at risk injury psychological sequelae. Literature review revealed no investigations that have identified optimal screening, intervention, and referral procedures in the wake of the College requirement. METHODS: The single-site pragmatic trial investigation will individually randomize 424 patients (212 intervention and 212 control) to a brief stepped care intervention versus College required mental health screening and referral control conditions. Blinded follow-up interviews at 1-, 3-, 6-, and 12-months post-injury will assess the symptoms of PTSD and related comorbidity for all patients. The emergency department information exchange (EDIE) will be used to capture population-level automated emergency department and inpatient utilization data for the intent-to-treat sample. The investigation aims to test the primary hypotheses that intervention patients will demonstrate significant reductions in PTSD symptoms and emergency department/inpatient utilization when compared to control patients. The study incorporates a Rapid Assessment Procedure-Informed Clinical Ethnography (RAPICE) implementation process assessment. CONCLUSIONS: The overarching goal of the investigation is to advance the sustainable delivery of high-quality trauma center mental health screening, intervention, and referral procedures for diverse injury survivors. An end-of-study policy summit will harness pragmatic trial data to inform the capacity for US trauma centers to implement high-quality acute care mental health screening, intervention and referral services for diverse injured patient populations. TRIAL REGISTRATION: Clinicaltrials.govNCT05632770.

Deubiquitinase USP9X loss sensitizes renal cancer cells to mTOR inhibition.

Mammalian target of rapamycin (mTOR) is a central regulator of mammalian metabolism and physiology. Aberrant hyperactivation of the mTOR pathway promotes tumor growth and metastasis, and can also promote tumor resistance to chemotherapy and cancer drugs; this makes mTOR an attractive cancer therapeutic target. mTOR inhibitors have been approved to treat cancer; however, the mechanisms underlying drug sensitivity remain poorly understood. Here, whole exome sequencing of three chromophobe renal cell carcinoma (chRCC) patients with exceptional mTOR inhibitor sensitivity revealed that all three patients shared somatic mutations in the deubiquitinase gene USP9X. The clonal characteristics of the mutations, which were amassed by studying multiple patients' primary and metastatic samples from various years, together with the low USP9X mutation rate in unselected chRCC series, reinforced a causal link between USP9X and mTOR inhibitor sensitivity. Rapamycin treatment of USP9X-depleted HeLa and renal cancer 786-O cells, along with the pharmacological inhibition of USP9X, confirmed that this protein plays a role in patients' sensitivity to mTOR inhibitors. USP9X was not found to exert a direct effect on mTORC1, but subsequent ubiquitylome analyses identified p62 as a direct USP9X target. Increased p62 ubiquitination and the augmented rapamycin effect upon bortezomib treatment, together with the results of p62 and LC3 immunofluorescence assays, suggested that dysregulated autophagy in USP9X-depleted cells can have a synergistic effect with mTOR inhibitors. In summary, we show that USP9X constitutes a potential novel marker of sensitivity to mTOR inhibitors in chRCC patients, and represents a clinical strategy for increasing the sensitivity to these drugs.

Reproducibility of the anorectal angle with transperineal ultrasound.

Background: The anorectal angle (ARA) has been assessed with different imaging methods and its measurement has traditionally been based on defecography or magnetic resonance studies. Different ultrasound methodologies have also been used for ARA assessment and have been validated as alternatives for the ARA measurement, such as three-dimensional (3D) endovaginal ultrasound and 3D transperineal ultrasound. 3D transperineal ultrasound does not require the introduction of ultrasound transducers inside the anal canal. Therefore, it is reasonable to think that the use of transperineal ultrasound can provide more reproducible ARA measurements, something that has not been established by 3D endovaginal probe or defecography. Our objective is to determine the intraobserver and interobserver variability of transperineal ultrasound for the assessment of ARA. Methods: A retrospective observational study was performed with 40 patients. The study of the ARA was performed from the mid-sagittal plane (at rest, Valsalva and maximum contraction), visualizing the anorectal canal, the anorectal junction and the rectal ampulla. ARA measurements were performed initially by explorer 1 (E1), subsequently by explorer 2 (E2) and finally again by E1. Intraobserver and interobserver variability was calculated by calculating the intraclass correlation coefficient (ICC) with 95% confidence interval (CI). Results: Intraobserver variability was excellent for all measurements of the ARA at rest, Valsalva and maximal contraction, with ICC ranging from 0.968 to 0.975. Interobserver variability was also superb for all measurements of the ARA at rest, Valsalva and maximal contraction, with ICC ranging from 0.971 to 0.979. Conclusions: Intraobserver and interobserver variability were excellent for the ARA measurements by transperineal ultrasound.

Genomic and immune landscape Of metastatic pheochromocytoma and paraganglioma.

The mechanisms triggering metastasis in pheochromocytoma/paraganglioma are unknown, hindering therapeutic options for patients with metastatic tumors (mPPGL). Herein we show by genomic profiling of a large cohort of mPPGLs that high mutational load, microsatellite instability and somatic copy-number alteration burden are associated with ATRX/TERT alterations and are suitable prognostic markers. Transcriptomic analysis defines the signaling networks involved in the acquisition of metastatic competence and establishes a gene signature related to mPPGLs, highlighting CDK1 as an additional mPPGL marker. Immunogenomics accompanied by immunohistochemistry identifies a heterogeneous ecosystem at the tumor microenvironment level, linked to the genomic subtype and tumor behavior. Specifically, we define a general immunosuppressive microenvironment in mPPGLs, the exception being PD-L1 expressing MAML3-related tumors. Our study reveals canonical markers for risk of metastasis, and suggests the usefulness of including immune parameters in clinical management for PPGL prognostication and identification of patients who might benefit from immunotherapy.

Malformación arteriovenosa uterina como causa de hemorragia puerperal tardía / Uterine arteriovenous malformation as a cause of late puerperal hemorrhage

Resumen ANTECEDENTES: Las malformaciones arteriovenosas uterinas constituyen una causa infrecuente de hemorragia puerperal, en la bibliografía solo se encontraron 150 casos. Su conocimiento es importante porque son potencialmente mortales y porque se ha registrado un aumento en los últimos años. Suelen estar relacionadas con intervenciones en el útero: legrados, cesáreas o miomectomías o asociadas con neoplasias (enfermedad trofoblástica gestacional o adenocarcinoma endometrial), aunque otras son congénitas. CASO CLÍNICO: Paciente de 32 años, con una conización cervical y ablación de un mioma uterino mediante radiofrecuencia como únicos antecedentes de interés. A los 15 días posteriores a un parto eutócico, que fue el primero en su historial, tuvo un episodio de abundante metrorragia. En el puerperio inmediato tuvo una hemorragia abundante que requirió la transfusión de dos concentrados de hematíes. En la ecografía transvaginal el útero se observó de 22 x 44 mm, que podría corresponder a un cotiledón retenido. Ante la persistencia del sangrado se colocó un taponamiento intracavitario con una sonda de Foley con lo que se consiguió el cese del sangrado. Luego de descartar la embolización de las arterias uterinas debido al gran tamaño de la malformación arteriovenosa, se procedió a la histerectomía total simple por vía laparotómica. CONCLUSIÓN: Las malformaciones arteriovenosas uterinas, aunque son una causa infrecuente de hemorragia puerperal, deben ser sospechadas en virtud de ser potencialmente mortales.

Abstract BACKGROUND: Uterine arteriovenous malformations are a rare cause of puerperal hemorrhage, with only 150 cases reported in the literature. Their knowledge is important because they are life-threatening and because there has been an increase in recent years. They are usually related to interventions in the uterus: curettage, caesarean section or myomectomy or associated with neoplasms (gestational trophoblastic disease or endometrial adenocarcinoma), although others are congenital. CLINICAL CASE: A 32-year-old patient with a cervical conization and ablation of a uterine myoma by radiofrequency as the only history of interest. Fifteen days after a euthecological delivery, which was the first in her history, she had an episode of abundant metrorrhagia. In the immediate postpartum period, she had a heavy hemorrhage that required the transfusion of two red blood cell concentrates. Transvaginal ultrasound showed a uterus measuring 22 x 44 mm, which could correspond to a retained cotyledon. In view of the persistent bleeding, intracavitary tamponade was placed with a Foley catheter, which led to cessation of bleeding. After ruling out embolization of the uterine arteries due to the large size of the arteriovenous malformation, a simple total hysterectomy by laparotomy was performed. CONCLUSION: Uterine arteriovenous malformations, although an infrequent cause of puerperal hemorrhage, should be suspected because they are potentially fatal.

Long-Term Effectiveness of a Smartphone App and a Smart Band on Arterial Stiffness and Central Hemodynamic Parameters in a Population with Overweight and Obesity (Evident 3 Study): Randomised Controlled Trial.

BACKGROUND: mHealth technologies could help to improve cardiovascular health; however, their effect on arterial stiffness and hemodynamic parameters has not been explored to date. OBJECTIVE: To evaluate the effect of a mHealth intervention, at 3 and 12 months, on arterial stiffness and central hemodynamic parameters in a sedentary population with overweight and obesity. METHODS: Randomised controlled clinical trial (Evident 3 study). 253 subjects were included: 127 in the intervention group (IG) and 126 in the control group (CG). The IG subjects were briefed on the use of the Evident 3 app and a smart band (Mi Band 2, Xiaomi) for 3 months to promote healthy lifestyles. All measurements were recorded in the baseline visit and at 3 and 12 months. The carotid-femoral pulse wave velocity (cfPWV) and the central hemodynamic parameters were measured using a SphigmoCor System® device, whereas the brachial-ankle pulse wave velocity (baPWV) and the Cardio Ankle Vascular Index (CAVI) were measured using a VaSera VS-2000® device. RESULTS: Of the 253 subjects who attended the initial visit, 237 (93.7%) completed the visit at 3 months of the intervention, and 217 (85.3%) completed the visit at 12 months of the intervention. At 12 months, IG showed a decrease in peripheral augmentation index (PAIx) (-3.60; 95% CI -7.22 to -0.00) and ejection duration (ED) (-0.82; 95% CI -1.36 to -0.27), and an increase in subendocardial viability ratio (SEVR) (5.31; 95% CI 1.18 to 9.44). In CG, cfPWV decreased at 3 months (-0.28 m/s; 95% CI -0.54 to -0.02) and at 12 months (-0.30 m/s, 95% CI -0.54 to -0.05), central diastolic pressure (cDBP) decreased at 12 months (-1.64 mm/Hg; 95% CI -3.19 to -0.10). When comparing the groups we found no differences between any variables analyzed. CONCLUSIONS: In sedentary adults with overweight or obesity, the multicomponent intervention (Smartphone app and an activity-tracking band) for 3 months did not modify arterial stiffness or the central hemodynamic parameters, with respect to the control group. However, at 12 months, CG presented a decrease of cfPWV and cDBP, whereas IG showed a decrease of PAIx and ED and an increase of SEVR.

Are Transperineal Ultrasound Parameters Useful to Predict Incontinence in Patients with Single-Incision Mini-Slings?

It would be logical to think that single-incision mini-slings (SIMS) should behave like the rest of the tension-free vaginal tape and, therefore, to believe that they present a similar ultrasound appearance, but there are no studies on this matter. Therefore, the main aim of our research is to determine which ultrasound parameters are associated with stress urinary incontinence (SUI) in patients carrying SIMS. A prospective observational study was carried out including 94 patients who were candidates for SUI corrective surgery with SIMS between 1 January 2021 to 31 December 2021 at the Universitary Hospital of Valme (Seville, Spain). A transperineal ultrasound evaluation was performed (six months after surgery) in order to study: the bladder neck-symphyseal distance, the posterior urethro-vesical angle, the pubic symphysis-tape gap, the tape-urethral lumen distance, the sagittal tape angle, the tape position, the concordance of movement between the tape and the urethra, and the axial tape angle. A total of 92 patients completed the study (63 asymptomatic and 29 symptomatic). Statistical differences were observed in the concordance of movement between the tape and the urethra (84.1% vs. 25.0%; p: 0.001) and in the axial tape angle at rest (139.3 ± 19.0 vs. 118.3 ± 15.4; p: 0.003) and at Valsalva (145.1 ± 20.2 vs. 159.1 ± 9.0; p: 0.034). Sagittal tape angle at rest was higher in urge urinary incontinence (UUI) patients (132.5 ± 35.7 vs. 143.3 ± 29.8; p: 0.001) and mixed urinary incontinence (MUI) patients (132.5 ± 35.7 vs. 157.8 ± 23.6; p: 0.025) compared to asymptomatic patients. In conclusion, the concordance between the movement of the tape and the urethra is the most useful ultrasound parameter to define continence in patients with SIMS.

Comprehensive molecular analysis of immortalization hallmarks in thyroid cancer reveals new prognostic markers.

BACKGROUND: Comprehensive molecular studies on tumours are needed to delineate immortalization process steps and identify sensitive prognostic biomarkers in thyroid cancer. METHODS AND RESULTS: In this study, we extensively characterize telomere-related alterations in a series of 106 thyroid tumours with heterogeneous clinical outcomes. Using a custom-designed RNA-seq panel, we identified five telomerase holoenzyme-complex genes upregulated in clinically aggressive tumours compared to tumours from long-term disease-free patients, being TERT and TERC denoted as independent prognostic markers by multivariate regression model analysis. Characterization of alterations related to TERT re-expression revealed that promoter mutations, methylation and/or copy gains exclusively co-occurred in clinically aggressive tumours. Quantitative-FISH (fluorescence in situ hybridization) analysis of telomere lengths showed a significant shortening in these carcinomas, which matched with a high proliferative rate measured by Ki-67 immunohistochemistry. RNA-seq data analysis indicated that short-telomere tumours exhibit an increased transcriptional activity in the 5-Mb-subtelomeric regions, site of several telomerase-complex genes. Gene upregulation enrichment was significant for specific chromosome-ends such as the 5p, where TERT is located. Co-FISH analysis of 5p-end and TERT loci showed a more relaxed chromatin configuration in short telomere-length tumours compared to normal telomere-length tumours. CONCLUSIONS: Overall, our findings support that telomere shortening leads to a 5p subtelomeric region reorganization, facilitating the transcription and accumulation of alterations at TERT-locus.

The Role of Transperineal Ultrasound for the Assessment of the Anorectal Angle and Its Relationship with Levator Ani Muscle Avulsion.

The relationship between the anorectal angle (ARA) and the levator ani muscle (LAM) is well known. In this study, we aimed to demonstrate that the ARA changes when LAM avulsion occurs after vaginal delivery. This was a secondary, observational retrospective study with data obtained from three previous studies. Using transperineal ultrasound, the presence of avulsion was assessed when abnormal insertion of the LAM was observed in three central slices. In addition, the ARA was assessed in the midsagittal plane (at rest, in Valsalva and at maximum contraction) as the angle between the posterior border of the distal part of the rectum and the central axis of the anal canal. The ARA was higher in patients with bilateral LAM avulsion than in patients without LAM avulsion at rest (131.8 ± 14.1 vs. 136.2 ± 13.8), in Valsalva (129.4 ± 15.5 vs. 136.5 ± 14.4) and at maximum contraction (125.7 ± 15.5 vs. 132.3 ± 13.2). The differences between both groups expressed as the odds ratio (OR) adjusted for maternal age were 1.031 (95% confidence interval (CI), 1.001-1.061; p = 0.041) at rest, 1.036 (95% CI, 1.008-1.064; p = 0.012) in Valsalva and 1.031 (95% CI, 1.003-1.059; p = 0.027) at maximum contraction. In conclusion, LAM avulsion produces an increase in the ARA at rest, during contraction and in Valsalva, especially in cases of bilateral LAM avulsion.

Correction: Díaz-Talavera et al. PrimPol: A Breakthrough among DNA Replication Enzymes and a Potential New Target for Cancer Therapy. Biomolecules 2022, 12, 248.

To improve the quality of the original article [...].

Long-term Effectiveness of a Smartphone App Combined With a Smart Band on Weight Loss, Physical Activity, and Caloric Intake in a Population With Overweight and Obesity (Evident 3 Study): Randomized Controlled Trial.

BACKGROUND: Multicomponent mobile health approaches can improve lifestyle intervention results, although little is known about their long-term effectiveness. OBJECTIVE: This study aims to evaluate the long-term effectiveness (12 months) of a multicomponent mobile health intervention-combining a smartphone app, an activity tracker wristband, and brief counseling, compared with a brief counseling group only-on weight loss and improving body composition, physical activity, and caloric intake in Spanish sedentary adults with overweight or obesity. METHODS: We conducted a randomized controlled, multicenter clinical trial (Evident 3). A total of 650 participants were recruited from 5 primary care centers, with 318 participants in the intervention group (IG) and 332 in the control group (CG). All participants were briefly counseled about a healthy diet and physical activity at the baseline visit. For the 3-month intervention period, the IG received training to use the app to promote healthy lifestyles and the smart band (Mi Band 2, Xiaomi). All measurements were performed at baseline and at 3 and 12 months. Physical activity was measured using the International Physical Activity Questionnaire-Short Form. Nutritional habits were assessed using the Food Frequency Questionnaire and Adherence to Mediterranean diet questionnaire. RESULTS: Of the 650 participants included, 563 (86.6%) completed the 3-month visit and 443 (68.2%) completed the 12-month visit. After 12 months, the IG showed net differences in weight (-0.26, 95% CI -1.21 to 0.70 kg; P=.02), BMI (-0.06, 95% CI -0.41 to 0.28 points; P=.01), waist-height ratio (-0.25, 95% CI -0.94 to 0.44; P=.03), body adiposity index (-0.33, 95% CI -0.77 to 0.11; P=.03), waist circumference (-0.48, 95% CI -1.62 to 0.66 cm, P=.04) and hip circumference (-0.69, 95% CI -1.62 to 0.25 cm; P=.03). Both groups lowered daily caloric intake and increased adherence to the Mediterranean diet, with no differences between the groups. The IG increased light physical activity time (32.6, 95% CI -30.3 to 95.04 min/week; P=.02) compared with the CG. Analyses by subgroup showed changes in body composition variables in women, people aged >50 years, and married people. CONCLUSIONS: The low-intensity intervention of the Evident 3 study showed, in the IG, benefits in weight loss, some body composition variables, and time spent in light physical activity compared with the CG at 3 months, but once the devices were collected, the downward trend was not maintained at the 12-month follow-up. No differences in nutritional outcomes were observed between the groups. TRIAL REGISTRATION: ClinicalTrials.gov NCT03175614; https://clinicaltrials.gov/ct2/show/NCT03175614. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1097/MD.0000000000009633.

PrimPol: A Breakthrough among DNA Replication Enzymes and a Potential New Target for Cancer Therapy.

DNA replication can encounter blocking obstacles, leading to replication stress and genome instability. There are several mechanisms for evading this blockade. One mechanism consists of repriming ahead of the obstacles, creating a new starting point; in humans, PrimPol is responsible for carrying out this task. PrimPol is a primase that operates in both the nucleus and mitochondria. In contrast with conventional primases, PrimPol is a DNA primase able to initiate DNA synthesis de novo using deoxynucleotides, discriminating against ribonucleotides. In vitro, PrimPol can act as a DNA primase, elongating primers that PrimPol itself sythesizes, or as translesion synthesis (TLS) DNA polymerase, elongating pre-existing primers across lesions. However, the lack of evidence for PrimPol polymerase activity in vivo suggests that PrimPol only acts as a DNA primase. Here, we provide a comprehensive review of human PrimPol covering its biochemical properties and structure, in vivo function and regulation, and the processes that take place to fill the gap-containing lesion that PrimPol leaves behind. Finally, we explore the available data on human PrimPol expression in different tissues in physiological conditions and its role in cancer.

Analysis of the Different Scenarios of Coach's Anger on the Performance of Youth Basketball Teams.

In spite of the negative effects of anger, coaches are often seen becoming angry during games. This is especially worrying in U18 categories. Thus, the objective of this study was to identify the influence that the coach's anger has on the performance of a basketball team in competition. For this, an ad hoc observation tool was designed, in which 587 moments of anger from the coaching staff (64 coaches) were recorded in the 24 semi-final and final matches of the Spanish Autonomous Region Team Championships in 2019 and 2020 in the infantil (M = 14 years old) and cadete (M = 16 years old) categories. The results show that, in response to most incidents of coach anger, the performance of the team did not change. Significant differences were identified in some scenarios, with low- or medium-intensity anger targeted at the defence, where the team performance improved. However, anger towards the referee in the last quarter with scores level had a negative influence on the team's performance.

Lactose and Casein Cause Changes on Biomarkers of Oxidative Damage and Dysbiosis in an Experimental Model of Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: Experimental Autoimmune Encephalomyelitis (EAE) in rats closely reproduces Multiple Sclerosis (MS), a disease characterized by neuroinflammation and oxidative stress that also appears to extend to other organs and their compartments. The origin of MS is a matter for discussion, but it would seem that altering certain bacterial populations present in the gut may lead to a proinflammatory condition due to the bacterial Lipopolysaccharides (LPS) in the so-called brain-gut axis. The casein and lactose in milk confer anti-inflammatory properties and immunomodulatory effects. The objectives of this study were to evaluate the effects of administration of casein and lactose on the oxidative damage and the clinical status caused by EAE and to verify whether both casein and lactose had any effect on the LPS and its transport protein -LBP-. METHODS: Twenty male Dark Agouti rats were divided into control rats (control), EAE rats, and EAE rats, to which casein and lactose, EAE+casein, and EAE+lactose, respectively, were administered. Fifty-one days after casein and lactose administration, the rats were sacrificed, and different organs were studied (brain, spinal cord, blood, heart, liver, kidney, small, and large intestine). In the latter, products derived from oxidative stress were studied (lipid peroxides and carbonylated proteins) as well as the glutathione redox system, various inflammation factors (total nitrite, Nuclear Factor-kappa B p65, the Rat Tumour Necrosis Factor-α), and the LPS and LBP values. RESULTS AND CONCLUSION: Casein and lactose administration improved the clinical aspect of the disease at the same time as reducing inflammation and oxidative stress, exerting its action on the glutathione redox system, or increasing GPx levels.

Retinal blood vessel calibre and vascular ageing in a general Spanish population: A EVA study.

INTRODUCTION: The aim of this work was to analyse the association of the retinal arteriolar calibre and the arteriole/venule index (AV index) with vascular ageing in a general population without previous cardiovascular disease. MATERIALS AND METHODS: Descriptive cross-sectional study. A total of 482 individuals without cardiovascular disease (mean age: 55.6 ± 14.2 years) were selected by random sampling, stratified by age and sex. The retinal arteriolar calibre was measured using digital fundus images of the back of the eye captured with a validated, semiautomatized and computer-assisted software (Index calculator). Vascular ageing was defined using three criteria based on the values of: (1) Carotid-femoral Pulse Wave Velocity (cfPWV), (2) Brachial-ankle Pulse Wave Velocity (baPWV) and (3) Carotid Intima-Media Thickness. RESULTS: The AV index and arteriolar calibre show a negative correlation with age, arterial pressure, cardiovascular risk and parameters of vascular structure and function (p < 0.001 in all cases). We found lower mean values of the AV index and arteriolar calibre in the individuals with early vascular ageing compared to those with healthy vascular ageing. AV index was negatively correlated with cfPWV ((ß=-2.9; 95% CI (-4.7; -1.1)), baPWV ((ß=-3.2; 95% CI (-5.4; -0.9)) and vascular ageing index ((ß=-1.7; 95% CI (-2.7; -0.7)). Arteriolar calibre showed a negative correlation with baPWV (ß=-0.1; 95% CI (-0.2; -0.1)). In the logistic regression analysis, lower values of AV index ((OR=0.01; 95% CI (0.01-0.10), OR=0.03; 95% CI (0.01-0.11) and OR=0.09; 95% CI (0.01-0.67)) were associated with EVA defined with cfPWV, baPWV and vascular ageing index respectively, and lower values of arteriolar calibre ((OR=0.71; 95% CI (0.55-0.91)) were associated with EVA defined with vascular ageing index. CONCLUSIONS: Lower values of AV index and retinal arteriolar calibre were associated with vascular ageing in a general Spanish population without previous cardiovascular disease.