Sequential RAS mutations evaluation in cell-free DNA of patients with tissue RAS wild-type metastatic colorectal cancer: the PERSEIDA (Cohort 2) study.

PURPOSE: RAS (KRAS/NRAS) mutational status on a tumor biopsy is mandatory to guide the best treatment in metastatic colorectal cancer (mCRC). Determining the RAS mutational status by tumor-tissue biopsy is essential in guiding the optimal treatment decision for mCRC. RAS mutations are negative predictive factors for the use of EGFR monoclonal antibodies. Cell-free DNA (cfDNA) analysis enables minimally invasive monitoring of tumor evolution. METHODS/PATIENTS: PERSEIDA was an observational, prospective study assessing cfDNA RAS, BRAF and EGFR mutations (using Idylla™) in first-line mCRC, RAS wild-type (baseline tumor-tissue biopsy) patients (cohort 2). Plasma samples were collected before first-line treatment, after 20 ± 2 weeks, and at disease progression. RESULTS: 117 patients were included (103 received panitumumab + chemotherapy as first-line treatment). At baseline, 7 (6.8%) patients had RAS mutations, 4 (3.9%) BRAF mutations and no EGFR mutations were detected (cfDNA, panitumumab + chemotherapy subpopulation [panitumumab + Ch]). The baseline RAS mutational status concordance between tissue and liquid biopsies was 94.0% (93.2%, panitumumab + Ch). At 20 weeks, only one patient in the study (included in the panitumumab + Ch) had an emerging cfDNA RAS mutation. No emerging BRAF or EGFR mutations were reported. At disease progression, 6 patients had emergent mutations not present at baseline (RAS conversion rate: 13.3% [6/45]; 15.0% [6/40], panitumumab + Ch). CONCLUSIONS: The concordance rate between liquid and solid biopsies at baseline was very high, as previously reported, while our results suggest a considerable emergence of RAS mutations during disease progression. Thus, the dynamics of the genomic landscape in ctDNA may provide relevant information for the management of mCRC patients.

Effects of the menstrual cycle on the performance of female football players. A systematic review.

Background: Women's football has been booming for a few years now, which has led to an increase in the expectation of the players' performance, leading to a more detailed study of women's physiology in the field of sports. Objectives: To analyze the scientific evidence on the influence of menstruation on the performance of female footballers, as well as to analyze the methodological quality of the studies included in this review. Materials and methods: The possible hormonal effects of the menstrual cycle phases on the performance of female footballers were analyzed. The databases used to conduct the searches were Pubmed, Scopus, Virtual Health Library, Web of Science, EBSCO and the Cochrane Library. All included studies met the inclusion criteria. The Cochrane risk of bias tool was used. This systematic review protocol was registered at the International Prospective Register of Systematic Reviews (PROSPERO: CRD42023390652). Results: A total of nine clinical trials were included in this review. A low quality of evidence was observed in the studies. Not all the results support the idea that the menstrual cycle phases can alter the performance of female footballers. Conclusion: This systematic review shows that there is a great deal of controversy about the influence of the menstrual cycle phases on the performance of female footballers. Studies are focused on solely biological factors and gender is normally no part of those studies. Further research with larger samples, and taking not only biological but also sociological factors, are necessary to determine the effects of menstruation on the performance of female footballers.

Objective Assessment of Equine Locomotor Symmetry Using an Inertial Sensor System and Artificial Intelligence: A Comparative Study.

In horses, quantitative assessment of gait parameters, as with the use of inertial measurement units (IMUs) systems, might help in the decision-making process. However, it requires financial investment, is time-consuming, and lacks accuracy if displaced. An innovative artificial intelligence marker-less motion tracking system (AI-MTS) may overcome these limitations in the field. Our aim was to compare the level of agreement and accuracy between both systems and visual clinical assessment. Twenty horses underwent locomotion analysis by visual assessment, IMUs, and AI-MTS systems, under the following conditions: straight hard (SH), straight soft (SS), left and right circle hard (LCH, RCH), and soft (LCS, RCS). A greater number of horses were considered sound by clinical examination, compared to those identified as symmetric by the two gait analysis systems. More limbs were considered asymmetric by the AI-MTS compared to IMUs, suggesting its greater sensitivity. The greatest agreement between the two systems was found for the difference between two minima in vertical head position in SH, while the lowest for the difference between two minima in vertical pelvis position in SS, reflecting the difficulties in assessing asymmetry of the hindlimbs. It is unknown what degree of asymmetry is clinically relevant, suggesting that more consistent use in training horses may help determine the thresholds for asymmetry. Some degree of asymmetry may be clinically relevant, suggesting its regular use in training horses.

Productos alimenticios etiquetados como “orgánicos” a basede cultivos andinos: un estudio de sus bio-componentes y actividad antioxidante in vitro / Food products labeled as “organic” based on Andean crops: a study of their biocomponents and antioxidant activity in vitro

Objetivo: En este estudio se plantea la evaluación de sus propiedades antioxidantes de varios productos con etiquetado “orgánico” elaborados con matrices alimentarias de cultivos andinos.Materiales y métodos: Las diferentes muestras con etiquetado “orgánico” fueron evaluadas en función a sus propiedades antioxidantes y evaluadas mediante métodos espectrofotométricos. Resultados: Los resultados de este estudio muestran que las semillas seguido de las mezclas de harinas (PM1 y PM3) presentan altos contenidos de proteínas, mientras que la semilla de chía (S2) fueron ricos en lípidos y cenizas. Mejores contenidos de polifenoles, flavonoides, flavanoles, flavonoles y antocianinas fueron observados en las mezclas de harinas (PM1 a PM5), estas mezclas fueron obtenidas a partir de maca, quinua, maíz morado, cacao, y lúcuma, mientras que las semillas como quinua perlada roja, amaranto, quinua roja, quinua negra, y quinua tricolor contribuyeron con betaxantinas y betacianinas. El orden de clasificación de los productos alimenticios en función del valor antioxidante y composición nutricional ubicó en primer lugar a PM2 (quinua, cacao criollo, maíz morado, algarrobo, canela), segundo lugar para maíz morado y en tercer lugar para flakes.Conclusiones: Los hallazgos de este estudio permitieron establecer que las mezclas de harinas con etiquetado “orgánico” mostraron un alto potencial antioxidante.(AU)

Objective: In this study, the evaluation of the antioxidantproperties of several products labeled “organic” made withfood matrices of Andean crops is proposed.Material and methods: A total of 23 samples with “or-ganic” labelling based on Andean crops were evaluated withrespect to their nutritional composition, antioxidant properties(total polyphenols, total flavonoids, anthocyanins, betalains,and DPPH radical scavenging activity).Result: The results of this study show that the seeds (S1to S7) followed by the flour mixtures (PM1 and PM3) presenthigh protein contents, while the chia seed (S2) was rich inlipids and ashes. Regarding polyphenols, flavonoids, fla-vanols, flavonols and anthocyanins, it was observed that theflour mixtures (PM1 to PM5) presented better contents, these mixtures were obtained from maca, quinoa, purple corn, co-coa, and lucuma, while the seeds as red pearl quinoa, ama-ranth, red quinoa, black quinoa, and tri-color quinoa con-tributed betaxanthins and betacyanins. The order ofclassification of the food products with the “organic” labelbased on the antioxidant value and nutritional compositionplaced the PM2 sample in first place (quinoa, Criollo cocoa,purple corn, carob powder, cinnamon), followed by purplecorn flour (P1) and in third place for flakes (FL). Conclusion: The findings of this study allowed us to es-tablish that the flour mixtures labeled “organic” showedgreater DPPH radical scavenging activity.(AU)

Outcomes of whole-body photobiomodulation on pain, quality of life, leisure physical activity, pain catastrophizing, kinesiophobia, and self-efficacy: a prospective randomized triple-blinded clinical trial with 6 months of follow-up.

Background: The management of fibromyalgia (FM) symptoms on a global scale remains a complex endeavor. This study endeavors to assess the impact of whole-body photobiomodulation (PBM) compared to placebo PBM on pain, functionality, and psychological symptoms in individuals afflicted with fibromyalgia. Objectives: The primary objectives of this research were to conduct a comparative analysis of the effects of whole-body photobiomodulation (PBM) and placebo PBM on pain, functionality, and psychological symptoms in patients suffering from fibromyalgia (FM). Methods: A total of 42 subjects were recruited from a private care practice for participation in this triple-blinded, placebo-controlled, randomized clinical trial. Participants underwent 12 treatment sessions, and assessments were conducted at various intervals, including baseline (T0), midway through the 12-session treatment (T1), at the completion of the 12 sessions (T2), and follow-ups at 2 weeks (T3), 3 months (T4), and 6 months (T5). Results: Statistical analysis revealed significant reductions in pain at T2, T3, and T5. Additionally, quality of life exhibited marked improvements after sessions at T1, T2, T3, T4, and T5. Leisure activity also demonstrated statistically significant improvements at T2, T3, T4, and T5. Furthermore, kinesiophobia showed significant differences between groups immediately after treatment at T2, T3, T4, and T5. Self-efficacy, when compared between groups, demonstrated significant differences at T3, T4, and T5 (two weeks after treatment). Lastly, pain catastrophizing exhibited significant differences only at T5. Conclusion: The findings of this study indicate that whole-body PBM treatment for 4 weeks resulted in significant pain reduction and improved quality of life in individuals suffering from FM. Furthermore, kinesiophobia and self-efficacy demonstrated improvements in both short-term and long-term assessments, while pain catastrophizing showed improvement at the 6-month follow-up. Consequently, whole-body PBM emerges as a promising multifactorial treatment option for FM patients, though further studies are required to validate and strengthen these results.Clinical Trial Registration:Clinicaltrials.gov, NCT0424897.

Cyclic Fatigue Resistance of Rotary versus Reciprocating Endodontic Files: A Systematic Review and Meta-Analysis.

(1) Background: The failure of nickel-titanium (NiTi) rotary files is a complication related to endodontic instruments. The aim of this study was to compare the resistance to cyclic fatigue between rotary and reciprocating file systems. (2) Methods: Specific PICO: Population (P): artificial root canals; Interventions (I): instrumentation with NiTi rotary and reciprocating files; Comparison (C): rotary versus reciprocating files; Outcome (O): cyclic fatigue resistance. Studies were identified through bibliographic research using electronic databases (Medline, Embase, Scopus, SciELO, and WOS). The studies were combined using a random effects model by the inverse variance method. The effect size was the mean of the time to fracture (TTF) and number of cycles to fracture (NCF). Heterogeneity was assessed using the p value of the Q test for heterogeneity and the I2. (3) Results: TTF for rotary files was determined in 474.5 s and 839.1 for reciprocating without statistically significant differences. NCF for rotary systems was determined in 1444.2 and for reciprocating file systems in 4155.9 with statistically significant differences (p = 0.035), making reciprocating files more resistant. (4) Conclusions: Reciprocating files have better resistance to cyclic fatigue than rotary files. When tested in double curvature canals, reciprocating files also showed higher resistance.

Physical Activity, Insulin Resistance and Cancer: A Systematic Review.

INTRODUCTION: Insulin resistance (IR), a key aspect of type 2 diabetes and a defining characteristic of obesity and its associated conditions, emerges as a mechanistic pathway potentially implicated in cancer pathophysiology. This presents an appealing intervention target for cancer patients. The objective of this study is to conduct a systematic review, examining the scientific evidence regarding the impact of physical activity on modifying insulin resistance in individuals with cancer. METHODS: The selection criteria were specific: only randomized controlled clinical trials published in the last 13 years and written in English or Spanish were included. The databases utilized for the search included PubMed, Scopus, Cochrane Library, EBSCO, and WEB OF SCIENCE. The protocol for this review was duly registered in the International Register of Systematic Reviews (CRD42023435002). The final search was conducted on 14 May 2023. RESULTS: The outcomes were assessed using the tool proposed by the Cochrane Handbook to evaluate the risk of bias in the included studies. Among the 12 studies incorporated, 8 demonstrated a low risk of bias, two had an unclear risk of bias, and the remaining two showed a high risk of bias. The variety of exercise types used across all studies was extensive, making definitive conclusions challenging. Physical activity was linked to enhanced insulin sensitivity in seven studies, while five studies showed no significant changes in insulin resistance between the intervention and control groups. Importantly, none of the interventions employed in the included studies exhibited adverse effects on the study participants. CONCLUSIONS: The role of exercise as a medicine against insulin resistance has been evidenced in many different studies, mostly related to obesity and cardiovascular diseases. Engaging in physical activity could be a healthy option to combat the effects of insulin resistance in cancer patients, although evidence is weak and limited, according to the results of our systemic review. We further found that literature is lacking at the level of optimal doses, timing, and type of exercise. More studies are needed with more defined PA programs in type and length.

Quantitative detection of chikungunya, Zika, and dengue viruses by one-step real-time PCR in different cell substrates.

Chikungunya (CHIKV), Zika (ZIKV), and dengue viruses (DENV) are vector-borne pathogens that cause emerging and re-emerging epidemics throughout tropical and subtropical countries. The symptomatology is similar among these viruses and frequently co-circulates in the same areas, making the diagnosis arduous. Although there are different methods for detecting and quantifying pathogens, real-time reverse transcription-polymerase chain reaction (real-time RT-qPCR) has become a leading technique for detecting viruses. However, the currently developed assays frequently involve probes and high-cost reagents, limiting access in low-income countries. Therefore, this study aims to design and evaluate a quantitative one-step RT-qPCR assay to detect CHIKV, ZIKV, and DENV with high specificity, reproducibility, and low cost in multiple cell substrates. We established a DNA intercalating green dye-based RT-qPCR test that targets nsP1 of CHIKV, and NS5 gene of ZIKV, and DENV for the amplification reaction. The assay exhibited a high specificity confirmed by the melting curve analysis. No cross-reactivity was observed between the three viruses or unspecific amplification of host RNA. The sensitivity of the reaction was evaluated for each virus assay, getting a limit of detection of one RNA copy per virus. Standard curves were constructed, obtaining a reaction efficiency of ~ 100%, a correlation coefficient (R2) of ~ 0.97, and a slope of -3.3. The coefficient of variation (CV) ranged from 0.02 to 1.43. In addition, the method was optimized for viral quantification and tested in Vero, BHK-21, C6/36, LULO, and the Aedes cell lines. Thus, the DNA intercalating green dye-based RT-qPCR assay was a highly specific, sensitive, reproducible, and effective method for detecting and quantifying CHIKV, ZIKV, and DENV in different cell substrates that could also be applied in clinical samples.

Dynamic nature of BRAF or KRAS p.G12C mutations in second-line therapy for advanced colorectal cancer patients: do early and late effects exist?

INTRODUCTION: The mitogen-activated protein kinase (MAPK) signalling network aberrations in metastatic colorectal cancer (mCRC) generate intrinsic dynamic effects and temporal variations that are crucial but often overlooked in clinical trial populations. Here, we investigate the time-varying impact of MAPK pathway mutation genotype on each treatment line's contribution to the overall clinical course. METHODS: The PROMETEO study focused on mCRC patients undergoing second-line treatment at 20 hospitals. We evaluated genotypes and employed flexible models to analyse the dynamic effect of each mutation. RESULTS: We examined data derived from 1160 patients. The effects of KRAS G12C or G12V, and BRAF V600E are clearly time-varying, with unexpected consequences such as the deleterious effect of BRAF V600E vs other genotypes dissipating over time when subjects receive antiangiogenics, or KRAS G12V and G12C showing increasing aggressiveness over time. Thus, contrary to expectations, the 12-month survival rate from the second line for those who survived >6 months was 49.9% (95% CI, 32.7-67.3) for KRAS G12C and 59% (95% CI, 38.5-80.6) for BRAF V600E. CONCLUSIONS: The dynamic perspective is essential for understanding the behaviour of tumours with specific genotypes, especially from the second line onward. This may be relevant in patient monitoring and treatment decision-making, particularly in cases with distinct mutations.

Anticaries properties of natural berries: systematic literature review.

CONTEXT: Anticariogenic properties have been ascribed to polyphenolic compounds present in high concentrations in numerous fruits. Berries, in particular, have been reported as potentially having an inhibitory effect on the dental biofilm and subsequently on caries, but the evidence is unclear. OBJECTIVE: The objective of this review was to explore the literature and summarize the evidence for berries having an inhibitory effect on the dental biofilm and an anticariogenic effect. DATA SOURCES: Following Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines, the PubMed, Web of Science, and SCOPUS databases were scanned using predefined and accessible terms, with a search strategy based on a structured PICO question. DATA EXTRACTION: After article selection, 23 studies met the inclusion criteria, most of them being in vitro studies. A risk assessment was performed, and data were extracted and presented in a table for qualitative analysis. DATA ANALYSIS: Meta-analyses were conducted using standardized mean differences (SMDs) with a 95% confidence interval (CI) by Review manager 5.4. RESULTS: Only 3 types of berries were found to have a reported anticaries effect: grape seed extract (GSE), cranberry, and sour cherry. Nine studies that fulfilled the eligibility criteria were subjected to quantitative analysis. Meta-analyses showed GSE was associated with enhanced remineralization of dental enamel (SMD = .96 95% CI [.45, 1.46], P < .0002) and of dentin (SMD = .65 95% CI [.13, 1.17], P = .01). Cranberry extracts positively influenced the cariogenic dental biofilm by decreasing the biofilm biomass (SMD = -2.23 95% CI [-4.40, -.05], P = .04), and biovolume (SMD = -2.86 95% CI [-4.34, -1.37], P = .0002), and increasing the biofilm pH (SMD = 7.9 95% CI [3.49, 12.31], P < .0004). CONCLUSION: Within the limitations of this systematic review and metaanalysis, GSE and cranberries or their active compounds could represent an alternative for caries management. Further clinical trials are needed to verify this effect in a clinical setting. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42020223579.

Stage IV perihilar cholangiocarcinoma with loss of expression of MSH2 and MSH6: hereditary cancer syndrome?

We present the case of a 69-year-old male diagnosed with stage IV perihilar cholangiocarcinoma with loss of expression of MSH2 and MSH6 proteins, but somatic wild type MSH2 and MSH6 genes with Oncomine Comprehensive Assay (OCA) genomic sequencing panel. In his cancer family history, there was a maternal aunt with sigmoid colon adenocarcinoma also missing MSH2 and MSH6 protein expression. Subsequently, we will discuss whether or not we are facing a hereditary cancer syndrome. (AU)

KRAS mutations in pancreatic cancer: could we talk about a risk factor for the development of thromboembolic phenomena?

The oncogenic KRAS mutation is associated with increased tissue factor expression and thus hypercoagulability. In this regard, numerous studies published in the last decade have shown that KRAS mutations are an important risk factor for the development of thromboembolic phenomena in neoplasms of the digestive tract, such as colorectal cancer. On the other hand, some recently published studies suggest that KRAS mutations are also associated with an increased risk of developing thromboembolic phenomena in pancreatic cancer. Based on these premises, we have conducted a single-centre retrospective study on a cohort of patients with pancreatic cancer. Our aim is to demonstrate whether there is an association between the presence of KRAS mutations in our cohort of pancreatic cancer patients and an increased risk of developing thromboembolic phenomena. (AU)

Association between elasticity of tissue and pain pressure threshold in the tender points present in subjects with fibromyalgia: a cross-sectional study.

Fibromyalgia (FM) is a multicomponent illness and despite its worldwide prevalence, a complete understanding of its aetiology and pathogenesis remains unclear. The goal of the study is to analyze the level of association between elastic properties of tissue measured by strain elastography (SEL) and pain pressure threshold (PPT) in the characteristic painful points described in patients suffering from FM. This was a cross-sectional, observational study. A sample comprised of 42 subjects with FM was recruited from a private care centre. The occiput, low cervical, trapezius, supraspinatus, paraspinous, lateral pectoral, second rib, lateral epicondyle, medial epicondyle, gluteus, greater trochanter, knee, and anterior tibial PPTs were bilaterally assessed using a standard pressure algometer and elastic properties of tissue were evaluated by SEL. Linear regression analysis showed significant associations between SEL and dominant trapezius PPT (ß = 0.487, 95% CI [0.045, 0.930], p = 0.032) after adjustments for the age, body mass index, and menopause status (higher SEL and higher pain sensitivity). No significant associations between SEL and the other PPTs variables were found in women diagnosed with FM. The PPT of the dominant trapezius is associated with SEL measurements in subjects suffering from FM. More studies are required to fully explain the underlying mechanisms.

Boolean analysis shows a high proportion of dopamine D2 receptors interacting with adenosine A2A receptors in striatal medium spiny neurons of mouse and non-human primate models of Parkinson's disease.

The antagonistic effect of adenosine on dopaminergic transmission in the basal ganglia indirect motor control pathway is mediated by dopamine D2 (D2R) and adenosine A2A (A2AR) receptors co-expressed on medium spiny striatal neurons. The pathway is unbalanced in Parkinson's disease (PD) and an A2AR blocker has been approved for use with levodopa in the therapy of the disease. However, it is not known whether the therapy is acting on individually expressed receptors or in receptors forming A2A-D2 receptor heteromers, whose functionality is unique. For two proteins prone to interact, a very recently developed technique, MolBoolean, allows to determine the number of proteins that are either non-interacting or interacting. After checking the feasibility of the technique and reliability of data in transfected cells and in striatal primary neurons, the Boolean analysis of receptors in the striatum of rats and monkeys showed a high percentage of D2 receptors interacting with the adenosine receptor, while, on the contrary, a significant proportion of A2A receptors do not interact with dopamine receptors. The number of interacting receptors increased when rats and monkeys were lesioned to become a PD model. The use of a tracer of the indirect pathway in monkeys confirmed that the data was restricted to the population of striatal neurons projecting to the GPe. The results are not only relevant for being the first study quantifying individual versus interacting G protein-coupled receptors, but also for showing that the D2R in these specific neurons, in both control and PD animals, is under the control of the A2AR. The tight adenosine/dopamine receptor coupling suggest benefits of early antiparkinsonian treatment with adenosine receptor blockers.

Statin treatment is not associated with an increased risk of adrenal insufficiency in real-world setting.

Introduction: Statins could reduce the synthesis of steroid hormones, thereby could cause adrenal insufficiency. We investigated this risk in a large nationwide database. Methods: We conducted a nested case-control study using a cohort of individuals affiliated to the French health insurance system in 2010, ≥18y and without adrenal insufficiency history. Each case had a first event of adrenal insufficiency between 2015 and 2017 and was matched to up to ten controls on age, sex, and prior treatment with corticosteroids. Statin exposure was measured over the five years preceding the index date, considering a six-month censoring lag-time. Association was estimated using a conditional logistic regression adjusted for confounders included in a disease risk score. Analyses were stratified on age, sex and corticosteroid history of use. Results: 4 492 cases of adrenal insufficiency were compared with 44 798 controls (median age 66y, 58% women), of which 39% vs. 33% were exposed to statins, respectively. No association between statin use and adrenal insufficiency was found when adjusting the model for confounders (adjusted odds ratio 0.98; 95% confidence interval 0.90-1.05). These results were consistent regardless of the exposure definition and stratifications considered. Conclusion: Statin-related adrenal insufficiency risk, if any, seems to be very limited and does not compromise the benefit of statin treatment.

Pharmacogenetics May Prevent Psychotropic Adverse Events in Autism Spectrum Disorder: An Observational Pilot Study.

INTRODUCTION: Up to 73% of individuals with autism spectrum disorder (ASD) and intellectual disability (ID) currently have prescriptions for psychotropic drugs. This is explained by a higher prevalence of medical and psychiatric chronic comorbidities, which favors polypharmacy, increasing the probability of the appearance of adverse events (AEs). These could be a preventable cause of harm to patients with ASD and an unnecessary waste of healthcare resources. OBJECTIVE: To study the impact of pharmacogenetic markers on the prevention of AE appearance in a population with ASD and ID. METHODS: This is a cross-sectional, observational study (n = 118, 72 participants completed all information) in the ASD population. Sociodemographic and pharmacological data were gathered. The Udvalg for Kliniske Undersøgelser Scale (UKU Scale) was used to identify AEs related to the use of psychotropic medication. Polymorphisms of DOP2, ABCB1, and COMT were genotyped and correlated with the AE to find candidate genes. Furthermore, a review of all medications assessed in a clinical trial for adults with autism was performed to enrich the search for potential pharmacogenetic markers, keeping in mind the usual medications. RESULTS: The majority of the study population were men (75%) with multiple comorbidities and polypharmacy, the most frequently prescribed drugs were antipsychotics (69%); 21% of the participants had four or more AEs related to psychotropic drugs. The most common were "Neurological" and" Psychiatric" (both 41%). Statistical analysis results suggested a significant correlation between the neurological symptoms and the DOP2 genotype, given that they are not equally distributed among its allelic variants. The final review considered 19 manuscripts of medications for adults with ASD, and the confirmed genetic markers for those medications were consulted in databases. CONCLUSION: A possible correlation between neurologic AEs and polymorphisms of DOP2 was observed; therefore, studying this gene could contribute to the safety of this population's prescriptions. The following studies are underway to maximize statistical power and have a better representation of the population.

Osteogenic potential of apical papilla stem cells mediated by platelet-rich fibrin and low-level laser.

To evaluate the osteogenic potential of platelet-rich fibrin (PRF) and low-level laser therapy (LLLT) on human stem cells from the apical papilla (SCAP) we isolated, characterized, and then cultured in an osteogenic medium cells with PRF and/or LLLT (660 nm, 6 J/m2-irradiation). Osteogenic differentiation was assessed by bone nodule formation and expression of bone morphogenetic proteins (BMP-2 and BMP-4), whereas the molecular mechanisms were achieved by qRT-PCR and RNA-seq analysis. Statistical analysis was performed by ANOVA and Tukey's post hoc tests (p < 0.05* and p < 0.01**). Although PRF and LLLT increased bone nodule formation after 7 days and peaked at 21 days, the combination of PRF + LLLT led to the uppermost nodule formation. This was supported by increased levels of BMP-2 and -4 osteogenic proteins (p < 0.005). Furthermore, the PRF + LLLT relative expression of specific genes involved in osteogenesis, such as osteocalcin, was 2.4- (p = 0.03) and 28.3- (p = 0.001) fold higher compared to the PRF and LLLT groups, and osteopontin was 22.9- and 1.23-fold higher, respectively (p < 0.05), after 7 days of interaction. The transcriptomic profile revealed that the combination of PRF + LLLT induces MSX1, TGFB1, and SMAD1 expression, after 21 days of osteogenic differentiation conditions exposition. More studies are required to understand the complete cellular and molecular mechanisms of PRF plus LLLT on stem cells. Overall, we demonstrated for the first time that the combination of PRF and LLLT would be an excellent therapeutic tool that can be employed for dental, oral, and craniofacial repair and other tissue engineering applications.

Effectiveness of Treatments That Alter Metabolomics in Cancer Patients-A Systematic Review.

INTRODUCTION: Cancer is the leading cause of death worldwide, with the most frequent being breast cancer in women, prostate cancer in men and colon cancer in both sexes. The use of metabolomics to find new biomarkers can provide knowledge about possible interventions based on the presence of oncometabolites in different cancer types. OBJECTIVES: The primary purpose of this review is to analyze the characteristic metabolome of three of the most frequent cancer types. We further want to identify the existence and success rate of metabolomics-based intervention in patients suffering from those cancer types. Our conclusions are based on the analysis of the methodological quality of the studies. METHODS: We searched for studies that investigated the metabolomic characteristics in patients suffering from breast cancer, prostate cancer or colon cancer in clinical trials. The data were analyzed, as well as the effects of specific interventions based on identified metabolomics and one or more oncometabolites. The used databases were PubMed, Virtual Health Library, Web of Science, EBSCO and Cochrane Library. Only nine studies met the selection criteria. Study bias was analyzed using the Cochrane risk of bias tool. This systematic review protocol was registered at the International Prospective Register of Systematic Reviews (PROSPERO: CRD42023401474). RESULTS: Only nine studies about clinical trials were included in this review and show a moderate quality of evidence. Metabolomics-based interventions related with disease outcome were conflictive with no or small changes in the metabolic characteristics of the different cancer types. CONCLUSIONS: This systematic review shows some interesting results related with metabolomics-based interventions and their effects on changes in certain cancer oncometabolites. The small number of studies we identified which fulfilled our inclusion criteria in this systematic review does not allow us to draw definitive conclusions. Nevertheless, some results can be considered as promising although further research is needed. That research must focus not only on the presence of possible oncometabolites but also on possible metabolomics-based interventions and their influence on the outcome in patients suffering from breast cancer, prostate cancer or colon cancer.

Efficacy of Boswellia serrata Extract and/or an Omega-3-Based Product for Improving Pain and Function in People Older Than 40 Years with Persistent Knee Pain: A Randomized Double-Blind Controlled Clinical Trial.

A single-center, randomized, double-blind, controlled clinical trial with four arms was conducted in healthy subjects with persistent knee discomfort (pain intensity on 1-10 cm visual analog scale (VAS) > 3) aged 40 years and older treated with a dietary supplement for 8 weeks. The study groups were Boswellia serrata extract (n = 29), an omega-3-based product (AvailOm® 50 High EPA) (n = 31), Boswellia + AvailOm® (n = 30), and placebo (n = 30). The intake of Boswellia + AvailOm® improved the quality of life (QoL) (WOMAC index) and some variables of muscle strength. Statistically significant differences between the AvailOm® and the placebo groups in the decrease of pain intensity were found. Weekly VAS scores showed a significant decrease in pain perception when comparing the AvailOm® product to the placebo, with the lowest VAS scores at week 8. Consumption of Boswellia improved sleep latency. The time to perform the Up and Go test decreased after the intake of AvailOm®. There was an increase in the omega-3 fatty acids, with the greatest increase in the Boswellia + AvailOm® group. AvailOm® was safe and effective in reducing pain and improving the QoL and functionality of subjects over 40 years with persistent knee pain.