Non-HLA angiotensin-type-1 receptor autoantibodies mediate the long-term loss of grafted neurons in Parkinson's disease models.

BACKGROUND: Clinical trials have provided evidence that transplants of dopaminergic precursors, which may be replaced by new in vitro stem cell sources, can integrate into the host tissue, and alleviate motor symptoms in Parkinson´s disease (PD). In some patients, deterioration of graft function occurred several months after observing a graft-derived functional improvement. Rejection of peripheral organs was initially related to HLA-specific antibodies. However, the role of non-HLA antibodies is now considered also relevant for rejection. Angiotensin-II type-1 receptor autoantibodies (AT1-AA) act as agonists of the AT1 receptors. AT1-AA are the non-HLA antibodies most widely associated with graft dysfunction or rejection after transplantation of different solid organs and hematopoietic stem cells. However, it is not known about the presence and possible functional effects of AT1-AA in dopaminergic grafts, and the effects of treatment with AT1 receptor blockers (ARBs) such as candesartan on graft survival. METHODS: In a 6-hydroxydopamine PD rat model, we studied the short-term (10 days)- and long-term (3 months) effects of chronic treatment with the ARB candesartan on survival of grafted dopaminergic neurons and microglial graft infiltration, as well as the effects of dopaminergic denervation and grafting on serum and CSF AT1-AA levels. The expression of AT1 receptors in grafted neurons was determined by laser capture microdissection. RESULTS: At the early period post-grafting, the number of grafted dopaminergic neurons that survived was not significantly different between treated and untreated hosts (i.e., control rats and rats treated with candesartan), probably because, just after grafting, other deleterious factors are predominant for dopaminergic cell death, such as mechanical trauma, lack of growth factors/nutrients and ischemia. However, several months post-grafting, we observed a significantly higher number of surviving dopaminergic neurons and a higher density of striatal dopaminergic terminals in the candesartan-treated group. For several months, grafted rats showed blood and cerebrospinal fluid levels of AT1-AA higher than normal controls, and also higher AT1-AA levels than non-grafted parkinsonian rats. CONCLUSIONS: The results suggest the use of ARBs such as candesartan in PD patients, particularly before and after dopaminergic grafts, and the need to monitor AT1-AA levels in PD patients, particularly in those candidates for dopaminergic grafting.

Carotenoid, Tocopherol, and Volatile Aroma Compounds in Eight Sacha Inchi Seed (Plukenetia volubilis L.) Oil Accessions.

Sacha inchi seed oil is a food matrix rich in bioactive constituents, mainly polyunsaturated fatty acids. In this study, the characteristics of color, carotenoid content, tocopherols, and volatile aroma compounds in eight sacha inchi seed (Plukenetia volubilis L.) oil accessions were evaluated. Results showed that the oil obtained from the accessions presented a lightness and chroma of 91 to 98 units and 6 to 10 units respectively, while the hue angle ranged between 93 to 97 units. The total carotenoid content in the different accessions ranged from 0.6 to 1.5 mg/kg, while γ- and δ-tocopherol ranged from 861.6 to 1142 mg/kg and 587 to 717.1 mg/kg. In addition, the total content of tocopherols varied between 1450 and 1856 mg/kg and the δ/γ ratio ranged between 0.58 and 0.70. The oils from the accessions PER000408 (861 µg/kg) and PER000411 (896 µg/kg) were those with the higher volatile concentration, especially 1-hepten-3-ol, 2-nonanol, (E)-3-hexen- 1-ol, (E)-2-hexenal, and 1-hexanol. In this study, the variability of the oil obtained from 8 accessions were observed, from which promising accessions can be selected for continuous investigations of the new sacha inchi seed genotypes.

The Relationship between Abdominal Diastasis and Lumbar Pain Pressure Threshold in Women Who Have Given Birth between the Ages of 30 and 45 Years-An Observational Pilot Study.

Background and Objectives: Current evidence confirms that the magnitude of the inter-rectus distance (IRD) is associated with the severity of abdominal pain. Furthermore, evidence exists in the literature about the impact abdominal muscles have on low back pain, lumbopelvic pain, breathing and lumbar abdominal strength; however, no studies analysing the level of association between abdominal diastasis and lumbar pain pressure threshold (PPT) exist. The aim of this study was to analyse the level of association between the rectus abdominis distance and pain pressure threshold in the lumbar spinous processes in women who have given birth between the ages of 30 and 45 years. Secondly, it was to study the level of association between the time elapsed since the last delivery and low back pain in women who have given birth between 30 and 45 years of age. Material and Methods: This was a pilot observational study in which 21 females participated. The abdominal diastasis was measured by ultrasound, the pain pressure threshold was assessed by an algometer and the pain perception by the Mc Gill questionnaire. Results: There was no significant relationship between increased abdominal distance and increased lumbopelvic pain in women who gave birth between the ages of 30 and 45 years. However, there was a correlation between the time that had elapsed since the last delivery and low back pain. Conclusions: there was a correlation between the time that had elapsed since the last delivery and low back pain. Further studies analysing factors that may perpetuate the chronicity of symptoms, such as lifestyle and intrinsic factors, are needed.

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.

Impact of physical therapy techniques and common interventions on sleep quality in patients with chronic pain: A systematic review.

This systematic review aims to find effectful healthcare strategies, with special focus on drug-free interventions and physical therapy, as part of the treatment for sleep in patients with chronic musculoskeletal pain. Data search was conducted across seven scientific databases. This review is deposited in the Prospero International prospective register of systematic reviews (CRD42023452574). Seventeen RCTs from different healthcare fields complied with our inclusion criteria. Two RCTs investigated manual therapy, five RCTs therapeutic exercise, one RCT Fu's subcutaneous needling, two RCTs physical agents (one on balneotherapy and one on cryo-stimulation), two RCTs cognitive-behavioral therapy, and four RCTs pharmacological therapy and their effect on sleep quality and/or quantity in patients suffering from chronic pain. We included the four RCT's in this systematic review with the purpose to be able to compare natural interventions with allopathic ones. As allopathic interventions are more prone to have secondary negative effects than physical therapy, compare the two types of interventions could be in favor of choosing the most effective treatment with the least secondary negative effects. Additionally, two RCTs on neurofeedback and limbic neuromodulation were also included. The results of the included studies suggest that strategies such as manual therapy, therapeutic exercise, Fu's subcutaneous needling, balneotherapy, cryo-stimulation, neurofeedback, limbic neuromodulation, cognitive-behavioral therapy, and pharmacological therapies have positive effects on patients suffering from chronic pain and sleep disturbances, especially when they suffer musculoskeletal pain. Secondary negative effects were found for the possible overuse of certain medicines such as morphine, a huge problem in the United States. Sleep deficiency is an independent risk factor for many diseases, including chronic pain syndrome and therefore more studies are needed to find non-toxic interventions for people suffering sleep disorders associated with systemic diseases and pain.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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)