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.

Rational Design of Molecularly Imprinted Polymers for Curcuminoids Binding: Computational and Experimental Approaches for the Selection of Functional Monomers.

Molecularly imprinted polymers (MIPs) have emerged as bespoke materials with versatile molecular applications. In this study, we propose a proof of concept for a methodology employing molecular dynamics (MD) simulations to guide the selection of functional monomers for curcuminoid binding in MIPs. Curcumin, demethoxycurcumin, and bisdemethoxycurcumin are phenolic compounds widely employed as spices, pigments, additives, and therapeutic agents, representing the three main curcuminoids of interest. Through MD simulations, we investigated prepolymerization mixtures composed of various functional monomers, including acrylamide (ACA), acrylic acid (AA), methacrylic acid (MAA), and N-vinylpyrrolidone (NVP), with ethylene glycol dimethacrylate (EGDMA) as the cross-linker and acetonitrile as the solvent. Curcumin was selected as the template molecule due to its structural similarity to the other curcuminoids. Notably, the prepolymerization mixture containing NVP as the functional monomer demonstrated superior molecular recognition capabilities toward curcumin. This observation was supported by higher functional monomer molecules surrounding the template, a lower total nonbonded energy between the template and monomer, and a greater number of hydrogen bonds in the aggregate. These findings suggest a stronger affinity between the functional monomer NVP and the template. We synthesized, characterized, and conducted binding tests on the MIPs to validate the MD simulation results. The experimental binding tests confirmed that the MIP-NVP exhibited higher binding capacity. Consequently, based on MD simulations, our computational methodology effectively guided the selection of the functional monomer, leading to MIPs with binding capacity for curcuminoids. The outcomes of this study provide a valuable reference for the rational design of MIPs through MD simulations, facilitating the selection of components for MIPs. This computational approach holds the potential for extension to other templates, establishing a robust methodology for the rational design of MIPs.

Short-term effects of 448 kilohertz radiofrequency stimulation on plantar fascia measured by quantitative ultrasound elastography and thermography on active healthy subjects: an open controlled clinical trial.

Objective: This study is an open clinical trial. The aim of this study was to show the changes that occur in the viscoelastic properties of the plantar fascia (twenty healthy volunteers) measured by SEL and the changes in the plantar fascia temperature measured by thermography after the application of a 448 kHz capacitive resistive monopolar radiofrequency (CRMR) in active healthy subjects immediately after treatment and at the 1-week follow-up.Methods: Furthermore, to analyze if an intervention with 448 kHz CRMR in the plantar fascia of the dominant lower limb produces a thermal response in the plantar fascia of the non-dominant lower limb. The final objective was to analyze the level of association between the viscoelastic properties of the PF and the temperature before and after the intervention with 448 kHz CRMR.Results: Our results showed that a temperature change, which was measured by thermography, occurred in the plantar fascia after a single intervention (T0-T1) and at the 1-week follow up (T1-T2).Conclusion: However, no changes were found in the viscoelastic properties of the plantar fascia after the intervention or at the 1-week follow up. This is the first study to investigate changes in both plantar fascia viscoelastic properties and in plantar fascia temperature after a radiofrequency intervention.

The application of a single session of capacitive resistive electric transfer 24 h before exercise modifies the accelerometric pattern in standardbred racing trotters.

BACKGROUND: It has been reported that capacitive resistive electric transfer (CRET) increases blood circulation, hemoglobin oxygenation and temperature in muscles. The attributed benefits of these changes have been linked to improved athletic performance, enhanced muscle flexibility and fastening recovery from exercise-induced fatigue. For all of this, the present research aims to investigate whether the application of CRET 24 h before exercise affects the accelerometric pattern in horses during exercise. Six sound Standardbred trotters were subjected to a CRET session of 40 min of duration, applied on both sides of the neck, back and croup, 24 h before a training session. Training sessions consisted of a warming-up (WU) for 6400 m and a training bout (TB) at their maximal training speed for 1600 m. The same protocol was followed for the device off (sham protocol), also applied 24 h before the training session. CRET and sham experiments were separated by one week, the order of application of both was randomly defined for each individual and drivers were blinded for the duration of the experiment. During the training sessions, horses wore an accelerometer fixed at the sternal level. Speed, stride frequency (SF), length (SL), regularity and symmetry and accelerometric activities were measured during WU and TB. RESULTS: CRET increased speed, mediolateral and total accelerometric activities during WU and speed, SL, dorsoventral, longitudinal and total accelerometric activities during TB, but stride regularity and symmetry decreased. CONCLUSION: The application of CRET 24 h before exercise increased speed and accelerometric activities, results that highlight the need to evaluate the interaction between CRET and training in order to develop new methods to limit fatigue. However, the decrease in stride regularity and symmetry after CRET application could be negative effects, which could be attributed to the increased speed.

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.

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.

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.

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.

Pretransplant evaluation and the risk of glucose metabolic alterations after renal transplantation: a prospective study.

BACKGROUND: Post-transplant prediabetes (PreDM) and diabetes (PTDM) are common and have an impact on cardiovascular events. We sought to investigate the pathogenesis and best approach for prediction. METHODS: We prospectively studied 115 waitlisted patients from a single center without manifest diabetes. An oral glucose tolerance test (OGTT) was performed yearly until transplantation and 12 months later. Insulin secretion, insulin sensitivity (IS) and disposition index (DI) were derived from the OGTT. RESULTS: PreDM and PTDM were observed in 27% and 28.6% of patients, respectively. Pretransplant age, body mass index (BMI), 120 min glucose, IS, DI, and prediabetes or undiagnosed diabetes were significantly associated with these alterations. In multivariate analysis, pretransplant age [odds ratio (OR) 1.5; 95% confidence interval (CI) 1.04-2.1], BMI (OR 1.16; 95% CI 1.04-1.3) and cumulative steroids (OR 1.5; 95% CI 1.02-2.2) were predictors of PreDM or PTDM. Receiver operating characteristic curve analysis showed that pretransplant BMI and 120 min glucose had the highest area under the curve (0.72; 95% CI 0.62-0.8; and 0.69; 95% CI 0.59-0.79, respectively). The highest discrimination cut-off for BMI (≥28.5 kg/m2) and 120 min glucose (≥123.5 mg/dL) yielded a similar number needed to diagnose (2.5). CONCLUSIONS: PreDM or PTDM develops in waitlisted patients with an ineffective insulin secretion and BMI shows a similar diagnostic capacity to OGTT. Pretransplant interventions may reduce post-transplant glucose alterations.

Ploidy effects on the relationship between floral phenotype, reproductive investment, and fitness in an autogamous species complex.

PREMISE: The relationships between reproductive investment, phenotype, and fitness have been broadly studied in cross-pollinated plants in contrast to selfing species, which are considered less interesting in this area because they are supposed to be a dead end in any evolutionary pathway. Still, selfing plants are unique systems to study these questions since the position of reproductive structures and traits related to flower size play an important role in female and male pollination success. METHODS: Erysimum incanum s.l. is a selfing species complex that has three levels of ploidy (diploids, tetraploids, and hexaploids) and traits that are typically associated with the selfing syndrome. Here, we used 1609 plants belonging to these three ploidies to characterize the floral phenotype and spatial configuration of reproductive structures, reproductive investment (pollen and ovule production), and plant fitness. Then, we used structural equation modelling to analyze the relationship between all these variables across ploidy levels. RESULTS: An increase in ploidy level leads to bigger flowers with anthers exserted farther and more pollen and ovules. In addition, hexaploid plants had higher absolute values for herkogamy, which is positively correlated with fitness. Ovule production significantly mediated the natural selection acting on different phenotypic traits and pollen production, a pattern that is maintained across ploidies. CONCLUSIONS: The changes in floral phenotypes, reproductive investment, and fitness with ploidy level suggest that genome duplication can be a driver for transitions in reproductive strategy by modifying the investment in pollen and ovules and linking them with plant phenotype and fitness.

Risk of suicide attempt and suicide associated with benzodiazepine: A nationwide case crossover study.

BACKGROUND: Previous studies that found an association between benzodiazepines and suicidal behaviours were confounded by indication bias. AIMS: To limit this bias, a case crossover study (CCO) was conducted to estimate the risk of suicide attempt and suicide associated with benzodiazepines. METHOD: Patients ≥16 years, with hospitalised suicide attempt or suicide between 2013 and 2016, and at least one benzodiazepine dispensing within the 120 days before their act were selected in the nationwide French reimbursement healthcare system databases (SNDS). For each patient, frequency of benzodiazepine dispensing was compared between a risk period (days -30 to -1 before the event) and two matched reference periods (days -120 to -91, and -90 to -61). RESULTS: A total of 111,550 individuals who attempted suicide and 12,312 suicide victims were included, of who, respectively, 77,474 and 7958 had recent psychiatric history. Benzodiazepine dispensing appeared higher in the 30-day risk period than in reference ones. The comparison yielded adjusted odds ratios of 1.74 for hospitalised suicide attempt (95% confidence interval 1.69-1.78) and 1.45 for suicide (1.34-1.57) in individuals with recent psychiatric history, and of 2.77 (2.69-2.86) and 1.80 (1.65-1.97) for individuals without. CONCLUSION: This nationwide study supports an association between recent benzodiazepine use and both suicide attempt and suicide. These results strengthen the need for screening for suicidal risk carefully before initiation and during treatment when prescribing benzodiazepines. REGISTRATION NO: EUPAS48070 (http://www.ENCEPP.eu).

Risk factors associated with acute kidney injury in a cohort of hospitalized patients with COVID-19.

BACKGROUND: Patients with COVID-19 have a high incidence of acute kidney injury (AKI), which is associated with mortality. The objective of the study was to determine the factors associated with AKI in patients with COVID-19. METHODOLOGY: A retrospective cohort was established in two university hospitals in Bogotá, Colombia. Adults hospitalized for more than 48 h from March 6, 2020, to March 31, 2021, with confirmed COVID-19 were included. The main outcome was to determine the factors associated with AKI in patients with COVID-19 and the secondary outcome was estimate the incidence of AKI during the 28 days following hospital admission. RESULTS: A total of 1584 patients were included: 60.4% were men, 738 (46.5%) developed AKI, 23.6% were classified as KDIGO 3, and 11.1% had renal replacement therapy. The risk factors for developing AKI during hospitalization were male sex (OR 2.28, 95% CI 1.73-2.99), age (OR 1.02, 95% CI 1.01-1.03), history of chronic kidney disease (CKD) (OR 3.61, 95% CI 2.03-6.42), High Blood Pressure (HBP) (OR 6.51, 95% CI 2.10-20.2), higher qSOFA score to the admission (OR 1.4, 95% CI 1.14-1.71), the use of vancomycin (OR 1.57, 95% CI 1.05-2.37), piperacillin/tazobactam (OR 1.67, 95% CI 1.2-2.31), and vasopressor support (CI 2.39, 95% CI 1.53-3.74). The gross hospital mortality for AKI was 45.5% versus 11.7% without AKI. CONCLUSIONS: This cohort showed that male sex, age, history of HBP and CKD, presentation with elevated qSOFA, in-hospital use of nephrotoxic drugs and the requirement for vasopressor support were the main risk factors for developing AKI in patients hospitalized for COVID-19.

Antioxidant Activity in Extracts from Zingiberaceae Family: Cardamom, Turmeric, and Ginger.

An increase in life expectancy leads to a greater impact of chronic non-communicable diseases. This is even more remarkable in elder populations, to whom these become main determinants of health status, affecting mental and physical health, quality of life, and autonomy. Disease appearance is closely related to the levels of cellular oxidation, pointing out the importance of including foods in one's diet that can prevent oxidative stress. Previous studies and clinical data suggest that some plant-based products can slow and reduce the cellular degradation associated with aging and age-related diseases. Many plants from one family present several applications that range from the food to the pharmaceutical industry due to their characteristic flavor and scents. The Zingiberaceae family, which includes cardamom, turmeric, and ginger, has bioactive compounds with antioxidant activities. They also have anti-inflammatory, antimicrobial, anticancer, and antiemetic activities and properties that help prevent cardiovascular and neurodegenerative diseases. These products are abundant sources of chemical substances, such as alkaloids, carbohydrates, proteins, phenolic acids, flavonoids, and diarylheptanoids. The main bioactive compounds found in this family (cardamom, turmeric, and ginger) are 1,8-cineole, α-terpinyl acetate, ß-turmerone, and α-zingiberene. The present review gathers evidence surrounding the effects of dietary intake of extracts of the Zingiberaceae family and their underlying mechanisms of action. These extracts could be an adjuvant treatment for oxidative-stress-related pathologies. However, the bioavailability of these compounds needs to be optimized, and further research is needed to determine appropriate concentrations and their antioxidant effects in the body.

Diffuse gastric adenocarcinoma during pregnancy and genetic counseling.

We present the case of a 38-year-old woman who, in the context of a 22-week gestation, was diagnosed with diffuse gastric adenocarcinoma. The age of the patient and the way in which the cancer presented itself, make genetic counseling mandatory to rule out hereditary diffuse gastric carcinoma syndrome. This rare entity, of autosomal dominant inheritance and closely linked to mutations in the CDH1 (in most cases) and CTNNA1 genes, is associated with a greater predisposition to develop malignant neoplasms of the breast and stomach. Genetic sequencing ruled out hereditary diffuse gastric cancer syndrome. Unfortunately, 24 months after the cesarean section, our patient dies.

Nutritional and antioxidant profile of the Physalis fruit grown in three Andean regions of Peru.

Background: Physalis peruviana L. fruit contains nutritional and bioactive compounds of immense importance to public health and represents a potential ingredient for the development of functional foods and beverages. Objective: This study aimed to determine the chemical and nutritional composition as well as the antioxidant capacity of the P. peruviana L. fruit grown in Peru in three areas of the Central Andean region. Material and methods: Proximal and physicochemical analyses and estimation of mineral content, vitamin C, total carotenoids, total polyphenols, and antioxidant capacity (2, 2-diphenyl-1-picrylhydrazyl [DPPH] and 2, 2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) [ABTS] assays) were performed using standardized methods. Results: The fruits were collected from three regions of the Peruvian Andes (Ancash, Cajamarca, and Cusco). The results showed that the content of potassium (306.54-327.60 mg/100 g) and iron (12.93-14.47 mg/kg) was prominent. The Physalis fruit had high levels of vitamin C (47.20-52.20 mg/100 g), total polyphenols (68.17-83.40 mg equivalents of gallic acid/100 g), and carotenoids (1.12-1.73 mg ß-carotene/100 g). Higher values for antioxidant capacity were obtained with the ABTS method (896-1003.33 µmol Trolox/100 g) than with the DPPH method (290-309 µmol Trolox/100 g). Conclusions: This study confirms that the P. peruviana fruit has properties that could provide important health benefits and that it could be used for the development of functional foods and food supplement.

Diabetes, insulin and new therapeutic strategies for Parkinson's disease: Focus on glucagon-like peptide-1 receptor agonists.

Parkinson's disease and diabetes mellitus are two chronic disorders associated with aging that are becoming increasingly prevalent worldwide. Parkinson is a multifactorial progressive condition with no available disease modifying treatments at the moment. Over the last few years there is growing interest in the relationship between diabetes (and impaired insulin signaling) and neurodegenerative diseases, as well as the possible benefit of antidiabetic treatments as neuroprotectors, even in non-diabetic patients. Insulin regulates essential functions in the brain such as neuronal survival, autophagy of toxic proteins, synaptic plasticity, neurogenesis, oxidative stress and neuroinflammation. We review the existing epidemiological, experimental and clinical evidence that supports the interplay between insulin and neurodegeneration in Parkinson's disease, as well as the role of antidiabetic treatments in this disease.

Effectiveness of a polyphenolic extract (Lippia citriodora and Hibiscus sabdariffa) on appetite regulation in overweight and obese grade I population: an 8-week randomized, double-blind, cross-over, placebo-controlled trial.

INTRODUCTION: Polyphenols have shown capacity to improve appetite sensation, leading to enhanced control of body weight. However, despite being related with hunger-related hormones, metabolic and mechanism are not well known. METHODS: The effectiveness of a nutraceutical composed of extract to Lippia citriodora and Hibiscus sabdarrifa (Lc-Hs) for controlling satiety and hunger was analyzed in a cross-over, placebo-controlled (Pla) clinical intervention. The study was divided in two 60-day periods separated by 30-day length wash-out period. At the end of each period, overweight and obese subjects (n = 33; age = 33.76 ± 12.23; BMI = 28.20 kg/m2 ± 2.47; fat mass 30.65 ± 8.39%; both sexes were proposed to eat an ad-libitum meal. Meanwhile, appetite sensation was determined by visual analog scales at different times. Moreover, blood extraction was performed to determine biochemical parameters (lipid and glucidic profile and safety parameters) and to evaluate hunger-related hormones (insulin, leptin, ghrelin, adiponectin, GLP-1 and peptide YY). RESULTS: A decrease in appetite sensation was observed in Lc-Hs treatment, showing higher satiety quotient (Pla = 3.36 ± 2.33%mm/kcal; Lc-Hs = 5.53 ± 2.91%mm/kcal; p < 0.0001). Area under the curve was higher in Pla compared to Lc-Hs during the test, from baseline to minute 240 (240 (Pla 9136.65 ± 2261.46% x min-1; Lc-Hs 8279.73 ± 2745.71% x min-1; p < 0.014). Energy consumption was lower for subjects treated with Lc-Hs (774.44 ± 247.77 kcal) compared to those treated with Pla (849.52 ± 246.54 kcal) (p < 0.004). Leptin values varied from baseline (Pla 12.36 ± 1.98 ng/mL; Lc-Hs 13.13 ± 1.99 ng/mL) to the end of the study (Pla 12.60 ± 2.02 ng/mL; Lc-Hs 12.06 ± 2.05 ng/mL; p < 0.047). GLP-1 values varied (p < 0.001) in Lc-Hs treatment from baseline (4.34 ± 0.49 ng/mL) to the end of the study (3.23 ± 0.52 ng/mL). CONCLUSION: The supplementation with the Lc-Hs extract decreases appetite sensation in overweight and obese population, reducing calorie intake after an ad-libitum meal. Due to variation on hunger-related hormones and the relationship between satiety feeling, it would be interesting to develop future research focused on the variation of the hormones themselves.

Tolerability of Oral Supplementation with Microencapsulated Ferric Saccharate Compared to Ferrous Sulphate in Healthy Premenopausal Woman: A Crossover, Randomized, Double-Blind Clinical Trial.

A single-center, crossover, randomized, double-blind, and controlled clinical study was conducted to assess the tolerability profile, especially with regard to gastrointestinal complaints, of oral supplementation with AB-Fortis®, a microencapsulated ferric saccharate (MFS), as compared with conventional ferrous sulphate (FS) in healthy premenopausal women. A dose of 60 mg/day of elemental iron was used. The test products were administered for 14 consecutive days with a washout period of two menstrual episodes and a minimum of one month between the two intervention periods. The subjects completed simple-to-answer questionnaires daily for 14 days during both the intervention and the washout periods, capturing the symptoms associated with oral iron supplementation and overall health aspects. Following product consumption, the incidences of symptoms, numbers of complaints/symptoms, overall intensity, and total days with symptoms were found to be significantly higher for FS consumption as compared to MFS. The better tolerability profile of MFS over FS was further substantiated when both products were compared to a real-life setting (i.e., the washout period). Overall, the administration of both study products was safe with no serious or significant adverse events reported. In summary, the current study shows the better tolerability of the MFS preparation when compared to that of the FS, presenting MFS as a well-tolerated and safe option for improving iron nutrition.

[Embolization of spontaneous portosystemic shunts as treatment for refractory hepatic encephalopathy]. / Embolización de colaterales portosistémicas espontáneas como tratamiento de la encefalopatía hepática refractaria.

BACKGROUND: Hepatic encephalopathy (HE) is a common complication of cirrhosis associated with a reduced survival. The presence of high-flux spontaneous porto-systemic shunts can induce HE even in patients with preserved liver function. AIM: To evaluate the effect of spontaneous porto-systemic shunt embolization (SPSE) over HE and its long-term evolution. MATERIAL AND METHODS: Retrospective analysis of 11 patients (91% males) with severe HE non-responsive to medical treatment in whom a SPSE was performed. The grade of HE (employing West Haven score), survival, MELD and Child-Pugh score, ammonia levels, degree of disability (employing the modified Rankin scale (mRs)) were evaluated before and at thirty days after procedure. RESULTS: The most common etiology found was non-alcoholic steatohepatitis (63.6%). A reduction of at least two score points of HE was observed in all patients after thirty days. There was a significant reduction on median (IQR) West Haven score from 3 (2-3) at baseline to 1 (0-1) after the procedure (p < 0.01). Twelve months survival was 63.6%. There was a decrease in median ammonia level from 106.5 (79-165) (ug/dL) to 56 (43-61) after SPSE (p = 0.006). The median mRS score before and after the procedure was 3 (3-5) and 1 (1-2.5), respectively (p < 0.01). CONCLUSIONS: According to our experience, SPSE is a feasible and effective alternative to improve HE and functionality of patients with refractory EH.