The Diagnostic and Prognostic Potentials of Non-Coding RNA in Cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a rare biliary tract tumor with high malignancy. CCA is the second most common primary hepatobiliary cancer after hepatocarcinoma. Despite its rarity, the incidence of CCA is steadily increasing globally. Most patients with CCA are asymptomatic in the early stages, resulting in a late-stage diagnosis and poor prognosis. Finding reliable biomarkers is essential to improve CCA's early diagnosis and survival rate. Non-coding RNAs (ncRNAs) are non-protein coding RNAs produced by genomic transcription. This includes microRNAs, long non-coding RNAs, and circular RNAs. ncRNAs have multiple functions in regulating gene expression and are crucial for maintaining normal cell function and developing diseases. Many studies have shown that aberrantly expressed ncRNAs can regulate the occurrence and development of CCA. ncRNAs can be easily extracted and detected through tumor tissue and liquid biopsies, representing a potential tool for diagnosing and prognosis CCA. This review will provide a detailed update on the diagnostic and prognostic potentials of lncRNAs and cirRNAs as biomarkers in CCA.

Prediabetes blunts DPP4 genetic control of postprandial glycaemia and insulin secretion.

AIMS/HYPOTHESIS: Imbalances in glucose metabolism are hallmarks of clinically silent prediabetes (defined as impaired fasting glucose and/or impaired glucose tolerance) representing dysmetabolism trajectories leading to type 2 diabetes. CD26/dipeptidyl peptidase 4 (DPP4) is a clinically proven molecular target of diabetes-controlling drugs but the DPP4 gene control of dysglycaemia is not proven. METHODS: We dissected the genetic control of post-OGTT and insulin release responses by the DPP4 gene in a Portuguese population-based cohort of mainly European ancestry that comprised individuals with normoglycaemia and prediabetes, and in mouse experimental models of Dpp4 deficiency and hyperenergetic diet. RESULTS: In individuals with normoglycaemia, DPP4 single-nucleotide variants governed glycaemic excursions (rs4664446, p=1.63x10-7) and C-peptide release responses (rs2300757, p=6.86x10-5) upon OGTT. Association with blood glucose levels was stronger at 30 min OGTT, but a higher association with the genetic control of insulin secretion was detected in later phases of the post-OGTT response, suggesting that the DPP4 gene directly senses glucose challenges. Accordingly, in mice fed a normal chow diet but not a high-fat diet, we found that, under OGTT, expression of Dpp4 is strongly downregulated at 30 min in the mouse liver. Strikingly, no genetic association was found in prediabetic individuals, indicating that post-OGTT control by DPP4 is abrogated in prediabetes. Furthermore, Dpp4 KO mice provided concordant evidence that Dpp4 modulates post-OGTT C-peptide release in normoglycaemic but not dysmetabolic states. CONCLUSIONS/INTERPRETATION: These results showed the DPP4 gene as a strong determinant of post-OGTT levels via glucose-sensing mechanisms that are abrogated in prediabetes. We propose that impairments in DPP4 control of post-OGTT insulin responses are part of molecular mechanisms underlying early metabolic disturbances associated with type 2 diabetes.

Comparative randomized trial study about the efficacy of photobiomodulation and curcumin antimicrobial photodynamic therapy as a coadjuvant treatment of oral mucositis in oncologic patients: antimicrobial, analgesic, and degree alteration effect.

INTRODUCTION: As conventional treatments currently available for mucositis are not considerably effective, there is a need to implement an adjuvant protocol for the treatment of oral mucositis in patients undergoing radiotherapy and chemotherapy. PURPOSE: To evaluate the effect of photobiomodulation (PBM) and antimicrobial photodynamic therapy (aPDT) mediated by curcumin and blue LED as an adjunct treatment of oral mucositis for oncology patients using chemotherapy and/or radiotherapy. METHODS: Clinical, randomized study, in a single location, in an oncology service of a general hospital, with a total of 30 patients (over 18 years old) with stable oral mucosa lesions in the process of chemotherapy and/or radiotherapy. The patients were divided into 3 groups: control group (treated with nystatin), PBM group (treated with low-level laser therapy), and the aPDT group (treated with 450-nm blue LED and curcumin photosensitizer). RESULTS: The results showed, by means of intra-group comparisons, that the two experimental treatments promoted yeast reduction of the genus Candida in the last two evaluations (21 days and 30 days), but not in the first two evaluations (7 days and 14 days). The intra-group comparisons showed that the control and aPDT group showed a significant difference in the degree of mucositis over the four evaluations performed, with the results pointing out that the mucositis worsened in the control group from the 14th day, while reduced in the aPDT group from the 21st day of treatment. CONCLUSION: A reduction in the degree of mucositis and pain score was observed in the PBM and aPDT groups, with the aPDT group standing out when presenting early clinical improvement in relation to the PBM group and the control group, thus emphasizing its effectiveness within the desired aspects. Regarding the antimicrobial effect, aPDT showed a greater reduction of yeasts of the genus Candida in the tested parameters.

Impact of blinded retrospective continuous glucose monitoring on clinical decision making and glycemic control in persons with type 2 diabetes on insulin therapy.

BACKGROUND AND AIMS: Blinded retrospective continuous glucose monitoring (rCGM) provides detailed information about real-life glycaemic profile. In persons with type 2 diabetes without adequate glycaemic control, the structured introduction of rCGM may be beneficial to sustain improvements in diabetes management. METHODS AND RESULTS: 102 individuals with insulin-treated type 2 diabetes, age less than 66 years old and HbA1c >7.5%, were recruited. Participants performed a 7-day blinded rCGM (iPro2) every four months for one year. Biochemical, anthropometric, and rCGM data was collected. Participants' and healthcare professionals' perceptions were assessed. 90 participants completed the protocol. HbA1c was 9.1 ± 0.1% one year prior to enrolment and 9.4 ± 0.1% at enrolment (p < 0.01). With the rCGM-based intervention, a decrease in HbA1c was achieved at 4 months (8.4 ± 0.1%, p < 0.0001), and 12 months (8.1 ± 0.1%, p < 0.0001). A significant increase in time-in-range was observed (50.8 ± 2.4 at baseline vs 61.5 ± 2.2% at 12 months, for 70-180 mg/dL, p < 0.001), with no difference in exposure time to hypoglycaemia. After 12 months, there was an increase in self-reported diabetes treatment satisfaction (p < 0.05). CONCLUSION: In persons with type 2 diabetes and poor metabolic control, specific data from blinded rCGM informed therapeutic changes and referral to targeted education consultations on nutrition and insulin administration technique. Therapeutic changes were made more frequently and targeted to changes in medication dose, timing, and/or type, as well as to lifestyle. Together, these brought significant improvements in clinical outcomes, effective shared decision-making, and satisfaction with treatment. REGISTRATION NUMBER: NCT04141111.

Combined effect of interventions with pure or enriched mixtures of (poly)phenols and anti-diabetic medication in type 2 diabetes management: a meta-analysis of randomized controlled human trials.

PURPOSE: (Poly)phenols have been reported to confer protective effects against type 2 diabetes but the precise association remains elusive. This meta-analysis aimed to assess the effects of (poly)phenol intake on well-established biomarkers in people with type 2 diabetes or at risk of developing diabetes. METHODS: A systematic search was conducted using the following selection criteria: (1) human randomized controlled trials involving individuals with prediabetes and type 2 diabetes; (2) one or more of the following biomarkers: glucose, glycated haemoglobin (HbA1c), insulin, pro-insulin, homeostatic model assessment of insulin resistance (HOMA-IR), islet amyloid polypeptide (IAPP)/amylin, pro-IAPP/pro-amylin, glucagon, C-peptide; (3) chronic intervention with pure or enriched mixtures of (poly)phenols. From 488 references, 88 were assessed for eligibility; data were extracted from 27 studies and 20 were used for meta-analysis. The groups included in the meta-analysis were: (poly)phenol mixtures, isoflavones, flavanols, anthocyanins and resveratrol. RESULTS: Estimated intervention/control mean differences evidenced that, overall, the consumption of (poly)phenols contributed to reduced fasting glucose levels (- 3.32 mg/dL; 95% CI - 5.86, - 0.77; P = 0.011). Hb1Ac was only slightly reduced (- 0.24%; 95% CI - 0.43, - 0.044; P = 0.016) whereas the levels of insulin and HOMA-IR were not altered. Subgroup comparative analyses indicated a stronger effect on blood glucose in individuals with diabetes (- 5.86 mg/dL, 95% CI - 11.34, - 0.39; P = 0.036) and this effect was even stronger in individuals taking anti-diabetic medication (- 10.17 mg/dL, 95% CI - 16.59, - 3.75; P = 0.002). CONCLUSIONS: Our results support that the consumption of (poly)phenols may contribute to lower glucose levels in individuals with type 2 diabetes or at risk of diabetes and that these compounds may also act in combination with anti-diabetic drugs.

Effectiveness of high-intensity interval training combined with resistance training versus continuous moderate-intensity training combined with resistance training in patients with type 2 diabetes: A one-year randomized controlled trial.

AIMS: To evaluate the impact of one-year high intensity interval training (HIIT) combined with resistance training (RT) vs continuous moderate intensity training (MCT) combined with RT on glycaemic control, body composition and cardiorespiratory fitness (CRF) in patients with type 2 diabetes. MATERIALS AND METHODS: A randomized controlled trial included 96 participants with type 2 diabetes for a one-year supervised exercise intervention with three groups: Control, HIIT with RT and MCT with RT). The control group received standard counseling regarding general PA guidelines, with no structured exercise sessions. The main outcome variable was HbA1c (%). Secondary outcomes were other glycaemic variables, body composition, anthropometry measurements, CRF and enjoyment of exercise. Generalized estimating equations (GEE) were used to model outcomes. RESULTS: Among the 96 participants enrolled in the intervention, 80 were randomized, with a mean (SD) age of 58.5 years (7.7) and a mean HbA1c of 7.2% (1.6). After adjusting the model for sex and total moderate-to-vigorous physical activity (MVPA), we found that both the MCT with RT (ß, 0.003; P, 0.921) and the HIIT with RT (ß, 0.025; P, 0.385) groups had no effect on HbA1c. A favourable effect was observed in the MCT with RT group, with a reduction in whole body fat index (ß, -0.062; P, 0.022), android fat index (ß, -0.010; P, 0.010) and gynoid fat index (ß, -0.013; P, 0.014). Additionally, CRF increased during the intervention, but only in the MCT with RT group (ß, 0.185; P, 0.019). CONCLUSIONS: The results from this study suggest that there was no effect of either MCT with RT or HIIT with RT on glycaemic control in individuals with type 2 diabetes. However, the combination of MCT and RT improved body composition and CRF following a one-year intervention.

Association between glycated haemoglobin, glycated albumin and fructosamine with neonatal birthweight and large-for-date status infants in gestational diabetes mellitus: a prospective cohort study.

This study aims to investigate associations between glycated haemoglobin (HbA1c), glycated albumin (GA) and fructosamine with neonatal birthweight in gestational diabetes mellitus (GDM). The prospective cohort consisted of 82 women with GDM and their newborns, enrolled between November 2016 and September 2017. Considering neonatal birthweight and birthweights ≥90th percentile for gestational age as outcomes, linear and logistic regression models were used, respectively. Fructosamine (R2=0.62) and GA (R2=0.61) performed very similarly between them and best than HbA1c (R2=0.58). The added value of GA or fructosamine to HbA1c resulted in increase in models' performances. GA attained the best discriminative ability regarding large-for-date status babies (AUC = 0.80, OR-estimate 1.58, p=.001) followed by fructosamine (AUC = 0.78, OR-estimate 1.42, p=.001) and HbA1c (AUC = 0.69, OR-estimate 3.09, p=.070). GA and fructosamine, besides from providing additional information to HbA1c, when used separately perform better than the traditional biomarker in predicting neonatal birthweight and large-for-date babies in pregnant women with GDM. Impact statement What is already known on this subject? HbA1c is the standard glycaemic indicator used in GDM. Its association with birthweight and large-for-date status has been previously reported. However, it has become increasingly questionable whether it is a suitable glycaemic marker in pregnancy. There is a growing interest in other non-traditional shorter-term glycaemic indicators, such as GA and fructosamine. Nevertheless, few studies exist and almost all are retrospective and with ethnically homogeneous study populations composed by pregnant women not only with GDM but also type 1 and type 2 diabetes mellitus. What do the results of this study add? Our prospective multi-ethnic cohort composed solely on pregnant women with GDM and their infants show that even though all of the aforementioned biomarkers are associated with birthweight and large-for-date status in GDM when used separately, GA and fructosamine seem to perform better than HbA1c. When used with HbA1c, they improve the predicting performance of the traditional marker. What are the implications of these findings for future clinical practice and/or further research? These findings suggest that GA and fructosamine can provide important additional or substitute information to HbA1c in GDM, namely in predicting birthweight and large-for-date status babies. Larger studies are needed to confirm if this non-traditional biomarkers can change clinical practice.

Infidelity in Dating Relationships: Gender-Specific Correlates of Face-to-Face and Online Extradyadic Involvement.

This study examined the gender-specific correlates of face-to-face and online extradyadic involvement (EDI) in dating relationships. The sample consisted of 561 women (M age = 23.19 years) and 222 men (M age = 23.97 years), all of whom reported being in an exclusive dating relationship for an average of 35 months. Participants completed the following self-report measures: Extradyadic Behavior Inventory, Attitudes toward Infidelity Scale, and Investment Model Scale. During the current relationship, men were more likely than women to report engagement in face-to-face physical/sexual EDI (23.4 vs. 15.5 %) and online sexual EDI (15.3 vs. 4.6 %). Both men and women with a history of infidelity in a prior relationship were more likely to engage in EDI. More positive attitudes toward infidelity, lower relationship satisfaction, lower commitment, and higher quality of alternatives were significantly associated with EDI, regardless of gender. Women reporting infidelity of a partner in a prior relationship were more likely to engage in face-to-face and online emotional EDI; a longer relationship and a younger age at the first sexual encounter were significant correlates of the engagement in face-to-face emotional EDI. Women with higher education were approximately three times more likely to engage in online sexual EDI. Although men and women are converging in terms of overall EDI, men still report higher engagement in physical/sexual extradyadic behaviors, and the correlates of sexual and emotional EDI vary according to gender. This study contributes to a comprehensive approach of factors influencing the likelihood of EDI and encourages future research in this area.

Analysis of the effect of soil saprophytic fungi on the eggs of Baylisascaris procyonis.

Baylisascaris procyonis is a soil-transmitted helminth mainly found in raccoons (Procyon lotor) which can also affect other domestic and sylvatic animals, as well as humans, when the eggs released in the feces of parasitized raccoons are accidentally ingested. Three assays have been conducted to assess the effect of three saprophytic fungi, Mucor circinelloides, Paecilomyces lilacinus, and Verticillium sp., on the eggs of B. procyonis. Firstly, their ovicidal effect was in vitro ascertained by placing 1 mL with 2 × 10(6) spores of each fungus in Petri plates with water-agar (2 %) and simultaneously adding 200 eggs of Baylisascaris/plate. Two in vivo probes were carried out, by spraying the fungal spores (3 mL containing about 2 × 10(6) spores/mL) on the feces of raccoons and coatis (Nasua narica) passing eggs of B. procyonis in a zoological park; the other assay consisted of evaluating the activity of the fungi after adding sand to fecal samples from raccoons. An ovicidal type 3 activity characterized by morphological damage of the eggshell with hyphal penetration, internal egg colonization, and embryo alteration was observed for all the tested fungi. In the plate assays, viability of Baylisascaris eggs reduced significantly by 53-69 % with Mucor, 45-62 % with Paecilomyces, and 52-67 % with Verticillium. A similar ovicidal effect was detected in the feces with sand. These results demonstrate the usefulness of spraying spores of M. circinelloides, Pa. lilacinus, or Verticillium sp. on the feces of animals infected by Baylisascaris to decrease the numbers of viable eggs and, thus, the risk of infection.

Transcription readthrough is prevalent in healthy human tissues and associated with inherent genomic features.

Transcription termination is a crucial step in the production of conforming mRNAs and functional proteins. Under cellular stress conditions, the transcription machinery fails to identify the termination site and continues transcribing beyond gene boundaries, a phenomenon designated as transcription readthrough. However, the prevalence and impact of this phenomenon in healthy human tissues remain unexplored. Here, we assessed transcription readthrough in almost 3000 transcriptome profiles representing 23 human tissues and found that 34% of the expressed protein-coding genes produced readthrough transcripts. The production of readthrough transcripts was restricted in genomic regions with high transcriptional activity and was associated with inefficient splicing and increased chromatin accessibility in terminal regions. In addition, we showed that these transcripts contained several binding sites for the same miRNA, unravelling a potential role as miRNA sponges. Overall, this work provides evidence that transcription readthrough is pervasive and non-stochastic, not only in abnormal conditions but also in healthy tissues. This suggests a potential role for such transcripts in modulating normal cellular functions.

Formulating Parasiticidal Fungi in Dried Edible Gelatins to Reduce the Risk of Infection by Trichuris sp. among Continuous Grazing Bison.

Control of infection by gastrointestinal nematodes remains a big problem in ruminants under continuous grazing. For the purpose of decreasing the risk of infection by Trichuris sp. in captive bison (Bison bison) always maintained in the same plot, dried gelatins having ≥106 chlamydospores of both Mucor circinelloides and Duddingtonia flagrans were given to them for one week, and at the end, fecal samples (FF) collected each week for four weeks were analyzed immediately. Feces taken one week prior to gelatin administration served as controls (CF). Eggs of Trichuris sp. were sorted into non-viable and viable, then classified into viable undeveloped (VU), viable with cellular development (VCD), or viable infective (VI). Ovistatic and ovicidal effects were determined throughout the study. In FF, viability of Trichuris eggs decreased between 9% (first week) and 57% (fourth week), egg development was delayed during the first two weeks, and VI percentages were significantly lower than in CF (p = 0.001). It is concluded that the preparation of gelatins with chlamydospores of parasiticidal fungi and their subsequent dehydration offer an edible formulation that is ready to use, stress-free to supply, and easy to store, as well as being well-accepted by ruminants and highly efficient to reduce the risk of Trichuris sp. infection among animals under continuous grazing regimes.

Interaction time with conspecifics induces food preference or aversion in the wild Algerian mouse.

The social transmission of a novel food preference can avoid unnecessary costs arising from tasting nonedible foods. This type of social learning has been demonstrated in laboratory rats and mice. However, among wild animals, there may be several constraints that make it less effective. Using wild Algerian mice (Mus spretus) tested in the laboratory, we demonstrate that a preference for a novel food can be transmitted between Observer and Demonstrator individuals and that it is maintained for at least 30 days. However, only half of the Observers acquired a preference for the same food as the Demonstrators, and only when the duration of oronasal investigation was above a certain threshold (≥122 s); below this threshold (<122 s), Observers acquired a preference for the alternative food offered, which was maintained for a shorter time. Sex, size, and identity of individuals did not influence the transmission of social information. The results show that different interaction times will result in animals copying or avoiding the food choices of others. This suggests that the transmission of social information among wild animals is complex and probably influenced by many factors (e.g., dominance, familiarity, and health condition), ultimately conditioning the type of interaction between individuals and its outcome. Testing wild animals and the ecological and social constraints they face is, therefore, an important step in our understanding of how effectively social information is transmitted in nature.

Liver fat accumulation more than fibrosis causes early liver dynamic dysfunction in patients with non-alcoholic fatty liver disease.

INTRODUCTION: In Non-Alcoholic Fatty Liver Disease (NAFLD), events driving early hepatic dysfunction with respect to specific metabolic pathways are still poorly known. METHODS: We enrolled 84 subjects with obesity and/or type 2 diabetes (T2D). FibroScan® served to assess NAFLD by controlled attenuation parameter (CAP), and fibrosis by liver stiffness (LS). Patients with LS above 7 kPa were excluded. APRI and FIB-4 were used as additional serum biomarkers of fibrosis. The stable-isotope dynamic breath test was used to assess the hepatic efficiency of portal extraction (as DOB15) and microsomal metabolization (as cPDR30) of orally-administered (13C)-methacetin. RESULTS: NAFLD occurred in 45%, 65.9%, and 91.3% of normal weight, overweight, and obese subjects, respectively. Biomarkers of liver fibrosis were comparable across subgroups, and LS was higher in obese, than in normal weight subjects. DOB15 was 23.2 ± 1.5‰ in normal weight subjects, tended to decrease in overweight (19.9 ± 1.0‰) and decreased significantly in obese subjects (16.9 ± 1.3, P = 0.008 vs. normal weight). Subjects with NAFLD had lower DOB15 (18.7 ± 0.9 vs. 22.1 ± 1.2, P = 0.03) but higher LS (4.7 ± 0.1 vs. 4.0 ± 0.2 kPa, P = 0.0003) than subjects without NAFLD, irrespective of fibrosis. DOB15 (but not cPDR30) decreased with increasing degree of NAFLD (R = -0.26; P = 0.01) and LS (R = -0.23, P = 0.03). Patients with T2D showed increased rate of NAFLD than those without T2D but similar LS, DOB15 and cPDR30. CONCLUSIONS: Overweight, obesity and liver fat accumulation manifest with deranged portal extraction efficiency of methacetin into the steatotic hepatocyte. This functional alteration occurs early, and irrespective of significant fibrosis and presence of T2D.

Enzyme-linked immunosorbent assays for the detection of equine antibodies specific to a recombinant Fasciola hepatica surface antigen in an endemic area.

The utility of an enzyme-linked immunosorbent assay to determine the sensitization against the trematode Fasciola hepatica in horses from an endemic area (NW Spain) was assessed. Blood samples were collected from 536 horses and tested against a 2.9-kDa recombinant surface protein (FhrAPS) to estimate the presence of IgG antibodies. Data were analysed regarding several intrinsic (age, gender and breed) and extrinsic factors (aptitude and housing). The farm size (number of horses/farm) was also considered. Sixty percent (95% CI 56, 64) of the horses were positive to the FhrAPS-ELISA, with a significantly higher seroprevalence in the mares (67%). Foals reached the lowest percentage of sensitization against the trematode (12%), and a significant positive correlation between the seroprevalence of fasciolosis and the age of the horses was established. When considering all the factors together, the seroprevalence of fasciolosis was initially classified into two groups (nodes) regarding the age of the horses. The node composed of the horses older than 1 year was then divided into two other clusters according to their gender. The mares were finally classified and grouped into two nodes regarding their breed. We concluded that the FhrAPS-ELISA is very useful for the demonstration of specific equine IgG antibodies against F. hepatica. An elevated risk of exposition to this trematode in horses maintained in endemic areas was proven. The possible role of horses as reservoirs for F. hepatica infections is discussed.

Increased Intake of Both Caffeine and Non-Caffeine Coffee Components Is Associated with Reduced NAFLD Severity in Subjects with Type 2 Diabetes.

Coffee may protect against non-alcoholic fatty liver disease (NAFLD), but the roles of the caffeine and non-caffeine components are unclear. Coffee intake by 156 overweight subjects (87% with Type-2-Diabetes, T2D) was assessed via a questionnaire, with 98 subjects (all T2D) also providing a 24 h urine sample for quantification of coffee metabolites by LC-MS/MS. NAFLD was characterized by the fatty liver index (FLI) and by Fibroscan® assessment of fibrosis. No associations were found between self-reported coffee intake and NAFLD parameters; however, total urine caffeine metabolites, defined as Σcaffeine (caffeine + paraxanthine + theophylline), and adjusted for fat-free body mass, were significantly higher for subjects with no liver fibrosis than for those with fibrosis. Total non-caffeine metabolites, defined as Σncm (trigonelline + caffeic acid + p-coumaric acid), showed a significant negative association with the FLI. Multiple regression analyses for overweight/obese T2D subjects (n = 89) showed that both Σcaffeine and Σncm were negatively associated with the FLI, after adjusting for age, sex, HbA1c, ethanol intake and glomerular filtration rate. The theophylline fraction of Σcaffeine was significantly increased with both fibrosis and the FLI, possibly reflecting elevated CYP2E1 activity-a hallmark of NAFLD worsening. Thus, for overweight/obese T2D patients, higher intake of both caffeine and non-caffeine coffee components is associated with less severe NAFLD. Caffeine metabolites represent novel markers of NAFLD progression.

A New Comestible Formulation of Parasiticide Fungi to Reduce the Risk of Soil-Transmitted Helminth Infections in a Canine Shelter.

Dogs cared for in a shelter are dewormed every three-four months, but they all become infected one-two months later by the soil-transmitted helminths (STHs) Toxocara canis, Toxascaris leonina, Trichuris vulpis, and Ancylostoma caninum. For the purpose of reducing their risk of infection by decreasing the survival of helminths' infective stages in soil, chlamydospores of two parasiticide fungi, Mucor circinelloides (ovicide) and Duddingtonia flagrans (larvicide) were formulated as handmade edible gelatins and given three days per week for 17 months to 18 dogs (DRF, dogs receiving fungi); a second group was maintained without fungi (CD, control dogs). All individuals were dewormed at months 0, 3, 7, 10 and 13, and it was observed that the levels of helminths egg-output were reduced by 96-98% fourteen days after each treatment. Fecal egg counts of STHs were similar in both groups until the 6th-8th months, and then remained significantly lower in DRF than in CD (42-100% ascarids; 30-100% trichurids and ancylostomatids). According to the results, and considering that gelatin treats have always been fully accepted, it is concluded that this new formulation offers an efficient solution to decrease the risk of infection among dogs maintained in shelters, and is therefore recommended.

Facial lipodystrophy in an HIV-positive patient using an orthodontic appliance.

The aim of this article was to relate the clinical case of an HIV-positive orthodontic patient who reported that her cheeks had been hurting since treatment began. We started with the data collected in anamnesis and by contact with the patient's physician, and a diagnosis of facial lipodystrophy as a result of the use of retroviral drugs was reached. The patient was referred to a dermatologist for treatment of the facial lipodystrophy.

Effects of Meal Fructose/Glucose Composition on Postprandial Glucose Appearance and Hepatic Glycogen Synthesis in Healthy Subjects.

Dietary fructose overshadows glucose in promoting metabolic complications. Intestinal fructose metabolism (IFM) protects against these effects in rodents, by favoring gluconeogenesis, but the extent of IFM in humans is not known. We therefore aimed to infer the extent of IFM by comparing the contribution of dietary fructose to systemic glucose and hepatic glycogen appearance postprandially. Twelve fasting healthy subjects ingested two protein meals in random order, one supplemented with 50 g 5/95 fructose/glucose (LF) and the other with 50 g 55/45 fructose/glucose (HF). Sources of postprandial plasma glucose appearance and hepatic glycogen synthesis were determined with deuterated water. Plasma glucose excursions, as well as pre- and post-meal insulin, c-peptide, and triglyceride levels were nearly identical for both meals. The total gluconeogenic contribution to plasma glucose appearance was significantly higher for HF versus LF (65 ± 2% vs. 34 ± 3%, p < 0.001). For HF, Krebs cycle anaplerosis accounted for two-thirds of total gluconeogenesis (43 ± 2%) with one-third from Triose-P sources (22 ± 1%). With LF, three-quarters of the total gluconeogenic contribution originated via Krebs cycle anaplerosis (26 ± 2%) with one-quarter from Triose-P sources (9 ± 2%). HF and LF gave similar direct and indirect pathway contributions to hepatic glycogen synthesis. Increasing the fructose/glucose ratio had significant effects on glucose appearance sources but no effects on hepatic glycogen synthesis sources, consistent with extensive IFM. The majority of fructose carbons were converted to glucose via the Krebs cycle.

Loss of postprandial insulin clearance control by Insulin-degrading enzyme drives dysmetabolism traits.

Systemic insulin availability is determined by a balance between beta-cell secretion capacity and insulin clearance (IC). Insulin-degrading enzyme (IDE) is involved in the intracellular mechanisms underlying IC. The liver is a major player in IC control yet the role of hepatic IDE in glucose and lipid homeostasis remains unexplored. We hypothesized that IDE governs postprandial IC and hepatic IDE dysfunction amplifies dysmetabolic responses and prediabetes traits such as hepatic steatosis. In a European/Portuguese population-based cohort, IDE SNPs were strongly associated with postprandial IC in normoglycemic men but to a considerably lesser extent in women or in subjects with prediabetes. Liver-specific knockout-mice (LS-IDE KO) under normal chow diet (NCD), showed reduced postprandial IC with glucose intolerance and under high fat diet (HFD) were more susceptible to hepatic steatosis than control mice. This suggests that regulation of IC by IDE contributes to liver metabolic resilience. In agreement, LS-IDE KO hepatocytes revealed reduction of Glut2 expression levels with consequent impairment of glucose uptake and upregulation of CD36, a major hepatic free fatty acid transporter. Together these findings provide strong evidence that dysfunctional IC due to abnormal IDE regulation directly impairs postprandial hepatic glucose disposal and increases susceptibility to dysmetabolic conditions in the setting of Western diet/lifestyle.

Control of Strongyles in First-Season Grazing Ewe Lambs by Integrating Deworming and Thrice-Weekly Administration of Parasiticidal Fungal Spores.

Parasiticidal fungi have been used in several in vivo experiments in livestock farms worldwide, constituting an effective tool for the biocontrol of gastrointestinal parasites in grazing animals. In the first year of study, two groups of eight first-season pasturing ewe lambs infected by strongyles were dewormed with albendazole, and then, the test group received an oral dose of 106 chlamydospores of Mucor circinelloides and 106 Duddingtonia flagrans individually and thrice a week from mid-September to May (FS1), while the control group remained without fungi (CT1). In the second year, two new groups of first-season grazing ewe lambs were treated with ivermectin and subjected to the same experimental design (FS2 and CT2, respectively). The anthelmintic efficacy was 96.6% (CT1), 95.6% (FS1), 96.1% (CT2), and 95.1% (FS2). The counts of strongyle egg output increased in the control groups (CT1 and CT2) throughout the study and reached numbers higher than 600 eggs per gram of feces (EPG), while in FS1 and FS2, they were <250 EPG. The values of red blood cell parameters registered for CT1 and CT2 were lower than those of the reference standards, while a significant increment was recorded in FS1 and FS2, and values within the physiological range were attained. It is concluded that integrating efficient anthelminthic deworming with rotational pasturing and the regular intake of chlamydospores of M. circinelloides and D. flagrans provides a helpful strategy for maintaining low levels of strongyle egg output in first-season grazing ewe lambs and improves their health status.