Minimally Invasive Pancreas Surgery: Is There a Benefit?

Minimally invasive procedures minimize trauma to the human body while maintaining satisfactory therapeutic results. Minimally invasive pancreas surgery (MIPS) was introduced in 1994, but questions regarding its efficacy compared to an open approach were widespread. MIPS is associated with several perioperative advantages while maintaining oncological standards when performed by surgeons with a robust training regimen and frequent practice. Future research should focus on addressing learning curve discrepancies while identifying factors associated with shortening the time needed to attain technical proficiency.

Propensity score matched analysis of laparoscopic revisional and conversional sleeve gastrectomy with concurrent hiatal hernia repair.

INTRODUCTION: The primary aim of this study was to evaluate outcomes associated with concurrent hiatal hernia repair (CHHR) when performing a conversional or revisional vertical sleeve gastrectomy (VSG). CHHR is often necessary during VSG due to potential gastroesophageal reflux disease (GERD) development or obstructive symptoms. METHODS: The Metabolic and Bariatric Surgery Accreditation and Quality Improvement (MBSAQIP) participant use file was assessed for the years 2015-2020 for revisional/conversional VSG procedures. The presence of CHHR was used to create two groups. Propensity score matching (PSM) was performed with E-analysis. RESULTS: There were 33,909 patients available, with 5986 undergoing the VSG procedure with CHHR. In the unmatched analysis, there was an increased frequency of patients being female (85.72 vs 83.30%; p < 0.001), having a history of GERD (38.01 vs 31.25%; p < 0.001), and being of older age (49.59 ± 10.97 vs 48.70 ± 10.83; p < 0.001). Patients undergoing VSG with CHHR experienced decreased sleep apnea (25.00 vs 28.84%; p < 0.001) and diabetes (14.27 vs 17.80%; p < 0.001). PSM yielded 5986 patient pairs. Matched patients with CHHR experienced increased operative time (115 min ± 53 vs 103 min ± 51; p < 0.001), increased risk of postoperative pneumonia (0.45 vs 0.15%; p = 0.005) and readmission (4.69 vs 3.58%; p = 0.002) within thirty days. However, patients undergoing CHHR with revisional or conversional VSG did not experience increased risk of death, postoperative bleeding, postoperative leak, or reoperations. CONCLUSION: Despite a small association with increased postoperative pneumonia, the rate of complications in patients undergoing laparoscopic revisional/conversional VSG and CHHR are low. CHHR is a safe option when combined with the laparoscopic revisional/conversional VSG procedure in the early postoperative period.

The Roles of Drift and Selection on Short Stamen Loss in Arabidopsis thaliana along an Elevational Gradient in the Spanish Pyrenees.

Traits that have lost function sometimes persist through evolutionary time. These traits may be maintained by a lack of standing genetic variation for the trait, if selection against the trait is weak relative to drift, or if they have a residual function. To determine the evolutionary processes shaping whether nonfunctional traits are retained or lost, we investigated short stamens in 16 populations of Arabidopsis thaliana along an elevational cline in the Spanish Pyrenees. We found a cline in short stamen number from retention of short stamens in high elevation populations to incomplete loss in low elevation populations. We did not find evidence that limited genetic variation constrains the loss of short stamens at high elevations nor evidence for divergent selection on short stamens between high and low elevations. Finally, we identified loci associated with short stamens in the Spanish Pyrenees that are different from loci associated with variation in short stamen number across latitudes from a previous study. Overall, we did not identify the evolutionary mechanisms maintaining an elevational cline in short stamen number but did identify different genetic loci underlying the variation in short stamen along similar phenotypic clines.

Stevia rebaudiana Bertoni, an American plant used as sweetener: Study of its effects on body mass control and glycemia reduction in Wistar male and female rats.

Stevia rebaudiana Bertoni water extracts have been used as a natural sweetener and customary medicine by the indigenous inhabitants of South America for several hundred years. This plant was sent to Europe in the 16th century and was described by Peter Jacob Esteve in Spain. Recently the food industry has started to employ S. rebaudiana as sweetener using its glycosides after purification. Advertisement claims that Stevia glycosides is good for controling body mass and reducing glycemia. This study's objective was to evaluate the effect of S. rebaudiana leaf extract on Wistar rats as animal model to prove its effectiveness on body mass control, glycemia reduction, and other biochemical parameters. Three groups were randomly formed with 24 males and 24 females: A blank group without any sweetener, a control group drinking water with 10% glucose, and the test group ingesting a 0.94% water extract of S. rebaudiana. Body mass measurements as well as food and drink consumption were daily performed. The experiment lasted 120 days after the specimens were weaned and got used to eating solid food. Euthanasia was done and blood serum was collected to evaluate the following biochemical parameters: Glucose, triglycerides, cholesterol, insulin, glucagon, leptin, ghrelin, and glucose-dependent insulinotropic peptide, GIP. Results indicated that only female rats had statistical differences in body mass gain. No relevant effects either positive or negative were found in the biochemical parameters measured. The crude extracts of S. rebaudiana did not show any relevant changes in biochemical and hormonal profiles, changes nor body mass with respect to the blank and control groups of young and healthy rats in the age range of infancy to youth. According to the results obtained, the therapeutic properties that have been associated to S. rebaudiana consumption especially for body mass control and glycemia reduction, did not occur in young and healthy male and female rats in equivalent age to infants, young children, and youths.

Laparoscopic Conversion of Gastric Bypass to Distal Gastric Bypass for Inadequate Weight Loss.

BACKGROUND: Although uncommon, significant weight recurrence after Roux-en-Y gastric bypass (RYGB) can occur. Options are limited to help patients achieve additional weight loss, and improved techniques for revisional/conversional surgery are needed to achieve optimal outcomes while avoiding significant side effects. Although limited data exist regarding distalization of the Roux limb to achieve a longer biliopancreatic limb leading to some level of malabsorption, we have seen adequate weight loss with minimal significant side effects in patients undergoing this procedure with our approach. An appropriate technical approach to this procedure is important to avoid immediate and long-term complications. METHODS AND RESULTS: We present a video describing our approach to Roux limb distalization for weight gain after gastric bypass, describing our approach for work-up, operative technical pearls, and postoperative monitoring in these patients. A 61 year-old female who initially had good weight loss after RYGB with a body mass index (BMI) nadir of 33, from a preoperative BMI of 53, experienced weight recurrence with her BMI increasing to 48. After preoperative nutritional optimization, dietary counseling, and behavioral counseling, she underwent conversion of RYGB to distalization of Roux limb to create a distal RYGB. She tolerated the procedure well and was discharged on postoperative day 2. At 1-year follow-up, her BMI had decreased to 37 with improvement in dyslipidemia, elevation of liver transaminases, and improvement in hemoglobin A1C. This reflects the impact of this procedure on not only weight loss but also concurrent metabolic diseases associated with obesity. CONCLUSION: We present a case of distalization of a RYGB for weight recurrence, highlighting the technical pearls when performing the procedure. Accurate, intraoperative measurement of the total alimentary limb length is essential to achieve weight loss while minimizing malnutrition and vitamin deficiencies. Assessment of preoperative nutritional levels for evidence of any protein calorie malnutrition is important during surgical decision-making when this conversional metabolic operation is considered. Frequent, postoperative nutritional monitoring is important and occurs with a full bariatric nutritional panel at 3, 6, 9, and 12 months then yearly thereafter. Using our approach, we feel that conversion of RYGB to distalization of Roux limb can lead to improved weight loss without significant side effects.

Concurrent paraesophageal hernia repair in revisional/conversional laparoscopic Roux-en-Y gastric bypass: propensity score-matched analysis of the MBSAQIP database.

BACKGROUND: Patients requiring concurrent paraesophageal hernia repair (CPHR) have been shown to have favorable outcomes in primary bariatric surgery. However, patients requiring revisional or conversional surgery represent a group of patients with higher perioperative risk. Currently, few reports on concurrent paraesophageal hernia repair utilizing the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) database are available. The primary aim of this study was to determine perioperative complications associated with CPHR and the Roux-en-Y gastric bypass (RYGB) as a revisional/conversional operation. METHODS: In this study, patients undergoing revisional/conversional RYGB between 2015 and 2020 were accessed via the MBSAQIP database. Patients were categorized based on the presence of a paraesophageal hernia as a concurrent procedure. Patients who underwent revisional/conversional surgery without additional procedures were utilized for controls. A propensity score-matched cohort was generated and E-analysis utilized to assess unmeasured confounding. RESULTS: After exclusions, 35,698 patients were available. Patients receiving CPHR were more likely to be female (90.79% vs 87.37%; p < 0.001) and have increased frequency of gastroesophageal reflux disease (69.20% vs 51.69%; p < 0.001). However, these patients had lower frequencies of sleep apnea (24.12% vs 30.13%; p < 0.001), hypertension requiring medication (38.51% vs 42.59%; p < 0.001), and decreased frequency of hyperlipidemia (19.44% vs 21.60%;p < 0.001). After matching, 6,231 patient pairs were developed and showed that patients undergoing CPHR were at increased risk of readmission (9.44% vs 7.58%; p < 0.001), intervention (3.56% vs 2.79%; p = 0.018), increased requirement for outpatient dehydration treatment (5.87% vs 4.67%;p = 0.004), and overall increased operation time (169.3 min ± 76.0 vs 153.5 ± 73.3; p < 0.001). However, there were no significant increases in the rates of reoperation, death, postoperative leak complications, or bleeding complications after CPHR. CONCLUSION: Patients undergoing revisional/conversional RYGB with CPHR may be at higher risk for a small number of rare postoperative complications. CPHR is a safe procedure in patients undergoing revisional/conversional RYGB in the short-term postoperative period.

Jackfruit: Composition, structure, and progressive collapsibility in the largest fruit on the Earth for impact resistance.

The jackfruit is the largest fruit on the Earth, reaching upwards of 35 kg and falling from heights of 25 m. To survive such high energy impacts, it has evolved a unique layered configuration with a thorny exterior and porous tubular underlayer. During compression, these layers exhibit a progressive collapse mechanism where the tubules are first to deform, followed by the thorny exterior, and finally the mesocarp layer in between. The thorns are composed of lignified bundles which run longitudinally from the base of the thorn to the tip and are embedded in softer parenchymal cells, forming a fiber reinforced composite. The mesocarp contains more lignin than any of the other layers while the core appears to contain more pectin giving rise to variations in compressive and viscoelastic properties between the layers. The surface thorns provide a compelling impact-resistant feature for bioinspiration, with a cellular structure that can withstand large deformation without failing and wavy surface features which densify during compression without fracturing. Even the conical shape of the thorns is valuable, presenting a gradually increasing surface area during axial collapse. A simplified model of this mechanism is put forward to describe the force response of these features. The thorns also distribute damage laterally during impact and deflect cracks along their interstitial valleys. These phenomena were observed in 3D printed, jackfruit-inspired designs which performed markedly better than control prints with the same mass. STATEMENT OF SIGNIFICANCE: Many biological materials have evolved remarkable structures that enhance their mechanical performance and serve as sources of inspiration for engineers. Plants are often overlooked in this regard yet certain botanical components, like nuts and fruit, have shown incredible potential as blueprints for improved impact resistant designs. The jackfruit is the largest fruit on Earth and generates significant falling impact energies. Here, we explore the jackfruit's structure and its mechanical capabilities for the first time. The progressive failure imparted by its multilayered design and the unique collapse mode of the surface thorns are identified as key mechanisms for improving the fruit's impact resistance. 3D printing is used to show that these structure-property benefits can be successfully transferred to engineering materials.

Pentacoordinated Organotin(IV) Complexes as an Alternative in the Design of Highly Efficient Optoelectronic and Photovoltaic Devices: Synthesis and Photophysical Characterization.

The synthesis of four pentacoordinated organotin(IV) complexes prepared in a one-pot reaction from 2-hydroxy-1-naphthaldehyde, 2-amino-3-hydroxypyridine and organotin oxides is reported. The complexes were characterized by UV-Vis, IR, MS, 1H, 13C and 119Sn NMR techniques. The compound based on 2,2-diphenyl-6-aza-1,3-dioxa-2-stannanaphtho[1,2-h]pyrido[3,2-d]cyclononene revealed the formation of a monomeric complex with a distorted five-coordinated molecular geometry intermediate between the trigonal bipyramidal and square pyramidal. In order to find possible applications in photovoltaic devices, hybrid films of organotin(IV) complexes embedded in poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) with graphene were deposited. The topographic and mechanical properties were examined. The film with the complex integrated into the cyclohexyl substituent has high plastic deformation, with a maximum stress of 1.69 × 107 Pa and a Knoop hardness of 0.061. The lowest values of 1.85 eV for the onset gap and 3.53 eV for the energy gap were obtained for the heterostructure having the complex with the phenyl substituent. Bulk heterojunction devices were fabricated; these devices showed ohmic behavior at low voltages and a space-charge-limited current (SCLC) conduction mechanism at higher voltages. A value of 0.02 A was found for the maximum carried current. The SCLC mechanism suggests hole mobility values of between 2.62 × 10-2 and 3.63 cm2/V.s and concentrations of thermally excited holes between 2.96 × 1018 and 4.38 × 1018 m-3.

Amphiphilic Phosphorus Dendrons Associated with Anti-inflammatory siRNA Reduce Symptoms in Murine Collagen-Induced Arthritis.

Small interfering RNA (siRNA) holds promise for treating rheumatoid arthritis by inhibiting major cytokines such as tumor necrosis factor-α (TNF-α). We developed original cationic amphiphilic phosphorus dendrons to produce dendriplexes associated with TNF-α siRNA. The dendrons were made of 10 pyrrolidinium end groups and a C17 aliphatic chain. The dendriplexes demonstrated the ability to protect siRNA from nuclease degradation and to promote macrophage uptake. Moreover, they led to potent inhibition of TNF-α expression in the lipopolysaccharide-activated mouse macrophage cell line RAW264.7 in vitro model. A significant anti-inflammatory effect in the murine collagen-induced arthritis model was observed through arthritis scoring and histological observations. These results open up essential perspectives in using this original amphiphilic dendron to reduce the disease burden and improve outcomes in chronic inflammatory diseases.

Hypoalbuminemia as a risk factor for complications in revisional/conversional bariatric surgery: an MBSAQIP analysis.

BACKGROUND: Hypoalbuminemia (HA) is a risk factor for serious complications after elective bariatric surgery. Patients undergoing revisional/conversional bariatric surgery may represent a higher-risk group who often have underlying co-morbid medical illnesses and more complex surgery. OBJECTIVES: This study investigated the postoperative complications in patients with HA undergoing revisional/conversional bariatric surgery. SETTING: Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP), years 2015-2019. METHODS: The MBSAQIP database was used to evaluate patients undergoing non-banding revisional/conversional bariatric surgery between 2015 and 2019. Patients were categorized by serum albumin (≤3.5 g/dL). Variables were assessed via bivariate analysis and multivariable regression. Propensity score matching was conducted to compare gastric bypass (RYGB) to sleeve gastrectomy (VSG). RESULTS: One hundred forty-seven thousand four hundred thirty patients underwent revisional/conversional procedures. After applied exclusions, 58,777 patients were available for analysis. The HA group had a significantly (P < .05) higher prevalence of being black (22.95% versus 17.76%), renal insufficiency (1.08% versus .36%), smoking history (9.47% versus 6.91%), chronic obstructive pulmonary disease (COPD) (2.54% versus 1.33%), and history of deep vein thrombosis (DVT) (4.03% versus 2.3%). Postoperative complications associated with HA included perioperative blood transfusion (3.1% versus 1.27%; P < .001), 30day readmission (10.87 versus 6.77%; P < .001), 30day reoperation (4.9% versus 3.18%; P < .001), and 30day mortality (.40% versus .14%; P < .0001). HA was a significant predictor of 30day readmission in the RYGB versus VSG matched cohort (odds ratio [OR], 1.30; 95% confidence interval [CI], [1.14, 1.48]; P < .001). CONCLUSIONS: HA is a risk factor requiring attention for patients undergoing revisional/conversional bariatric surgery and optimization of nutritional status or medical comorbidities associated with HA prior to bariatric surgery may help avoid postoperative complications.

Histones and their chaperones: Adaptive remodelers of an ever-changing chromatinic landscape.

Chromatin maintenance and remodeling are processes that take place alongside DNA repair, replication, or transcription to ensure the survival and adaptability of a cell. The environment and the needs of the cell dictate how chromatin is remodeled; particularly where and which histones are deposited, thus changing the canonical histone array to regulate chromatin structure and gene expression. Chromatin is highly dynamic, and histone variants and their chaperones play a crucial role in maintaining the epigenetic regulation at different genomic regions. Despite the large number of histone variants reported to date, studies on their roles in physiological processes and pathologies are emerging but continue to be scarce. Here, we present recent advances in the research on histone variants and their chaperones, with a focus on their importance in molecular mechanisms such as replication, transcription, and DNA damage repair. Additionally, we discuss the emerging role they have in transposable element regulation, aging, and chromatin remodeling syndromes. Finally, we describe currently used methods and their limitations in the study of these proteins and highlight the importance of improving the experimental approaches to further understand this epigenetic machinery.

An insight into embryogenesis interruption by carbon nitride dots: can they be nucleobase analogs?

The carbon nitride dot (CND) is an emerging carbon-based nanomaterial. It possesses rich surface functional moieties and a carbon nitride core. Spectroscopic data have demonstrated the analogy between CNDs and cytosine/uracil. Recently, it was found that CNDs could interrupt the normal embryogenesis of zebrafish. Modifying CNDs with various nucleobases, especially cytosine, further decreased embryo viability and increased deformities. Physicochemical property characterization demonstrated that adenine- and cytosine-incorporated CNDs are similar but different from guanine-, thymine- and uracil-incorporated CNDs in many properties, morphology, and structure. To investigate the embryogenesis interruption at the cellular level, bare and different nucleobase-incorporated CNDs were applied to normal and cancerous cell lines. A dose-dependent decline was observed in the viability of normal and cancerous cells incubated with cytosine-incorporated CNDs, which matched results from the zebrafish embryogenesis experiment. In addition, nucleobase-incorporated CNDs were observed to enter cell nuclei, demonstrating a possibility of CND-DNA interactions. CNDs modified by complementary nucleobases could bind each other via hydrogen bonds, which suggests nucleobase-incorporated CNDs can potentially bind the complementary nucleobases in a DNA double helix. Nonetheless, neither bare nor nucleobase-incorporated CNDs were observed to intervene in the amplification of the zebrafish polymerase-alpha 1 gene in quantitative polymerase chain reactions. Thus, in conclusion, the embryogenesis interruption by bare and nucleobase-incorporated CNDs might not be a consequence of CND-DNA interactions during DNA replication. Instead, CND-Ca2+ interactions offer a plausible mechanism that hindered cell proliferation and zebrafish embryogenesis originating from disturbed Ca2+ homeostasis by CNDs. Eventually, the hypothesis that raw or nucleobase-incorporated CNDs can be nucleobase analogs proved to be invalid.

Atherogenic indices in pediatric population in South-Southeast region of Mexico.

BACKGROUND: Atherosclerosis is a cardiovascular disease, highly predictable, and associated with different atherogenic indices (AI) in adults. However, such indexes in the pediatric population are far less explored. The objective of this study was to evaluate the AI and the cardiovascular factors in the pediatric population in the South-Southeast of México. METHODS: A total of 481 children between 2 and 17 years old were recruited. Anthropometric evaluation, blood pressure (BP), lipid profile, apolipoprotein A-I (ApoA-I) and apolipoprotein B (ApoB) were measured, and AI were calculated. The population was grouped by age, binary logistic regression analysis was performed to analysis for associations of AI and cardiovascular risk factors. Sensibility and specificity of AI to detect metabolic alteration were evaluated for curve ROC. RESULTS: The atherogenic risk presented a high prevalence in the pediatric population, such as LDL-c/ApoB (86.9%), AIP (78%) and AC (36.6%). Preschoolers showed a higher risk of ApoB/ApoA-I and ApoB/LDL-c, while adolescents have a high risk of AIP. CRI-I and AC were associated with elements of lipid profile and body mass index (BMI). ROC curves analysis shows that AIP is the best index evaluating metabolic syndrome (MS) (0.87) and dyslipidemia (0.91). CONCLUSION: Such pediatric population showed a high risk of AI, mainly by LDL-c/ApoB and AIP. The BMI was the cardiovascular risk factors most frequently related to AI, AIP is the best index for detecting cases of MS and dyslipidemia. This is the first study carried out in the pediatric population from the South-Southeast of Mexico that evaluated the AI.

Equine hoof wall: Structure, properties, and bioinspired designs.

The horse hoof wall exhibits exceptional impact resistance and fracture control due to its unique hierarchical structure which contains tubular, lamellar, and gradient configurations. In this study, structural characterization of the hoof wall was performed revealing features previously unknown. Prominent among them are tubule bridges, which are imaged and quantified. The hydration-dependent viscoelasticity of the hoof wall is described by a simplified Maxwell-Weichert model with two characteristic relaxation times corresponding to nanoscale and mesoscale features. Creep and relaxation tests reveal that the specific hydration gradient in the hoof keratin likely leads to reduced internal stresses that arise from spatial stiffness variations. To better understand realistic impact modes for the hoof wall in-vivo, drop tower tests were executed on hoof wall samples. Fractography revealed that the hoof wall's reinforced tubular structure dominates at lower impact energies, while the intertubular lamellae are dominant at higher impact energies. Broken fibers were observed on the surface of the tubules after failure, suggesting that the physically intertwined nature of the tubule reinforcement and intertubular matrix improves the toughness of this natural fiber reinforced composite. The augmented understanding of the structure-mechanical property relationship in dynamic loading led to the design of additively manufactured bioinspired structures, which were evaluated in quasistatic and dynamic loadings. The inclusion of gradient structures and lamellae significantly reduced the damage sustained in drop tower tests, while tubules increased the energy absorption of samples tested in compact tension. The samples most similar to the hoof wall displayed remarkably consistent fracture control properties. STATEMENT OF SIGNIFICANCE: The horse hoof wall, capable of withstanding large, repeated, dynamic loads, has been touted as a candidate for impact-resistant bioinspiration. However, our understanding of this biological material and its translation into engineered designs is incomplete. In this work, new features of the horse hoof wall are quantified and the hierarchical failure mechanisms of this remarkable material under near-natural loading conditions are uncovered. A model of the hoof wall's viscoelastic response, based on studies of other keratinous materials, was developed. The role of hydration, strain rate, and impact energy on the material's response were elucidated. Finally, multi-material 3D printed designs based on the hoof's meso/microstructure were fabricated and exhibited advantageous energy absorption and fracture control relative to control samples.

Glioblastoma Treatment: State-of-the-Art and Future Perspectives.

(1) Background: Glioblastoma is the most frequent and lethal primary tumor of the central nervous system. Through many years, research has brought various advances in glioblastoma treatment. At this time, glioblastoma management is based on maximal safe surgical resection, radiotherapy, and chemotherapy with temozolomide. Recently, bevacizumab has been added to the treatment arsenal for the recurrent scenario. Nevertheless, patients with glioblastoma still have a poor prognosis. Therefore, many efforts are being made in different clinical research areas to find a new alternative to improve overall survival, free-progression survival, and life quality in glioblastoma patients. (2) Methods: Our objective is to recap the actual state-of-the-art in glioblastoma treatment, resume the actual research and future perspectives on immunotherapy, as well as the new synthetic molecules and natural compounds that represent potential future therapies at preclinical stages. (3) Conclusions: Despite the great efforts in therapeutic research, glioblastoma management has suffered minimal changes, and the prognosis remains poor. Combined therapeutic strategies and delivery methods, including immunotherapy, synthetic molecules, natural compounds, and glioblastoma stem cell inhibition, may potentiate the standard of care therapy and represent the next step in glioblastoma management research.

Chronic intake of nutritive sweeteners and saccharin increases levels of glycolytic and lipogenic enzymes in rat liver.

There are doubts about the impact of non-nutritive sweeteners consumption on lipogenic and glycolytic metabolism. Therefore, the objective was to determine the effects of chronic consumption of sweeteners on the activity levels of the enzymes glucokinase (GK), phosphofructokinase-1 (PFK-1), pyruvate kinase (PKL), acetyl coenzyme A carboxylase (ACC), and fatty acid synthase (FAS) in livers' extracts. Groups of male and female Wistar rats drank solutions of sweeteners for 480 days: Sucrose 10%, glucose 14%, fructose 7%, acesulfame K 0.05%, aspartame:acesulfame mixture 1.55%, sucralose 0.017%, saccharin 0.033%, and a control group. The enzymatic activity in livers' extracts was determined. Likewise, the levels of glucose, triglycerides, insulin, glucagon, and leptin were determined. In both genders, there were significant differences in the levels of enzymatic activity, hormonal, and biochemical parameters due to sweeteners consumption. The highest glycolytic and lipogenic enzyme activity levels were observed in the groups that ingested nutritive sweeteners and saccharin.

Evaluation of the uptake, retention and effectiveness of exercise referral schemes for the management of mental health conditions in primary care: a systematic review.

BACKGROUND: Exercise is a recognised element of health-care management of mental-health conditions. In primary health care, it has been delivered through exercise referral schemes (ERS). The National Institute for Health and Care Excellence has highlighted uncertainty regarding the effectiveness of ERS in improving exercise participation and health outcomes among those referred for mental-health reasons. This review aims, therefore, to evaluate ERSs for individuals who are referred specifically for mental-health reasons. METHODS: Studies were reviewed that assessed the effectiveness of ERSs in improving initiation of and/or adherence to exercise and/or their effectiveness in improving long-term participation in exercise and health outcomes among primary care patients who had been referred to the scheme for mental-health reasons. The data were extracted and their quality assessed. Data were analysed through a narrative synthesis approach. RESULTS: Nine studies met the eligibility criteria. Three assessed clinical effectiveness of the schemes, eight assessed ERS uptake and/or adherence to the exercise schedule, and two assessed the impact of the ERSs on long-term exercise levels. In one study, it was found that ERSs that were based in leisure centres significantly improved long-term symptoms in those who had been referred due to their mental ill health (P<0.05). ERSs that involved face-to-face consultations and telephone calls had the highest rates of mean uptake (91.5%) and adherence (71.7%), but a difference was observed between uptake/adherence in trials (86.8%/55.3%) and in routine practice (57.9%/37.2%). ERSs that included face-to-face consultations and telephone calls increased the amount of long-term physical activity that was undertaken by people who had been referred for mental-health reasons (P=0.003). CONCLUSIONS: Uptake and effectiveness of ERSs for mental health conditions was related to programme content and setting with more effective programmes providing both face-to-face and telephone consultations. Good uptake of yoga among those referred for mental health reasons suggests that mindful exercise options should be investigated further. Existing ERSs could be improved through application of individual tailoring and the provision of more face-to-face consultations, and social support. Further research is required to identify the types of ERSs that are most clinically effective for those with mental ill health.

Hypoxia and TLR9 activation drive CXCL4 production in systemic sclerosis plasmacytoid dendritic cells via mtROS and HIF-2α.

OBJECTIVE: SSc is a complex disease characterized by vascular abnormalities and inflammation culminating in hypoxia and excessive fibrosis. Previously, we identified chemokine (C-X-C motif) ligand 4 (CXCL4) as a novel predictive biomarker in SSc. Although CXCL4 is well-studied, the mechanisms driving its production are unclear. The aim of this study was to elucidate the mechanisms leading to CXCL4 production. METHODS: Plasmacytoid dendritic cells (pDCs) from 97 healthy controls and 70 SSc patients were cultured in the presence of hypoxia or atmospheric oxygen level and/or stimulated with several toll-like receptor (TLR) agonists. Further, pro-inflammatory cytokine production, CXCL4, hypoxia-inducible factor (HIF) -1α and HIF-2α gene and protein expression were assessed using ELISA, Luminex, qPCR, FACS and western blot assays. RESULTS: CXCL4 release was potentiated only when pDCs were simultaneously exposed to hypoxia and TLR9 agonist (P < 0.0001). Here, we demonstrated that CXCL4 production is dependent on the overproduction of mitochondrial reactive oxygen species (mtROS) (P = 0.0079) leading to stabilization of HIF-2α (P = 0.029). In addition, we show that hypoxia is fundamental for CXCL4 production by umbilical cord CD34 derived pDCs. CONCLUSION: TLR-mediated activation of immune cells in the presence of hypoxia underpins the pathogenic production of CXCL4 in SSc. Blocking either mtROS or HIF-2α pathways may therapeutically attenuate the contribution of CXCL4 to SSc and other inflammatory diseases driven by CXCL4.