Women's health: optimal nutrition throughout the lifecycle.

Sex differences are an important consideration when researching and establishing policies for nutrition and optimal health. For women's health, there are important physiologic, neurologic, and hormonal distinctions throughout the lifecycle that impact nutritional needs. Distinct from those for men, these nutritional needs must be translated into appropriate nutrition policy that aims to not only avoid overt nutritional deficiency, but also to promote health and minimize risk for chronic disease. Through a series of webinars, scientific experts discussed the advances in the understanding of the unique nutritional needs, challenges and opportunities of the various life stages for women across the life course and identified emerging nutritional interventions that may be beneficial for women. Nevertheless, there is concern that existing nutrition policy intended for women's health is falling short with examples of programs that are focused more on delivering calories than achieving optimal nutrition. To be locally effective, targeted nutrition needs to offer different proposals for different cultural, socio-economic, and geographic communities, and needs to be applicable at all stages of growth and development. There must be adequate access to nutritious foods, and the information to understand and implement proven nutritional opportunities. Experts provided recommendations for improvement of current entitlement programs that will address accessibility and other social and environmental issues to support women properly throughout the lifecycle.

Application of parelectric spectroscopy to detect skin cancer-A pilot study.

BACKGROUND: The early detection of skin cancer is still challenging and calls for objective, fast diagnostic, and ideally non-invasive methods in order to leave the potentially malignant tumor cells unaltered. In this paper, the parelectric spectroscopy was applied to evaluate the potential of a non-invasive detection of basal cell carcinoma (BCC) and malignant melanoma. MATERIALS AND METHODS: A prototype of parelectric spectroscopy was used to investigate non-invasively dipole density and mobility of suspicious skin lesions. The differences in investigated tissue were analyzed compared to pathohistological findings in a clinical study on 51 patients with suspected BCC and malignant melanoma. RESULTS: The non-invasive parelectric spectroscopy could differentiate between normal skin, BCC, and melanoma but failed to distinguish between different types of skin cancer. The data were normalized to unsuspected nearby skin because the different skin locations influence dipole density and mobility. CONCLUSION: The results of the pilot study indicate that the parelectric spectroscopy might be an additional, useful non-invasive diagnostic procedure to distinguish between normal skin and skin cancer.

Decreased CK1δ expression predicts prolonged survival in colorectal cancer patients.

Cancers arising from the large intestine or rectum are called colorectal cancer (CRC) and represent the fourth leading cause of cancer-related death worldwide. Since casein kinase 1 (CK1) isoforms are involved in many cellular processes and have been reported to be deregulated in various tumor entities, CK1 has become an interesting drug target. In this study, we examined the potential of CK1δ expression levels in tumor tissue of CRC patients as a prognostic biomarker. We show by quantitative RNA expression analyses that decreased CK1δ expression levels in tumor tissue predict prolonged survival rates. Random sampling of CK1δ stained tumor tissue indicates that CK1δ gene expression corresponds with CK1δ protein expression. Especially in low grade (grade 1, grade 2) and in UICC II/III classified tumors decreased CK1δ RNA levels correlate with significantly improved survival rates when the tumor was located in the right colon. We furthermore found gender-specific differences within these subgroups, revealing most significant increase in overall survival rates in male patients with tumors in right colon expressing low levels of CK1δ RNA. Results become even clearer, when only male patients over 50 years were considered. Together, these findings support the assumption that CK1δ might be a prognostic biomarker for CRC thereby providing an interesting drug target for the development of new therapy concepts.

Impact of age and gender on tumor related prognosis in gastrointestinal stromal tumors (GIST).

BACKGROUND: Risk classification and prediction of prognosis in GIST is still a matter of debate. Data on the impact of age and gender as potential confounding factors are limited. Therefore we comprehensively investigated age and gender as independent risk factors for GIST. METHODS: Two independent patient cohorts (cohort I, n = 87 [<50 years]; cohort II, n = 125 [≥50 years]) were extracted from the multicentre Ulmer GIST registry including a total of 659 GIST patients retrospectively collected in 18 collaborative German oncological centers. Based on demographic and clinicopathological parameters and a median follow-up time of 4.3 years (range 0.56; 21.33) disease-specific-survival (DSS), disease-free-survival (DFS) and overall survival (OS) were calculated. RESULTS: GIST patients older than fifty years showed significantly worse DSS compared to younger patients (p = 0.021; HR = 0.307, 95% CI [0.113; 0.834]). DSS was significantly more favorable in younger female GIST patients compared with elderly females (p = 0.008). Female gender resulted again in better prognosis in younger patients (p = 0.033). CONCLUSIONS: Patient age (<50 years) and female gender were significantly associated with a more favourable prognosis in GIST. Extended studies are warranted to confirm our clinical results and to elucidate underlying pathophysiological mechanisms.

Interhospital air transport of a blind patient on extracorporeal life support with consecutive and successful left ventricular assist device implantation.

The use of extracorporeal life support systems (ECLS) in patients with postcardiotomy low cardiac output syndrome (LCO) as a bridge to recovery and bridge to implantation of ventricular assist device (VAD) is common nowadays. A 59-year-old patient with acute myocardial infarction received a percutaneous transluminal angioplasty and stenting of the circumflex artery. During catheterization of the left coronary artery (LAD), the patient showed ventricular fibrillation and required defibrillation and cardiopulmonary resuscitation. After implantation of an intra-aortic balloon pump, the patient immediately was transmitted to the operating room. He received emergency coronary artery bypass grafting in a beating heart technique using pump-assisted minimal extracorporeal circulation circuit (MECC). Two bypass grafts were performed to the LAD and the right posterior descending artery. Despite initial successful weaning off cardiopulmonary bypass with high-dose inotropic support, the patient presented postcardiotomy LCO and an ECLS was implanted. The primary setup of the heparin-coated MECC system was modified and used postoperatively. As a result of the absence of an in-house VAD program, the patient was switched to a transportable ECLS the next day and was transferred by helicopter to the nearest VAD center where the patient received a successful insertion of a left VAD 3 days later.

Integrative Nursing Interventions for Cancer-Related Symptoms in Oncology Inpatients: Results of a Descriptive Pilot Study.

BACKGROUND: Integrative nursing (IN) is an essential component of integrative medicine and integrative oncology. IN includes a range of external naturopathic, integrative nursing interventions, such as compresses, embrocation, and foot/hand baths, aimed at alleviating symptoms and side effects of conventional treatment. The project IMPLEMENT-UKU ("Implementation of IN at the University Hospital Ulm") was accompanied by a descriptive pilot study on the use of IN interventions on cancer-related symptoms in oncology inpatients, the characterization of these patients and the evaluation of the impact. METHODS: A single-arm study was conducted using a paper-based questionnaire administered before the IN interventions (t0) and 24 hours after the IN interventions (t1). Topics included sociodemographic data, symptoms, quality of life, health status, psychological burden, attitudes, and experience and satisfaction with the IN interventions. Analyses were descriptive using absolute and relative frequencies. RESULTS: During the 6-month study period out of 66 patients recommended for IN consultation by medical and nursing staff on 2 wards, 62 (93.9%) accepted the offer. Of those patients who received IN, 21 patients (33.9%) participated in the study. The number of IN interventions received per patient ranged from 1 to 3 during the 24-hour survey period. And a total of 36 IN interventions were performed: The most treated body region was the feet/legs (50.0%), followed by the back (25.0%), using oils such as solum oil (41.7%) and lavender oil (13.9%). Embrocation (77.8%) was the predominant type of IN intervention. For patients, the mean FACIT-F score was 29.2 ± 12.5. The mean PHQ-4 score was 3.0 ± 1.9. Regarding sleep quality in the last 4 weeks, 13 participants (61.9%) described it as rather or very poor. Satisfaction with the IN was high, with a large proportion of participants evaluating the IN interventions very positively. CONCLUSION: The study's findings suggest that there is a great need for IN among oncology inpatients. These patients are open to and interested in IN interventions and evaluate them positively. IN provides a promising opportunity to provide non-pharmacological support to inpatients. The integration of IN in conventional oncology care settings may enhance patient-centered care and contribute to improved patient wellbeing.

Reno-protective effects of epigallocatechingallate in a small piglet model of extracorporeal circulation.

Cardiopulmonary bypass still often is a necessary tool in cardiac surgery in particular in the correction of congenital heart defects in small infants. Nevertheless, among the complications linked to extracorporeal circulation (ECC) with cardiopulmonary bypass (CPB) in both infants and adults one of the most serious problems is renal impairment. Since this might be caused by ischemia/reperfusion injury and accumulation of free radicals, we used (-)-epigallocatechin-3-gallate (EGCG), a derivate from green tea, which is known to possess antioxidant, antiapoptotic and NO-scavenging properties in order to find out whether EGCG may protect the kidney. 23 four-week-old Angler Sattelschwein-piglets (8-15 kg) were divided into three groups: control-group (n=7), ECC-group (n=10), EGCG-group (n=6). The ECC- and EGCG-group were thoracotomized and underwent CPB for 120 min followed by a 90-min recovery-time. The EGCG-group received 10 mg/kg EGCG before and after CPB. Histology revealed that CPB led to widening of Bowman's capsule, and to vacuolization of proximal tubular cells (p<0.05) which could be prevented by EGCG (p<0.05). Using immunohistology, we found significant nuclear translocation of hypoxia-inducible-factor-1-alpha (HIF-1-alpha) and increased nitrotyrosine formation in the ECC-group. Both were significantly (p<0.05) inhibited by EGCG. ECC-induced loss of energy-rich phosphates was prevented by EGCG. In blood samples we found that CPB resulted in increases in creatinine and urea (in serum) and led to loss of total protein (p<0.05), which all was not present in EGCG-treated animals. We conclude that CPB causes damage in the kidney which can be attenuated by EGCG.

Prehabilitation in an Integrative Medicine Day Clinic for Patients Undergoing Neoadjuvant Treatment: Single-Center Feasibility Pilot Study.

BACKGROUND: Patients with cancer receiving neoadjuvant treatment prior to surgery are in a very stressful situation. Chemotherapy and radiation therapy put a strain on the quality of life and the pending surgery poses a relevant burden for many patients. Preparation of these patients for the intervention in terms of prehabilitation has great potential to reduce the burden of postoperative complications and may improve the clinical outcome. A prehabilitation approach also yields the possibility to address unmet patients' needs and to help them modify their lifestyle in a maintainable way. Therefore, a multimodal approach is mandatory during this critical period. OBJECTIVE: The aim of this study is to assess the feasibility of prehabilitation in an integrative medicine day clinic (PRIME-DC) prior to cancer surgery at a major university clinic. PRIME-DC is considered feasible if 80% of enrolled patients are willing and able to complete at least 6 out of the 8 weekly meetings, each lasting 6.5 hours, at such a clinic. Secondary end points aim to evaluate this multimodal program. METHODS: The PRIME-DC intervention combines mind-body medicine, exercise therapy, nutrition therapy, naturopathic counseling, and the application of a yarrow liver compress. Adult patients with cancer, with a primary tumor in the abdomen (including intraperitoneal cancer, stomach cancer, and extraperitoneal cancers such as pancreatic, bladder, rectal, esophageal, endometrial, ovarian, and cervical cancer) or the breast requiring a neoadjuvant oncological treatment setting are eligible to participate. The addressed cancer entities imply either an extensive surgical intervention with an expected need for prehabilitation (eg, abdominal surgery) or a neoadjuvant treatment of several months with a high burden of treatment-associated side effects (breast cancer). Adherence to the day clinic program is the primary end point being defined as presence during the day clinic session. Secondary end points are physical assessment and quality of life, together with a structured assessment of neoadjuvant treatment-associated side effects. Furthermore, to collect qualitative data voluntary participants of the day clinic will be interviewed in a semistructured way after completion of the day clinic program on each component of the study (mind-body intervention, exercise, nutrition, naturopathic counseling, and a yarrow liver compress). RESULTS: The procedures used in this study adhere to the tenets of the Declaration of Helsinki. As of February 2023, we enrolled 23 patients; the dominant cancer entity is breast cancer (18 enrolled patients). CONCLUSIONS: The presented protocol combines prehabilitation, lifestyle modification, naturopathic counseling, dietary assistance, and naturopathic treatment in an innovative and integrative way. TRIAL REGISTRATION: Deutsches Register Klinischer Studien German Clinical Trials Register DRKS00028126; https://drks.de/search/de/trial/DRKS00028126. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/46765.

Naturopathy, complementary and integrative medicine in medical education - position paper by the GMA Committee Integrative Medicine and Perspective Pluralism.

Background: A large part of the population in Germany makes use of naturopathic, complementary and integrative medical treatments. There are now numerous scientific studies that provide evidence of efficacy for certain indications. At German medical faculties, selected procedures and their application are taught within the cross-sectoral unit called QB 12 and some elective courses, with a focus on specific aspects are offered. So far, however, there has been no structured curriculum that longitudinally anchors teaching across medical studies and enables all students to consider naturopathic and complementary medical options for patient care later on and to integrate them effectively into the diagnostic and treatment process. Objective: The aim of this position paper is to show the relevance of this topic for medical education, to clarify terminology and to present core competencies and possible implementation options for training. Method: The Integrative Medicine and Perspective Pluralism Committee of the German Association for Medical Education developed this position paper in a multi-stage consensual process, in cooperation with the Forum of University Work Groups on Naturopathic Treatment and Complementary Medicine. Results: First, different umbrella terms were discussed and an existing definition of integrative medicine and health was chosen for subsequent use. Building on this step, the status of education and its scientific foundation in Germany was considered in an international context. In the next step, a competency profile for medical training, consisting of seven areas of competency, was developed and described in detail with regard to naturopathic, complementary and integrative medicine. Implementation options were identified using possible starting points in the curriculum and using established examples of best practice. Conclusion: Despite different priorities at each faculty, it was possible to find an agreement on the development of competencies and anchoring them in medical education on the basis of a common definition of terms. Currently, the implementation in the mandatory and elective areas is very heterogeneous. As part of the current revision of the Medical Licensure Act, there are many possible starting points for the integration of naturopathic and complementary medical teaching content, especially in interprofessional and general practice courses. The implementation and accompanying research of targeted teaching settings should lay the foundations for a long-term and binding integration into medical education. Overall, it is clear that medical education in the field of naturopathy and complementary and integrative medicine has the potential to develop comprehensive core medical competencies.

Interprofessional evidence-based counselling programme for complementary and integrative healthcare in patients with cancer: study protocol for the controlled implementation study CCC-Integrativ.

INTRODUCTION: According to international literature, patients with cancer wish to have information on complementary and integrative healthcare (CIH). Medical guidelines recommend actively approaching patients with cancer discussing potential benefits and risks of individual CIH methods. While some CIH methods, for example, acupuncture and yoga, have been proven effective in high-quality studies, other CIH methods lack studies or bear the risk of interactions with chemotherapeutics, for example, herbal drugs. Therefore, an evidence-based interprofessional counselling programme on CIH will be implemented at four Comprehensive Cancer Centres in the federal state of Baden-Wuerttemberg, Germany. METHODS AND ANALYSIS: A complex intervention consisting of elements on patient, provider and system levels will be developed and evaluated within a multilayer evaluation design with confirmatory evaluation on patient level. Patients with a cancer diagnosis within the last 6 months will receive three individual counselling sessions on CIH within 3 months (=intervention on patient level). The counselling will be provided by an interprofessional team of medical and nursing staff. For this purpose, an intensive online training programme, a CIH knowledge database and an interprofessional team-building process were developed and implemented (=intervention on provider level). Moreover, training events on the basics of CIH are offered in the outpatient setting (=intervention on system level). Primary outcome of the evaluation at the patient level is patient activation measured (PAM) with the PAM-13 after 3 months. Secondary outcomes, for example, quality of life, self-efficacy and clinical parameters, will be assessed at baseline, after 3 months and at 6 months follow-up. The intervention group (n=1000) will be compared with a control group (n=500, treatment as usual, no CIH counselling. The outcomes and follow-up times in the control group are the same as in the intervention group. Moreover, the use of health services will be analysed in both groups using routine data. A qualitative-quantitative process evaluation as well as a health economic evaluation will identify relevant barriers and enabling factors for later roll-out. ETHICS AND DISSEMINATION: The study has been approved by the appropriate Institutional Ethical Committee of the University of Tuebingen, No. 658/2019BO1. The results of these studies will be disseminated to academic audiences and in the community. TRIAL REGISTRATION NUMBER: DRKS00021779; Pre-results.

Design, development, and local production of lipid-based nutritional supplements to enhance the complementary feeding diet: A model for collaboration for a feeding trial in Bangladesh.

Background: Lipid-based nutrient supplements (LNS) are effective for treating childhood wasting and for preventing stunting, wasting, and anemia, but large-scale production and programmatic use are a barrier. Locally-developed and produced LNS may be more affordable and reduce logistical procurement and importation hurdles, while promoting private sector engagement and partnership. Methods: In northwestern Bangladesh, we conducted a community-based trial of complementary food supplementation to test its efficacy to reduce childhood stunting. Two locally-developed, small-quantity LNS (20g/day, rice-lentil and chick-pea based) were designed, developed first at small scale in the 'kitchen' laboratory under controlled conditions, followed by taking them to a local food manufacturer for larger production for the study. We describe here the partnership, required expertise and capacity, experiences, and lessons learned that made this uniquely complex undertaking possible Results: Key steps in the journey included addressing the dynamics of clear communication between partners, executing on carefully assigned tasks and roles, correcting course when needed, and maintaining timeliness and roadmaps. Knowledge of food science and technology was key in solving many food-production challenges that were encountered in taking the laboratory recipe to the factory. Factory production was established and had to meet quality and hygiene criteria set for young children. Conclusions: We provide documentation of this experience as a model to describe the various steps and considerations and what is entailed in local LNS production. We highlight the importance of a well-conceived collaboration with clear roles that created a 'win-win' situation for all partners for achieving common goals, establishing improved technology at the factory, and building new capacity to produce such products for children in a low resource setting. Key words: micronutrient, lipid-based nutrient supplements, maternal and child, malnutrition, multiagency collaboration.

Cyclin H expression is increased in GIST with very-high risk of malignancy.

BACKGROUND: Risk estimation of gastrointestinal stromal tumours (GIST) is based on tumour size and mitotic rate according to the National Institutes of Health consensus classification. The indication for adjuvant treatment of patients with high risk GIST after R0 resection with small molecule inhibitors is still a controversial issue, since these patients represent a highly heterogeneous population. Therefore, additional prognostic indicators are needed. Here, we evaluated the prognostic value of cyclin H expression in GIST. METHODS: In order to identify prognostic factors of GIST we evaluated a single centre cohort of ninety-five GIST patients. First, GISTs were classified with regard to tumour size, mitotic rate and localisation according to the NIH consensus and to three additional suggested risk classifications. Second, Cyclin H expression was analysed. RESULTS: Of ninety-five patients with GIST (53 female/42 male; median age: 66.78a; range 17-94a) risk classification revealed: 42% high risk, 20% intermediate risk, 23% low risk and 15% very low risk GIST. In patients with high risk GIST, the expression of cyclin H was highly predictive for reduced disease-specific survival (p = 0.038). A combination of cyclin H expression level and high risk classification yielded the strongest prognostic indicator for disease-specific and disease-free survival (p < or = 0.001). Moreover, in patients with tumour recurrence and/or metastases, cyclin H positivity was significantly associated with reduced disease-specific survival (p = 0.016) regardless of risk-classification. CONCLUSION: Our data suggest that, in addition to high risk classification, cyclin H expression might be an indicator for "very-high risk" GIST.

Multiple gastrointestinal stromal tumors and bilateral pheochromocytoma in neurofibromatosis.

The coincidence of a gastrointestinal stromal tumor (GIST) and a neuroendocrine tumor (NET) in neurofibromatosis type 1 (NF1) is described only five times within the literature. We report on a 63 year old Caucasian female with the rare condition of neurofibromatosis type 1 coinciding with recurrent gastrointestinal stromal tumor plus bilateral pheochromocytoma (PCC). After a history of palpitations and dizziness that lasted for years, a left adrenal mass was detected by CT. Laparotomy revealed a pheochromocytoma of the left adrenal gland while an ileoterminal GIST was found incidentally intraoperatively. After six months contralateral PCC and multiple recurrent GIST were resected again. After four years the patient is doing well without any signs of further recurrent tumors. Discussion includes review of the literature.

The microwave absorption of emulsions containing aqueous micro- and nanodroplets: a means to optimize microwave heating.

The microwave absorption at frequencies between 10 MHz and 4 GHz is measured for aqueous brine droplets dispersed in a dielectric medium (epsilon(')=2.0). By varying the size of the droplets, ion type and ion concentration, it is found that the microwave absorption goes through a maximum which depends on the type of ions and their concentration. The absorption process is attributed to the polarization of the microdroplets through surface charges. Means to optimize microwave heating in emulsions is discussed.

Comparison of Different Risk Classification Systems in 558 Patients with Gastrointestinal Stromal Tumors after R0-Resection.

Background: Due to adjuvant treatment concepts for patients with R0-resected gastrointestinal stromal tumors (GIST), a reproducible and reliable risk classification system proved of utmost importance for optimal treatment of patients and prediction of prognosis. The aim of this study was to reevaluate the impact of five widely-applied and well-established GIST risk classification systems (i.e., scores by Fletcher, Miettinen, Huang, Joensuu, and TNM classification) on a series of 558 GIST patients with long-term follow-up after R0 resection. Methods: Tumor size, mitotic count and site were used in variable combination to predict high- and low risk patients by the use of the five risk classification models. For survival analyses disease-specific survival, disease-free survival and overall-survival were investigated. Patients with initial metastatic disease or incompletely resectable tumors were excluded. Results: All GIST classification models distinguished well between patients with high-risk and low-risk tumors and none of the five risk systems was superior to predict patient outcome. The models showed significant heterogeneity. There was no significant difference between the different risk-groups regarding overall-survival. Subdivision of GIST patients with very low- and low-risk appeared to be negligible. Conclusions: Currently applied GIST risk classification systems are comparable to predict high- or low-risk patients with initial non-metastatic and completely resected GIST. However, the heterogeneity of the high-risk group and the absence of differences in overall survival indicate the need for more precise tumor- and patient-related criteria for better stratification of GIST and identification of patients who would benefit best from adjuvant tyrosine kinase inhibitor therapy.

Gastrointestinal stromal tumors of the esophagus: evaluation of a pooled case series regarding clinicopathological features and clinical outcome.

BACKGROUND AND OBJECTIVES: To elucidate diagnostic criteria, clinicopathological features and clinical outcome in patients with esophageal gastrointestinal stromal tumors (GIST), representing an extremely rare subform of GIST with an estimated incidence of about 0.1 to 0.3 per million people. PATIENTS AND METHODS: Esophageal GIST cases from the Ulmer GIST registry consisting of 1077 cases were pooled with case reports and case series of esophageal GIST extracted from MEDLINE. Data were compared with those from 683 cases with gastric GIST from the Ulmer GIST registry. RESULTS: In comparison to gastric GIST, esophageal GIST (n = 55) occurred significantly more frequent in men (p = 0.035) as well as in patients younger than 60 at diagnosis (p < 0.001). Primary tumor sizes were significantly larger (p < 0.001), thereby resulting more frequently in a high-risk classification (OR = 4.53, CI 95% 2.41-8.52, p < 0.001). The 5-year rates of disease-specific survival (DSS), disease-free survival (DFS), and overall survival (OS) were 50.9%, 65.3% and 48.3%, respectively. The prognosis of esophageal GIST was less favorable compared with gastric GIST (DSS: p < 0.001, HR = 0.158, 95% CI: 0.087-0.288; DFS: p = 0.023, HR 0.466, 95% CI: 0.241-0.901; OS p = 0.003, HR = 0.481, 95% CI: 0.294-0.785; univariate Cox model) after a median follow-up time of 28 months (range 1.9 to 202). Mutational analysis for KIT showed more frequently wild-type status in esophageal GIST (OR = 10.13, CI 95% 3.02-33.96, p < 0.001). CONCLUSIONS: Esophageal GIST differ significantly from gastric GIST in respect to clinicopathological features and clinical outcome. To optimize treatment options further prospective data on patients with esophageal GIST are urgently warranted.

Effects of surgical and dietary weight loss therapy for obesity on gut microbiota composition and nutrient absorption.

Evidence suggests a correlation between the gut microbiota composition and weight loss caused by caloric restriction. Laparoscopic sleeve gastrectomy (LSG), a surgical intervention for obesity, is classified as predominantly restrictive procedure. In this study we investigated functional weight loss mechanisms with regard to gut microbial changes and energy harvest induced by LSG and a very low calorie diet in ten obese subjects (n = 5 per group) demonstrating identical weight loss during a follow-up period of six months. For gut microbiome analysis next generation sequencing was performed and faeces were analyzed for targeted metabolomics. The energy-reabsorbing potential of the gut microbiota decreased following LSG, indicated by the Bacteroidetes/Firmicutes ratio, but increased during diet. Changes in butyrate-producing bacterial species were responsible for the Firmicutes changes in both groups. No alteration of faecal butyrate was observed, but the microbial capacity for butyrate fermentation decreased following LSG and increased following dietetic intervention. LSG resulted in enhanced faecal excretion of nonesterified fatty acids and bile acids. LSG, but not dietetic restriction, improved the obesity-associated gut microbiota composition towards a lean microbiome phenotype. Moreover, LSG increased malabsorption due to loss in energy-rich faecal substrates and impairment of bile acid circulation. This trial is registered with ClinicalTrials.gov NCT01344525.

Organ-protective effects on the liver and kidney by minocycline in small piglets undergoing cardiopulonary bypass.

Cardiopulmonary bypass (CPB) often is required for the operative correction of congenital heart defects in small infants. Unfortunately, CPB is associated with injury of inner organs such as the brain, kidney, lung, and liver. Renal failure and increase in liver enzymes are typical side effects observed after CPB. Here, we investigate whether organ protection of the kidney and liver can be achieved with the application of minocycline, which is known-besides its anti-infective effects-to act as a poly-ADP-ribose-polymerase inhibitor. Twenty-nine 4-week-old Angler Sattelschwein-piglets (8-15 kg) were divided into four groups: control group (n = 8), CPB group (n = 9), minocycline-control group (n = 6), and the minocycline-CPB group (n = 6). CPB groups were thoracotomized and underwent CPB for 120 min (cross-clamp, 90 min; reperfusion, 30 min) followed by a 90-min recovery time. The control groups also were thoracotomized but not connected to CPB. The minocycline group received 4 mg/kg minocycline before and 2 mg/kg after CPB. In the kidneys, CPB histologically resulted in widening of Bowman's capsule, and-mainly in tubules-formation of poly-ADP-ribose, nitrosylation of tyrosine-residues, nuclear translocation of hypoxia-induced factor HIF-1α, and of apoptosis-inducing factor (AIF). In addition, we found significantly less ATP in the kidney and significantly increased plasma urea and creatinine. Similar but gradually attenuated changes were found in the liver together with significantly elevated de-Ritis coefficient. These changes in the kidney and liver were significantly diminished by minocycline (except AIF in the liver which was similar in all groups). In conclusion, CPB causes damage in the kidney and-to a lower degree-in the liver, which can be attenuated by minocycline.

Photoprotective potential of lycopene, beta-carotene, vitamin E, vitamin C and carnosic acid in UVA-irradiated human skin fibroblasts.

The photoprotective potential of the dietary antioxidants vitamin C, vitamin E, lycopene, beta-carotene, and the rosemary polyphenol, carnosic acid, was tested in human dermal fibroblasts exposed to ultraviolet-A (UVA) light. The carotenoids were prepared in special nanoparticle formulations together with vitamin C and/or vitamin E. Nanoparticle formulations, in contrast to dimethylsulphoxide, stablized lycopene in the cell culture medium and allowed efficient cellular uptake. The presence of vitamin E in the formulation further increased the stability and cellular uptake of lycopene. UVA irradiation of the human skin fibroblasts led to a 10-15-fold rise in metalloproteinase 1 (MMP-1) mRNA. This rise was suppressed in the presence of low microM concentrations of vitamin E, vitamin C, or carnosic acid but not with beta-carotene or lycopene. Indeed, in the presence of 0.5-1.0 microM beta-carotene or lycopene, the UVA-induced MMP-1 mRNA was further increased by 1.5-2-fold. This increase was totally suppressed when vitamin E was included in the nanoparticle formulation. Heme-oxygenase 1 (HO-1) mRNA expression was strongly induced by UVA irradiation but none of the antioxidants inhibited this effect at the concentrations used in this study. Indeed, beta-carotene or lycopene (0.5-1.0 microM) led to a further 1.5-fold rise in the UVA-induced HO-1 mRNA levels. In conclusion, vitamin C, vitamin E, and carnosic acid showed photoprotective potential. Lycopene and beta-carotene did not protect on their own but in the presence of vitamin E, their stability in culture was improved and the rise in MMP-1 mRNA expression was suppressed, suggesting a requirement for antioxidant protection of the carotenoids against formation of oxidative derivatives that can influence the cellular and molecular responses.

Effective prevention of adhesions with hyaluronate.

HYPOTHESIS: Hyaluronate sodium in the form of a bioresorbant membrane reduces the development of intra-abdominal adhesions frequently found after implantation of synthetic mesh in the context of surgical hernia repair. DESIGN: The effect of hyaluronate on the formation of adhesions was evaluated when applied laparoscopically as a bioresorbant membrane to protect the peritoneal surface of a synthetic mesh. SETTING: Experimental animal model. INTERVENTIONS: A peritoneal defect 5 cm in diameter was bilaterally created in the abdominal wall of each of 9 pigs by laparoscopy. A polypropylene mesh was fixed with clips onto these defects on both sides. In each of the animals, only on one side, the synthetic mesh was also covered by a hyaluronate membrane. MAIN OUTCOME MEASURES: The incidence and severity of adhesions (grade 0-4, where 0 indicates no adhesion; 1, filmy avascular adhesions; 2, vascular adhesions; 3, cordlike fibrous adhesions; and 4, plain fibrous adhesions) were determined after 45 days, comparing treated and untreated sides by autopsy results and histological features. RESULTS: Adhesions, mainly grades 3 and 4, occurred in 7 of the 9 animals in those meshes not covered by hyaluronate; 2 untreated animals did not develop adhesions. On the other hand, only 1 of the 9 animals developed adhesions (grade 2) at the mesh concealed by the hyaluronate membrane. CONCLUSIONS: The bioresorbant hyaluronate membrane significantly reduced the formation of peritoneal adhesions (1-sided sign test, P<.05) induced by the insertion of a polypropylene mesh, when compared with the contralateral implants not protected by hyaluronate. Thus, hyaluronate membranes are efficient for reducing the incidence of peritoneal adhesions.