A Vicious Cycle of Osteosarcopenia in Inflammatory Bowel Diseases—Aetiology,Clinical Implications and Therapeutic Perspectives

Sarcopenia is a disorder characterized by a loss of muscle mass which leads to the reduction of muscle strength and a decrease in the quality and quantity of muscle. It was previously thought that sarcopenia was specific to ageing. However, sarcopenia may affect patients suffering from chronic diseases throughout their entire lives. A decreased mass of muscle and bone is common among patients with inflammatory bowel disease (IBD). Since sarcopenia and osteoporosis are closely linked, they should be diagnosed as mutual consequences of IBD. Additionally, multidirectional treatment of sarcopenia and osteoporosis including nutrition, physical activity, and pharmacotherapy should include both disorders, referred to as osteosarcopenia.     

Is There a FADS2-Modulated Link between Long-Chain Polyunsaturated Fatty Acids in Plasma Phospholipids and Polyphenol Intake in Adult Subjects Who Are Overweight?

Dietary polyphenols promote cardiometabolic health and are linked with long-chain polyunsaturated fatty acids in plasma phospholipids (LC-PUFA). The FADS2 polymorphisms are associated with LC-PUFA metabolism and overweight/obesity. This 4-week study examined the link between polyphenol intake, FADS2 variants (rs174593, rs174616, rs174576) and obesity in 62 overweight adults (BMI ≥ 25), allocated to consume 100 mL daily of either: Aronia juice, a rich source of polyphenols, with 1177.11 mg polyphenols (expressed as gallic acid equivalents)/100 mL (AJ, n = 22), Aronia juice with 294.28 mg polyphenols/100 mL (MJ, n = 20), or nutritionally matched polyphenol-lacking placebo as a control (PLB, n = 20). We analyzed LC-PUFA (% of total pool) by gas chromatography and FADS2 variants by real-time PCR. Four-week changes in LC-PUFA, BMI, and body weight were included in statistical models, controlling for gender and PUFA intake. Only upon AJ and MJ, the presence of FADS2 variant alleles affected changes in linoleic, arachidonic, and eicosapentaenoic acid (EPA). Upon MJ treatment, changes in EPA were inversely linked with changes in BMI (β= −0.73, p = 0.029) and weight gain (β= −2.17, p = 0.024). Only in subjects drinking AJ, the link between changes in EPA and anthropometric indices was modified by the rs174576 variant allele. Our results indicate the interaction between FADS2, fatty acid metabolism, and polyphenol intake in overweight subjects.     

The impact of COVID-19 and healthcare system changes on the well-being of rheumatic patients

ObjectivesThe COVID-19 pandemic has significantly impacted the healthcare systems. Many Polish outpatient clinics have been implementing telemedical consultations as a tool to ensure the continuity of care for patients with chronic diseases. The aim of the study was to evaluate patients’ satisfaction with telemedical appointments, as well as availability of the various medical services and patients’ well-being during the pandemic.Material and methodsAn online-based questionnaire on the experience with telemedical consultations, availability of medical services and current state of health was conducted among Polish rheumatology patients approximately 6 months after the outbreak of the COVID-19 pandemic.ResultsThe survey was completed by 107 respondents with a mean age of 41.52 ±14.33 years. The overall level of satisfaction from telemedical consultations, evaluated with a VAS 1–10 scale, was assessed as 6.23 ±3.04 for teleconsultations in primary healthcare units and 6.00 ±2.80 for rheumatology outpatient units. 42.99% of the respondents were in favour of maintaining telemedical appointments even after the pandemic. Incidences of reduced access to medical services during the COVID-19 pandemic were reported by 77.57% of the patients. Almost half of the respondents reported reduced accessibility to rheumatological care. An alarming decline in health self-esteem, evaluated with a VAS 1–10 scale, was noted from the average 6.37 ±1.92 before COVID-19 to the current rating of 5.78 ±1.91 (p = 0.0087).ConclusionsPolish rheumatology patients are moderately satisfied with the medical teleconsultations in primary health care units and rheumatology outpatient clinics. A substantial number of patients experienced deterioration of well-being as well as limited access to traditional healthcare services, including rheumatology care.     

Establishing a national HTA program for medical devices in Italy: Overhauling a fragmented system to ensure value and equal access to new medical technologies

Differing contexts have greatly influenced HTA development in various countries, with considerable effort recently made by international HTA networks (e.g., EUnetHTA) and the European Union (EU) to make HTA a more coherent, equal, and efficient process. Medical devices (MDs) present particular challenges for HTA because of frequent, rapid innovation, outcomes influenced by end-user competence, dynamic pricing and often low-quality scientific evidence. Our objective is to describe the development, structure and governance of a National HTA Program for MDs (PNHTADM) in Italy, a highly participatory, stakeholder-engaged, evidence-based process to reform a fragmented system of appraisal and approval. Based largely on EUnetHTA methods, the resulting process delineates a standardized system for proposing MDs by any stakeholders, accrediting HTA producers, setting criteria for prioritization and appraisals, and innovatively linking recommendations with coverage, reimbursement and procurement of MDs. Expected benefits include reduced disparities in pricing and reimbursement policies and improved access to new technologies across 21 regional healthcare systems in Italy's decentralized, universal system, complete with provisions to require additional evidence collection and centrally monitor diffusion. Though devised for Italy, the design, resources and underlying analysis provide a framework for other nations seeking to consolidate HTA initiatives, particularly in light of new EU regulation.     

Isoform selectivity and kinetics of morphine 3- and 6-glucuronidation by human udp-glucuronosyltransferases: evidence for atypical glucuronidation kinetics by UGT2B7.

Morphine elimination involves UDP-glucuronosyltransferase (UGT) catalyzed conjugation with glucuronic acid to form morphine 3- and 6-glucuronides (M3G and M6G, respectively). It has been proposed that UGT2B7 is the major enzyme involved in these reactions, but there is evidence to suggest that other isoforms also catalyze morphine glucuronidation in man. Thus, we have characterized the selectivity and kinetics of M3G and M6G formation by recombinant human UGTs. UGT 1A1, 1A3, 1A6, 1A8, 1A9, 1A10, and 2B7 all catalyzed M3G formation, but only UGT2B7 formed M6G. The kinetics of M3G formation by the UGT1A family isoforms was consistent with a single enzyme Michaelis-Menten model, with apparent Km values ranging from 2.6 to 37.4 mM. In contrast, M3G and M6G formation by UGT2B7 exhibited atypical kinetics. The atypical kinetics may be described by a model with high- and low-affinity Km values (0.42 and 8.3 mM for M3G, and 0.97 and 7.4 mM for M6G) from fitting to a biphasic Michaelis-Menten model. However, a multisite model with an interaction between two identical binding sites in a negative cooperative manner provides a more realistic approach to modeling these data. According to this model, the respective binding affinities (Ks) for M3G and M6G were 1.76 and 1.41 mM, respectively. These data suggest that M6G formation may be used as a selective probe for UGT2B7 activity, and morphine glucuronidation by UGT2B7 appears to involve the simultaneous binding of two substrate molecules, highlighting the need for careful analysis of morphine glucuronidation kinetics in vitro.     

Patterns of cyclin E, retinoblastoma protein, and p21Cip1/WAF1 immunostaining in the oncogenesis of papillary thyroid carcinoma.

PURPOSE: Uncontrolled cell proliferation, a hallmark of cancer, may result from an increased expression of cell cycle up-regulators, and/or from a reduced expression of cell cycle down-regulators. In the present study, we analyzed, by immunohistochemistry, the expression of a panel of three proteins: cyclin E and two cell cycle inhibitors, p21(Cip1/WAF1) and retinoblastoma protein (pRb) product, in different stages of papillary thyroid carcinomas (PTC). EXPERIMENTAL DESIGN: We investigated immunostaining patterns of the proteins in question in 51 resected PTC in pathologic stages, ranging from pT(1a) to pT(4), taking into consideration their relation to clinicohistopathologic factors. RESULTS: We observed a significant, progressive loss of expression of p21(Cip1/WAF1) with advancing tumor grade. The differences reached values of significance between pT(1a) [papillary thyroid microcarcinomas (PMC)] and pT(2) and between PMC and pT(4) stages of PTC. pRb presented a similar immunostaining pattern to that of p21(Cip1/WAF1) and the differences reached values of significance between pT(1a) and pT(2), and between PMC and pT(4) stages of PTC. The results of cyclin E immunostaining corresponded to our recently published result, and a negative correlation was observed between the immunostaining index of cyclin E and pRb. CONCLUSIONS: The results of the present study suggest that cyclin E expression and suppression of pRb and p21(Cip1/WAF1) may be characteristic patterns of immunostaining for PTC with a tendency to early metastasizing. If our results are confirmed in a larger study, the diagnostic panel, constructed of the antibodies against these proteins, may become a valuable tool in predicting the metastatic potential in PTC.     

Allogeneic hematopoietic cell transplantation in chemotherapy‐induced aplasia in children with high‐risk acute myeloid leukemia or myelodysplasia

Relapse remains the most common cause of treatment failure after hematopoietic cell transplantation for acute myeloid leukemia. Inability to achieve hematologic complete remission has been a barrier to transplant for patients with refractory disease. We describe six children with refractory myeloid disease undergoing transplant in chemotherapy‐induced aplasia, as a strategy to facilitate curative therapy in refractory patients. Clofarabine‐ or high‐dose cytarabine‐based chemotherapy regimens were used to achieve marrow aplasia, followed by reduced‐intensity conditioning and allogeneic transplant before hematologic recovery. Long‐term disease control was achieved in five, with one transplant‐related mortality, suggesting the feasibility of this approach.     

Dietary-Lifestyle Patterns Associated with Bone Turnover Markers,and Bone Mineral Density in Adult Male Distance Amateur Runners—A Cross-Sectional Study

Background: Excessive mileage can be detrimental to bone mineral density among long-distance runners. The negative effects of mileage could be alleviated by appropriate nutrition. The purpose of this study was to analyse the dietary-lifestyle patterns in relation to bone mineral density and bone turnover markers among amateur marathoners. Methods: A total of 53 amateur male distance runners were divided into two clusters by k-means cluster analysis. Bone mineral density was measured by dual X-ray absorptiometry (DXA). Blood was drawn to analyse bone resorption marker C-terminal telopeptide (cTX) and bone formation marker amino-terminal propeptide of type I collagen (PINP). Food frequency intake and lifestyle information were measured by multicomponent questionnaire KomPAN^®. Yearly average mileage per month was taken from each participant. Results: There were two distinguished clusters: Less-healthy-more-active-low-Z-score (LessHA) (n = 33) and More-healthy-less-active-high-Z-score (MoreHLA) (n = 20). LessHA had a lower frequency intake of pro-healthy food groups, a lower number of meals during a typical day, and a higher mileage training than the group of athletes who followed the MoreHLA. Athletes following the LessHA pattern also had a lower Z-score in the lumbar spine and femoral bone and a lower PINP. Conclusion: The current study suggests that pro-healthy dietary patterns and lower mileage may favour higher bone mineral density in male amateur marathoners.     

Satiety of Edible Insect-Based Food Products as a Component of Body Weight Control

Among the many aspects determining the nutritional potential of insect-based foods, research into the satiating potential of foods is an important starting point in the design of new functional foods, including those based on edible insects. The aim of this study was to assess the satiating value of products with the addition of freeze-dried insect flour. The test material included wheat pancakes in which corresponding proportions of wheat flour were substituted with 10% Mw, 0% Mw, and 30% Mw of flour from freeze-dried Tenebrio molitor, 10% Bw, 20% Bw, and 30% Bw of flour from Alphitobius diaperinus, and 10% Cr, 20% Cr, and 30% Cr of flour from Acheta domesticus. The study included the characterisation of physico-chemical properties and their effect on the satiating potential of the analysed pancakes. A total of 71 healthy volunteers (n = 39 women, n = 32 men) with no food phobias were qualified for the study. Each subject rated the level of hunger and satiety before and after ingestion at 30 min intervals over the subsequent 180 min on two separate graphical scales. The rating was done on an unstructured 100 mm visual analogue scale (VAS). A portion intended for testing had a value of 240 kcal. The highest average satiety values were noted for the pancakes with an addition of 30% Alphitobius diaperinus (Bw) and with the addition of 20% and 30% addition of Acheta domesticus flour (Cr). The Tenebrio molitor-based products were the least satiating. However, the largest addition of 30% of an insect flour for each variant considerably increased the satiating potential as compared to the control sample. Satiety was influenced the most by the protein content in the test wheat pancakes. The results support the idea of a possible usage of insect-based food products in the composition of obesity treatment diets, carbohydrate-limiting diets, and as alternative sources of protein.     

Artificial Anisotropy in Ge2Sb2Te5 Thin Films after Femtosecond Laser Irradiation

Ge₂Sb₂Te₅ (GST225) looks to be a promising material for rewritable memory devices due to its relatively easy processing and high optical and electrophysical contrast for the crystalline and amorphous phases. In the present work, we combined the possibilities of crystallization and anisotropic structures fabrication using femtosecond laser treatment at the 1250 nm wavelength of 200 nm thin amorphous GST225 films on silicon oxide/silicon substrates. A raster treatment mode and photoexcited surface plasmon polariton generation allowed us to produce mutually orthogonal periodic structures, such as scanline tracks (the period is 120 ± 10 μm) and laser-induced gratings (the period is 1100 ± 50 nm), respectively. Alternating crystalline and amorphous phases at the irradiated surfaces were revealed according to Raman spectroscopy and optical microscopy studies for both types of structures. Such periodic modulation leads to artificial optical and electrophysical anisotropy. Reflectance spectra in the near infrared range differ for various polarizations of probing light, and this mainly results from the presence of laser-induced periodic surface structures. On the other hand, the scanline tracks cause strong conductivity anisotropy for dc measurements in the temperature range of 200–400 K. The obtained results are promising for designing new GST225-based memory devices in which anisotropy may promote increasing the information recording density.