Convergent total synthesis of (±) myricanol, a cyclic natural diarylheptanoid.

Myricanol 1, a constituent of Myrica species, has been reported to lower the levels of the microtubule-associated protein tau (MAPT), whose accumulation plays an important role in some neurodegenerative diseases, such as Alzheimer's disease (AD). Herein we described a new synthetic route to prepare myricanol in 9 steps and 4.9% overall yield starting from commercially available 2,3-dimethoxyphenol and methyl 3-(4-benzyloxyphenyl)propanoate. The key steps are a cross-metathesis to obtain a linear diarylheptanoid intermediate and a Suzuki-Miyaura domino reaction to generate the challenging macrocycle.

Patient adherence in following a prescribed diet and micronutrient supplements after laparoscopic sleeve gastrectomy: our experience during 1 year of follow-up.

BACKGROUND: One of the most effective surgeries for sustainable weight loss in morbidly obese patients is laparoscopic sleeve gastrectomy (LSG). The present study aimed to assess the adherence of LSG patients with respect to following post-operative dietary requirements and micronutrient supplementation, as well as to investigate their perceived barriers in achieving optimal adherence. METHODS: Retrospective data analysis was performed (3, 6, 9 and 12 months after LSG) using the medical records of 96 morbidly obese patients who had undergone LSG at our institution during 2011-2013. Data collected from patient records were: adherence to prescribed diet; adherence to prescribed consumption of fruit, vegetables, legumes and cereals; use of prescribed micronutrient supplements; and barriers to diet and micronutrient therapy adherence. Data were analysed using spss, version 14.0 (SPSS Inc., Chicago, IL, USA). RESULTS: At 3, 6, 9 and 12 months post-LSG, the rates of patient non-adherence to a prescribed diet were 39%, 45%, 51% and 74%, respectively. In particular, there was a low consumption of fruit, vegetables, legumes and cereals compared to the post-surgery prescription. In addition, the rates of patient non-adherence to prescribed micronutrient supplements at 3, 6, 9 and 12 months post-LSG were 43%, 51%, 59% and 67%, respectively. The main reasons for patient non-adherence to diet were poor self-discipline (72%) and poor family support (11%) whereas difficulty swallowing pills or capsules (61%) and cost (20%) were reported as the main barriers to post-LSG adherence. CONCLUSIONS: Morbidly obese patients who have undergone LSG do not follow exactly the post-operative dietary guidelines, including micronutrient therapy.

Transmission of canine transmissible venereal tumour between two dogs in the UK.

Canine transmissible venereal tumour (CTVT) is a contagious cancer spread by transfer of living cancer cells. Occasional cases are observed in the UK in dogs imported from endemic regions. Here, we report a case of imported canine transmissible venereal tumour that was transmitted to a second dog within the UK. Transmission of genital canine transmissible venereal tumour occurred despite neutered status of the second dog. The aggressive course of disease in both cases, which included metastasis, resistance to therapeutic interventions and ultimate euthanasia of both dogs, is described. The diagnosis of canine transmissible venereal tumour was made using a combination of cytology, histology, immunohistochemistry and PCR to detect the LINE-MYC rearrangement. Practitioners unfamiliar with canine transmissible venereal tumour are reminded of this disease of concern, particularly when imported dogs are placed in multi-dog households, irrespective of neuter status.

Optimizing PANi doped electroactive substrates as patches for the regeneration of cardiac muscle.

In scaffold aided regeneration of muscular tissue, composite materials are currently utilized as a temporary substrate to stimulate tissue formation by controlled electrochemical signals as well as continuous mechanical stimulation until the regeneration processes are completed. Among them, composites from the blending of conductive (CPs) and biocompatible polymers are powerfully emerging as a successful strategy for the regeneration of myocardium due to their unique conductive and biological recognition properties able to assure a more efficient electroactive stimulation of cells. Here, different composite substrates made of synthesized polyaniline (sPANi) and polycaprolactone (PCL) were investigated as platforms for cardiac tissue regeneration. Preliminary, a comparative analysis of substrates conductivity performed on casted films endowed with synthesized polyaniline (sPANi) short fibres or blended with emeraldine base polyaniline (EBPANi) allows to study the attitude of charge transport, depending on the conducting filler amount, shape and spatial distribution. In particular, conducibility tests indicated that sPANi short fibres provide a more efficient transfer of electric signal due to the spatial organization of electroactive needle-like phases up to form a percolative network. On the basis of this characterization, sPANi/PCL electrospun membranes have been also optimized to mimic either the morphological and functional features of the cardiac muscle ECM. The presence of sPANi does not relevantly affect the fibre architecture as confirmed by SEM/image analysis investigation which shows a broader distribution of fibres with only a slight reduction of the average fibre diameter from 7.1 to 6.4 µm. Meanwhile, biological assays--evaluation of cell survival rate by MTT assay and immunostaining of sarcomeric α-actinin of cardiomyocites-like cells--clearly indicate that conductive signals offered by PANi needles, promote the cardiogenic differentiation of hMSC into cardiomyocite-like cells. These preliminary results concur to promise the development of electroactive biodegradable substrates able to efficiently stimulate the basic cell mechanisms, paving the way towards a new generation of synthetic patches for the support of the regeneration of damaged myocardium.

Innovative electrochemical approach for an early detection of microRNAs.

The recent findings of circulating cell-free tissue specific microRNAs in the systemic circulation and the potential of their use as specific markers of disease highlight the need to make microRNAs testing a routine part of medical care. At the present time, microRNAs are detected by long and laborious techniques such as Northern blot, RT-PCR, and microarrays. The originality of our work consists in performing microRNAs detection through an electrochemical genosensor using a label-free method. We were able to directly detect microRNAs without the need of PCR and a labeling reaction. The test is simple, very fast and ultrasensitive, with a detection limit of 0.1 pmol. Particularly feasible for a routine microRNAs detection in serum and other biological samples, our technical approach would be of great scientific value and become a common method for simple miRNAs routine detection in both clinical and research settings.

Hypothalamic and pituitary expression of ghrelin receptor message is increased during lactation.

In the lactating rat there is a dramatic increase in food intake that peaks at around day 15 postpartum, a time when pups are near weaning age, yet still fully dependant on maternal nourishment. We examined whether the orexigenic hormone ghrelin plays a role in increasing food intake during lactation. To do this, we compared plasma levels ghrelin, as well as brain and pituitary expression of the growth hormone secretagogue receptor (GHS-R 1a) rats in one of three groups: (1) dams whose litters were removed the day after giving birth (non-lactating); (2) dams whose litters were removed on day 13 postpartum (litter removed), and dams allowed keeping their litters (lactating). On day 15 postpartum, all dams were decapitated and trunk blood collected for plasma analysis of active ghrelin levels. Also, brain and pituitaries were collected and snap frozen using liquid nitrogen and stored at -80 degrees C before mRNA extraction and RT-PCR analysis. Results show no differences in ghrelin concentrations between lactating and non-lactating rats. Hypothalamic and pituitary expression of GHS-R 1a, however, was significantly increased in lactating animals compared to non-lactating animals. Interestingly, litter removed dams had higher levels of plasma ghrelin concentrations than either lactating or non-lactating females. Furthermore, GHS-R mRNA expression in these animals remained elevated in the pituitary but not the hypothalamus. These data suggest that the hypothalamus and pituitary of lactating rats are more sensitive to the effects of ghrelin, and that hypothalamic sensitivity to ghrelin depends on the presence of a suckling litter.

Catalytic Effect of Pd Clusters in the Poly(N-vinyl-2-pyrrolidone) Combustion.

Pd(0) is able to catalyze oxygen-involving reactions because of its capability to convert molecular oxygen to the very reactive atomic form. Consequently, the embedding of a little amount of Pd(0) clusters in polymeric phases can be technologically exploited to enhance the incineration kinetic of these polymers. The effect of nanostructuration on the Pd(0) catalytic activity in the polymer incineration reaction has been studied using poly(N-vinyl-2-pyrrolidone) ([Formula: see text] = 10,000 gmol-1) as polymeric model system. A change in the PVP incineration kinetic mechanism with significant increase in the reaction rate was experimentally found. The kinetic of the Pd(0)-catalyzed combustion has been studied by isothermal thermogravimetric analysis. After a short induction time, the combustion in presence of Pd(0) clusters shifted to a zero-order kinetic from a second-order kinetic control, which is operative in pure PVP combustion reaction. In addition, the activation energy resulted much lowered compared to the pure PVP incineration case (from 300 to 260 kJ/mol).

Gastroprotective and toxicological evaluation of the Lithothamnion calcareum algae.

Lithothamnion calcareum is a red alga of the Corallinacea family whose main feature is the formation of calcium carbonate precipitate in its cell walls. L. calcareum is marketed as a nutritional supplement for calcium and other minerals in Brazil and other countries under the pharmaceutical name of Vitality 50+. In this study, gastroprotective and pre-clinical toxicity assays were performed on this product. Doses of 30, 120 and 480 mg/kg were used in the gastroprotective study on Wistar rats. A dose of 2000 mg/kg was used in the preclinical acute toxicity study and oral doses of 1000 and 2000 mg/kg were used in the subchronic toxicity evaluation. L. calcareum played no significant role in the protection of the rats' gastric mucosa, nor did it cause increase in gastric irritation. No impact on the acute toxicity test was identified. In the subchronic toxicity test, serum levels of albumin, total protein and calcium decreased, and creatinine levels increased, suggesting hypercalcemia and possible kidney damage associated with liver damage, given that the majority of these parameters were irreversible. Thus, this work aims to discuss the relationship of the high concentration of calcium in the product with the observed effects.

Thyroid hormones as molecular determinants of thermogenesis.

Thyroid hormones (TH) are major modulators of energy metabolism and thermogenesis. It is generally believed that 3,5,3'-triiodo-l-thyronine (T3) is the only active form of TH, and that most of its effects are mediated by nuclear T3 receptors, which chiefly affect the transcription of target genes. Some of these genes encode for the proteins involved in energy metabolism. However, a growing volume of evidence now indicates that other iodothyronines may be biologically active. Several mechanisms have been proposed to explain the calorigenic effect of TH, but none has received universal acceptance. Cold acclimation/exposure and altered nutritional status are physiological conditions in which a modulation of energy expenditure is particularly important. TH seem to be deeply involved in this modulation, and this article will review some aspects of their possible influence in these conditions.

Self-reports of HIV risk factors by patients at a sexually transmitted disease clinic: audio vs written questionnaires.

OBJECTIVES: The purpose of this study was to determine how the method of assessment affects patient report of human immunodeficiency virus (HIV) risks. METHODS: Patients at a sexually transmitted disease clinic randomly received either a written self-administered questionnaire or an audio self-administered questionnaire delivered by cassette player and headset. These questionnaires were followed by face-to-face interviews. RESULTS: Audio questionnaires had fewer missing responses than written questionnaires. Audio questionnaires also identified more unprotected vaginal intercourse and sexual partners suspected or known to have HIV infection or acquired immunodeficiency syndrome than did written questionnaires. Although both the audio and written questionnaires identified more risks than the face-to-face interviews, the difference in the mean number of reported risks between the audio questionnaires and the face-to-face interviews was greater than that between the written questionnaires and the face-to-face interviews. CONCLUSIONS: Audio questionnaires may obtain more complete data and identify more HIV risk than written questionnaires. Research is warranted about whether audio questionnaires overcome barriers to the completion and accuracy of HIV risk surveys. This study emphasizes the need to elucidate the relative strengths and weaknesses of written questionnaires, audio questionnaires, and face-to-face interviews for HIV risk assessment.