The multidisciplinary therapy in binge eating disorder is able to influence the interdaily stability and sleep quality?

ABSTRACT

We have recently shown that rest-activity circadian rhythm significantly differed in women with Binge Eating Disorder (BED) compared to the Ctrl group. In details, patients with BED exhibited significantly reduced levels of MESOR and Amplitude with respect to the Ctrl group. In addition, in this previous study, the results of the actigraphic sleep monitoring provided no evidence of differences in sleep parameters between the two groups. We expanded the original sample obtaining a total of 28 volunteered women, 14 BED women, and 14 Ctrl. We recorded in all 28 participants a 5-day actigraphic monitoring to detect the rhythmometric parameters, interdaily stability, intradaily variability, L5, M10, and sleep parameters. During the study, BED’s women group kept an individual multidisciplinary therapy lasting five weekly days, from Monday to Friday, consisting in cognitive-behavioral therapy and nutritional program, administered in outpatient care from 8:00 a.m. at 5:00 p.m. The combination of both our previous and current study supports the conclusion that the sleep quality of the BED group is significantly better compared to Ctrl. The non-parametric indexes showed how interdaily stability, significantly correlated to sleep efficiency, was higher in BED group compared to the Ctrl group, indicating a better synchronization of rest-activity circadian rhythm. In conclusion, the maintenance of a regular lifestyle, such as imposed by the multidisciplinary therapy, is important to avoid alterations in the sleep-wake cycle, particularly in patients with eating disorders.     

Melatonin Entrains Free‐running Blind People According to a Physiological Dose‐response Curve

The specific circadian role proposed for endogenous melatonin production was based on a study of sighted people who took low pharmacological doses (500 µg) of this chemical signal for the “biological night”: the magnitude and direction of the induced phase shifts were dependent on what time of day exogenous melatonin was administered and were described by a phase‐response curve that turned out to be the opposite of that for light. We now report that lower (physiological) doses of up to 300 µg can entrain (synchronize) free‐running circadian rhythms of 10 totally blind subjects that would otherwise drift later each day. The resulting log‐linear dose‐response curve in the physiological range adds support for a circadian function of endogenous melatonin in humans. Efficacy of exogenous doses in the physiological range are of clinical significance for totally blind people who will need to take melatonin daily over their entire lifetimes in order to remain entrained to the 24 h day. Left untreated, their free‐running endocrine, metabolic, behavioral, and sleep/wake cycles can be almost as burdensome as not having vision.     

Mucosal Immunization of Lactating Female Rhesus Monkeys with a Transmitted/Founder HIV-1 Envelope Induces Strong Env-Specific IgA Antibody Responses in Breast Milk

We previously demonstrated that vaccination of lactating rhesus monkeys with a DNA prime/vector boost strategy induces strong T-cell responses but limited envelope (Env)-specific humoral responses in breast milk. To improve vaccine-elicited antibody responses in milk, hormone-induced lactating rhesus monkeys were vaccinated with a transmitted/founder (T/F) HIV Env immunogen in a prime-boost strategy modeled after the moderately protective RV144 HIV vaccine. Lactating rhesus monkeys were intramuscularly primed with either recombinant DNA (n = 4) or modified vaccinia virus Ankara (MVA) poxvirus vector (n = 4) expressing the T/F HIV Env C.1086 and then boosted twice intramuscularly with C.1086 gp120 and the adjuvant MF59. The vaccines induced Env-binding IgG and IgA as well as neutralizing and antibody-dependent cellular cytotoxicity (ADCC) responses in plasma and milk of most vaccinated animals. Importantly, plasma neutralization titers against clade C HIV variants MW965 (P = 0.03) and CAP45 (P = 0.04) were significantly higher in MVA-primed than in DNA-primed animals. The superior systemic prime-boost regimen was then compared to a mucosal-boost regimen, in which animals were boosted twice intranasally with C.1086 gp120 and the TLR 7/8 agonist R848 following the same systemic prime. While the systemic and mucosal vaccine regimens elicited comparable levels of Env-binding IgG antibodies, mucosal immunization induced significantly stronger Env-binding IgA responses in milk (P = 0.03). However, the mucosal regimen was not as potent at inducing functional IgG responses. This study shows that systemic MVA prime followed by either intranasal or systemic protein boosts can elicit strong humoral responses in breast milk and may be a useful strategy to interrupt postnatal HIV-1 transmission.     

Routes into education and employment for young Pakistani and Bangladeshi women in the UK

The article examines the educational and employment experiences and aspirations of young Pakistani and Bangladeshi people living in Oldham, in Great Manchester. Many young people demonstrated high aspirations and high levels of participation, particularly in relation to the educational and occupational level of their parents. Explanatory factors include the cultural value of education among Asian groups, the desire by parents to ensure success for their children and the ethnic penalty which these young people incur in the labour market. However, not all Pakistani and Bangladeshi young people have these aspirations. Girls who wished to continue their education faced a more complex situation than boys; for girls it was important to avoid jeopardizing the family honour. Nonetheless, national statistics show a marked increase in the numbers of young Pakistani and Bangladeshi women in full-time undergraduate courses in recent years. Women with degree level qualifications showed considerable determination to combine paid employment with family life.     

Blood Metals Concentration in Type 1 and Type 2 Diabetics

Mechanisms for the onset of diabetes and the development of diabetic complications remain under extensive investigations. One of these mechanisms is abnormal homeostasis of metals, as either deficiency or excess of metals, can contribute to certain diabetic outcomes. Therefore, this paper will report the blood levels of chromium (Cr), copper (Cu), iron (Fe), manganese (Mn), mercury (Hg), nickel (Ni), lead (Pb), selenium (Se), and zinc (Zn) in subjects with type 1 diabetes (n?=?192, mean age 48.8 years, mean disease duration 20.6 years), type 2 diabetes (n?=?68, mean age 68.4 years, mean disease duration 10.2 years), and in control subjects (n?=?59, mean age 57.2 years), and discuss the results indicating their possible role in diabetes. The metal concentrations were measured by sector field inductively coupled plasma mass spectrometry after microwave-induced acid digestion of blood samples. The accuracy was checked using a blood-based certified reference material, and recoveries of all elements were in the range of 92–101 % of certified values. Type 1 diabetes was found to be associated with Cr (p?=?0.02), Mn (p?<?0.001), Ni (p?<?0.001), Pb (p?=?0.02), and Zn (p?<?0.001) deficiency, and type 2 diabetes with Cr (p?=?0.014), Mn (p?<?0.001), and Ni (p?<?0.001) deficiency. These deficiencies were appreciated also subdividing the understudied patients for gender and age groups. Furthermore, in type 1 diabetes, there was a positive correlation between Pb and age (p?<?0.001, ρ?=?0.400) and Pb and BMI (p?<?0.001, ρ?=?0.309), while a negative correlation between Fe and age (p?=?0.002, ρ?=??0.218). In type 2 diabetes, there was a negative correlation between Fe and age (p?=?0.017, ρ?=??0.294) and Fe and BMI (p?=?0.026, ρ?=??0.301). Thus, these elements may play a role in both forms of diabetes and combined mineral supplementations could have beneficial effects.     

Obscurin is required for ankyrinB-dependent dystrophin localization and sarcolemma integrity

Obscurin is a large myofibrillar protein that contains several interacting modules, one of which mediates binding to muscle-specific ankyrins. Interaction between obscurin and the muscle-specific ankyrin sAnk1.5 regulates the organization of the sarcoplasmic reticulum in striated muscles. Additional muscle-specific ankyrin isoforms, ankB and ankG, are localized at the subsarcolemma level, at which they contribute to the organization of dystrophin and β-dystroglycan at costameres. In this paper, we report that in mice deficient for obscurin, ankB was displaced from its localization at the M band, whereas localization of ankG at the Z disk was not affected. In obscurin KO mice, localization at costameres of dystrophin, but not of β-dystroglycan, was altered, and the subsarcolemma microtubule cytoskeleton was disrupted. In addition, these mutant mice displayed marked sarcolemmal fragility and reduced muscle exercise tolerance. Altogether, the results support a model in which obscurin, by targeting ankB at the M band, contributes to the organization of subsarcolemma microtubules, localization of dystrophin at costameres, and maintenance of sarcolemmal integrity.     

Fluoro‐Sorafenib (Regorafenib) effects on hepatoma cells: Growth inhibition,quiescence, and recovery

To evaluate the growth‐inhibitory properties of the potent multi‐kinase antagonist Regorafenib (Fluoro‐Sorafenib), which was synthesized as a more potent Sorafenib, a Raf inhibitor and to determine whether similar mechanisms were involved, human hepatoma cell lines were grown in the presence or absence of Regorafanib and examined for growth inhibition. Western blots were performed for Raf targets, apoptosis, and autophagy. Regorafenib inhibited growth of human Hep3B, PLC/PRF/5, and HepG2 cells in a concentration‐ and time‐dependent manner. Multiple signaling pathways were altered, including MAP kinases phospho‐ERK and phospho‐JNK and its target phospho‐c‐Jun. There was evidence for apoptosis by FACS, cleavage of caspases and increased Bax levels; as well as induction of autophagy, as judged by increased Beclin‐1 and LC3 (II) levels. Prolonged drug exposure resulted in cell quiescence. Full growth recovery occurred after drug removal, unlike with doxorubicin chemotherapy. Regorafenib is a potent inhibitor of cell growth. Cells surviving Regorafenib treatment remain viable, but quiescent and capable of regrowth following drug removal. The reversibility of tumor cell growth suppression after drug removal may have clinical implications. J. Cell. Physiol. 228: 292–297, 2013. © 2012 Wiley Periodicals, Inc.     

A Model of the Membrane-bound Cytochrome b5-Cytochrome P450 Complex from NMR and Mutagenesis Data

Microsomal cytochrome b₅ (cytb₅) is a membrane-bound protein that modulates the catalytic activity of its redox partner, cytochrome P4502B4 (cytP450). Here, we report the first structure of full-length rabbit ferric microsomal cytb₅ (16 kDa), incorporated in two different membrane mimetics (detergent micelles and lipid bicelles). Differential line broadening of the cytb₅ NMR resonances and site-directed mutagenesis data were used to characterize the cytb₅ interaction epitope recognized by ferric microsomal cytP450 (56 kDa). Subsequently, a data-driven docking algorithm, HADDOCK (high ambiguity driven biomolecular docking), was used to generate the structure of the complex between cytP4502B4 and cytb₅ using experimentally derived restraints from NMR, mutagenesis, and the double mutant cycle data obtained on the full-length proteins. Our docking and experimental results point to the formation of a dynamic electron transfer complex between the acidic convex surface of cytb₅ and the concave basic proximal surface of cytP4502B4. The majority of the binding energy for the complex is provided by interactions between residues on the C-helix and β-bulge of cytP450 and residues at the end of helix α4 of cytb₅. The structure of the complex allows us to propose an interprotein electron transfer pathway involving the highly conserved Arg-125 on cytP450 serving as a salt bridge between the heme propionates of cytP450 and cytb₅. We have also shown that the addition of a substrate to cytP450 likely strengthens the cytb₅-cytP450 interaction. This study paves the way to obtaining valuable structural, functional, and dynamic information on membrane-bound complexes.