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In vivo, in a high-salt administration experiment, male and female Dahl salt-sensitive rats became hypertensive after 4 weeks on a high-NaCl diet, their plasma marinobufagenin levels doubled, and adrenocortical CYP27A1 mRNA and protein increased 1.6-fold and 2.0-fold.

Therefore, the endogenous steroidal Na/K-ATPase inhibitor, marinobufagenin, is synthesized in mammalian placenta and adrenal cortex from cholesterol through the novel acidic bile acid pathway. These findings will help to understand the role of marinobufagenin in highly prevalent human cardiovascular diseases.

Therefore, the endogenous steroidal Na/K-ATPase inhibitor, marinobufagenin, is synthesized in mammalian placenta and adrenal cortex from cholesterol through the novel acidic bile acid pathway. These findings will help to understand the role of marinobufagenin in highly prevalent human cardiovascular diseases.

Patients with PCSK9 gene gain of function (GOF) mutations have a rare form of autosomal dominant hypercholesterolemia. However, data examining their clinical characteristics and geographic distribution are lacking. Furthermore, no randomized treatment study in this population has been reported.

We compiled clinical characteristics of PCSK9 GOF mutation carriers in a multinational retrospective, cross-sectional, observational study. We then performed a randomized placebo-phase, double-blind study of alirocumab 150 mg administered subcutaneously every 2 weeks to 13 patients representing 4 different PCSK9 GOF mutations with low-density lipoprotein cholesterol (LDL-C) ≥70 mg/dL on their current lipid-lowering therapies at baseline. Observational study among 164 patients, 16 different PCSK9 GOF mutations distributed throughout the gene were associated with varying severity of untreated LDL-C levels. Coronary artery disease was common (33%; average age of onset, 49.4 years), and untreated LDL-C concentrations were higher compared with matched carriers of mutations in the LDLR (n=2126) or apolipoprotein B (n=470) genes. Intervention study in PCSK9 GOF mutation patients randomly assigned to receive alirocumab, mean percent reduction in LDL-C at 2 weeks was 62.5% (P<0.0001) from baseline, 53.7% compared with placebo-treated PCSK9 GOF mutation patients (P=0.0009; primary end point). After all subjects received 8 weeks of alirocumab treatment, LDL-C was reduced by 73% from baseline (P<0.0001).

PCSK9 GOF mutation carriers have elevated LDL-C levels and are at high risk of premature cardiovascular disease. Alirocumab, a PCSK9 antibody, markedly lowers LDL-C levels and seems to be well tolerated in these patients.

URL http//www.clinicaltrials.gov. Unique Identifier NCT01604824.

URL http//www.clinicaltrials.gov. Unique Identifier NCT01604824.Three species of Pseudodactylogyrus Gusev, 1965 (Monogenea Pseudodactylogyridae) were collected from the gills of Anguilla reinhardtii Steindachner and A. australis Richardson from several localities in Australia and eels imported to Japan from Australia. Pseudodactylogyrus gusevi sp. n. from A. reinhardtii (type host) and A. australis in Queensland, Australia is most similar to P. bini (Kikuchi, 1929), but can be differentiated by the shorter male copulatory tube, heavy sclerotisation of the vaginal tube and the presence of a small projection of the supplementary piece of the hamulus. Pseudodactylogyrus rohdei sp. n. from A. australis (type host) in Queensland, Australia is most similar to P. anguillae (Yin et Sproston, 1948), but differs in the possession of a longer cement gland and the presence of a small projection on the supplementary piece of the hamulus. Pseudodactylogyrus bini sensu Gusev, 1965 and P. anguillae sensu Gusev, 1965 are synonymised with P. gusevi sp. n. and P. rohdei sp. n., respectively. Pseudodactylogyrus mundayi sp. n. from A. australis, originating in Tasmania, Australia and sent alive to Japan, is most similar to P. kamegaii Iwashita, Hirata et Ogawa, 2002, from which it can be discriminated by the shorter male copulatory tube and the shorter vaginal tube. Dactylogyrus bialatus Wu, Wang et Jian, 1988 from Synechogobius ommaturus (Richardson) (Gobiidae) is transferred to Pseudodactylogyrus as P. bialatus comb. n. A phylogenetic tree based on the ITS2 region of six species of Pseudodactylogyrus including P. gusevi and P. mundayi shows that P. haze from a goby diverged first, and that species from eels are monophyletic, forming three lineages differing by their zoogeographical distribution. With the three new species and one new combination proposed in this paper, Pseudodactylogyrus is now comprised of eight species infecting anguillid and gobiid fish, and a key to species is presented.Phenotypic heterogeneity of human carcinoma lesions, including heterogeneity in expression of tumor-associated antigens (TAAs), is a well-established phenomenon. Carcinoembryonic antigen (CEA), MUC1, and brachyury are diverse TAAs, each of which is expressed on a wide range of human tumors. We have previously reported on a novel adenovirus serotype 5 (Ad5) vector gene delivery platform (Ad5 [E1-, E2b-]) in which regions of the early 1 (E1), early 2 (E2b), and early 3 (E3) genes have been deleted. The unique deletions in this platform result in a dramatic decrease in late gene expression, leading to a marked reduction in host immune response to the vector. Ad5 [E1-, E2b-]-CEA vaccine (ETBX-011) has been employed in clinical studies as an active vaccine to induce immune responses to CEA in metastatic colorectal cancer patients. We report here the development of novel recombinant Ad5 [E1-, E2b-]-brachyury and-MUC1 vaccine constructs, each capable of activating antigen-specific human T cells in vitro and inducing antigen-specific CD4+ and CD8+ T cells in vaccinated mice. We also describe the use of a combination of the three vaccines (designated Tri-Ad5) of Ad5 [E1-, E2b-]-CEA, Ad5 [E1-, E2b-]-brachyury and Ad5 [E1-, E2b-]-MUC1, and demonstrate that there is minimal to no "antigenic competition" in in vitro studies of human dendritic cells, or in murine vaccination studies. The studies reported herein support the rationale for the application of Tri-Ad5 as a therapeutic modality to induce immune responses to a diverse range of human TAAs for potential clinical studies.One of the more common reasons patients seek medical advice after traveling in tropical countries are skin eruptions. Here we describe two cases of individuals who, after traveling to south east Asia, developed a skin eruption later diagnosed as cutaneous larva migrans. This particular skin condition is common among travelers to countries where the hookworm responsible is endemic. The diagnosis is based on travel history and clinical examination. The patients were treated with albendazole with good results and complete resolution of the symptoms.

Present study examines the prevalence of type 2 diabetes (DM2) in patients attending cardiac rehabilitation (CR) compared to the general population utilising data from the Icelandic Heart Association population study. The study also examined the efficacy of CR for promoting health behaviors.

A prospective study among DM2 patients attending CR at Reykjalundur Rehabilitation centre. selleck chemicals The DM2 group was compared to other cardiac patients, with respect to obesity and exercise capacity at the beginning and end of 4-6 weeks of CR. Additionally, in the DM2 group, weight, smoking cessation, physical activity and walking capacity were assessed at 3 and 6 months follow-ups.

The prevalence of DM2 was 2-4 times higher in CR participants than in the general population. Compared to other CR participants, the DM2 group was heavier, with increased waist circumference and less exercise capacity. During the CR both groups lost weight and waist circumference decreased to similar extent, but the exercise capacity increased less in the DM2 group. In follow up after 6 months the DM2 group´s weight and glucose values were back to same level as before CR, but waist circumference was still decreased and they retained increased physical activity and walking capacity.

DM2 is more prevalent among patients in cardiac rehabilitation than in the general population. The DM2 group was more obese, had lower exercise capacity and responded somewhat less to CR than other cardiac patients. Follow up after 6 months did however show that they continued their regular exercise and walking capacity was still retained.

DM2 is more prevalent among patients in cardiac rehabilitation than in the general population. The DM2 group was more obese, had lower exercise capacity and responded somewhat less to CR than other cardiac patients. Follow up after 6 months did however show that they continued their regular exercise and walking capacity was still retained.

Childhood obesity is a growing health problem worldwide. Body mass index (BMI) has been used as the main measurement of obesity for years but its quality for children has been questioned. In 2011 the Health School was formed at the Childrens Medical Center at Landspitali University Hospital for treatment of obese children and their families. The aim of this study was to find the best predictor of blood test abnormalities and to get a clear picture of abnormalities in blood values in the group of obese children referred to the Health School.

All children referred to the Health School from January 1st 2011 until March 15th 2013 were retrospectively studied (n=181). Information was gathered on height, weight, BMI, waist circumference and available blood variables.

Abnormal blood values were found in 54 cases (47%). Of the children where information was available, four (4%) had Non-Alchoholic Fatty Liver Disease (NAFLD) and 28 (28%) had a raised fasting insulin levels whereof 8 (8%) needed treatment. One child had both NAFLD and raised fasting insulin.

Abnormal blood values are common in obese children. Waist circumference appears to have a better predictive value of these abnormalities than BMI-SDS. Waist circumference could be used to screen for children who need physician supervision because of risk of metabolic disorders. Waist circumference adds important information to the risk assessment of obese children. This study emphasises the importance of care givers measuring waist circumference in obese children.

Abnormal blood values are common in obese children. Waist circumference appears to have a better predictive value of these abnormalities than BMI-SDS. Waist circumference could be used to screen for children who need physician supervision because of risk of metabolic disorders. Waist circumference adds important information to the risk assessment of obese children. This study emphasises the importance of care givers measuring waist circumference in obese children.

In England, antenatal pertussis immunization using a tetanus/low-dose diphtheria/5-component acellular-pertussis/inactivated-polio (TdaP5/IPV) vaccine was introduced in October 2012. We assessed infant responses to antigens in the maternal vaccine and to those conjugated to tetanus (TT) or the diphtheria toxin variant, CRM.

Infants of 141 TdaP5/IPV-vaccinated mothers in Southern England immunized with DTaP5/IPV/Haemophilus influenzae b (Hib-TT) vaccine at 2-3-4 months, 13-valent pneumococcal vaccine (PCV13, CRM-conjugated) at 2-4 months and 1 or 2 meningococcal C vaccine (MCC-CRM- or MCC-TT) doses at 3-4 months had blood samples taken at 2 and/or 5 months of age.

Antibody responses to pertussis toxin (PT), filamentous hemagglutinin (FHA), fimbriae 2 + 3 (FIMs), diphtheria, tetanus, Hib, MCC and PCV13 serotypes were compared to responses in a historical cohort of 246 infants born to mothers not vaccinated in pregnancy. Infants had high pertussis antibody concentrations pre-immunization but only PT antibodies increased post-immunization (fold-change, 2.