Ainhum or Dactylolysis Spontanea: a Missing Toe

Keywords: Ainhum; Toes.

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Thirty Six Views of Mount Fuji and the First Oncology Appointment

Keywords: Appointments and Schedules; Medicine in Art; Neoplasms; Paintings.

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Assisted Reproductive Technology in Female Transplant Recipients: Experience of a Reproductive Medicine Unit and Literature Review

Diseases in end stage typically occur with hypothalamic-pituitary-ovarian axis disorders, with consequent anovulation and infertility. The solid organ transplantation increased survival of patients with end-stage organs disease and the vast majority of women improve their reproductive capacity after transplantation. Although adoption can always be a possibility, the transplanted infertile woman has the right to self-reproductive determination using assisted reproductive techniques. While it is known that pregnancies in transplanted
women are at high risk, there is no evidence of differences in pregnancy outcome in pregnant transplanted subject to technical, compared with spontaneous pregnancies. The use of assisted reproductive techniques in transplanted women is a medical, ethical and psychosocial challenge, whose approach must be multidisciplinary, to ensure reproductive success without compromising the function of the transplanted organ or maternal health, allowing the birth of a healthy child. The literature remains scarce. Three clinical cases are presented.

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Ectopic Decidualization: A Forgotten Entity

Introduction: Although ectopic decidualization is an entity often underdiagnosed, it may have adverse clinical impact on maternal-fetal morbimortality. The objective of this study was to review the scientific evidence regarding the etiology, clinical features, diagnosis and therapeutic approach on this issue.
Material and Methods: The search for this literature review was conducted in PubMed, Web of Science and Scopus, through the query ('deciduosis' OR 'ectopic decidualization' OR 'ectopic decidua' OR 'ectopic decidua reaction'), considering articles of all evidence levels published up to 31/06/2014.
Results: Ectopic decidualization is, usually, a benign condition, asymptomatic and does not require therapeutic intervention. It occurs mostly during pregnancy, with complete regression in the postpartum period. The frequency of the diagnosis depends on the clinical suspicion and its location, being the omentum and the ovary the most common sites. When symptomatic, the main clinical manifestations are genital bleeding and hemoperitoneum. Differential diagnosis includes malignant disease and histopathological confirmation is essential in these situations. The low index of suspicion may lead to a biopsy, which can have serious adverse outcomes due to the high friability of these lesions.
Discussion and Conclusion: The recognition of this entity and its clinical features are essential for the management of these patients. On one side this allows an early and proper medical approach in severe cases, on the other side (the majority of cases) maintaining an expectant attitude avoiding iatrogeny, does not compromise, in most cases, the favorable outcome of ectopic decidualization.

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Are Amyotrophic Lateral Sclerosis Caregivers at Higher Risk for Health Problems?

Introduction: Amyotrophic lateral sclerosis is a rare neurodegenerative disease affecting motor neurons. Patients present with progressive physical impairment, respiratory failure being the main cause of death. A significant portion of patients presents neurobehavioral problems as well. As severe impairment occurs, patients become highly dependent and in general, their families assume the role of primary caregivers, exposing them to stress and other potential causes of disease like insomnia, physical strain from patients' mobilization and changes on eating habits. The aim of this work is to understand if taking care of patients with amyotrophic lateral sclerosis increases disease and health problems on caregivers.
Material and Methods: Comprehensive review of the literature published on the electronic databases PubMed and Scopus between 2010 and 2014.
Results: Eighteen studies met the inclusion criteria. We found that amyotrophic lateral sclerosis caregivers have higher levels of burden, depression and anxiety with lower quality of life. This is associated to age and gender of caregivers, time spent caring, patients' disability and neurobehavioral changes. Higher sense of support and spirituality on family seem to promote wellbeing.
Discussion: On our work, we were able to understand that several factors have influenced caregivers' quality of life and affect their health. Besides, we could understand that the outcomes studied are related between themselves and, as seen in some of the studies, related to patients' quality of life itself. Consequently, it has become essential to adopt a holistic approach of these patients and their families, fighting the deteriorating risk factors and investing on health promoters.
Conclusion: Despite the large body of research on family caregiving for amyotrophic lateral sclerosis patients, little has changed and the outcomes measured remain almost the same before and after 2010. The work indicates that caregivers have lower levels of health than the general population. Still additional research is required, in order to better understand and characterized the changes on caregivers' health. It is nevertheless clear that health care professionals cannot ignore these health changes and need an approach focused not only on patients but also on caregivers.

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Syphilis: Prevalence in a Hospital in Lisbon

Introduction: Syphilis is a sexual and vertical transmitted disease. Its incidence is increasing in Europe, particularly, in Portugal.
Material and Methods: A descriptive, retrospective study was performed based on positive treponemal tests from January to December 2013, at the Santa Maria Hospital, Lisbon. In-patients and out-patients evaluated in medical appointments and at the emergency department were included. We proceeded to epidemiological characterization, disease classification and definition of risk factors.
Results: We obtained a sample of 580 patients, of whom 51 with no clinical data and 45 with false positive serologies were excluded. There was a predominance of male patients (75%) and a mean age of 47 years. Most (59%) had syphilis successfully treated in the past and 3.7% were in follow-up. We recorded 13 primaries syphilis, 71 cases of secondary syphilis, 40 cases of early latent syphilis, 49 unknown duration syphilis and five cases of late latent syphilis. In the early syphilis group, 42% (n = 124) were HIV-positive and, in 8% both diagnosis were done simultaneously.
Discussion: We emphasize the high prevalence of syphilis/HIV co-infection in patients with early syphilis, reinforcing the importance of promoting the use of preventive measures. We obtained 11% of patients with late clinical forms, which are notifiable since June 2014, in Portugal. All serological tests for the diagnosis of syphilis have limitations which emphasizes the importance of clinical-laboratory correlation.
Conclusion: Syphilis remains an important public health problem. It is necessary to establish education programs, screening and follow-up strategies to reduce their prevalence and to perform more efficient screening of the partners.

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A Neurologist’s Hard Day’s Work: Impact of Inpatient Neurology Consultation in a Tertiary Hospital

Introduction: Consultation of hospitalized patients under the responsibility of other specialties is a very demanding work. However, it is often under-recognized and poorly documented. The aim of the present study was to assess the burden of the inpatient neurology consultation in a Portuguese hospital and to evaluate the performance of our Neurology department regarding this issue.
Material and Methods: A retrospective study was conducted during 2013, reviewing clinical and demographic data.
Results: Over one year, the neurologists of our department evaluated 632 inpatients. The commonest reasons for consultation were altered mental state/behavior, focal neurological deficit and seizures. Requests came mainly from medical departments but also from Intermediate and Intensive Care Units. Neurologists suggested further investigation in almost one half of patients and management changes in a similar proportion of patients. A new diagnosis could be established in 63% of cases and the most frequent diagnosis were neurological manifestations of systemic disorders, epilepsy and cerebrovascular disease. Our intervention had impact on the care of 68% of patients.
Discussion and Conclusion: Different studies in the literature support our findings and highlight the economic and patient care benefits of this activity. Our results suggest that neurological inpatient observation generates useful interventions for the clinical management of these patients.

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Prevalence of Pre-Obesity/Obesity in Pre and Basic School Children at Vila Nova de Gaia, Portugal

Introduction: Over 30% of Portuguese children present overweight. Being a serious public health problem with multiple causes, only a cross-sectorial and concerted action could contribute to their resolution. Municipalities have a set of skills that make them ideal for effective intervention in the fight against this problem. For this action to be effective there must be a local assessment of the extent of the problem and their spatial distribution. The aim of this study was to characterize, from the point of view of the prevalence of overweight, the population of pre-school and first cycle basic education under the responsibility of the municipality of Vila Nova de Gaia, the third most populous municipality in the country.
Material and Methods: Were evaluated 8 974 pre and basic-school children, in school year 2013/14. The assessment of the nutritional status of the sample was made using anthropometric measures height and weight. In the classification of nutritional status was considered z-scores or percentiles of body mass index for age according to the World Health Organization, Centers for Disease Control and Prevention and International Obesity Task Force.
Results: The prevalence of overweight by the World Health Organization requirements was 37.4%. There were some disparities in the distribution of overweight in schools of the municipality.
Discussion: The results were slightly higher than those of other national and international studies, being the sampling size the possible justification for the differences founded.
Conclusion: The prevalence found is high and with irregular geographical distribution, which could help identifying the main causes of the problem at the local level.

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β-Tricalcium Phosphate in the Surgical Treatment of Proximal Humeral Fractures

Introduction: The proximal humeral fractures are becoming more frequent, with a greater tendency for its surgical treatment by osteosynthesis with plate and locked screws. The mechanical and biological failure in these fractures and devices, despite the evolution of this type of implants, highlighted the synthetic bone grafts became an option.
Material and Methods: Over a period of 96 months, patients considered were those with proximal humeral fractures treated surgically with a plate and locked screws, and in which β-tricalcium phosphate bone graft had been used. Functional results were evaluated by the shoulder range of motion as the radiological results.
Results: In 19 patients, with a medial follow up of 53 months, we obtained an average shoulder range of motion of 140º in abduction, 142º in forward flexion, 37º in external rotation and L3 hand position in internal rotation for a cefalo-diaphyseal angle of 136º.
Discussion: The β-tricalcium phosphate synthetic bone graft allows the maintenance of reduction after fixation of proximal humeral fractures stabilized with plate and locked screws. This reduction which means the maintenance of cefalo-diaphyseal angle is in close relationship with functional results as shown by shoulder range of motion in all planes.
Conclusion: The β-tricalcium phosphate synthetic bone graft should be seen as an adjuvant therapy in extramedullary fixation of proximal humeral fractures, especially those with greater comminution of the medial calcar.

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Burnout in Portuguese Healthcare Professionals: An Analysis at the National Level

Introduction: Burnout is a psychological syndrome, characterized by a state of high emotional exhaustion, high depersonalization and low personal accomplishment, which leads to erosion of personal, professional and health values. This study reports the incidence of burnout in Portuguese Healthcare professionals.
Material and Methods: Burnout in Portugal's health professionals was assessed with the Maslach Burnout Inventory - Human Services Survey, using a zero (never) to six (always) ordinal scale, on a sample of 1 262 nurses and 466 physicians with mean age of 36.8 year (SD = 12.2) and 38.7 (SD = 11.0), respectively. Participants came from all national districts (35% Lisbon, 18% Oporto, 6% Aveiro, 6% Setúbal, 5% Coimbra, 5% Azores and Madeira), working in hospitals (54%), Families' Health Units (30%), Personalized Health Units (8%) and other public or private institutions (8%).
Results: Analysis of MBI-HSS scores, stratified by district, revealed that both types of professionals had moderate to high levels of burnout (M = 3.0, SD = 1.7) with no significant differences between the two groups. Vila Real (M = 3.8, SD = 1.7) and Madeira (M = 2.5, SD = 1.5) were the regions where burnout levels were higher and lower, respectively. Burnout levels did not differ significantly between Hospital, Personalized Health Units and Families' Health Centers. Professionals with more years in the function were less affected by Burnout (r = -0.15). No significant association was observed with the duration of the working day (r = 0.04). The strongest predictor of burnout was the perceived quality of working conditions (r = -0.35).
Discussion: The occurrence of the burnout syndrome in Portuguese health professionals is frequent, being associated with a poor working conditions perception and reduced professional experience. The incidence of the burnout syndrome shows regional differences which may be associated with different and suboptimal conditions for health care delivery. Results suggest the need for interventions aimed at improving working conditions and initial job training of health professionals, as requisites for a good professional practice and personal well-being.
Conclusions: At the national level, between 2011 and 2013, 21.6% of healthcare professionals showed moderate burnout and 47.8% showed high burnout. The perception of poor working conditions was the main predictor of burnout occurrence among the Portuguese health professionals.

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Oncology Referral Concerning Paediatric Neurosurgery? Analysis of the Situation between 2008-2013 in the North of Portugal

Introduction: Primary central nervous system tumours represent the second most frequent neoplasm and are the leading cause of death from solid tumours in children. Our study aimed to provide the most up-to-date epidemiological analysis of primary central nervous system tumours in children living in the north of Portugal and to explore a possible effect of the centralisation of care on outcomes.
Material and Methods: This population-based study included all newly diagnosed and histologically confirmed primary central nervous system tumours in people below 18 years old, living in the north of Portugal, from January 2008 to December 2013. Data were collected through access to clinical files. We described children and tumour characteristics, and analysed patient: paediatric neurosurgeon and histological tumour type: paediatric neurosurgeon ratios.
Results: A total of 147 cases was recorded. Mean age at diagnosis of primary central nervous system tumours was 8.0 ± 5.2 years. Astrocytomas were the most common histological type (34%). We found that World Health Organization Tumour Grade was the only variable of statistically significant influence in mortality (p = 0.001). 1-, 3- and 5-year survivals related to 2008-2013 period were statistically higher than 2005 - 2007. Astrocytomas have the highest survival rate, with statistically significant difference from other tumours (p = 0.015). We estimated a mean of 12.25 treated cases per year by each paediatric neurosurgeon at our institution.
Discussion: Our results are globally consistent with those published all over the world, but we reported the highest survival rates. The number of cases treated per year by each neurosurgeon is accordant to the recommended.
Conclusion: We showed an improvement when comparing to data previous to 2008 and better results than those from previous studies, namely higher survival at 1-, 3- and 5-years from the diagnosis, with low complication and relapsing rates. Therefore, the referral of primary central nervous system tumours cases to centres with larger experience can be invaluable for the achievement of the best outcomes.

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Analysis of the Cochrane Review: Incentives for Smoking Cessation. Cochrane Database Syst Rev. 2015;5:CD004307.

Material incentives for alteration or reinforcement of healthy behaviours have been widely used in several health systems. These incentives, which are used in various contexts such as workplaces, health facilities or community programs, have been successfully implemented in smoking cessation programs. This systematic review - a third updated version of two published previously - sought to determine if a given set of incentives increased abstinence rates in smokers of medium and high risk (pregnant women). The authors searched several databases until December 2014: the Cochrane Tobacco Addiction Group Specialised Register, MEDLINE, EMBASE, CINAHL and PsycINFO. Two trials published in 2105 were included. The main results were:
- In mixed populations (medium risk) six months after the onset there is a greater probability of withdrawal in patients subject to incentives. Direct payments to smokers - through different forms - were particularly effective (North American studies);
- In populations of pregnant women (high risk), incentives caused a higher abstinence rate either during pregnancy or in the long term (up to 24 weeks postpartum).
The authors conclude that the incentives appear to be effective in increasing the rate of smoking cessation in medium-risk as well as high-risk populations (e.g. pregnant women).

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Heart Failure: A New Epidemic of Cardiovascular Disease

Keywords: Cardiovascular Diseases; Heart Failure.

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Thank You, Reviewers of Acta Médica Portuguesa

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General Practitioner Sentinel Network as a Tool of [Public] Health Surveillance

Current strategies of European health advocate the strengthening of the role of public health, requiring from decision-makers the ability to defend and enhance the health of individuals and populations in all policies. In the pursuit of this objective, public health should be evidence-based and so public health surveillance, seen as an important tool of public health since the nineteenth century, plays a central role in public health practice through the production and dissemination of the health information necessary for health planning and for evaluation of public health actions. Within the practice of public health estimations of disease frequency are important for outbreak control, health assessment, health needs assessment and estimation of health gains, but unfortunately these estimations are not always available for the entire population. In those cases and for diseases with high prevalence sentinel surveillance based in sentinel networks have some advantages for specific groups, namely needed of scarce resources and obtainment of quick results.
The central role of family doctors in chronic disease management, their knowledge on individuals and families and their responsibilities in the management of a clear defined patients list are characteristics that make general practice an appropriate context to develop a sentinel network. In fact, in Portugal there is a general practitioner sentinel network named Rede Médicos-Sentinela working since 1989 which estimated, for the last 25 years, incidence rates of several chronic diseases, some of them targeted on national priority health programs. Thus, we consider that Rede Médicos-Sentinela can be integrated in a national surveillance system for chronic diseases in Portugal.

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Life, Vol. 6, Pages 7: Regulation of Expression and Evolution of Genes in Plastids of Rhodophytic Branch

A novel algorithm and original software were used to cluster all proteins encoded in plastids of 72 species of the rhodophytic branch. The results are publicly available at http://ift.tt/1Pn5srs in a database that allows fast identification of clusters (protein families) both by a fragment of an amino acid sequence and by a phylogenetic profile of a protein. No such integral clustering with the corresponding functions can be found in the public domain. The putative regulons of the transcription factors Ycf28 and Ycf29 encoded in the plastids were identified using the clustering and the database. A regulation of translation initiation was proposed for the ycf24 gene in plastids of certain red algae and apicomplexans as well as a regulation of a putative gene in apicoplasts of Babesia spp. and Theileria parva. The conserved regulation of the ycf24 gene expression and specificity alternation of the transcription factor Ycf28 were shown in the plastids. A phylogenetic tree of plastids was generated for the rhodophytic branch. The hypothesis of the origin of apicoplasts from the common ancestor of all apicomplexans from plastids of red algae was confirmed.

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A photo-cleavable biotin affinity tag for the facile release of a photo-crosslinked carbohydrate-binding protein

Publication date: Available online 27 January 2016
Source:Bioorganic & Medicinal Chemistry
Author(s): Tsung-Che Chang, Avijit K. Adak, Ting-Wei Lin, Pei-Jhen Li, Yi-Ju Chen, Chain-Hui Lai, Chien-Fu Liang, Yu-Ju Chen, Chun-Cheng Lin
The use of photo-crosslinking glycoprobes represents a powerful strategy for the covalent capture of labile protein complexes and allows detailed characterization of carbohydrate-mediated interactions. The selective release of target proteins from solid support is a key step in functional proteomics. We envisaged that light activation can be exploited for releasing labeled protein in a dual photo-affinity probe-based strategy. To investigate this possibility, we designed a trifunctional, galactose-based, multivalent glycoprobe for affinity labeling of carbohydrate-binding proteins. The resulting covalent protein-probe adduct is attached to a photo-cleavable biotin affinity tag; the biotin moiety enables specific presentation of the conjugate on streptavidin-coated beads, and the photolabile linker allows the release of the labeled proteins. This dual probe promotes both the labeling and the facile cleavage of the target protein complexes from the solid surfaces and the remainder of the cell lysate in a completely unaltered form, thus eliminating many of the common pitfalls associated with traditional affinity-based purification methods.

Graphical abstract

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Synthesis and cytotoxicity of thieno[2,3-b]quinoline-2-carboxamide and cycloalkyl[b]thieno[3,2-e]pyridine-2-carboxamide derivatives

Publication date: Available online 27 January 2016
Source:Bioorganic & Medicinal Chemistry
Author(s): Euphemia Leung, Lisa I. Pilkington, Michelle van Rensburg, Chae Yeon Jeon, Mirae Song, Homayon J. Arabshahi, Gayan Heruka De Zoysa, Vijayalekshmi Sarojini, William A. Denny, Jóhannes Reynisson, David Barker
Seventy nine derivatives of thieno[2,3–b]quinolines, tetrahydrothieno[2,3-b]quinoline, dihydrocyclopenta[b]thieno[3,2-e]pyridine, cyclohepta[b]thieno[3,2-e]pyridine and hexahydrocycloocta[b]thieno[3,2-e]pyridine were either synthesized or obtained commercially and tested for their antiproliferative activity against HCT116, MDA-MB-468 and MDA-MB-231 human cancer cell lines. The most potent eight compounds were active against all cell lines with IC50 values in the 80-250 nM range. In general hexahydrocycloocta[b]thieno[3,2-e]pyridines were most active with increasing activity observed as larger cycloalkyl rings were fused to the pyridine ring.

Graphical abstract

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Design, Synthesis and Biological Evaluation of Dinucleotide mRNA Cap Analog Containing Propargyl Moiety

Publication date: Available online 29 January 2016
Source:Bioorganic & Medicinal Chemistry
Author(s): Muthian Shanmugasundaram, Irudaya Charles, Anilkumar R. Kore
The first example of the synthesis of new dinucleotide cap analog containing propargyl group such as ^{m7,3'-O-propargylG}[5']ppp[5']G is reported. The effect of propargyl cap analog with standard cap was evaluated with respect to their capping efficiency, in vitro T7 RNA polymerase transcription efficiency, and translation activity using cultured HeLa cells. It is noteworthy that propargyl cap analog outperforms standard cap by 3.1 fold in terms of translational properties. The propargyl cap analog forms a more stable complex with translation initiation factor eIF4E based on the molecular modeling studies.

Graphical abstract

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Synthesis and Biological Evaluation of Novel Inhibitors against 1,3,8-trihydroxynaphthalene Reductase from Magnaporthe grisea

Publication date: Available online 29 January 2016
Source:Bioorganic & Medicinal Chemistry
Author(s): Haifeng Chen, Xinya Han, Nian Qin, Lin Wei, Yue Yang, Li Rao, Bo Chi, Lingling Feng, Yanliang Ren, Jian Wan
1,3,8-trihydroxynaphthalene reductase (3HNR) is an essential enzymes that is involved in fungal melanin biosynthesis. Based on the structural informations of active site of 3HNR, a series of β-Nitrostyrene compounds were rationally designed and synthesized. The enzymatic activities of these compounds showed that most of them exhibited high inhibitory activities (< 5.0 μM) against 3HNR; Compound 3-2 exhibit the highest inhibitory activity (IC50 = 0.29 μM). In particular, some of these compounds had moderate fungicidal activity against M. grisea. Compound 3-4 showed high in vivo activities against M. grisea (EC50 = 9.5 ppm). Furthermore, Compound 3-2 was selected as a representative molecule, and the probable binding mode of this compound and the surrounding residues in the active site of 3HNR was elucidated by using molecular dock. The positive results suggest that β-Nitrostyrene Derivatives are most likely to be promising leads toward the discovery of novel agent of rice blast.

Graphical abstract

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Micromachines, Vol. 7, Pages 22: CD-Based Microfluidics for Primary Care in Extreme Point-of-Care Settings

We review the utility of centrifugal microfluidic technologies applied to point-of-care diagnosis in extremely under-resourced environments. The various challenges faced in these settings are showcased, using areas in India and Africa as examples. Measures for the ability of integrated devices to effectively address point-of-care challenges are highlighted, and centrifugal, often termed CD-based microfluidic technologies, technologies are presented as a promising platform to address these challenges. We describe the advantages of centrifugal liquid handling, as well as the ability of a standard CD player to perform a number of common laboratory tests, fulfilling the role of an integrated lab-on-a-CD. Innovative centrifugal approaches for point-of-care in extremely resource-poor settings are highlighted, including sensing and detection strategies, smart power sources and biomimetic inspiration for environmental control. The evolution of centrifugal microfluidics, along with examples of commercial and advanced prototype centrifugal microfluidic systems, is presented, illustrating the success of deployment at the point-of-care. A close fit of emerging centrifugal systems to address a critical panel of tests for under-resourced clinic settings, formulated by medical experts, is demonstrated. This emphasizes the potential of centrifugal microfluidic technologies to be applied effectively to extremely challenging point-of-care scenarios and in playing a role in improving primary care in resource-limited settings across the developing world.

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Regulation of endothelial dynamics by PGC-1α relies on ROS control of VEGF-A signaling

Publication date: Available online 29 January 2016
Source:Free Radical Biology and Medicine
Author(s): Nieves García-Quintans, Ignacio Prieto, Cristina Sánchez-Ramos, Alfonso Luque, Elvira Arza, Yolanda Olmos, María Monsalve
Peroxisome proliferator activated receptor γ co-activator 1α (PGC-1α) is a regulator of mitochondrial metabolism and reactive oxygen species (ROS) that is known to play a relevant role in angiogenesis. Aims: This study aims to investigate the role of ROS on the regulation by PGC-1α of angiogenesis. Methods and Results: We found that endothelial cells (ECs) from mice deleted for PGC-1α display attenuated adhesion to the extracellular matrix, together with slower and reversible spreading. Structural analysis demonstrates unstable formation of focal adhesions, defective cytoskeleton reorganization in response to cellular matrix adhesion, cell migration and cell-cell adhesion. Confluent cultures showed also a reduction of membrane bound VE-cadherin, suggesting defective inter-cellular junction formation. Functional consequences included impaired directional migration, and enhanced tip phenotype in aortic explants sprouting assays. At the molecular level, PGC-1α-deleted ECs exhibit a constitutive activation of the vascular endothelial growth factor-A (VEGF-A) signaling pathway and a defective response to VEGF-A. All these alterations are partially reversed by administration of the antioxidant EUK-189. The contribution of mitochondrial ROS and NOX activation was confirmed using a mitochondrial targeted antioxidant (MitoTEMPO) and a NOX inhibitor (VAS-2870). These results indicate that elevated production of ROS in the absence of PGC-1α is a key factor in the alteration of the VEGF-A signaling pathway and the capacity of endothelial cells to form stable interactions with other endothelial cells and with the extracellular matrix. Our findings show that PGC-1α control of ROS homeostasis plays an important role in the control of endothelial response to VEGF-A.

Graphical abstract

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Effect of the SOD mimetic MnL4 on in vitro and in vivo oxaliplatin toxicity: Possible aid in chemotherapy induced neuropathy

Publication date: Available online 28 January 2016
Source:Free Radical Biology and Medicine
Author(s): Lorenzo Di Cesare Mannelli, Matteo Zanardelli, Ida Landini, Alessandra Pacini, Carla Ghelardini, Enrico Mini, Andrea Bencini, Barbara Valtancoli, Paola Failli
BackgrouOne of the most discomfortable dose-limiting adverse reaction of effective drugs for the treatment of solid tumors is a peripheral neuropathy which is the main reason for dose reduction and discontinuation of the therapy. We identified oxidative stress as one target of oxaliplatin toxicity in the search of possible adjuvant therapies to prevent neuropathy and alleviate pain. Therefore, we studied an effective SOD mimetic compound, MnL4, as a possible adjuvant treatment in in vitro cellular cultures and in vivo on a rat model of oxaliplatin-induced neuropathy. Methods and results-All rat manipulations were carried out according to the European Community guidelines for animal care. We performed experiments on SH-SY5Y, HT-29 and primary cortical rat astrocytes. Incubation with 100µM oxaliplatin increased superoxide anion production and caspase 3/7 activity in the neuronal cell line SH-SY5Y and cortical astrocytes. MnL4 (10µM) significantly reduced the increase in superoxide anion in both cell types, but prevented caspase 3/7 activity only in astrocytes. MnL4 reduced lipid peroxidation induced by oxaliplatin and normalized the intracellular calcium signal evoked by ATP and acetylcholine in astrocytes, preincubated with oxaliplatin. MnL4 did not interfere with the concentration- and time-dependent cytotoxic effects of oxaliplatin on the cancer cell lines HT-29 and LoVo. In vivo MnL4 reduced the response at mechanical noxious and mechanical and thermal non-noxious stimuli in oxaliplatin treated animals. Rat rota-rod performances were improved.ConclusionSince MnL4 exertes its beneficial effects without interfering with the anticancer activity of oxaliplatin, it could be proposed as adjuvant to prevent and reduce oxaliplatin induced neuropathy.



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Physical exercise, reactive oxygen species and neuroprotection

Publication date: Available online 28 January 2016
Source:Free Radical Biology and Medicine
Author(s): Zsolt Radak, Katsuhiko Suzuki, Mitsuru Higuchi, Laszlo Balogh, Istvan Boldogh, Erika Koltai
Regular exercise has systemic beneficial effects, including the promotion of brain function. The adaptive response to regular exercise involves the up-regulation of the enzymatic antioxidant system and modulation of oxidative damage. Reactive oxygen species (ROS) are important regulators of cell signaling. Exercise, via intensity- dependent modulation of metabolism and/or directly activated ROS generating enzymes, regulates the cellular redox state of the brain. ROS are also involved in the self-renewal and differentiation of neuronal stem cells and the exercise-mediated neurogenesis could be partly associated with ROS production. Exercise has strong effects on the immune system and readily alters the production of cytokines. Certain cytokines, especially IL-6, IL-1, TNF-α, IL-18 and IFN gamma, are actively involved in the modulation of synaptic plasticity and neurogenesis. Cytokines can also contribute to ROS production. ROS- mediated alteration of lipids, protein, and DNA could directly affect brain function, while exercise modulates the accumulation of oxidative damage. Oxidative alteration of macromolecules can activate signaling processes, membrane remodeling, and gene transcription. The well known neuroprotective effects of exercise are partly due to redox- associated adaptation.



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Case Report of Cirrhosis following Yttrium-90 Radioembolization for Pancreatic Neuroendocrine Liver Metastases

Background: Management options for pancreatic neuroendocrine tumors (pNETs) metastatic to the liver include surgical, ablative, cytotoxic, and radioisotope approaches. One potential local treatment option includes selective internal radiotherapy utilizing yttrium-90 (⁹⁰Y) microspheres. ⁹⁰Y has also been used in the treatment of hepatocellular carcinoma and tumors metastatic to the liver. It appears to be well tolerated; however, there is no randomized controlled trial reporting long-term toxicities. Previous retrospective reports have described biliary damage as a potential complication of therapy with ⁹⁰Y and chemoembolization; however, the long-term sequelae of ⁹⁰Y treatment are poorly understood. Case Presentation: We present the case of a 65-year-old Caucasian woman who suffered biliary damage following ⁹⁰Y administration for metastatic pNETs and subsequently developed cirrhosis. Given the timeline of her various treatments and the lack of any other identifiable etiology for her cirrhosis, we believe this to be a potential long-term complication of ⁹⁰Y therapy. Conclusion: This case provides pathologic confirmation of cirrhosis as a potential long-term sequela of ⁹⁰Y treatment. This long-term risk needs to be considered when sequencing therapy for patients with neuroendocrine tumors who have a good prognosis. There are now several other systemic and ablative treatment options available to these patients, and long-term complications must be considered during treatment.
Case Rep Oncol 2016;9:76-82

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Medicines, Vol. 3, Pages 5: The Effects of Yin, Yang and Qi in the Skin on Pain

The most effective and safe treatment site for pain is in the skin. This chapter discusses the reasons to treat pain in the skin. Pain is sensed in the skin through transient receptor potential cation channels and other receptors. These receptors have endogenous agonists (yang) and antagonists (yin) that help the body control pain. Acupuncture works through modulation of these receptor activities (qi) in the skin; as do moxibustion and liniments. The treatment of pain in the skin has the potential to save many lives and improve pain therapy in most patients.

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Metals, Vol. 6, Pages 29: Effect of Laser Surface Treatment on the Corrosion Behavior of FeCrAl-Coated TZM Alloy

The current study involves the coating of Titanium-Zirconium-Molybdenum (TZM) alloy with FeCrAl through plasma thermal spraying which proved effective in improving the oxidation resistance of the substrate. A post-laser surface melting treatment further enhanced the surface protection of the TZM alloy. Oxidation tests conducted at 1100 °C in air indicated that some Mo oxides were formed at the surface but a relatively small amount of weight reduction was observed for FeCrAl-coated TZM alloys up to 60 min of treatment. The post-laser surface treatment following the plasma thermal spray process apparently delayed the severe oxidation process and surface spalling of the alloy. It was suggested that the slow reduction in weight in the post-laser-treated specimen was related to fewer defects in the coating layer. It was also found that a surface reaction layer formed through the diffusion of Fe into the Mo alloy substrate at high temperature. The layer mainly consisted of Fe-saturated Mo and FeMo intermetallic compounds. In order to observe the corrosion behavior of the laser-treated alloy in 3.5% NaCl solution, electrochemical characteristics were also investigated. A proposed equivalent circuit model for the specimen indicated localized corrosion of coated alloy with some permeable defects in the coating layer.

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Quantitative electrochemical metalloimmunoassay for TFF3 in urine using a paper analytical device

Analyst, 2016, Advance Article
DOI: 10.1039/C5AN02386F, Paper

Paul R. DeGregory, Yi-Ju Tsai, Karen Scida, Ian Richards, Richard M. Crooks
An inexpensive electrochemical paper biosensor that can quantify TFF3, a kidney disease marker, in human urine in <10 min.
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry

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Molecules, Vol. 21, Pages 171: Synthesis and Characterization of Macrocyclic Polyether N,N′-Diallyl-7,16-diaza-1,4,10,13-tetraoxa-dibenzo-18-crown-6

In this study an efficient and direct production procedure for a macrocyclic polyether N,N′-diallyl-7,16-diaza-1,4,10,13-tetraoxa-dibenzo-18-crown-6 from the reaction of catechol and N,N-bis(2-chloroethyl)prop-2-en-1-amine in n-butanol in the presence of a strong base is reported. The synthesis involves a two-step addition of sodium hydroxide to enhance the cyclization process, and at the end of the reaction, the reaction mixture is neutralized and the solvent replaced with water in-situ through distillation to afford a relatively pure precipitate that is easily recrystallized from acetone. The yield of the macrocycle was 36%–45% and could be scaled-up to one-mole quantities. The structure and purity of this compound was verified on the basis of elemental analysis, IR, UV-Vis, 1H-, 13C-NMR, 2D-NMR, mass spectroscopy, and thermal analysis. The white crystalline compound has a sharp melting point of 124 °C and a crystallization temperature of 81.4 °C determined by differential scanning calorimetry. Our motivation behind the synthesis of the bibracchial lariat azacrown polyether ligand was to examine its possible applications in ion-selective polymer-supported materials.

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Molecules, Vol. 21, Pages 167: Insight of Saffron Proteome by Gel-Electrophoresis

Saffron is a spice comprised of the dried stigmas and styles of Crocus sativus L. flowers and, since it is very expensive, it is frequently adulterated. So far, proteomic tools have never been applied to characterize the proteome of saffron or identify possible cases of fraud. In this study, 1D-Gel Electrophoresis was carried out to characterize the protein profile of (i) fresh stigmas and styles of the plant; (ii) dried stigmas and styles from different geographical origins (Spanish, Italian, Greek and Iranian) that had been stored for various periods of time after their processing; and (iii) two common plant adulterants, dried petals of Carthamus tinctorius L. and dried fruits of Gardenia jasminoides Ellis. A selective protein extraction protocol was applied to avoid interference from colored saffron metabolites, such as crocins, during electrophoretic analyses of saffron. We succeeded in separating and assigning the molecular weights to more than 20 proteins. In spite of the unavailability of the genome of saffron, we were able to identify five proteins by Peptide Mass Fingerprinting: phosphoenolpyruvate carboxylase 3, heat shock cognate 70 KDa protein, crocetin glucosyltransferase 2, α-1,4-glucan-protein synthase and glyceraldehydes-3-phosphate dehydrogenase-2. Our findings indicate that (i) few bands are present in all saffron samples independently of origin and storage time, with amounts that significantly vary among samples and (ii) aging during saffron storage is associated with a reduction in the number of detectable bands, suggesting that proteases are still active. The protein pattern of saffron was quite distinct from those of two common adulterants, such as the dried petals of Carthamus tinctorius and the dried fruits of Gardenia jasminoides indicating that proteomic analyses could be exploited for detecting possible frauds.

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Langerhans Cell Histiocytosis of the Rib in an Adult: A Case Report

Single-site, single-system Langerhans cell histiocytosis (LCH) of the rib is one of the rarest causes of bone tumor in adults. Herein, we report a case of a healthy 35-year-old male who presented with upper back pain that was attributed to a solitary osteolytic lesion at the posterolateral aspect of his sixth rib. For diagnostic confirmation and treatment, partial resection of the sixth rib was performed and pathologic finding was consistent with LCH. At the final follow-up after 2 years, no local recurrence or metastasis was observed.
Case Rep Oncol 2016;9:83-88

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Atmosphere, Vol. 7, Pages 18: Solar Forecasting in a Challenging Insular Context

This paper aims at assessing the accuracy of different solar forecasting methods in the case of an insular context. Two sites of La Réunion Island, Le Tampon and Saint-Pierre, are chosen to do the benchmarking exercise. Réunion Island is a tropical island with a complex orography where cloud processes are mainly governed by local dynamics. As a consequence, Réunion Island exhibits numerous micro-climates. The two aforementioned sites are quite representative of the challenging character of solar forecasting in the case of a tropical island with complex orography. Hence, although distant from only 10 km, these two sites exhibit very different sky conditions. This work focuses on day-ahead and intra-day solar forecasting. Day-ahead solar forecasts are provided by the European Center for Medium-Range Weather Forecast (ECMWF). This organization maintains and runs the Numerical Weather Prediction (NWP) model named Integrated Forecast System (IFS). In this work, post-processing techniques are applied to refine the output of the IFS model for day-ahead forecasting. Statistical models like a recursive linear model or a nonlinear model such as an artificial neural network are used to produce the intra-day solar forecasts. It is shown that a combination of the IFS model and the neural network model further improves the accuracy of the forecasts.

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Water, Vol. 8, Pages 42: Using a Geospatial Model to Relate Fluvial Geomorphology to Macroinvertebrate Habitat in a Prairie River—Part 1: Genus-Level Relationships with Geomorphic Typologies

Modern river ecosystems undergo constant stress from disturbances such as bank stabilization, channelization, dams, and municipal, agricultural, and industrial water use. As these anthropogenic water requirements persist, more efficient methods of characterizing river reaches are essential. Benthic macroinvertebrates are helpful when evaluating fluvial health, because they are often the first group to react to contaminants that can then be transferred through them to other trophic levels. Hence, the purpose of this research is to use a geospatial model to differentiate instream macroinvertebrate habitats, and determine if the model is a viable method for stream evaluation. Through the use of ArcGIS and digital elevation models, the fluvial geomorphology of the Qu'Appelle River in Saskatchewan (SK) was assessed. Four geomorphological characteristics of the river were isolated (sinuosity, slope, fractal dimension, and stream width) and clustered through Principle Component Analysis (PCA), yielding sets of river reaches with similar geomorphological characteristics, called typologies. These typologies were mapped to form a geospatial model of the river. Macroinvertebrate data were aligned to the locations of the typologies, revealing several relationships with the fluvial geomorphology. A Kruskal-Wallis analysis and post hoc pairwise multiple comparisons were completed with the macroinvertebrate data to pinpoint significant genera, as related to the geospatial model.

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Polymers, Vol. 8, Pages 37: Investigations of the Ligand Electronic Effects on α-Diimine Nickel(II) Catalyzed Ethylene Polymerization

The synthesis and characterization of a series of dibenzhydryl-based α-diimine Ni(II) complexes bearing a range of electron-donating or -withdrawing groups are described. Polymerization with ethylene is investigated in detail, involving the activator effect, influence of polymerization conditions on catalyst activity, thermal stability, polymer molecular weight and melting point. All of these Ni(II) complexes show great activity (up to 6 × 106 g of PE (mol of Ni)−1·h−1), exceptional thermal stability (stable at up to 100 °C) and generate polyethylene with very high molecular weight (Mn up to 1.6 × 106) and very narrow molecular weight distribution. In the dibromo Ni(II) system, the electronic perturbations exhibit little variation on the ethylene polymerization. In the Ni(acac) system, dramatic ligand electronic effects are observed in terms of catalytic activity and polyethylene molecular weight.

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IJMS, Vol. 17, Pages 178: Induction of Apoptosis by PQ1, a Gap Junction Enhancer that Upregulates Connexin 43 and Activates the MAPK Signaling Pathway in Mammary Carcinoma Cells

The mechanism of gap junction enhancer (PQ1) induced cytotoxicity is thought to be attributed to the change in connexin 43 (Cx43) expression; therefore, the effects of Cx43 modulation in cell survival were investigated in mammary carcinoma cells (FMC2u) derived from a malignant neoplasm of a female FVB/N-Tg(MMTV-PyVT)634Mul/J (PyVT) transgenic mouse. PQ1 was determined to have an IC50 of 6.5 µM in FMC2u cells, while inducing an upregulation in Cx43 expression. The effects of Cx43 modulation in FMC2u cell survival was determined through transfection experiments with Cx43 cDNA, which induced an elevated level of protein expression similar to that seen with PQ1 exposure, or siRNA to silence Cx43 protein expression. Overexpression or silencing of Cx43 led to a reduction or an increase in cell viability, respectively. The mitogen-activated protein kinase (MAPK) family has been implicated in the regulation of cell survival and cell death; therefore, the gap junctional intercellular communication (GJIC)-independent function of PQ1 and Cx43 in the Raf/Mitogen-activated protein kinase/ERK kinase/extracellular-signal-regulated kinase (Raf-MEK-ERK) cascade of cellular survival and p38 MAPK-dependent pathway of apoptosis were explored. PQ1 treatment activated p44/42 MAPK, while the overexpression of Cx43 resulted in a reduced expression. This suggests that PQ1 affects the Raf-MEK-ERK cascade independent of Cx43 upregulation. Both overexpression of Cx43 and PQ1 treatment stimulated an increase in the phosphorylated form of p38-MAPK, reduced levels of the anti-apoptotic protein Bcl-2, and increased the cleavage of pro-caspase-3. Silencing of Cx43 protein expression led to a reduction in the phosphorylation of p38-MAPK and an increase in Bcl-2 expression. The mechanism behind PQ1-induced cytotoxicity in FMC2u mammary carcinoma cells is thought to be attributed to the change in Cx43 expression. Furthermore, PQ1-induced apoptosis through the upregulation of Cx43 may depend on p38 MAPK, highlighting that the effect of PQ1 on gap junctions as well as cellular survival via a MAPK-dependent pathway.

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IJMS, Vol. 17, Pages 179: Plasma Monocyte Chemoattractant Protein-1 Level as a Predictor of the Severity of Community-Acquired Pneumonia

Monocyte chemoattractant protein (MCP)-1 increases in the serum of immunocompetent patients with community-acquired pneumonia (CAP). However, the correlation between the circulating level of MCP-1 and severity of CAP remains unclear. This study investigated differential changes in the plasma MCP-1 levels of patients with CAP before and after an antibiotic treatment and further analyzes the association between the CAP severity and MCP-1 levels. We measured the plasma MCP-1 levels of 137 patients with CAP and 74 healthy controls by using a commercial enzyme-linked immunosorbent assay. Upon initial hospitalization, Acute Physiology and Chronic Health Evaluation II (APACHE II); confusion, urea level, respiratory rate, blood pressure, and age of >64 years (CURB-65); and pneumonia severity index (PSI) scores were determined for assessing the CAP severity in these patients. The antibiotic treatment reduced the number of white blood cells (WBCs) and neutrophils as well as the level of C-reactive protein (CRP) and MCP-1. The plasma MCP-1 level, but not the CRP level or WBC count, correlated with the CAP severity according to the PSI (r = 0.509, p < 0.001), CURB-65 (r = 0.468, p < 0.001), and APACHE II (r = 0.360, p < 0.001) scores. We concluded that MCP-1 levels act in the development of CAP and are involved in the severity of CAP.

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IJMS, Vol. 17, Pages 176: Melatonin Suppresses the Growth of Ovarian Cancer Cell Lines (OVCAR-429 and PA-1) and Potentiates the Effect of G1 Arrest by Targeting CDKs

Melatonin is found in animals as well as plants. In animals, it is a hormone that anticipates the daily onset of darkness and regulates physiological functions, such as sleep timing, blood pressure, and reproduction. Melatonin has also been found to have anti-tumor properties. Malignant cancers are the most common cause of death, and the mortality rate of ovarian tumor is the highest among gynecological diseases. This study investigated the anti-tumor effects of melatonin on the ovarian cancer lines, OVCAR-429 and PA-1. We observed the accumulation of melatonin-treated cells in the G1 phase due to the down-regulation of CDK 2 and 4. Our results suggest that in addition to the known effects on prevention, melatonin may also provide anti-tumor activity in established ovarian cancer.

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IJMS, Vol. 17, Pages 180: Clinical Genetic Aspects of ASD Spectrum Disorders

Early presumptions opined that autism spectrum disorder (ASD) was related to the rearing of these children by emotionally-distant mothers. Advances in the 1960s and 1970s clearly demonstrated the biologic basis of autism with a high heritability. Recent advances have demonstrated that specific etiologic factors in autism spectrum disorders can be identified in 30%–40% of cases. Based on early reports newer, emerging genomic technologies are likely to increase this diagnostic yield to over 50%. To date these investigations have focused on etiologic factors that are largely mono-factorial. The currently undiagnosed causes of ASDs will likely be found to have causes that are more complex. Epigenetic, multiple interacting loci, and four dimensional causes (with timing as a variable) are likely to be associated with the currently unidentifiable cases. Today, the "Why" is more important than ever. Understanding the causes of ASDs help inform families of important issues such as recurrence risk, prognosis, natural history, and predicting associated co-morbid medical conditions. In the current era of emerging efforts in "personalized medicine", identifying an etiology will be critical in identifying endo-phenotypic groups and individual variations that will allow for tailored treatment for persons with ASD.

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IJMS, Vol. 17, Pages 177: Ginsenoside-Rd Promotes Neurite Outgrowth of PC12 Cells through MAPK/ERK- and PI3K/AKT-Dependent Pathways

Panax ginseng is a famous herbal medicine widely used in Asia. Ginsenosides have been identified as the principle active ingredients for Panax ginseng's biological activity, among which ginsenoside Rd (Rd) attracts extensive attention for its obvious neuroprotective activities. Here we investigated the effect of Rd on neurite outgrowth, a crucial process associated with neuronal repair. PC12 cells, which respond to nerve growth factor (NGF) and serve as a model for neuronal cells, were treated with different concentrations of Rd, and then their neurite outgrowth was evaluated. Our results showed that 10 μM Rd significantly increased the percentages of long neurite- and branching neurite-bearing cells, compared with respective controls. The length of the longest neurites and the total length of neurites in Rd-treated PC12 cells were much longer than that of respective controls. We also showed that Rd activated ERK1/2 and AKT but not PKC signalings, and inhibition of ERK1/2 by PD98059 or/and AKT by LY294002 effectively attenuated Rd-induced neurite outgrowth. Moreover, Rd upregulated the expression of GAP-43, a neuron-specific protein involved in neurite outgrowth, while PD98059 or/and LY294002 decreased Rd-induced increased GAP-43 expression. Taken together, our results provided the first evidence that Rd may promote the neurite outgrowth of PC12 cells by upregulating GAP-43 expression via ERK- and ARK-dependent signaling pathways.

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IJMS, Vol. 17, Pages 182: miR-30-5p Regulates Muscle Differentiation and Alternative Splicing of Muscle-Related Genes by Targeting MBNL

MicroRNAs (miRNAs), a class of single stranded, small (~22 nucleotides), non-coding RNAs, play an important role in muscle development. We focused on the role of the miR-30-5p family during bovine muscle development from previous high-throughput sequencing results and analyzed their expression profiles. MHC and MyoG mRNAs expression as well as their proteins were suppressed in differentiated C2C12 cells, suggesting the importance of miR-30-5p in muscle development. MBNL, the candidate target of miR-30-5p, is an alternative splicing regulation factor. MBNL1 and MBNL3 have opposite effects on muscle differentiation. Our results confirmed that miR-30a-5p and miR-30e-5p repress the expression of MBNL1, MBNL2 and MBNL3, whereas miR-30b-5p inhibits MBNL1 and MBNL2 expression. This provides direct evidence that MBNL expression can be flexibly regulated by miR-30-5p. Previous studies showed that MBNL1 promotes exon inclusion of two muscle-related genes (Trim55 and INSR). Through RNA splicing studies, we found that miR-30-5p had an effect on their alternative splicing, which means miR-30-5p via MBNL1 could be integrated into muscle signaling pathways in which INSR or Trim55 are located. In conclusion, miR-30-5p could inhibit muscle cell differentiation and regulate the alternative splicing of Trim55 and INSR by targeting MBNL. These results promote the understanding of the function of miRNAs in muscle development.

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IJMS, Vol. 17, Pages 182: miR-30-5p Regulates Muscle Differentiation and Alternative Splicing of Muscle-Related Genes by Targeting MBNL

MicroRNAs (miRNAs), a class of single stranded, small (~22 nucleotides), non-coding RNAs, play an important role in muscle development. We focused on the role of the miR-30-5p family during bovine muscle development from previous high-throughput sequencing results and analyzed their expression profiles. MHC and MyoG mRNAs expression as well as their proteins were suppressed in differentiated C2C12 cells, suggesting the importance of miR-30-5p in muscle development. MBNL, the candidate target of miR-30-5p, is an alternative splicing regulation factor. MBNL1 and MBNL3 have opposite effects on muscle differentiation. Our results confirmed that miR-30a-5p and miR-30e-5p repress the expression of MBNL1, MBNL2 and MBNL3, whereas miR-30b-5p inhibits MBNL1 and MBNL2 expression. This provides direct evidence that MBNL expression can be flexibly regulated by miR-30-5p. Previous studies showed that MBNL1 promotes exon inclusion of two muscle-related genes (Trim55 and INSR). Through RNA splicing studies, we found that miR-30-5p had an effect on their alternative splicing, which means miR-30-5p via MBNL1 could be integrated into muscle signaling pathways in which INSR or Trim55 are located. In conclusion, miR-30-5p could inhibit muscle cell differentiation and regulate the alternative splicing of Trim55 and INSR by targeting MBNL. These results promote the understanding of the function of miRNAs in muscle development.

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Nutrients, Vol. 8, Pages 73: Resveratrol Supplementation in Schizophrenia Patients: A Randomized Clinical Trial Evaluating Serum Glucose and Cardiovascular Risk Factors

Background: Patients with schizophrenia (SZ) are generally overweight or obese and have several metabolic disorders. Additionally, such patients have a lower life expectancy and the main cause of their increased mortality is cardiovascular disease (CVD). The objective of this study was to determine the efficacy of resveratrol supplementation on serum glucose and CVD risk factors in individuals with SZ. Methods and Results: This is a four-week randomized, double-blind controlled trial (registration No.: NCT 02062190) in which 19 men with a diagnosis of SZ, aged 18 to 65, were assigned to either a resveratrol supplement group (200 mg/day) or a placebo group (200 mg/day). In short, we did not observe significant changes after resveratrol supplementation. In the placebo group, we found a significant increase in total cholesterol levels (p = 0.024) and in LDL-cholesterol (p = 0.002), as well as a decrease in body fat percentage (p = 0.038). The placebo group also showed an increase in triglycerides (9.19%) and a reduction in HDL-cholesterol (4.88%). In the resveratrol group, triglycerides decreased (7.64%). Conclusion: In summary, oral resveratrol in reasonably low dosages (200 mg daily) brought no differences to body weight, waist circumference, glucose, and total cholesterol. It was possible to note that the lipid profile in the placebo group worsened and, although no significant differences were found, we can assume that resveratrol might prevent lipid profile damage and that the intervention affected the lipoprotein metabolism at various levels.

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IJMS, Vol. 17, Pages 179: Plasma Monocyte Chemoattractant Protein-1 Level as a Predictor of the Severity of Community-Acquired Pneumonia

Monocyte chemoattractant protein (MCP)-1 increases in the serum of immunocompetent patients with community-acquired pneumonia (CAP). However, the correlation between the circulating level of MCP-1 and severity of CAP remains unclear. This study investigated differential changes in the plasma MCP-1 levels of patients with CAP before and after an antibiotic treatment and further analyzes the association between the CAP severity and MCP-1 levels. We measured the plasma MCP-1 levels of 137 patients with CAP and 74 healthy controls by using a commercial enzyme-linked immunosorbent assay. Upon initial hospitalization, Acute Physiology and Chronic Health Evaluation II (APACHE II); confusion, urea level, respiratory rate, blood pressure, and age of >64 years (CURB-65); and pneumonia severity index (PSI) scores were determined for assessing the CAP severity in these patients. The antibiotic treatment reduced the number of white blood cells (WBCs) and neutrophils as well as the level of C-reactive protein (CRP) and MCP-1. The plasma MCP-1 level, but not the CRP level or WBC count, correlated with the CAP severity according to the PSI (r = 0.509, p < 0.001), CURB-65 (r = 0.468, p < 0.001), and APACHE II (r = 0.360, p < 0.001) scores. We concluded that MCP-1 levels act in the development of CAP and are involved in the severity of CAP.

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Animals, Vol. 6, Pages 9: Heat Tolerance in Curraleiro Pe-Duro, Pantaneiro and Nelore Cattle Using Thermographic Images

The objective of this study was to compare physiological and thermographic responses to heat stress in three breeds of cattle. Fifteen animals of each of the Nelore, Pantaneiro and Curraleiro Pe-Duro breeds, of approximately two years of age, were evaluated. Heart and respiratory rates, rectal and surface temperature of animals as well as soil temperature were recorded at 8:30 and 15:30 on six days. Variance, correlation, principal factors and canonical analyses were carried out. There were significant differences in the rectal temperature, heart and respiratory rate between breeds (p < 0.001). Nelore and Pantaneiro breeds had the highest rectal temperatures and the lowest respiratory rate (p < 0.001). Breed was also significant for surface temperatures (p < 0.05) showing that this factor significantly affected the response of the animal to heat tolerance in different ways. The Curraleiro Pe-Duro breed had the lowest surface temperatures independent of the period evaluated, with fewer animals that suffered with the climatic conditions, so this may be considered the best adapted when heat challenged under the experimental conditions. Thermography data showed a good correlation with the physiological indexes, and body area, neck and rump were the main points.

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Polymers, Vol. 8, Pages 22: Artificial Neural Network and Response Surface Methodology Modeling in Ionic Conductivity Predictions of Phthaloylchitosan-Based Gel Polymer Electrolyte

A gel polymer electrolyte system based on phthaloylchitosan was prepared. The effects of process variables, such as lithium iodide, caesium iodide, and 1-butyl-3-methylimidazolium iodide were investigated using a distance-based ternary mixture experimental design. A comparative approach was made between response surface methodology (RSM) and artificial neural network (ANN) to predict the ionic conductivity. The predictive capabilities of the two methodologies were compared in terms of coefficient of determination R2 based on the validation data set. It was shown that the developed ANN model had better predictive outcome as compared to the RSM model.

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Nutrients, Vol. 8, Pages 72: Supplementation with Guanidinoacetic Acid in Women with Chronic Fatigue Syndrome

A variety of dietary interventions has been used in the management of chronic fatigue syndrome (CFS), yet no therapeutic modality has demonstrated conclusive positive results in terms of effectiveness. The main aim of this study was to evaluate the effects of orally administered guanidinoacetic acid (GAA) on multidimensional fatigue inventory (MFI), musculoskeletal soreness, health-related quality of life, exercise performance, screening laboratory studies, and the occurrence of adverse events in women with CFS. Twenty-one women (age 39.3 ± 8.8 years, weight 62.8 ± 8.5 kg, height 169.5 ± 5.8 cm) who fulfilled the 1994 Centers for Disease Control and Prevention criteria for CFS were randomized in a double-blind, cross-over design, from 1 September 2014 through 31 May 2015, to receive either GAA (2.4 grams per day) or placebo (cellulose) by oral administration for three months, with a two-month wash-out period. No effects of intervention were found for the primary efficacy outcome (MFI score for general fatigue), and musculoskeletal pain at rest and during activity. After three months of intervention, participants receiving GAA significantly increased muscular creatine levels compared with the placebo group (36.3% vs. 2.4%; p < 0.01). Furthermore, changes from baseline in muscular strength and aerobic power were significantly greater in the GAA group compared with placebo (p < 0.05). Results from this study indicated that supplemental GAA can positively affect creatine metabolism and work capacity in women with CFS, yet GAA had no effect on main clinical outcomes, such as general fatigue and musculoskeletal soreness.

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Polymers, Vol. 8, Pages 36: l-Cystine-Crosslinked Polypeptide Nanogel as a Reduction-Responsive Excipient for Prostate Cancer Chemotherapy

Smart polymer nanogel-assisted drug delivery systems have attracted more and more attention in cancer chemotherapy because of their well-defined morphologies and pleiotropic functions in recent years. In this work, an l-cystine-crosslinked reduction-responsive polypeptide nanogel of methoxy poly(ethylene glycol)-poly(l-phenylalanine-co-l-cystine) (mPEG-P(LP-co-LC)) was employed as a smart excipient for RM-1 prostate cancer (PCa) chemotherapy. Doxorubicin (DOX), as a regular chemotherapy drug, was embedded in the nanogel. The loading nanogel marked as NG/DOX was shown to exhibit glutathione (GSH)-induced swelling and GSH-accelerated DOX release. Subsequently, NG/DOX showed efficient cellular uptake and proliferation inhibition. Furthermore, NG/DOX presented enhanced antitumor efficacy and security in an RM-1 PCa-grafted mouse model in vivo, indicating its great potential for clinical treatment.

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Mitochondrial calcium uniporter opener spermine attenuates the cerebral protection of mitochondrial ATP-sensitive potassium channels through peroxidation in rats

OBJECTIVE: Animal models of transient ischemia suggest that mitochondrial ATP-sensitive potassium channels (mitoKATP) could constitute the main protectve effect of ischemia-reperfusion injury. While the mechanism of diazoxide is vague, the role of mitochondrial calcium uniporter (MCU) in the effect of diazoxide remain unknown. We aimed to determine the effect of mitochondrial calcium uniporter opener spermine on the protection of diazoxide against transient cerebral ischemia-reperfusion injury in rats.

MATERIALS AND METHODS: We chose adult male Wistar rats to constitute the transient middle cerebral artery occlusion (MCAO) model. Animals were randomly divided into five groups: the Sham group, the I/R group, the Dzx + I/R group, the Dzx + Sper +I/R group, and the Sper + I/R group. Rats were exposed to 24h reperfusion after 2h ischemia. All rats were given neurological performance tests after 24h reperfusion, then their brains were excised for infarct volume and biochemical evaluation and analysis.

RESULTS: The beneficial effects of diazoxide were significantly attenuated by treated with spermine through aggravating neurological deficits, infarct volume and oxidative stress (evidenced by increased malondialdehyde and nitric oxide, while decreased antioxidant enzymes [e.g., superoxide dismutase and glutathione peroxide]).

CONCLUSIONS: The present results suggested diazoxide-induced cerebral protection against transient cerebral ischemia-reperfusion is mediated by mitochondrial calcium uniporter.

L'articolo Mitochondrial calcium uniporter opener spermine attenuates the cerebral protection of mitochondrial ATP-sensitive potassium channels through peroxidation in rats sembra essere il primo su European Review.

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IJMS, Vol. 17, Pages 176: Melatonin Suppresses the Growth of Ovarian Cancer Cell Lines (OVCAR-429 and PA-1) and Potentiates the Effect of G1 Arrest by Targeting CDKs

Melatonin is found in animals as well as plants. In animals, it is a hormone that anticipates the daily onset of darkness and regulates physiological functions, such as sleep timing, blood pressure, and reproduction. Melatonin has also been found to have anti-tumor properties. Malignant cancers are the most common cause of death, and the mortality rate of ovarian tumor is the highest among gynecological diseases. This study investigated the anti-tumor effects of melatonin on the ovarian cancer lines, OVCAR-429 and PA-1. We observed the accumulation of melatonin-treated cells in the G1 phase due to the down-regulation of CDK 2 and 4. Our results suggest that in addition to the known effects on prevention, melatonin may also provide anti-tumor activity in established ovarian cancer.

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Forests, Vol. 7, Pages 32: Developing Aboveground Biomass Equations Both Compatible with Tree Volume Equations and Additive Systems for Single-Trees in Poplar Plantations in Jiangsu Province, China

We developed aboveground biomass equations for poplar plantations in Jiangsu Province, China, both compatible with tree volume equations and additive systems. Biomass equations were fitted with 80 selected and previously harvested sample trees. Additivity property was assured by applying a "controlling directly under total biomass proportion function" approach. Weighted regression was used to correct heteroscedasticity. Parameters were estimated using a nonlinear error-in-variable model. The results indicated that (1), on average, stems constituted the largest proportion (71.5%) of total aboveground biomass; (2) the aboveground biomass equations, both compatible with tree volume equations and additive systems, obtained good model fitting and prediction, of which the coefficient of determination ranged from 0.903 to 0.987, and the total relative error and the mean prediction error were less than 2.0% and 10.0%, respectively; (3) adding H and CW into the additive system of biomass equations did not improve model fitting and performance as expected, especially for branches and foliage biomass; and (4) the additive systems of biomass equations presented here provided more reliable and accurate biomass predictions than the independent biomass equations fitted by ordinary least square regression. This system of additive biomass equations will prove to be applicable for estimating biomass of poplar plantations in Jiangsu Province of China.

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Antibacterial and Anti-Inflammatory Activities of Physalis Alkekengi var. franchetii and Its Main Constituents

This study was designed to determine whether the 50% EtOH fraction from AB-8 macroporous resin fractionation of a 70% EtOH extract of P. Alkekengi (50-EFP) has antibacterial and/or anti-inflammatory activity both in vivo and in vitro and to investigate the mechanism of 50-EFP anti-inflammatory activity. Additionally, this study sought to define the chemical composition of 50-EFP. Results indicated that 50-EFP showed significant antibacterial activity in vitro and efficacy in vivo. Moreover, 50-EFP significantly reduced nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-α), interleukin 1 (IL-1), and interleukin 6 (IL-6) production in lipopolysaccharide- (LPS-) stimulated THP-1 cells. Nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) (examined at the protein level) in THP-1 cells were suppressed by 50-EFP, which inhibited nuclear translocation of p65. Consistent with this anti-inflammatory activity in vitro, 50-EFP reduced inflammation in both animal models. Finally, seventeen compounds (8 physalins and 9 flavones) were isolated as major components of 50-EFP. Our data demonstrate that 50-EFP has antibacterial and anti-inflammatory activities both in vitro and in vivo. The anti-inflammatory effect appears to occur, at least in part, through the inhibition of nuclear translocation of p65. Moreover, physalins and flavones are probably the active components in 50-EFP that exert antibacterial and anti-inflammatory activities.

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Future Internet, Vol. 8, Pages 4: Context-Based Energy Disaggregation in Smart Homes

In this paper, we address the problem of energy conservation and optimization in residential environments by providing users with useful information to solicit a change in consumption behavior. Taking care to highly limit the costs of installation and management, our work proposes a Non-Intrusive Load Monitoring (NILM) approach, which consists of disaggregating the whole-house power consumption into the individual portions associated to each device. State of the art NILM algorithms need monitoring data sampled at high frequency, thus requiring high costs for data collection and management. In this paper, we propose an NILM approach that relaxes the requirements on monitoring data since it uses total active power measurements gathered at low frequency (about 1 Hz). The proposed approach is based on the use of Factorial Hidden Markov Models (FHMM) in conjunction with context information related to the user presence in the house and the hourly utilization of appliances. Through a set of tests, we investigated how the use of these additional context-awareness features could improve disaggregation results with respect to the basic FHMM algorithm. The tests have been performed by using Tracebase, an open dataset made of data gathered from real home environments.

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Pseudomyxoma Peritonei: Symptom Control and Objective Radiological Response after Treatment with Lanreotide Autogel

Peritoneal mucinous carcinomatosis is an aggressive subtype of pseudomyxoma peritonei, which often leads to inoperable bowel obstruction and, ultimately, death. Due to the poor prognosis, treatment is often symptomatic and aimed at alleviating the symptoms - pain, nausea, and vomiting - associated with gastrointestinal obstruction. Due to their antisecretory activity, somatostatin analogues are commonly prescribed in such cases. In the case presented here, a patient diagnosed with disseminated peritoneal mucinous carcinomatosis of appendiceal origin responded well to symptomatic treatment with lanreotide Autogel® at a dose of 120 mg/28 days. More importantly, radiological evidence of a reduction in peritoneal ascites, indicative of antiproliferative activity, was observed. These findings are important, particularly given the negative impact of this disease on both quality of life and survival. This case adds to the growing body of evidence supporting the antiproliferative and antisecretory activity of lanreotide Autogel.
Case Rep Oncol 2016;9:56-61

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Partial Response to Platinum Doublets in Refractory EGFR-Positive Non-Small Cell Lung Cancer Patients after RRx-001: Evidence of Episensitization

RRx-001, an experimental systemically non-toxic epi-immunotherapeutic agent, which potentiates the resensitization of resistant cancer cells to formerly effective therapies, is under active investigation in several clinical trials that are based on sequential or concomitant rechallenge to resistant first- or second-line regimens. One of these trials is designated TRIPLE THREAT (NCT02489903), because it explores the conditioning or priming effect of RRx-001 on three tumor types - non-small cell lung cancer (NSCLC), small cell lung cancer and high-grade neuroendocrine tumors - prior to re-administration of platinum doublets. In follow-up to a recent case study, which describes early monotherapeutic benefit with RRx-001 in a refractory EGFR-mutated NSCLC tumor, we present subsequent evidence of a radiological partial response to reintroduced platinum doublets after RRx-001. For the 50% of patients with EGFR-mutated NSCLC who progress on EGFR-tyrosine kinase inhibitors (without evidence of a T790M mutations) as well as platinum doublets and pemetrexed/taxane, no other clinically established treatment options exist. A retrial of these therapies in EGFR-positive NSCLC patients via priming with epigenetic agents such as RRx-001 constitutes a strategy to 'episensitize' tumors (i.e. reverse resistance by epigenetic means) and to extend overall survival.
Case Rep Oncol 2016;9:62-67

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The importance of determining the limit of detection of non invasive prenatal testing methods

Abstract

Objective

Several non-invasive prenatal testing (NIPT) methods, which analyze circulating fetal cell-free DNA (cfDNA) in maternal plasma, suggest a fetal fraction (FF) ≥4% for a reportable result, with the assumption that fetal aneuploidies may not be detectable at lower FF. This study determined the actual Limit of Detection (LOD) of a Massively Parallel Sequencing (MPS)-based NIPT method and evaluated its performance in testing samples with low FF.

Method

An experimental model, involving the creation of artificial plasma mixtures with a final aneuploid FF ranging from 1–4%, simulated samples at different proportions of fetal cfDNA. We then analyzed 7103 blood samples, from pregnant women undergoing NIPT, to assess the impact of low FF on the performance of cfDNA testing.

Results

Detection of common aneuploidies in samples with a FF as low as 2% is well within the ability of this technology. Of 105 pregnancies confirmed chromosomally abnormal, 25 (23.8%) involving a 2%<FF<4% were consistently detected. These high risk pregnancies would have not been identified using the suggested 4% FF cut-off.

Conclusion

This study underscores the importance of determining the actual LOD for each specific NIPT methodology. It may reduce the incidence of test cancellations and shorten the time required for the diagnosis of aneuploidy.

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Atypical early histories predict lower extraversion in captive chimpanzees

ABSTRACT

Although much research has been conducted to understand personality development in humans, there remain substantial gaps in our understanding of these processes, particularly in relation to social influences. As such, investigations into personality development in our closest living relative, the chimpanzee, may provide useful insight. We evaluated the impact of early social exposure (to both humans and conspecifics) on personality development by studying 88 chimpanzees, including former pets and entertainers, living in accredited zoos and sanctuaries. During infancy, subjects varied in the amount of time spent with conspecifics compared with humans. Caregivers familiar with the chimpanzees rated them using a modified version of the Hominoid Personality Questionnaire (HPQ) and the ratings were found to have strong inter-rater reliability. We used the published structure of the HPQ to evaluate our results in relation to differences in early life experience. Chimpanzees who as infants spent less time with conspecifics were rated as lower in Extraversion later in life in comparison with chimpanzees who as infants spent more time with conspecifics. These results suggest that a broad range of social influences should be considered when evaluating the impact of early social environment on later personality expression. © 2016 Wiley Periodicals, Inc. Dev Psychobiol 9999: 1–9, 2016.

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Development of a Backbone Cyclic Peptide Library as Potential Antiparasitic Therapeutics Using Microwave Irradiation

A simple and general method for the synthesis of cyclic peptides using microwave irradiation is outlined. This procedure enables the synthesis of backbone cyclic peptides with a collection of different conformations while retaining the side chains and the pharmacophoric moieties., and therefore, allows to screen for the bioactive conformation.

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A Method to Manipulate Surface Tension of a Liquid Metal via Surface Oxidation and Reduction

We present a method to control the interfacial energy of a liquid metal in an electrolyte via electrochemical deposition (or removal) of a surface oxide layer. This simple method can control the capillary behavior of gallium-based liquid metals by tuning the interfacial energy rapidly, significantly, and reversibly using modest voltages.

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Cooling Rate Dependent Ellipsometry Measurements to Determine the Dynamics of Thin Glassy Films

Here, we present a protocol for cooling rate dependent ellipsometry experiments, which can determine the glass transition temperature (Tg), average dynamics, fragility and the expansion coefficient of the super-cooled liquid and glass for a variety of glassy materials.

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Pleural effusion in a child with a ventriculoperitoneal shunt and congenital heart disease

We present the unique case of an 8 month old infant who required extracorporeal membrane oxygenation (ECMO) after neonatal repair of tetralogy of Fallot. While on ECMO, he developed grade 3 intraventricular hemorrhage resulting in hydrocephalus requiring ventriculoperitoneal (VP) shunt placement at 5 months of life. He presented to cardiology clinic with a 2-month history of poor weight gain, tachypnea, and grunting and was found to have a large right sided pleural effusion. This was proven to be cerebrospinal fluid (CSF) accumulation secondary to poor peritoneal absorption with subsequent extravasation of CSF into the thoracic cavity via a diaphragmatic defect. After diaphragm repair, worsening ascites from peritoneal malabsorption led to shunt externalization and ultimate conversion to a ventriculoatrial (VA) shunt. This is the second reported case of VA shunt placement in a child with congenital heart disease and highlights the need to consider CSF extravasation as the cause of pleural effusions in children with VP shunts.

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Inaugurating the Everett Mendelsohn Prize

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Materials, Vol. 9, Pages 71: Numerical Characterization of Piezoceramics Using Resonance Curves

Piezoelectric materials characterization is a challenging problem involving physical concepts, electrical and mechanical measurements and numerical optimization techniques. Piezoelectric ceramics such as Lead Zirconate Titanate (PZT) belong to the 6 mm symmetry class, which requires five elastic, three piezoelectric and two dielectric constants to fully represent the material properties. If losses are considered, the material properties can be represented by complex numbers. In this case, 20 independent material constants are required to obtain the full model. Several numerical methods have been used to adjust the theoretical models to the experimental results. The continuous improvement of the computer processing ability has allowed the use of a specific numerical method, the Finite Element Method (FEM), to iteratively solve the problem of finding the piezoelectric constants. This review presents the recent advances in the numerical characterization of 6 mm piezoelectric materials from experimental electrical impedance curves. The basic strategy consists in measuring the electrical impedance curve of a piezoelectric disk, and then combining the Finite Element Method with an iterative algorithm to find a set of material properties that minimizes the difference between the numerical impedance curve and the experimental one. Different methods to validate the results are also discussed. Examples of characterization of some common piezoelectric ceramics are presented to show the practical application of the described methods.

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Azocasein Substrate for Determination of Proteolytic Activity: Reexamining a Traditional Method Using Bromelain Samples

Given the importance of protease's worldwide market, the determination of optimum conditions and the development of a standard protocol are critical during selection of a reliable method to determine its bioactivity. This paper uses quality control theory to validate a modified version of a method proposed by Charney and Tomarelli in 1947. The results obtained showed that using azocasein substrate bromelain had its optimum at 45°C and pH 9 (Glycine-NaOH 100 mM). We also quantified the limit of detection (LoD) and limit of quantification (LoQ) in the above-mentioned optimum (0.072 and 0.494 mg·mL−1 of azocasein, resp.) and a calibration curve that correlates optical density with the amount of substrate digested. In all analysed samples, we observed a significant decrease in response after storage (around 17%), which suggests its use must be immediately after preparation. Thus, the protocol presented in this paper offers a significant improvement, given that subjective definitions are commonly used in the literature and this simple mathematical approach makes it clear and concise.

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Synergistic Effects of ACE Insertion/Deletion and GNB3 C825T Polymorphisms on the Efficacy of PDE-5 Inhibitor in Patients with Pulmonary Hypertension

Background: The insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme gene (ACE) and the C825T polymorphism in the G-protein β3 subunit gene (GNB3) are associated with the efficacy of phosphodiesterase-5 inhibitor (PDE-5I) in erectile dysfunction. In addition, GNB3 genotypes could be associated with clinical worsening in pulmonary hypertension (PH) treated with PDE-5I. However, no studies have described the synergistic effects of gene polymorphisms on drug efficacy in patients with PH. Objectives: We aimed to examine the effects of combined ACE/GNB3 polymorphisms on the efficacy of PDE-5I in patients with PH. Methods: This was a retrospective uncontrolled study. Ninety patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic PH (CTEPH) were treated with PDE-5I. Freedom from clinical worsening and pre- and post-treatment parameters, including the 6-min walk distance (6MWD) and serum brain natriuretic peptide (BNP) levels, were compared between patients with ACE/GNB3 II/TT and non-II/TT genotypes. Results: Time to clinical worsening was significantly longer in patients with the II/TT genotype than in those with the non-II/TT genotype (5-year freedom from clinical worsening: 100 vs. 48.8%, respectively; p = 0.018), even in patients with CTEPH alone. Post-treatment 6MWD and BNP levels in patients with the II/TT genotype tended to be better than those in patients with the non-II/TT genotype. The ACE/GNB3 genotype was a significant predictor of clinical worsening, even after adjusting for pulmonary vascular resistance and 6MWD. Conclusions:ACE and GNB3 polymorphisms may synergistically influence the efficacy of PDE-5I in patients with PH.
Respiration

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IJERPH, Vol. 13, Pages 166: Biomarker-Based Approaches for Assessing Alcohol Use Disorders

Although alcohol use disorders rank among the leading public health problems worldwide, hazardous drinking practices and associated morbidity continue to remain underdiagnosed. It is postulated here that a more systematic use of biomarkers improves the detection of the specific role of alcohol abuse behind poor health. Interventions should be initiated by obtaining information on the actual amounts of recent alcohol consumption through questionnaires and measurements of ethanol and its specific metabolites, such as ethyl glucuronide. Carbohydrate-deficient transferrin is a valuable tool for assessing chronic heavy drinking. Activities of common liver enzymes can be used for screening ethanol-induced liver dysfunction and to provide information on the risk of co-morbidities including insulin resistance, metabolic syndrome and vascular diseases. Conventional biomarkers supplemented with indices of immune activation and fibrogenesis can help to assess the severity and prognosis of ethanol-induced tissue damage. Many ethanol-sensitive biomarkers respond to the status of oxidative stress, and their levels are modulated by factors of life style, including weight gain, physical exercise or coffee consumption in an age- and gender-dependent manner. Therefore, further attention should be paid to defining safe limits of ethanol intake in various demographic categories and establishing common reference intervals for biomarkers of alcohol use disorders.

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Catalysts, Vol. 6, Pages 21: Competition of CO and H2 for Active Oxygen Species during the Preferential CO Oxidation (PROX) on Au/TiO2 Catalysts

Aiming at an improved mechanistic understanding of the preferential oxidation of CO on supported Au catalysts, we have investigated the competition between CO and H2 for stable, active oxygen (Oact) species on a Au/TiO2 catalyst during the simultaneous exposure to CO and H2 with various CO/H2 ratios at 80 °C and 400 °C by quantitative temporal analysis of products (TAP) reactor measurements. It is demonstrated that, at both higher and lower temperature, the maximum amount of active oxygen removal is (i) independent of the CO/H2 ratio and (ii) identical to the amount of active oxygen removal by CO or H2 alone. Hence, under preferential CO oxidation (PROX) reaction conditions, in the simultaneous presence of CO and H2, CO and H2 compete for the same active oxygen species. In addition, also the dependency of the selectivity towards CO oxidation on the CO/H2 ratio was evaluated from these measurements. Consequences of these findings on the mechanistic understanding of the PROX reaction on Au/TiO2 will be discussed.

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JDB, Vol. 4, Pages 6: Alterations in Synthesis and Repair of DNA during the Development of Loach Misgurnus fossilis

Using a modified radiolabeled primer extension method (we named this modification misGvA—"misincorporation of G versus A") we have investigated the DNA synthesis and repair at early and late stages of development of loach Misgurnus fossilis. The misincorporation activity of DNA polymerase iota (Pol ι) in wild-type loach could not be detected by this method at any stage of loach development. In transgenic loach overexpressing human Pol ι we have shown that the bypassing of DNA synthesis arrest after incorporation of mismatched nucleotide by Pol ι (the T-stop) was not associated with this enzyme. Non-transgenic loach larvae are virtually lacking the capacity for error correction of DNA duplex containing a mismatched nucleotide. Such repair activity develops only in the adult fish. It appears that the initial stages of development are characterized by more intensive DNA synthesis, while in terminal stages the repair activities become more prominent. The misGvA approach clearly indicates substantial changes in the DNA synthesis intensity, although the role of particular replicative and repair DNA polymerases in this process requires further study.

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IJERPH, Vol. 13, Pages 169: Seasonal Shifts in Primary Water Source Type: A Comparison of Largely Pastoral Communities in Uganda and Tanzania

Many water-related illnesses show an increase during the wet season. This is often due to fecal contamination from runoff, yet, it is unknown whether seasonal changes in water availability may also play a role in increased illness via changes in the type of primary water source used by households. Very little is known about the dynamic aspects of access to water and changes in source type across seasons, particularly in semi-arid regions with annual water scarcity. The research questions in this study were: (1) To what degree do households in Uganda (UG) and Tanzania (TZ) change primary water source type between wet and dry seasons?; and (2) How might seasonal changes relate to water quality and health? Using spatial survey data from 92 households each in UG and TZ this study found that, from wet to dry season, 26% (UG) and 9% (TZ) of households switched from a source with higher risk of contamination to a source with lower risk. By comparison, only 20% (UG) and 0% (TZ) of households switched from a source with lower risk of contamination to a source with higher risk of contamination. This research suggests that one pathway through which water-related disease prevalence may differ across seasons is the use of water sources with higher risk contamination, and that households with access to sources with lower risks of contamination sometimes choose to use more contaminated sources.

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Translating knowledge for action against stroke – using 5-minute videos for stroke survivors and caregivers to improve post-stroke outcomes: study protocol for a randomized controlled trial (Movies4Stroke)

Background: Two thirds of the global mortality of stroke is borne by low and middle income countries (LMICs). Pakistan is the world's sixth most populous country with a stroke-vulnerable population and is without a single dedicated chronic care center. In order to provide evidence for a viable solution responsive to this health care gap, and leveraging the existing >70 % mobile phone density, we thought it rational to test the effectiveness of a mobile phone-based video intervention of short 5-minute movies to educate and support stroke survivors and their primary caregivers. Methods: Movies4Stroke will be a randomized control, outcome assessor blinded, parallel group, single center superiority trial. Participants with an acute stroke, medically stable, with mild to moderate disability and having a stable primary caregiver will be included. After obtaining informed consent the stroke survivor-caregiver dyad will be randomized. Intervention participants will have the movie program software installed in their phone, desktop, or Android device which will allow them to receive, view and repeat 5-minute videos on stroke-related topics at admission, discharge and first and third months after enrollment. The control arm will receive standard of care at an internationally accredited center with defined protocols. The primary outcome measure is medication adherence as ascertained by a locally validated Morisky Medication Adherence Scale and control of major risk factors such as blood pressure, blood sugar and blood cholesterol at 12 months post discharge. Secondary outcome measures are post-stroke complications and mortality, caregiver knowledge and change in functional outcomes after acute stroke at 1, 3, 6, 9 and 12 months. Movies4Stroke is designed to enroll 300 participant dyads after inflating 10 % to incorporate attrition and non-compliance and has been powered at 95 % to detect a 15 % difference between intervention and usual care arm. Analysis will be done by the intention-to-treat principle.DiscussionMovies4Stroke is a randomized trial testing an application aimed at supporting caregivers and stroke survivors in a LMIC with no rehabilitation or chronic support systems.Trial registrationNCT02202330 (28 January 2015)

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Pharmacy, Vol. 4, Pages 10: Testing of Candidate Icons to Identify Acetaminophen-Containing Medicines

Adding icons on labels of acetaminophen-containing medicines could help users identify the active ingredient and avoid concomitant use of multiple medicines containing acetaminophen. We evaluated five icons for communication effectiveness. Adults (n = 300) were randomized to view a prescription container label or over-the-counter labels with either one or two icons. Participants saw two icon candidates, and reported their interpretation; experts judged whether these reflected critical confusions that might cause harm. Participants rated how effectively each icon communicated key messages. Icons based on abbreviations of "acetaminophen" ("Ac", "Ace", "Acm") were rated less confusing and more effective in communicating the active ingredient than icons based on "APAP" or an abstract symbol. Icons did not result in critical confusion when seen on a readable medicine label. Icon implementation on prescription labels was more effective at communicating the warning against concomitant use than implementation on over-the-counter (OTC) labels. Adding an icon to a second location on OTC labels did not consistently enhance this communication, but reduced rated effectiveness of acetaminophen ingredient communication among participants with limited health literacy. The abbreviation-based icons seem most suitable for labeling acetaminophen-containing medications to enable users to identify acetaminophen-containing products.

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Improving delivery of secondary prophylaxis for rheumatic heart disease in remote Indigenous communities: study protocol for a stepped-wedge randomised trial

Background: Rheumatic heart disease (RHD), caused by acute rheumatic fever (ARF), is a major health problem in Australian Aboriginal communities. Progress in controlling RHD requires improvements in the delivery of secondary prophylaxis, which comprises regular, long-term injections of penicillin for people with ARF/RHD.Methods/DesignThis trial aims to improve uptake of secondary prophylaxis among Aboriginal people with ARF/RHD to reduce progression or worsening of RHD. This is a stepped-wedge, randomised trial in consenting communities in Australia's Northern Territory. Pairs of randomly-chosen clinics from among those consenting enter the study at 3-monthly steps. The intervention to which clinics are randomised comprises a multi-faceted systems-based package, in which clinics are supported to develop and implement strategies to improve penicillin delivery, aligned with elements of the Chronic Care Model. Continuous quality improvement processes will be used, including 3-monthly feedback to clinic staff of adherence rates of their ARF/RHD clients.The primary outcome is the proportion of people with ARF/RHD receiving ≥80 % of scheduled penicillin injections over a minimum 12-month period. The sample size of 300 ARF/RHD clients across five community clusters will power the study to detect a 20 % increase in the proportion of individuals achieving this target, from a worrying low baseline of 20 %, to 40 %. Secondary outcomes pertaining to other measures of adherence will be assessed. Within the randomised trial design, a mixed-methods evaluation will be embedded to evaluate the efficiency, effectiveness, impact and relevance, sustainability, process and fidelity, and performance of the intervention. The evaluation will establish any causal link between outcomes and the intervention. The planned study duration is from 2013 to 2016.DiscussionContinuous quality improvement has a strong track record in Australia's Northern Territory, and its use has resulted in modest benefits in a pilot, non-randomised ARF/RHD study. If successful, this new intervention using the Chronic Care Model as a scaffold and evaluated using a well-developed theory-based framework, will provide a practical and transferable approach to ARF/RHD control.Trial registrationAustralian New Zealand Clinical Trials Registry: ACTRN12613000223730. Date registered: 25 February 2013

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