bluuebunny/crossref_metadata_2025 huggingface dataset:
An Internet‐based programme to promote adequate UV exposure behaviour in adolescents in Spain
Authors: Buendía Eisman A. , Arias Santiago S. , Moreno‐Gimenez J.C. , Cabrera‐León A. , Prieto L. , Castillejo I. , Conejo‐Mir J.
Published: February 2012

Background  The exponential rise in the incidence of cutaneous cancers underscores the need to promote primary prevention. Adolescents are highly familiar with the use of Internet, and new technologies and Internet systems have proven especially useful to educate this age group in other health problems. To date, there have been no reports of Internet‐based primary prevention campaigns for adolescents against skin cancer.

Objectives  To determine the knowledge and behaviour of a Spanish adolescent population in relation to sun exposure through an Internet‐based system and to describe the use of an Internet‐based school intervention programme to improve the sun exposure knowledge and behaviour in adolescents.

Methods  The cross‐sectional study included 2170 school pupils aged between 12 and 16 years from public secondary schools. Pupils in the participating centres completed the survey via the website, which contained a total of 35 questions and three information blocks. For the intervention programme, a sub‐sample of 12 secondary schools (total of 1290 pupils) was randomly selected.

Results  About 56.7% of the female pupils and 52.6% of the male pupils reported having suffered from sunburn in the previous summer. Sunburn risk increased with the frequency of sun exposure between 12 and 6 pm (OR of 3.59), null knowledge of the negative effects of sun exposure (OR of 2.102), the use of sun protection cream (OR of 0.695 for non‐use) and physical sun protection measures (OR of 2.21 for 0–1 physical measures). A significant reduction in self‐reported sunburns was observed in the quasi‐experimental group in comparison with controls after adjusting for sex and inland or coastal location of the centre (OR = 0.45, 95% CI = 0.23–0.87, P = 0.018). Adjusted OR showed that there was a significant improvement in the use of physical measures, use of sun cream, frequency of sun cream application every 2 h and use of protection on cloudy days.

Conclusions  This is the first study to demonstrate that a programme entirely conducted via Internet significantly reduces by half self‐reported sunburn risk in an adolescent population achieving very high satisfaction rates.
Singing the new Nepal
Authors: Hutt Michael
Published: February 2012

Nepal's adoption of a new national anthem in 2007 reflected a decision to establish a new social and political order that was republican, federal and inclusive of the country's many minority communities. It came after a ten‐year internal conflict, and was followed by the abolition of the Shah monarchy that had ruled the country since the late eighteenth century. This article describes the historical and political context of the decision to replace the old anthem, the selection of the new anthem, and the debates that arose in the Nepali media and public sphere after its lyrics and the identity of its author were made known. The discussion refers to arguments made by Karen Cerulo about the relationship between the syntactic structure of national anthems and the stage reached in the process of political modernisation of the nation‐state in question, and provides some comparative perspectives on the Nepali case.
A randomized controlled pilot study into the effects of a restricted elimination diet on family structure in families with ADHD and ODD
Authors: Pelsser Lidy M , van Steijn Daphne J , Frankena Klaas , Toorman Jan , Buitelaar Jan K , Rommelse Nanda N
Published: February 2012

Background

Behavioural improvements of children with attention‐deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) following a restricted elimination diet (RED), may be due to concurrent changes in family environment.

Methods

Twenty‐four children with ADHD, were randomized to either a 5‐week RED intervention, or a control intervention consisting of healthy food advices in a pilot study.

Results

No differences in family environment were found, neither at baseline nor when comparing the start and end measurements of both groups.

Conclusions

In this pilot study, the effects of an RED on ADHD and ODD are not mediated by improvement of family environment in families motivated to follow an RED. Replication of this preliminary study in larger groups of children is advised.
“Shotgunning” in a Population of Patients with Severe Mental Illness and Comorbid Substance Use Disorders
Authors: Welsh Christopher , Goldberg Richard , Tapscott Stephanie , Medoff Deborah , Rosenberg Stanley , Dixon Lisa
Published: February 2012

“Shotgunning” refers to the practice of one individual forcibly exhaling smoke into the mouth of another, and may increase the risk of transmission of respiratory pathogens. The extent of shotgunning among individuals with co‐occurring serious mental illness and substance use is unknown. We included questions about shotgunning in an interview of 236 participants of a study testing a model to prevent and treat HIV and hepatitis. Shotgunning was common (61%[145/236]) and correlated with increased substance use severity and several high‐risk behaviors. Only 8% (11/145) understood that shotgunning could transmit disease. Further research and patient education on shotgunning is warranted. (Am J Addict 2012;21:120–125)
Punjabi Sikh Patients’ Perceived Barriers to Engaging in Physical Exercise Following Myocardial Infarction
Authors: Galdas Paul M. , Oliffe John L. , Kang H. Bindy K. , Kelly Mary T.
Published: February 2012

Objective

The aim of this research was to describe Punjabi Sikh patients’ perceived barriers to engaging in physical exercise following myocardial infarction (MI).

Design and Sample

A qualitative, interpretive descriptive methodology was used. The sample included 15 Punjabi Sikh patients who were attending a cardiac rehabilitation education program in an urban center of British Columbia, Canada, following MI.

Measurements

Data were collected via semi‐structured interviews and were audio recorded, translated from Punjabi to English, and transcribed verbatim. Data were analyzed using an interpretive thematic approach that involved a process of coding and constant comparison.

Results

Four key factors emerged that related to participants’ perceived barriers to sustained engagement in physical activity: (1) difficulty in determining safe exertion levels independently; (2) fatigue and weakness; (3) preference for ‘informal’ exercise; and (4) migration‐related challenges.

Conclusions

The findings have implications for the design and delivery of health promotion strategies aimed at Punjabi Sikh patients’ post‐MI that is contingent on the use of ‘formal’ exercise settings to promote regular physical activity. The willingness among Punjabi Sikh patients to practise brisk walking offers a positive direction that public health nurses and other healthcare professionals may want to capitalize on in the delivery of exercise‐related health promotion.
Generalized Lichen Nitidus in Russell‐Silver Syndrome
Authors: Kanai Chie , Terao Mika , Tanemura Atsushi , Miyoshi Yoko , Ozono Keiichi , Katayama Ichiro
Published: February 2012

Abstract:  Generalized lichen nitidus is a rare disease, and there are only a few reports associating it with a genetic disorder. Here we report a case of generalized lichen nitidus in Russell‐Silver syndrome.
Extensive Facial and Orbital Infantile Hemangiomas Associated with High Intraocular Pressure
Authors: Shatriah Ismail , Norazizah Mohd‐Amin , Wan‐Hitam Wan‐Hazabbah , Wong Abd‐Rahim , Yunus Rohaizan , Leo Seo‐Wei
Published: February 2012

Abstract:  High intraocular pressure is a rare ophthalmic condition associated with infantile hemangiomas that involves the orbit, eyelid, or both. Here, we describe a patient with extensive facial and orbital infantile hemangiomas associated with high intraocular pressure in the affected eye. The prompt management of this challenging condition is essential.
Death from Mast Cell Leukemia: A Young Patient with Longstanding Cutaneous Mastocytosis Evolving into Fatal Mast Cell Leukemia
Authors: Chantorn Rattanavalai , Shwayder Tor
Published: February 2012

Abstract:   Mastocytosis is a broad term used for a group of disorders characterized by accumulation of mast cells in the skin with or without extracutaneous involvement. The clinical spectrum of the disease varies from only cutaneous lesions to highly aggressive systemic involvement such as mast cell leukemia. Mastocytosis can present from birth to adulthood. In children, mastocytosis is usually benign, and there is a good chance of spontaneous regression at puberty, unlike adult‐onset disease, which is generally systemic and more severe. Moreover, individuals with systemic mastocytosis may be at risk of developing hematologic malignancies. We describe a girl who presented to us with a solitary mastocytoma at age 5 and later developed maculopapular cutaneous mastocytosis. At age 23, after an episode of anaphylactic shock, a bone marrow examination revealed mast cell leukemia. She ultimately died despite aggressive chemotherapy and bone marrow transplantation.
Modern technology calls for a modern approach to classification of epileptic seizures and the epilepsies
Authors: Lüders Hans O. , Amina Shahram , Baumgartner Christopher , Benbadis Selim , Bermeo‐Ovalle Adriana , Devereaux Michael , Diehl Beate , Edwards Jonathan , Baca‐Vaca Guadalupe Fernandez , Hamer Hajo , Ikeda Akio , Kaiboriboon Kitti , Kellinghaus Christoph , Koubeissi Mohamad , Lardizabal David , Lhatoo Samden , Lüders Jürgen , Mani Jayanti , Mayor Luis Carlos , Miller Jonathan , Noachtar Soheyl , Pestana Elia , Rosenow Felix , Sakamoto Americo , Shahid Asim , Steinhoff Bernhard J. , Syed Tanvir , Tanner Adriana , Tsuji Sadatoshi
Published: February 2012

In the last 10–15 years the ILAE Commission on Classification and Terminology has been presenting proposals to modernize the current ILAE Classification of Epileptic Seizures and Epilepsies. These proposals were discussed extensively in a series of articles published recently inEpilepsiaandEpilepsy Currents. There is almost universal consensus that the availability of new diagnostic techniques as also of a modern understanding of epilepsy calls for a complete revision of the Classification of Epileptic Seizures and Epilepsies. Unfortunately, however, the Commission is still not prepared to take a bold step ahead and completely revisit our approach to classification of epileptic seizures and epilepsies. In this manuscript we critically analyze the current proposals of the Commission and make suggestions for a classification system that reflects modern diagnostic techniques and our current understanding of epilepsy.
End‐of‐Life Care for People with Dementia from Ethnic Minority Groups: A Systematic Review
Authors: Connolly Amanda , Sampson Elizabeth L. , Purandare Nitin
Published: February 2012

A systematic review of the literature was conducted to examine the relationship between ethnic minority status and provision of end‐of‐life care for people with dementia. It included all empirical research on people with dementia or severe cognitive impairment or their caregivers and with ethnic minority people as a subgroup in examining an outcome involving end‐of‐life care processes or attitudes toward end‐of‐life care. Two authors independently rated quality of included studies; 20 studies met eligibility criteria and were included in the review: 19 quantitative and one qualitative. All articles were based in the United States, with African American, Hispanic, and Asian groups being the ethnic minorities. Artificial nutrition and other life‐sustaining treatments were more frequent and decisions to withhold treatment less common in African American and Asian groups. The qualitative evidence, albeit limited, found that attitudes toward end‐of‐life care were more similar than different between different ethnic groups. Differences in hospice usage patterns were less consistent and potentially influenced by factors such as study setting and dementia severity. Caregivers' experiences differed between ethnic groups, whereas levels of strain experienced were similar. Disparities in end‐of‐life care for people with dementia from ethnic minority groups appear to exist and may be due to the double disadvantage of dementia and ethnic minority status. Further research is needed in other western multicultural countries, with a focus on prospective qualitative studies to understand the underlying reasons for these differences, not just their occurrence.
Good Death in Elderly Adults with Cancer in Japan Based on Perspectives of the General Population
Authors: Akechi Tatsuo , Miyashita Mitsunori , Morita Tatsuya , Okuyama Toru , Sakamoto Masaki , Sagawa Ryuichi , Uchitomi Yosuke
Published: February 2012

Objectives

To investigate concepts relevant to a good death in elderly adults with cancer.

Design

Cross‐sectional.

Setting

Japan.

Participants

A national sample of 2,595 adults, including 466 aged 70 to 79.

Measurements

An anonymous questionnaire covering 18 domains (physical and psychological comfort, dying in a favorite place, good relationship with medical staff, maintaining hope and pleasure, not being a burden to others, good relationship with family, physical and cognitive control, environmental comfort, being respected as an individual, life completion, natural death, preparation for death, role accomplishment and contribution to others, unawareness of death, fighting against cancer, pride and beauty, control over the future, and religious and spiritual comfort) and two additional concepts (pokkuri (sudden death) and omakase (leaving the decisions to a medical expert) was completed. The difference in importance of the concept between two age groups (40–69 and 70–79) was investigated using effect sizes (ESs).

Results

Clinically significant differences in the concept of good death were observed for two domains and one component: not being a burden to others (ES = −0.24), role accomplishment and contribution to others (ES = 0.29), and omakase (leaving the decisions to a medical expert; ES = 0.60).

Conclusion

Only a few differences in the concept of good death existed between elderly and younger adults. When caring for terminally ill elderly Japanese adults, medical staff should acknowledge that some elderly adults value the traditional paternalistic attitude of physicians and that not all people want to be actively involved in decision‐making.
Different Tests for a Difference: How do we do Research?
Authors: DRUMMOND GORDON B. , VOWLER SARAH L.
Published: February 2012

Please cite this paper as: Drummond GB and Vowler SL. Different Tests for a Difference: How do we do Research? Microcirculation 19: 188–191, 2012.
Residents’ Perceptions of Food and Nutrition Services at Assisted Living Facilities
Authors: Strohl Melissa , Bednar Carolyn , Longley Carol
Published: February 2012

Food and nutrition services in assisted living facilities (ALFs) are important factors in overall quality of life and health status of the elderly. This cross‐sectional study examined the relationship between ALF food and nutrition services theme and resident perceptions of food and service quality and foodservice satisfaction at Texas ALFs. Participants completed a questionnaire that asked them to self‐report demographics, functional status, and perceptions of food quality, service quality, and foodservice satisfaction. Eighty‐five individuals ranging in age from 58 to 99 years residing at six ALFs in north Texas participated. Facilities included two from each of the following food and nutrition service themes (restaurant/resort, medical/health, and home‐style). Residents of the three ALF themes gave similar ratings for food quality, overall foodservice, and foodservice satisfaction. However, residents at home‐style theme facilities rated service quality more highly than those at restaurant/resort facilities. Menu choices and mealtime flexibility associated with the home‐style food and nutrition services theme may make these facilities a preferred choice for elderly individuals who are no longer able to remain in their own homes.
L‐asparaginase inhibits invasive and angiogenic activity and induces autophagy in ovarian cancer
Authors: Yu Minshu , Henning Ryan , Walker Amanda , Kim Geoffrey , Perroy Alyssa , Alessandro Riccardo , Virador Victoria , Kohn Elise C.
Published: February 2012

Recent work identified L‐asparaginase (L‐ASP) as a putative therapeutic target for ovarian cancer. We suggest that L‐ASP, a dysregulator of glycosylation, would interrupt the local microenvironment, affecting the ovarian cancer cell—endothelial cell interaction and thus angiogenesis without cytotoxic effects. Ovarian cancer cell lines and human microvascular endothelial cells (HMVEC) were exposed to L‐ASP at physiologically attainable concentrations and subjected to analyses of endothelial tube formation, invasion, adhesion and the assessment of sialylated proteins involved in matrix‐associated and heterotypic cell adhesion. Marked reduction in HMVEC tube formation in vitro, HMVEC and ovarian cancer cell invasion, and heterotypic cell‐cell and cell‐matrix adhesion was observed (P < 0.05–0.0001). These effects were associated with reduced binding to ß1integrin, activation of FAK, and cell surface sialyl LewisX (sLex) expression. No reduction in HMVEC E‐selectin expression was seen consistent with the unidirectional inhibitory actions observed. L‐ASP concentrations were non‐toxic to either ovarian cancer or HMVEC lines in the time frame of the assays. However, early changes of autophagy were observed in both cell types with induction of ATG12, beclin‐1, and cleavage of LC‐3, indicating cell injury did occur. These data and the known mechanism of action of L‐ASP on glycosylation of nascent proteins suggest that L‐ASP reduces of ovarian cancer dissemination and progression through modification of its microenvironment. The reduction of ovarian cancer cell surface sLex inhibits interaction with HMVEC and thus HMVEC differentiation into tubes, inhibits interaction with the local matrix reducing invasive behaviour, and causes cell injury initiating autophagy in tumour and vascular cells.
SZ95 sebocytes induce epidermal melanocyte dendricity and proliferation in vitro
Authors: Abdel‐Naser Mohamed Badawy , Seltmann Holger , Zouboulis Christos C.
Published: February 2012

Abstract:  The regulatory effects of sebocytes on melanocytes (HMel) are unknown. In this study, SZ95 sebocytes co‐cultured with HMel, whether in direct cell contact or with SZ95 sebocytes in inserts, resulted in epidermal HMel flattening with increase in surface area and multiple small dendrites formation. Only in high Ca2+ level and direct cell contact co‐culture, the HMel dendrites were remarkably long and preferentially targeted and attached to SZ95 sebocytes. Likewise, only high Ca2+ SZ95 sebocyte conditioned medium stimulated HMel proliferation in a time‐dependent manner at days 9 (142.9%, P < 0.01) and 12 (179.2%, P < 0.0001) of incubation when compared with day 0. In contrast, melanin contents significantly decreased on incubation with high Ca2+ SZ95 sebocytes in comparison with low Ca2+ SZ95 sebocytes at days 6 (P < 0.01) and 9 (P < 0.05) of incubation. These results denote that sebocytes also modulate HMel functions and may contribute to skin colour in sebaceous glands‐rich body regions.
Assessment of the effect of Advanced Paediatric Life Support training on level of self‐perceived preparedness among health‐care workers in Cambodia
Authors: Dhingra Prateek , Ngeth Pises , Prak Manila , Ung Setthy
Published: February 2012

Objective: The objective of this study was to survey the self‐perceived preparedness of Cambodia's Advanced Paediatric Life Support (APLS) providers towards their APLS training and accreditation 5 years post‐implementation.

Methods: A cross‐sectional survey was administered in December 2009 to APLS providers who had been trained throughout the 5 year period from December 2005 to May 2009.

Results: One hundred and two (93%) APLS providers responded. The median rating for their original APLS learning experience was 6 out of 10, and the reported median recall of the APLS teaching content was 7 out of 10. Since their training, 80% had managed a child in cardiac arrest, 85% a child with serious illness and 72% with serious injury. Their subjective preparedness from APLS training for each of the three resuscitation types, on a scale of 1–10, were medians of 7, 7 and 6, respectively. For all groups, perceived preparedness for all three resuscitation types did not differ despite varying lengths of time from their original training.

Conclusion: APLS training has increased the self‐perceived preparedness of paediatric health‐care workers in Cambodia. Results indicate moderate relevance to real patient resuscitations experienced by health workers, and the perceived recall of the teachings and sense of preparation from APLS training does not significantly decline over time. However, our results suggest subsequent further APLS instructor courses might maintain resuscitation preparedness.
How useful are the Heart Foundation risk criteria for assessment of emergency department patients with chest pain?
Authors: Kelly Anne‐Maree
Published: February 2012

Objective: To investigate the prognostic utility of Heart Foundation (Australia) risk stratification table in an ED chest pain population.

Methods: A planned sub‐study of a prospective observational study of adult patients with potentially cardiac chest pain who underwent evaluation for acute coronary syndrome (ACS) was conducted. Data collected included demographical, clinical, ECG, biomarker and outcome data. Outcome of interest was diagnostic utility of the classification system for ACS or myocardial infarction (MI) at index presentation and major adverse cardiac events (MACE) within 7 and 30 days. MACE included death, cardiac arrest, revascularization, cardiogenic shock, arrhythmia and prevalent (cause of presentation) and incident (occurring within the follow‐up period) MI. Analysis was by descriptive and receiver–operator curve analyses.

Results: Seven hundred and sixty‐eight patients were studied; 109 had MI (14.2%, 95% confidence interval [CI] 11.9–16.8%). There were 88 MACE at 7 days (13.5%, 95% CI 11.1–16.4%) and 93 MACE at 30 days (14.4%%, 95% CI 11.9–17.3%). Diagnostic performance (c‐statistic) of the National Heart Foundation risk classification for ACS, MI, 7 and 30 day MACE was 0.74 for each (95% CI 0.71–0.77). Although sensitivity of the high‐risk classification for MI, 7 and 30 day MACE was high (99–100%), specificity was low (48–50%).

Conclusion: The Heart Foundation risk classification shows only fair predictive performance for MI, 7 and 30 day MACE. With specificity of approximately 50%, the recommendation for coronary care admission for all high‐risk patients is hard to justify.
Dynamic Oxidative Stress and DNA Damage Induced by Oestrogen Deficiency and Protective Effects of Puerarin and 17β‐Oestradiol in Ovariectomized Rats
Authors: Tang Xu‐Lei , Liu Xiao‐Ju , Tian Quan , Zhang Wei
Published: February 2012

Oxidative stress plays an essential role in the pathogenesis of cardiovascular diseases and osteoporosis resulting from oestrogen deficiency in the postmenopausal period. In this report, we observed a dynamic change of oxidative stress and DNA damage after ovariectomy in female rats. We then compared phytoestrogen puerarin and 17β‐oestradiol (E2) in their effects on oestrogen deficiency‐induced oxidative stress and DNA damage. Serum total antioxidant capacity (TAC), malondialdehyde (MDA) and lymphocytes DNA damage (comet%) were measured. There was a gradual increase in oxidative stress in the ovariectomized (OVX) rats over time after ovariectomy, as compared to rats receiving sham operation. OVX rats that were on puerarin and E2 showed increased TAC and decreased MDA in the serum, as well as decreased lymphocytes comet%. Puerarin appeared to have a more powerful protective effect on DNA oxidative damage than E2. The study indicates that postmenopausal women may benefit from phytoestrogen puerarin.
Determinants of Regular and Occasional Consumers' Intentions to Buy Organic Food
Authors: PINO GIOVANNI , PELUSO ALESSANDRO M. , GUIDO GIANLUIGI
Published: February 2012

This study analyzes the impact of ethical motivations, food safety and health‐related concerns on purchasing intentions of habitual and less frequent consumers of organic food. A sample of 291 subjects was surveyed through a paper‐and‐pencil questionnaire and classified either as “regular” or “occasional” purchasers of organic food according to their buying frequency. Results show different determinants of intention for the two groups of subjects: ethical motivations affect the purchase intentions of regular consumers, whereas food safety concerns influence the purchase intentions of occasional consumers. Implications are discussed.
Phthalocyanine Thio‐Pyridinium Derivatives as Antibacterial Photosensitizers†
Authors: Pereira Joana B. , Carvalho Eliana F. A. , Faustino Maria A. F. , Fernandes Rosa , Neves Maria G. P. M. S. , Cavaleiro José A. S. , Gomes Newton C. M. , Cunha Ângela , Almeida Adelaide , Tomé João P. C.
Published: February 2012

This study describes the synthesis of three new tetra‐ and octa‐thio‐pyridinium phthalocyanine derivatives. PSs 3a and 4a were prepared from the tetramerization of phthalonitriles 1 and 2, respectively, whereas PS 5 was prepared from the nucleophilic substitution of the 8 beta fluor atoms of hexadecafluorophthalocyaninatozinc(II) by mercaptopyridine, followed by cationization. The recombinant bioluminescent Escherichia coli strain was used to assess, in real time, the photoinactivation efficiency of these cationic phthalocyanines, under white and red light. The cellular localization and uptake were also determined to assess the potential of the new phthalocyanines as antibacterial agents. Derivative 3a was the most effective PS, causing a 5 logs reduction in bioluminescence after 30 min of irradiation under white or red lights. The photoinactivation efficiency of the phthalocyanine 4a was similar (5 logs reduction in bioluminescence) to that of 3a when irradiated with white light, but the efficiency of inactivation was reduced (2.1 logs reduction in bioluminescence) under red light. The tetra‐substituted phthalocyanine 3a also generates high amounts of singlet oxygen, does not aggregate in PBS and is highly fluorescent, which makes it an effective PS and a promising fluorescent labeling.
Is obesity an indicator of complications and mortality in acute pancreatitis? An updated meta‐analysis
Authors: CHEN Su Mei , XIONG Guang Su , WU Shu Ming
Published: February 2012

OBJECTIVE:  To provide a meta‐analyisis on whether obesity could be a prognostic indicator on the severity, development of complications and mortality of acute pancreatitis (AP).

METHODS:  Eligible articles were retrieved using electronic databases. Clinical studies evaluating the association between obesity and disease course of patients with AP were included. Weighted mean difference (WMD) and 95% confidence interval (CI) were estimated and pooled using RevMan 4.2.8.

RESULTS:  In all, 12 clinical studies with a total of 1483 patients were included in the analysis. Obese patients had a significantly increased risk of severe acute pancreatitis (SAP; RR = 2.20, 95% CI 1.82–2.66, P < 0.05), local complication (RR = 2.68, 95% CI 2.09–3.43, P < 0.05), systemic complication (RR = 2.14, 95% CI 1.42–3.21, P < 0.05) and in‐hospital mortality (RR = 2.59, 95% CI 1.66–4.03, P < 0.05) compared with non‐obese patients.

CONCLUSIONS:  Obesity is a definite risk factor of morbidity and in‐hospital mortality for AP and may serve as a prognostic indicator.
How to sell Russian gas to Europe via Ukraine?
Authors: Chernavsky Sergei , Eismont Oleg
Published: February 2012

In recent years, the problems of Russian gas supplies to Europe got quite serious as the events of January 2009 have shown. From an economic point of view, the sources of these problems are the monopoly of Ukraine as a transit country, on one hand, and Russian monopoly on supplies of gas to Ukraine, on the other. The paper analyses different schemes of supplying Russian gas to Europe and Ukraine. It is shown that under existing agreements on supplies of Russian gas to Europe, Ukraine does not take proper advantage of its position as a monopoly transit country. On its part, Russia could benefit by setting the price of gas supplied to Ukraine as a function of transit tariff set by Ukraine.
CHRONIC KIDNEY DISEASE, DIABETES MELLITUS AND CARDIOVASCULAR DISEASE: RISKS AND COMMONALITIES
Authors: Suckling Rebecca , Gallagher Hugh
Published: February 2012

The prevalence of chronic kidney disease (CKD) and diabetes mellitus (DM) is increasing worldwide. CKD and diabetes are important risk factors for cardiovascular disease and all three conditions are key components of the multiple morbidities increasingly evident as population age in the developed world. Shared risk factors, both traditional and nontraditional, contribute to these associations, and are important targets for public health and both primary and secondary care. Prevention and early detection in combination with a holistic approach to vascular care will be key to improving outcomes and reducing costs. Routine reporting of estimated glomerular filtration rate to aid early identification, risk stratification through quantitative proteinuria testing, appropriate use of renin‐angiotensin system antagonists and optimal blood pressure control are important strategies to improve the care of people with or at risk of CKD.
EXERCISE IN KIDNEY DISEASE AND DIABETES: TIME FOR ACTION
Authors: Smith Alice C. , Burton James O.
Published: February 2012

Physical inactivity is well recognised as a major health issue in today's society. Regular exercise is important in maintaining health and preventing chronic disease, it is increasingly accepted as a valuable therapeutic intervention in many long‐term conditions. Unfortunately the role of physical activity in renal disease has been largely overlooked and provision of exercise advice and rehabilitation programmes for kidney patients lags well behind that of cardiology and pulmonary services. Research indicates that exercise can impact positively upon many of the health issues associated with declining renal function and renal replacement therapy, as concluded by a recent Cochrane review on the topic. As exercise should be integral to the management of diabetes, the issue is particularly relevant for patients with diabetic kidney disease. This paper summarises what is known about the main effects of exercise training in chronic kidney disease and diabetic kidney disease, and suggests how adaptations in the attitudes and approaches of the multidisciplinary renal and diabetes healthcare teams can help patients to enjoy the diverse benefits of an appropriately active lifestyle.
FOOT PROBLEMS IN PATIENTS WITH DIABETES AND CHRONIC KIDNEY DISEASE
Authors: Valabhji Jonathan
Published: February 2012

There is a much higher incidence of diabetic foot disease in those with concurrent renal disease and outcomes, including amputation and mortality, are generally poorer. The risk factors contributing to the higher incidence of foot disease in those with both diabetes and renal disease are outlined, and the evidence explored demonstrating higher incidence of foot disease across categories of renal disease, including impaired renal function (chronic kidney disease stages 3 and 4), haemodialysis, continuous ambulatory peritoneal dialysis, renal transplantation and simultaneous pancreas and kidney transplantation. Three major pathological aspects of diabetic foot disease in which concurrent renal disease either contributes to a higher incidence, or modifies the clinical manifestations and outcomes, are described: ulceration; Charcot neuroarthropathy and necrotic toes. Pathophysiology, clinical features and management strategies for these three conditions are described. Finally, the evidence for preventative strategies for foot disease is explored, and the important role of speed of access to specialist multi‐disciplinary diabetic foot services discussed.
High Wire Act: Building Brand Value During an M&A Transition
Authors: Lucas Scott , Richards Dyfed “Fred” , Taylor Mike , Campbell Jean , Hiatt Rhonda
Published: February 2012

When brands join forces during a merger or acquisition, adopting an integrated, collaborative approach to rebranding can help to build brand value and manage corporate differences.
Never Innovate Alone: How to Collaborate for Organizational Impact
Authors: Das Kingshuk
Published: February 2012

Successful innovators know how to build strategic partnerships within organizations.
Orchestrating Design Collaborations: Think Like a Family
Authors: Jani Harnish , Sawhney Ravi
Published: February 2012

The lessons we learn as parents, friends, spouses, and children can be put to good use in managing design collaborations.
Effect of ageing on left ventricular compliance and distensibility in healthy sedentary humans
Authors: Fujimoto Naoki , Hastings Jeffrey L. , Bhella Paul S. , Shibata Shigeki , Gandhi Nainesh K. , Carrick‐Ranson Graeme , Palmer Dean , Levine Benjamin D.
Published: February 2012

Key points 

Healthy sedentary ageing leads to stiffening of the heart; however, when this process occurs during ageing has been unknown.

In this study, 70 healthy sedentary subjects were stratified into four groups: ‘young’– G21−34: 21–34 years; ‘early middle‐age’– G35−49: 35–49 years; ‘late middle‐age’– G50−64: 50–64 years; and ‘seniors’– G≥65: ≥65 years.

Invasive catheter measurements showed a substantially greater left ventricular (LV) compliance (more flexible/less stiff) in G21−34 than G50−64 and G≥65.

Although LV chamber compliance in G50−64 and G≥65 appeared identical, pressure–volume curves were shifted leftward, exhibiting a smaller volume for any given pressure with increasing age.

Our results suggest that LV stiffening with ageing occurs during the transition between youth and middle‐age and becomes manifest between the ages of 50–64; LV volume contraction and remodelling follow in the senior years. Early–late middle age thus may represent a ‘sweet spot’ when interventions to prevent stiff ageing hearts may be most effective.
A role for xanthine oxidase in the control of fetal cardiovascular function in late gestation sheep
Authors: Herrera E. A. , Kane A. D. , Hansell J. A. , Thakor A. S. , Allison B. J. , Niu Y. , Giussani D. A.
Published: February 2012

Key points 

There is growing physiological and clinical interest in the role of the enzyme xanthine oxidase in the regulation of fetal cardiovascular function.

The xanthine oxidase inhibitor allopurinol is undergoing human clinical trials in complicated pregnancy to protect the fetal brain from injury by decreasing excessive generation of reactive oxygen species (ROS) and increasing nitric oxide (NO) availability. However, the effects on fetal cardiovascular physiology of xanthine oxidase inhibition are largely unknown.

We have previously reported that the balance between ROS and NO plays an important physiological role in the control of fetal cardiovascular function. Therefore, it seems likely that allopurinol might perturb this balance and alter fetal cardiovascular homeostasis.

Here, we report that maternal allopurinol treatment in late gestation ovine pregnancy has significant in vivo effects on umbilical blood flow and the cardiovascular system of the mother and fetus by altering NO and β1‐adrenergic mechanisms.

The evidence suggests that xanthine oxidase has an important role in basal cardiovascular function in the fetus during late gestation. Therefore, further research is warranted before safe clinical application of maternal allopurinol during pregnancy in humans.
Augmented cholesterol absorption and sarcolemmal sterol enrichment slow small intestinal transit in mice, contributing to cholesterol cholelithogenesis
Authors: Xie Meimin , Kotecha Vijay R. , Andrade Jon David P. , Fox James G. , Carey Martin C.
Published: February 2012

Key points 

Peristaltic function of the small intestine is compromised in cholelithogenic humans and in animal models of cholesterol gallstones.

In a mouse gallstone model fed a cholesterol‐ and cholic acid‐enriched diet, we show that slowing of small intestinal transit is due to absorption of excess cholesterol molecules from the upper small intestine followed by their incorporation into sarcolemmal membranes of smooth muscle cells.

Blocking cholesterol absorption with ezetimibe (Zetia), an inhibitor of intestinal sterol transport, prevents cholesterol enrichment of sarcolemmal membranes and normalizes the motility disorder.

Although the primary source of intestinal cholesterol in mice is the lithogenic diet, in most cholesterol gallstone‐prone humans, the small intestine is flooded continuously with an abundance of liver‐secreted cholesterol molecules via bile.

Our findings imply that small intestinal hypomotility will amplify the cholelithogenic state because of hyperabsorption of cholesterol and ‘secondary’ bile salt synthesis by the gut's anaerobic microbiota.
Histone deacetylase 6 gates the synaptic action of acute stress in prefrontal cortex
Authors: Lee Janine B. , Wei Jing , Liu Wenhua , Cheng Jia , Feng Jian , Yan Zhen
Published: February 2012

Key points 

Acute stress, via glucocorticoid receptors (GRs), enhances glutamatergic signalling in the prefrontal cortex, a region responsible for high‐order cognitive functions.

We found that inhibition or knockdown of histone deacetylase 6 (HDAC6) blocked the enhancement of glutamatergic signalling by acute stress.

Inhibition or knockdown of the GR chaperone protein HSP90 (a substrate of HDAC6) produced a similar blockade of the acute stress‐induced enhancement of glutamatergic signalling.

These results suggest that HDAC6 is a key molecule regulating the synaptic effects of acute stress in the prefrontal cortex.
Measurement of cAMP in an Undergraduate Teaching Laboratory, Using ALPHAscreen Technology
Authors: Bartho Joseph D. , Ly Kien , Hay Debbie L.
Published: February 2012

Students measure the changes in cyclic AMP, a second messenger molecule, with a light-based assay.
Science Signaling
Podcast: 14 February 2012
Authors: Peters-Golden Marc , VanHook Annalisa M.
Published: February 2012

The protein phosphatase activity of PTEN impairs macrophage phagocytosis of a fungal pathogen by promoting actin depolymerization.
Challenging the Mushroom Bodies
Authors: Stern Peter R.
Published: February 2012

Protein synthesis underlying olfactory memory storage takes place outside the mushroom body—the site of memory storage.
Keeping a Kinase in Check
Authors: Vinson Valda
Published: February 2012

Details are revealed as to how cyclic adenosine monophosphate (cAMP) binding causes dissociation and activation of cAMP-dependent protein kinase.
A Coincidence Detector with a Memory
Authors: Gough Nancy R.
Published: February 2012

The transcription factor NFAT converts a short calcium signal into a long-term, all-or-none gene expression response.
Screening for Interactions
Authors: Foley John F.
Published: February 2012

An RNAi-based screen reveals that the energy-sensing protein AMPK is acetylated by p300 and deacetylated by HDAC1.
Mycobacterium tuberculosis Population Structure Determines the Outcome of Genetics-Based Second-Line Drug Resistance Testing
Authors: Streicher E. M. , Bergval I. , Dheda K. , Böttger E. C. , Gey van Pittius N. C. , Bosman M. , Coetzee G. , Anthony R. M. , van Helden P. D. , Victor T. C. , Warren R. M.
Published: February 2012

The global emergence of multidrug-resistant tuberculosis has highlighted the need for the development of rapid tests to identify resistance to second-line antituberculosis drugs. Resistance to fluoroquinolones and aminoglycosides develops through nonsynonymous single nucleotide polymorphisms in the
gyrA
and
gyrB
genes and the
rrs
gene, respectively. Using DNA sequencing as the gold standard for the detection of mutations conferring resistance, in conjunction with spoligotyping, we demonstrated heteroresistance in 25% and 16.3% of
Mycobacterium tuberculosis
isolates resistant to ofloxacin and amikacin, respectively. Characterization of follow-up isolates from the same patients showed that the population structure of clones may change during treatment, suggesting different phases in the emergence of resistance. The presence of underlying mutant clones was identified in isolates which failed to show a correlation between phenotypic resistance and mutation in the
gyrA
or
rrs
gene. These clones harbored previously described mutations in either the
gyrA
or
rrs
gene, suggesting that rare mutations conferring resistance to ofloxacin or amikacin may not be as important as was previously thought. We concluded that the absence of a correlation between genotypic and phenotypic resistance implies an early phase in the emergence of resistance within the patient. Thus, the diagnostic utility of genetics-based drug susceptibility tests will depend on the proportion of patients whose bacilli are in the process of acquiring resistance in the study setting. These data have implications for the interpretation of molecular and microbiological diagnostic tests for patients with drug-susceptible and drug-resistant tuberculosis who fail to respond to treatment and for those with discordant results.
An Isoniazid Analogue Promotes Mycobacterium tuberculosis-Nanoparticle Interactions and Enhances Bacterial Killing by Macrophages
Authors: de Faria Tatiany J. , Roman Mariane , de Souza Nicole M. , De Vecchi Rodrigo , de Assis João Vitor , dos Santos Ana Lúcia Gomes , Bechtold Ivan H. , Winter Nathalie , Soares Maurilio José , Silva Luciano Paulino , De Almeida Mauro V. , Báfica André
Published: February 2012

Nanoenabled drug delivery systems against tuberculosis (TB) are thought to control pathogen replication by targeting antibiotics to infected tissues and phagocytes. However, whether nanoparticle (NP)-based carriers directly interact with
Mycobacterium tuberculosis
and how such drug delivery systems induce intracellular bacterial killing by macrophages is not defined. In the present study, we demonstrated that a highly hydrophobic citral-derived isoniazid analogue, termed JVA, significantly increases nanoencapsulation and inhibits
M. tuberculosis
growth by enhancing intracellular drug bioavailability. Importantly, confocal and atomic force microscopy analyses revealed that JVA-NPs associate with both intracellular
M. tuberculosis
and cell-free bacteria, indicating that NPs directly interact with the bacterium. Taken together, these data reveal a nanotechnology-based strategy that promotes antibiotic targeting into replicating extra- and intracellular mycobacteria, which could actively enhance chemotherapy during active TB.
Crystal Structures of KPC-2 β-Lactamase in Complex with 3-Nitrophenyl Boronic Acid and the Penam Sulfone PSR-3-226
Authors: Ke Wei , Bethel Christopher R. , Papp-Wallace Krisztina M. , Pagadala Sundar Ram Reddy , Nottingham Micheal , Fernandez Daniel , Buynak John D. , Bonomo Robert A. , van den Akker Focco
Published: February 2012

Class A carbapenemases are a major threat to the potency of carbapenem antibiotics. A widespread carbapenemase, KPC-2, is not easily inhibited by β-lactamase inhibitors (i.e., clavulanic acid, sulbactam, and tazobactam). To explore different mechanisms of inhibition of KPC-2, we determined the crystal structures of KPC-2 with two β-lactamase inhibitors that follow different inactivation pathways and kinetics. The first complex is that of a small boronic acid compound, 3-nitrophenyl boronic acid (3-NPBA), bound to KPC-2 with 1.62-Å resolution. 3-NPBA demonstrated a

K
m

value of 1.0 ± 0.1 μM (mean ± standard error) for KPC-2 and blocks the active site by making a reversible covalent interaction with the catalytic S70 residue. The two boron hydroxyl atoms of 3-NPBA are positioned in the oxyanion hole and the deacylation water pocket, respectively. In addition, the aromatic ring of 3-NPBA provides an edge-to-face interaction with W105 in the active site. The structure of KPC-2 with the penam sulfone PSR-3-226 was determined at 1.26-Å resolution. PSR-3-226 displayed a

K
m

value of 3.8 ± 0.4 μM for KPC-2, and the inactivation rate constant (
k
inact
) was 0.034 ± 0.003 s
−1
. When covalently bound to S70, PSR-3-226 forms a
trans
-enamine intermediate in the KPC-2 active site. The predominant active site interactions are generated via the carbonyl oxygen, which resides in the oxyanion hole, and the carboxyl moiety of PSR-3-226, which interacts with N132, N170, and E166. 3-NPBA and PSR-3-226 are the first β-lactamase inhibitors to be trapped as an acyl-enzyme complex with KPC-2. The structural and inhibitory insights gained here could aid in the design of potent KPC-2 inhibitors.
Pharmacokinetics of Sequential Doses of Capreomycin Powder for Inhalation in Guinea Pigs
Authors: Garcia-Contreras L. , Muttil Pavan , Fallon John K. , Kabadi Mohan , Gerety Robert , Hickey Anthony J.
Published: February 2012

The global control of tuberculosis (TB) is at risk by the spread of multidrug-resistant TB (MDR TB). Treatment of MDR TB is lengthy and involves injected drugs, such as capreomycin, that have severe side effects. It was previously reported that a single daily dose of inhaled capreomycin had a positive effect on the bacterial burden of TB-infected guinea pigs. The modest effect observed was possibly due to a dose that resulted in insufficient time of exposure to therapeutic systemic and local levels of the drug. In order to determine the length of time that systemic and local drug concentrations are above therapeutic levels during the treatment period, the present study investigated the disposition of capreomycin powders after sequential pulmonary administration of doses of 20 mg/kg of body weight. Capreomycin concentrations in bronchoalveolar lavage fluid and lung tissue of animals receiving a series of one, two, or three doses of capreomycin inhalable powder were significantly higher (50- to 100-fold) at all time points than plasma concentrations at the same time points or those observed in animals receiving capreomycin solution by intramuscular (i.m.) injection (10- to 100-fold higher). Notably, at the end of each dosing period, capreomycin concentrations in the lungs were approximately 100-fold higher than those in plasma and severalfold higher than the MIC, suggesting that sufficient capreomycin remains in the lung environment to kill
Mycobacterium tuberculosis
. No accumulation of capreomycin powder was detected in the lungs after 3 pulmonary doses. These results indicate that the systemic disposition of capreomycin after inhalation is the same as when injected i.m. with the advantage that higher drug concentrations are present at all times in the lungs, the primary site of infection.