bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term outcomes of passive bullying during childhood: Suicide attempts, victimization and offending
Authors: Staubli Silvia , Killias Martin
Published: September 2011

The long-term effects of bullying at elementary school have attracted increasing interest in recent years. The present study is based on a cross-sectional survey of over 21,000 young Swiss men. The sample covered about 70 percent of the cohort of Swiss males drafted into the Army in 1997, and born in or around 1977. The instrument covered many retrospective items, including experiencing bullying before age 12 and conduct problems including violent victimization and suicide attempts in the recent past. The results show that victims of bullying during childhood are still negatively affected in young adulthood. A causal role of bullying experiences in these long-term outcomes is plausible, although alternative explanations cannot be ruled out.
Do people comply with the law because they fear getting caught?
Authors: Wikström Per-Olof H. , Tseloni Andromachi , Karlis Dimitris
Published: September 2011

Do people comply with the law because they fear the consequences? Guided by the theoretical framework of Situational Action Theory we argue that most people abide by the law not because they fear the consequences but because they do not perceive crime as an ‘action alternative’. We propose that the potential influence of threats of punishment on people’s law abidance is specific to those who regularly are motivated and consider committing acts of crime. Using data from the Peterborough Adolescent and Young Adult Development Study (PADS+) we empirically explore the relationships between crime propensity, deterrence perceptions and crime involvement for four specific types of crime: shoplifting, theft from cars, vandalism and assault. The findings support the notion that the influence of deterrence perceptions on an individual’s crime involvement is dependent on his or her crime propensity. Moreover, and crucially, results suggest that deterrence perceptions are largely irrelevant for those who lack a propensity to commit acts of crime (or specific acts of crime).
The Role of Chief Executive Officer
Authors: Glick Margaret B.
Published: September 2011

The chief executive officer (CEO) holds one of the most important and influential roles in an organization, yet research on the role remains ambiguous, conflicted, and outdated. The purpose of this study was to address the gap between what is reported in the literature and what is known in current practice on the role of CEO. A major goal of this research was to use the insights provided by CEOs to improve our general understanding of the major roles played by CEOs and how they generally allocate their time in various critical functions. This research was also intended to serve those responsible for identifying CEO candidates, recruiting CEOs, coaching CEOs, sustaining an organization’s leadership system, and developing performance matrices for boards of directors who are ultimately responsible for making sure the CEO is effective and efficient.
The West Virginia Prescription Drug Abuse Quitline
Authors: White Rebecca J. , Zullig Keith J. , Lander Laura , Shockley Clara , Pack Robert , Sullivan Carl
Published: September 2011

The West Virginia Prescription Drug Abuse Quitline (WVPDAQ) is a resource that offers education and support to individuals and families affected by prescription drug abuse. The WVPDAQ began functioning September 11, 2008, through the use of mobile phone and laptop technology. Although some helplines and quitlines use some aspects of remote technology, most function through traditional call center and landline technology, making the WVPDAQ unique. This article describes the process evaluation of the WVPDAQ and outlines both the positive findings and challenges faced by the WVPDAQ. Lessons learned and future recommendations for remote quitline endeavors are also presented. It is hoped that the experiences and information regarding the WVPDAQ presented can provide best-practice insight for public health practitioners and evaluation personnel who are considering using alternative technologies to deliver quitline services.
Negative Lobbying and Policy Outcomes
Authors: McKay Amy
Published: September 2011

What explains policy outcomes? Using a data set containing the actions and assessments of 776 lobbyists working closely on 77 policy proposals, combined with newly collected data on each proposal, I show that the intensity of lobbying against a proposal is a powerful predictor of the likelihood that the proposal is adopted in Congress or a federal agency. This negative lobbying is more effective than positive lobbying: it takes 3.5 lobbyists working for a new proposal to counteract the effect of just one lobbyist against it. Negative lobbying is a more important predictor of the policy outcome than the level of conflict, the preference of the majority of lobbyists, and differences in interest group resources. Several institutional factors—presidential support for the measure, congressional polarization, and whether the proposal was initiated by a federal agency—are found to affect policy outcomes, but only presidential support matters more than negative lobbying.
Validity, Reliability, and Feasibility of Clinical Staging Scales in Dementia
Authors: Olde Rikkert Marcel G. M. , Tona Klodiana Daphne , Janssen Lieneke , Burns Alistair , Lobo Anatonio , Robert Philippe , Sartorius Norman , Stoppe Gabriela , Waldemar Gunhild
Published: September 2011

New staging systems of dementia require adaptation of disease management programs and adequate staging instruments. Therefore, we systematically reviewed the literature on validity and reliability of clinically applicable, multidomain, and dementia staging instruments. A total of 23 articles describing 12 staging instruments were identified (N = 6109 participants, age 65-87). Reliability was studied in most (91%) of the articles and was judged moderate to good. Approximately 78% of the articles evaluated concurrent validity, which was good to very good, while discriminant validity was assessed in only 25%. The scales can be applied in ±15 minutes. Clinical Dementia Rating (CDR), Global Deterioration scale (GDS), and Functional Assessment Staging (FAST) have been monitored on reliability and validity, and the CDR currently is the best-evidenced scale, also studied in international perspective, and is available in 14 languages. Taking into account the increasing differentiation of Alzheimer’s disease in preclinical and predementia stages, there is an urgent need for global rating scales to be refined as well.
Concomitant Reconstruction of Infrarenal Aorta and Inferior Vena Cava After En Bloc Resection of Retroperitoneal Rhabdomyosarcoma
Authors: Anaya-Ayala Javier E. , Cheema Zulfiqar F. , Davies Mark G. , Lumsden Alan B. , Reardon Michael J.
Published: September 2011

Adult paratesticular rhabdomyosarcoma (PRMS) with invasion of the retroperitoneum and involvement of the infrarenal aorta and inferior vena cava (IVC) is rare. We describe a 23-year-old male diagnosed with PRMS in 2008, previously treated with right orchiectomy, chemotherapy, and radiation, who presented with new onset of lower back pain. Computed tomography (CT) scan revealed a 4.8 × 4.2 cm mass involving both the infrarenal aorta and the IVC. We resected the tumor en bloc with in situ reconstruction of the aorta utilizing a Dacron graft and the IVC with a bovine pericardium roll graft. His postoperative period was uneventful, and he was discharged on postoperative day 6 in stable condition. At 2-month follow-up, the patient recovered well from the surgery, patent grafts on CT scan with no clinical signs of lower extremity ischemia or edema, and he continues to receive cycles of chemotherapy.
Evaluation of visual cues of three-dimensional virtual environments for helicopter simulators
Authors: Çetin Yasemin , Yılmaz Erdal , Çetin Yasemin Yardımcı
Published: September 2011

Visual cues are an essential part of helicopter flight simulators. The required cues for hover are particularly large, due to closeness to the ground and small movements. However, the research on low-altitude helicopter flight is limited. In this research, the density and height of the three-dimensional (3D) objects in the scene are analysed to find their effect on hovering and low-altitude helicopter flight. An experiment is conducted using a personal computer-based flight simulator on 10 professional military pilots. The results revealed that 3D object density and 3D object height affect both horizontal and vertical hovering performance. In hover and low-altitude flight, altitude control is positively affected by smaller object height. Paradoxically, the pilots preferred the scenes composed of tall and mixture objects. Pilot distance estimation was significantly affected by the knowledge of both object density and object height, but these factors do not individually improve distance estimation.
Burst Strength Testing of Porcine Intestinal Anastomoses Following Negative Pressure Therapy
Authors: Norbury Kenneth C. , Kilpadi Deepak V. , Collins Barbara A. , Cunningham Mark R.
Published: September 2011

The effect of negative pressure therapy (NPT; The ABThera™ Open Abdomen Negative Pressure Therapy System, KCI USA, Inc., San Antonio, TX) on the integrity of small intestinal anastomoses was evaluated using in situ burst strength testing in a domestic pig model. In each of 3 swine, 8 anastomoses were created, 4 using sutures and 4 using staples. After 24 hours of continuous NPT, each anastomosis was subjected to burst strength testing in situ. Mean ratios of burst strength of sutured anastomoses to baseline intraluminal pressure were 9.0 to 10.9. Stapled anastomoses had significantly lower burst strength than sutured anastomoses, but mean values were still at least 4.6 times greater than baseline. No differences were seen between anastomoses that were located in close proximity with treatment and those remotely placed or when measured with negative pressure on or off at burst assessment. NPT had no acute adverse effect on intestinal anastomoses in swine.
Single Port Access Surgery With a Novel Port Camera System
Authors: Terry Benjamin S. , Schoen Jonathan , Mills Zachary , Rentschler Mark E.
Published: September 2011

In this work, the authors designed, built, and tested a novel port camera system for single port access (SPA) laparoscopic surgery. This SPA Port Camera device integrates the monitor, laparoscopic camera, and light source into an inexpensive, portable cannula port. The device uses a 2-channel SPA port inserted through an umbilical incision, similar to traditional SPA. After insertion into a channel, the device deploys a small camera module and LED lamp in vivo. An integrated, on-patient LCD provides the view of the surgical site. The design intent of the port camera is to enhance SPA by ( a) reducing the size of the SPA port through the elimination of the dedicated laparoscope channel; ( b) reducing equipment cost by integrating an inexpensive CMOS sensor and LED lamp at the port tip; ( c) eliminating the need for an assistant who operates the laparoscope; and ( d) mechanically coupling the camera, tool port, and on-patient LCD screen. The effectiveness of the device was evaluated by comparing the video performance with a leading industry laparoscope and by performing a user evaluation study and live porcine surgery with the device. Effectiveness of the device was mixed. Overall video system performance of the device is better than an industry standard high-definition laparoscope, implying that significant cost savings over a traditional system are possible. Participant study results suggest that simulated laparoscopic tasks are as efficient with the SPA Port Camera as they are with a typical SPA configuration. However, live surgery revealed several shortcomings of the SPA Port Camera.
Single-Center Experience in Systemic Stress and Short-Term Morbidity of Single-Incision Cholecystectomy
Authors: Froghi Farid , Sodergren Mikael H. , Wright Victoria J. , Coomber Ross , Courtney Alan P. , Darzi Ara , Paraskeva Paraskevas
Published: September 2011

Single-incision laparoscopic surgery (SILS) aims to reduce the number and size of skin incisions. The authors compared systemic stress and perioperative outcome of SILS and laparoscopic (LAP) cholecystectomy. Twenty-nine subjects (8 males and 21 females; mean age = 47 years; mean body mass index = 27) were included in the study. There was no statistical difference in mean operative time (LAP = 89 minutes; SILS = 113 minutes; P = ns), and no intraoperative complications were reported. There were no statistically significant differences observed in white cell count, C-reactive protein, interleukin-6, and tumor necrosis factor-α between SILS and LAP groups. The mean hospital length of stay (LAP = 1.8 days; SILS = 1.4 days) and Visual Analogue Scale scores for pain at 6 hours (LAP = 5.14; SILS = 4.46) and 24 hours (LAP = 3.9; SILS = 2.815) were similar with no perioperative morbidity. These results suggest that the systemic stress response in LAP and SILS cholecystectomy does not appear to be significantly different. SILS cholecystectomy appears safe with no perioperative morbidity or complications encountered in this series.
Severe ulnar nerve entrapment at the elbow: functional outcome after minimally invasive in situ decompression
Authors: Karthik K. , Nanda R. , Storey S. , Stothard J.
Published: September 2011

The role of in situ decompression in patients with severe ulnar nerve compression is still controversial. Thirty patients with severe ulnar nerve compression confirmed clinically and electrophysiologically underwent simple decompression. The mean age of the patients was 58 (range 26–87) years. Through incisions ≤4 cm the nerves were fully visualized and decompressed. Outcome was measured prospectively using Modified Bishop’s score (BS), grip and pinch strengths and two-point discrimination (2PD). Significant improvement in power (p = 0.01) and pinch grip (p = 0.001) was noted at 1 year. The grip strength continued to improve up to 1 year. According to the BS, 24 patients (80%) had good to excellent results at 1 year. Minimally invasive in situ decompression is technically simple, safe and gives good results in patients with severe nerve compression. The BS and 2PD were more reliable than grip strength in assessing these patients at follow-up.
Patient-reported outcomes after Silastic replacement of the trapezium for osteoarthritis
Authors: Burke N. G. , Walsh J. , Moran C. J. , Cousins G. , Molony D. , Kelly E. P.
Published: September 2011

This retrospective study evaluated 69 Swanson trapezium replacements performed between 1990 and 2009 for trapeziometacarpal osteoarthritis in 58 patients. Pain and function were assessed using the Michigan Hand Questionnaire and the Disability of the Arm, Shoulder and Hand questionnaire. Patients had a mean age of 62 years at the time of surgery, with a mean time of 7.7 years (range 9 months to 19 years) from surgery to follow-up interview. There was no association between outcome scores and the length of follow-up, suggesting that the results are maintained over time (Spearman’s rank correlation test < ±0.2). Scores for activities of daily living and work-related activities were higher when surgery was on the dominant hand ( p < 0.05). Silicone trapezium replacement remains a good option for patients with painful trapeziometacarpal osteoarthritis that has not responded to nonoperative management.
Management of colonic diverticular disease with poorly absorbed antibiotics and other therapies
Authors: Sopeña Federico , Lanas Angel
Published: September 2011

Colonic diverticular disease is common in Western countries and its prevalence increases with age. The large majority of patients (80–85%) will remain entirely asymptomatic throughout their life. In symptomatic cases, most patients will have diverticulosis without inflammation while the remainder will have diverticulitis with or without complications. About 1–2% will require hospitalization and 0.5% will require surgery. Factors predicting the development of symptoms remain to be identified. However, it is generally recognized that diverticular disease is probably related to complex interactions between colon structure, intestinal motility, diet, and genetic features. Epidemiologic studies have demonstrated an association between diverticulosis and diets that are low in fiber and high in refined carbohydrates. Although the causes of symptom development are still unclear, it is thought that previous episodes of intestinal inflammation may play a role. Changes in intestinal microflora could be one of the putative mechanisms responsible for low-grade inflammation. In patients with uncomplicated diverticulosis, a diet abundant in fruit and vegetables is recommended. The current therapeutic approaches in preventing recurrence of symptoms are based on nonabsorbable antibiotics, mesalazine, and/or probiotics. Cyclic rifaximin administration seems to be an adequate approach to relieving symptoms and preventing acute diverticulitis in patients with symptomatic diverticulosis.
The cognitive impact of antiepileptic drugs
Authors: Eddy Clare M. , Rickards Hugh E. , Cavanna Andrea E.
Published: September 2011

Effective treatment of epilepsy depends on medication compliance across a lifetime, and studies indicate that drug tolerability is a significant limiting factor in medication maintenance. Available antiepileptic drugs (AEDs) have the potential to exert detrimental effects on cognitive function and therefore compromise patient wellbeing. On the other hand, some agents may serve to enhance cognitive function. In this review paper, we highlight the range of effects on cognition linked to a variety of newer and older AEDs, encompassing key alterations in both specific executive abilities and broader neuropsychological functions. Importantly, the data reviewed suggest that the effects exerted by an AED could vary depending on both patient characteristics and drug-related variables. However, there are considerable difficulties in evaluating the available evidence. Many studies have failed to investigate the influence of patient and treatment variables on cognitive functioning. Other difficulties include variation across studies in relation to design, treatment group and assessment tools, poor reporting of methodology and poor specification of the cognitive abilities assessed. Focused and rigorous experimental designs including a range of cognitive measures assessing more precisely defined abilities are needed to fill the gaps in our knowledge and follow up reported patterns in the literature. Longitudinal studies are needed to improve our understanding of the influence of factors such as age, tolerance and the stability of cognitive effects. Future trials comparing the effects of commonly prescribed agents across patient subgroups will offer critical insight into the role of patient characteristics in determining the cognitive impact of particular AEDs.
Improved responsiveness and reduced sample size requirements of PROMIS physical function scales with item response theory
Authors: Fries James F , Krishnan Eswar , Rose Matthias , Lingala Bharathi , Bruce Bonnie
Published: September 2011

Introduction

The Health Assessment Questionnaire Disability Index (HAQ) and the SF-36 PF-10, among other instruments, yield sensitive and valid Disability (Physical Function) endpoints. Modern techniques, such as Item Response Theory (IRT), now enable development of more precise instruments using improved items. The NIH Patient Reported Outcomes Measurement Information System (PROMIS) is charged with developing improved IRT-based tools. We compared the ability to detect change in physical function using original (Legacy) instruments with Item-Improved and PROMIS IRT-based instruments.

Methods

We studied two Legacy (original) Physical Function/Disability instruments (HAQ, PF-10), their item-improved derivatives (Item-Improved HAQ and PF-10), and the IRT-based PROMIS Physical Function 10- (PROMIS PF 10) and 20-item (PROMIS PF 20) instruments. We compared sensitivity to detect 12-month changes in physical function in 451 rheumatoid arthritis (RA) patients and assessed relative responsiveness using P-values, effect sizes (ES), and sample size requirements.

Results

The study sample was 81% female, 87% Caucasian, 65 years of age, had 14 years of education, and had moderate baseline disability. All instruments were sensitive to detecting change (< 0.05) in physical function over one year. The most responsive instruments in these patients were the Item-Improved HAQ and the PROMIS PF 20. IRT-improved instruments could detect a 1.2% difference with 80% power, while reference instruments could detect only a 2.3% difference (P < 0.01). The best IRT-based instruments required only one-quarter of the sample sizes of the Legacy (PF-10) comparator (95 versus 427). The HAQ outperformed the PF-10 in more impaired populations; the reverse was true in more normal populations. Considering especially the range of severity measured, the PROMIS PF 20 appears the most responsive instrument.

Conclusions

Physical Function scales using item improved or IRT-based items can result in greater responsiveness and precision across a broader range of physical function. This can reduce sample size requirements and thus study costs.
Binding immunoglobulin protein resolves rheumatoid synovitis: a xenogeneic study using rheumatoid arthritis synovial membrane transplants in SCID mice
Authors: Yoshida Kaoru , Ochiai Akira , Matsuno Hiroaki , Panayi Gabriel S , Corrigall Valerie M
Published: September 2011

Introduction

Binding immunoglobulin protein (BiP) has previously shown powerful anti-inflammatory properties in the collagen-induced arthritis (CIA) model, where a single dose of BiP has proved to be both a long-term prophylactic and therapeutic. In both CIA and human in vitro studies, BiP induced regulatory T cells. The present investigation looked at the anti-inflammatory effect of BiP on inflamed human synovial tissue transplanted into severe combined immunodeficient mice (SCID), a chimaeric in vivo model previously used to test the efficacy of biologic therapies.

Methods

Rheumatoid arthritis synovial membrane (RASM) was engrafted into SCID mice. Following successful engraftment, mice were intravenously injected with BiP or human serum albumin in the presence or absence of anti-IL-10 mAb. Twelve days later the grafts were removed for analysis and human cytokines in the sera were quantified by ELISA. The extent of residual inflammatory cellular infiltrate in the synovial explants was determined by weight of the explants.

Results

The RASM transplants from mice treated with BiP showed visual reduction in cellular infiltrate and downregulation of all quantifiable features of inflammation as assessed by the Koizumi or Rooney histological criteria. Also downregulated were HLA-DR, CD86, IL-6 and TNFα expression as assessed by immunohistology. ELISA detected significantly less human IL-6 circulating in the BiP-treated mouse serum. After removal of transplanted tissue 12 days post administration of BiP, the RASM explants from the BiP-treated SCID mice weighed significantly less, indicating a suppression of tissue inflammation. Mice given concomitant neutralising anti-IL-10 antibody and BiP showed no such suppression.

Conclusions

BiP has anti-inflammatory properties partially dependent on the downregulation of HLA-DR and co-stimulatory molecules and the predominant production of IL-10.
Suppression of apoptosis inhibitor c-FLIP selectively eliminates breast cancer stem cell activity in response to the anti-cancer agent, TRAIL
Authors: Piggott Luke , Omidvar Nader , Pérez Salvador Martí , Eberl Matthias , Clarkson Richard WE
Published: September 2011

Introduction

It is postulated that breast cancer stem cells (bCSCs) mediate disease recurrence and drive formation of distant metastases - the principal cause of mortality in breast cancer patients. Therapeutic targeting of bCSCs, however, is hampered by their heterogeneity and resistance to existing therapeutics. In order to identify strategies to selectively remove bCSCs from breast cancers, irrespective of their clinical subtype, we sought an apoptosis mechanism that would target bCSCs yet would not kill normal cells. Suppression of the apoptosis inhibitor cellular FLICE-Like Inhibitory Protein (c-FLIP) partially sensitizes breast cancer cells to the anti-cancer agent Tumour Necrosis Factor-Related Apoptosis Inducing Ligand (TRAIL). Here we demonstrate in breast cancer cell lines that bCSCs are exquisitely sensitive to the de-repression of this pro-apoptotic pathway, resulting in a dramatic reduction in experimental metastases and the loss of bCSC self-renewal.

Methods

Suppression c-FLIP was performed by siRNA (FLIPi) in four breast cancer cell lines and by conditional gene-knockout in murine mammary glands. Sensitivity of these cells to TRAIL was determined by complementary cell apoptosis assays, including a novel heterotypic cell assay, while tumour-initiating potential of cancer stem cell subpopulations was determined by mammosphere cultures, aldefluor assay and in vivo transplantation.

Results

Genetic suppression of c-FLIP resulted in the partial sensitization of TRAIL-resistant cancer lines to the pro-apoptotic effects of TRAIL, irrespective of their cellular phenotype, yet normal mammary epithelial cells remained refractory to killing. While 10% to 30% of the cancer cell populations remained viable after TRAIL/FLIPi treatment, subsequent mammosphere and aldefluor assays demonstrated that this pro-apoptotic stimulus selectively targeted the functional bCSC pool, eliminating stem cell renewal. This culminated in an 80% reduction in primary tumours and a 98% reduction in metastases following transplantation. The recurrence of residual tumour initiating capacity was consistent with the observation that post-treated adherent cultures re-acquired bCSC-like properties in vitro. Importantly however this recurrent bCSC activity was attenuated following repeated TRAIL/FLIPi treatment.

Conclusions

We describe an apoptotic mechanism that selectively and repeatedly removes bCSC activity from breast cancer cell lines and suggest that a combined TRAIL/FLIPi therapy could prevent metastatic disease progression in a broad range of breast cancer subtypes.
Improved ICU design reduces acquisition of antibiotic-resistant bacteria: a quasi-experimental observational study
Authors: Levin Phillip D , Golovanevski Mila , Moses Allon E , Sprung Charles L , Benenson Shmuel
Published: September 2011

Introduction

The role of ICU design and particularly single-patient rooms in decreasing bacterial transmission between ICU patients has been debated. A recent change in our ICU allowed further investigation.

Methods

Pre-move ICU-A and pre-move ICU-B were open-plan units. In March 2007, ICU-A moved to single-patient rooms (post-move ICU-A). ICU-B remained unchanged (post-move ICU-B). The same physicians cover both ICUs. Cultures of specified resistant organisms in surveillance or clinical cultures from consecutive patients staying >48 hours were compared for the different ICUs and periods to assess the effect of ICU design on acquisition of resistant organisms.

Results

Data were collected for 62, 62, 44 and 39 patients from pre-move ICU-A, post-move ICU-A, pre-move ICU-B and post-move ICU-B, respectively. Fewer post-move ICU-A patients acquired resistant organisms (3/62, 5%) compared with post-move ICU-B patients (7/39, 18%; P = 0.043, P = 0.011 using survival analysis) or pre-move ICU-A patients (14/62, 23%; P = 0.004, P = 0.012 on survival analysis). Only the admission period was significant for acquisition of resistant organisms comparing pre-move ICU-A with post-move ICU-A (hazard ratio = 5.18, 95% confidence interval = 1.03 to 16.06; P = 0.025). More antibiotic-free days were recorded in post-move ICU-A (median = 3, interquartile range = 0 to 5) versus post-move ICU-B (median = 0, interquartile range = 0 to 4; P = 0.070) or pre-move ICU-A (median = 0, interquartile range = 0 to 4; P = 0.017). Adequate hand hygiene was observed on 140/242 (58%) occasions in post-move ICU-A versus 23/66 (35%) occasions in post-move ICU-B (P < 0.001).

Conclusions

Improved ICU design, and particularly use of single-patient rooms, decreases acquisition of resistant bacteria and antibiotic use. This observation should be considered in future ICU design.
Human and Quail Aromatase Activity Is Rapidly and Reversibly Inhibited by Phosphorylating Conditions
Authors: Charlier Thierry D. , Harada Nobuhiro , Balthazart Jacques , Cornil Charlotte A.
Published: September 2011

Besides their slow genomic actions, estrogens also induce rapid physiological responses. To be functionally relevant, these effects must be associated with rapid changes in local concentrations of estrogens. Rapid changes in aromatase activity (AA) controlled by calcium-dependent phosphorylations of the enzyme can alter in a rapid manner local estrogen concentrations, but so far this mechanism was identified only in the avian (quail) brain. We show here that AA is also rapidly down-regulated by phosphorylating conditions in quail ovary homogenates and in various cell lines transfected with human aromatase (HEK 293, Neuro2A, and C6). Enzymatic activity was also rapidly inhibited after depolarization of aromatase-expressing HEK 293 cells with 100 mm KCl, and activity was fully restored when cells returned to control conditions. Western blot analysis demonstrated that the reduction of enzymatic activity is not due to protein degradation. We next investigated by site-directed mutagenesis the potential implication in the control of AA of specific aromatase residues identified by bioinformatic analysis. Mutation of the amino acids S118, S247, S267, T462, T493, or S497 to alanine, alone or in combination, did not block the rapid inhibition of enzymatic activity induced by phosphorylating conditions, but basal AA was markedly decreased in the S118A mutant. Altogether, these results demonstrate that the rapid inhibition of AA is a widespread and fully reversible process and that phosphorylation of specific residues modulate AA. These processes provide a new general mechanism by which local estrogen concentration can be rapidly altered in the brain and other tissues.
Chronic Central Leptin Decreases Food Intake and Improves Glucose Tolerance in Diet-Induced Obese Mice Independent of Hypothalamic Malonyl CoA Levels and Skeletal Muscle Insulin Sensitivity
Authors: Keung Wendy , Palaniyappan Arivazhagan , Lopaschuk Gary D.
Published: September 2011

Although acute leptin administration in the hypothalamus decreases food intake and increases peripheral energy metabolism, the peripheral actions of central chronic leptin administration are less understood. In this study, we investigated what effects chronic (7 d) intracerebroventricular (ICV) administration of leptin has on energy metabolism and insulin sensitivity in diet-induced obese mice. C57/BL mice were fed a low-fat diet (LFD; 10% total calories) or high-fat diet (HFD; 60% total calories) for 8 wk after which leptin was administered ICV for 7 consecutive days. Mice fed a HFD showed signs of insulin resistance, as evidenced by an impaired glucose tolerance test. Chronic leptin treatment resulted in a decrease in food intake and body weight and normalization of glucose clearance but no improvement in insulin sensitivity. Chronic ICV leptin increased hypothalamic signal transducer and activator of transcription-3 and AMP-activated protein kinase phosphorylation but did not change hypothalamic malonyl CoA levels in HFD fed and LFD-fed mice. In the gastrocnemius muscles, the levels of malonyl CoA in both leptin-treated groups were lower than their respective control groups, suggesting an increase in fatty acid oxidation. However, only in the muscles of ICV leptin-treated LFD mice was there a decrease in lipid metabolites including diacylglycerol, triacylglycerol, and ceramide. Our results suggest that chronic ICV leptin decreases food consumption and body weight via a mechanism different from acute ICV leptin administration. Although chronic ICV leptin treatment in HFD mice improves glucose tolerance, this occurs independent of changes in insulin sensitivity in the muscles of HFD mice.
Doctors attitudes to a culture of safety: lessons for organizational change
Authors: Grant Paul
Published: September 2011

Healthcare is a highly regulated environment. This has driven what could be characterized as a paper-safe approach, whereby organizations are required to demonstrate to a multiplicity of regulators, inspectorates and accrediting bodies that they are paper safe. However, for many organizations, this has not produced a system which is actually patient safe; rather it has in practice operated as a parallel system that does not reflect the true state of safety. This project looks at a quality improvement and patient safety programme and critically asks the question of whether it is flawed because of failure to address issues surrounding Doctors and cultural change. We used Johnson & Schole's cultural web framework to explore the attitudes of junior doctors towards a patient safety and quality improvement programme. Data collection was through the use of focus groups backed up with quantitative data from a web based questionnaire survey. It has been demonstrated that Doctors represent a dominant sub-culture within the NHS and their beliefs, attitudes and value are often at odds or unrecognized by senior healthcare managers. Unless the cultural differences are adequately addressed then transformational change projects such as ‘Best and Safest Care’ are unlikely to succeed. A better understanding of the organizational context allows for more appropriate change interventions to be developed.
Reform cannot overlook regulation
Authors: Burge Anne
Published: September 2011

Government reforms and restructuring of the NHS are hitting the headlines. But its policy on voluntary registration over statutory regulation has been largely overlooked – and in the case of clinical physiology is a tragedy waiting to happen, according to Anne Burge, Chair of the Registration Council for Clinical Physiologists.
Consent and Children: A Practical Summary
Authors: Wright Tim
Published: September 2011

This article addresses consent generally and specifically as applied to children.
Profile of patients with gastrointestinal TB at a tertiary care centre in western India
Authors: Jain Mayank , Baijal Rajiv , Kumar Praveen , Gupta Deepak
Published: September 2011

Gastrointestinal TB is a common problem. We report a series of 32 cases diagnosed at our centre in 2009. Peritoneal and ileocaecal TB are the most common manifestations and diagnosis was confirmed in 87.5% patients. The response to treatment was favourable
Once-daily antiretroviral therapy among treatment-experienced Muslim patients fasting for the month of Ramadan
Authors: Yakasai Ahmed M , Muhammad Hamza , Babashani Musa , Jumare Jibreel , Abdulmumini Murjanatu , Habib Abdulrazaq G
Published: September 2011

Many countries with a considerable burden of human immunodeficiency virus (HIV) infection in Africa and Asia also have a substantial Muslim population. Anti-retroviral therapy (ART) has led to reductions in HIV morbidity and mortality in those areas. However, for ART to remain durably effective its provision should be adapted to local and religious customary practices such as Ramadan fasting. The fasting is often observed by Muslims with HIV infection and ART might be compromised by sub-optimal adherence during fasting as it precludes the ingestion of oral substances during the daytime and is often associated with an alteration of meals/sleeping patterns. We studied once-daily compared to twice-daily dosed ritonovir boosted lopinavir with fixed-dose tenofovir-emtricitabine once-daily among 17 heavily treatment-experienced stable FT patients in Nigeria. No changes in adherence, diarrhoea, CD4 cell counts, viral load, haematocrit, kidney, liver and lipid tests were observed. Effectiveness, safety and tolerability appeared unaffected by the changes.
Hypertrophic pyloric stenosis in the Third World
Authors: Saula P W , Hadley G P
Published: September 2011

The relative rarity of hypertrophic pyloric stenosis (HPS) in the developing world makes its diagnosis a challenge to many physicians. This study audits the management of HPS at a tertiary hospital in South Africa, with a view to defining its regional pattern. This is a retrospective review of records of all patients ( n = 63) managed for HPS over an eight-year period (2002–2010). The mean age at presentation was 6.2 weeks and the male/female ratio was 6:1. The majority of patients presented with non-bilious vomiting. Abdominal ultrasound had a sensitivity of 65% and 81.3% when the criteria of pyloric muscle thickness >4 mm and pyloric channel length >16 mm were used, respectively. The overall complication rate was 14.3% and the mortality rate was 0%. Despite the rarity of HPS in the Third World, the outcome of its management is favourable. However, the sensitivity of abdominal ultrasound for diagnosing HPS is low.
An uncommon infectious cause of pleural effusion
Authors: Aggarwal Amitesh , Rajashekaraiah Lokesh Champally , Misra Kiran , Dev Munish , Sharma Vishal
Published: September 2011

Lymphatic filariasis is one of the major public health problems across the globe. Clinical manifestations usually depend on the site of lymphatic involvement. A 21-year-old female resident of a non-endemic filarial region presented with axillary lymphadenopathy, bilateral pleural effusion, ascites and pedal oedema. Fine-needle aspiration cytology (FNAC) of axillary lymph nodes revealed microfilariae. On the administration of diethyl carbamazine, lymph nodes gradually disappeared, the patient improved symptomatically and the filarial antigen test after treatment was negative. We report this case of bilateral axillary lymphadenopathy with pleural effusion and ascites as a rare manifestation of filariasis.
CD4+ T lymphocyte reference values of immunocompetent subjects in an African university
Authors: Pennap Grace R , Adoga Moses P , Forbi Joseph C , Ojobo Friday , Agwale Simon M
Published: September 2011

CD4+ T cells play critical roles in the immune system and, being primary targets of HIV infection, they are used to measure disease progression and response to combination antiretroviral therapy (cART), alongside other parameters, in HIV/AIDS patients. The aim of this study was to determine the reference values of CD4+ T cells in a student population that was HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV) negative. After ethical clearance and informed consent, 500 subjects (mean age = 26 years) were recruited, of whom 56 (11.2%) had HIV, HBV or HCV and were excluded. Blood samples were collected from the remaining 444 subjects into vacutainer tubes and analysed using the BD FACScount cytometer according to the manufacturer's instructions. Of the 444 subjects, 266 (59.9%) were male and 178 (40.1%) were female. The mean (± standard deviation) CD4+ T cell count was 987 cells/µL (± 336). The mean counts among males and females were 957 cells/µL (± 306) and 991 cells/µL (± 340), respectively. Values of CD4+ T cells ranged from 651 cells/µL to 1705 cells/µL. Subjects with higher CD4+ T Cells were more likely to be female than male. There was no direct correlation between CD4+ T cell values and age of the participants. Our findings offer the first insight into the CD4+ T cell reference values of a Nigerian student population and provide useful data that will guide future cART decisions and other immune-based therapies.
The Vaccine-Autism Connection: A Public Health Crisis Caused by Unethical Medical Practices and Fraudulent Science
Authors: Flaherty Dennis K
Published: September 2011

In 1998. Dr. Andrew Wakefield, a British gastroenterologist, described a new autism phenotype called the regressive autism-enterocolitis syndrome triggered by environmental factors such as measles, mumps, and rubella (MMR) vaccination. The speculative vaccination-autism connection decreased parental confidence in public health vaccination programs and created a public health crisis in England and questions about vaccine safety in North America. After 10 years of controversy and investigation, Dr. Wakefield was found guilty of ethical, medical, and scientific misconduct in the publication of the autism paper. Additional studies showed that the data presented were fraudulent. The alleged autism-vaccine connection Is, perhaps, the most damaging medical hoax of the last 100 years.
High-Throughput Simultaneous Analysis of RNA, Protein, and Lipid Biomarkers in Heterogeneous Tissue Samples
Authors: Reiser Vladimír , Smith Ryan C , Xue Jiyan , Kurtz Marc M , Liu Rong , LeGrand Cheryl , He Xuanmin , Yu Xiang , Wong Peggy , Hinchcliffe John S , Tanen Michael R , Lazar Gloria , Zieba Renata , Ichetovkin Marina , Chen Zhu , O'Neill Edward A , Tanaka Wesley K , Marton Matthew J , Liao Jason , Morris Mark , Hailman Eric , Tokiwa George Y , Plump Andrew S
Published: September 2011

BACKGROUND

With expanding biomarker discovery efforts and increasing costs of drug development, it is critical to maximize the value of mass-limited clinical samples. The main limitation of available methods is the inability to isolate and analyze, from a single sample, molecules requiring incompatible extraction methods. Thus, we developed a novel semiautomated method for tissue processing and tissue milling and division (TMAD).

METHODS

We used a SilverHawk atherectomy catheter to collect atherosclerotic plaques from patients requiring peripheral atherectomy. Tissue preservation by flash freezing was compared with immersion in RNAlater®, and tissue grinding by traditional mortar and pestle was compared with TMAD. Comparators were protein, RNA, and lipid yield and quality. Reproducibility of analyte yield from aliquots of the same tissue sample processed by TMAD was also measured.

RESULTS

The quantity and quality of biomarkers extracted from tissue prepared by TMAD was at least as good as that extracted from tissue stored and prepared by traditional means. TMAD enabled parallel analysis of gene expression (quantitative reverse-transcription PCR, microarray), protein composition (ELISA), and lipid content (biochemical assay) from as little as 20 mg of tissue. The mean correlation was r = 0.97 in molecular composition (RNA, protein, or lipid) between aliquots of individual samples generated by TMAD. We also demonstrated that it is feasible to use TMAD in a large-scale clinical study setting.

CONCLUSIONS

The TMAD methodology described here enables semiautomated, high-throughput sampling of small amounts of heterogeneous tissue specimens by multiple analytical techniques with generally improved quality of recovered biomolecules.
The estimation of selected endogenous anticoagulation system parameters in patients with subclinical Cushing's syndrome
Authors: Świątkowska-Stodulska Renata , Kaniuka-Jakubowska Sonia , Wiśniewski Piotr , Skibowska-Bielińska Anna , Sworczak Krzysztof
Published: September 2011

Objective

An increased tendency towards thromboembolic events is observed in patients with Cushing's syndrome. There are much fewer publications available about thromboembolic complications in patients with subclinical Cushing's syndrome (SCS). Therefore, a question arises whether hemostatic disturbances appear in this particular disease phase.

Aim of study

Estimation of protein C (PC), free protein S (FPS), antithrombin (AT) activity, thrombomodulin (TM) concentration and activated PC resistance (APCR) in patients with SCS.

Materials and methods

We studied 35 patients with SCS. The control group consisted of 33 healthy volunteers. The activity of PC, AT, FPS, APCR and the concentration of TM was estimated in all representatives.

Results

The comparison of the examined coagulation parameters between the patients with SCS and the healthy individuals revealed significantly higher mean PC activity and mean FPS activity in the SCS group. Mean TM concentration was significantly lower in patients with SCS compared with the control group. The differences in APCR and AT activity were not significant. We did not prove any statistically significant correlations between the examined coagulation parameters and hormonal parameters. We did not find any correlation between the concentration of cortisol and basic coagulation parameters such as international normalized ratio, activated partial thromboplastin time or fibrinogen in the group with SCS either.

Conclusions

The patients with SCS present disturbances in endogenous anticoagulation system defined as PC, FPS activity and TM concentration. This finding suggests an impact of mild autonomic cortisol overproduction on coagulation system.
Plant breeding for harmony between agriculture and the environment
Authors: Brummer E Charles , Barber Wesley T , Collier Sarah M , Cox Thomas S , Johnson Randy , Murray Seth C , Olsen Richard T , Pratt Richard C , Thro Ann Marie
Published: September 2011

Plant breeding programs primarily focus on improving a crop's environmental adaptability and biotic stress tolerance in order to increase yield. Crop improvements made since the 1950s – coupled with inexpensive agronomic inputs, such as fertilizers, pesticides, and water – have allowed agricultural production to keep pace with human population growth. Plant breeders, particularly those at public institutions, have an interest in reducing agriculture's negative impacts and improving the natural environment to provide or maintain ecosystem services (eg clean soil, water, and air; carbon sequestration), and in creating new agricultural paradigms (eg perennial polycultures). Here, we discuss recent developments in, as well as the goals of, plant breeding, and explain how these may be connected to the specific interests of ecologists and naturalists. Plant breeding can be a powerful tool to bring “harmony” between agriculture and the environment, but partnerships between plant breeders, ecologists, urban planners, and policy makers are needed to make this a reality.
Product Market Competition and Investments in Cooperative R&D
Authors: Hinloopen Jeroen , Vandekerckhove Jan
Published: September 2011

Building on the framework developed by Qiu (1997) we investigate the influence of product market competition on incentives to invest in cooperative R&D. For that we disentangle the three components that make up the combined-profits externality. The strategic component is always negative and the size component is always positive. The spillover component is negative (positive) with Bertrand (Cournot) competition. Cournot competition thus yields more cooperative R&D, which could drive the Cournot-Nash price below the Bertrand-Nash price. Our decomposition also explains why, under Cournot competition, cooperative R&D exceeds non-cooperative R&D only if spillovers are “high enough.”
Influence of parental germplasm for fruit characters in F1, F2 and F3 generations of pepper (Capsicum annuum L.)
Authors: Zecevic Bogoljub , Djordjevic Radisa , Balkaya Ahmet , Damnjanovic Jelena , Djordjevic Mladen , Vujosevic Ana
Published: September 2011

The aim of this research was to determine genetic values for the fruit width
and fruit length in F1 and F2 generation of diallely crossed pepper
genotypes, and to evaluate the effects of applying the pedigree and bulk
breeding method for producing F3 hybrid populations. Hybrid populations were
formed by crossing divergent genotypes belonging to different varieties of
species Capsicum annuum L. The research of parental lines lasted for three
years, experiments with F1 generation two years, while the analysis of
results for F3 hybrid population has been done regarding the data from one
year experiment. The heterosis effect in F1 generation for all researched
traits and in all crossing combinations was very low. Genetic analysis of F2
generation showed that all researched traits were inherited with partial
domination. In F3 generation, hybrid populations formed by using the pedigree
method of selection had traits which are more valuable for further breeding
than the hybrid population formed by using modified bulk method.