bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic tubulointerstitial nephritis induced by 5-aminosalicylate in an ulcerative colitis patient: a rare but serious adverse event
Authors: Magalhães-Costa Pedro , Matos Leopoldo , Chagas Cristina
Published: May 2015

The 5-aminosalicylate is widely prescribed in inflammatory bowel disease patients. Its potential for renal damage has been seldom described. We report a case of a 23-year-old man who started 5-aminosalicylate after being diagnosed with ulcerative colitis. One year after, a significant decline on his creatinine clearance was noted, however, at that time, he was on an acute flare of his bowel disease and the 5-aminosalicylate dose was increased. Six months later, his renal function kept worsening and, on drug-induced toxicity suspicion, 5-aminosalicylate was halted and a kidney biopsy demonstrated a chronic tubulointerstitial nephritis. Steroids and azathioprine were started leading to partial recovery and stabilisation of his renal function. Physicians who prescribe 5-aminosalicylate to patients with inflammatory bowel disease should be aware of this adverse event.
Squamous cell carcinoma arising in a mature cystic teratoma invading the sigmoid colon: a rare presentation
Authors: Gooneratne Alena Talia , James Alexander Owen , Gupta Jyoti , Abdulaal Yasser
Published: May 2015

We discuss a rare presentation of malignant teratoma in a 63-year-old woman who was admitted to accident and emergency with abdominal distension, bloody diarrhoea and peritonitis. CT of the abdomen and pelvis showed free air in the abdomen and a gas-fluid filled cavity measuring 12×6 cm in the mid-pelvis with possible fistulation that was suspicious for malignancy. A 10×12 cm ruptured dermoid cyst was found intraoperatively, which was adherent to the bowel wall. Bulky lymph nodes were also appreciated. The surgeon suspected a metastatic malignant teratoma, and a Hartmann's procedure, total abdominal hysterectomy and bilateral salpingoopherectomy were performed with clearance of the para-aortic lymph nodes. Subsequent histological analysis revealed a squamous cell carcinoma arising from an ovarian malignant teratoma. The patient went on to have carboplatin and paclitaxel chemotherapy and is alive at 6 months follow-up.
Primary mediastinal (thymic) B-cell lymphoma presenting as cutaneous vasculitis
Authors: De Sousa Lages Adriana , Esperto Helder , Santos Lèlita , Carvalho Armando
Published: May 2015

Cutaneous small vessel vasculitis is a severe neutrophilic vascular inflammation mediated by immune complexes that involves the dermal postcapillary venules. Neoplasms represent 2–5% of all causes of secondary cutaneous vasculitis. We present a case of a 52-year-old man who was admitted due to a 10-day history of respiratory symptoms and myalgia. From the third day of symptoms onwards, the patient noticed the appearance of cutaneous lesions in the lower limbs with palpable purpura and erythematous papules. Additionally, he reported of asthenia, anorexia and weight loss during the prior month. Chest radiography showed an enlarged mediastinum and thoracoabdominal-pelvic CT scan revealed a bulky left hilar mass. Biopsy of the left superior lobar bronchus’ mucosa allowed for the histological diagnosis of diffuse large B-cell lymphoma (DLBL) of the thymus. The patient received symptomatic treatment with improvement of the purpuric lesions and a multiagent chemotherapy regimen was initiated.
Rare adverse effect of a common drug: nitrofurantoin-induced ANCA-associated vasculitis
Authors: Agarwal Abhishek , Agrawal Abhinav , Nathan Karim , Roy Satyajeet
Published: May 2015

Nitrofurantoin is commonly prescribed to treat urinary tract infections (UTI). Reported adverse effects include gastrointestinal, pulmonary, hepatic and neurological disorders. We report a case of a 67-year-old woman treated for UTI with nitrofurantoin who presented with antineutrophilic cytoplasmic antibody (ANCA)-associated renal and skin vasculitis 3 days after starting treatment. The symptoms resolved following withdrawal of the drug and treatment with steroids. This is the first reported case of nitrofurantoin causing ANCA-associated vasculitis.
Breathlessness in a drug user
Authors: Yip Ivan Yeu Ming
Published: May 2015

A 40-year-old heroin smoking man presented with acute onset severe shortness of breath. Radiological investigations revealed an unexpected loculated pneumothorax. Respiratory physicians inserted a chest drain which relieved his breathlessness. His exercise tolerance is much improved 6 months on. The side effects of smoking illicit substances are poorly understood. There is a growing trend for drug users to smoke rather than intravenously inject. It is therefore important for clinicians to be aware of the associated morbidity. The authors believe this is the first ever reported case of loculated pneumothorax associated with heroin smoking.
Loperamide dependence and abuse
Authors: MacDonald Ryan , Heiner Jason , Villarreal Joshua , Strote Jared
Published: May 2015

Loperamide is a common over-the-counter antidiarrheal considered safe in a broad range of dosages and thought devoid of abuse potential. We describe the first case of a patient with loperamide dependence due to misuse of its opiate-like effects achieved by chronic massive oral ingestions. A 26-year-old man who was taking 800 mg of loperamide per day presented requesting detoxification referral. Loperamide has potential for euphoric effects and information on how to facilitate such effects is easily available. It is important for physicians to be aware of the potential for misuse of and dependence on loperamide, with symptoms mimicking opiate use.
Body mass index in school-aged children and the risk of routinely diagnosed non-alcoholic fatty liver disease in adulthood: a prospective study based on the Copenhagen School Health Records Register
Authors: Zimmermann Esther , Gamborg Michael , Holst Claus , Baker Jennifer L , Sørensen Thorkild I A , Berentzen Tina L
Published: May 2015

Objective

The relation between childhood overweight and adult non-alcoholic fatty liver disease (NAFLD) is largely unknown. We investigated if weight and weight gain in childhood increases the risk of being diagnosed with NAFLD in routine clinical settings in adulthood.

Participants

We studied 244 464 boys and girls, born between 1930 and 1989, who attended school in Copenhagen, Denmark. Their heights and weights were measured by physicians or nurses at mandatory school health examinations at ages 7–13 years. Body mass index (BMI) z-scores were calculated from an internal age-specific and sex-specific reference.

Outcome measures

NAFLD reported in the National Patient Register and the National Register of Pathology at 18 years of age or older. HRs with 95% CIs were estimated.

Results

During follow-up, 1264 and 1106 NAFLD cases, respectively, occurred in men and women. In both sexes, childhood BMI z-score was not consistently associated with adult NAFLD. Change in BMI z-score between 7 and 13 years of age was positively associated with NAFLD in both sexes. When adjusted for BMI z-score at age 7 years, the HRs of adult NAFLD were 1.15 (95% CI 1.05 to 1.26) and 1.12 (95% CI 1.02 to 1.23) per 1-unit gain in BMI z-score in men and women, respectively. Associations were similar when adjusted for BMI z-score at age 13 years, and were consistent across birth years.

Conclusions

A BMI gain in school-aged children is associated with adult NAFLD. Intriguingly, BMI gain appears to have an effect on adult NAFLD irrespective of either the initial or the attained BMI. Taken together, our results suggest that BMI gain in childhood, rather than the level of BMI per se, is important in the development of adult NAFLD.
3D-manufactured patient-specific models of congenital heart defects for communication in clinical practice: feasibility and acceptability
Authors: Biglino Giovanni , Capelli Claudio , Wray Jo , Schievano Silvia , Leaver Lindsay-Kay , Khambadkone Sachin , Giardini Alessandro , Derrick Graham , Jones Alexander , Taylor Andrew M
Published: May 2015

Objectives

To assess the communication potential of three-dimensional (3D) patient-specific models of congenital heart defects and their acceptability in clinical practice for cardiology consultations.

Design

This was a questionnaire-based study in which participants were randomised into two groups: the ‘model group’ received a 3D model of the cardiac lesion(s) being discussed during their appointment, while the ‘control group’ had a routine visit.

Setting

Outpatient clinic, cardiology follow-up visits.

Participants

103 parents of children with congenital heart disease were recruited (parental age: 43±8 years; patient age: 12±6 years). In order to have a 3D model made, patients needed to have a recent cardiac MRI examination; this was the crucial inclusion criterion.

Interventions

Questionnaires were administered to the participants before and after the visits and an additional questionnaire was administered to the attending cardiologist.

Main outcome measures

Rating (1–10) for the liking of the 3D model, its usefulness and the clarity of the explanation received were recorded, as well as rating (1–10) of the parental understanding and their engagement according to the cardiologist. Furthermore, parental knowledge was assessed by asking them to mark diagrams, tick keywords and provide free text answers. The duration of consultations was recorded and parent feedback collected.

Results

Parents and cardiologists both found the models to be very useful and helpful in engaging the parents in discussing congenital heart defects. Parental knowledge was not associated with their level of education (p=0.2) and did not improve following their visit. Consultations involving 3D models lasted on average 5 min longer (p=0.02).

Conclusions

Patient-specific models can enhance engagement with parents and improve communication between cardiologists and parents, potentially impacting on parent and patient psychological adjustment following treatment. However, in the short-term, parental understanding of their child's condition did not improve.
Subacute complications during recovery from severe traumatic brain injury: frequency and associations with outcome
Authors: Godbolt Alison K , Stenberg Maud , Jakobsson Jan , Sorjonen Kimmo , Krakau Karolina , Stålnacke Britt-Marie , Nygren DeBoussard Catharina
Published: May 2015

Background

Medical complications after severe traumatic brain injury (S-TBI) may delay or prevent transfer to rehabilitation units and impact on long-term outcome.

Objective

Mapping of medical complications in the subacute period after S-TBI and the impact of these complications on 1-year outcome to inform healthcare planning and discussion of prognosis with relatives.

Setting

Prospective multicentre observational study. Recruitment from 6 neurosurgical centres in Sweden and Iceland.

Participants and assessments

Patients aged 18–65 years with S-TBI and acute Glasgow Coma Scale 3–8, who were admitted to neurointensive care. Assessment of medical complications 3 weeks and 3 months after injury. Follow-up to 1 year. 114 patients recruited with follow-up at 1 year as follows: 100 assessed, 7 dead and 7 dropped out.

Outcome measure

Glasgow Outcome Scale Extended.

Results

68 patients had ≥1 complication 3 weeks after injury. 3 weeks after injury, factors associated with unfavourable outcome at 1 year were: tracheostomy, assisted ventilation, on-going infection, epilepsy and nutrition via nasogastric tube or percutaneous endoscopic gastroscopy (PEG) tube (univariate logistic regression analyses). Multivariate analysis demonstrated that tracheostomy and epilepsy retained significance even after incorporating acute injury severity into the model. 3 months after injury, factors associated with unfavourable outcome were tracheostomy and heterotopic ossification (Fisher's test), infection, hydrocephalus, autonomic instability, PEG feeding and weight loss (univariate logistic regression). PEG feeding and weight loss at 3 months were retained in a multivariate model.

Conclusions

Subacute complications occurred in two-thirds of patients. Presence of a tracheostomy or epilepsy at 3 weeks, and of PEG feeding and weight loss at 3 months, had robust associations with unfavourable outcome that were incompletely explained by acute injury severity.
Development and validation of a socioculturally competent trust in physician scale for a developing country setting
Authors: Gopichandran Vijayaprasad , Wouters Edwin , Chetlapalli Satish Kumar
Published: May 2015

Trust in physicians is the unwritten covenant between the patient and the physician that the physician will do what is in the best interest of the patient. This forms the undercurrent of all healthcare relationships. Several scales exist for assessment of trust in physicians in developed healthcare settings, but to our knowledge none of these have been developed in a developing country context.

Objectives

To develop and validate a new trust in physician scale for a developing country setting.

Methods

Dimensions of trust in physicians, which were identified in a previous qualitative study in the same setting, were used to develop a scale. This scale was administered among 616 adults selected from urban and rural areas of Tamil Nadu, south India, using a multistage sampling cross sectional survey method. The individual items were analysed using a classical test approach as well as item response theory. Cronbach's α was calculated and the item to total correlation of each item was assessed. After testing for unidimensionality and absence of local dependence, a 2 parameter logistic Semajima's graded response model was fit and item characteristics assessed.

Results

Competence, assurance of treatment, respect for the physician and loyalty to the physician were important dimensions of trust. A total of 31 items were developed using these dimensions. Of these, 22 were selected for final analysis. The Cronbach's α was 0.928. The item to total correlations were acceptable for all the 22 items. The item response analysis revealed good item characteristic curves and item information for all the items. Based on the item parameters and item information, a final 12 item scale was developed. The scale performs optimally in the low to moderate trust range.

Conclusions

The final 12 item trust in physician scale has a good construct validity and internal consistency.
Neighbourhood environment, sitting time and motorised transport in older adults: a cross-sectional study in Hong Kong
Authors: Barnett Anthony , Cerin Ester , Ching Claudia S-K , Johnston Janice M , Lee Ruby S Y
Published: May 2015

Objectives

Sitting time is a public health concern. This study examined associations of objectively measured neighbourhood environmental attributes with non-transport sitting time and motorised transport in 484 Hong Kong older adults. Neighbourhood attributes encouraging walking may help older adults replace some sitting time at home and on motorised transport with light-to-moderate-intensity activities such as strolling around the neighbourhood or walking to/from neighbourhood destinations. Thus, we hypothesised environmental attributes found to be related to walking would show associations with non-transport sitting time and motorised transport opposite to those seen for walking.

Design

Cross-sectional.

Setting

Hong Kong, an ultradense urban environment.

Participants

484 ethnic Chinese Hong Kong residents aged 65+ recruited from membership lists of four Hong Kong Elderly Health Centres representing catchment areas of low and high transport-related walkability stratified by socioeconomic status (response rate: 78%).

Primary and secondary outcome measures

Attributes of participants’ neighbourhood environments were assessed by environmental audits, while non-transport sitting time and motorised transport were ascertained using the International Physical Activity Questionnaire—Long Form (Chinese version).

Results

Daily non-transport sitting minutes were 283 (SD=128) and motorised transport 23 (SD=28). Prevalence of signs of crime/disorder, streetlights, public facilities (toilets and benches) and pedestrian safety were independently negatively related, and sloping streets positively related, to sitting outcomes. Places of worship in the neighbourhood were predictive of more, and prevalence of public transit points of less, non-transport sitting. Associations of either or both sitting outcomes with prevalence of food/grocery stores and presence of parks were moderated by path obstructions and signs of crime/disorder.

Conclusions

The findings suggest that access to specific destinations and relatively low-cost, minimal impact modifications to the urban form, such as street lighting, public toilets, benches and public transit points, could potentially reduce sitting time and associated negative health outcomes in Hong Kong older adults.
Improving critical care discharge summaries: a collaborative quality improvement project using PDSA
Authors: Goulding Lucy , Parke Hannah , Maharaj Ritesh , Loveridge Robert , McLoone Anne , Hadfield Sophie , Helme Eloise , Hopkins Philip , Sandall Jane
Published: May 2015

Around 110,000 people spend time in critical care units in England and Wales each year. The transition of care from the intensive care unit to the general ward exposes patients to potential harms from changes in healthcare providers and environment. Nurses working on general wards report anxiety and uncertainty when receiving patients from critical care.

An innovative form of enhanced capability critical care outreach called ‘iMobile’ is being provided at King’s College Hospital (KCH). Part of the remit of iMobile is to review patients who have been transferred from critical care to general wards. The iMobile team wished to improve the quality of critical care discharge summaries.

A collaborative evidence-based quality improvement project was therefore undertaken by the iMobile team at KCH in conjunction with researchers from King's Improvement Science (KIS). Plan, Do, Study, Act (PDSA) methodology was used. Three PDSA cycles were undertaken.

Methods adopted comprised: a scoping literature review to identify relevant guidelines and research evidence to inform all aspects of the quality improvement project; a process mapping exercise; informal focus groups / interviews with staff; patient story-telling work with people who had experienced critical care and subsequent discharge to a general ward; and regular audits of the quality of both medical and nursing critical care discharge summaries.

The following behaviour change interventions were adopted, taking into account evidence of effectiveness from published systematic reviews and considering the local context: regular audit and feedback of the quality of discharge summaries, feedback of patient experience, and championing and education delivered by local opinion leaders.

The audit results were mixed across the trajectory of the project, demonstrating the difficulty of sustaining positive change. This was particularly important as critical care bed occupancy and through-put fluctuates which then impacts on work-load, with new cohorts of staff regularly passing through critical care. In addition to presenting the results of this quality improvement project, we also reflect on the lessons learned and make suggestions for future projects.
Threats of dismissal and symptoms of major depression: a study using repeat measures in the Swedish working population
Authors: Magnusson Hanson Linda L , Chungkham Holendro Singh , Ferrie Jane , Sverke Magnus
Published: May 2015

Background

Job insecurity is considered a profound work stressor. While previous research has indicated that job insecurity represents a substantial mental health burden, few studies have examined its relationship with symptoms of major depression. The aim of this study was to assess whether episodic and repeated self-reported threats of dismissal increase the risk of subsequent symptoms of major depression and whether symptoms of major depression are related to subsequent experience of threats of dismissal.

Methods

The study is based on the Swedish Longitudinal Occupational Survey of Health (SLOSH) study, a cohort study with multiple repeated measurements. The sample consisted of 6275 participants who were in regular paid employment and who provided data in 2008, 2010 and 2012. Severity of depression was assessed with a brief Symptom Checklist scale and categorised according to symptoms of major depression or not.

Results

Results based on generalised estimating equations logit models showed that prior threats of dismissal predicted symptoms of major depression OR 1.37; 95% CI 1.04 to 1.81) after adjustment for prior depression and major confounders. Especially related threats increased the risk of major depression symptoms (OR 1.74 CI 1.09 to 2.78). Major depression symptoms also increased the odds of subsequent threats of dismissal (OR 1.52, CI 1.17 to 1.98).

Conclusions

These findings support a prospective association between threats of dismissal and symptoms of major depression, in particular repeated exposure to threats of dismissal. The results also indicate that threats of dismissal are more likely to be reported by workers with symptoms of major depression.
Impact of clinical follow-up and diagnostic testing on intervention for tetralogy of Fallot
Authors: House Aswathy Vaikom , Danford David A , Spicer Robert L , Kutty Shelby
Published: May 2015

Objective

Our purpose was to evaluate yield of tools commonly advocated for surveillance of tetralogy of Fallot (TOF).

Methods

All patients (pts) with TOF, seen at any time from 1/2008 to 9/2013 in an academic cardiology practice were studied. At the first and each subsequent outpatient visit, the use of tools including history and physical (H&P), ECG, Holter (HOL), echocardiogram (Echo), MR or CT (MR-CT) and stress testing (STR) were noted. Recommendations for intervention (INT) and for time to next follow-up were recorded; rationale for each INT with attribution to one or more tools was identified.

Results

There were 213 pts (mean 11.5 years, 130 male) who had 916 visits, 123 of which (13.4%) were associated with 138 INTs (47 surgical, 54 catheter-mediated, 37 other medical). Recommended follow-up interval was 9.44±6.5 months, actual mean follow-up interval was 11.7 months. All 916 (100%) patient visits had a H&P which contributed to 47.2% of INT decisions. Echo was performed in 652 (71.2%) of visits, and contributed to 53.7% of INTs. MR-CT was obtained in 129 (14.1%) of visits, and contributed to 30.1% of INTs. ECG was applied in 137 (15%) visits, and contributed to 1.6% of INTs. HOL was obtained in 188 (20.5%) visits, and contributed to 11.3% of INTs. STR was performed at 101 (11%) of visits, and contributed to 8.9% of INTs.

Conclusions

INTs are common in repaired TOF, but when visits average every 11–12 months, most visits do not result in INT. H&P, Echo and HOL were the most frequently applied screens, and all frequently yielded relevant information to guide INT decisions. STR and MR/CT were applied as targeted testing and in this limited, non-screening role had high relevance for INT. There was low utilisation of ECG and major impact on INT was not demonstrated. Risk stratification in TOF may be possible, and could result in more efficient surveillance and targeted testing.
Biological treatment in systemic juvenile idiopathic arthritis: achievement of inactive disease or clinical remission on a first, second or third biological agent
Authors: Woerner A , Uettwiller F , Melki I , Mouy R , Wouters C , Bader-Meunier B , Quartier P
Published: May 2015

Objectives

To analyse the effect of biological agents (BAs) in terms of achieving inactive disease (ID) or clinical remission (CR) in patients with systemic juvenile idiopathic arthritis (SJIA), to describe effects of switching or discontinuing a BA and to assess the proportion of patients able to maintain ID or CR off steroids and after withdrawing BA therapy.

Methods

Retrospective study in a French paediatric rheumatology reference centre using the CEMARA (CEntre des MAladies RAres) register.

Results

Seventy-seven patients were included with a cumulative follow-up of 245.5 patient-years (median 1.1, range 0.5–8.0). On a first BA, ID was achieved in 37 patients, including 1 patient out of 12 patients on etanercept, 26 patients out of 51 on anakinra and 7 out of 10 on canakinumab. One patient on abatacept and two patients on tocilizumab also achieved ID. Switching of BA was common. The switch to a second (n=34), third (n=18) or fourth (n=4) BA resulted in ID in a further 13 patients, either on canakinumab (n=6) or tocilizumab (n=7). At last follow-up, 40 patients were in CR (27 patients off steroids, 5 patients having never received steroid treatment), either on (n=29) or off (n=11) BA.

Conclusions

In this series of patients with SJIA, interleukin-1 inhibitors were associated with a higher proportion of ID than tumour necrosis factor inhibitors when used as first BA. Switching allowed some patients to achieve ID when treated with canakinumab or tocilizumab. CR was eventually achieved in more than half of the patients.
ACPA-positive primary Sjögren's syndrome: true primary or rheumatoid arthritis-associated Sjögren's syndrome?
Authors: Payet J , Belkhir R , Gottenberg J E , Bergé E , Desmoulins F , Meyer O , Mariette X , Seror R
Published: May 2015

Objectives

Anticyclic citrullinated protein antibodies (ACPA) are highly specific of rheumatoid arthritis (RA). However, they have also been detected in 5–10% of primary Sjögren's syndrome (pSS). We compared ACPA-positive and negative patients with pSS and assessed the risk of evolution to RA.

Patients and methods

ACPA-positive and negative patients with pSS were included in this study. For ACPA-positive patients, clinical and radiological re-evaluation was systematically performed after at least 5 years of follow-up. Diagnosis was reassessed at the end of the follow-up to identify patients that developed RA according to the American College of Rheumatology 1987 classification criteria.

Results

At inclusion in the cohort 16 patients with pSS were ACPA positive and 278 were ACPA negative. ACPA-positive patients, had more frequently arthritis (43.7% vs 12.2%; p=0.003) but not arthralgias. They also had more frequent lung involvement (25% vs 8.1%; p=0.05). After median follow-up of 8 (5–10) years, 7/16 (43.8%) patients developed RA including 5 (31.25%) with typical RA erosions. Elevation of acute phase reactants at inclusion was the only parameter associated with progression to erosive RA.

Conclusions

Median term follow-up of ACPA-positive patients with pSS showed that almost half of them developed RA, particularly in the presence of elevation of acute phase reactants. These results support the usefulness of a close radiological monitoring of these patients for early detection of erosive change not to delay initiation of effective treatment. Indeed, number of these patients with ACPA-positive pSS may actually have RA and associated SS.
Isolation of peripheral populations of Canada lynx (Lynx canadensis)
Authors: Koen E.L. , Bowman J. , Wilson P.J.
Published: May 2015

Landscape barriers to gene flow, such as rivers, can affect animal populations by limiting the potential for rescue of these isolated populations. We tested the riverine barrier hypothesis, predicting that the St. Lawrence River in eastern Canada would cause genetic divergence of Canada lynx (Lynx canadensis Kerr, 1792) populations by restricting dispersal and gene flow. We sampled 558 lynx from eastern Canada and genotyped these at 14 microsatellite loci. We found three genetic clusters, defined by the St. Lawrence River and the Strait of Belle Isle, a waterway separating Newfoundland from mainland Canada. However, these waterways were not absolute barriers, as we found 24 individuals that appeared to have crossed them. Peripheral populations of lynx are threatened in parts of Canada and the USA, and it is thought that these populations are maintained by immigration from the core. Our findings suggest that in eastern North America, rescue might be less likely because the St. Lawrence River restricts dispersal. We found that ice cover was often sufficient to allow lynx to walk across the ice in winter. If lynx used ice bridges in winter, then climate warming could cause a reduction in the extent and longevity of river and sea ice, further isolating these peripheral lynx populations.
Bird communities and vegetation associations across a treeline ecotone in the Mealy Mountains, Labrador, which is an understudied part of the boreal forest
Authors: Lewis Keith P. , Starzomski Brian M.
Published: May 2015

We examined the factors structuring bird communities across a complex subarctic treeline in the Mealy Mountains, Labrador, Canada. Using point counts of bird abundance in 2007 and 2008, we show that changes in vegetation driven by elevation are strongly correlated with avian community structure in this treeline ecotone system. Overall, avian diversity was higher in the forest compared with other habitat classes (krummholz, deciduous shrub, and alpine). There were strong correlations between avian diversity and vegetation richness, as well as structure, among and within habitat class in 2008. Numerous habitat types (subset of habitat class) were correlated with avian composition, although some species were clearly habitat generalists. Contrary to expectation, avian species composition was associated with physiognomy (vegetation structure) in alpine and deciduous shrub, and with either physiognomy or floristics (vegetation species composition) in krummholz and forest. Given the strong impact of elevation on vegetation and the demonstrated influence on bird communities, we note that for bird species whose near-southernmost populations are found in the Mealy Mountains, climate change is likely to have a strong negative effect if alpine tundra habitat is lost. Furthermore, forest bird species are likely to benefit from the increased tree cover as treeline moves poleward and upward.
Angiotensin II blockade: how its molecular targets may signal to mitochondria and slow aging. Coincidences with calorie restriction and mTOR inhibition
Authors: de Cavanagh Elena M. V. , Inserra Felipe , Ferder León
Published: May 2015

Caloric restriction (CR), renin angiotensin system blockade (RAS-bl), and rapamycin-mediated mechanistic target of rapamycin (mTOR) inhibition increase survival and retard aging across species. Previously, we have summarized CR and RAS-bl's converging effects, and the mitochondrial function changes associated with their physiological benefits. mTOR inhibition and enhanced sirtuin and KLOTHO signaling contribute to the benefits of CR in aging. mTORC1/mTORC2 complexes contribute to cell growth and metabolic regulation. Prolonged mTORC1 activation may lead to age-related disease progression; thus, rapamycin-mediated mTOR inhibition and CR may extend lifespan and retard aging through mTORC1 interference. Sirtuins by deacetylating histone and transcription-related proteins modulate signaling and survival pathways and mitochondrial functioning. CR regulates several mammalian sirtuins favoring their role in aging regulation. KLOTHO/fibroblast growth factor 23 (FGF23) contribute to control Ca2+, phosphate, and vitamin D metabolism, and their dysregulation may participate in age-related disease. Here we review how mTOR inhibition extends lifespan, how KLOTHO functions as an aging suppressor, how sirtuins mediate longevity, how vitamin D loss may contribute to age-related disease, and how they relate to mitochondrial function. Also, we discuss how RAS-bl downregulates mTOR and upregulates KLOTHO, sirtuin, and vitamin D receptor expression, suggesting that at least some of RAS-bl benefits in aging are mediated through the modulation of mTOR, KLOTHO, and sirtuin expression and vitamin D signaling, paralleling CR actions in age retardation. Concluding, the available evidence endorses the idea that RAS-bl is among the interventions that may turn out to provide relief to the spreading issue of age-associated chronic disease.
Functional impact of diaphragm muscle sarcopenia in both male and female mice
Authors: Greising Sarah M. , Mantilla Carlos B. , Medina-Martínez Juan S. , Stowe Jessica M. , Sieck Gary C.
Published: May 2015

To perform a range of ventilatory and nonventilatory behaviors, the diaphragm muscle (DIAm) must be able to generate sufficient forces throughout the lifespan. We hypothesized that sarcopenia impacts DIAm force generation and thus limits performance of expulsive, higher force, nonventilatory behaviors. Male and female mice ( n = 79) at 6 and 24 mo of age (100 vs. 70–75% survival, respectively) were used to examine transdiaphragmatic pressure (Pdi) generation across motor behaviors in vivo and in vitro DIAm specific force. We found a significant effect of age on maximum Pdi (20–41% decline during tracheal occlusion and bilateral phrenic nerve stimulation), maximum DIAm specific force (30% decline), and DIAm fatigue resistance (15% increase). There were no differences between sexes in these age effects on DIAm performance. These results support our hypothesis that sarcopenia primarily impacts higher force, nonventilatory motor behaviors of the DIAm. Such functional limitations may have negative implications in the ability of the DIAm to generate forces needed for airway clearance in old age and thereby contribute to age-related respiratory complications.
Neutrophil elastase-induced elastin degradation mediates macrophage influx and lung injury in 60% O2-exposed neonatal rats
Authors: Masood Azhar , Yi Man , Belcastro Rosetta , Li Jun , Lopez Lianet , Kantores Crystal , Jankov Robert P. , Tanswell A. Keith
Published: May 2015

Neutrophil (PMNL) influx precedes lung macrophage (LM) influx into the lung following exposure of newborn pups to 60% O2. We hypothesized that PMNL were responsible for the signals leading to LM influx. This was confirmed when inhibition of PMNL influx with a CXC chemokine receptor-2 antagonist, SB-265610, also prevented the 60% O2-dependent LM influx, LM-derived nitrotyrosine formation, and pruning of small arterioles. Exposure to 60% O2was associated with increased lung contents of neutrophil elastase and α-elastin, a marker of denatured elastin, and a decrease in elastin fiber density. This led us to speculate that neutrophil elastase-induced elastin fragments were the chemokines that led to a LM influx into the 60% O2-exposed lung. Inhibition of neutrophil elastase with sivelestat or elafin attenuated the LM influx. Sivelestat also attenuated the 60% O2-induced decrease in elastin fiber density. Daily injections of pups with an antibody to α-elastin prevented the 60% O2-dependent LM influx, impaired alveologenesis, and impaired small vessel formation. This suggests that neutrophil elastase inhibitors may protect against neonatal lung injury not only by preventing structural elastin degradation, but also by blocking elastin fragment-induced LM influx, thus preventing tissue injury from LM-derived peroxynitrite formation.
High Levels of Perfluorooctane Sulfonate in Children at the Onset of Diabetes
Authors: Predieri Barbara , Iughetti Lorenzo , Guerranti Cristiana , Bruzzi Patrizia , Perra Guido , Focardi Silvano E.
Published: May 2015

Background. Impairments of endocrine system may be associated with exposure to perfluorinated compounds that are able to bind nuclear receptors, including the peroxisome proliferator-activating receptors. Aim of this study was to assess perfluorooctane sulfonate and perfluorooctanoic acid concentrations in children and adolescents at the onset of type 1 diabetes compared to healthy controls.Methods. Forty-four children and adolescents were recruited and subdivided into two groups: (A) 25 subjects with type 1 diabetes and (B) 19 healthy controls. Perfluorinated compounds were measured using high performance liquid chromatography with electrospray ionization tandem mass spectrometry. Nonparametric statistical analysis was performed.Results. Perfluorooctane sulfonate concentrations were significantly higher in patients with type 1 diabetes compared to controls (1.53 ± 1.50 versus 0.55 ± 0.15 ng/mL, resp.;p<0.001). Multivariate linear regression analysis identified lipid levels as significant predictive factors for perfluorooctane sulfonate levels.Conclusions. Our data suggests that higher serum levels of perfluorooctane sulfonate may be considered a biomarker of exposure and susceptibility to develop type 1 diabetes.
Advances in Anti-IgE Therapy
Authors: Yalcin Arzu Didem
Published: May 2015

Omalizumab depletes free IgE in the blood and interstitial space and inhibits IgE binding to FcεRI on basophils, mast cells, and dendritic cells. We stopped omalizumab treatment after four years. Recurrences of urticaria symptoms were found to be higher in patients with chronic urticaria than recurrences of asthmatic symptoms in severe persistent asthma patients. For the very first time, we used omalizumab in symptomatic therapy of recurrent laryngeal oedema and urticaria attacks in a patient with postoperative pulmonary carcinoid tumor for eight months. During the four years of follow-up, no recurrence was noted in pulmonary carcinoid tumor. Control PET CT results revealed normal findings. After omalizumab treatment, laryngeal oedema and urticaria symptoms were decreased. The most common adverse reaction from omalizumab is injection site induration, injection site itching, injection site pain, and bruising but the package insert contains warnings regarding parasitic infections. While there are no reports of fatal anaphylaxis as a result of omalizumab, some cases have been serious and potentially life-threatening. Therefore, the FDA requires that people receiving omalizumab be monitored in the physician’s office for a period of time after their injections.
Existence of Center for Planar Differential Systems with Impulsive Perturbations
Authors: Xu Dengguo
Published: May 2015

We present a method that uses successor functions in ordinary differential systems to address the “center-focus” problem of a class of planar systems that have an impulsive perturbation. By deriving solution formulae for impulsive systems, several interesting criteria for distinguishing between the center and the focus of linear and nonlinear planar systems with state-dependent impulsions are established. The conditions describing the stability of the focus of the considered models are also given. The computing methods presented here are more convenient for determining the center of impulsive systems than those in the literature. Numerical examples are given to show the effectiveness of the theoretical results.
Allicin Alleviates Dextran Sodium Sulfate- (DSS-) Induced Ulcerative Colitis in BALB/c Mice
Authors: Pandurangan Ashok Kumar , Ismail Salmiah , Saadatdoust Zeinab , Esa Norhaizan Mohd.
Published: May 2015

The objective of this study is to evaluate the effect of allicin (10 mg/kg body weight, orally) in an experimental murine model of UC by administering 2.5% dextran sodium sulfate (DSS) in drinking water to BALB/c mice. DSS-induced mice presented reduced body weight, which was improved by allicin administration. We noted increases in CD68 expression, myeloperoxidase (MPO) activities, and Malonaldehyde (MDA) and mRNA levels of proinflammatory cytokines, such astumor necrosis factor- (TNF-)α, interleukin- (IL-) 1β, IL-6, andIL-17, and decrease in the activities of enzymic antioxidants such as superoxide dismutase (SOD), Catalase (CAT), Glutathione reductase (GR), and Glutathione peroxidase (GPx) in DSS-induced mice. However, allicin treatment significantly decreased CD68, MPO, MDA, and proinflammatory cytokines and increased the enzymic antioxidants significantly (P<0.05). In addition, allicin was capable of reducing the activation and nuclear accumulation of signal transducer and activator of transcription 3 (STAT3), thereby preventing degradation of the inhibitory protein IκB and inducing inhibition of the nuclear translocation of nuclear factor (NF)-κB-p65 in the colonic mucosa. These findings suggest that allicin exerts clinically useful anti-inflammatory effects mediated through the suppression of the NF-κB and IL-6/p-STAT3Y705pathways.
H∞LPV Control with Pole Placement Constraints for Synchronous Buck Converters with Piecewise-Constant Loads
Authors: Joo Hwanyub , Kim Sung Hyun
Published: May 2015

This paper addresses the output regulation problem of synchronous buck converters with piecewise-constant load fluctuations via linear parameter varying (LPV) control scheme. To this end, an output-error state-space model is first derived in the form of LPV systems so that it can involve a mismatch error that temporally arises from the process of generating a feedforward control. Then, to attenuate the mismatch error in parallel with improving the transient behavior of the converter, this paper proposes an LMI-based stabilization condition capable of achieving bothH∞and pole-placement objectives. Finally, the simulation and experimental results are provided to show the validity of our approach.
Surface-Applied Biosolids Enhance Soil Organic Carbon and Nitrogen Stocks but Have Contrasting Effects on Soil Physical Quality
Authors: Jin Virginia L. , Potter Kenneth N. , Johnson Mari-Vaughn V. , Harmel R. Daren , Arnold Jeffrey G.
Published: May 2015

Mid- to long-term impacts of land applying biosolids will depend on application rate, duration, and method; biosolids composition; and site-specific characteristics (e.g., climate, soils). This study evaluates the effects of surface-broadcast biosolids application rate and duration on soil organic carbon (SOC) stocks, soil aggregate stability, and selected soil hydraulic properties in a municipally operated, no-till forage production system. Total SOC stocks (0–45 cm soil) increased nonlinearly with application rate in perennial grass fields treated for 8 years with 0, 20, 40, or 60 Mg of Class B biosolids (DM) ha−1 yr−1(midterm treatments). Soil organic C stocks in long-term treatment fields receiving 20 years of 20 Mg ha−1 yr−1were 36% higher than those in midterm fields treated at the same rate. Surface-applying biosolids had contrasting effects on soil physical properties. Soil bulk density was little affected by biosolids applications, but applications were associated with decreased water-stable soil aggregates, increased soil water retention, and increased available water-holding capacity. This study contrasts the potential for C storage in soils treated with surface-applied biosolids with application effects on soil physical properties, underscoring the importance of site-specific management decisions for the beneficial reuse of biosolids in agricultural settings.
Maneuvering Target Tracking Algorithm Based on Interacting Multiple Models
Authors: Yuan Gannan , Zhu Wei , Wang Wei , Yin Bo
Published: May 2015

Aiming at improving the accuracy and quick response of the filter in nonlinear maneuvering target tracking problems, the Interacting Multiple Models Cubature Information Filter (IMMCIF) is proposed. In IMMCIF, the Cubature Information Filter (CIF) is brought into Interacting Multiple Model (IMM), which can not only improve the accuracy but also enhance the quick response of the filter. CIF is a multisensor nonlinear filtering algorithm; it evaluates the information vector and information matrix rather than state vector and covariance, which can reduce the error of nonlinear filtering algorithm. IMM disposes all the models simultaneously through Markov Chain, which can enhance the quick response of the filter. Finally, the simulation results show that the proposed filter exhibits fast and smooth switching when disposing different maneuver models; it performs better than the IMMCKF and IMMUKF on tracking accuracy.
Rho Kinase Inhibitor Fasudil Suppresses the Vasculogenic Mimicry of B16 Mouse Melanoma Cells Both In Vitro and In Vivo
Authors: Xia Yun , Cai Xian-Yi , Fan Ji-Quan , Zhang Li-Ling , Ren Jing-Hua , Chen Jing , Li Zhen-Yu , Zhang Rui-Guang , Zhu Fang , Wu Gang
Published: May 2015

The aim of this study was to investigate the biologic role of the Rho kinase inhibitor fasudil in the vasculogenic mimicry (VM) of B16 mouse melanoma cells. It was previously reported that RhoA plays a critical role in angiogenesis by coordinating endothelial cell cytoskeleton remodeling and promoting endothelial cell motility. Although RhoA has been implicated in the regulation of angiogenesis, little has been described regarding its control of these tumor cell–lined channels. In this study, we established an in vitro model of VM using 3-dimensional cell culturing of mouse B16 melanoma cells and studied VM in vivo by transplanting B16 cells into C57/BL mice. Next, we explored the effect of RhoA and Rho-associated, coiled-coil containing protein kinase (ROCK) on VM formation using the Rho kinase inhibitor fasudil. We provide direct evidence that fasudil leads to reduced vascular-like channels in Matrigel. Additional experiments suggested that fasudil prevents both initial cellular architecture changes and cell migration in vitro. Finally, we provide in-depth evidence for the underlying mechanisms of fasudil-induced VM destruction using the Rho-GTPase agonist lysophosphatidic acid. In vivo studies revealed that fasudil reduced B16 melanoma cell xenograft tumor growth without causing significant toxicity in mice. Fasudil-treated tumors also displayed fewer VM channels. These results suggest that fasudil may be an emerging therapeutic option for targeting cancer VM. Mol Cancer Ther; 14(7); 1582–90. ©2015 AACR.
Preclinical Test of Dacomitinib, an Irreversible EGFR Inhibitor, Confirms Its Effectiveness for Glioblastoma
Authors: Zahonero Cristina , Aguilera Pilar , Ramírez-Castillejo Carmen , Pajares Marta , Bolós Maria Victoria , Cantero Diana , Perez-Nuñez Angel , Hernández-Laín Aurelio , Sánchez-Gómez Pilar , Sepúlveda Juan Manuel
Published: May 2015

Glioblastomas (GBM) are devastating tumors in which there has been little clinical improvement in the last decades. New molecularly directed therapies are under development. EGFR is one of the most promising targets, as this receptor is mutated and/or overexpressed in nearly half of the GBMs. However, the results obtained with first-generation tyrosine-kinase inhibitors have been disappointing with no clear predictive markers of tumor response. Here, we have tested the antitumoral efficacy of a second-generation inhibitor, dacomitinib (PF299804, Pfizer), that binds in an irreversible way to the receptor. Our results confirm that dacomitinib has an effect on cell viability, self-renewal, and proliferation in EGFR-amplified ± EGFRvIII GBM cells. Moreover, systemic administration of dacomitinib strongly impaired the in vivo tumor growth rate of these EGFR-amplified cell lines, with a decrease in the expression of stem cell–related markers. However, continuous administration of the compound was required to maintain the antitumor effect. The data presented here confirm that dacomitinib clearly affects receptor signaling in vivo and that its strong antitumoral effect is independent of the presence of mutant receptor isoforms although it could be affected by the PTEN status (as it is less effective in a PTEN-deleted GBM line). Dacomitinib is being tested in second line for EGFR-amplified GBMs. We hope that our results could help to select retrospectively molecular determinants of this response and to implement future trials with dacomitinib (alone or in combination with other inhibitors) in newly diagnosed GBMs. Mol Cancer Ther; 14(7); 1548–58. ©2015 AACR.