bluuebunny/crossref_metadata_2025 huggingface dataset:
High-resolution records detect human-caused changes to the boreal forest wildfire regime in interior Alaska
Authors: Gaglioti Benjamin V , Mann Daniel H , Jones Benjamin M , Wooller Matthew J , Finney Bruce P
Published: March 2016

Stand-replacing wildfires are a keystone disturbance in the boreal forest, and they are becoming more common as the climate warms. Paleo-fire archives from the wildland–urban interface can quantify the prehistoric fire regime and assess how both human land-use and climate change impact ecosystem dynamics. Here, we use a combination of a sedimentary charcoal record preserved in varved lake sediments (annually layered) and fire scars in living trees to document changes in local fire return intervals (FRIs) and regional fire activity over the last 500 years. Ace Lake is within the boreal forest, located near the town of Fairbanks in interior Alaska, which was settled by gold miners in AD 1902. In the 400 years before settlement, fires occurred near the lake on average every 58 years. After settlement, fires became much more frequent (average every 18 years), and background charcoal flux rates rose to four times their preindustrial levels, indicating a region-wide increase in burning. Despite this surge in burning, the preindustrial boreal forest ecosystem and permafrost in the watershed have remained intact. Although fire suppression has reduced charcoal influx since the 1950s, an aging fuel load experiencing increasingly warm summers may pose management problems for this and other boreal sites that have similar land-use and fire histories. The large human-caused fire events that we identify can be used to test how increasingly common megafires may alter ecosystem dynamics in the future.
A sediment-based reconstruction of Caribbean effective precipitation during the ‘Little Ice Age’ from Freshwater Pond, Barbuda
Authors: Burn Michael J , Holmes Jonathan , Kennedy Lisa M , Bain Allison , Marshall Jim D , Perdikaris Sophia
Published: March 2016

Contemporary climate dynamics of the circum-Caribbean region are characterised by significant precipitation variability on interannual and interdecadal timescales controlled primarily by El Niño Southern Oscillation (ENSO) and the Atlantic Multidecadal Oscillation (AMO). However, our understanding of pre-industrial climate variability in the region is hampered by the sparse geographic distribution of palaeoclimate archives. Here, we present a high-resolution reconstruction of effective precipitation for Barbuda since the mid-16th century, based on biostratigraphic and stable isotope analyses of fossil ostracods and gastropods recovered from lake sediment cores from Freshwater Pond, the only freshwater lake on the island. We interpret episodic fluctuations in shell accumulation in the sediment record to represent changes in the balance between precipitation and evaporation during the ‘Little Ice Age’ (LIA; ~1400–1850 CE) and Industrial (1850–present) periods. Comparisons between indices of reconstructed ENSO and AMO variability, the abundance of the freshwater gastropod Pyrgophorus parvulus and the δ18O records from ostracod calcite suggest that the relative influence of ENSO and AMO on long-term rainfall patterns in Barbuda has changed over the last 400 years. Our findings are in agreement with other high-resolution palaeoclimate studies that suggest that long-term changes in effective precipitation during the LIA were much more variable, temporally and spatially, than previously suggested.
Disease activity and transition outcomes in a childhood-onset systemic lupus erythematosus cohort
Authors: Son M B , Sergeyenko Y , Guan H , Costenbader KH
Published: March 2016

Objective

The chronicity and severity of childhood-onset systemic lupus erythematosus (cSLE) necessitate effective transition from pediatric to adult providers. We studied transition outcomes in a cSLE cohort.

Methods

We identified patients at an adult lupus clinic diagnosed with SLE ≤ 18 years who had been followed by a pediatric rheumatologist. Data extracted from the first three years in adult care (“post-transition period”) included: sociodemographics, depression, anxiety, SLE manifestations, SLE Disease Activity Index (SLEDAI) and Systemic Lupus International Collaborating Clinics/ACR Damage Index for SLE (SLICC) scores, non-adherence, and gaps in care (no appointments in the recommended time frame). Multivariable logistic regression analyses for predictors of: (1) time between pediatric and adult providers, (2) gaps in care, (3) unscheduled utilization (emergency department visits and admissions) (4) depression and/or anxiety were performed, as was a multivariable Poisson regression analysis for number of missed appointments.

Results

In 50 patients, SLEDAI scores were stable (mean 5.7 ± 5.0 at start vs. 4.7 ± 4.8 at year 3, p = 0.2), but SLICC scores increased (0.46 ± 0.84, vs. 0.78 ± 1.25, p = 0.01). Depression and anxiety increased significantly (10% vs. 26%, p = 0.02). Mean time from last pediatric to first adult provider visit was almost nine months (253 ± 392 days). Nearly 75% of patients had ≥ 1 gap in care. White race, low education level and non-adherence were significantly associated with missed appointments.

Conclusion

Despite moderate disease activity in this cSLE transition cohort, prolonged time between pediatric and adult providers and gaps in care in the post-transition period occurred. Anxiety and depression were frequently reported. Future work should identify methods to improve transition.
Standard of treatment and outcomes of adults with lupus nephritis in Africa: a systematic review
Authors: Ameh O I , Kengne A P , Jayne D , Bello A K , Hodkinson B , Gcelu A , Okpechi I G
Published: March 2016

Background

Lupus nephritis (LN) is a significant cause of mortality and morbidity in patients with systemic lupus erythematosus (SLE) and the severity of disease has been described to be increased in Africans. Observational studies have been conducted; however, the treatment and outcome of African patients with LN has not been rigorously assessed.

Methods

We conducted a systematic review of studies selected from a PubMed search of outcome in Africans with biopsy-proven LN from 1 January 1990 to 30 June 2015. Studies that gave information on histology, treatment and outcome of patients were included.

Results

Sixteen studies were selected from a search that yielded 302 papers; half were from North Africa, 2/16 (12.5%) were prospective studies and 2/16 (12.5%) were multi-centre studies. The sample size of reported biopsies in the studies ranged from 22 to 246 patients. Only 3/16 (18.8%) studies used more recent criteria for the classification and reporting of renal histology, and proliferative LN (class III and IV) were reported with increased frequency from the studies. For induction therapy, all the studies reported use of corticosteroids while 15/16 (93.8%) of the studies also used cyclophosphamide (CYC) as an induction agent. Overall mortality rates ranged from 7.9% to 34.9% with increased disease activity, kidney failure and infections cited as common causes of mortality. Five-year renal survival was 48–84% while five-year patient survival was 54%–94%. Survival rates were higher for studies reported from North Africa.

Conclusion

This analysis highlights diagnostic challenges in LN in Africa and shows that a CYC/glucocorticoid-based regimen remains the standard of treatment for adult patients. The contributions of this therapy to reported outcomes of LN in Africa require further exploration.
Multimodal Therapy Involving High-Intensity Interval Training Improves the Physical Fitness, Motor Skills, Social Behavior, and Quality of Life of Boys With ADHD: A Randomized Controlled Study
Authors: Meßler Carolin Friederike , Holmberg Hans-Christer , Sperlich Billy
Published: March 2016

Objective: To compare the effects of multimodal therapy including supervised high-intensity interval training (HIIT) with those of standard multimodal therapy (TRAD) concerning key variables of physical fitness (peak power and oxygen uptake), motor skills, social behavior, and quality of life in boys with ADHD. Method: A single-center, two-arm randomized, controlled design was used, with 28 boys (8-13 years of age, IQ = 83-136) being randomly assigned to multimodal HIIT (three sessions/week, 4 × 4-min intervals at 95% of peak heart rate) or TRAD. The Movement Assessment Battery for Children II evaluated motor skills and the German version of the hyperkinetic disorder questionnaire for external evaluation by the guardians (FBB-HKS) or German version of the hyperkinetic disorder questionnaire for self-assessment by the children (SBB-HKS) and the KINDL-R questionnaires mental health and health-related quality of life. Results: Both interventions enhanced peak power, and HIIT also reduced submaximal oxygen uptake. HIIT was more effective than TRAD in improving the total score for motor skills (including manual dexterity and ball skills; p < .05), self-esteem, friends, and competence ( p < .05) and, moreover, improved subjective ratings of attention. Conclusion: Three weeks of multimodal therapy including HIIT improved physical fitness, motor skills, certain aspects of quality of life, competence, and attention in boys with ADHD.
Toxicologic Pathology Analysis for Translational Neuroscience
Authors: Sharma Alok K. , Morrison James P. , Rao Deepa B. , Pardo Ingrid D. , Garman Robert H. , Bolon Brad
Published: March 2016

A half-day American College of Toxicology continuing education course presented key issues often confronted by translational neuroscientists when predicting human risk from animal-derived toxicologic pathology data. Two talks correlated discrete structures with major functions in brains of rodents and nonrodents. The third lecture provided practical advice to obtain highly homologous rodent brain sections for quantitative morphometry in developmental neurotoxicity testing. The last presentation discussed demographic influences (eg, species, strain, sex, age), physiological attributes (eg, body composition, brain vascularity, pharmacokinetic/pharmacodynamic patterns, etc), and husbandry parameters (eg, group housing) recognized to impact the actions of neuroactive chemicals. Speakers described common cases of real-world challenges to animal data interpretation encountered when designing studies or extrapolating biological responses across species. The efficiency of translational neuroscience efforts will likely be enhanced as new methods (eg, high-resolution non-invasive imaging) improve our capability to cross-connect subtle anatomic and/or biochemical lesions with functional changes over time.
Reversible cerebral vasoconstriction syndrome associated with interferon beta-1a use for multiple sclerosis
Authors: Strohm Tamara , Chaudhry Burhan , Willis Mary A , Shook Steven
Published: March 2016

Background:

Reversible cerebral vasoconstriction syndrome (RCVS) has been associated with multiple medications, cocaine, pregnancy, migraine, and other conditions.

Objectives:

RCVS associated with interferon beta use has never before been described.

Methods:

We describe the case of a 20-year-old female who developed acute onset severe headache and was found to have subarachnoid hemorrhage 2 months after initiating Rebif (Interferon beta-1a) for multiple sclerosis (MS). Cerebral angiography showed multiple areas of distal stenosis and dilatation with radiographic resolution 1 month later.

Results/conclusions:

This is the first case report of RCVS in an MS patient treated with Rebif.
Fenestrated stent grafts for the treatment of complex aortic aneurysm disease: A mature treatment paradigm
Authors: Georgiadis George S , van Herwaarden Joost A , Antoniou George A , Giannoukas Athanasios D , Lazarides Miltos K , Moll Frans L
Published: March 2016

The introduction of fenestrated stent grafts (SGs) to treat abdominal aortic aneurysms (AAAs) with short proximal necks began in 1999. Nowadays, the whole visceral aorta can be treated totally by endovascular means. The established use of fenestrated devices to treat complex AAAs as a first-line management option has been previously reported. An up-to-date evaluation of the literature was performed including all types of publications regarding the use of fenestrated technology to repair complex AAAs. Fenestrated repair is now an established alternative to hybrid/chimney/snorkel repairs. However, specific criteria and prerequisites are required for the use and improvement of this method. Multiple device morphologies have been used incorporating the visceral arteries in various combinations. This modular strategy connects different devices (bridging covered stents and bifurcated SGs) with the aortic main body, thus excluding the aneurysm from the circulation. Precise deployment of the fenestrated SG is mandatory for successful visceral vessel revascularization. Accurate SG sizing and customization, a high level of technical skill, and facilities with modern imaging techniques including 3D road mapping and dedicated hybrid rooms are required. Most experience has been with the custom-made Zenith Cook platform, although off-the-shelf devices have been recently implanted. More complex repairs have been performed over the last few years, but device complexity has also increased. Perioperative, mid-term, and a few recently reported long-term results are encouraging. Secondary interventions remain the main problem, similar to that observed after traditional endovascular abdominal aortic aneurysm repair (EVAR).
Epiaortic fat pad area: A novel index for the dimensions of the ascending aorta
Authors: Toufan Mehrnoush , Pourafkari Leili , Boudagh Shabnam , Nader Nader D
Published: March 2016

We sought to investigate the possible association between the area of the epiaortic fat pad (EAFP) and dimensions of the ascending aorta. A total of 193 individuals underwent transthoracic echocardiography (TTE) prospectively. The area of the EAFP was traced anterior to the aortic root and correlated with the diameter of the aorta. The mean area of the EAFP was 5.16 ± 2.28 cm2. Absolute and indexed dimensions of the ascending aorta had a significant correlation with the area of the EAFP ( p <0.001 for all). In a multivariate linear regression model, age >65 ( p <0.001), body mass index >30 kg/m2 ( p = 0.02) and a history of hyperlipidemia ( p = 0.003) were identified as independent predictors of the area for EAFP. In conclusion, both the absolute and indexed diameters of the ascending aorta at the different segments that directly come into contact with the EAFP linearly correlate with the area of the EAFP measured by TTE.
Synthesis and photocatalytic activity of N-doped BixTi1-xO2 photocatalysts under energy saving lamp illumination
Authors: Huang Qiong , Wang Peng , Fan Yingzheng , Wang Qiu
Published: March 2016

This study presents a synthesis of N-doped BixTi1-xO2 photocatalysts using a sol-gel method. To obtain the optimum doping of N and Bi and operational conditions for photocatalytic oxidation of formaldehyde, several key elements, including nitrogen and bismuth doping, initial concentration of formaldehyde, amount of photocatalysts among others were investigated under energy saving lamp illumination. The properties of the N-doped BixTi1-xO2 photocatalysts were characterized by X-ray diffraction (XRD), Brunauer–Emmett–Teller (BET), scanning electron microscope (SEM), transmission electron microscope (TEM) and UV–visible reflectance diffuse spectroscopy. Experimental results show that an appropriate amount of N and Bi doping incorporated into the TiO2 had produced an increase in photocatalytic activities. The BixTi1-xO2–N(Y) photocatalysts with Bi/(Bi + Ti) and N/Ti molar ratio of 0.15 and 0.2, respectively, showed the highest photocatalytic activity. The highest activity was shown at 92% efficiencies for energy with 24-h continuous lighting of energy saving lamp illumination.
Personalisation, personal budgets and family carers. Whose assessment? Whose budget?
Authors: Brooks Jenni , Mitchell Wendy , Glendinning Caroline
Published: March 2016

The policy of personalisation in English adult social care prioritises choice and control by service users over the support they receive. Carers also have rights to assessments and support, but these rights have developed separately, so interdependencies between carers and service users may be overlooked. Moreover, it may be difficult to reconcile these divergent policies in routine practice. This article reports findings from a study examining the roles played by carers in England in the processes of assessment, support planning and management of personal budgets for disabled and older people. The study was conducted between January 2011 and February 2013. It involved a survey of 16 adult social care departments across 2 English regions, and interviews with personalisation and carers lead officers in three local authorities. The Framework approach was used to manage the data, and analysis was done thematically.

Findings

Practice was fragmented and inconsistent. Carers were reported to be involved in service users' assessments, and also asked about their willingness and ability to continue caring, but not necessarily about their own needs. Separate carers' assessments were reported to be usually offered, but take-up was low and lead officers' opinions about their value varied. Any help given by carers reduced the level of service users' personal budgets, but there was no evidence that carers' own needs (as identified in carers' assessments) were taken into account.

Applications

Greater clarity and consistency is needed, especially the linking of service users' and carers' assessments and finding appropriate ways to meet both. These changes will become increasingly urgent with the implementation of the 2014 Care Act.
Detection of inflammatory biomarkers in saliva and urine: Potential in diagnosis, prevention, and treatment for chronic diseases
Authors: Prasad Sahdeo , Tyagi Amit K , Aggarwal Bharat B
Published: March 2016

Inflammation is a part of the complex biological response of inflammatory cells to harmful stimuli, such as pathogens, irritants, or damaged cells. This inflammation has been linked to several chronic diseases including cancer, atherosclerosis, rheumatoid arthritis, and multiple sclerosis. Major biomarkers of inflammation include tumor necrosis factor, interleukins (IL)-1, IL-6, IL-8, chemokines, cyclooxygenase, 5-lipooxygenase, and C-reactive protein, all of which are regulated by the transcription factor nuclear factor-kappaB. Although examining inflammatory biomarkers in blood is a standard practice, its identification in saliva and/or urine is more convenient and non-invasive. In this review, we aim to (1) discuss the detection of these inflammatory biomarkers in urine and saliva; (2) advantages of using salivary and urinary inflammatory biomarkers over blood, while also weighing on the challenges and/or limitations of their use; (3) examine their role(s) in connection with diagnosis, prevention, treatment, and drug development for several chronic diseases with inflammatory consequences, including cancer; and (4) explore the use of innovative salivary and urine based biosensor strategies that may permit the testing of biomarkers quickly, reliably, and cost-effectively, in a decentralized setting.
Carotid siphon morphology: Is it associated with posterior communicating aneurysms?
Authors: Labeyrie Paul-Emile , Gory Benjamin , Huguet Nazyad , Grenier Charlotte , Ditac Geoffroy , Sadeh-Gonik Udi , Riva Roberto , Turjman Francis
Published: March 2016

Background and purpose

Posterior communicating artery (PComA) aneurysm seems to behave uniquely compared with other intracranial aneurysms at different locations. The association between the morphology of the carotid siphon and PComA aneurysms is not well known. This study aimed to investigate whether the anatomical characteristics of the carotid siphon are associated with the formation and rupture of PComA aneurysms.

Methods

One hundred and thirty-two patients were retrospectively reviewed in a monocentric case–control study. Sixty-seven consecutive patients with PComA aneurysms were included in the case group, and 65 patients with anterior circulation aneurysm situated in other intracranial locations were included in the control group, matched by age and sex. Morphological characteristics of the carotid siphon were analyzed using angiography images. A univariate analysis was used to investigate the association between the morphological characteristics and the formation of PComA aneurysms. Furthermore, a subgroup analysis within the case group compared ruptured and non-ruptured PComA aneurysms.

Results

Patients with PComA aneurysm had a significantly (1.31 ± 0.70 vs. 0.82 ± 0.46; P < 0.001) larger PComA. No association was observed between the morphological characteristics of the carotid siphon and the presence of a PComA aneurysm. Likewise, subgroup analysis showed no significant association between morphological characteristics of the carotid siphon and aneurysm rupture.

Conclusions

This case–control study shows that the carotid siphon morphology seems not to be related to PComA aneurysm formation or rupture.
Socioeconomic deprivation and mortality in people after ischemic stroke: The China National Stroke Registry
Authors: Pan Yuesong , Song Tian , Chen Ruoling , Li Hao , Zhao Xingquan , Liu Liping , Wang Chunxue , Wang Yilong , Wang Yongjun
Published: March 2016

Background

Previous findings of the association between socioeconomic deprivation and mortality after ischemic stroke are inconsistent. There is a lack of data on the association with combined low education, occupational class, and income. We assessed the associations of three indicators with mortality.

Methods

We examined data from the China National Stroke Registry, recording all stroke patients occurred between September 2007 and August 2008. Baseline socioeconomic deprivation was measured using low levels of education at <6 years, occupation as manual laboring, and average family income per capita at ≤¥1000 per month. A total of 12,246 patients with ischemic stroke were analyzed.

Results

In a 12-month follow-up 1640 patients died. After adjustment for age, sex, cardiovascular risk factors, severity of stroke, and prehospital medications, odds ratio for mortality in patients with low education was 1.25 (95%CI 1.05–1.48), manual laboring 1.37 (1.09–1.72), and low income 1.19 (1.03–1.37). Further adjustment for acute care and medications in and after hospital made no substantial changes in these odds ratios, except a marginal significant odds ratio for low income (1.15, 0.99–1.33). The odds ratio for low income was 1.27 (1.01–1.60) within patients with high education. Compared with no socioeconomic deprivation, the odds ratio in patients with socioeconomic deprivation determined by any one indicator was 1.33 (1.11–1.59), by any two indicators 1.36 (1.10–1.69), and by all three indicators 1.56 (1.23–1.97).

Conclusions

There are significant inequalities in survival after ischemic stroke in China in terms of social and material forms of deprivation. General socioeconomic improvement, targeting groups at high risk of mortality is likely to reduce inequality in survival after stroke.
Prostate cancer
Authors: Cooper Sian , Linch Mark
Published: March 2016

Prostate cancer accounts for a quarter of the male cancers managed in a GP’s everyday practice. As GPs are the patient’s primary point of contact, this article will outline when and how to investigate prostate cancer and discuss the ramifications of investigations such as the prostate-specific antigen test. Treatment options, their relative benefits and risks are discussed along with the role of the GP in palliative care, coordinating symptom control and planning for end of life.
Human African Trypanosomiasis Encephalitis in the United States
Authors: Denny Mary Carter , Lai Leon L. , Laureno Robert
Published: March 2016

It is important to recognize the signs and symptoms of human African trypanosomiasis (HAT) in order to facilitate early diagnosis and treatment. A 36-year-old man developed encephalitis caused by HAT. This encephalitis can appear many years after well-tolerated systemic infection. The neurologic manifestations developed 7 years after he had emigrated from Cameroon to the United States. We demonstrate the magnetic resonance imaging before, during, and after his treatment with intravenous eflornithine. Clinical signs and symptoms of HAT can be nonspecific and precede abnormalities on magnetic resonance imaging. Human African trypanosomiasis should be considered in the differential diagnosis of patients who have lived in sub-Saharan Africa and have a clinical presentation of subacute encephalitis.
Chronic Student Absenteeism
Authors: Jacobsen Kathleen , Meeder Linda , Voskuil Vicki R.
Published: March 2016

Routine school attendance is necessary for youth to develop into well-educated, successful adult citizens who will make significant contributions to society. Yet over 5 million students in the United States are chronically absent missing more than 10% of school in a year. The growing problem of chronic absenteeism among youth can be linked to increases in chronic health conditions in childhood such as allergies, asthma, diabetes, and obesity. School nurses are in an ideal position to play a vital role in reducing chronic student absenteeism, enabling youth to achieve their maximum learning potential. However, the role of the school nurse has not historically been recognized as a key factor for assisting youth to be present and regularly engaged in school. This feature article highlights a hospital-funded school nurse program within the state of Michigan that has reduced chronic absenteeism rates by placing school nurses into schools where previously there were none. The program implemented a number of initiatives that were instrumental in increasing the health and safety of students and provides a unique “before and after” glimpse of how school nursing reduces chronic student absenteeism rates and validates the essential role of the nurse within the educational system.
Moving treatment-free remission into mainstream clinical practice in CML
Authors: Hughes Timothy P. , Ross David M.
Published: March 2016

The dramatic success of tyrosine kinase inhibitors (TKIs) has led to the widespread perception that chronic myeloid leukemia (CML) has become another chronic disease, where lifelong commitment to pharmacologic control is the paradigm. Recent trials demonstrate that some CML patients who have achieved stable deep molecular response can safely cease their therapy without relapsing (treatment free remission [TFR]). Furthermore, those who are unsuccessful in their cessation attempt can safely re-establish remission after restarting their TKI therapy. Based on the accumulated data on TFR, we propose that it is now time to change our approach for the many CML patients who have achieved a stable deep molecular response on long-term TKI therapy. Perhaps half of these patients could successfully achieve TFR if offered the opportunity. For many of these patients ongoing therapy is impairing quality of life and imposing a heavy financial burden while arguably achieving nothing. This recommendation is based on the evident safety of cessation attempts and TFR in the clinical trial setting. We acknowledge that there are potential risks associated with cessation attempts in wider clinical practice, but this should not deter us. Instead we need to establish criteria for safe and appropriate TKI cessation. Clinical trials will enable us to define the best strategies to achieve TFR, but clinicians need guidance today about how to approach this issue with their patients. We outline circumstances in which it would be in the patient's best interest to continue TKI, as well as criteria for a safe TFR attempt.
Homozygous calreticulin mutations in patients with myelofibrosis lead to acquired myeloperoxidase deficiency
Authors: Theocharides Alexandre P. A. , Lundberg Pontus , Lakkaraju Asvin K. K. , Lysenko Veronika , Myburgh Renier , Aguzzi Adriano , Skoda Radek C. , Manz Markus G.
Published: March 2016

Key Points

Acquired MPO deficiency in patients with MPN is uniquely associated with homozygous CALR mutations. In line with a posttranscriptional defect, MPO deficiency results from reduced MPO protein levels, but not from decreased MPO mRNA.
Existence of solution and algorithms for a class of bilevel variational inequalities with hierarchical nesting structure
Authors: Li Gaoxi , Wan Zhongping , Chen Jia-wei , Zhao Xiaoke
Published: March 2016

In this paper we consider a class of bilevel variational inequalities with hierarchical nesting structure. We first of all get the existence of a solution for this problem by using the Himmelberg fixed point theorem. Then the uniqueness of the solution for an upper-level variational inequality is given under some mild conditions. By using gap functions of the upper-level and lower-level variational inequalities, we transform bilevel variational inequalities into a one-level variational inequality. Moreover, we propose two iterative algorithms to find the solutions of the bilevel variational inequalities. Finally, the convergence of the proposed algorithm is derived under some mild conditions.
Investigation of mechanical properties of Armco-iron during fatigue test
Authors: Vshivkov А. , Prokhorov А. , Uvarov S. , Plekhov O.
Published: March 2016

Background

In this paper the mechanical properties of armco-iron are studied experimentally. The ultrasonic testing machine USF-2000 was used to carry out fatigue tests involving 106–1010 loading cycles. The frequency of loading is 19.5 ± 0.5 kHz. Based on the experimental data, the Wöhler curve was obtained.

Methods

For the analysis of physical condition, two new sensors were designed, one of which measured the electric resistance of the sample and the other measured the magnetic permeability. Second measuring method can be applied to ferromagnetic materials only, though it may be useful for studying the mechanical properties of metals in general.

Results

It was shown that the significant changes in physical processes accompanying the evolution of structural defects in the material were observed in the final stages of the experiment.

Conclusions

The applied measurement techniques allowed us to exactly determine the time of fatigue crack initiation below the surface the material, which cannot be monitored by the standard optic methods.
The p.Leu167del Mutation in APOE Gene Causes Autosomal Dominant Hypercholesterolemia by Down-regulation of LDL Receptor Expression in Hepatocytes
Authors: Cenarro Ana , Etxebarria Aitor , de Castro-Orós Isabel , Stef Marianne , Bea Ana M. , Palacios Lourdes , Mateo-Gallego Rocío , Benito-Vicente Asier , Ostolaza Helena , Tejedor Teresa , Martín César , Civeira Fernando
Published: March 2016

Context:

The p.Leu167del mutation in the APOE gene has been associated with hyperlipidemia.

Objectives:

Our objective was to determine the frequency of p.Leu167del mutation in APOE gene in subjects with autosomal dominant hypercholesterolemia (ADH) in whom LDLR, APOB, and PCSK9 mutations had been excluded and to identify the mechanisms by which this mutant apo E causes hypercholesterolemia.

Design:

The APOE gene was analyzed in a case-control study.

Setting:

The study was conducted at a University Hospital Lipid Clinic.

Patients or Other Participants:

Two groups (ADH, 288 patients; control, 220 normolipidemic subjects) were included.

Intervention:

We performed sequencing of APOE gene and proteomic and cellular experiments.

Main Outcome Measure:

To determine the frequency of the p.Leu167del mutation and the mechanism by which it causes hypercholesterolemia.

Results:

In the ADH group, nine subjects (3.1%) were carriers of the APOE c.500_502delTCC, p.Leu167del mutation, cosegregating with hypercholesterolemia in studied families. Proteomic quantification of wild-type and mutant apo E in very low-density lipoprotein (VLDL) from carrier subjects revealed that apo E3 is almost a 5-fold increase compared to mutant apo E. Cultured cell studies revealed that VLDL from mutation carriers had a significantly higher uptake by HepG2 and THP-1 cells compared to VLDL from subjects with E3/E3 or E2/E2 genotypes. Transcriptional down-regulation of LDLR was also confirmed.

Conclusions:

p.Leu167del mutation in APOE gene is the cause of hypercholesterolemia in the 3.1% of our ADH subjects without LDLR, APOB, and PCSK9 mutations. The mechanism by which this mutation is associated to ADH is that VLDL carrying the mutant apo E produces LDLR down-regulation, thereby raising plasma low-density lipoprotein cholesterol levels.
Pubertal Onset in Boys and Girls Is Influenced by Pubertal Timing of Both Parents
Authors: Wohlfahrt-Veje Christine , Mouritsen Annette , Hagen Casper P. , Tinggaard Jeanette , Mieritz Mikkel Grunnet , Boas Malene , Petersen Jørgen Holm , Skakkebæk Niels E. , Main Katharina M.
Published: March 2016

Context:

Epidemiological evidence on maternal and paternal heritability of the wide normal variation within pubertal timing is sparse.

Objective:

We aimed to estimate the impact of parental pubertal timing on the onset of puberty in boys and girls.

Design:

Annual pubertal examinations of healthy children in a longitudinal cohort study. Information on parental timing of puberty (earlier, comparable to, or later compared to peers) and menarche age was retrieved from questionnaires.

Participants:

A total of 672 girls and 846 boys.

Main Outcome Measures:

Age at onset of pubic hair (PH2+), breasts (B2+), and menarche in girls; and PH2+, genital stage (G2+), and testis >3 mL with orchidometer (Tvol3+) in boys.

Results:

In boys, pubertal onset was significantly associated with pubertal timing of both parents. PH2+ and Tvol3+ were earlier: −11.8 months (95% confidence interval, −16.8, −6.8)/−8.9 (−12.8, −4.9), and −9.5 (−13.9, −5.1)/−7.1 (−10.4, −3.7) if the father/mother, respectively, had early pubertal development compared to late. In girls, menarche was significantly associated with both parents' pubertal timing: −10.5 months (−15.9, −5.1)/−10.1 (−14.3, −6.0) if father/mother had early pubertal development compared to late. For the onset of PH2+ and B2+ in girls, estimates were −7.0 months (−12.6, −1.4) and −4.1 (−10.6, +2.4)/−6.7 (−11.0, −2.5), and −6.7 (−11.0, −2.0) for fathers/mothers, respectively. Maternal age of menarche was significantly associated with the onset of all pubertal milestones except PH2+ in girls.

Conclusions:

Maternal as well as paternal pubertal timing was a strong determinant of age at pubertal onset in both girls and boys. Age at breast and pubic hair development in girls, which has declined most during recent years, seemed to be least dependent on heritability.
The Relationship Between Oxygen Reserve Index and Arterial Partial Pressure of Oxygen During Surgery
Authors: Applegate Richard L. , Dorotta Ihab L. , Wells Briana , Juma David , Applegate Patricia M.
Published: March 2016

BACKGROUND:

The use of intraoperative pulse oximetry (Spo
2) enhances hypoxia detection and is associated with fewer perioperative hypoxic events. However, Spo
2 may be reported as 98% when arterial partial pressure of oxygen (Pao
2) is as low as 70 mm Hg. Therefore, Spo
2 may not provide advance warning of falling arterial oxygenation until Pao
2 approaches this level. Multiwave pulse co-oximetry can provide a calculated oxygen reserve index (ORI) that may add to information from pulse oximetry when Spo
2 is >98%. This study evaluates the ORI to Pao
2 relationship during surgery.

METHODS:

We studied patients undergoing scheduled surgery in which arterial catheterization and intraoperative arterial blood gas analysis were planned. Data from multiple pulse co-oximetry sensors on each patient were continuously collected and stored on a research computer. Regression analysis was used to compare ORI with Pao
2 obtained from each arterial blood gas measurement and changes in ORI with changes in Pao
2 from sequential measurements. Linear mixed-effects regression models for repeated measures were then used to account for within-subject correlation across the repeatedly measured Pao
2 and ORI and for the unequal time intervals of Pao
2 determination over elapsed surgical time. Regression plots were inspected for ORI values corresponding to Pao
2 of 100 and 150 mm Hg. ORI and Pao
2 were compared using mixed-effects models with a subject-specific random intercept.

RESULTS:

ORI values and Pao
2 measurements were obtained from intraoperative data collected from 106 patients. Regression analysis showed that the ORI to Pao
2 relationship was stronger for Pao
2 to 240 mm Hg (r
2 = 0.536) than for Pao
2 over 240 mm Hg (r
2 = 0.0016). Measured Pao
2 was ≥100 mm Hg for all ORI over 0.24. Measured Pao
2 was ≥150 mm Hg in 96.6% of samples when ORI was over 0.55. A random intercept variance component linear mixed-effects model for repeated measures indicated that Pao
2 was significantly related to ORI (β[95% confidence interval] = 0.002 [0.0019–0.0022]; P < 0.0001). A similar analysis indicated a significant relationship between change in Pao
2 and change in ORI (β [95% confidence interval] = 0.0044 [0.0040–0.0048]; P < 0.0001).

CONCLUSIONS:

These findings suggest that ORI >0.24 can distinguish Pao
2 ≥100 mm Hg when Spo
2 is over 98%. Similarly, ORI > 0.55 appears to be a threshold to distinguish Pao
2 ≥150 mm Hg. The usefulness of these values should be evaluated prospectively. Decreases in ORI to near 0.24 may provide advance indication of falling Pao
2 approaching 100 mm Hg when Spo
2 is >98%. The clinical utility of interventions based on continuous ORI monitoring should be studied prospectively.
Retrotransposon derepression leads to activation of the unfolded protein response and apoptosis in pro-B cells
Authors: Pasquarella Alessandra , Ebert Anja , de Almeida Gustavo Pereira , Hinterberger Maria , Kazerani Maryam , Nuber Alexander , Ellwart Joachim , Klein Ludger , Busslinger Meinrad , Schotta Gunnar
Published: March 2016

The H3K9me3-specific histone methyltransferase Setdb1 impacts on transcriptional regulation by repressing both developmental genes and retrotransposons. How impaired retrotransposon silencing may lead to developmental phenotypes is currently unclear. Here we show that loss of Setdb1 in pro-B cells completely abrogates B cell development. In pro-B cells, Setdb1 is dispensable for silencing of lineage-inappropriate developmental genes. Instead, we detect strong derepression of endogenous Murine Leukemia Virus (MLV) copies. This activation coincides with an unusual change in chromatin structure with only partial loss of H3K9me3 and unchanged DNA methylation, but strongly increased H3K4me3. Production of MLV proteins leads to activation of the unfolded protein response pathway and apoptosis. Thus, our data demonstrate that B cell development critically depends on the proper repression of retrotransposon sequences through Setdb1.
SUMO regulates somatic cyst stem cells maintenance and directly targets hedgehog pathway in adult Drosophila testis
Authors: Lv Xiangdong , Pan Chenyu , Zhang Zhao , Xia Yuanxin , Chen Hao , Zhang Shuo , Guo Tong , Han Hui , Song Haiyun , Zhang Lei , Zhao Yun
Published: March 2016

SUMO (Small ubiquitin-related modifier) modification (SUMOylation) is a highly dynamic post-translational modification (PTM) playing important roles in tissue development and disease progression. However, its function in adult stem cell maintenance is largely unknown. Here we report the function of SUMOylation in somatic cyst stem cells (CySCs) self-renewal in adult Drosophila testis. The SUMO pathway cell-autonomously regulates CySCs maintenance. Reduction of SUMOylation promotes premature differentiation of CySCs and impedes the proliferation of CySCs, which finally reduce the number of CySCs. Consistently, CySC clones carrying mutation of the SUMO conjugating enzyme are rapidly lost. Furthermore, inhibition of SUMO pathway phenocopies the disruption of Hedgehog (Hh) pathway, and can block the promoted proliferation of CySCs by Hh activation. Importantly, SUMO pathway directly regulates the SUMOylation of Hh pathway transcriptional factor, Cubitus interruptus (Ci), which is required for promoting CySCs proliferation. Thus, we conclude that SUMO directly targets Hh pathway and regulates CySCs maintenance in adult Drosophila testis.
Regional signals in the planarian body guide stem cell fate in the presence of DNA instability
Authors: Peiris T. Harshani , Ramirez Daniel , Barghouth Paul G. , Ofoha Udokanma , Davidian Devon , Weckerle Frank , Oviedo Néstor J.
Published: March 2016

Cellular fate decisions are influenced by their topographical location in the adult body. For instance, tissue repair and neoplastic growth are greater in anterior than in posterior regions of adult animals. However, the molecular underpinnings of these regional differences are unknown. We identified a regional switch in the adult planarian body upon systemic disruption of homologous recombination with RNA-interference of Rad51. Rad51 knock-down increases DNA double strand breaks (DSB) throughout the body, but stem cells react differently depending on their location along the anteroposterior axis. In the presence of extensive DSB, cells in the anterior part of the body resist death, whereas cells in the posterior region undergo apoptosis. Furthermore, we found that presence of brain tissue is capable of inducing proliferation of cells with DNA damage and that the retinoblastoma pathway enables overproliferation of cells with DSB while attending to the demands of tissue growth and repair. Our results implicate both autonomous and non-autonomous mechanisms as key mediators of regional cell behavior and cellular transformation in the adult body.
JNK signaling regulates E-cadherin junctions in germline cysts and determines primordial follicle formation in mice
Authors: Niu Wanbao , Wang Ye , Wang Zhengpin , Xin Qiliang , Wang Yijing , Feng Lizhao , Zhao Lihua , Wen Jia , Zhang Hua , Wang Chao , Xia Guoliang
Published: March 2016

Physiologically, the size of the primordial follicle pool determines the reproductive lifespan of female mammals, while its establishment largely depends on a proper process of germline cyst breakdown during the perinatal period. However, the mechanisms regulating this process are poorly understood. Here we demonstrate that c-Jun amino-terminal kinase (JNK) signaling is crucial for germline cyst breakdown and primordial follicle formation. JNK was specifically localized in oocytes and its activity was increased as germline cyst breakdown progressed. Importantly, the disruption of JNK signaling with its specific inhibitor (SP600125) or knock-down technology (Lenti-JNK-shRNAs) resulted in significantly suppressed cyst breakdown and primordial follicle formation in cultured mouse ovaries. Our results show that E-cadherin is intensely expressed in germline cysts, and that its decline is necessary for oocyte release from the cyst. However, the inhibition of JNK signaling leads to aberrantly enhanced localization of E-cadherin at oocyte–oocyte contact sites. Meanwhile, WNT4 expression is upregulated after SP600125 treatment. Additionally, similar to SP600125 treatment, WNT4 overexpression delays cyst breakdown; and is accompanied by abnormal E-cadherin expression patterns. In conclusion, our results suggest that JNK signaling, which is inversely correlated with WNT4, plays an important role in perinatal germline cyst breakdown and primordial follicle formation by regulating E-cadherin junctions between oocytes in mouse ovaries.
Spontaneous shaker rat mutant – a new model for X-linked tremor/ataxia
Authors: Figueroa Karla P. , Paul Sharan , Calì Tito , Lopreiato Raffaele , Karan Sukanya , Frizzarin Martina , Ames Darren , Zanni Ginevra , Brini Marisa , Dansithong Warunee , Milash Brett , Scoles Daniel R. , Carafoli Ernesto , Pulst Stefan M.
Published: March 2016

The shaker rat is an X-linked recessive spontaneous model of progressive Purkinje cell (PC) degeneration exhibiting a shaking ataxia and wide stance. Generation of Wistar Furth (WF)/Brown Norwegian (BN) F1 hybrids and genetic mapping of F2 sib-sib offspring using polymorphic markers narrowed the candidate gene region to 26 Mbp denoted by the last recombinant genetic marker DXRat21 at 133 Mbp to qter (the end of the long arm). In the WF background, the shaker mutation has complete penetrance, results in a stereotypic phenotype and there is a narrow window for age of disease onset; by contrast, the F2 hybrid phenotype was more varied, with a later age of onset and likely non-penetrance of the mutation. By deep RNA-sequencing, five variants were found in the candidate region; four were novel without known annotation. One of the variants caused an arginine (R) to cysteine (C) change at codon 35 of the ATPase, Ca2+ transporting, plasma membrane 3 (Atp2b3) gene encoding PMCA3 that has high expression in the cerebellum. The variant was well supported by hundreds of overlapping reads, and was found in 100% of all affected replicas and 0% of the wild-type (WT) replicas. The mutation segregated with disease in all affected animals and the amino acid change was found in an evolutionarily conserved region of PMCA3. Despite strong genetic evidence for pathogenicity, in vitro analyses of PMCA3R35C function did not show any differences to WT PMCA3. Because Atp2b3 mutation leads to congenital ataxia in humans, the identified Atp2b3 missense change in the shaker rat presents a good candidate for the shaker rat phenotype based on genetic criteria, but cannot yet be considered a definite pathogenic variant owing to lack of functional changes.
Increased oxidative stress and apoptosis in the hypothalamus of diabetic male mice in the insulin receptor substrate-2 knockout model
Authors: Baquedano Eva , Burgos-Ramos Emma , Canelles Sandra , González-Rodríguez Agueda , Chowen Julie A. , Argente Jesús , Barrios Vicente , Valverde Angela M. , Frago Laura M.
Published: March 2016

Insulin receptor substrate-2-deficient (IRS2−/−) mice are considered a good model to study the development of diabetes because IRS proteins mediate the pleiotropic effects of insulin-like growth factor-I (IGF-I) and insulin on metabolism, mitogenesis and cell survival. The hypothalamus might play a key role in the early onset of diabetes, owing to its involvement in the control of glucose homeostasis and energy balance. Because some inflammatory markers are elevated in the hypothalamus of diabetic IRS2−/− mice, our aim was to analyze whether the diabetes associated with the absence of IRS2 results in hypothalamic injury and to analyze the intracellular mechanisms involved. Only diabetic IRS2−/− mice showed increased cell death and activation of caspase-8 and -3 in the hypothalamus. Regulators of apoptosis such as FADD, Bcl-2, Bcl-xL and p53 were also increased, whereas p-IκB and c-FLIPL were decreased. This was accompanied by increased levels of Nox-4 and catalase, enzymes involved in oxidative stress. In summary, the hypothalamus of diabetic IRS2−/− mice showed an increase in oxidative stress and inflammatory markers that finally resulted in cell death via substantial activation of the extrinsic apoptotic pathway. Conversely, non-diabetic IRS2−/− mice did not show cell death in the hypothalamus, possibly owing to an increase in the levels of circulating IGF-I and in the enhanced hypothalamic IGF-IR phosphorylation that would lead to the stimulation of survival pathways. In conclusion, diabetes in IRS2-deficient male mice is associated with increased oxidative stress and apoptosis in the hypothalamus.
Research of perimeter reinforcement of the ground base by cement-sand mortar injection
Authors: Нуждин Леонид , Nuzhdin Leonid , Нуждин Матвей , Nuzhdin Matvey
Published: March 2016

The article analyzes the results of a series of full-scale experiments for studying consolidation of foundations by perimeter reinforcement of the soil by rigid incompressible irregularly shaped inclusions. The experiments modeled consolidation of a shallow soil foundation base by directed high-pressure injection of mobile cement and sand mixtures. Generalization and analysis of the results of several dozens of laboratory experiments allowed to establish approaches to setting rational parameters of perimeter reinforcement of soil foundations by creation of rigid incompressible inclusions using injection of mobile cement-sand mixtures.