bluuebunny/crossref_metadata_2025 huggingface dataset:
Utility of Pediatric Appendicitis Score in Female Adolescent Patients
Authors: Scheller RoseAnn L. , Depinet Holly E. , Ho Mona L. , Hornung Richard W. , Reed Jennifer L.
Published: January 2016

Objectives

Acute appendicitis is common in the pediatric population and is difficult to diagnose in adolescent females. The validated Pediatric Appendicitis Score (PAS) has unclear utility in female adolescents. The purpose of this study is to determine the sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of the PAS for female adolescents compared to all other patients.

Methods

This study examined a retrospective observational cohort of patients ages 3 to 21 years in a pediatric emergency department with prospectively assigned PAS from an existing database. We compared the sensitivity, specificity, PPV, and NPV of the PAS for acute appendicitis among female adolescent patients (13 to 21 years) and all other patients.

Results

Of the 1,228 patients enrolled, 901 (73.4%) had a complete PAS. Among the 901 patients, 249 (27.6%) had pathology‐proven appendicitis, 494 (54.8%) were female, and 272 (30.2%) were adolescent females. At a cutoff of ≥8, the PAS showed a specificity of 89% for adolescent females and 78% for all other patients (p < 0.001), although the specificities did not differ at a cutoff of ≥7. At both cutoffs, the PPVs were poor in both groups. At a cutoff of ≥3, the PAS showed similar sensitivities in both groups. At a cutoff of <3, the NPVs did not significantly differ between groups.

Conclusion

At a cutoff of ≥8 (although not ≥7), the PAS demonstrated a higher specificity among female adolescents compared to all other patients. The PPV for both cutoffs in both groups were poor. At a cutoff of ≥3, sensitivities were equivalent. The NPV for a cutoff of <3 was acceptable but similar in both groups. While sensitivities were similar to previously reported, specificities in both groups were lower. This highlights the need for further investigation of the PAS's performance in specific subpopulations.
The Use of Intravenous Acetaminophen for Acute Pain in the Emergency Department
Authors: Sin Billy , Wai Mabel , Tatunchak Tamara , Motov Sergey M.
Published: January 2016

Objectives

Acetaminophen (APAP) is a mainstay for pain management worldwide. The intravenous (IV) formulation has been widely used in Europe for more than 20 years in adults and children. In the United States, IV APAP obtained full approval from the Food and Drug Administration in 2010. There is emerging literature to suggest the use of IV APAP for pain reduction in the emergency department (ED). This evidence‐based review examines the evidence pertaining to the use of IV APAP for acute pain control in the ED.

Methods

The MEDLINE and EMBASE databases were searched. Randomized controlled trials (RCTs) that described or evaluated the use of IV APAP for acute pain in the ED were included. Duplicate articles, unpublished reports, abstracts, review articles, and non‐English literature were excluded. The primary outcome of interest in this review was the difference in pain score between IV APAP and active comparator or placebo from baseline to a cutoff time specified in the original trials. Secondary outcome measures were the incidence of adverse events and reduction in the amount of adjuvant analgesics consumed by patients who received IV APAP. Methodologic quality of the trials was assessed using the Grading of Recommendations Assessment, Development, and Evaluation criteria.

Results

Fourteen RCTs with various methodologic flaws, which enrolled a total of 1,472 patients, met the inclusion criteria. The level of evidence for the individual trials ranged from very low to moderate. In three of the 14 trials, a significant reduction in pain scores was observed in patients who received IV APAP. The first trial found a significant reduction in mean pain scores when IV APAP was compared to IV morphine at 30 minutes after drug administration (4.7 ± 2.3 vs. 2.9 ± 2.2). In the second trial, patients who received IV APAP reported of lower pain scores (31.7 ± 18 mm, 95% confidence interval [CI] = 8.2 to 25.2 mm) compared to those who received IV morphine (48.3 ± 14.1 mm, 95% CI = 8.2 to 25.2 mm), 15 minutes after drug administration. A third trial found a significant reduction (p = 0.005) in the mean pain scores when IV APAP was compared to intramuscular piroxicam at 90 minutes after drug administration. In the remaining eight trials, pain scores were not statistically different when IV APAP was compared to other pain medications. The incidence of side effects associated with IV APAP was very low.

Conclusions

Fourteen RCTs with various methodologic flaws provided limited evidence to support the use of IV APAP as the primary analgesic for acute pain control in patients who present to the ED.
Diffusion‐weighted imaging predicts upgrading of Gleason score in biopsy‐proven low grade prostate cancers
Authors: Park Sung Yoon , Oh Young Taik , Jung Dae Chul , Cho Nam Hoon , Choi Young Deuk , Rha Koon Ho , Hong Sung Joon
Published: January 2016

Objective

To analyse whether diffusion‐weighted imaging (DWI) predicts Gleason score (GS) upgrading in biopsy‐proven low grade prostate cancer (PCa).

Patients and Methods

A total of 132 patients who had biopsy‐proven low grade (GS < 7) PCa, 3T DWI results, and surgical confirmation were retrospectively included in the study. Clinical variables (prostate‐specific antigen, greatest percentage of cancer in a biopsy core and percentage of positive cores) and DWI variables (minimum apparent diffusion coefficient [ADCmin] and mean ADC [ADCmean]) were evaluated. ADCmin was measured, by two independent, blinded readers, using a region of interest (ROI) of 5–10 mm2 at the area of lowest ADC value within a cancer, while ADCmean was measured using an ROI covering more than half of a cancer. Logistic regression and receiver‐operating characteristic curve analyses were performed.

Results

The rate of GS upgrading was 46.1% (61/132). In both univariate and multivariate analyses, ADCmin and ADCmean were persistently significant for predicting GS upgrading (P < 0.05), whereas clinical variables were not (P > 0.05). In both readers’ results, the area under the curve (AUC) of ADCmin was significantly greater than that of ADCmean (reader 1: AUC 0.760 vs 0.711; P < 0.001; reader 2: AUC 0.752 vs 0.714; P = 0.003).

Conclusion

Our results showed that DWI may predict GS upgrading of biopsy‐proven low grade PCa. The variable ADCmin in PCa may perform better than ADCmean.
Neuroprotective Effects of Hydrogen Sulfide Against Early Brain Injury and Secondary Cognitive Deficits Following Subarachnoid Hemorrhage
Authors: Li Tong , Liu Hansen , Xue Hao , Zhang Jinsen , Han Xiao , Yan Shaofeng , Bo Shishi , Liu Song , Yuan Lin , Deng Lin , Li Gang , Wang Zhen
Published: January 2016

Although the neuroprotective effects of hydrogen sulfide (H2S) have been demonstrated in several studies, whether H2S protects against early brain injury (EBI) and secondary cognitive dysfunction in subarachnoid hemorrhage (SAH) model remains unknown. This study was undertaken to evaluate the influence of H2S on both acute brain injury and neurobehavioral changes as well as the underlying mechanisms after SAH. The H2S donor, NaHS, was administered via an intraperitoneal injection at a dose of 5.6 mg/kg at 2 h, 6 h, 24 h, and 46 h after SAH in rat model. The results showed that NaHS treatment significantly improved brain edema and neurobehavioral function, and attenuated neuronal cell death in the prefrontal cortex, associated with a decrease in Bax/Bcl‐2 ratio and suppression of caspase‐3 activation at 48 h after SAH. NaHS also promoted phospho‐Akt and phospho‐ERK levels. Furthermore, NaHS treatment significantly enhanced the levels of brain‐derived neurotrophic factor (BDNF) and phospho‐CREB. Importantly, NaHS administration improved learning and memory performance in the Morris water maze test at 7 days post‐SAH in rats. These results demonstrated that NaHS, as an exogenous H2S donor, could significantly alleviate the development of EBI and cognitive dysfunction induced by SAH via Akt/ERK‐related antiapoptosis pathway, and upregulating BDNF‐CREB expression.
SLC20A2 Deficiency in Mice Leads to Elevated Phosphate Levels in Cerbrospinal Fluid and Glymphatic Pathway‐Associated Arteriolar Calcification, and Recapitulates Human Idiopathic Basal Ganglia Calcification
Authors: Wallingford Mary Catherine , Chia Jia Jun , Leaf Elizabeth M. , Borgeia Suhaib , Chavkin Nicholas W. , Sawangmake Chenphop , Marro Ken , Cox Timothy C. , Speer Mei Y. , Giachelli Cecilia M.
Published: January 2016

Idiopathic basal ganglia calcification is a brain calcification disorder that has been genetically linked to autosomal dominant mutations in the sodium‐dependent phosphate co‐transporter, SLC20A2. The mechanisms whereby deficiency of Slc20a2 leads to basal ganglion calcification are unknown. In the mouse brain, we found that Slc20a2 was expressed in tissues that produce and/or regulate cerebrospinal fluid, including choroid plexus, ependyma and arteriolar smooth muscle cells. Haploinsufficient Slc20a2 +/− mice developed age‐dependent basal ganglia calcification that formed in glymphatic pathway‐associated arterioles. Slc20a2 deficiency uncovered phosphate homeostasis dysregulation characterized by abnormally high cerebrospinal fluid phosphate levels and hydrocephalus, in addition to basal ganglia calcification. Slc20a2 siRNA knockdown in smooth muscle cells revealed increased susceptibility to high phosphate‐induced calcification. These data suggested that loss of Slc20a2 led to dysregulated phosphate homeostasis and enhanced susceptibility of arteriolar smooth muscle cells to elevated phosphate‐induced calcification. Together, dysregulated cerebrospinal fluid phosphate and enhanced smooth muscle cell susceptibility may predispose to glymphatic pathway‐associated arteriolar calcification.
Mutational randomness as conditional independence and the experimental vindication of mutationalLamarckism
Authors: Razeto‐Barry Pablo , Vecchi Davide
Published: January 2016

TheModernSynthesis enshrined natural selection as the driver of adaptive evolution mainly by eliminating competing explanations. One of the eliminated competitors wasLamarckism, particularly ‘mutationalLamarckism’, a hypothesis according to which mutations may be directed towards producing phenotypes that improve the performance of the organism in a particular environment. Contrary to this hypothesis, theModernSynthesis' view claims that mutations are ‘random’, even though the precise meaning of the term was never formally explicated. Current evidence seemingly in favour of the existence of legitimate cases of mutationalLamarckism has revitalized interest to seek a clarification of the meaning of the term ‘random’ in this context. Herein we analyse previous definitions of random mutations and show that they are deficient in three ways: either they are too wide, or too narrow, or dyadic. We argue that the linguistic expression ‘random mutation’ refers to a triadic rather than a dyadic relationship, propose a new, formal and precise definition based on the probabilistic concept of conditional independence, and finally provide examples of its application. One important consequence of our analysis is that the genomic specificity of the mutational process is not a necessary condition for the existence of mutationalLamarckism.
Local and Landscape Factors Driving the Structure of Tropical Anuran Communities: Do Ephemeral Ponds have a Nested Pattern?
Authors: Almeida‐Gomes Mauricio , Rocha Carlos F. D. , Vieira Marcus V.
Published: January 2016

The sets of species in animal and plant communities often comprise nested subsets of the species in broader communities. Although most mechanisms causing nested patterns are known and have been demonstrated for different environments and taxa, how amphibian communities are structured in ephemeral ponds in tropical disturbed landscapes remains unknown. We investigated if pond size, duration, presence of trees (local factors), and the proportion of forest cover surrounding ponds (landscape factor) affect anuran species richness and composition, and if pond assemblages showed a nested pattern. We sampled 11 ephemeral ponds in a pasture matrix near a large Atlantic Forest remnant in Brazil and measured local and landscape variables inside two buffer zones around each pond (100 and 500 m). We marked 1514 individuals from 23 anuran species, and found that richness in ponds ranged from 3–14 species. Both local and landscape factors explained frog species richness in the sampled ponds, and seemed to affect community composition. Frog communities occurred in a non‐nested pattern, contrary to our expectations: species found in poor subsets were not found in larger, more complex ponds. Local and landscape characteristics create a variety of environments in ephemeral ponds, even in impoverished ones; these characteristics restrict pond occupancy for some species, and result in a non‐nested pattern.
Facing complexity in tropical conservation: how reduced impact logging and climatic extremes affect beta diversity in tropical amphibian assemblages
Authors: Hölting Monique , Bovolo C. Isabella , Ernst Raffael
Published: January 2016

Biodiversity in pristine forest biomes is increasingly disturbed by human activity. Drivers such as logging and climate extremes are thought to collectively erode diversity, but their interactions are not well understood. However, ignoring such complexities may result in poor conservation management decisions. Here, we present the first study dealing with the complexity arising from the effects of interactions of two increasingly important disturbance factors (selective logging and climatic extreme events) on beta diversity patterns at different scales. Specifically, we examined extensive amphibian assemblage datasets obtained within a quasi‐experimental pre‐/post‐harvesting scheme in the lowland rainforests of Central Guyana. Changes in small‐scale patterns of beta diversity were not detectable at the higher landscape level, indicating that local‐scale dynamics are more informative for evaluating disturbance impacts. The results also underscore the importance of including abundance data when investigating homogenization or heterogenization effects, which should be considered when designing post‐logging impact assessments and selecting impact indicators. Moreover, logging should be regarded as a multifaceted driver that contributes to changes in biodiversity patterns in different ways, depending on interactions with other drivers. The effects of extreme climate events were significantly more pronounced in unlogged forest, while logged forest assemblages appeared buffered due to the presence of novel habitats. Imprudent post‐logging renaturation measures may thus counteract conservation targets. These findings highlight the fact that indicator bias and unaccounted interactions between multiple drivers can lead to misguided management strategies.
Caregiver perceptions of childhood weight: demographic moderators and correlates
Authors: Miller D. , Johnson W. , Miller M. , Miller J. , Sutin A. R.
Published: January 2016

Background

To examine whether ethnicity moderates the association between caregiver characteristics and perceptions of childhood weight and whether these perceptions are associated with their child's obesity status.

Methods

Caregivers recruited from paediatricians' offices (n = 453) completed a survey about childhood health; nurses weighed and measured the children. Caregivers reported their own weight and height, demographic information about their family and made ratings of healthy weight for children in general and for their own child in particular.

Results

African American caregivers were more likely to view heavier girls as healthier, but this association held only for lower income families or caregivers with higher body mass index. Hispanic caregivers were more likely to misperceive their own child's weight if either the caregiver or the child had a higher body mass index. Parents who perceived heavier weight as healthier or misperceived their own child's weight were more likely to have a child with obesity. This latter association held regardless of ethnicity.

Conclusion

The association between ethnicity and perceptions of healthy childhood weight are complex. The relation between caregivers' perceptions of healthy weight and their own child's obesity status, however, was similar regardless of ethnicity.
Prenatal Maternal Stress Predicts Methylation of Genes Regulating the Hypothalamic–Pituitary–Adrenocortical System in Mothers and Newborns in the Democratic Republic of Congo
Authors: Kertes Darlene A. , Kamin Hayley S. , Hughes David A. , Rodney Nicole C. , Bhatt Samarth , Mulligan Connie J.
Published: January 2016

Exposure to stress early in life permanently shapes activity of the hypothalamic–pituitary–adrenocortical (HPA) axis and the brain. Prenatally, glucocorticoids pass through the placenta to the fetus with postnatal impacts on brain development, birth weight (BW), and HPA axis functioning. Little is known about the biological mechanisms by which prenatal stress affects postnatal functioning. This study addresses this gap by examining the effect of chronic stress and traumatic war‐related stress on epigenetic changes in four key genes regulating the HPA axis in neonatal cord blood, placenta, and maternal blood: CRH, CRHBP, NR3C1, and FKBP5. Participants were 24 mother–newborn dyads in the conflict‐ridden region of the eastern Democratic Republic of Congo. BW data were collected at delivery and maternal interviews were conducted to assess culturally relevant chronic and war‐related stressors. Chronic stress and war trauma had widespread effects on HPA axis gene methylation, with significant effects observed at transcription factor binding (TFB) sites in all target genes tested. Some changes in methylation were unique to chronic or war stress, whereas others were observed across both stressor types. Moreover, stress exposures impacted maternal and fetal tissues differently, supporting theoretical models that stress impacts vary according to life phase. Methylation in several NR3C1 and CRH CpG sites, all located at TFB sites, was associated with BW. These findings suggest that prenatal stress exposure impacts development via epigenetic changes in HPA axis genes.
Introduction to the Special Section on Epigenetics
Authors: Lester Barry M. , Conradt Elisabeth , Marsit Carmen
Published: January 2016

Epigenetics provides the opportunity to revolutionize our understanding of the role of genetics and the environment in explaining human behavior, although the use of epigenetics to study human behavior is just beginning. In this introduction, the authors present the basics of epigenetics in a way that is designed to make this exciting field accessible to a wide readership. The authors describe the history of human behavioral epigenetic research in the context of other disciplines and graphically illustrate the burgeoning of research in the application of epigenetic methods and principles to the study of human behavior. The role of epigenetics in normal embryonic development and the influence of biological and environmental factors altering behavior through epigenetic mechanisms and developmental programming are discussed. Some basic approaches to the study of epigenetics are reviewed. The authors conclude with a discussion of challenges and opportunities, including intervention, as the field of human behavioral epigenetics continue to grow.
Middle Childhood Support‐Seeking Behavior During Stress: Links With Self‐Reported Attachment and Future Depressive Symptoms
Authors: Dujardin Adinda , Santens Tara , Braet Caroline , De Raedt Rudi , Vos Pieter , Maes Bea , Bosmans Guy
Published: January 2016

This study tested whether children's more anxious and avoidant attachment is linked to decreased support‐seeking behavior toward their mother during stress in middle childhood, and whether children's decreased support‐seeking behavior enhances the impact of experiencing life events on the increase of depressive symptoms 18 months later. Ninety‐eight 8‐ to 12‐year‐old children filled out questionnaires assessing their level of anxious and avoidant attachment and depressive symptoms. Children's support‐seeking behavior was observed through measuring the time children waited before calling for their mother's help while carrying out a stressful task. Results supported the hypothesis that more anxiously or avoidantly attached children waited longer before seeking maternal support. Moreover, waiting longer was related to increased depressive symptoms at follow‐up in children who reported more experienced life events.
Is insulin‐like growth factor‐I a good marker for treatment adherence in growth hormone deficiency in adulthood?
Authors: Auer Matthias K. , Stieg Mareike R. , Hoffmann Janis , Stalla Günter K.
Published: January 2016

Objective

There is a paucity of studies on adherence to growth hormone treatment in growth hormone deficient (GHD) adults. Therefore, this study reports on adherence to GH‐replacement therapy in adults with GHD, with a special focus on the course and potential predictors of nonadherence.

Design

Retrospective single‐centre cohort study.

Patients

From the local patient database, 179 suitable patients with GHD were identified.

Measurements

The primary outcome was adherence assessed by calculating the percentage of available prescription data in comparison with recommended GH dosages over a mean follow‐up period of 92·4 months. Patients were categorized into five adherence categories ranging from <20% to >80%.

Results

Mean overall adherence was 74·0%, with 52·9% of patients falling into the adherence group of >80% and 8·8% of <20%. There was a significant drop in adherence (9·8%) between the first and second years of treatment (P < 0·001). Patients with childhood‐onset GHD were significantly less adherent to GH treatment than patients with adult‐onset GHD (62·0% vs 77·0%, P = 0·012); however, this finding was no longer significant after including age as a covariate. Frequency of IGF‐1 levels lying outside the age‐ and sex‐specific reference range was not a good indicator for adherence.

Conclusion

Although overall adherence was relatively high in our study sample, there is a significant amount of patients who should be regarded as nonadherent. This applies in particular to younger patients. Treating physicians should be aware of the fact that IGF‐1 levels do not seem to be a good indicator for adherence.
Comparison of clinical and radiographic status of platform‐switched implants placed in patients with and without type 2 diabetes mellitus: a 24‐month follow‐up longitudinal study
Authors: Al Amri Mohammad D. , Abduljabbar Tariq S.
Published: January 2016

Objective

The purpose of the present 24‐month follow‐up longitudinal study was to compare the clinical and radiographic status of platform‐switched implants placed in patients with and without type 2 diabetes mellitus (T2DM).

Material and methods

In total, 45 male non‐smokers were included. In Group‐1, there were 23 patients with T2DM, and patients in Group‐2 comprised of 22 self‐reported non‐diabetic controls. Under local anesthesia, platform‐switched implants were placed in the mandible. Peri‐implant bleeding on probing (BOP), probing depth (PD), marginal bone loss (MBL) and hemoglobin A1c (HbA1c) levels were measured at 12 and 24 months of follow‐up. Participants were also enrolled in a biannual oral hygiene maintenance program.

Results

The mean age of participants in groups 1 and 2 were 42.4 years (40–46 years) and 41.8 years (39–44 years), respectively. In Group‐1, the mean duration of T2DM was 14.5 ± 0.7 months. At 12 and 24 months of follow‐up, there was no significant difference in the mean HbA1c levels among patients in groups 1 and 2. At 12 and 24 months of follow‐up, there was no significant difference in peri‐implant BOP, PD and MBL in both groups.

Conclusions

Platform‐switched implants can remain clinically and radiographically stable in patients with T2DM in a manner similar to non‐diabetic individuals. However, it is emphasized that bone loss around implants is influenced by several factors (such as oral hygiene status, glycemic control and tobacco smoking) and not merely platform switching.
Determinants of epoxy allergy in the construction industry: a case–control study
Authors: Spee Ton , Timmerman Johan G. , Rühl Reinhold , Kersting Klaus , Heederik Dick J. J. , Smit Lidwien A. M.
Published: January 2016

Background

Workers exposed to epoxy products are at risk of developing allergic contact dermatitis.

Objectives

To compare workers throughout the German construction industry with and without skin allergy to epoxy resins, hardeners, and/or reactive diluents, and to investigate which determinants are related to the development of epoxy allergy.

Methods

A questionnaire was completed by 179 epoxy allergy cases, and 151 epoxy workers as controls. Crude and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by the use of backwards stepwise logistic regression analysis. A multiple imputation approach was used to deal with missing data.

Results

Epoxy allergy was associated with an unusually high level of exposure to epoxy products [OR 2.13 (95%CI: 1.01–4.51)], wearing short sleeves or short trousers [OR 2.38 (95%CI: 1.03–5.52)], and not always using the correct type of gloves [OR 2.12 (95%CI: 1.12–4.01)]. A monotonic increasing risk was found with increasing exposure hours per week [OR 1.72 (95%CI: 1.39–2.14)]. Not using skin cream was inversely associated with epoxy allergy [OR 0.22 (95%CI: 0.08–0.59)]. Years working with epoxy products were inversely associated with epoxy allergy [OR 0.41 (95%CI: 0.27–0.61) per 10‐year increase], suggesting a healthy worker survivor effect.

Conclusions

Occupational epoxy allergy may be prevented by improving occupational hygiene behaviour and personal protection.
The Echocardiographic “Spike and Dome” – Obstruction It Is But Where?
Authors: Fadel Bahaa M. , Bazari Rasha , Husain Aysha , Fathala Ahmed , Dahdouh Ziad , Mohty Dania , Di Salvo Giovanni
Published: January 2016

Spectral Doppler interrogation of the descending thoracic and abdominal aorta provides valuable information regarding cardiac and vascular hemodynamics. An abnormal aortic Doppler profile is encountered in pathological conditions that affect the aorta and its branches, the aortic valve, the left ventricle, and the pericardium. Characteristic findings on Doppler interrogation of the aorta are often noted in individuals with obstructive atherosclerotic disease of the aorto‐iliac system including severe stenosis or occlusion of the distal aorta and/or iliac arteries. In this manuscript, we highlight the findings on spectral Doppler that led to the identification of occlusive disease in the distal aorta.
Dothistroma needle blight, weather and possible climatic triggers for the disease's recent emergence
Authors: Woods A. J. , Martín‐García J. , Bulman L. , Vasconcelos M. W. , Boberg J. , La Porta N. , Peredo H. , Vergara G. , Ahumada R. , Brown A. , Diez J. J.
Published: January 2016

Dothistroma needle blight (DNB), caused by the two fungiDothistroma septosporumandD. pini,is a major disease of pines with a worldwide distribution. Increases in the incidence and severity of disease in areas where the disease has long been established and notable range expansions have both recently been observed. The aim of this review was to assess the relationship betweenDNB, weather factors and climate to better understand possible underlying causes of this recent intensification in disease. A substantial body of literature shows that the life cycles of the fungi are closely related to weather factors such as precipitation and temperature. Given the rapid response ofDNBto favourable weather conditions, it seems plausible that changes in disease behaviour could be due to changes in climate. The recurrent El Niño‐Southern oscillation (ENSO) phenomenon influences patterns of temperature and precipitation in many regions of the world, often resulting in warmer and wetter conditions than normal. We found that since the 1950s, four of the past five strong El Niño events appear to have coincided with reports of increasedDNBactivity on an intercontinental scale. The lack of long‐term standardized data records limits our ability to fully interpret this relationship, but the projected future climatic conditions in the Northern Hemisphere appear to be increasingly favourable for the disease. Still, other areas of the world may become less favourable, and further research is required to be able to accurately predictDNBoutbreaks and their impact on pine forests in the future.
Temporal evolution of collar lesions associated with ash dieback and the occurrence of Armillaria in Belgian forests
Authors: Chandelier A. , Gerarts F. , San Martin G. , Herman M. , Delahaye L.
Published: January 2016

Ash dieback, caused by the fungus Hymenoscyphus fraxineus, has been observed in Europe for several years. In Belgium, the disease was first reported in 2010. Besides crown defoliation and dieback, collar lesions have sometimes been reported. To evaluate the prevalence and the progression of collar lesions and crown defoliation in ash dieback‐affected stands of various ages, a survey was conducted in 2013 and 2014 on 268 ash trees (Fraxinus excelsior) originating from 17 Walloon forest stands. The results showed that the proportion of trees with collar lesions greatly increased between June 2013 and September 2014 and that there appeared to be no significant link between a tree's diameter‐at‐breast height (DBH) and collar lesion occurrence. The mean percentage of defoliation increased in each forest stand across time, with observations conducted in September 2013 and 2014 showing a positive correlation with the mean percentage of trees with collar lesions. Molecular tests were carried out on 103 additional trees originating from 12 of the 17 stands to evaluate the occurrence of H. fraxineus and Armillaria spp. at the collar level. Most of the trees (98%) were infected by H. fraxineus. In contrast, only 41% of the samples were infected with Armillaria spp., most commonly A. gallica and A. cepistipes. This study discusses the role of Armillaria spp. and the rapid increase in the number of trees with collar lesions within the context of the evolution of ash dieback in Europe.
Polyphyllin I induces cell cycle arrest and apoptosis in human myeloma cells via modulating β‐catenin signaling pathway
Authors: Liang Yun , Li Xian , He Xin , Qiu Xi , Jin Xue‐li , Zhao Xiao‐ying , Xu Rong‐zhen
Published: January 2016

Multiple myeloma (MM) is an indolent B‐cell disease characterized by clonal proliferation of malignant plasma cells. Multiple myeloma remains incurable despite new targeted drugs and development of drug resistance or intolerable toxicity emerges as a major problem. Therefore, design, identification, and validation of novel chemicals with therapeutic potential are clearly needed for MM treatment. Here, we explore polyphyllin I (PPI), a major active constituent extracted from Paris polyphyllin, its inhibitory effects and its mechanisms in MM cells in vitro. We found that PPI inhibited the proliferation of myeloma cells. The combination of PPI with dexamethasone, doxorubicin, arsenic trioxide, or bortezomib enhanced the inhibition of cell growth. As analyzed by flow cytometry, MM cells were arrested at G2/M phase and apoptotic cells increased in a time‐dependent manner. Morphological changes of cells undergoing apoptosis were observed under light microscope. To explore the mechanism of apoptosis induced by PPI, we next examined whether the Wingless‐Int (Wnt)/β‐catenin signaling pathway played a role in the PPI‐induced growth inhibition in MM cells. The canonical Wnt signaling pathway is activated in MM cells through constitutively active β‐catenin, a messenger molecule relevant to growth, survival, and migration of MM cells. Western blotting was used to measure the protein levels of β‐catenin, and PPI treatment led to downregulating the expression of β‐catenin protein and was followed by inhibition of β‐catenin nuclear localization. As a result, β‐catenin downstream targets, such as cyclin D1 and survivin, were downregulated. To the best of our knowledge, this is the first report identifying anti‐proliferative potency of PPI against myeloma cells. PPI blocks β‐catenin nuclear translocation and decreasing expression of the downstream targets of β‐catenin. Our results suggest that PPI is a novel inhibitor of β‐catenin activity with potential anti‐myeloma efficacy.
Cerebrospinal fluid markers of neuronal and glial cell damage to monitor disease activity and predict long‐term outcome in patients with autoimmune encephalitis
Authors: Constantinescu R. , Krýsl D. , Bergquist F. , Andrén K. , Malmeström C. , Asztély F. , Axelsson M. , Menachem E. B. , Blennow K. , Rosengren L. , Zetterberg H.
Published: January 2016

Background and purpose

Clinical symptoms and long‐term outcome of autoimmune encephalitis are variable. Diagnosis requires multiple investigations, and treatment strategies must be individually tailored. Better biomarkers are needed for diagnosis, to monitor disease activity and to predict long‐term outcome. The value of cerebrospinal fluid (CSF) markers of neuronal [neurofilament light chain protein (NFL), and total tau protein (T‐tau)] and glial cell [glial fibrillary acidic protein (GFAP)] damage in patients with autoimmune encephalitis was investigated.

Methods

Demographic, clinical, magnetic resonance imaging, CSF and antibody‐related data of 25 patients hospitalized for autoimmune encephalitis and followed for 1 year were retrospectively collected. Correlations between these data and consecutive CSF levels of NFL, T‐tau and GFAP were investigated. Disability, assessed by the modified Rankin scale, was used for evaluation of disease activity and long‐term outcome.

Results

The acute stage of autoimmune encephalitis was accompanied by high CSF levels of NFL and T‐tau, whereas normal or significantly lower levels were observed after clinical improvement 1 year later. NFL and T‐tau reacted in a similar way but at different speeds, with T‐tau reacting faster. CSF levels of GFAP were initially moderately increased but did not change significantly later on. Final outcome (disability at 1 year) directly correlated with CSF‐NFL and CSF‐GFAP levels at all time‐points and with CSF‐T‐tau at 3 ± 1 months. This correlation remained significant after age adjustment for CSF‐NFL and T‐tau but not for GFAP.

Conclusion

In autoimmune encephalitis, CSF levels of neuronal and glial cell damage markers appear to reflect disease activity and long‐term disability.
Metabolomics in amyotrophic lateral sclerosis: how far can it take us?
Authors: Blasco H. , Patin F. , Madji Hounoum B. , Gordon P. H. , Vourc'h P. , Andres C. R. , Corcia P.
Published: January 2016

Amyotrophic lateral sclerosis (ALS) is the most common adult‐onset motor neuron disease. Alongside identification of aetiologies, development of biomarkers is a foremost research priority. Metabolomics is one promising approach that is being utilized in the search for diagnosis and prognosis markers. Our aim is to provide an overview of the principal research in metabolomics applied to ALS. References were identified using PubMed with the terms ‘metabolomics’ or ‘metabolomic’ and ‘ALS’ or ‘amyotrophic lateral sclerosis’ or ‘MND’ or ‘motor neuron disorders’. To date, nine articles have reported metabolomics research in patients and a few additional studies examined disease physiology and drug effects in patients or models. Metabolomics contribute to a better understanding of ALS pathophysiology but, to date, no biomarker has been validated for diagnosis, principally due to the heterogeneity of the disease and the absence of applied standardized methodology for biomarker discovery. A consensus on best metabolomics methodology as well as systematic independent validation will be an important accomplishment on the path to identifying the long‐awaited biomarkers for ALS and to improve clinical trial designs.
Apathy is associated with poor prognosis in amyotrophic lateral sclerosis
Authors: Caga J. , Turner M. R. , Hsieh S. , Ahmed R. M. , Devenney E. , Ramsey E. , Zoing M. C. , Mioshi E. , Kiernan M. C.
Published: January 2016

Background and purpose

Apathy is the most commonly reported behavioural change in amyotrophic lateral sclerosis (ALS). However, the degree to which it affects prognosis and overlaps with depression in this population is unknown. The present study examined the relationship between level of apathy, mortality and survival time and whether apathy was linked to specific symptom clusters of depression.

Methods

A cohort of 76 consecutive ALS patients attending specialized multidisciplinary clinics were classified according to level of apathy. The effects of clinical factors and apathy on survival time were analysed using univariate and multivariate methods.

Results

The majority of patients with moderate to severe apathy died during the study (P = 0.003) and had a median survival time of 21.7 months, considerably shorter than patients with mild apathy (46.9 months) and no apathy (51.9 months) (P = 0.0001). Apathy remained a significant predictor of survival even after controlling for clinical factors and symptom duration at the time of study entry (hazard ratio 3.8, 95% confidence interval 1.9–7.5, P = 0.0001). Depression with demoralization was not associated with level of apathy (P = 0.172) whereas depression with anhedonia was more common in patients with apathy than in those without apathy (P = 0.006).

Conclusions

The presence of severe apathy is an independent, negative prognostic factor in ALS.
Relationship between restraint use, engagement in social activity, and decline in cognitive status among residents newly admitted to long‐term care facilities
Authors: Freeman Shannon , Spirgiene Lina , Martin‐Khan Melinda , Hirdes John P
Published: January 2016

Aim

Declining cognitive function can negatively affect residents' quality of life (QOL) in long‐term care facilities (LTCFs). The present study examined the role of physical restraint use, use of antipsychotic medications, and engagement in social activities to affect change in cognitive status and drive cognitive decline among residents newly admitted to a LTCF.

Methods

Secondary data analysis used interRAI Minimum Data Set 2.0 data gathered at admission and first follow‐up assessment (n = 111,052). The interRAI Minimum Data Set 2.0 collects comprehensive information as part of regular clinical care, and is mandated for all LTCF in Ontario, Canada. Bivariate and logistic regression analyses investigated the roles of physical restraint use, antipsychotic medication use and social engagement affecting cognition, and were stratified based on the presence/absence of diagnosis of dementia.

Results

At follow up, 16.1% of residents (n = 16 414) showed decline in cognition. Residents with one or more physical restraints (chair, trunk and limb) were at increased risk for cognitive decline evidenced among residents with and without a diagnosis of dementia. Antipsychotic medication use did not emerge as a strong predictor of cognitive decline. Social engagement was protective against cognitive decline, and more pronounced for residents without a diagnosis of dementia.

Conclusion

Physical restraint use should be avoided, or used as a last resort. LTCFs should prioritize resident engagement in social activities in either formal activities or ad hoc, as soon as possible on entry to the LTCFs. Prioritizing social networks and greater participation in activities might decrease the risk for cognitive decline, thereby improving or maintaining resident quality of life. Geriatr Gerontol Int 2017; 17: 246–255.
Survival rates of captive‐bred Asian Houbara Chlamydotis macqueenii in a hunted migratory population
Authors: Burnside Robert J. , Collar Nigel J. , Scotland Keith M. , Dolman Paul M.
Published: January 2016

Asian Houbara Chlamydotis macqueenii numbers are declining as a result of unsustainable levels of hunting and poaching, with the main conservation response being population reinforcement through the release of captive‐bred birds. We assessed the contribution of captive breeding to the species’ conservation by examining the fates of 65 captive‐bred birds fitted with satellite transmitters and released during spring (March–May) and autumn (August) into breeding habitat in Uzbekistan. Of the released birds, 58.5% survived to October, the month favoured by Emirati hunters in Uzbekistan, but only 10.8% of those released survived the winter to return as subadults next spring. To mitigate and compensate for the loss of wild adults to hunting, the number of released birds needs to be an order of magnitude higher than hunting quotas (with a release of between 1640 and 1920 required for a hypothetical quota of 200), indicating that releases may be costly and do not remove the need for a biologically determined sustainable hunting quota.
Value of Quantitative assessment of Myeloid Nuclear Differentiation Antigen expression and other flow cytometric parameters in the diagnosis of Myelodysplastic syndrome
Authors: Somasundaram V. , Soni S. , Chopra A. , Rai S. , Mahapatra M. , Kumar R. , Pati H.
Published: January 2016

Introduction

The diagnosis of myelodysplastic syndrome (MDS) based on morphology is particularly difficult in low‐gradeMDS. Thus, the role of myeloid nuclear differentiation antigen (MNDA) and other flow cytometric (FCM) parameters inMDSwas evaluated.

Methods

Bone marrow aspirates (BMA) collected from 52 patients with unexplained persistent cytopenias were divided into three groups: (i) provenMDS(n= 12) based on morphology and/or cytogenetics; (ii) suspectedMDS(n= 6), noncontributory morphology, and cytogenetics; and (iii) non‐MDS(n= 34). Sixteen controlBMAwere studied. Cases were analyzed forMNDAexpression (on granulocytes, blasts, monocytes, and lymphocytes) and for seven quantitative parameters:CD34+myeloblasts % in nucleated cells,CD34+B‐cell progenitor% inCD34+cells, lymphocyte/myeloblastCD45MFIratio, granulocyte/lymphocyteSSCpeak channel ratio and the proportion ofCD34+myeloblasts expressingCD15,CD11b, andCD56. A score of 1 was given to each parameter beyond the cutoff, and score ≥3 was consideredFCMpositive.

Results

MNDAexpression on granulocytes and blasts was significantly lower in provenMDSand suspectedMDSvs. non‐MDS. QuantitativeFCMparameters successfully distinguishedMDSand suspectedMDSfrom non‐MDS.

Conclusion

MNDAexpression is an independent marker for the evaluation of dyspoiesis and may be added to the standard panel for quantitative assessment byFCM.
Nurses' knowledge of advance directives and perceived confidence in end‐of‐life care: a cross‐sectional study in five countries
Authors: Coffey Alice , McCarthy Geraldine , Weathers Elizabeth , Friedman M. Isabel , Gallo Katherine , Ehrenfeld Mally , Chan Sophia , Li William H.C. , Poletti Piera , Zanotti Renzo , Molloy D. William , McGlade Ciara , Fitzpatrick Joyce J. , Itzhaki Michal
Published: January 2016

Nurses' knowledge regarding advance directives may affect their administration and completion in end‐of‐life care. Confidence among nurses is a barrier to the provision of quality end‐of‐life care. This study investigated nurses' knowledge of advance directives and perceived confidence in end‐of‐life care, in Hong Kong, Ireland, Israel, Italy and the USA using a cross‐sectional descriptive design (n = 1089). In all countries, older nurses and those who had more professional experience felt more confident managing patients' symptoms at end‐of‐life and more comfortable stopping preventive medications at end‐of‐life. Nurses in the USA reported that they have more knowledge and experience of advance directives compared with other countries. In addition, they reported the highest levels of confidence and comfort in dealing with end‐of‐life care. Although legislation for advance directives does not yet exist in Ireland, nurses reported high levels of confidence in end‐of‐life care.
Using Social Indicators to Evaluate the Effectiveness of Outreach in Two Indiana Watersheds
Authors: Busse Rebecca , Ulrich‐Schad Jessica D. , Crighton Lyn , Peel Sara , Genskow Ken , Prokopy Linda Stalker
Published: January 2016

Nonpoint source pollution is recognized as one of the greatest threats to water quality in the United States. Outreach is one tool that can be used to help increase public awareness and motivate action towards addressing water issues. In order to create effective outreach, we must understand public perceptions of water quality, perceived barriers to implementing environmental solutions, and what types of outreach best connect with target audiences. In 2010, social indicator surveys were distributed in two watersheds in Indiana to gather baseline data on urban and agricultural residents' attitudes towards and usage of water quality conservation practices. Local watershed organizations then used various outreach methods to encourage residents to implement specific practices. In 2014, post‐project surveys were conducted in both watersheds to assess whether the outreach efforts had been effective. Even with outreach efforts, many residents still were unaware that specific water pollutants were problems in their watershed. There were, however, positive changes in overall water quality attitudes. Changes in awareness and adoption of conservation practices varied by watershed and resident type, yet generally moved in a positive direction or were unchanged. The primary barrier to practice adoption for all respondents was cost. Outreach events were generally not well attended and did little to change attendee behavior. Some outreach activities seem to be more useful than others in terms of self‐reported effectiveness while others are clearly visible to the community and may be a helpful way to raise awareness.
Water Quality and Nutrient Management Extension Programs in Ohio
Authors: Londo Andrew J. , LaBarge Greg , Watters Harold , Culman Steve , Rose Mary Ann , Hall Peggy , Arnold Glen , Custer Sam , Richer Eric , Noggle Sarah , Penrose Chris
Published: January 2016

Extension has a long history of conducting educational programs for agricultural producers on a wide array of issues, including water quality. In Ohio, the focus of these educational efforts has grown to include best management practices for nutrient management. The need for education in nutrient management began in earnest in the 1970s due to the presence of harmful algal blooms (HAB) in the Western Lake Erie Basin. International actions taken during that time all but eliminated the HABs from the lake until they made a resurgence in the 1990s. Twenty years later, the HAB threat in Lake Erie is still present and has major implications for commerce, tourism, and human and environmental health. The HAB threat has spurred outcries from the general public, resulting in the creation of new laws by the Ohio Legislature, and an expanded and enhanced focus area for Ohio State University Extension (OSUE) programming. In this paper, we describe the conditions that have led to the development of the HAB in Lake Erie, the legislative action that has been taken in attempts to curb the problem, and the educational programs developed by OSUE in partnership with state agencies, non‐government organizations, and other interested parties to address these water quality issues with Ohio agricultural producers and the general public.