Quadriceps foam rolling and rolling massage increases hip flexion and extension passive range-of-motion.
Increases in joint range-of-motion may be beneficial for improving performance and reducing injury risk. This study investigated the effects of different self-massage volumes and modalities on passive hip range-of-motion. Twenty-five recreationally resistance-trained men performed four experimental protocols using a counterbalanced, randomized, and within-subjects design; foam rolling (FR) or roller massage (RM) for 60 or 120-s. Passive hip flexion and extension range-of-motion were measured in a counterbalanced and randomized order via manual goniometry before self-massage (baseline) and immediately, 10-, 20-, and 30-min following each self-massage intervention. Following FR or RM of quadriceps, there was an increase in hip flexion range-of-motion at Post-0 (FR: Δ = 19.28°; RM: Δ = 14.96°), Post-10 (FR: Δ = 13.03°; RM: Δ = 10.40°), and Post-20 (FR: Δ = 6.00°; RM: Δ = 4.64°) for all protocols, but these did not exceed the minimum detectable change at Post-10 for RM60 and RM120, and Post-20 for FR60, FR120, RM60, and RM120. Similarly, hip extension range-of-motion increased at Post-0 (FR: Δ = 8.56°; RM: Δ = 6.56°), Post-10 (FR: Δ = 4.64°; RM: Δ = 3.92°), and Post-20 (FR: Δ = 2.80°; RM: Δ = 1.92°), but did not exceed the minimum detectable change at Post-10 for FR60, RM60, and RM120, and Post-20 for FR60, FR120, RM60, and RM120. In conclusion, both FR and RM increased hip range-of-motion but larger volumes (120- vs. 60-second) and FR produced the greatest increases. These findings have implications for self-massage prescription and implementation, in both rehabilitation and athletic populations.


The specificity of autobiographical memory and imageability of the future.
Three studies examined whether the specificity with which people retrieve episodes from their past determines the specificity with which they imagine the future. In the first study, suicidal patients and nondepressed controls generated autobiographical events and possible future events in response to cues. Suicidal subjects' memory and future responses were more generic, and specificity level for the past and the future was significantly correlated for both groups. In the second and third studies, the effect of experimental manipulation of retrieval style was examined by instructing subjects to retrieve specific events or summaries of events from their past (Experiment 2) or by giving high- or low-imageable words to cue memories (Experiment 3). Results showed that induction of a generic retrieval style reduced the specificity of images of the future. It is suggested that the association between memory retrieval and future imaging arises because the intermediate descriptions used in searching autobiographical memory are also used to generate images of possible events in the future.


Interleukin-10 promoter polymorphisms and the outcome of hepatitis C virus infection.
The natural outcome and response to treatment in hepatitis C virus (HCV) infection varies between individuals. Whereas some variation may be attributable to viral and environmental variables, it is probable that host genetic background also plays a significant role. Interleukin (IL)-10 has a key function in the regulation of cellular immune responses and in the suppression of pro-inflammatory cytokine secretion. Functional polymorphisms in the IL-10 gene have been described. We investigated the role of these polymorphisms in the outcome of HCV infection, treatment response and development of fibrosis in a case-control association study. Self-limiting infection was associated with the IL-10 (-592) AA genotype (OR=2.05; P=0.028). Persistent infection was associated with the IL-10 (-1082) GG genotype (OR=0.48; P=0.018). Sustained response to interferon therapy was associated with the IL-10 (-1082) GG genotype (OR=2.28; P=0.005) and the haplotype GCC (OR=2.27; P=0.020). The IL-10 (-1082) AA genotype and the ATA/ATA and ACC/ACC homozygous haplotypes were more frequent among patients with rapid fibrosis. Furthermore, the microsatellites IL-10.R and IL-10.G were associated with interferon response with IL-10R.2 conveying susceptibility (OR=1.80; P=0.034), and IL-10R.3 and IL-10.G13 being protective (OR=0.47; P=0.003 and OR=0.59; P=0.042, respectively). We conclude that polymorphisms in the IL-10 promoter appear to have some influence on the outcome of HCV infection, treatment and development of fibrosis.


A new glucocorticoid hypothesis of brain aging: implications for Alzheimer's disease.
The original glucocorticoid (GC) hypothesis of brain aging and Alzheimer's disease proposed that chronic exposure to GCs promotes hippocampal aging and AD. This proposition arose from a study correlating increasing plasma corticosterone with hippocampal astrocyte reactivity in aging rats. Numerous subsequent studies have found evidence consistent with this hypothesis, in animal models and in humans. However, several results emerged that were inconsistent with the hypothesis, highlighting the need for a more definitive test with a broader panel of biomarkers. We used microarray analyses to identify a panel of hippocampal gene expression changes that were aging-dependent, and also corticosterone-dependent. These data enabled us to test a key prediction of the GC hypothesis, namely, that the expression of most target biomarkers of brain aging should be regulated in the same direction (increased or decreased) by both GCs and aging. This prediction was decisively contradicted, as a majority of biomarker genes were regulated in opposite directions by aging and GCs, particularly inflammatory and astrocyte-specific genes. Thus, the initial hypothesis of simple positive cooperativity between GCs and aging must be rejected. Instead, our microarray data suggest that in the brain GCs and aging interact in more complex ways that depend on the cell type. Therefore, we propose a new version of the GC-brain aging hypothesis; its main premise is that aging selectively increases GC efficacy in some cell types (e.g., neurons), enhancing catabolic processes, whereas aging selectively decreases GC efficacy in other cell types (e.g., astrocytes), weakening GC anti-inflammatory activity. We also propose that changes in GC efficacy might be mediated in part by cell type specific shifts in the antagonistic balance between GC and insulin actions, which may be of relevance for Alzheimer's disease pathogenesis.


Application of Cannabinoids in Neurosciences: Considerations and Implications.
Medicinal cannabinoid use continues to evolve across the United States, although legitimate federal recognition for medicinal purpose is lacking. Variability exists across states within the United States with respect to legislation, and health care institutions encounter challenges when patients present with a history of medicinal cannabinoid use. Emerging evidence in the field of neurosciences suggests a role of cannabinoids for neurologic medical conditions such as Parkinson disease, multiple sclerosis, and epilepsy. We aim to provide an overview of cannabinoids including a historical perspective, pharmacology, applications in neurosciences, and challenges in health care and academia. Knowledge of the appropriate role of cannabinoids in the clinical setting is essential for all health care practitioners including nursing.


Large RNA segment of Dugbe nairovirus encodes the putative RNA polymerase.
The nucleotide sequence of the large (L) RNA segment of Dugbe (DUG) virus (Nairovirus, Bunyaviridae) was determined, completing the first entire genome sequence of a nairovirus. The L segment comprised 12255 nucleotides, making a total genome size of 18855 nucleotides, and the ends showed identity with the ends of the medium (M) and small (S) genomic segments. A single open reading frame (ORF) was present in the viral complementary strand, sufficient to encode a protein of 459 kDa. The predicted protein sequence showed the core polymerase motifs characteristic of the RNA-dependent RNA polymerases of segmented negative-stranded viruses. Comparison of the conserved motifs with the corresponding region of other segmented negative-strand viruses showed a closer relationship between nairoviruses and phleboviruses than with other Bunyaviridae or with other virus families. However, the core polymerase was the only function that could be assigned to a region of the DUG L gene.


A recent deep earthquake doublet in light of long-term evolution of Nazca subduction.
Earthquake faulting at ~600 km depth remains puzzling. Here we present a new kinematic interpretation of two Mw7.6 earthquakes of November 24, 2015. In contrast to teleseismic analysis of this doublet, we use regional seismic data providing robust two-point source models, further validated by regional back-projection and rupture-stop analysis. The doublet represents segmented rupture of a ∼30-year gap in a narrow, deep fault zone, fully consistent with the stress field derived from neighbouring 1976-2015 earthquakes. Seismic observations are interpreted using a geodynamic model of regional subduction, incorporating realistic rheology and major phase transitions, yielding a model slab that is nearly vertical in the deep-earthquake zone but stagnant below 660 km, consistent with tomographic imaging. Geodynamically modelled stresses match the seismically inferred stress field, where the steeply down-dip orientation of compressive stress axes at ∼600 km arises from combined viscous and buoyant forces resisting slab penetration into the lower mantle and deformation associated with slab buckling and stagnation. Observed fault-rupture geometry, demonstrated likelihood of seismic triggering, and high model temperatures in young subducted lithosphere, together favour nanometric crystallisation (and associated grain-boundary sliding) attending high-pressure dehydration as a likely seismogenic mechanism, unless a segment of much older lithosphere is present at depth.


Pragmatic Recommendations for Safety while Caring for Hospitalized Patients with COVID-19 in Low- and Middle-Income Countries.
Infection prevention and control measures to control the spread of COVID-19 are challenging to implement in many low- and middle-income countries (LMICs). This is compounded by the fact that most recommendations are based on evidence that mainly originates in high-income countries. There are often availability, affordability, and feasibility barriers to applying such recommendations in LMICs, and therefore, there is a need for developing recommendations that are achievable in LMICs. We used a modified version of the GRADE method to select important questions, searched the literature for relevant evidence, and formulated pragmatic recommendations for safety while caring for patients with COVID-19 in LMICs. We selected five questions related to safety, covering minimal requirements for personal protective equipment (PPE), recommendations for extended use and reuse of PPE, restriction on the number of times healthcare workers enter patients' rooms, hand hygiene, and environmental ventilation. We formulated 21 recommendations that are feasible and affordable in LMICs.


Pharmacology as a foreign language: a preliminary evaluation of podcasting as a supplementary learning tool for non-medical prescribing students.
Nurses and other health professionals in the U.K. can gain similar prescribing rights to doctors by undertaking a non-medical prescribing course. Non-medical prescribing students must have a thorough understanding of the pharmacology of prescribing to ensure safe practice. Pharmacology education at this level is complicated by the variation in students' prior subject knowledge of, and anxiety about, the subject. The recent advances in technology, particularly the potential for mobile learning, provide increased opportunities for students to familiarise themselves with lecture materials and hence promote understanding. The objective of this study was therefore to evaluate both the subjective (student perception) and objective (student use and exam results) usefulness of podcasts of pharmacology lectures which were provided as an extra learning tool to two cohorts (n = 69) of non-medical prescribing students. The podcasts were made available to students through the virtual learning environment WebCT. Use of podcasts by two successive cohorts of nurse prescribing students (n = 69) was tracked through WebCT. Survey data, which was collected from 44 of these students, investigated patterns of/reasons for podcast use and perceived usefulness of podcasts as a learning tool. Of these 69 students, 64 completed the pharmacology exam. In order to examine any impact of podcasts on student knowledge, their exam results were compared with those of two historical cohorts who did not have access to podcasts (n = 70). WebCT tracking showed that 91% of students accessed at least one podcast. 93% of students used the podcasts to revisit a lecture, 85% used podcasts for revision, and 61% used the podcasts when they had a specific question. Only 22% used the podcasts because they had missed a pharmacology session. Most students (81%) generally listened to the entire podcast rather than specific sections and most (73%) used them while referring to their lecture handouts. The majority of students found the podcasts helpful as a learning tool, as a revision aid and in promoting their understanding of the subject. Evaluation of the range of marks obtained, mode mark and mean mark suggested improved knowledge in students with access to podcasts compared to historical cohorts of students who did not have access to pharmacology podcasts. The results of this study suggest that non-medical prescribing students utilised podcasts of pharmacology lectures, and have found the availability of these podcasts helpful for their learning. Exam results indicate that the availability of podcasts was also associated with improved exam performance.


AGR2 associates with HER2 expression predicting poor outcome in subset of estrogen receptor negative breast cancer patients.
Expression of the AGR2 oncogene was shown to be associated with estrogen receptor positive tumors. This gene contributes to enhanced cellular proliferation, drug resistance, metastasis development and may also serve as a predictor of poor prognosis. However, our analysis of AGR2 expression in a subset of estrogen-receptor negative tumors revealed that AGR2 could also be upregulated in hormone-independent manner. AGR2 expression was shown to be significantly increased in HER2 positive breast tumors on both the mRNA and the protein level. Moreover, in a subset of estrogen- and progesterone-receptor negative and simultaneously HER2-positive cases, increased AGR2 expression significantly correlated with worse patient prognosis. Subsequent analysis of independent data sets either collected in our institute or obtained from Oncomine cancer microarray database confirmed all these findings.


Breakfast and exercise contingently affect postprandial metabolism and energy balance in physically active males.
The present study examined the impact of breakfast and exercise on postprandial metabolism, appetite and macronutrient balance. A sample of twelve (blood variables n 11) physically active males completed four trials in a randomised, crossover design comprising a continued overnight fast followed by: (1) rest without breakfast (FR); (2) exercise without breakfast (FE); (3) breakfast consumption (1859 kJ) followed by rest (BR); (4) breakfast consumption followed by exercise (BE). Exercise was continuous, moderate-intensity running (expending approximately 2·9 MJ of energy). The equivalent time was spent sitting during resting trials. A test drink (1500 kJ) was ingested on all trials followed 90 min later by an ad libitum lunch. The difference between the BR and FR trials in blood glucose time-averaged AUC following test drink consumption approached significance (BR: 4·33 (SEM 0·14) v. FR: 4·75 (SEM 0·16) mmol/l; P=0·08); but it was not different between FR and FE (FE: 4·77 (SEM 0·14) mmol/l; P=0·65); and was greater in BE (BE: 4·97 (SEM 0·13) mmol/l) v. BR (P=0·012). Appetite following the test drink was reduced in BR v. FR (P=0·006) and in BE v. FE (P=0·029). Following lunch, the most positive energy balance was observed in BR and least positive in FE. Regardless of breakfast, acute exercise produced a less positive energy balance following ad libitum lunch consumption. Energy and fat balance is further reduced with breakfast omission. Breakfast improved the overall appetite responses to foods consumed later in the day, but abrogated the appetite-suppressive effect of exercise.


Radiographic changes in Thoroughbred yearlings in South Africa.
This study involves the evaluation of pre-purchase radiographic studies of South African Thoroughbred yearlings. Radiographic changes were recorded and compared with similar international studies. The study differs from other studies in that a lower prevalence of pedal osteitis (1.26%), dorsal osteochondral fragmentation of the metatarsophalangeal joint (1.60%), distal metacarpal sagittal ridge changes (15.7%), ulnar carpal bone lucencies (8.33%), carpal osteophytes (1.19%), distal intertarsal and tarsometatarsal joint radiographic changes (9.92%), tarsal osteochondrosis lesions (4.40%) and stifle osteochondrosis lesions (0.4%) was found. The prevalence of dorsal osteochondral fragments in the metacarpophalangeal joint was similar to other studies (1.60%). A higher prevalence of vascular channels as well as irregular borders and lucencies was evident in the proximal sesamoid bones. There was a higher prevalence of palmar metacarpophalangeal and plantar metatarsophalangeal osteochondral fragments (2% and 7.10% respectively). Palmar metacarpal disease, metacarpal supracondylar lysis, proximal sesamoid bone fractures and carpal osteochondral fragmentation were absent in the current study. Additional findings recorded in the current study were proximal interphalangeal joint hyperextension (left front 15.13%, right front 18.91%), the solar angle (right front 2.38 degrees, left front 2.79 degrees), the prevalence of carpal bone 1 (30.95%) and carpal bone 5 (1.59%). Management, nutrition and genetics in the various groups of Thoroughbred yearlings should be further investigated in order to explain the reasons for the differences recorded in the current study.


Towards the co-ordination of terrestrial ecosystem protocols across European research infrastructures.
The study of ecosystem processes over multiple scales of space and time is often best achieved using comparable data from multiple sites. Yet, long-term ecological observatories have often developed their own data collection protocols. Here, we address this problem by proposing a set of ecological protocols suitable for widespread adoption by the ecological community. Scientists from the European ecological research community prioritized terrestrial ecosystem parameters that could benefit from a more consistent approach to data collection within the resources available at most long-term ecological observatories. Parameters for which standard methods are in widespread use, or for which methods are evolving rapidly, were not selected. Protocols were developed by domain experts, building on existing methods where possible, and refined through a process of field testing and training. They address above-ground plant biomass; decomposition; land use and management; leaf area index; soil mesofaunal diversity; soil C and N stocks, and greenhouse gas emissions from soils. These complement existing methods to provide a complete assessment of ecological integrity. These protocols offer integrated approaches to ecological data collection that are low cost and are starting to be used across the European Long Term Ecological Research community.


Multiscale Centerline Detection.
Finding the centerline and estimating the radius of linear structures is a critical first step in many applications, ranging from road delineation in 2D aerial images to modeling blood vessels, lung bronchi, and dendritic arbors in 3D biomedical image stacks. Existing techniques rely either on filters designed to respond to ideal cylindrical structures or on classification techniques. The former tend to become unreliable when the linear structures are very irregular while the latter often has difficulties distinguishing centerline locations from neighboring ones, thus losing accuracy. We solve this problem by reformulating centerline detection in terms of a regression problem. We first train regressors to return the distances to the closest centerline in scale-space, and we apply them to the input images or volumes. The centerlines and the corresponding scale then correspond to the regressors local maxima, which can be easily identified. We show that our method outperforms state-of-the-art techniques for various 2D and 3D datasets. Moreover, our approach is very generic and also performs well on contour detection. We show an improvement above recent contour detection algorithms on the BSDS500 dataset.


Impact of the severity of distance and near-vision impairment on depression and vision-specific quality of life in older people living in residential care.
To determine the relationship between the severity of distance and near-vision impairment on vision-specific quality of life (QoL) and depression in residential care residents. Residents from three low-level residential care facilities in Victoria (Australia) were recruited. All participants were assessed for cognitive impairment, distance and near-vision impairment (VI), and depression. Sociodemographic and other clinical data were also collected. The subscales of the Nursing Home Vision-Targeted Health-Related Quality-of-Life questionnaire (NHVQoL) were the main outcome measures and were validated by Rasch Analysis. Seventy-six residents were enrolled. The mean +/- SD of the participants' age was 83.9 +/- 9.9 years, and most were women (n = 44; 60%); 46.4% (n = 35) had binocular presenting VI (<6/12), and 59% (n = 44) had at least mild near VI (worse than N8); 16% (n = 14) recorded depression symptoms, although depression was not associated with VI (P > 0.05). In linear regression models, distance and near VI was independently associated with poorer QoL on seven of the eight subscales of the NHVQoL scale (P < 0.05). The beta coefficients ranged from -12.3 to -80.2, which suggests that, on average, people with vision loss had poorer QoL, ranging between 12 and 80 points (scale range: 0-100) than did those with no VI. The QoL aspects most affected by vision loss were related to general vision, reading, hobbies, emotional well-being, and social interaction. VI remains a major form of disability in individuals living in residential care facilities and affects vision-specific functioning and socioemotional aspects of daily living. A larger study is needed to confirm these findings.


Co-administration of IGF-I and glycosaminoglycans greatly delays motor neurone disease and affects IGF-I expression in the wobbler mouse: a long-term study.
The study on wobbler mouse has shown that the combined treatment with low doses of glycosaminoglycans (GAGs) and insulin-like growth factor-I (IGF-I) fully prevented motor neurone death and forelimb impairment up to 9-12 weeks of a mouse's life. The effect was accompanied by the prevention of the early hypertrophy of wobbler neurones, an effect likely due to the promotion of neuronal survival. At the 18th week, wobbler mice treated with IGF-I + GAGs still showed significantly improved forelimb function, reduced muscle atrophy and a higher number of cervical motor neurones. IGF-I alone and GAGs alone were active up to the 3rd week of treatment; thereafter the beneficial effects of single treatments decreased drastically. GAGs and IGF-I treatments also affected IGF-I plasma and muscle levels. In wobbler mice there was a progressive reduction in IGF-I plasma levels that was prevented by IGF-I or GAGs alone and greatly increased, even above heterozygote levels, by the combination treatment. Such a powerful increase was correlated by a small enhancement in insulin-like growth factor binding protein-3 (IGFBP-3) plasma levels, while treatment with IGF-I alone affected very significantly both IGFBP-1 and IGFBP-3. Co-treatment also prevented the decrease in IGF-I content observed in vehicle-treated wobbler mice forelimb muscles.


Modulation of the response to a somatosensory stimulation of the hand during the observation of manual actions.
Observation of hand movements has been repeatedly demonstrated to increase the excitability of the motor cortical representation of the hand. Little attention, however, has been devoted to its effect on somatosensory processing. Movement execution is well known to decrease somatosensory cortical excitability, a phenomenon termed 'gating'. As executed and observed actions share common cortical representations, we hypothesized that action observation (hand movements) should also modulate the cortical response to sensory stimulation of the hand. Seventeen healthy subjects participated in these experiments in which electroencephalographic (EEG) recordings of the somatosensory steady-state response (SSSR) were obtained. The SSSR provides a continuous measure of somatosensory processing. Recordings were made during a baseline condition and five observation conditions in which videos showed either a: (1) hand action; (2) passive stimulation of a hand; (3) static hand; (4) foot action; or (5) static object. The method employed consisted of applying a continuous 25 Hz vibratory stimulation to the index finger during the six conditions and measuring potential gating effects in the SSSR within the 25 Hz band (corresponding to the stimulation frequency). A significant effect of condition was found over the contralateral parietal cortex. Observation of hand actions resulted in a significant gating effect when compared to baseline (average gating of 22%). Observation of passive touch of the hand also gated the response (17% decrease). In conclusion, the results show that viewing a hand performing an action or being touched interferes with the processing of somatosensory information arising from the hand.


Risk factors and interventions with statistically significant tiny effects.
Large studies may identify postulated risk factors and interventions with very small effect sizes. We aimed to assess empirically a large number of statistically significant relative risks (RRs) of tiny magnitude and their interpretation by investigators. RRs in the range between 0.95 and 1.05 were identified in abstracts of articles of cohort studies; articles published in NEJM, JAMA or Lancet; and Cochrane reviews. For each eligible tiny effect and the respective study, we recorded information on study design, participants, risk factor/intervention, outcome, effect estimates, P-values and interpretation by study investigators. We also calculated the probability that each effect lies outside specific intervals around the null (RR interval 0.97-1.03, 0.95-1.05, 0.90-1.10). We evaluated 51 eligible tiny effects (median sample size 112 786 for risk factors and 36 021 for interventions). Most (37/51) appeared in articles published in 2006-10. The effects pertained to nutrition (n = 19), genetic and other biomarkers (n = 8), correlates of health care (n = 8) and diverse other topics (n = 16) of clinical or public health importance and mostly referred to major clinical outcomes. A total of 15 of the 51 effects were >80% likely to lie outside the RR interval 0.97-1.03, but only 8 were >40% likely to lie outside the RR interval 0.95-1.05 and none was >1.7% likely to lie outside the RR interval 0.90-1.10. The authors discussed at least one concern for 23 effects (small magnitude n = 19, residual confounding n = 11, selection bias n = 1). No concerns were expressed for 28 effects. Statistically significant tiny effects for risk factors and interventions of clinical or public health importance become more common in the literature. Cautious interpretation is warranted, since most of these effects could be eliminated with even minimal biases and their importance is uncertain.


Expression of c-fos protooncogene in normal human peripheral blood granulocytes.
We have investigated by Northern blot analysis the expression of c-fos protooncogene in human peripheral blood polymorphonuclear leukocytes (PMN). Freshly isolated PMN, unlike highly purified circulating lymphoid cells, showed high levels of c-fos transcripts. Appreciable c-fos mRNA was detected in monocytes, but in lesser amounts compared with PMN. Upon exposure to a series of agents that functionally stimulate granulocytes (PMA, inactivated streptococci, TNF, granulocyte and granulocyte/macrophage colony-stimulating factor), a considerable increase in c-fos transcripts was detected. Expression of c-fos in PMN was superinduced by exposure to cycloheximide. These data indicate that the myelomonocytic differentiation pathway c-fos expression is not peculiar to monocytes/macrophages and that PMN may represent a suitable system with which to investigate the link between protooncogene expression and functional activation.


Multiple Oral Mucosal Hamartomas in a 34-Year Old Female.
A case of Cowden syndrome (CS) is described in a 34-year-old African American female who reported a history of breast and thyroid malignancies. Clinical examination demonstrated multiple soft, white-pink papules across multiple mucosal surfaces of the oral cavity. Microscopy of the lesions revealed hyperkeratotic surface squamous epithelium with papillomatosis and acanthosis along with elongated rete processes. A genomic polymerase chain reaction direct sequencing using the patient's blood was positive for mutations of the PTEN gene typical of CS.


Differential habituation to repeated sounds in infants at high risk for autism.
It has been suggested that poor habituation to stimuli might explain atypical sensory behaviours in autism. We investigated habituation to repeated sounds using an oddball paradigm in 9-month-old infants with an older sibling with autism and hence at high risk for developing autism. Auditory-evoked responses to repeated sounds in control infants (at low risk of developing autism) decreased over time, demonstrating habituation, and their responses to deviant sounds were larger than responses to standard sounds, indicating discrimination. In contrast, neural responses in infants at high risk showed less habituation and a reduced sensitivity to changes in frequency. Reduced sensory habituation may be present at a younger age than the emergence of autistic behaviour in some individuals, and we propose that this could play a role in the over responsiveness to some stimuli and undersensitivity to others observed in autism.


Machine learning and atherosclerotic cardiovascular disease risk prediction in a multi-ethnic population.
The pooled cohort equations (PCE) predict atherosclerotic cardiovascular disease (ASCVD) risk in patients with characteristics within prespecified ranges and has uncertain performance among Asians or Hispanics. It is unknown if machine learning (ML) models can improve ASCVD risk prediction across broader diverse, real-world populations. We developed ML models for ASCVD risk prediction for multi-ethnic patients using an electronic health record (EHR) database from Northern California. Our cohort included patients aged 18 years or older with no prior CVD and not on statins at baseline (n = 262,923), stratified by PCE-eligible (n = 131,721) or PCE-ineligible patients based on missing or out-of-range variables. We trained ML models [logistic regression with L2 penalty and L1 lasso penalty, random forest, gradient boosting machine (GBM), extreme gradient boosting] and determined 5-year ASCVD risk prediction, including with and without incorporation of additional EHR variables, and in Asian and Hispanic subgroups. A total of 4309 patients had ASCVD events, with 2077 in PCE-ineligible patients. GBM performance in the full cohort, including PCE-ineligible patients (area under receiver-operating characteristic curve (AUC) 0.835, 95% confidence interval (CI): 0.825-0.846), was significantly better than that of the PCE in the PCE-eligible cohort (AUC 0.775, 95% CI: 0.755-0.794). Among patients aged 40-79, GBM performed similarly before (AUC 0.784, 95% CI: 0.759-0.808) and after (AUC 0.790, 95% CI: 0.765-0.814) incorporating additional EHR data. Overall, ML models achieved comparable or improved performance compared to the PCE while allowing risk discrimination in a larger group of patients including PCE-ineligible patients. EHR-trained ML models may help bridge important gaps in ASCVD risk prediction.


Extracellular matrix: recent advances on its role in junction dynamics in the seminiferous epithelium during spermatogenesis.
Spermatogenesis takes place in the seminiferous epithelium of the mammalian testis in which one type A1 spermatogonium (diploid, 2n) gives rise to 256 spermatids (haploid, 1n). To accomplish this, developing germ cells, such as preleptotene and leptotene spermatocytes, residing in the basal compartment of the seminiferous epithelium must traverse the blood-testis barrier (BTB) entering into the adluminal compartment for further development into round, elongating, and elongate spermatids. Recent studies have shown that the basement membrane in the testis (a modified form of extracellular matrix, ECM) is important to the event of germ cell movement across the BTB because proteins in the ECM were shown to regulate BTB dynamics via the interactions between collagens, proteases, and protease inhibitors, possibly under the regulation of cytokines. While these findings are intriguing, they are not entirely unexpected. For one, the basement membrane in the testis is intimately associated with the BTB, which represents the basolateral region of Sertoli cells. Also, Sertoli cell tight junctions (TJs) that constitute the BTB are present side-by-side with cell-cell actin-based adherens junctions (AJ, such as basal ectoplasmic specialization [ES]) and intermediate filament-based desmosome-like junctions. As such, the relative morphological layout between TJs, AJs, and desmosome-like junctions in the seminiferous epithelium is in sharp contrast to other epithelia where TJs are located at the apical portion of an epithelium or endothelium, furthest away from ECM, to be followed by AJs and desmosomes, which in turn constitute the junctional complex. For another, anchoring junctions between a cell epithelium and ECM found in multiple tissues, also known as focal contacts (or focal adhesion complex, FAC, an actin-based cell-matrix anchoring junction type), are the most efficient junction type that permits rapid junction restructuring to accommodate cell movement. It is therefore physiologically plausible, and perhaps essential, that the testis is using some components of the focal contacts to regulate rapid restructuring of AJs between Sertoli and germ cells when germ cells traverse the seminiferous epithelium. Indeed, recent findings have shown that the apical ES, a testis-specific AJ type in the seminiferous epithelium, is equipped with proteins of FAC to regulate its restructuring. In this review, we provide a timely update on this exciting yet rapidly developing field regarding how the homeostasis of basement membrane in the tunica propria regulates BTB dynamics and spermatogenesis in the testis, as well as a critical review on the molecular architecture and the regulation of ES in the seminiferous epithelium.


The reliability of a rugby league movement-simulation protocol designed to replicate the performance of interchanged players.
This study assessed the reliability of a rugby league movement-simulation protocol, relative to interchanged players (RLMSP-i). Fifteen male participants completed 2 trials of the RLMSP-i, separated by 1 wk. The RLMSP-i comprised low- to moderate-intensity running, interspersed by high-intensity sprinting and tackling activity, based on global positioning system (GPS) data recorded during Super League performances. The lowest coefficient of variation (CV ± 95% CI) was observed for total m/min during both interchange bout 1 (1.1% ± 0.2%) and bout 2 (1.0% ± 0.2%). The percentage of heart rate peak and ratings of perceived exertion demonstrated CVs of 1.2-2.0% and 2.9-3.5%, respectively. The poorest agreement between trials was found for blood lactate concentration (16.2% ± 2.8%). In no case was the CV smaller than the smallest worthwhile change, yet in every case the moderate changes were larger than the CV. The RLMSP-i's reliability is sufficient to enable the detection of moderate changes in various performance and physiological measurements that accurately simulate some, but not all, aspects of rugby league matches.


The lived experience of the early postoperative period after colorectal cancer surgery.
Colorectal cancer is one of the most common cancer diagnoses and undergoing colorectal cancer surgery is reported to be associated with physical symptoms and psychological reactions. Social support is described as important during the postoperative period. The purpose of this paper was to describe how patients experience the early postoperative period after colorectal cancer surgery. Interviews according a phenomenological approach were performed with 13 adult participants, within 1 week after discharge from hospital. Data were collected from August 2006 to February 2007. Analysis of the interview transcripts was conducted according to Giorgi. The essence of the phenomenon was to regain control over ones body in the early postoperative period after colorectal cancer surgery. Lack of control, fear of wound and anastomosis rupture, insecurity according to complications was prominent findings. When caring for these patients it is a challenge to be sensitive, encourage and promote patients to express their feelings and needs. One possibility to empower the patients and give support could be a follow up phone call within a week after discharge.


Experimental diabetic neuropathy: an update.
Diabetic neuropathy consists of several clinical syndromes affecting motor, sensory and autonomic nerves. Of these the most common is distal symmetric sensory polyneuropathy usually referred to as diabetic neuropathy. Animal studies, mainly in diabetic rodents, have contributed tremendously to our understanding of this disease. From these it is clear that the pathogenesis of diabetic neuropathy is multifactorial involving sequentially occurring and often closely interrelated metabolic aberrations. Major pathogenetic mechanisms include increased activity of the polyol pathway, abnormalities in vasoactive substances, non-enzymatic glycation, increased presence of free radicals, and perturbed neurotrophism. Traditionally the neuropathies accompanying Type I (insulin-dependent) and Type II (non-insulin-dependent) diabetes mellitus have been regarded as identical. Recent investigations have, however, clearly delineated distinct differences in the functional and structural expressions of the neuropathies in the two types of diabetes. Major future challenges are the identification of the differences in underlying pathogenetic mechanisms in the two types of neuropathy and in gaining a better understanding of the hierarchy of the multifactorial mechanisms underlying the disease. This will be important for designing meaningful therapies which to date have failed miserably in diabetic neuropathy.


The effect of neuromuscular training on the incidence of knee injury in female athletes. A prospective study.
To prospectively evaluate the effect of neuromuscular training on the incidence of knee injury in female athletes, we monitored two groups of female athletes, one trained before sports participation and the other not trained, and a group of untrained male athletes throughout the high school soccer, volleyball, and basketball seasons. Weekly reports included the number of practice and competition exposures and mechanism of injury. There were 14 serious knee injuries in the 1263 athletes tracked through the study. Ten of 463 untrained female athletes sustained serious knee injuries (8 noncontact), 2 of 366 trained female athletes sustained serious knee injuries (0 noncontact), and 2 of 434 male athletes sustained serious knee injuries (1 noncontact). The knee injury incidence per 1000 athlete-exposures was 0.43 in untrained female athletes, 0.12 in trained female athletes, and 0.09 in male athletes (P = 0.02, chi-square analysis). Untrained female athletes had a 3.6 times higher incidence of knee injury than trained female athletes (P = 0.05) and 4.8 times higher than male athletes (P = 0.03). The incidence of knee injury in trained female athletes was not significantly different from that in untrained male athletes (P = 0.86). The difference in the incidence of noncontact injuries between the female groups was also significant (P = 0.01). This prospective study demonstrated a decreased incidence of knee injury in female athletes after a specific plyometric training program.


Genistein reduces proliferation of EP3-expressing melanoma cells through inhibition of PGE2-induced IL-8 expression.
Genistein, a natural isoflavone found in soybean products, is considered as a powerful anti-cancer agent, although the involved mechanisms are not fully understood. There is a growing body of evidence that, among the genes inhibited by genistein and responsible for cell cycle progression, invasion, metastasis, and angiogenesis, IL-8 occupies a relevant place. On the other hand, it is equally well documented that IL-8 is upregulated by prostaglandin E2 (PGE2) in different pathological conditions, particularly in neoplastic disease. Here we investigated whether genistein could affect cell growth in a panel of oral, uveal and cutaneous melanoma cell lines by interfering with basal or PGE2-induced IL-8 production. To this end, experiments were performed to evaluate the effect of PGE2 treatment on IL-8 levels, the expression and the role of PGE2 receptors and whether genistein could be able to interfere with these events. Finally, it was evaluated whether the inhibition of oral, uveal and cutaneous melanoma cell proliferation in the presence of genistein could be related to a reduction of IL-8 levels. We show that PGE2 enhances IL-8 synthesis via the EP3 receptor and that genistein is able to down-regulate the latter, as well as to decrease IL-8 mRNA and protein expression, thereby inhibiting oral, uveal and cutaneous melanoma cell proliferation. Taken together, our data provide new insights into the anti-cancer properties of genistein by showing that this flavonoid may affect the development and growth of melanoma at oral, uveal and cutaneous sites. Moreover, these results provide evidence that genistein may exert its therapeutic activity through its ability to prevent PGE2-mediated IL-8 induction.


The role of high carbohydrate-rich food intake and severity of asthma exacerbation in children between 2 to 6 years aged.
Over the last decades, dietary habits in developing countries have been characterized by low intake of fruits and vegetables and high consumption of sweetened drinks. Most of the evidence linking carbohydrate intake and asthma comes from children over 6 years of age. The aim of this study was to examine the association between macronutrient intake and the severity of asthma exacerbations in children aged 2-6 years. We performed a cross-sectional study that included all children aged 2-6 years hospitalized due to an asthma exacerbation. Dietary data were collected using a food frequency questionnaire (FFQ) validated in the Colombian population. The GINA classification of acute asthma was used to define the severity. To identify factors independently associated with asthma exacerbation severity, we fit the data to ordinal logistic regression. During the study period, 228 cases of patients with asthma exacerbation were included. Asthma severity was dose-dependently associated with protein and carbohydrate-rich intake. The variables included in the multivariable analysis included reactive C protein (OR 1.05, CI 95% (1.03-1.07)), smoking at home (OR 3.92 (1.82-8.44)), atopic dermatitis (OR 3.82 (1.59-9.21)), and protein and carbohydrate-rich food intake (OR 0.11 (0.03-0.33)) and (OR 2.42 (1.09-5.80)), respectively. High carbohydrate-rich food intake is associated with the severity of asthma exacerbation adjusted by other known risk factors such as atopy, smoking, and reactive C protein. This evidence should motivate the development of public health policies to control the consumption of sugar-rich products in children under 6 years.


Mouse Phenome Database (MPD).
The Mouse Phenome Database (MPD; http://www.jax.org/phenome) is a repository of phenotypic and genotypic data on commonly used and genetically diverse inbred strains of mice. Strain characteristics data are contributed by members of the scientific community. Electronic access to centralized strain data enables biomedical researchers to choose appropriate strains for many systems-based research applications, including physiological studies, drug and toxicology testing and modeling disease processes. MPD provides a community data repository and a platform for data analysis and in silico hypothesis testing. The laboratory mouse is a premier genetic model for understanding human biology and pathology; MPD facilitates research that uses the mouse to identify and determine the function of genes participating in normal and disease pathways.


Diagnosis and prognosis-review of biomarkers for mesothelioma.
Malignant pleural mesothelioma (MPM) is an aggressive disease arising in pleural cell lining and is associated with asbestos exposure. Today, there is a rising incidence of MPM reaching 3,000 annual cases nationally, primarily from the large population occupationally exposed to asbestos between 1940 and 1980. With a prolonged latency period, presenting clinically 10 to 40 years after exposure, MPM is often diagnosed in late stages and presents median survival time of less than 12 months. There is a serious need for improvement in prognostic and diagnostic tools for MPM. Recent investigation and discovery of various biomarkers has shown promise, including Osteopontin, Fibulin-3, Soluble Mesothelin-Related Proteins (SMRP), High Mobility Group Box 1 (HMGB1), micro-RNA's, peripheral blood-based markers, and Slow Off-rate Modified Aptamer (SOMAmer) proteomic assays. In this review, we explore these current major biomarkers and their prognostic and diagnostic potential, highlighting the most recent large studies and developments for each. While progress has been made in mesothelioma research, many questions remain unanswered. Increased international cooperation is necessary for improving validity of results for current biomarkers through repeated investigation and increasing cohort sizes, as well as for the continued search for new and better markers.


Airway manifestations of pediatric eosinophilic esophagitis: a clinical and histopathologic report of an emerging association.
Pediatric eosinophilic esophagitis (EE) typically presents with dysphagia, vomiting, dyspepsia, or food impaction. The purpose of this study was to highlight the emerging association of pediatric EE and airway disease. An additional goal of this study was to describe the unique histopathologic findings found in EE and specifically explore the potential role of the cytotoxic protein called eosinophil major basic protein (MBP) in the pathophysiology of the disease. A retrospective review of 3 children with EE and airway symptoms included symptom presentation, aerodigestive tract endoscopic findings, ambulatory 24-hour dual pH-metry, allergy tests, treatment modalities, and treatment response. Esophageal tissue obtained from biopsies of each patient was evaluated by hematoxylin and eosin to determine the number of eosinophils per high-power field, by immunofluorescent anti-MBP staining to determine the presence of MBP, and by standard light and transmission electron microscopy to evaluate eosinophil migration patterns. All patients had airway inflammation that included nonspecific laryngeal edema and grade I or II subglottic stenosis. Allergy testing was positive in the 2 patients who were tested. All patients had symptoms refractory to standard reflux therapy. Ambulatory pH-metry findings were normal in 2 patients and abnormal in 1 patient despite maximum treatment. Two patients had visual abnormalities seen during esophageal examination. The number of eosinophils ranged from 20 to 45 per high-power field. Intracellular and extracellular MBP deposition was found in all esophageal biopsy specimens. All patients were treated with swallowed fluticasone, and 2 had symptom relapses that required repeat treatment. The spectrum of pediatric EE can include upper airway disease. Intracellular and extracellular MBP deposition is present in EE, which potentially releases cytotoxic mediators that explain the esophageal and airway clinical symptoms seen in those with the disease. Eosinophilic esophagitis should be considered in patients with a history of atopic diseases and unexplained upper airway findings refractory to reflux treatment. Treatment with swallowed fluticasone is successful; however, relapses are common and require repeat treatment and close follow-up.


ACOG Committee Opinion No. 747: Gynecologic Issues in Children and Adolescent Cancer Patients and Survivors.
The diagnosis of cancer in females younger than 20 years is rare, with the incidence of 17 cases per 100,000 individuals per year in the United States. Although advancements in cancer therapy have dramatically improved childhood cancer survival, gynecologists should be aware of the increased risk of adverse reproductive health effects from each type of therapy. Cancer and its treatment may have immediate or delayed adverse effects on reproductive health. Gynecologists may be consulted for the following issues: pubertal concerns; menstrual irregularities; heavy menstrual bleeding and anemia; sexuality; contraception; ovarian function, including fertility preservation; breast and cervical cancer screening; hormone therapy; and graft-versus-host disease. Approximately 75% of pediatric cancer survivors experience at least one late effect on their health or quality of life. Vigilance in screening and observation on behalf of the health care provider with respect to menstrual irregularities, weight changes, sexual health, growth abnormalities, and bone density are important. In addition to pretreatment fertility conservation counseling, sexually active young women should be thoroughly educated about the risks of becoming pregnant during cancer treatment and strongly encouraged to use effective contraception; contraceptive choices should be discussed with the oncology team. A multidisciplinary approach to cancer survival care is encouraged. This Committee Opinion has been updated to include current data on sexuality and contraception, sexual dysfunction, risk of graft-versus-host disease after stem cell transplant, and updated references and recommendations for fertility preservation.


Retinitis pigmentosa caused by mutations in the ciliary MAK gene is relatively mild and is not associated with apparent extra-ocular features.
Defects in MAK, encoding a protein localized to the photoreceptor connecting cilium, have recently been associated with autosomal recessive retinitis pigmentosa (RP). The aim of this study is to describe our detailed clinical observations in patients with MAK-associated RP, including an assessment of syndromic symptoms frequently observed in ciliopathies. In this international collaborative study, 11 patients carrying nonsense or missense mutations in MAK were clinically evaluated, including extensive assessment of the medical history, slit-lamp biomicroscopy, ophthalmoscopy, kinetic perimetry, electroretinography (ERG), spectral-domain optical coherence tomography (SD-OCT), autofluorescence imaging and fundus photography. Additionally, we used a questionnaire to evaluate the presence of syndromic features and tested the olfactory function. MAK-associated RP is not associated with syndromic features, not even with subclinical dysfunction of the olfactory apparatus. All patients experienced typical RP symptoms of night blindness followed by visual field constriction. Symptoms initiated between childhood and the age of 43 (mean: 23 years). Although some patients experienced vision loss, the visual acuity remained normal in most patients. ERG and ophthalmoscopy revealed classic RP characteristics, and SD-OCT demonstrated thinning of the overall retina, outer nuclear layer and photoreceptor-pigment epithelium complex. Nonsense and missense mutations in MAK give rise to a non-syndromic recessive RP phenotype without apparent extra-ocular features. When compared to other retinal ciliopathies, MAK-associated RP appears to be relatively mild and shows remarkable resemblance to RP1-associated RP, which could be explained by the close functional relation of these proteins.


Health-related quality of life in people with type 2 diabetes participating in the LEADER trial.
To assess health-related quality of life (HRQoL) in people with type 2 diabetes (T2D) participating in the LEADER cardiovascular outcomes trial using the five-dimension European Quality of Life questionnaire (EQ-5D). The EQ-5D was administered every 12 months in a subset of patients from Canada, Denmark, Germany, Ireland, Italy, Netherlands, Spain, Sweden, the United Kingdom and the United States. We compared changes in utility index scores and visual analogue scale (VAS) scores from baseline to 36 months in participants treated with liraglutide and placebo. We also assessed which complications had the greatest impact on quality of life. At 36 months, less deterioration in EQ-5D utility index score was seen in the liraglutide group (-0.058) than in the placebo group (-0.082; estimated treatment difference [ETD] 0.023, 95% confidence interval [CI] 0.004;0.043; P = 0.020). A smaller decrease in EQ-5D VAS score was also demonstrated in the liraglutide group (-3.51) vs. the placebo group (-5.45; ETD 1.94, 95% CI 0.32;3.57; P = 0.019). The benefits of liraglutide treatment compared with placebo were driven primarily by shifts in the domains of mobility and self-care. The most influential events contributing to poorer HRQoL were stroke, heart failure, malignant neoplasm and confirmed hypoglycaemia. Liraglutide demonstrated a modest but significant benefit in patient-reported health status using the EQ-5D, compared with placebo. This benefit may be of clinical relevance and requires further study.


First Report of Diplodia seriata as Causal Agent of Olive Dieback in Croatia.
In August 2010, a dieback of young olive (Olea europea L.) trees (cvs. Pendolino and Leccino) occurred in two orchards in Istria, Croatia. According to the producers, low temperatures during the winter severely damaged the plants and led to their decline. Distinctive symptoms, assumed fungal infection, were observed in internal tissue of stems and branches. Elongated brown necrosis, sometimes with black streaks, was visible under the bark, therefore Verticillium wilt was suspected. Of 1,086 trees in two orchards (4 ha), 165 (15%) showed symptoms. To isolate the causal agent, surface-sterilized wood chips of symptomatic tissue were placed on potato dextrose agar (PDA). Fungal colonies resembling Botryosphaeriaceae spp. grew from all wood fragments placed on PDA, and from these colonies, monohyphal isolates were obtained. For morphological identification, pycnidial formation was stimulated by growing the isolates on 2% water agar that included stems of plant species Foeniculum vulgare Mill. at room temperature under diffuse light. Pycnidia contained conidia that initially showed as hyaline, becoming light to dark brown as they matured, ovoid with truncated or rounded base and obtuse apex, aseptate, with wall moderately thick, externally smooth, roughened on the inner surface, and 22.8 to 23.5 × 9.6 to 10.5 μm. On the basis of these morphological characters, fungal species Diplodia seriata (teleomorph "Botryosphaeria" obtusa) was suspected (3). For molecular identification, four isolates (MN3, MN4, MN5, and MN6) were used for PCR to amplify the internal transcribed spacer (ITS) region and partial translation elongation factor 1-alpha (EF1-α) gene, using primers ITS4/ITS5 and EF1-728F/EF1-986R, respectively. Sequencing was performed with those amplified genes, then sequences were deposited in GenBank. Comparison of these sequences with GenBank sequences for referent D. seriata isolate CBS 112555 (AY259094 and AY573220) (3) showed 100% homology. On the basis of molecular data, the isolates were confirmed to be species D. seriata De Not. Pathogenicity tests were performed by inoculation of 2-year-old olive plants, six plants per tested cultivar (Pendolino and Leccino). For every cultivar, four plants were wounded and mycelium plugs from D. seriata cultures on PDA were placed on the wounds and sealed with Parafilm. Two control plants per tested cultivar were inoculated with sterile PDA plugs. After 2 months, six of eight inoculated plants wilted completely, and under the bark, brown necrosis was observed. D. seriata was constantly reisolated from the inoculated plants and fulfilled Koch's postulates and confirmed pathogenicity of D. seriata on olive as causal agent of olive dieback. Control plants showed no symptoms of the disease. This fungus has been recognized as the cause of fruit rot of olive (1) and branch canker or dieback in Spain (2). To our knowledge, this is the first report of D. seriata as a pathogen of olive in Croatia. Also, this is one of the first reports of D. seriata as the cause of olive dieback in the world, while Moral et al. (1,2) mostly reported it as the cause of olive fruit rot. Since the same symptoms of olive dieback were observed at other localities in Croatia, the disease could represent a serious threat, particularly for young olive orchards. References: (1) J. Moral et al. Plant Dis. 92:311, 2008. (2) J. Moral et al. Phytopathology 100:1340, 2010. (3) A. J. L. Phillips et al. Fungal Divers. 25:141, 2007.


Validity of resting energy expenditure predictive equations before and after an energy-restricted diet intervention in obese women.
We investigated the validity of REE predictive equations before and after 12-week energy-restricted diet intervention in Spanish obese (30 kg/m(2)>BMI<40 kg/m(2)) women. We measured REE (indirect calorimetry), body weight, height, and fat mass (FM) and fat free mass (FFM, dual X-ray absorptiometry) in 86 obese Caucasian premenopausal women aged 36.7±7.2 y, before and after (n = 78 women) the intervention. We investigated the accuracy of ten REE predictive equations using weight, height, age, FFM and FM. At baseline, the most accurate equation was the Mifflin et al. (Am J Clin Nutr 1990; 51: 241-247) when using weight (bias:-0.2%, P = 0.982), 74% of accurate predictions. This level of accuracy was not reached after the diet intervention (24% accurate prediction). After the intervention, the lowest bias was found with the Owen et al. (Am J Clin Nutr 1986; 44: 1-19) equation when using weight (bias:-1.7%, P = 0.044), 81% accurate prediction, yet it provided 53% accurate predictions at baseline. There is a wide variation in the accuracy of REE predictive equations before and after weight loss in non-morbid obese women. The results acquire especial relevance in the context of the challenging weight regain phenomenon for the overweight/obese population.


Maternal iodine status, intrauterine growth, birth outcomes and congenital anomalies in a UK birth cohort.
Severe iodine insufficiency in pregnancy has significant consequences, but there is inadequate evidence to indicate what constitutes mild or moderate insufficiency, in terms of observed detrimental effects on pregnancy or birth outcomes. A limited number of studies have examined iodine status and birth outcomes, finding inconsistent evidence for specific outcomes. Maternal iodine status was estimated from spot urine samples collected at 26-28 weeks' gestation from 6971 mothers in the Born in Bradford birth cohort. Associations with outcomes were examined for both urinary iodine concentration (UIC) and iodine-to-creatinine ratio (I:Cr). Outcomes assessed included customised birthweight (primary outcome), birthweight, small for gestational age (SGA), low birthweight, head circumference and APGAR score. There was a small positive association between I:Cr and birthweight in adjusted analyses. For a typical participant, the predicted birthweight centile at the 25th percentile of I:Cr (59 μg/g) was 2.7 percentage points lower than that at the 75th percentile of I:Cr (121 μg/g) (99% confidence interval (CI) 0.8 to 4.6), birthweight was predicted to be 41 g lower (99% CI 13 to 69) and the predicted probability of SGA was 1.9 percentage points higher (99% CI 0.0 to 3.7). There was no evidence of associations using UIC or other birth outcomes, including stillbirth, preterm birth, ultrasound growth measures or congenital anomalies. Lower maternal iodine status was associated with lower birthweight and greater probability of SGA. Whilst small, the effect size for lower iodine on birthweight is comparable to environmental tobacco smoke exposure. Iodine insufficiency is avoidable, and strategies to avoid deficiency in women of reproductive age should be considered. ClinicalTrials.gov NCT03552341. Registered on June 11, 2018.


Phase-to-amplitude data page conversion for holographic storage and optical encryption.
A new phase-to-amplitude data page conversion method is proposed for efficient recovery of the data encoded in phase-modulated data pages used in holographic storage and optical encryption. The method is based on the interference between the data page and its copy shifted by an integral number of pixels. Key properties such as Fourier plane homogeneity, bit error rate, and positioning tolerances are investigated by computer modeling, and a comparison is provided with amplitude-modulated data page holographic storage with and without static phase masks. The feasibility and the basic properties of the proposed method are experimentally demonstrated. The results show that phase-modulated data pages can be used efficiently with reduced system complexity.


Effect of Breast Milk Calcium and Fluidity on Breast Cancer Cells: An In Vitro Cell Culture Study.
The aims of this study were to investigate the effects of calcium at the same concentration as that found in human milk on the viability, proliferation, and adhesion of MCF-7 human breast ductal carcinoma cells by exposing them to calcium at the same frequency as in breastfeeding. High-concentration calcium was applied for 30 minutes every 4 hours for 24, 48, and 72 hours. Cell proliferation and viability were measured using a hemocytometer and the MTT cell viability assay. The effects of calcium treatment were evaluated by a comparison among a multiple-, single-dose calcium treatment, and a control group. We show that calcium at the same concentration as that in milk caused a decrease in the number of cells but did not affect cell viability. The results of this study suggest that calcium caused a lowering of the number of cells from the luminal surface of the breast by triggering proliferation under the condition of fluidity. Calcium and fluidity together serve to eliminate breast cancer stem cells during the lactation period. Effects of the other components of milk can be analyzed by the new method developed in this study.


Stressor-Dependant Changes in Immune Parameters in the Terrestrial Isopod Crustacean, Porcellio scaber: A Focus on Nanomaterials.
We compared the changes of selected immune parameters of Porcellio scaber to different stressors. The animals were either fed for two weeks with Au nanoparticles (NPs), CeO2 NPs, or Au ions or body-injected with Au NPs, CeO2 NPs, or lipopolysaccharide endotoxin. Contrary to expectations, the feeding experiment showed that both NPs caused a significant increase in the total haemocyte count (THC). In contrast, the ion-positive control resulted in a significantly decreased THC. Additionally, changes in phenoloxidase (PO)-like activity, haemocyte viability, and nitric oxide (NO) levels seemed to depend on the stressor. Injection experiments also showed stressor-dependant changes in measured parameters, such as CeO2 NPs and lipopolysaccharide endotoxin (LPS), caused more significant responses than Au NPs. These results show that feeding and injection of NPs caused an immune response and that the response differed significantly, depending on the exposure route. We did not expect the response to ingested NPs, due to the low exposure concentrations (100 μg/g dry weight food) and a firm gut epithelia, along with a lack of phagocytosis in the digestive system, which would theoretically prevent NPs from crossing the biological barrier. It remains a challenge for future research to reveal what the physiological and ecological significance is for the organism to sense and respond, via the immune system, to ingested foreign material.


Use of a Digital Health Application for Influenza Surveillance in China.
To examine whether a commercial digital health application could support influenza surveillance in China. We retrieved data from the Thermia online and mobile educational tool, which allows parents to monitor their children's fever and infectious febrile illnesses including influenza. We modeled monthly aggregated influenza-like illness case counts from Thermia users over time and compared them against influenza monthly case counts obtained from the National Health and Family Planning Commission of the People's Republic of China by using time series regression analysis. We retrieved 44 999 observations from January 2014 through July 2016 from Thermia China. Thermia appeared to predict influenza outbreaks 1 month earlier than the National Health and Family Planning Commission influenza surveillance system (P = .046). Being younger, not having up-to-date immunizations, and having an underlying health condition were associated with participant-reported influenza-like illness. Digital health applications could supplement traditional influenza surveillance systems in China by providing access to consumers' symptom reporting. Growing popularity and use of commercial digital health applications in China potentially affords opportunities to support disease detection and monitoring and rapid treatment mobilization.


Enzyme-bound intermediates in the biosynthesis of bacitracin.
1. Bacitracin synthetase, a three-component enzyme complex which catalyzes synthesis of the dodecapeptide bacitracin A, has been prepared from Bacillus licheniformis strains ATCC 10716, AL and SB 319. During synthesis of bacitracin, the amino acids (smaller amounts) and peptides are covalently bound to the enzyme complex. The nature of the bindings suggest that the amino acids and peptides are thioester linked. 2. The peptides, identified by thin-layer chromatography after performic acid liberation were Ile-Cys, Ile-Cys-Leu, Ile-Cys-Leu-Glu, Ile-Cys-Leu-Glu, Ile-Cys-Leu-Glu-Ile, Ile-Cys-Leu-Glu-Ile-Lys-Orn, Ile-Cys-Leu-Glu-Ile-Ile-Orn-Ile, Ile-Cys-L-EU-Glu-Ile-Lys-Orn-Ile-Phe, Ile-Cys-Leu-Glu-Ile-L-YS-Orn-Ile-Phe-His-Phe-His and Ile-Cys-Leu-Glu-Ile-Lys-Orn-Ile-Phe-His-Asp. 3. The labelled peptides covalently bound to bacitracin synthetase were intermediates in bacitracin synthesis. 4. Chain growth is initiated on one enzyme component (A) by the addition of isoleucine and cysteine. The sequential addition of the other amino acids proceeds in the C-terminal direction until the pentapeptide is formed. Further addition of amino acids and production of bacitracin are obtained by adding the other enzyme components (B and C) to the incubation mixture.


Physicochemical properties and antidiabetic effects of a polysaccharide from corn silk in high-fat diet and streptozotocin-induced diabetic mice.
This study aimed to investigate the physicochemical properties and antidiabetic effects of a polysaccharide obtained from corn silk (PCS2). PCS2 was isolated and the physicochemical properties were characterized. The hypoglycemic effects were determined using the high-fat diet and streptozocin induced type 2 diabetic mellitus (T2DM) insulin resistance mice. The results showed that PCS2 was a heteropolysaccharide with the average molecular weight of 45.5kDa. PCS2 was composed of d-galactose, d-mannose, d-(+)-glucose, d-(+)-xylose, l-arabinose and l-rhamnose. PCS2 treatment significantly reduced the body weight loss, decreased blood glucose and serum insulin levels, and improved glucose intolerance (P<0.05). The levels of serum lipid profile were regulated and the levels of glycated serum protein, non-esterified fatty acid were decreased significantly (P<0.01). The activities of superoxide dismutase, glutathione peroxidase and catalase were notably improved (P<0.05). PCS2 also exerted cytoprotective action from histopathological observation. These results suggested that PCS2 could be a good candidate of functional food or medicine for T2DM treatment.


[Transition to adulthood of adolescents with inflammatory bowel disease].
Inflammatory bowel disease (IBD) is a prevalent chronic disorder, often diagnosed during childhood. Studies have suggested that the incidence of IBD in this group of patients is increasing. Children and adolescents with IBD frequently have more extensive and severe disease than adults. Transition is an important concept to ensure optimal health care management of adolescents and young adult patients with chronic physical and medical conditions. During this process there is a change in knowledge, attitudes and behavior towards the disease with a responsibility that gradually shifts from parents to the patient. The success of the transition process depends on the patient, pediatric and adult gastroenterologists. Thus, providers need to understand how to start, maintain and finish this process. When transition process is coordinated, staged and well planned, the adolescent and young adult will acquire the tools needed to successfully self-manage his or her own medical condition. Rather than a universal model of transition, each institution needs to adapt the most efficient model. The aim of this article is to review concepts pertinent to transition management for adolescents and young adults with IBD.


[The use of psychodiagnostic tests in forensic psychiatric reports within the framework of internment. An exploratory study of records on internees in the judicial district of Ghent].
In Belgium there is now a new law on the detention of mentally disordered offenders. The main problems with psychiatric reports compiled by experts concern the indistrict legal framework and the lack of financial resources; both of these factors may affect the quality of the reports. Earlier studies have shown that only a few standardised tests are used to substantiate the conclusions reached in the reports. To examine to what extent forensic psychiatrists use diagnostic tools to substantiate the conclusions in their reports. We based our study on a sample consisting of 84 records of recent cases dealt with by the Committee for the Protection of Society (CPS) of the judicial district of Ghent. We found that diagnostic tools were used in 63% of the cases studied. In spite of the difficult circumstances in which a forensic psychiatrist has to work, test instruments were used regularly in diagnostics. Moreover, most of the test instruments used were considered acceptable according to the scientific literature. The study has shown the need for a clear-cut legal framework involving criteria that forensic psychiatrists must meet when conducting their research. Inspiration for these criteria is to be found in the Netherlands where psychiatrists are already working with a specific format for forensic psychiatric reports.


Inhaled magnesium sulfate in the treatment of acute asthma.
Asthma exacerbations can be frequent and range in severity from relatively mild to status asthmaticus. The use of magnesium sulfate (MgSO(4)) is one of numerous treatment options available during acute exacerbations. While the efficacy of intravenous MgSO(4) has been demonstrated, little is known of the role of inhaled MgSO(4). To determine the efficacy of inhaled MgSO(4) administered in acute asthma on pulmonary functions and admission rates. To quantify the effects of inhaled MgSO(4) i) in addition to inhaled β(2)-agonist, ii) in comparison to inhaled β(2)-agonist alone or iii) in addition to combination treatment with inhaled β(2) -agonist and ipratropium bromide. Randomised controlled trials were identified from the Cochrane Airways Group register of trials in September 2012. These trials were supplemented with trials found in the reference list of published studies, studies found using extensive electronic search techniques, as well as a review of the grey literature and conference proceedings. Randomised (or pseudo-randomised) controlled trials including adults or children with acute asthma were eligible for inclusion in the review. Studies were included if patients were treated with nebulised MgSO(4) alone or in combination with β(2)-agonist and/or ipratropium bromide and were compared with β(2)-agonist alone or inactive control. Trial selection, data extraction and risk of bias were assessed independently by two review authors. Efforts were made to collect missing data from authors. Results are presented as standardised mean differences (SMD) for pulmonary function and risk ratios (RR) for hospital admission; both are displayed with their 95% confidence intervals (CI). Sixteen trials (21 references) of unclear and high risk of bias were eligible and included 896 patients who were randomised (838 patients completed). Seven of the 16 included studies involved adults exclusively, three included adults and paediatric patients, four studies enrolled paediatric patients and in the remaining two studies the age of participants was not stated.The design, definitions, intervention and outcomes were different in all 16 studies; this heterogeneity made direct comparisons difficult (see additional tables 1-3).The overall risk of bias among the included studies was variable and this is reflected in the 'Summary of findings' table with most outcomes being judged as only moderate or less.Inhaled magnesium sulfate in addition to inhaled β(2)-agonistThere was no statistically significant improvement in pulmonary function when inhaled MgSO(4) and β(2)-agonist was compared with β(2)-agonist alone (SMD 0.23; 95% CI -0.27 to 0.74; three studies, n = 188); however, there was considerable between study heterogeneity. There was no clear advantage in terms of hospital admissions (RR 0.76 95% CI 0.49, 1.16; four studies, n = 249), and there were no serious adverse events reported.Inhaled magnesium sulfate versus inhaled β(2)-agonistThe results of pulmonary function in three studies that compared inhaled MgSO(4) versus β(2)-agonist were too heterogeneous to combine; however, two of the studies found poorer lung function on MgSO(4). There was no significant difference in terms of hospital admissions in a single small study when MgSO(4) was compared to β(2)-agonist (RR 0.53 95% CI 0.05, 5.31; one study, n = 33), and there were no serious adverse events reported.Inhaled magnesium sulfate in addition to inhaled β(2)-agonist and ipratropiumA further comparison has been included in the 2012 update of this review of MgSO(4) given in addition to inhaled ipratropium and β(2)-agonist therapy (as recommended by the GINA guidelines). However, there is not yet enough data for this outcome to come to any definite conclusions, but both small studies in adults with severe asthma exacerbation found improvements in pulmonary function with additional inhaled MgSO(4). There is currently no good evidence that inhaled MgSO(4) can be used as a substitute for inhaled β(2)-agonists. When used in addition to inhaled β(2)-agonists (with or without inhaled ipratropium), there is currently no overall clear evidence of improved pulmonary function or reduced hospital admissions. However, individual study results from three trials suggest possible improved pulmonary function in those with severe asthma exacerbations (FEV1 less than 50% predicted). Heterogeneity among trials included in this review precludes a more definitive conclusion. Further studies should focus on inhaled MgSO(4) in addition to the current guideline treatment for acute asthma (inhaled β(2) -agonist and ipratropium bromide). As the evidence suggests that the most effective role of nebulised MgSO(4) may be in those with severe acute features and this is where future research should be focused. A set of core outcomes needs to be agreed upon both in adult and paediatric studies to allow improved study comparison in future.


Kihi-to, a herbal traditional medicine, improves Abeta(25-35)-induced memory impairment and losses of neurites and synapses.
We previously hypothesized that achievement of recovery of brain function after the injury requires the reconstruction of neuronal networks, including neurite regeneration and synapse reformation. Kihi-to is composed of twelve crude drugs, some of which have already been shown to possess neurite extension properties in our previous studies. The effect of Kihi-to on memory deficit has not been examined. Thus, the goal of the present study is to determine the in vivo and in vitro effects of Kihi-to on memory, neurite growth and synapse reconstruction. Effects of Kihi-to, a traditional Japanese-Chinese traditional medicine, on memory deficits and losses of neurites and synapses were examined using Alzheimer's disease model mice. Improvements of Abeta(25-35)-induced neuritic atrophy by Kihi-to and the mechanism were investigated in cultured cortical neurons. Administration of Kihi-to for consecutive 3 days resulted in marked improvements of Abeta(25-35)-induced impairments in memory acquisition, memory retention, and object recognition memory in mice. Immunohistochemical comparisons suggested that Kihi-to attenuated neuritic, synaptic and myelin losses in the cerebral cortex, hippocampus and striatum. Kihi-to also attenuated the calpain increase in the cerebral cortex and hippocampus. When Kihi-to was added to cells 4 days after Abeta(25-35) treatment, axonal and dendritic outgrowths in cultured cortical neurons were restored as demonstrated by extended lengths of phosphorylated neurofilament-H (P-NF-H) and microtubule-associated protein (MAP)2-positive neurites. Abeta(25-35)-induced cell death in cortical culture was also markedly inhibited by Kihi-to. Since NF-H, MAP2 and myelin basic protein (MBP) are substrates of calpain, and calpain is known to be involved in Abeta-induced axonal atrophy, expression levels of calpain and calpastatin were measured. Treatment with Kihi-to inhibited the Abeta(25-35)-evoked increase in the calpain level and decrease in the calpastatin level. In addition, Kihi-to inhibited Abeta(25-35)-induced calcium entry. In conclusion Kihi-to clearly improved the memory impairment and losses of neurites and synapses.


Epidemiology and clinical profile of Takotsubo cardiomyopathy.
First described in Japan over 2 decades ago, takotsubo cardiomyopathy (TTC) has emerged as a unique cardiomyopathy with world-wide recognition, mimicking acute coronary syndrome. In early TTC experience, typical patients were older women, with a triggering emotional event, ST-segment elevation, and apical ballooning left ventricular (LV) contraction pattern. However, TTC is now more heterogeneous, occurring in males and younger individuals, without ST-segment elevation, as a spontaneous event in the absence of a trigger, and with diverse LV contraction patterns. Furthermore, TTC is more common than initially thought, now constituting 10% of women with suspected acute coronary syndrome. TTC is also associated with a broader range of psychological or physical triggers, including presentation during outpatient medical evaluations or hospitalization for acute illness. Although TTC has been considered a benign condition, it now carries a small but important risk for adverse outcomes, including cardiac arrest in 5%. Hemodynamic instability requiring intervention with vasopressor drugs or intra-aortic balloon pump is necessary in 15% and in-hospital mortality is approximately 5%, largely because of refractory cardiogenic shock or irreversible major comorbid conditions. Although complete cardiac recovery usually occurs rapidly, post-hospital survival may be less than the general population of similar age, largely because of concomitant illnesses. TTC may reoccur in up to 10% of patients, but β-blocking drugs are not absolutely preventive for initial or subsequent events.


Atrioventricular block in the atypical form of junctional reciprocating tachycardia: evidence supporting the atrioventricular node as the site of reentry.
Serial electrophysiologic studies were performed in 19 patients with the atypical form of supraventricular tachycardia having a long RP and short PR interval. In all 19 patients, supraventricular tachycardia was found to have a 1:1 P-QRS relation during initial control electrophysiologic studies, and in all 19 patients, electrophysiologic studies suggested that junctional reentry was the mechanism of supraventricular tachycardia. Seven of the 19 patients developed atrioventricular (AV) block during initiation of supraventricular tachycardia or after induction of supraventricular tachycardia following various drug administrations in subsequent studies. In three patients, second degree block within the His bundle or block distal to the His bundle recording site occurred after administration of quinidine. In one patient it occurred after procainamide, and in another patient it occurred after atropine. In one patient, 2:1 block proximal to the His deflection occurred after verapamil. In the remaining patient, a transient Wenckebach block proximal to the His deflection was noted after adenosine triphosphate. In this latter patient, 2:1 AV block was also noted after propranolol and digoxin. The site of reentry in these seven patients with AV block during supraventricular tachycardia was confined to the AV node area. Their supraventricular tachycardia did not involve a slowly conducting paraseptal accessory pathway because the distal AV node, His bundle and ventricle were not found to be necessary links in the tachycardia circuit.


Bisdemethoxycurcumin inhibits ovarian cancer via reducing oxidative stress mediated MMPs expressions.
As one main active compound of curcuminoids, Bisdemethoxycurcumin (BDMC) possesses several biological activities, such as anti-inflammation and anti-cancer activities. However, the detailed mechanism of BDMC's anti-metastasis activity in ovarian cancer has not been clearly elucidated yet. In the present study, cell proliferation, wound healing motility, cell adhesion and invasion with or without BDMC were determined. In addition, western blot was used to examine proteins expressions. The lucigenin-enhanced luminescence was introduced to assess cellular oxidative stress. The luciferase reporter gene assay was introduced to evaluate the transcriptional activity of NF-κB. Finally, BDMC significantly inhibited the adhesion, migration, invasion and metastasis of SKOV-3 cells. Moreover, BDMC inhibited expressions of several degradation-associated proteins, such as matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), CD147, urokinase plasminogen activator (uPA), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), whereas increased expression of tissue inhibitor of metalloproteinase-1 (TIMP-1), in a dose-dependent manner. In addition, BDMC reduced generation of cellular superoxide in a dose-dependent manner. Furthermore, BDMC inhibited the phosphorylation levels of NF-κB p65 and IκB-α, and consequently reduced NF-κB-driven luciferase expression. Collectively, BDMC serves as a therapeutic medicine to suppress ovarian cancer, perhaps via inhibiting cellular oxidative stress and subsequently inactivating NF-κB pathway.


Relationship between General and Sport-Related Drinking Motives and Athlete Alcohol Use and Problems.
Alcohol use (and adverse consequences due to alcohol use) among college student-athletes is a common occurrence and consequently garners attention as a health concern within athletic departments and the NCAA. One of the strongest predictors of alcohol use in athletes is motivation to drink. However, not much is known about the influence of alcohol use motivations on drinking in collegiate athletes. Therefore, this study examined the influence of sport-related and general drinking motives on alcohol use and alcohol-related problems. Participants were female collegiate softball players (N = 721) from 62 NCAA teams. Athletes completed the Athlete Drinking Scale (Martens et al., 2005), the Drinking Motives Questionnaire, revised (Cooper, 1994; Cooper et al., 1992), alcohol consumption measures, and the Rutgers Alcohol Problems Index (White & Labouvie, 1989). Multilevel modeling was used to analyze the data. Higher scores on Positive Reinforcement motives were associated with greater alcohol consumption, heavy episodic drinking, and alcohol-related problems. Enhancement motives were positively associated with heavy episodic drinking and alcohol-related problems, while Coping motives were positively associated with alcohol-related problems. Lower scores on Conformity motives were related to higher alcohol consumption, whereas higher scores were related to more alcohol-related problems. These results assist in understanding salient drinking motives among athletes while accounting for nesting effects of athletes within teams. Results demonstrate alcohol use as a perceived means of reward for hard work or good athletic performance, thus attempts to control alcohol use in college athletics should emphasize alternative methods to positively reinforce efforts or celebrate victories.


Diabetes Prevention and Weight Loss with a Fully Automated Behavioral Intervention by Email, Web, and Mobile Phone: A Randomized Controlled Trial Among Persons with Prediabetes.
One-third of US adults, 86 million people, have prediabetes. Two-thirds of adults are overweight or obese and at risk for diabetes. Effective and affordable interventions are needed that can reach these 86 million, and others at high risk, to reduce their progression to diagnosed diabetes. The aim was to evaluate the effectiveness of a fully automated algorithm-driven behavioral intervention for diabetes prevention, Alive-PD, delivered via the Web, Internet, mobile phone, and automated phone calls. Alive-PD provided tailored behavioral support for improvements in physical activity, eating habits, and factors such as weight loss, stress, and sleep. Weekly emails suggested small-step goals and linked to an individual Web page with tools for tracking, coaching, social support through virtual teams, competition, and health information. A mobile phone app and automated phone calls provided further support. The trial randomly assigned 339 persons to the Alive-PD intervention (n=163) or a 6-month wait-list usual-care control group (n=176). Participants were eligible if either fasting glucose or glycated hemoglobin A1c (HbA1c) was in the prediabetic range. Primary outcome measures were changes in fasting glucose and HbA1c at 6 months. Secondary outcome measures included clinic-measured changes in body weight, body mass index (BMI), waist circumference, triglyceride/high-density lipoprotein cholesterol (TG/HDL) ratio, and Framingham diabetes risk score. Analysis was by intention-to-treat. Participants' mean age was 55 (SD 8.9) years, mean BMI was 31.2 (SD 4.4) kg/m(2), and 68.7% (233/339) were male. Mean fasting glucose was in the prediabetic range (mean 109.9, SD 8.4 mg/dL), whereas the mean HbA1c was 5.6% (SD 0.3), in the normal range. In intention-to-treat analyses, Alive-PD participants achieved significantly greater reductions than controls in fasting glucose (mean -7.36 mg/dL, 95% CI -7.85 to -6.87 vs mean -2.19, 95% CI -2.64 to -1.73, P<.001), HbA1c (mean -0.26%, 95% CI -0.27 to -0.24 vs mean -0.18%, 95% CI -0.19 to -0.16, P<.001), and body weight (mean -3.26 kg, 95% CI -3.26 to -3.25 vs mean -1.26 kg, 95% CI -1.27 to -1.26, P<.001). Reductions in BMI, waist circumference, and TG/HDL were also significantly greater in Alive-PD participants than in the control group. At 6 months, the Alive-PD group reduced their Framingham 8-year diabetes risk from 16% to 11%, significantly more than the control group (P<.001). Participation and retention was good; intervention participants interacted with the program a median of 17 (IQR 14) of 24 weeks and 71.1% (116/163) were still interacting with the program in month 6. Alive-PD improved glycemic control, body weight, BMI, waist circumference, TG/HDL ratio, and diabetes risk. As a fully automated system, the program has high potential for scalability and could potentially reach many of the 86 million US adults who have prediabetes as well as other at-risk groups. Clinicaltrials.gov NCT01479062; https://clinicaltrials.gov/ct2/show/NCT01479062 (Archived by WebCite at http://www.webcitation.org/6bt4V20NR).


Balancing the risks and benefits associated with cosmetic dentistry - a joint statement by UK specialist dental societies.
Cosmetic dentistry has become increasingly popular, largely as a result of social trends and increased media coverage. This understandable desire for the alleged 'perfect smile' needs to be tempered with an appropriate awareness of the significant risks associated with invasive cosmetic procedures such as veneers and crowns. Patients need to be properly informed that elective removal of healthy enamel and dentine can result in pulpal injury and poorer periodontal health in the longer term, particularly if they are young. The duty of candour means that they ought to be informed that aggressive reduction of sound tooth tissue is not biologically neutral and results in structural weakening of their teeth. Less invasive procedures such as bleaching on its own or for example, combined with direct resin composite bonding, can satisfy many patient's demands, while still being kinder to teeth and having much better fall-back positions for their future requirements. It is the opinion of the British Endodontic Society, British Society for Restorative Dentistry, Restorative Dentistry UK, Dental Trauma UK, British Society of Prosthodontics and the British Society of Paediatric Dentistry that elective invasive cosmetic dental treatments can result in great benefit to patients, but that some aggressive treatments used to achieve them can produce significant morbidities in teeth which were previously healthy. This is a worrying and growing problem with many ethical, legal and biologic aspects, but many adverse outcomes for patients who request cosmetic dental improvements are preventable by using biologically safer initial approaches to treatment planning and its provision.


Measuring assessors' experiences of grading marginal student performances in clinical assessments - The assess-safe tool: Development and preliminary psychometric validation.
Assessment of fitness for practice in the nursing student population is an essential yet challenging component of nursing education. The aim of this research was to describe the development and preliminary validation of the Assess-Safe instrument that explores assessors' experiences of grading nursing student performances in clinical courses when that performance is not a clear pass or fail. A 3 phase approach was used to develop and psychometrically test the instrument. Phase 1 involved the development of a pool of items following a literature review, coupled with findings from qualitative data. In phase 2, an expert panel rated the items for clarity and relevance, reducing the item pool. Assessors of Australian undergraduate nursing students from industry and academia were recruited for this study. A sample of 149 assessors across industry and academia completed the resultant survey to pilot test the instrument; constituting Phase 3. A high content validity index score of 0.95 was achieved through expert review. Construct validity using factor analysis revealed four factors including: assessor support; process support; assessor introspection; and student support. The Assess-Safe instrument achieved good internal reliability with an overall Cronbach's alpha coefficient of 0.77; and sub-scale scores ranging from 0.71 to 0.79. The Assess-Safe instrument demonstrated satisfactory psychometric properties and has utility for education programmes, research and policy development across a variety of practice based professions. Nonetheless, further psychometric validation is warranted.


Mapping efficacious deep brain stimulation for pediatric dystonia.
The objective of this study was to report the authors' experience with deep brain stimulation (DBS) of the internal globus pallidus (GPi) as a treatment for pediatric dystonia, and to elucidate substrates underlying clinical outcome using state-of-the-art neuroimaging techniques. A retrospective analysis was conducted in 11 pediatric patients (6 girls and 5 boys, mean age 12 ± 4 years) with medically refractory dystonia who underwent GPi-DBS implantation between June 2009 and September 2017. Using pre- and postoperative MRI, volumes of tissue activated were modeled and weighted by clinical outcome to identify brain regions associated with clinical outcome. Functional and structural networks associated with clinical benefits were also determined using large-scale normative data sets. A total of 21 implanted leads were analyzed in 11 patients. The average follow-up duration was 19 ± 20 months (median 5 months). Using a 7-point clinical rating scale, 10 patients showed response to treatment, as defined by scores < 3. The mean improvement in the Burke-Fahn-Marsden Dystonia Rating Scale motor score was 40% ± 23%. The probabilistic map of efficacy showed that the voxel cluster most associated with clinical improvement was located at the posterior aspect of the GPi, comparatively posterior and superior to the coordinates of the classic GPi target. Strong functional and structural connectivity was evident between the probabilistic map and areas such as the precentral and postcentral gyri, parietooccipital cortex, and brainstem. This study reported on a series of pediatric patients with dystonia in whom GPi-DBS resulted in variable clinical benefit and described a clinically favorable stimulation site for this cohort, as well as its structural and functional connectivity. This information could be valuable for improving surgical planning, simplifying programming, and further informing disease pathophysiology.


First case of B ALL with KMT2A-MAML2 rearrangement: a case report.
A large number of chromosomal translocations of the human KMT2A gene, better known as the MLL gene, have so far been characterized. Genetic rearrangements involving KMT2A gene are frequently involved in lymphoid, myeloid and mixed lineage leukemia. One of its rare fusion partners, the mastermind like 2 (MAML2) gene has been reported in four cases of myeloid neoplasms after chemotherapy so far: two acute myeloid leukemias (AML) and two myelodysplasic syndrome (MDS), and two cases of secondary T-cell acute lymphoblastic leukemia (T-ALL). Here we report the case of a KMT2A - MAML2 fusion discovered by Next-Generation Sequencing (NGS) analysis in front of an inv11 (q21q23) present in a 47-year-old female previously treated for a sarcoma in 2014, who had a B acute lymphoid leukemia (B ALL). It is, to our knowledge, the first case of B acute lymphoblastic leukemia with this fusion gene. At the molecular level, two rearrangements were detected using RNA sequencing juxtaposing exon 7 to exon 2 and exon 9 to intron 1-2 of the KMT2A and MAML2 genes respectively, and one rearrangement using Sanger sequencing juxtaposing exon 8 and exon 2.


Polyomavirus middle T-induced mammary intraepithelial neoplasia outgrowths: single origin, divergent evolution, and multiple outcomes.
The development of models to investigate the pathobiology of premalignant breast lesions is a critical prerequisite for development of breast cancer prevention and early intervention strategies. Using tissue transplantation techniques, we modified the widely used polyomavirus middle T (PyV-mT) transgenic mouse model of breast cancer to study the premalignant stages of tumorigenesis. Premalignant atypical lesions were isolated from PyV-mT transgenic mice and used to generate two sets of three mammary intraepithelial neoplasia (MIN) outgrowth lines. Investigation of these six unique lines, each of which fulfills the criteria for MIN, has provided new information regarding the biology of PyV-mT-induced neoplasia. Although expression of the PyV-mT transgene was the primary initiating event for all lines, they exhibited different tumor latencies, metastatic potentials, and morphologies. Six distinguishable morphologic patterns of differentiation were identified within the premalignant outgrowths that are likely to represent several tumorigenic pathways. Further, several tumor phenotypes developed from each line and the tumors developing from the six lines had different metastatic potentials. These observations are consistent with the hypothesis that distinct pathways of PyV-mT-initiated neoplastic progression lead to different outcomes with respect to latency and metastasis. The MIN outgrowth lines share several characteristics with precursors of human breast cancer including the observation that gene expression profiles of tumors are more similar to those of the MIN outgrowth line outgrowth from which they developed than to other tumors. These lines provide an opportunity to study the full range of events occurring secondary to PyV-mT expression in the mammary gland.