Patterns of cybervictimization and emotion regulation in adolescents and adults.
Research on cyberbullying has boomed in the past two decades. Findings from studies among adolescents suggest that they can be classified into distinct groups based on their cyberbullying experience, and that cyberbullying seems to be related to poor emotion regulation. So far, only a few studies have examined cyberbullying among adult workers and it is unclear whether cyberbullying develops similarly in that population. Therefore, in this study cyberbullying victimization was assessed in adolescents and adult workers simultaneously to address three aims: (1) to explore which groups can be distinguished based on their cyberbullying experience; (2) to analyze the associations of group membership with the way people regulate their emotions; and (3) to examine whether the results are comparable in adolescents and adults. Latent class analysis was used to analyze data from 1,426 employees and 1,715 adolescents in the first year of secondary education (12-13 years old). In each population, three profiles differing in their patterns of cybervictimization were identified: no cybervictimization (80%), work-related cybervictimization (18%), and pervasive cybervictimization (3%) for adults, and no cybervictimization (68%), similar-to-offline cybervictimization (27%), and pervasive cybervictimization (4%) for adolescents. Furthermore, these profiles differed in their use of emotion regulation strategies, with pervasive cyber-victims suppressing their emotions significantly more than other groups. Future research is needed to clarify the role of emotion regulation in cyberbullying as an antecedent or consequence of victimization.


Evaluation of Traffic Accident Risk in In-City Bus Drivers: The Use of Berlin Questionnaire.
Traffic accidents associated with high mortality rate may produce serious problems especially in highways. Obstructive sleep apnea (OSA) has been associated with a high risk for traffic accidents due to excessive daytime sleepiness even in in-city drivers. In the present study, it was aimed to evaluate the rate of OSA symptoms and to identify risk factors associated with traffic accidents in in-city bus drivers. A self-administered questionnaire including demographic and anthropometric features, sleep and work schedules, Berlin questionnaire, Epworth sleepiness score (ESS), and history of traffic accidents was used. The questionnaire was conducted for 1400 male bus drivers (mean age, 38.0±6.4 y, body mass index, 27.8±3.9 kg/m2). A total of 1058 (75.6%) drivers had one or more accidents while driving bus. According to the Berlin questionnaire, 176 (12.6%) drivers were found to have high OSA risk and the accident rate was 83.0% in high-risk group, whereas 74.5% of low-risk drivers had accidents (p=0.043). The drivers with a history of traffic accident were older (p=0.030), had higher ESS (p=0.019), and were more in the high-risk OSA group according to the Berlin questionnaire (p=0.015). In multivariate linear regression analysis, traffic accident was associated with only Berlin questionnaire (p=0.015). The present results support that city bus drivers with high OSA risk according to Berlin questionnaire have increased accident rates. Therefore, we suggest using Berlin questionnaire for screening sleep apnea not only in highway drivers but also in in-city bus drivers.


Experience With a Care Process Model in the Evaluation of Pediatric Musculoskeletal Infections in a Pediatric Emergency Department.
Care process models (CPMs) for certain conditions have improved clinical outcomes in children. This study describes the implementation and impact of a CPM for the evaluation of musculoskeletal infections in a pediatric emergency department (ED). A retrospective pre-post intervention study was performed to analyze the impact of a musculoskeletal infection CPM. Patients were identified retrospectively through electronic order history for imaging of an extremity or joint and recommended laboratory tests. Clinical outcomes evaluated included hospital length of stay (LOS), time to magnetic resonance imaging (MRI), time to administration of antibiotics, hospital admission rate, and 30-day readmission rate. Musculoskeletal infection evaluations completed in the ED were reviewed from 1 year before implementation (n = 383) and 2 years after implementation (n = 1219) of the CPM. A significant improvement in the time to antibiotic administration for all patients (4.3 vs 3.7 hours, P < 0.05) and for patients with confirmed musculoskeletal infections (9.5 vs 4.9 hours, P < 0.05) was observed after the implementation of the CPM. The overall time to MRI (13.2 vs 10.3 hours, P = 0.29) and hospital LOS (4.7 vs 3.7 days, P = 0.11) were improved for all patients but were not statistically significant. The admission rate and 30-day readmission were similar before and after the implementation of the CPM. The implementation of a musculoskeletal infection CPM has standardized the approach to the evaluation and diagnosis of musculoskeletal infections resulting in a significant decrease in the time to administer antibiotics and a downward trend in time to MRI and hospital LOS.


Synergism between halide binding and proton transport in a CLC-type exchanger.
The Cl-/H+ exchange-transporter CLC-ec1 mediates stoichiometric transmembrane exchange of two Cl- ions for one proton. A conserved tyrosine residue, Y445, coordinates one of the bound Cl- ions visible in the structure of this protein and is located near the intersection of the Cl- and H+ pathways. Mutants of this tyrosine were scrutinized for effects on the coupled transport of Cl- and H+ determined electrophysiologically and on protein structure determined crystallographically. Despite the strong conservation of Y445 in the CLC family, substitution of F or W at this position preserves wild-type transport behavior. Substitution by A, E, or H, however, produces uncoupled proteins with robust Cl- transport but greatly impaired movement of H+. The obligatory 2 Cl-/1 H+ stoichiometry is thus lost in these mutants. The structures of all the mutants are essentially identical to wild-type, but apparent anion occupancy in the Cl- binding region correlates with functional H+ coupling. In particular, as determined by anomalous diffraction in crystals grown in Br-, an electrophysiologically competent Cl- analogue, the well-coupled transporters show strong Br- electron density at the "inner" and "central" Cl- binding sites. However, in the uncoupled mutants, Br- density is absent at the central site, while still present at the inner site. An additional mutant, Y445L, is intermediate in both functional and structural features. This mutant clearly exchanges H+ for Cl-, but at a reduced H+-to-Cl- ratio; likewise, both the central and inner sites are occupied by Br-, but the central site shows lower Br- density than in wild-type (or in Y445F,W). The correlation between proton coupling and central-site occupancy argues that halide binding to the central transport site somehow facilitates movement of H+, a synergism that is not readily understood in terms of alternating-site antiport schemes.


A single-cell perspective on non-growing but metabolically active (NGMA) bacteria.
A long-standing and fundamental problem in microbiology is the non-trivial discrimination between live and dead cells. The existence of physically intact and possibly viable bacterial cells that fail to replicate during a more or less protracted period of observation, despite environmental conditions that are ostensibly propitious for growth, has been extensively documented in many different organisms. In clinical settings, non-culturable cells may contribute to non-apparent infections capable of reactivating after months or years of clinical latency, a phenomenon that has been well documented in the specific case of Mycobacterium tuberculosis. The prevalence of these silent but potentially problematic bacterial reservoirs has been highlighted by classical approaches such as limiting culture dilution till extinction of growing cells, followed by resuscitation of apparently "viable but non-culturable" (VBNC) subpopulations. Although these assays are useful to demonstrate the presence of VBNC cells in a population, they are effectively retrospective and are not well suited to the analysis of non-replicating cells per se. Here, we argue that research on a closely related problem, which we shall refer to as the "non-growing but metabolically active" state, is poised to advance rapidly thanks to the recent development of novel technologies and methods for real-time single-cell analysis. In particular, the combination of fluorescent reporter dyes and strains, microfluidic and microelectromechanical systems, and time-lapse fluorescence microscopy offers tremendous and largely untapped potential for future exploration of the physiology of non-replicating cells.


Carotenoid metabolism strengthens the link between feather coloration and individual quality.
Thirty years of research has made carotenoid coloration a textbook example of an honest signal of individual quality, but tests of this idea are surprisingly inconsistent. Here, to investigate sources of this heterogeneity, we perform meta-analyses of published studies on the relationship between carotenoid-based feather coloration and measures of individual quality. To create color displays, animals use either carotenoids unchanged from dietary components or carotenoids that they biochemically convert before deposition. We hypothesize that converted carotenoids better reflect individual quality because of the physiological links between cellular function and carotenoid metabolism. We show that feather coloration is an honest signal of some, but not all, measures of quality. Where these relationships exist, we show that converted, but not dietary, carotenoid coloration drives the relationship. Our results have broad implications for understanding the evolutionary role of carotenoid coloration and the physiological mechanisms that maintain signal honesty of animal ornamental traits.


Immunological instability of persistent adenovirus vectors in the brain: peripheral exposure to vector leads to renewed inflammation, reduced gene expression, and demyelination.
Nonreplicating adenovirus vectors are being developed as vehicles for the delivery of therapeutic genes in vivo. Whereas in many organs an antiviral T cell response eliminates the vector and damages local tissue, when adenovirus vectors are injected into the brain the subsequent immune attack can be ineffective, allowing the vector to persist. In the present study, E1-deleted human adenovirus vectors were injected into the caudate nucleus of rats. Two months later, expression of protein from the vector was still evident and little inflammation was seen. A subcutaneous injection of adenovirus vector at this time, however, led within 2 weeks to severe mononuclear inflammation and microglial activation in the caudate. This caused local demyelination and a decrease in detectable protein expression from the vector. Interestingly, intense microglial activation and numerous lymphocytes and monocytes were also seen in brain areas containing neurons capable of retrogradely transporting the adenovirus vector from the caudate. Control experiments established that this inflammation in distant brain areas was not a nonspecific consequence of degeneration. These experiments demonstrate that although adenovirus vectors can persist in the brain without causing chronic inflammation, they remain the potential target of a damaging cell-mediated immune response brought about by a subsequent peripheral exposure to vector. The finding of lymphocytes in brain areas that project to the caudate further shows that viral antigens that are retrogradely transported by neurons can also be the target of a T cell attack.


Combat-training stress in soldiers increases S100B, a marker of increased blood-brain-barrier permeability, and induces immune activation.
Experimental data suggest stress-related cognitive dysfunction may be associated with increased blood-brain-barrier (BBB) permeability secondary to immune activation. We investigated the relationship between prolonged and intense physical and psychological combat-training stress, immune activation and blood-brain-barrier permeability in 37 healthy male army medical rapid response troops. Soldiers during intense combat training showed greater self-reported stress, anxiety and depression levels than at rest, as assessed by specific questionnaires. S100B, a marker of BBB permeability, as well as serum cortisol, IL-6 and TNF-α concentrations, were significantly increased in soldiers during combat training compared to rest (all p<0.05). Serum S100B correlated negatively with morning serum cortisol in soldiers during combat training, but not during the rest period (r=-0.387, p<0.05). We conclude that combat training inducing significant levels of stress, depression and anxiety is accompanied by evidence of increased blood-brain barrier permeability and by increases in systemic pro-inflammatory mediators.


Relationship of 99mtechnetium labelled macroaggregated albumin (99mTc-MAA) uptake by colorectal liver metastases to response following Selective Internal Radiation Therapy (SIRT).
SIRT is an emerging treatment for liver tumours which relies on the selective uptake by tumour of 90Y microspheres following hepatic arterial injection. Response rates of around 90% are reported. Hepatic arterial injection of MAA gives an indication of the expected distribution of 90Y microspheres within the liver. This study sought to determine if the MAA scan could be predictive of subsequent tumour response. 58 patients with colorectal hepatic metastases received SIRT. All had pre-treatment MAA planar images and CT scans which were retrospectively reviewed. Tumours were qualitatively considered "cold", "equivocal" or "hot" based on MAA uptake and the ratio of uptake in tumour and normal liver tissue was calculated (TNR). Following SIRT (which included the administration of hepatic arterial Angiotensin 2) tumour response was assessed by CEA changes one to two months after treatment and by serial CT. Uptake was classified as "hot" in 37 patients (Group 1) and "equivocal" or "cold" in 21 (Group 2). CEA levels fell dramatically in over 90% of patients. The falls were not significantly different between the groups. There was no correlation between TNR and tumour response based on CEA changes (r2 = 0.004). CT responses after 3 months were not different in the 2 Groups. The pattern of MAA uptake by colorectal liver tumours after arterial injection is not a predictor of tumour response after treatment by SIRT. The results suggest the doses of 90Y microspheres used may be greater than is necessary.


Knowledge-based model of hydrogen-bonding propensity in organic crystals.
A new method is presented to predict which donors and acceptors form hydrogen bonds in a crystal structure, based on the statistical analysis of hydrogen bonds in the Cambridge Structural Database (CSD). The method is named the logit hydrogen-bonding propensity (LHP) model. The approach has a potential application in identifying both likely and unusual hydrogen bonding, which can help to rationalize stable and metastable crystalline forms, of relevance to drug development in the pharmaceutical industry. Whilst polymorph prediction techniques are widely used, the LHP model is knowledge-based and is not restricted by the computational issues of polymorph prediction, and as such may form a valuable precursor to polymorph screening. Model construction applies logistic regression, using training data obtained with a new survey method based on the CSD system. The survey categorizes the hydrogen bonds and extracts model parameter values using descriptive structural and chemical properties from three-dimensional organic crystal structures. LHP predictions from a fitted model are made using two-dimensional observables alone. In the initial cases analysed, the model is highly accurate, achieving approximately 90% correct classification of both observed hydrogen bonds and non-interacting donor-acceptor pairs. Extensive statistical validation shows the LHP model to be robust across a range of small-molecule organic crystal structures.


High-intensity aerobic interval training increases fat and carbohydrate metabolic capacities in human skeletal muscle.
High-intensity aerobic interval training (HIIT) is a compromise between time-consuming moderate-intensity training and sprint-interval training requiring all-out efforts. However, there are few data regarding the ability of HIIT to increase the capacities of fat and carbohydrate oxidation in skeletal muscle. Using untrained recreationally active individuals, we investigated skeletal muscle and whole-body metabolic adaptations that occurred following 6 weeks of HIIT (~1 h of 10 x 4 min intervals at ~90% of peak oxygen consumption (VO2 peak), separated by 2 min rest, 3 d.week-1). A VO2 peak test, a test to exhaustion (TE) at 90% of pre-training VO2 peak, and a 1 h cycle at 60% of pre-training VO2 peak were performed pre- and post-HIIT. Muscle biopsies were sampled during the TE at rest, after 5 min, and at exhaustion. Training power output increased by 21%, and VO2 peak increased by 9% following HIIT. Muscle adaptations at rest included the following: (i) increased cytochrome c oxidase IV content (18%) and maximal activities of the mitochondrial enzymes citrate synthase (26%), beta-hydroxyacyl-CoA dehydrogenase (29%), aspartate-amino transferase (26%), and pyruvate dehydrogenase (PDH; 21%); (ii) increased FAT/CD36, FABPpm, GLUT 4, and MCT 1 and 4 transport proteins (14%-30%); and (iii) increased glycogen content (59%). Major adaptations during exercise included the following: (i) reduced glycogenolysis, lactate accumulation, and substrate phosphorylation (0-5 min of TE); (ii) unchanged PDH activation (carbohydrate oxidation; 0-5 min of TE); (iii) ~2-fold greater time during the TE; and (iv) increased fat oxidation at 60% of pre-training VO2 peak. This study demonstrated that 18 h of repeated high-intensity exercise sessions over 6 weeks (3 d.week-1) is a powerful method to increase whole-body and skeletal muscle capacities to oxidize fat and carbohydrate in previously untrained individuals.


Covalent modification of all members of human cullin family proteins by NEDD8.
Recently we found that NEDD8, a ubiquitin-like protein, was linked covalently to human cullin-4A (abbreviated Cul-4A) by a new ubiquitin-related pathway that is analogous to but distinct from the ligating system for SUMO1, another ubiquitin-like protein. However, it remained unknown whether the other five members of the family of human cullin/Cdc53 proteins are modified by NEDD8. Here we report that all Hs-Cul family proteins, such as Cul-1, Cul-2, Cul-3, Cul-4B, and Cul-5, in addition to Cul-4A, were modified by covalent attachment of NEDD8 in rabbit reticulocyte lysates. Moreover, by comprehensive Northern-blot analyses, we examined multiple tissue distributions of the messages for all Cul-family proteins, NEDD8, and the NEDD8-ligating system consisting of APP-BP1/hUba3, and hUbc12, which function as E1- and E2-like enzymes, respectively. The expressions of Cul-1, Cul-2, and Cul-3 resembled each other and were apparently correlated to those of NEDD8 and the NEDD8-ligating system in various human cells and tissues. However, the mRNA levels of Cul-4A, Cul-4B, and Cul-5 differed considerably from each other as well as from other Cul-family proteins. The enhanced expression of all Cul-family proteins except Cul-5 was observed in a variety of tumor cell lines.


Extent of surgical resection is independently associated with survival in patients with hemispheric infiltrating low-grade gliomas.
It remains unknown whether the extent of surgical resection affects survival or disease progression in patients with supratentorial low-grade gliomas. We conducted a retrospective cohort study (n = 170) between 1996 and 2007 at a single institution to determine whether increasing extent of surgical resection was associated with improved progression-free survival (PFS) and overall survival (OS). Surgical resection of gliomas defined as gross total resection (GTR) (complete resection of the preoperative fluid-attenuated inversion recovery signal abnormality), near total resection (NTR) (<3-mm thin residual fluid-attenuated inversion recovery signal abnormality around the rim of the resection cavity only), or subtotal resection (STR) (residual nodular fluid-attenuated inversion recovery signal abnormality) based on magnetic resonance imaging performed less than 48 hours after surgery. Our main outcome measures were OS, PFS, and malignant degeneration-free survival (conversion to high-grade glioma). One hundred thirty-two primary and 38 revision resections were performed for low-grade astrocytomas (n = 93) or oligodendrogliomas (n = 77). GTR, NTR, and STR were achieved in 65 (38%), 39 (23%), and 66 (39%) cases, respectively. GTR versus STR was independently associated with increased OS (hazard ratio, 0.36; 95% confidence interval, 0.16-0.84; P = 0.017) and PFS (HR, 0.56; 95% confidence interval, 0.32-0.98; P = 0.043) and a trend of increased malignant degeneration-free survival (hazard ratio, 0.46; 95% confidence interval, 0.20-1.03; P = 0.060). NTR versus STR was not independently associated with improved OS, PFS, or malignant degeneration-free survival. Five-year OS after GTR, NTR, and STR was 95, 80, 70%, respectively, and 10-year OS was 76, 57, and 49%, respectively. After GTR, NTR, and STR, median time to tumor progression was 7.0, 4.0, and 3.5 years, respectively. Median time to malignant degeneration after GTR, NTR, and STR was 12.5, 5.8, and 7 years, respectively. GTR was associated with a delay in tumor progression and malignant degeneration as well as improved OS independent of age, degree of disability, histological subtype, or revision versus primary resection. GTR should be safely attempted when not limited by eloquent cortex.


Mental-physical co-morbidity and its relationship with disability: results from the World Mental Health Surveys.
The relationship between mental and physical disorders is well established, but there is less consensus as to the nature of their joint association with disability, in part because additive and interactive models of co-morbidity have not always been clearly differentiated in prior research. Eighteen general population surveys were carried out among adults as part of the World Mental Health (WMH) Survey Initiative (n=42 697). DSM-IV disorders were assessed using face-to-face interviews with the Composite International Diagnostic Interview (CIDI 3.0). Chronic physical conditions (arthritis, heart disease, respiratory disease, chronic back/neck pain, chronic headache, and diabetes) were ascertained using a standard checklist. Severe disability was defined as on or above the 90th percentile of the WMH version of the World Health Organization Disability Assessment Schedule (WHODAS-II). The odds of severe disability among those with both mental disorder and each of the physical conditions (with the exception of heart disease) were significantly greater than the sum of the odds of the single conditions. The evidence for synergy was model dependent: it was observed in the additive interaction models but not in models assessing multiplicative interactions. Mental disorders were more likely to be associated with severe disability than were the chronic physical conditions. This first cross-national study of the joint effect of mental and physical conditions on the probability of severe disability finds that co-morbidity exerts modest synergistic effects. Clinicians need to accord both mental and physical conditions equal priority, in order for co-morbidity to be adequately managed and disability reduced.


Combined 633-nm and 830-nm led treatment of photoaging skin.
To evaluate the clinical efficacy and ultrastructural changes in photodamaged skin after combined 633-nm and 830-nm light-emitting diode (LED) treatments. Thirty-six subjects received 9 LED treatments over the course of 5 weeks and were subsequently evaluated for final clinical improvement 12 weeks after treatment. Five subjects were also biopsied to determine the ultrastuctural posttreatment changes in collagen fibers. A statistically significant improvement in wrinkles was seen after profilometric analysis. The majority of subjects reported improvements in softness, smoothness, and firmness at all time points. Electron microscopic analysis showed evidence of post-LED treatment of thicker collagen fibers. 633-nm and 830-nm LED treatments play a role in the treatment of photodamaged skin. LED treatments can be used as either a primary or adjunctive treatment modality.


Evaluation of a preconditioned conjugate-gradient algorithm for weighted least-squares unwrapping of digital speckle-pattern interferometry phase maps.
Inasmuch as current fringe analysis techniques used in digital speckle-pattern interferometry (DSPI) yield a phase map modulo 2pi, phase unwrapping is the final step of any data evaluation process. The performance of a recently published algorithm used to unwrap DSPI phase maps is investigated. The algorithm is based on a least-squares minimization technique that is solvable by the discrete cosine transform. When phase inconsistencies are present, they are handled by exclusion of invalid pixels from the unwrapping process through the assignment of zero-valued weights. Then the weighted unwrapping problem is solved in an iterative manner by a preconditioned conjugate-gradient method. The evaluation is carried out with computer-simulated DSPI phase maps, an approach that permits the generation of phase fields without inconsistencies, which are then used to calculate phase deviations as a function of the iteration number. Real data are also used to illustrate the performance of the algorithm.


Identifying priority policy issues and health system research questions associated with recovery outcomes for burns survivors in India: a qualitative inquiry.
This study aimed to identify priority policy issues and health system research questions associated with recovery outcomes for burns survivors in India. Qualitative inquiry; data were collected through semistructured in-depth interviews and focus group discussions. Nine sites in urban and rural settings across India, through primary, secondary and tertiary health facilities. Healthcare providers, key informants, burns survivors and/or their carers. Participants acknowledged the challenges of burns care and recovery, and identified the need for prolonged rehabilitation. Challenges identified included poor communication between healthcare providers and survivors, limited rehabilitation services, difficulties with transportation to health facility and high cost associated with burns care. Burns survivors and healthcare providers identified the stigma attached with burns as the biggest challenge within the healthcare system, as well as in the community. Systems barriers (eg, limited infrastructure and human resources), lack of economic and social support, and poor understanding of recovery and rehabilitation were identified as major barriers to recovery. Though further research is needed for addressing gaps in data, strengthening of health systems can enable providers to address issues such as developing/providing, protocols, capacity building, effective coordination between key organisations and referral networks.


A long-term clinical study on individuals with amelogenesis imperfecta.
The aims of this study are to present sociodemographic and familial characteristics, clinical and systemic findings, dental treatment needs, and concomitant dental anomalies in patients with amelogenesis imperfecta (AI) and to evaluate time-varying conditions in these long-term follow-up patients. Records of patients with AI who were examined in the Department of Pediatric Dentistry between 1999 and 2017 were reviewed. Information about sociodemographic characteristics, history of AI and consanguinity in family, systemic conditions, reasons for referral to the clinic, oral hygiene habits and gingival health, occlusion findings, and performed treatments were gathered. Dental anomalies in radiographs were also evaluated. Baseline and final situations of the patients were assessed. Statistical analyses were performed. Of 75 patients aged 3-15 years with follow-ups up to 12 years, 34 had AI in their families and 15 were born from consanguineous marriages. Nephrocalcinosis has been observed in 5 patients. Main reasons for referral to the clinic were related to esthetic and hypersensitivity concerns. Twenty-two patients had gingivitis, and during follow-up process, gingival problems could not be completely prevented due to poor oral hygiene habits. Vertical dimension loss, open-bite, and cross-bite were seen in 16, 15, and 10 patients, respectively. Of the patients, 63% experienced restorative, 33% stainless steel crown, 17% endodontic, 8% prosthetic treatments, and 24% had retreatment needs. Concomitant dental anomalies were dens invaginatus, taurodontism, ectopic eruption, delayed eruption, hypodontia, and pulpal calcification. Early diagnosis and interventions considering the time-varying conditions with long-term follow-ups provide significant improvements in clinical maintenance of patients with AI.


Population policy options in the developing world.
The population of the developing world is currently expanding at the unprecedented rate of more than 800 million per decade, and despite anticipated reductions in growth during the 21st century, its size is expected to increase from 4.3 billion today to 10.2 billion in 2100. Past efforts to curb this growth have almost exclusively focused on the implementation of family planning programs to provide contraceptive information, services, and supplies. These programs have been partially successful in reducing birth rates. Further investments in them will have an additional but limited impact on population growth; therefore, other policy options, in particular measures to reduce high demand for births and limit population momentum, are needed.


Visual paired associate learning deficits associated with elevated beta-amyloid in cognitively normal older adults.
Previous studies have shown that paired associate learning (PAL), a type of episodic memory, is impaired in early Alzheimer's disease (AD). Such tasks require that a set of associations (e.g., pattern-location) be learned over several trials, and the objective is to reduce errors with each trial. Currently, the nature and magnitude of impairment and decline on PAL measures in cognitively normal (CN) older adults with elevated levels of beta-amyloid (Aβ+) is unknown. This study examined PAL errors in Aβ+ and Aβ - CN older adults, both within a single assessment and over time. Participants (210 Aβ - CN, 146 Aβ + CN) from the Australian Imaging, Biomarkers, and Lifestyle (AIBL) study underwent three assessments over 36-months (baseline, and 18- and 36-month follow-ups) using a computerized paired associate learning task (CPAL). Aβ status was determined by positron emission tomography (PET) neuroimaging. No significant group differences in PAL were evident at baseline. Significant groupxtime interactions were observed, with the Aβ - CN group, but not the Aβ + CN group, evidencing improvement over time (Cohen's d = 0.30 [0.08, 0.51]). Despite this, no group differences were evident at 36-months. Results suggest that PAL dysfunction is evident over time in Aβ + CNs. This indicates a lack of benefit from repeated exposure to the task over time associated with Aβ+, which is not the case for Aβ - CNs. Further, results suggest that assessing change in Aβ+ related cognition over time, rather than at a single assessment, provides greater understanding of dysfunction in early AD. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Fluid Balance and Hydration Considerations for Women: Review and Future Directions.
Although it is well understood that dehydration can have a major impact on exercise performance and thermoregulatory physiology, the potential for interactions between female sex hormone influences and the impact of dehydration on these variables is poorly understood. Female reproductive hormonal profiles over the course of the menstrual cycle have significant influences on thermoregulatory and volume regulatory physiology. Increased insight into the interactions among dehydration and menstrual cycle hormonal influences may have important implications for safety, nutritional recommendations, as well as optimal mental and physical performance. The purpose of this review is to summarize what is known in this area and highlight the areas that will be important for future work.


When the noise goes on: received sound energy predicts sperm whale responses to both intermittent and continuous navy sonar.
Anthropogenic noise sources range from intermittent to continuous, with seismic and navy sonar technology moving towards near-continuous transmissions. Continuous active sonar (CAS) may be used at a lower amplitude than traditional pulsed active sonar (PAS), but potentially with greater cumulative sound energy. We conducted at-sea experiments to contrast the effects of navy PAS versus CAS on sperm whale behaviour using animal-attached sound- and movement-recording tags (n=16 individuals) in Norway. Changes in foraging effort and proxies for foraging success and cost during sonar and control exposures were assessed while accounting for baseline variation [individual effects, time of day, bathymetry and blackfish (pilot/killer whale) presence] in generalized additive mixed models (GAMMs). We found no reduction in time spent foraging during exposures to medium-level PAS (MPAS) transmitted at the same peak amplitude as CAS. In contrast, we found similar reductions in foraging during CAS (d.f.=1, F=8.0, P=0.005) and higher amplitude PAS (d.f.=1, F=20.8, P<0.001) when received at similar energy levels integrated over signal duration. These results provide clear support for sound energy over amplitude as the response driver. We discuss the importance of exposure context and the need to measure cumulative sound energy to account for intermittent versus more continuous sources in noise impact assessments.


Promoting Healthy Sexuality for Children and Adolescents With Disabilities.
This clinical report updates a 2006 report from the American Academy of Pediatrics titled "Sexuality of Children and Adolescents With Developmental Disabilities." The development of a healthy sexuality best occurs through appropriate education, absence of coercion and violence, and developmental acquisition of skills to navigate feelings, desires, relationships, and social pressures. Pediatric health care providers are important resources for anticipatory guidance and education for all children and youth as they understand their changing bodies, feelings, and behaviors. Yet, youth with disabilities and their families report inadequate education and guidance from pediatricians regarding sexual health development. In the decade since the original clinical report was published, there have been many advancements in the understanding and care of children and youth with disabilities, in part because of an increased prevalence and breadth of autism spectrum disorder as well as an increased longevity of individuals with medically complex and severely disabling conditions. During this same time frame, sexual education in US public schools has diminished, and there is emerging evidence that the attitudes and beliefs of all youth (with and without disability) about sex and sexuality are being formed through media rather than formal education or parent and/or health care provider sources. This report aims to provide the pediatric health care provider with resources and tools for clinical practice to address the sexual development of children and youth with disabilities. The report emphasizes strategies to promote competence in achieving a healthy sexuality regardless of physical, cognitive, or socioemotional limitations.


Lead poisoning in China: a health and human rights crisis.
Acute and chronic lead poisoning is occurring throughout China and is a major cause of childhood morbidity. The Chinese government's emphasis on industrial development and poverty reduction has, over the past three decades, decreased by 500 million the number of people surviving on less than one dollar per day, but has caused significant environmental degradation that threatens public health. Drawing upon in-depth interviews conducted in 2009 and 2010 with families affected by lead poisoning, environmental activists, journalists, government and civil society organization officials in Shaanxi, Henan, Hunan, and Yunnan provinces, as well as a review of scientific and Chinese media, and health and environmental legal and policy analysis, we examine the intersection of civil, political, economic, and social rights related to access to information, screening, treatment, and remediation related to lead poisoning. In-depth interviews in each province uncovered: censorship and intimidation of journalists, environmental activists, and parents seeking information about sources and prevention of lead poisoning; denial of screening for lead poisoning, often based upon arbitrary eligibility criteria; and inadequate and inappropriate treatment being promoted and provided by health facilities. Over the past decade, the Chinese government has prioritized health care and invested billions of dollars towards universal health coverage, and strengthened environmental to address industrial pollution and guarantee access to information on the environment. Yet, despite these reforms, information remains constrained and citizens seeking information and redress are sometimes arrested, in violation of Chinese and international law. Local government officials and national environmental policies continue to prioritize economic development over environmental protection. To effectively address lead poisoning requires an emphasis on prevention, and to combat industrial pollution requires stronger enforcement of existing laws and regulations, as well as accountability of local authorities charged with upholding environmental regulations. In this context, restrictions on such rights as freedom of expression, assembly, and political participation have direct consequences on the realization of the right to health.


The relation between mental health problems and future violence among detained male juveniles.
Detention personnel may assume that mental health problems heighten the likelihood of future violence in detained youth. This study explored whether brief mental health screening tools are of value for alerting staff to a detained youth's potential for future violent offending. Boys (n = 1259; Mean age = 16.65) completed the Massachusetts Youth Screening Instrument-Second Version (MAYSI-2) and the Strengths and Difficulties Questionnaire (SDQ) as part of a clinical protocol. Official records were collected to index past and future violent offending. A few significant positive and negative relationships between MAYSI-2 and SDQ scale scores and future violent offending were revealed, after controlling for age, past violent offending, and follow-up time. These relations were almost entirely dissimilar across the ethnic groups, even to the extent of finding opposite relations for boys in different ethnic groups. The small number of relations and their small effect sizes suggest little likelihood that screening for mental health problems in boys who are detained in the Netherlands offers any potential for identifying youth at risk for committing future violent crimes. The current findings also suggest that ethnic differences in the relation between mental health problems and future criminality must be considered in future studies.


BioLitMine: Advanced Mining of Biomedical and Biological Literature About Human Genes and Genes from Major Model Organisms.
The accumulation of biological and biomedical literature outpaces the ability of most researchers and clinicians to stay abreast of their own immediate fields, let alone a broader range of topics. Although available search tools support identification of relevant literature, finding relevant and key publications is not always straightforward. For example, important publications might be missed in searches with an official gene name due to gene synonyms. Moreover, ambiguity of gene names can result in retrieval of a large number of irrelevant publications. To address these issues and help researchers and physicians quickly identify relevant publications, we developed BioLitMine, an advanced literature mining tool that takes advantage of the medical subject heading (MeSH) index and gene-to-publication annotations already available for PubMed literature. Using BioLitMine, a user can identify what MeSH terms are represented in the set of publications associated with a given gene of the interest, or start with a term and identify relevant publications. Users can also use the tool to find co-cited genes and a build a literature co-citation network. In addition, BioLitMine can help users build a gene list relevant to a MeSH term, such as a list of genes relevant to "stem cells" or "breast neoplasms." Users can also start with a gene or pathway of interest and identify authors associated with that gene or pathway, a feature that makes it easier to identify experts who might serve as collaborators or reviewers. Altogether, BioLitMine extends the value of PubMed-indexed literature and its existing expert curation by providing a robust and gene-centric approach to retrieval of relevant information.


Comparison of the effect of propofol and sevoflurane anaesthesia on acute and chronic postoperative pain after hysterectomy.
There is some evidence that propofol may reduce acute postoperative pain; however, the results are inconsistent. Furthermore, there is a paucity of information about the type of anaesthesia and chronic pain. This study was designed to evaluate the hypothesis that propofol reduces acute and chronic postoperative pain compared with sevoflurane. In a randomised, prospective, double-blind trial, we assigned 80 patients having open total abdominal hysterectomy surgery to anaesthesia with either sevoflurane or propofol. Anaesthesia was titrated to clinical needs and bispectral index values to between 40 and 60. Postoperative pain was managed with pethidine and diclofenac. Acute postoperative pain for 24 hours and chronic postoperative pain at one and three months after surgery were evaluated. The Hospital Anxiety and Depression Scale was used to evaluate patient anxiety and depression after one and three months. There were no significant differences between the groups for opioid consumption or opioid-induced side-effects. Pain scores in the first four hours were significantly higher in the sevoflurane group. Persistent surgical pain was observed less frequently (7 out of 40 patients in the propofol group and 21 out of 40 in the sevoflurane group at three months post-surgery, P <0.01) and pain scores were lower at one and three months in the propofol group (0.78±0.55 versus 2.23±0.73 for the sevoflurane group at three months post-surgery, P <0.01). Anxiety and depression scores were significantly lower in the propofol group at three months. In this study, general anaesthesia with propofol was associated with reduced early acute postoperative and persistent pain, compared to sevoflurane-based anaesthesia, among patients undergoing open abdominal hysterectomy.


Residential proximity to major roads and adverse birth outcomes: a hospital-based study.
Exposure to air pollution has been demonstrated to increase the risk of preterm birth and low birth weight (LBW). Although evidence has accumulated on characteristics associated with increased risk of air pollution-related health effects, most studies have been conducted in the adult population and evidence on reproductive outcomes is limited. We examined whether socio-economic position (SEP) and parental characteristics (parental behavior and co-morbidity) modified the relationship between air pollution and adverse birth outcomes. Data were extracted from a perinatal hospital database based in Shizuoka, Japan. We restricted the analysis to mothers who delivered live-born single births from January 1997 to December 2010 (n = 16,615). Each birth was assigned proximity to major roads. Multivariate adjusted odds ratios (ORs) and their 95% confidence intervals (CIs) were estimated for the outcomes of preterm birth and term LBW. We stratified subjects by individual/area-level SEP and parental characteristics. We then measured interactions on the additive scale between the respective factors and exposure. Lower SEP at both individual and area levels was associated with the increased occurrence of adverse birth outcomes. Living within 200 m from a major road increased the risk of preterm birth by 1.5 times (95% CI: 1.3-1.9) and LBW by 1.2 times (95% CI: 0.9-1.6). Mothers with lower individual SEP defined by household occupation experienced higher ORs for term LBW (OR = 3.1, 95% CI: 1.2-8.2) compared with those with higher individual SEP. In contrast, mothers who lived in the highest area-level SEP region (i.e., affluent areas) showed slightly higher point estimates compared with those who lived in middle or poor areas. In addition, maternal diabetic and hypertensive status modified the association between proximity and preterm birth, while maternal smoking status modified the association between proximity and term LBW. The present study demonstrated that air pollution is an independent risk factor for adverse birth outcomes. Mothers with lower individual SEP and mothers living in higher SEP region may be susceptible to the adverse effect of air pollution. Maternal diabetic, hypertensive, and smoking status may also increase susceptibility to this air pollution-related health effect.


Positive and Negative Signals in Mast Cell Activation.
Mast cells are powerful immune modulators of the tissue microenvironment. Within seconds of activation, these cells release a variety of preformed biologically active products, followed by a wave of mediator synthesis and secretion. Increasing evidence suggests that an intricate network of inhibitory and activating receptors, specific signaling pathways, and adaptor proteins governs mast cell responsiveness to stimuli. Here, we discuss the biological and clinical relevance of negative and positive signaling modalities that control mast cell activation, with an emphasis on novel FcεRI regulators, immunoglobulin E (IgE)-independent pathways [e.g., Mas-related G protein-coupled receptor X2 (MRGPRX2)], tetraspanins, and the CD300 family of inhibitory and activating receptors.


A pilot study of interferon alfa and ribavirin combination in liver transplant recipients with recurrent hepatitis C.
Although interferon alfa (IFN-alpha) and ribavirin are widely used in the treatment of hepatitis C, their role in the transplant recipient is unclear. We conducted a pilot study to determine the efficacy and safety of this therapy in transplant recipients with recurrent hepatitis C. Patients at least 6 months posttransplantation were treated with IFN-alpha 3 million units 3 times a week subcutaneously and ribavirin 800 mg daily by mouth for 48 weeks followed by ribavirin monotherapy for 24 weeks. The primary end point was sustained virologic response, and secondary end points included biochemical, virologic, and histologic responses at the end of combination treatment. Thirty-eight patients initiated therapy but 16 withdrew due to adverse effects, including 2 with myocardial infarction. Median age was 50 years; 74% were men, and 91% had genotype 1. The median interval between transplantation and enrollment was 23 months. On an intention-to-treat basis, 7 patients (18%) had a biochemical and 5 (13%) had a virologic response at the end of combination treatment. Inflammatory activity did not change, but fibrosis worsened in virologic nonresponders. Ribavirin maintenance caused a further decrease in serum alanine aminotransferase levels, but hepatitis C virus (HCV) RNA levels increased. Only 2 of the 38 patients (5%) had a sustained virologic response. Several patients required treatment with erythropoietin for anemia. In conclusion, IFN-alpha and ribavirin are effective in a small proportion of liver allograft recipients with recurrent hepatitis C. Adverse effects occur commonly, requiring dose reductions and treatment withdrawal.


CoPub update: CoPub 5.0 a text mining system to answer biological questions.
In this article, we present CoPub 5.0, a publicly available text mining system, which uses Medline abstracts to calculate robust statistics for keyword co-occurrences. CoPub was initially developed for the analysis of microarray data, but we broadened the scope by implementing new technology and new thesauri. In CoPub 5.0, we integrated existing CoPub technology with new features, and provided a new advanced interface, which can be used to answer a variety of biological questions. CoPub 5.0 allows searching for keywords of interest and its relations to curated thesauri and provides highlighting and sorting mechanisms, using its statistics, to retrieve the most important abstracts in which the terms co-occur. It also provides a way to search for indirect relations between genes, drugs, pathways and diseases, following an ABC principle, in which A and C have no direct connection but are connected via shared B intermediates. With CoPub 5.0, it is possible to create, annotate and analyze networks using the layout and highlight options of Cytoscape web, allowing for literature based systems biology. Finally, operations of the CoPub 5.0 Web service enable to implement the CoPub technology in bioinformatics workflows. CoPub 5.0 can be accessed through the CoPub portal http://www.copub.org.


Pectin recovery and characterization from lemon juice waste streams.
Pectin characteristics from different parts of lemon fruit (Citrus limon L.) were studied as a basis for assessing their suitability for functional applications. Pectin was extracted from lemon albedo, lemon core parts and membranes, and lemon extract using an aqueous extraction protocol. The composition and structural properties of the isolated pectins were examined by means of complementary analytical methods to assess their molecular characteristics for potential industrial applications. The isolation protocol yielded pectins that were predominantly composed of galacturonic acid, with differences in the degree of methylation and neutral sugars content, and with low protein content, indicating high-purity materials. The same extraction protocol resulted in differences in yield and purity between the three different parts of lemon fruit, and in structural variations in the pectin backbone, as evidenced by differences in sugar composition and molecular weight. Solutions of the isolated lemon pectins exhibited pseudoplastic behavior. Macromolecular characterization showed that the lemon extract pectin had the highest molecular weight and hydrodynamic volume, followed by lemon core and lemon albedo pectin. The work demonstrates that pectins with distinct structural properties may be extracted from different parts of lemon wastes and used for different technological purposes. © 2019 Society of Chemical Industry.


Chronic lung diseases are associated with gene expression programs favoring SARS-CoV-2 entry and severity.
Patients with chronic lung disease (CLD) have an increased risk for severe coronavirus disease-19 (COVID-19) and poor outcomes. Here, we analyze the transcriptomes of 611,398 single cells isolated from healthy and CLD lungs to identify molecular characteristics of lung cells that may account for worse COVID-19 outcomes in patients with chronic lung diseases. We observe a similar cellular distribution and relative expression of SARS-CoV-2 entry factors in control and CLD lungs. CLD AT2 cells express higher levels of genes linked directly to the efficiency of viral replication and the innate immune response. Additionally, we identify basal differences in inflammatory gene expression programs that highlight how CLD alters the inflammatory microenvironment encountered upon viral exposure to the peripheral lung. Our study indicates that CLD is accompanied by changes in cell-type-specific gene expression programs that prime the lung epithelium for and influence the innate and adaptive immune responses to SARS-CoV-2 infection.


A Guideline for Contextual Adaptation of Community-Based Health Interventions.
In Southeast Asia, community-based health interventions (CBHIs) are often used to target non-communicable diseases (NCDs). CBHIs that are tailored to sociocultural aspects of health and well-being: local language, religion, customs, traditions, individual preferences, needs, values, and interests, may promote health more effectively than when no attention is paid to these aspects. In this study, we aimed to develop a guideline for the contextual adaption of CBHIs. We developed the guideline in two stages: first, a checklist for contextual and cultural adaptation; and second, a guideline for adaptation. We performed participatory action research, and used the 'Appraisal of Guidelines for Research & Evaluation (AGREE) II' tool as methodological basis to develop the guideline. We conducted a narrative literature review, using a conceptual framework based on the six dimensions of 'Positive Health' and its determining contexts to theoretically underpin a checklist. we pilot tested a draft version of the guideline and included a total of 29 stakeholders in five informal meetings, two stakeholder meetings, and an expert review meeting. This yielded a guideline, addressing three phases: the preparation phase, the assessment phase, and the adoption phase, with integrated checklists comprising 34 cultural and contextual aspects for the adaption of CBHIs based on general health directives or health models. The guideline provides insight into how CBHIs can be tailored to the health perspectives of community members, and into the context in which the intervention is implemented. This tool can help to effect behavioral change, and improve the prevention and management of NCDs.


In vivo 13C NMR spectroscopy and metabolic modeling in the brain: a practical perspective.
In vivo 13C NMR spectroscopy has the unique capability to measure metabolic fluxes noninvasively in the brain. Quantitative measurements of metabolic fluxes require analysis of the 13C labeling time courses obtained experimentally with a metabolic model. The present work reviews the ingredients necessary for a dynamic metabolic modeling study, with particular emphasis on practical issues.


Genome sequencing of oomycete isolates from Chile supports the New Zealand origin of Phytophthora kernoviae and makes available the first Nothophytophthora sp. genome.
Genome sequences were generated for six oomycete isolates collected from forests in Valdivia, Chile. Three of the isolates were identified morphologically as Phytophthora kernoviae, whereas two were similar to other clade 10 Phytophthora species. One isolate was tentatively identified as Nothophytophthora valdiviana based on nucleotide sequence similarity in the cytochrome oxidase 1 gene. This is the first genome sequence for this recently described genus. The genome assembly was more fragmented and contained many duplicated genes when compared with the other Phytophthora sequences. Comparative analyses were performed with genomic sequences of the P. kernoviae isolates from the UK and New Zealand. Although the potential New Zealand origin of P. kernoviae has been suggested, new isolations from Chile had cast doubt on this hypothesis. We present evidence supporting P. kernoviae as having originated in New Zealand. However, investigation of the diversity of oomycete species in Chile has been limited and warrants further exploration. We demonstrate the expediency of genomic analyses in determining phylogenetic relationships between isolates within new and often scantly represented taxonomic groups, such as Phytophthora clade 10 and Nothophytophthora. Data are available on GenBank via BioProject accession number PRJNA352331.


Clinical arterial infusion of calcium gluconate: the preferred method for treating hydrofluoric acid burns of distal human limbs.
This study was designed to evaluate the efficiency and safety of arterial infusions of calcium gluconate to treat hydrofluoric (HF) acid burns of the distal human limbs. Eligible patients with HF burn limbs, collected from January 2008 to October 2011, were given the arterial infusion of calcium gluconate into the injured limbs. The measures of pain were conducted before the infusion, immediately after the infusion, 4 h after the infusion, and 2 days after the infusion by the visual analogy score (VAS). If the VAS score was higher than 4.0 at the time point 4 h after the first infusion, the infusion was repeated. The time of wound healing, and the number and ratio of the cases receiving the surgical operation were also evaluated. A total of 118 patients, male (107 cases) and female (11 cases), were collected, including 64 cases of outpatients and 54 cases of inpatients. The age of the subjects ranged from 16 to 60 years, with the mean age of 37.6. The burn sites were located in the lateral limbs (28 cases) and in the unilateral limbs (90 cases). For 107 cases, the pain scores decreased quickly after the first infusion. The other 11 cases, with the VAS score higher than 4.0 at the time point 4 h after the first infusion, received the second infusion. The average time of wound healing and the ratio of the cases receiving the surgical operation were closely related to the interval from the injury to the reception of infusion. Arterial infusion of calcium gluconate, effectively relieving the pain, blocking wound progressive deepening, and causing no adverse effects, could be the preferential method to treat hydrofluoric acid burns of the distal human limbs.


Antioxidative probiotic fermented goats' milk decreases oxidative stress-mediated atherogenicity in human subjects.
The increasing interest in a healthy diet is stimulating innovative development of novel scientific products in the food industry. The viable lactic acid bacteria in fermented milk products, such as yoghurt, have been associated with increased lactose tolerance, a well-balanced intestinal microflora, antimicrobial activity, stimulation of the immune system and antitumoural, anticholesterolaemic and antioxidative properties in human subjects. Recently, we have studied a human Lactobacillus spp. strain that possesses antioxidative activity. The aim of the present pilot study was to develop goats' milk fermented with the human antioxidative lactobacilli strain, Lactobacillus fermentum ME-3, and to test the effect of the fermented probiotic goats' milk on oxidative stress markers (including markers for atherosclerosis) in human blood and urine and on the gut microflora. Twenty-one healthy subjects were assigned to two treatment groups: goats' milk group and fermented goats' milk group (150 g/d) for a period of 21 d. Consumption of fermented goats' milk improved anti-atherogenicity in healthy subjects: it prolonged resistance of the lipoprotein fraction to oxidation, lowered levels of peroxidized lipoproteins, oxidized LDL, 8-isoprostanes and glutathione redox ratio, and enhanced total antioxidative activity. The consumption of fermented goats' milk also altered both the prevalence and proportion of lactic acid bacteria species in the gut microflora of the subjects. We conclude that the goats' milk fermented with our special antioxidative lactobacilli strain Lactobacillus fermentum ME-3 exhibits anti-atherogenic effects.


A care bundle including antenatal corticosteroids reduces preterm infant mortality in Tanzania a low resource country.
Preterm neonatal mortality (NM) has remained high and unchanged for many years in Tanzania, a resource-limited country. Major causes of mortality include birth asphyxia, respiratory insufficiency and infections. Antenatal corticosteroids (ACS) have been shown to significantly reduce mortality in developed countries. There is inconsistent use of ACS in Tanzania. To determine whether implementation of a care bundle that includes ACS, maternal antibiotics (MA), neonatal antibiotics (NA) and avoidance of moderate hypothermia (temperature < 36°C) targeting infants of estimated gestational age (EGA) 28 to 34 6/7 weeks would reduce NM (< 7 days) by 35%. A Pre (September 2014 to May 2015) and Post (June 2015 to June 2017) Implementation strategy was used and introduced at three University-affiliated and one District Hospital. Dexamethasone, as the ACS, was added to the national formulary in May 2015, facilitating its free use down to the district level. NM was reduced 26% from 166 to 122/1000 livebirths (P = 0.005) and fresh stillbirths (FSB) 33% from 162/1000 to 111/1000 (p = 0.0002) Pre versus Post Implementation. Medications including combinations increased significantly at all sites (p<0.0001). By logistic regression, combinations of ACS, maternal and NA (odds ratio (OR) 0.33), ACS and NA (OR 0.30) versus no treatment were significantly associated with reduced NM. NM significantly decreased per 250g birthweight increase (OR 0.59), and per one week increase in EGA (OR 0.87). Moderate hypothermia declined pre versus post implementation (p<0.0001) and was two-fold more common in infants who died versus survivors. A low-cost care bundle, ~$6 per patient, was associated with a significant reduction in NM and FSB rates. The former presumably by reducing respiratory morbidity with ACS and minimizing infections with antibiotics. If these findings can be replicated in other resource-limited settings, the potential for further reduction of <5 year mortality rates becomes enormous.


Linking NAADP to ion channel activity: a unifying hypothesis.
Nicotinic acid adenine dinucleotide phosphate (NAADP) is a potent Ca(2+)-releasing second messenger that might regulate different ion channels, including the ryanodine receptor, two-pore channels, and TRP-ML1 (transient receptor potential channel, subtype mucolipin 1), a Ca(2+) channel localized to lysosomes. New evidence suggests that a 22- and 23-kilodalton pair of proteins could be the receptor for NAADP. Labeling of NAADP binding proteins was independent of overexpression or knockout of two-pore channels, indicating that two-pore channels, although regulated by NAADP, are not the NAADP receptors. I propose that NAADP binding proteins could bind to different ion channels and thus may explain how NAADP regulates diverse ion channels.


The accuracy of fine-needle aspiration biopsy and frozen section in patients with thyroid cancer.
A total of 1076 patients with thyroid nodules were reviewed. The accuracy of fine needle aspiration biopsy (FNAB) and frozen section (FS) were compared and clinical risk factors were analyzed. Our results indicate that 67.9% are benign and 32.1% are malignant with the predominance of papillary thyroid cancer (75.1%). Overall diagnostic accuracy for FNAB and FS were 90.8%-91.2% and 89.1%-90.5%, respectively. There were no significant differences between the diagnostic accuracy on FNAB and FS in all tumors except the follicular adenoma and carcinoma. The diagnostic accuracy of FS was higher than FNAB in patients with follicular adenoma (89.3% vs. 58.9%, p < 0.001) and but lower than FNAB in patients with follicular carcinoma (46.2% vs. 92.3%, p < 0.001). In conclusion, FNAB is cost effective in the preoperative evaluation of thyroid nodule. FS could be eliminated in most cases except with follicular and Hürthle cell neoplasms. FS is valuable when result of FNAB is suspicious or unavailable. FS is more appropriate in deciding the extent of thyroidectomy in follicular neoplasm and FNAB is more reliable initial approach to surgery in patients with Hürthle cell neoplasm. Clinical risk factors may help in selecting patients for surgery but cannot exceed FS in deciding the extent of thyroidectomy in patients with follicular and Hürthle cell neoplasms.


Measuring Dipole Inversion in Self-Assembled Nano-Dielectric Molecular Layers.
A self-assembled nanodielectric (SAND) is an ultrathin film, typically with periodic layer pairs of high-k oxide and phosphonic-acid-based π-electron (PAE) molecular layers. IPAE, having a molecular structure similar to that of PAE but with an inverted dipole direction, has recently been developed for use in thin-film transistors. Here we report that replacing PAE with IPAE in SAND-based thin-film transistors induces sizable threshold and turn-on voltage shifts, indicating the flipping of the built-in SAND polarity. The bromide counteranion (Br-) associated with the cationic stilbazolium portion of PAE or IPAE is of great importance, because its relative position strongly affects the electric dipole moment of the organic layer. Hence, a set of X-ray synchrotron measurements were designed and performed to directly measure and compare the Br- distributions within the PAE and IPAE SANDs. Two trilayer SANDs, consisting of a PAE or IPAE layer sandwiched between an HfOx and a ZrOx layer, were deposited on the SiOx surface of Si substrates or periodic Si/Mo multilayer substrates for X-ray reflectivity and X-ray standing wave measurements, respectively. Along with complementary DFT simulations, the spacings, elemental (Hf, Br, and Zr) distributions, molecular orientations, and Mulliken charge distributions of the PAE and IPAE molecules within each of the SAND trilayers were determined and correlated with the dipole inversion.


FusX: A Rapid One-Step Transcription Activator-Like Effector Assembly System for Genome Science.
Transcription activator-like effectors (TALEs) are extremely effective, single-molecule DNA-targeting molecular cursors used for locus-specific genome science applications, including high-precision molecular medicine and other genome engineering applications. TALEs are used in genome engineering for locus-specific DNA editing and imaging, as artificial transcriptional activators and repressors, and for targeted epigenetic modification. TALEs as nucleases (TALENs) are effective editing tools and offer high binding specificity and fewer sequence constraints toward the targeted genome than other custom nuclease systems. One bottleneck of broader TALE use is reagent accessibility. For example, one commonly deployed method uses a multitube, 5-day assembly protocol. Here we describe FusX, a streamlined Golden Gate TALE assembly system that (1) is backward compatible with popular TALE backbones, (2) is functionalized as a single-tube 3-day TALE assembly process, (3) requires only commonly used basic molecular biology reagents, and (4) is cost-effective. More than 100 TALEN pairs have been successfully assembled using FusX, and 27 pairs were quantitatively tested in zebrafish, with each showing high somatic and germline activity. Furthermore, this assembly system is flexible and is compatible with standard molecular biology laboratory tools, but can be scaled with automated laboratory support. To demonstrate, we use a highly accessible and commercially available liquid-handling robot to rapidly and accurately assemble TALEs using the FusX TALE toolkit. Together, the FusX system accelerates TALE-based genomic science applications from basic science screening work for functional genomics testing and molecular medicine applications.


Windscapes shape seabird instantaneous energy costs but adult behavior buffers impact on offspring.
Windscapes affect energy costs for flying animals, but animals can adjust their behavior to accommodate wind-induced energy costs. Theory predicts that flying animals should decrease air speed to compensate for increased tailwind speed and increase air speed to compensate for increased crosswind speed. In addition, animals are expected to vary their foraging effort in time and space to maximize energy efficiency across variable windscapes. We examined the influence of wind on seabird (thick-billed murre Uria lomvia and black-legged kittiwake Rissa tridactyla) foraging behavior. Airspeed and mechanical flight costs (dynamic body acceleration and wing beat frequency) increased with headwind speed during commuting flights. As predicted, birds adjusted their airspeed to compensate for crosswinds and to reduce the effect of a headwind, but they could not completely compensate for the latter. As we were able to account for the effect of sampling frequency and wind speed, we accurately estimated commuting flight speed with no wind as 16.6 ms(?1) (murres) and 10.6 ms(?1) (kittiwakes). High winds decreased delivery rates of schooling fish (murres), energy (murres) and food (kittiwakes) but did not impact daily energy expenditure or chick growth rates. During high winds, murres switched from feeding their offspring with schooling fish, which required substantial above-water searching, to amphipods, which required less above-water searching. Adults buffered the adverse effect of high winds on chick growth rates by switching to other food sources during windy days or increasing food delivery rates when weather improved.


In vitro uptake and release of natamycin Dex-b-PLA nanoparticles from model contact lens materials.
To evaluate the uptake and release of the antifungal agent natamycin encapsulated within poly(D,L-lactide)-dextran nanoparticles (Dex-b-PLA NPs) from model contact lens (CL) materials. Six model CL materials (gel 1:poly(hydroxyethyl methacrylate, pHEMA); gel 2:85% pHEMA: 15% [Tris(trimethylsiloxy)silyl]-propyl methacrylate (TRIS); gel 3: 75% pHEMA: 25% TRIS; gel 4: 85% N,N dimethylacrylamide (DMAA): 15% TRIS; gel 5:75% DMAA: 25% TRIS; and gel 6: DMAA) were prepared using a photoinitiation procedure. The gels were incubated in: (1) natamycin dissolved in deionized (DI) water and (2) natamycin encapsulated within Dex-b-PLA NPs in dimethylsulfoxide/DI water. Natamycin release from these materials was monitored using UV-visible spectrophotometry at 304 nm over 7 d. Natamycin uptake by all model CL materials increased between 1 and 7 d (p < 0.001). The uptake of natamycin-NPs was higher than the uptake of the drug alone in DI water (p < 0.05). Drug release was higher in materials containing DMAA than pHEMA (p < 0.05). All gels loaded with natamycin-NPs also released more drug compared to gels soaked with natamycin in DI water (p < 0.001). After 1 h, CL materials loaded with natamycin alone released 28-82% of the total drug release. With the exception of gel 6, this burst released was reduced to 21-54% for CL materials loaded with natamycin-NPs. Model CL materials loaded with natamycin-Dex-b-PLA NPs were able to release natamycin for up to 12 h under infinite sink conditions. DMAA-TRIS materials may be more suitable for drug delivery of natamycin due to the higher drug release observed with these materials.


Impact of acute atrial fibrillation termination and prolongation of atrial fibrillation cycle length on the outcome of ablation of persistent atrial fibrillation: A substudy of the STAR AF II trial.
Controversy exists about the impact of acute atrial fibrillation (AF) termination and prolongation of atrial fibrillation cycle length (AFCL) during ablation on long-term procedural outcome. The purpose of this study was to analyze the influence of AF termination and AFCL prolongation on freedom from AF in patients from the STAR AF II (Substrate and Trigger Ablation for Reduction of Atrial Fibrillation Trial-Part II) trial. Acute changes in AFCL and AF termination were collected during the index procedure of the STAR AF II trial and compared to recurrence of AF at 18 months. Recurrence was assessed by ECG, Holter (3, 6, 9, 12, 18 months), and weekly transtelephonic ECG monitoring for 18 months. AF terminated in 8% of the pulmonary vein isolation (PVI) arm, 45% in the PVI+complex electrogram arm, and 22% of the PVI+linear ablation arm (P <.001), but freedom from AF did not differ among the 3 groups (P = .15). Freedom from AF was significantly higher in patients who presented to the laboratory in sinus rhythm (SR) compared to those without AF termination (63% vs 44%, P = .007). Patients with AF termination had an intermediate outcome (53%) that was not significantly different from those in SR (P = .84) or those who did not terminate (P = .08). AF termination was a univariable predictor of success (P = .007), but by multivariable analysis, presence of early SR was the strongest predictor of success (hazard ratio 0.67, P = .004). Prolongation of AFCL was not predictive of 18-month freedom from AF. Acute AF termination and prolongation in AFCL did not consistently predict 18-month freedom from AF. Presence of SR before or early during the ablation was the strongest predictor of better outcome.


Medical orders for life-sustaining treatment: is it time yet?
As the aging population faces complex end-of-life issues, we studied the intervals between long-term care admission and advance directive completion, and between completion and death. We also sought to determine the interdisciplinary team's compliance with documented wishes. A cross-sectional study of 182 long-term care residents in two facilities with and without completed medical orders for life-sustaining treatment (MOLST) in the New York Metropolitan area was conducted. Demographic variables included: gender, age, ethnicity, and diagnosis. Measures included: admission date, MOLST execution date, and date of death. Resident advance directive documentation was compared with clinical intervention at time of death, including intubation and mechanical ventilation. Of the residents studied, 68.7% were female, 91% were Caucasian and 91.8% were ≥ 65 years of age (mean age: 83). The median time from admission to MOLST signing was 48 days. Median time from admission to MOLST signing for Caucasians was 21 days; for non-Caucasians was 229 days. Fifty-two percent of MOLST were signed by children, and 24% by residents. Of those with signed forms, 25% signed on day of admission, 37% signed within 7 days, and 47% signed within 21 days. Only 3% of residents died the day their MOLST was signed, whereas 12% died within a week, and 22% died within 30 days. Finally, among the 68 subjects who signed a MOLST and died, 87% had their wishes met. In this era of growing time constraints and increased regulations, medical directors of long-term care facilities and those team members caring for residents urgently need a clear and simple approach to the goals of care for their residents. The MOLST is an ideal tool in caring for older adults at the end of life, providing concrete guidance, not only with regard to do not resuscitate (DNR) and do not intubate (DNI) orders, but also for practical approaches to daily care for the interdisciplinary team.


Effects of low dose tryptophan depletion on emotional processing in dieters.
Biased processing of ED-relevant stimuli (eg Fairburn, Shafran, & Cooper, 1999) and 5-HT function (Kaye, Fudge, & Paulus, 2009) are implicated in vulnerability to and the maintenance of eating disorders (EDs), but it is not known if these findings are connected: Could manipulating 5-HT function affect the processing of ED-relevant stimuli? To address this question we assessed emotional processing in female dieters (T+n=12, T-n=14) following acute low dose tryptophan depletion. ATD increased interference in the masked condition of the emotional Stroop to all negative emotional stimuli, in the absence of any other differences in emotional processing. These results suggest that ATD affects the processing of some negative (including ED-relevant) stimuli, and that reduced 5-HT function may be involved in some aspects of psychological vulnerability to EDs.


'It's the way that you look at it'--a cognitive neuropsychological account of SSRI action in depression.
The fact that selective serotonin reuptake inhibitors (SSRIs) have antidepressant effects in some patients supports the notion that serotonin plays a role in the mode of action of antidepressant drugs. However, neither the way in which serotonin may alleviate depressed mood nor the reason why several weeks needs to elapse before the full antidepressant effect of treatment is expressed is known. Here, we propose a neuropsychological theory of SSRI antidepressant action based on the ability of SSRIs to produce positive biases in the processing of emotional information. Both behavioural and neuroimaging studies show that SSRI administration produces positive biases in attention, appraisal and memory from the earliest stages of treatment, well before the time that clinical improvement in mood becomes apparent. We suggest that the delay in the clinical effect of SSRIs can be explained by the time needed for this positive bias in implicit emotional processing to become apparent at a subjective, conscious level. This process is likely to involve the re-learning of emotional associations in a new, more positive emotional environment. This suggests intriguing links between the effect of SSRIs to promote synaptic plasticity and neurogenesis, and their ability to remediate negative emotional biases in depressed patients.


Statins for age-related macular degeneration.
Age-related macular degeneration (AMD) is a progressive, late-onset disorder of the macula affecting central vision. It is the leading cause of blindness in people over 65 years in industrialized countries. Recent epidemiologic, genetic, and pathological evidence has shown that AMD shares a number of risk factors with atherosclerosis, leading to the hypothesis that statins may exert protective effects in AMD. The objective of this review was to examine the effectiveness of statins compared with other treatments, no treatment, or placebo in delaying the onset and progression of AMD. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 3), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to March 2016), EMBASE (January 1980 to March 2016), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to March 2016), PubMed (January 1946 to March 2016), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) (last searched 5 June 2014), ClinicalTrials.gov (www.clinicaltrials.gov), and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 31 March 2016. We included randomized controlled trials (RCTs) and quasi-randomized trials that compared statins with other treatments, no treatment, or placebo in people who were diagnosed as having the early stages of AMD. We used standard methodological procedures expected by Cochrane. Two review authors independently evaluated the search results against the selection criteria, abstracted data, and assessed risk of bias. We did not perform meta-analysis due to heterogeneity in the interventions and outcomes between the included studies. Two RCTs with a total of 144 participants met the selection criteria. Both trials compared simvastatin versus placebo in older people (older than 50 or 60 years) with high risk of developing AMD (drusen present on examination). Overall, we judged the quality of the evidence to be low, as we downgraded all outcomes due to limitations in the designs of the trials and insufficient outcome reporting. The larger trial, with 114 participants, was conducted in Australia and used a higher dose (40 mg daily) of simvastatin for three years. Participants and study personnel in this trial were adequately masked, however data were missing for 30% of participants at three years' follow-up. The smaller trial, with 30 participants, was conducted in Italy and used a lower dose (20 mg) of simvastatin for three months. This trial reported insufficient details to assess the risk of bias.Neither trial reported data for change in visual acuity. Low-quality evidence from the smaller trial, with 30 participants, did not show a statistically significant difference between the simvastatin and placebo groups in visual acuity values at three months of treatment (decimal visual acuity 0.21 ± 0.56 in simvastatin group and 0.19 ± 0.40 in placebo group) or 45 days after the completion of treatment (decimal visual acuity 0.20 ± 0.50 in simvastatin group and 0.19 ± 0.48 in placebo group). The lack of a difference in visual acuity was not explained by lens or retina status, which remained unchanged during and after the treatment period for both groups.Preliminary analyses of 42 participants who had completed 12 months' follow-up in the larger trial did not show a statistically significant difference between simvastatin and the placebo groups for visual acuity, drusen score, or visual function (effect estimates and confidence intervals were not available). Complete data for these outcomes at three years' follow-up were not reported. At three years, low-quality evidence showed an effect of simvastatin in slowing progression of AMD compared with placebo to be uncertain (odds ratio 0.51, 95% confidence interval 0.23 to 1.09).One trial did not report adverse outcomes. The second trial reported no difference between groups in terms of adverse events such as death, muscle aches, and acute hepatitis. Evidence from currently available RCTs is insufficient to conclude that statins have a role in preventing or delaying the onset or progression of AMD.


Using action planning to promote exercise behavior.
Action planning promotes exercise behavior and mediates intention-behavior relationships. The aim of this study is to provide correlational and experimental tests of action planning as mediator of intention-exercise behavior relationships controlling for Theory of Planned Behavior variables and past behavior. In study 1 (N = 777), young adults completed questionnaires assessing Theory of Planned Behavior variables, past behavior, and planning in relation to exercise and 2 weeks later reported exercise behavior. In study 2 (N = 356), young adults were randomly allocated to complete one of two questionnaires and 2 weeks later reported exercise behavior. Both questionnaires contained similar measures to study 1 (Theory of Planned Behavior variables, past behavior in relation to exercise), but one also contained an exercise planning measure. Planning partially mediated intention-behavior relationships and intentions showed a moderated mediation effect: stronger intention-planning-behavior relationships when intentions were strong (study 1). Exercise behavior was higher in planning compared to no planning group, and this difference was greater when intentions were strong (study 2). Action planning mediates intention-exercise behavior relationships, particularly when exercise intentions are strong. Interventions promoting exercise behavior should jointly target intentions and planning.


Twin peaks: an ERP study of action planning and control in co-acting individuals.
Previous studies have shown that perceiving another's actions activates corresponding representations in an observer's action system. The present study investigated how performing a task with another person affects action planning and control. Reaction times (RTs) and event-related potentials were measured while participants performed a go/no-go task alone and with another person. Three effects of acting together were observed. First, RTs were slowed when individuals had to respond to a stimulus referring to the other's action, suggesting that an action selection conflict occurred. Second, at frontal sites, a stimulus referring to the other's action elicited a similar electrophysiological response as a stimulus referring to one's own action. Finally, on no-go trials, P300 amplitude was significantly larger in a group setting, indicating that an action was suppressed. These findings provide evidence that individuals acting in a social context form shared action representations.


CRISPR-based strategies for studying regulatory elements and chromatin structure in mammalian gene control.
The development of high-throughput methods has enabled the genome-wide identification of putative regulatory elements in a wide variety of mammalian cells at an unprecedented resolution. Extensive genomic studies have revealed the important role of regulatory elements and genetic variation therein in disease formation and risk. In most cases, there is only correlative evidence for the roles of these elements and non-coding changes within these elements in pathogenesis. With the advent of genome- and epigenome-editing tools based on the CRISPR technology, it is now possible to test the functional relevance of the regulatory elements and alterations on a genomic scale. Here, we review the various CRISPR-based strategies that have been developed to functionally validate the candidate regulatory elements in mammals as well as the non-coding genetic variants found to be associated with human disease. We also discuss how these synthetic biology tools have helped to elucidate the role of three-dimensional nuclear architecture and higher-order chromatin organization in shaping functional genome and controlling gene expression.


Amplified spontaneous emission in phenylethylammonium methylammonium lead iodide quasi-2D perovskites.
Organo-metal-halide perovskites are a promising set of materials for optoelectronic applications such as solar cells, light emitting diodes and lasers. Perovskite thin films have demonstrated amplified spontaneous emission thresholds as low as 1.6 μJ cm-2 and lasing thresholds as low as 0.2 μJ cm-2. Recently the performance of perovskite light emitting diodes has rapidly risen due to the formation of quasi 2D films using bulky ligands such as phenylethylammonium. Despite the high photoluminescent yield and external quantum efficiency of quasi 2D perovskites, few reports exist on amplified spontaneous emission. We show within this report that the threshold for amplified spontaneous emission of quasi 2D perovskite films increases with the concentration of phenylethylammonium. We attribute this increasing threshold to a charge transfer state at the PEA interface that competes for excitons with the ASE process. Additionally, the comparatively slow inter-grain charge transfer process cannot significantly contribute to the fast radiative recombination in amplified spontaneous emission. These results suggest that relatively low order PEA based perovskite films that are suitable for LED applications are not well suited for lasing applications. However high order films were able to maintain their low threshold values and may still benefit from improved stability.


Performing ontology.
Ontology, and in particular, the so-called ontological turn, is the topic of a recent themed issue of Social Studies of Science (Volume 43, Issue 3, 2013). Ontology, or metaphysics, is in philosophy concerned with what there is, how it is, and forms of being. But to what is the science and technology studies researcher turning when he or she talks of ontology? It is argued that it is unclear what is gained by arguing that ontology also refers to constructed elements. The 'ontological turn' comes with the risk of creating a pseudo-debate or pseudo-activity, in which energy is used for no end, at the expense of empirical studies. This text rebuts the idea of an ontological turn as foreshadowed in the texts of the themed issue. It argues that there is no fundamental qualitative difference between the ontological turn and what we know as constructivism.


Nano-Inclusions Applied in Cement-Matrix Composites: A Review.
Research on cement-based materials is trying to exploit the synergies that nanomaterials can provide. This paper describes the findings reported in the last decade on the improvement of these materials regarding, on the one hand, their mechanical performance and, on the other hand, the new properties they provide. These features are mainly based on the electrical and chemical characteristics of nanomaterials, thus allowing cement-based elements to acquire "smart" functions. In this paper, we provide a quantitative approach to the reinforcements achieved to date. The fundamental concepts of nanoscience are introduced and the need of both sophisticated devices to identify nanostructures and techniques to disperse nanomaterials in the cement paste are also highlighted. Promising results have been obtained, but, in order to turn these advances into commercial products, technical, social and standardisation barriers should be overcome. From the results collected, it can be deduced that nanomaterials are able to reduce the consumption of cement because of their reinforcing effect, as well as to convert cement-based products into electric/thermal sensors or crack repairing materials. The main obstacle to foster the implementation of such applications worldwide is the high cost of their synthesis and dispersion techniques, especially for carbon nanotubes and graphene oxide.


Loss of protein kinase C-δ protects against LPS-induced osteolysis owing to an intrinsic defect in osteoclastic bone resorption.
Bone remodeling is intrinsically regulated by cell signaling molecules. The Protein Kinase C (PKC) family of serine/threonine kinases is involved in multiple signaling pathways including cell proliferation, differentiation, apoptosis and osteoclast biology. However, the precise involvement of individual PKC isoforms in the regulation of osteoclast formation and bone homeostasis remains unclear. Here, we identify PKC-δ as the major PKC isoform expressed among all PKCs in osteoclasts; including classical PKCs (-α, -β and -γ), novel PKCs (-δ, -ε, -η and -θ) and atypical PKCs (-ι/λ and -ζ). Interestingly, pharmacological inhibition and genetic ablation of PKC-δ impairs osteoclastic bone resorption in vitro. Moreover, disruption of PKC-δ activity protects against LPS-induced osteolysis in mice, with osteoclasts accumulating on the bone surface failing to resorb bone. Treatment with the PKC-δ inhibitor Rottlerin, blocks LPS-induced bone resorption in mice. Consistently, PKC-δ deficient mice exhibit increased trabeculae bone containing residual cartilage matrix, indicative of an osteoclast-rich osteopetrosis phenotype. Cultured ex vivo osteoclasts derived from PKC-δ null mice exhibit decreased CTX-1 levels and MARKS phosphorylation, with enhanced formation rates. This is accompanied by elevated gene expression levels of cathepsin K and PKC -α, -γ and -ε, as well as altered signaling of pERK and pcSrc416/527 upon RANKL-induction, possibly to compensate for the defects in bone resorption. Collectively, our data indicate that PKC-δ is an intrinsic regulator of osteoclast formation and bone resorption and thus is a potential therapeutic target for pathological osteolysis.


Effect of sustained maternal hyperglycaemia on the fetus in normal and diabetic pregnancies.
The effect of prolonged maternal hyperglycaemia on fetal plasma glucose and insulin concentrations was investigated in eight normal and nine diabetic patients. It was found that under fasting conditions the fetal glucose concentration in gestational diabetic pregnancies tended to be lower than in normal pregnancies. Insulin measurements suggested that this may be due to fetal hyperinsulinism in the diabetic group. During glucose infusion, regardless of the degree of maternal hyperglycaemia, the fetal glucose concentration was limited in 12 out of 13 cases to less than 200 mg/100 ml, with only small differences between normal and diabetic pregnancies. It is proposed that the placenta prevents unlimited transport of glucose to the fetus; yet in diabetic pregnancies a sequence of increased maternal-fetal glucose transport, fetal hyperinsulinism, and fetal hypoglycaemia may contribute to the observed perinatal mortality.


A Pivotal Study of Optoacoustic Imaging to Diagnose Benign and Malignant Breast Masses: A New Evaluation Tool for Radiologists.
Purpose To compare the diagnostic utility of an investigational optoacoustic imaging device that fuses laser optical imaging (OA) with grayscale ultrasonography (US) to grayscale US alone in differentiating benign and malignant breast masses. Materials and Methods This prospective, 16-site study of 2105 women (study period: 12/21/2012 to 9/9/2015) compared Breast Imaging Reporting and Data System (BI-RADS) categories assigned by seven blinded independent readers to benign and malignant breast masses using OA/US versus US alone. BI-RADS 3, 4, or 5 masses assessed at diagnostic US with biopsy-proven histologic findings and BI-RADS 3 masses stable at 12 months were eligible. Independent readers reviewed US images obtained with the OA/US device, assigned a probability of malignancy (POM) and BI-RADS category, and locked results. The same independent readers then reviewed OA/US images, scored OA features, and assigned OA/US POM and a BI-RADS category. Specificity and sensitivity were calculated for US and OA/US. Benign and malignant mass upgrade and downgrade rates, positive and negative predictive values, and positive and negative likelihood ratios were compared. Results Of 2105 consented subjects with 2191 masses, 100 subjects (103 masses) were analyzed separately as a training population and excluded. An additional 202 subjects (210 masses) were excluded due to technical failures or incomplete imaging, 72 subjects (78 masses) due to protocol deviations, and 41 subjects (43 masses) due to high-risk histologic results. Of 1690 subjects with 1757 masses (1079 [61.4%] benign and 678 [38.6%] malignant masses), OA/US downgraded 40.8% (3078/7535) of benign mass reads, with a specificity of 43.0% (3242/7538, 99% confidence interval [CI]: 40.4%, 45.7%) for OA/US versus 28.1% (2120/7543, 99% CI: 25.8%, 30.5%) for the internal US of the OA/US device. OA/US exceeded US in specificity by 14.9% (P < .0001; 99% CI: 12.9, 16.9%). Sensitivity for biopsied malignant masses was 96.0% (4553/4745, 99% CI: 94.5%, 97.0%) for OA/US and 98.6% (4680/4746, 99% CI: 97.8%, 99.1%) for US (P < .0001). The negative likelihood ratio of 0.094 for OA/US indicates a negative examination can reduce a maximum US-assigned pretest probability of 17.8% (low BI-RADS 4B) to a posttest probability of 2% (BI-RADS 3). Conclusion OA/US increases the specificity of breast mass assessment compared with the device internal grayscale US alone. Online supplemental material is available for this article. © RSNA, 2017.


Analysis of the factors that correlate with increased knee adduction moment during gait in the early postoperative period following total knee arthroplasty.
Analysis of dynamic knee loading during gait is essential to prevent mechanical failures following total knee arthroplasty. External knee adduction moment during gait is the primary factor producing medial joint reaction force, and an increase in the moment is directly related to an increase in the medial compartment load on the knee. Knee adduction moment during gait in 39 knees of 32 female patients following a posterior stabilized knee replacement with a single surgeon was evaluated at 1.3months following surgery. A cut-off moment was determined as mean+1 standard deviation (SD) of the moment from 10 healthy subjects, and patients' knees were divided into high- and normal-moment groups. Significant differences in clinical assessments and gait parameters between the two groups were assessed. Based on the cut-off moment, 23 knees were grouped into normal knees and 16 knees were grouped into high-moment knees. High-moment knees showed identical femorotibial angles and knee society scores but had greater toe-out angles and medially directed ground reaction forces compared to normal-moment knees. High-moment knees showed strong correlations between peak moment and knee adduction angle, and frontal plain moment arm. The clinical significance of a high knee adduction moment following total knee arthroplasty remains unclear, but dynamic frontal alignment during gait is one of the key factors for residual high-moment knees following surgery.


Prevalence and characteristics of malnutrition among community-dwelling older adults in Israel.
Limited data are available on the characteristics of older adults (age ≥ 65) diagnosed with malnutrition in the community in Israel. This retrospective cohort study describes the prevalence and characteristics of malnutrition among a representative cohort of Israeli community-dwelling older adults. To better understand the characteristics of oral nutritional supplement (ONS) users with malnutrition, we also compared this group to non-ONS users with malnutrition. Older adults enrolled in a large not-for-profit healthcare organization in Israel were defined as malnourished according to a diagnosis of malnutrition and/or body mass index (BMI) ≤ 20 kg/m2. Index date was defined by the earliest indication of malnutrition. ONS purchases in the year following index date were used to classify patients into ONS and non-ONS users. The malnutrition prevalence rate was 3.4%. ONS users comprised 19.9% (1881/9445) of the malnourished patients. The mean age of ONS users was higher than that of non-ONS users (80.5 vs. 75.4 years, P ≤ 0.001), and women were predominant in both groups (59.2% ONS users vs. 61.8% non-ONS users, P = 0.04). ONS users (vs. non-ONS users) were significantly (P < 0.05) more likely to have co-morbidities such as cardiovascular disease (49.5% vs. 35.1%), diabetes mellitus (26.5% vs. 20.9%), hypertension (72.2% vs. 57.4%), cancer (32.0% vs. 20.7%), and dementia (24.8% vs. 9.8%). Mean baseline BMI (up to a year before index date) was similar in ONS users (20.74 kg/m2) and non-ONS users (20.26 kg/m2). ONS users had higher health services utilization, including visits to primary care physicians and dietitians, and hospitalizations (P-values < 0.05). Malnutrition is prevalent among 3.4% of community-dwelling older Israeli adults. However, older adults are not screened and treated for malnutrition systematically. Improved guidance from healthcare professionals, including earlier nutrition screening and assessment, may lead to improved health outcomes and reduced healthcare services utilization.