Two-Dimensional Ti3C2 MXene-Based Novel Nanocomposites for Breath Sensors for Early Detection of Diabetes Mellitus.
The rates of diabetes throughout the world are rising rapidly, impacting nearly every country. New research is focused on better ways to monitor and treat this disease. Breath acetone levels have been defined as a biomarker for diabetes. The development of a method to monitor and diagnose diabetes utilizing breath acetone levels would provide a fast, easy, and non-invasive treatment option. An ideal material for point-of-care diabetes management would need to have a high response to acetone, high acetone selectivity, low interference from humidity, and be able to operate at room temperature. Chemiresistive gas sensors are a promising method for sensing breath acetone due to their simple fabrication and easy operation. Certain semiconductor materials in chemiresistive sensors can react to acetone in the air and produce changes in resistance that can be correlated with acetone levels. While these materials have been developed and show strong responses to acetone with good selectivity, most of them must operate at high temperatures (compared to RT), causing high power consumption, unstable device operation, and complex device design. In this paper, we systematically studied a series of 2-dimensional MXene-based nanocomposites as the sensing materials in chemiresistive sensors to detect 2.86 ppm of acetone at room temperature. Most of them showed great sensitivity and selectivity for acetone. In particular, the 1D/2D CrWO/Ti3C2 nanocomposite showed the best sensing response to acetone: nine times higher sensitivity than 1D KWO nanowires. To determine the sensing selectivity, a CrWO/Ti3C2 nanocomposite-based sensor was exposed to various common vapors in human breath. The result revealed that it has excellent selectivity for acetone, and far lower responses to other vapors. All these preliminary results indicate that this material is a promising candidate for the creation of a point-of-care diabetes management device.


Attenuation of myocardial injury in mice with functional deletion of the circadian rhythm gene mPer2.
Variations in circadian rhythms are evident in the incidence of cardiovascular disease, and the risk of cardiovascular events increases when rhythms are disrupted. The suprachiasmatic nucleus is the central circadian pacemaker that regulates the daily rhythm of peripheral organs. Diurnal rhythms have more recently been shown to exist in myocardial tissue and are involved in metabolism and contractile function. Thus we sought to determine whether the functional deletion of the circadian rhythm mouse periodic gene 2 (mPer2) would protect the heart against ischemic injury. Nonreperfused myocardial infarction was induced in anesthetized, ventilated C57 (n = 17) and mPer2 mutant (mPer2-M; n = 15) mice via permanent ligation of the left anterior descending coronary artery. At 4 days post-myocardial infarction, we observed a 43% reduction of infarct area in mPer2-M mice compared with wild-type mice. This is coincident with 25% less macrophage infiltration, 43% higher capillary density, 17% increase in hypertrophy, and 15% less cardiomyocyte apoptosis in the infarct zone. Also, matrix metalloproteinase-9 was expressed in inflammatory cells in both groups, but total protein was 40% higher in wild-type mice, whereas it was not elevated in mPer2-M mice in response to injury. The functional deletion of the mPer2 gene reduces the severity of myocardial infarct injury by limiting the inflammatory response, reducing apoptosis, and inducing cardiomyocyte hypertrophy, thus preserving cardiac function. These findings collectively imply that the disruption of the circadian clock gene mPer2 is protective. Understanding the interactions between circadian rhythm genes and cardiovascular disease may provide insights into potential preventative and therapeutic strategies for susceptible populations.


Tracheal gas insufflation during late exhalation efficiently reduces PaCO(2) in experimental acute lung injury.
Tracheal gas insufflation (TGI) reduces PaCO(2) by flushing the tracheal and mechanical deadspace, and may have its maximum benefit when TGI gas is unopposed by significant expiratory gas flow. Thus, limiting TGI to the late expiratory period may diminish tracheal exposure to TGI gas while preserving the efficacy of TGI. This study examined the gas exchange consequences of such late-expiratory TGI. Randomized controlled trial, animal study. Eleven pigs. After stable lung injury was established using oleic acid 11 pigs were ventilated using a standardized lung protective strategy. Phasic expiratory TGI was applied for 30 min stages during the last 20%, 40%, 60%, and 100% of expiration in random sequence. PaCO(2) was continuously measured via an indwelling blood gas analysis system. PaCO(2) at baseline was 86.1+/-4.7 mmHg, and decreased progressively with increasing TGI duration of 20%, 40%, and 60%, but not 100%, of expiration (PaCO(2)=75.7+/-5.2, 68.8+/-3.6, 65.1+/-5.3 and 65.2+/-5.2 mmHg, respectively). For all stages the reduction in PaCO(2) relative to baseline was significant. Trends of increasing PaO(2) and airway pressure with increasing TGI duration were noted and most likely associated with a TGI-induced increase in lung volume. Under these conditions confining TGI to the final 60% of expiration achieved effective PaCO(2) reduction, not significantly different from panexpiratory TGI, while limiting exposure of the trachea to TGI gas, and reducing the potential for TGI-induced hyperinflation. These findings suggest that TGI is most effectively applied in a phasic manner in late expiration, with its duration titrated to effect.


Characterization and comparison of imaging contrast enhancement with PEG-functionalized gold nanoparticles in kV cone beam computed tomography and computed tomography imaging.
The purpose of this study is to define a simplified method to accurately predict and characterize kV cone beam computed tomography (kV CBCT) and computed tomography (CT) image contrast enhancement from gold nanoparticles (GNPs). Parameters of the kV CBCT of a Varian Novalis Tx linear accelerator and of a GE LightSpeed 4 Big Bore CT machine were modeled using the MCNP 6.2 Monte Carlo code. A 0.25 × 0.25 cm2 source, defined with a 100 kVp energy spectrum with appropriate filtration, was implemented in the MCNP6.2 model for kV CBCT, which also contained x- and y-blades and a full bowtie filter. A 1 cm3 cube of GNP solution (modeled as a mass percentage of gold in water) was placed 100 cm below the source. For the CT-simulator model, a source was defined with energy spectra for 80 and 140 kVp x-rays with appropriate filtration and angular spectrum. A 1 cm3 GNP solution was modeled as before and a detector was placed 40 cm below that. Attenuation coefficients of four GNP solutions were computed and Hounsfield unit (HU) values were calculated. The computed HU values were compared against experimentally measured values obtained by scanning batches of GNPs of various sizes and concentrations using a GE LightSpeed 4 Big Bore CT scanner at 80 kVp and 140 kVp energies, as well as the kV CBCT capability of a Varian Novalis Tx linear accelerator. HU analysis was carried out using Velocity Medical Solutions clinical CT image analysis software. The MCNP calculated HU values matched the measured values to within ± 5%. Image contrast enhancement analysis showed a total increase in HU of up to 223. The sample having the highest gold mass percentage tested showed the greatest increase in HU number compared to water.


Lipid composition of the stratum corneum and cutaneous water loss in birds along an aridity gradient.
Intercellular and covalently bound lipids within the stratum corneum (SC), the outermost layer of the epidermis, are the primary barrier to cutaneous water loss (CWL) in birds. We compared CWL and intercellular SC lipid composition in 20 species of birds from desert and mesic environments. Furthermore, we compared covalently bound lipids with CWL and intercellular lipids in the lark family (Alaudidae). We found that CWL increases in birds from more mesic environments, and this increase was related to changes in intercellular SC lipid composition. The most consistent pattern that emerged was a decrease in the relative amount of cerebrosides as CWL increased, a pattern that is counterintuitive based on studies of mammals with Gaucher disease. Although covalently bound lipids in larks did not correlate with CWL, we found that covalently bound cerebrosides correlated positively with intercellular cerebrosides and intercellular cholesterol ester, and intercellular cerebrosides correlated positively with covalently bound free fatty acids. Our results led us to propose a new model for the organization of lipids in the avian SC, in which the sugar moieties of cerebrosides lie outside of intercellular lipid layers, where they may interdigitate with adjacent intercellular cerebrosides or with covalently bound cerebrosides.


Sensitive detection of fluorescence in western blotting by merging images.
The western blotting technique is widely used to analyze protein expression levels and protein molecular weight. The chemiluminescence method is mainly used for detection due to its high sensitivity and ease of manipulation, but it is unsuitable for detailed analyses because it cannot be used to detect multiple proteins simultaneously. Recently, more attention has been paid to the fluorescence detection method because it is more quantitative and is suitable for the detection of multiple proteins simultaneously. However, fluorescence detection can be limited by poor image resolution and low detection sensitivity. Here, we describe a method to detect fluorescence in western blots using fluorescence microscopy to obtain high-resolution images. In this method, filters and fluorescent dyes are optimized to enhance detection sensitivity to a level similar to that of the chemiluminescence method.


[Changes in the dendrites of the rat lateral hypothalamic region during food deprivation].
Electron microscopy was used to explore ultrastructural changes in the lateral hypothalamic area (LHA) of rats 1, 3, 5 and 7 days after food deprivation. Special attention was paid to studies on changes in LHA dendrites which carry out receptive function. The dendrites were shown to be the most vulnerable and to be affected earlier than other components of neurons (somas, axons). The time course of pathomorphological changes in the dendrites, namely from initial to gross destructive ones, was specified. The characteristic changes in the dendrites included invagination into the dendritic cytoplasm of adjacent structures, mostly axons, with destructive changes in the area of invaginated parts. Invagination could be observed since the third day and was the most demonstrable on the 7th day of food deprivation. The possible mechanisms of such invaginations are discussed.


Circularly polarized spatial solitons in Kerr media beyond paraxial approximation.
We show that, in (2+1)-D case, both bright and dark solitons can exist in optical Kerr media when the optical beams are cylindrically symmetric and almost circularly polarized. We characterize the dependence of the properties associated with these solitons, such as their spatial width and intensity profiles, on their normalized intensity and the non-paraxial degree.


Developmental characteristics of trisomy 19 mice.
Trisomy 19 (Ts19), the only murine trisomy compatible with survival beyond birth, allows systematic studies on the effect of an additional chromosome upon postnatal development. In this review, developmental consequences of murine Ts19 are presented. In Ts19 mice, viability is limited to a few weeks postpartum. Body weight is markedly reduced. The occurrence of malformations of the cardiovascular, skeletal and central nervous systems depends on the parental genetic background. In all organ systems examined, development is delayed by 1-2 days. Ts19 hematopoietic cells exhibit the same survival rate in lethally irradiated hosts as controls. In the CNS, morphological and morphometric studies fail to detect cytoarchitectonic abnormalities: the orderly pattern of development is not disturbed in the visual cortex, cerebellum, locus coeruleus (LC), optic nerve and retina; but neurogenesis, gliogenesis, myelination and invasion of blood vessels are each delayed by 1-2 days. In addition, size and cell number of different brain regions are reduced to a variable degree: the telencephalon and the cerebellar vermis are markedly hypoplastic, whereas the LC, the optic nerve and the retina are hardly reduced in size. Choline acetyltransferase activity is selectively reduced in the Ts19 telencephalon, whereas the activity of the marker enzyme of the GABAergic system is decreased in all brain regions examined. In behavioral tests, visual capacities and orientation ability of Ts19 mice develop with a 2-day delay, while motor coordination is more severely retarded; there is no response to auditory stimulation. Fetal Ts19 ovaries show excessive oocyte degeneration. Development of the testes is only disturbed postnatally: differentiation of gonocytes to A spermatogonia and formation of B spermatogonia are severely disrupted, resulting in a striking reduction in germ cell number and a predominance of Sertoli cells. Histopathological changes exhibit marked intra- and interindividual variations. In addition, growth and lumen formation are impaired in the seminiferous tubules. The proliferative capacity of cultured Ts19 cells is not altered. The activities of glutamate oxaloacetate transaminase-1 and phosphoglycerate mutase-1 are increased by 50%, compatible with a gene dosage effect of these two enzymes. Ganglioside composition is altered in the Ts19 liver, but not in the brain, spleen and heart. Two-dimensional protein patterns show both chromosome-specific and chromosome-nonspecific changes, their frequency being far lower than expected from the number of proteins coded on chromosome 19. Possible pathogenetic mechanisms are discussed.


Untangling structural factors driving genome stabilization in nascent Brassica napus allopolyploids.
Allopolyploids have globally higher fitness than their diploid progenitors; however, by comparison, most resynthesized allopolyploids have poor fertility and highly unstable genome. Elucidating the evolutionary processes promoting genome stabilization and fertility is thus essential to comprehend allopolyploid success. Using the Brassica model, we mimicked the speciation process of a nascent allopolyploid species by resynthesizing allotetraploid Brassica napus and systematically selecting for euploid individuals over eight generations in four independent allopolyploidization events with contrasted genetic backgrounds, cytoplasmic donors, and polyploid formation type. We evaluated the evolution of meiotic behavior and fertility and identified rearrangements in S1 to S9 lineages to explore the positive consequences of euploid selection on B. napus genome stability. Recurrent selection of euploid plants for eight generations drastically reduced the percentage of aneuploid progenies as early as the fourth generation, concomitantly with a decrease in number of newly fixed homoeologous rearrangements. The consequences of homoeologous rearrangements on meiotic behavior and seed number depended strongly on the genetic background and cytoplasm donor. The combined use of both self-fertilization and recurrent euploid selection allowed identification of genomic regions associated with fertility and meiotic behavior, providing complementary evidence to explain B. napus speciation success.


Recurrent Escherichia coli bacteremia.
Escherichia coli is the most common gram-negative organism associated with bacteremia. While recurrent E. coli urinary tract infections are well-described, recurrent E. coli bacteremia appears to be uncommon, with no episodes noted in multiple series of patients with gram-negative bacteremias. We report on 5 patients with recurrent bloodstream infections identified from a series of 163 patients with E. coli bacteremia. For each patient, the isolates from each episode were analyzed by pulsed-field gel electrophoresis (PFGE) and ribotyping and for the presence of E. coli virulence factors. For each of four patients, the index and recurrent episodes of bacteremia represented the same strain as defined by PFGE, and the strains were found to carry one or more virulence factors. The remaining patient, with two episodes of bloodstream infection separated by a 4-year interval, was infected with two isolates that did not carry any virulence factors and that were clonally related by ribotype analysis but differed by PFGE. All five patients had either a local host defense defect (three patients) or impaired systemic defenses (one patient) or both (one patient). Thus, recurrent E. coli bacteremia is likely to represent a multifactorial process that occurs in patients with impaired host defenses who are infected with virulent isolates.


Pre- and peri-natal environmental risks for attention-deficit hyperactivity disorder (ADHD): the potential role of epigenetic processes in mediating susceptibility.
Attention-deficit hyperactivity disorder (ADHD) is a common childhood neurobehavioural disorder defined by symptoms of developmentally inappropriate inattention, impulsivity and hyperactivity. As is the norm for most psychiatric phenotypes, traditional aetiological studies have focused primarily on the interplay between genetic and environmental factors. It is likely that epigenetic factors, i.e., heritable, but reversible changes to genomic function that are independent of DNA sequence, are also important. It is known that epigenetic processes can be induced following exposure to a range of external factors, and thus provide a mechanism by which the environment can lead to long-term alterations in phenotype. In this article we hypothesise that epigenetic dysregulation may mediate the association observed between early-development environmental insults and ADHD. We propose that understanding the epigenetic processes involved in linking specific environmental pathogens to an increased risk for ADHD may offer new possibilities for preventative and therapeutic intervention.


Polymeric 3D Printed Structures for Soft-Tissue Engineering.
3D printing, or rapid prototyping, is a fabrication technique that is used for various engineering applications with advantages such as mass production and fine tuning of spatial-dimensional properties. Recently, this fabrication method has been adopted for tissue engineering applications due to its ability to finely tune porosity and create precise, uniform, and repeatable structures. This review aims to introduce 3D printing applications in soft tissue engineering and regenerative medicine including state-of-the-art scaffolds and key future challenges. Furthermore, 3D printing of individual cells, an evolution of traditional 3D printing technology which represents a cutting-edge technique for the creation of cell seeded scaffolds in vitro, is discussed. Key advances demonstrate the advantages of 3D printing, while also highlighting potential shortcomings to improve upon. It is clear that as 3D printing technology continues to develop, it will serve as a truly revolutionary means for fabrication of structures and materials for regenerative applications.


Recombinant human growth hormone acts on intermediate-sized follicles and rescues growing follicles from atresia.
In order to clarify the role of ovarian function, recombinant human GH (rhGH) was administered to adult spontaneous dwarf rats (SDR) for 14 days. The SDR were sacrificed on the day of estrus and the effects of rhGH on ovarian weight, follicular population and the viability estimated by 5-bromodeoxyuridine (BrdU) incorporation, were studied. RhGH administration caused a significant gain in body weight of the SDR, and the ovarian weight of the GH-injected SDR showed a significant increase in comparison with saline injected SDR. The total population of follicles was significantly greater in the GH-treated group than in the control, and the difference was attributed to the increase in the number of large follicles more than 500 micrograms. Total uptake of BrdU into granulosa cells was significantly higher in GH-treated rats than in the control, and, in particular, the intermediate-sized follicles (300-500 micrograms) of the GH-treated rats showed signs of high incorporation of BrdU. These results suggest that hGH acts on intermediate follicles, stimulates their viability and increases the number of growing follicles.


Fetal Bone Formation Is Decreased from Middle Pregnancy to Birth.
Fetal bone development is a complex process that is regulated and maintained by minerals, hormones, and growth factors delivered from the mother via the placenta. Various biochemical markers of fetal bone development have been identified. However, many aspects of this process remain unclear. The aim of the study was to measure the activities of serum tartrate-resistant acid phosphatase type 5b (TRACP 5b) as a bone resorption marker and bone alkaline phosphatase (BAP) as a bone formation marker in preterm and term neonates, and to investigate fetal bone development in middle and late pregnancy. The study included 111 neonates (87 preterm and 24 term) born at Dokkyo Medical University Hospital. Neonates with illnesses and maternal diseases were excluded. Serum samples were collected within 3 hours after birth and stored at -80°C. Univariate and multivariate linear regression analyses were performed. The 111 neonates (median birth weight, 1,510 g) were born at a median of 31.3 weeks of gestation, and had TRACP 5b and BAP activities of 10.9 ± 4.0 U/L and 127.5 ± 49.2 U/L, respectively. TRACP 5b activity showed a tendency to be higher in term neonates, while BAP activity tended to be lower in term neonates. Importantly, TRACP 5b activity was positively correlated with gestational age and birth weight, and BAP activity was negatively correlated with gestational age, rate of born small-for-gestational-age neonates, and birth weight. These results suggest that bone formation during fetal growth is gradually decreased from middle pregnancy to birth, whereas bone resorption is gradually increased.


Systolic Heart Failure is Associated with Higher Mortality Among Patients Undergoing Transcatheter Aortic Valve Replacement: A Nationwide Analysis.
Heart failure (HF) is prevalent among patients with aortic stenosis and presents a poor prognosis. In order to better portray outcomes for HF patients undergoing transcatheter aortic valve replacement (TAVR), we evaluated clinical outcomes in patients with systolic vs diastolic heart failure who underwent TAVR in a large nationwide database. We searched the National Inpatient Sample (NIS) for hospitalized adult patients who underwent TAVR with coexisting history of systolic (SHF) or diastolic heart failure (DHF) as a secondary diagnosis using the ICD-10 codes. The primary outcome was in-hospital mortality, with secondary outcomes of cardiac arrest (CA), cardiogenic shock (CS), respiratory failure (RF), Non-ST elevation myocardial infarction (NSTEMI), acute kidney injury (AKI), use of cardiac and respiratory assist device, and health care utilization defined as length of stay, average hospital cost (AHC) and patient charge (APC). Both univariate and multivariate logistic, generalized linear, and Poisson regression analyses were used to evaluate and test the outcomes. A P-value of <0.05 was significant. A total of 106,815 patients were admitted to acute care hospitals for TAVR, and 73% had a secondary diagnosis of heart failure (41% had SHF and 59% DHF). SHF group were older (mean age of 78.9 years [SD ± 8.9] vs 79.9 years [SD ± 8.3]) with more males (61.8% vs 48.2%) and white predominant (whites [85.9% vs 87.9%]). Compared to DHF, SHF had higher inpatient mortality (1.75% vs 1.14%, P = 0.003), CA (1.31% vs 0.81%, P = 0.01), NSTEMI (2.52% vs 1.0%, P = 0.001), RF (10.87% vs 8.01%, P = 0.001), and CS (3.94% vs 1.14%, P = 0.001). In addition, SHF had greater LOS (5.1 days vs. .3.9, P = 0.0001) & AHC ($52,901 vs $48,070, P = 0.0001). HF is common among patients admitted for TAVR. SHF had worse CV outcomes, greater use of hospital resources, and higher acute care hospital mortality compared to those with DHF.


Obesity in multiracial schizophrenia patients receiving outpatient treatment in a regional tertiary hospital in malaysia.
OBJECTIVES. Obesity is an issue of concern among patients with schizophrenia as it is a co-morbid condition that is closely related to metabolic syndrome. The present study assessed the correlation of body mass index with antipsychotic use among multiracial schizophrenia outpatients. The study also compared the patients' body mass index with Malaysian Adult Nutrition Survey (MANS) data. METHODS. A total of 216 participants were recruited into a cross-sectional study conducted over 5 months, from December 2010 to April 2011. Body weight and height were measured using the standard methods. Demographic data and treatment variables were gathered through interview or review of the medical records. RESULTS. There were differences in mean body mass index between men and women (p = 0.02) and between Malay, Chinese and Indian races (p = 0.04). Stratified by sex, age, and race, the body mass index distributions of the patients were significantly different to those of the reference MANS population. The prevalence of obesity among patients was more than 2-fold greater than among the reference population in all variables. Although body mass index distribution was related to antipsychotic drugs (χ(2) = 33.42; p = 0.04), obesity could not be attributed to any specific drug. CONCLUSION. The prevalence of obesity among patients with schizophrenia was significantly greater than that in the healthy Malaysian population, and affects the 3 main races in Malaysia.


Panton-Valentine leukocidin Staphylococcus causing fatal necrotising pneumonia in a young boy.
Panton-Valentine leukocidin (PVL) toxin producing strains of Staphylococcus aureus are known to cause skin and soft tissue infection. They can also cause necrotising pneumonia in otherwise healthy individuals. Here we report a case of severe, necrotising, haemorrhagic pneumonia in a 12-year-old boy who presented with a four-day history of a sore throat and fever. During his admission he deteriorated and needed full ventilatory support but despite all efforts he died. Postmortem examination lung swabs confirmed the presence of PVL-associated S aureus. There is a need to improve awareness of this disease among medical practitioners as early diagnosis and appropriate management can save lives.


Health Outcomes and Costs of Social Work Services: A Systematic Review.
Efforts to reduce expensive health service utilization, contain costs, improve health outcomes, and address the social determinants of health require research that demonstrates the economic value of health services in population health across a variety of settings. Social workers are an integral part of the US health care system, yet the specific contributions of social work to health and cost-containment outcomes are unknown. The social work profession's person-in-environment framework and unique skillset, particularly around addressing social determinants of health, hold promise for improving health and cost outcomes. To systematically review international studies of the effect of social work-involved health services on health and economic outcomes. We searched 4 databases (PubMed, PsycINFO, CINAHL, Social Science Citation Index) by using "social work" AND "cost" and "health" for trials published from 1990 to 2017. Abstract review was followed by full-text review of all studies meeting inclusion criteria (social work services, physical health, and cost outcomes). Of the 831 abstracts found, 51 (6.1%) met criteria. Full text review yielded 16 studies involving more than 16 000 participants, including pregnant and pediatric patients, vulnerable low-income adults, and geriatric patients. We examined study quality, health and utilization outcomes, and cost outcomes. Average study quality was fair. Studies of 7 social work-led services scored higher on quality ratings than 9 studies of social workers as team members. Most studies showed positive effects on health and service utilization; cost-savings were consistent across nearly all studies. Despite positive overall effects on outcomes, variability in study methods, health problems, and cost analyses render generalizations difficult. Controlled hypothesis-driven trials are needed to examine the health and cost effects of specific services delivered by social workers independently and through interprofessional team-based care. Public Health Implications. The economic and health benefits reported in these studies suggest that the broad health perspective taken by the social work profession for patient, personal, and environmental needs may be particularly valuable for achieving goals of cost containment, prevention, and population health. Novel approaches that move beyond cost savings to articulate the specific value-added of social work are much needed. As health service delivery focuses increasingly on interprofessional training, practice, and integrated care, more research testing the impact of social work prevention and intervention efforts on the health and well-being of vulnerable populations while also measuring societal costs and benefits is essential.


Change of visual acuity recording methods in clinical studies across the years.
To report any differences in the visual acuity (VA) recording method used in peer-reviewed ophthalmology clinical studies over the past decade. We reviewed the method of assessing and reporting VA in 160 clinical studies from 2 UK and 2 US peer-reviewed journals, published in 1994 and 2004. The method used to assess VA was specified in 62.5% of UK-published and 60% of US-published papers. In the results sections of the UK publications the VA measurements presented were Snellen acuity (n = 58), logMAR acuity (n = 20) and symbol acuity (n = 1). Similarly in the US publications the VA was recorded in the results section using Snellen acuity (n = 60) and logMAR acuity (n = 14). Overall 10% of the authors appeared to convert Snellen acuity measurements to logMAR format. Five studies (3%) chose to express Snellen-type acuities in decimal form, a method which can easily lead to confusion given the increased use of logMAR scoring systems. The authors recommend that to ensure comparable visual results between studies and different study populations it would be useful if clinical scientists worked to standardized VA testing protocols and reported results in a manner consistent with the way in which they are measured.


[Expert consensus on the strategy and measures to interrupt the transmission of schistosomiasis in China].
Since 2015 when the transmission of schistosomiasis was controlled in China, the country has been moving towards elimination of schistosomiasis, with the surveillance-response as the main interventions for schistosomiasis control. During the period of the 13th Five-Year Plan, the transmission of schistosomiasis had been interrupted in four provinces of Sichuan, Jiangsu, Yunnan and Hubei and the prevalence of schistosomiasis has been at the historically lowest level in China. As a consequence, the goal set in The 13th Five-Year National Schistosomiasis Control Program in China is almost achieved. However, there are multiple challenges during the stage moving towards elimination of schistosomiasis in China, including the widespread distribution of intermediate host snails and complicated snail habitats, many types of sources of Schistosoma japonicum infections and difficulty in management of bovines and sheep, unmet requirements for the current schistosomiasis control program with the currently available tools, and vulnerable control achievements. During the 14th Five-Year period, it is crucial to consolidate the schistosomiasis control achievements and gradually solve the above difficulties, and critical to provide the basis for achieving the ultimate goal of elimination of schistosomiasis in China. Based on the past experiences from the national schistosomiasis control program and the challenges for schistosomiasis elimination in China, an expert consensus has been reached pertaining to the objectives, control strategy and measures for The 14th Five-Year National Schistosomiasis Control Program in China, so as to provide insights in to the development of The 14th Five-Year National Schistosomiasis Control Program in China.


[The differential effect of damage to the motor cortex on the precise reactions of avoidance and escape in dogs].
Effects of ablation of the forelimb area in the motor cortex on the precise lifting of this limb were studied. Even inaccurate avoidance reactions to the sound signal did not recover spontaneously. In the course of retraining irregular reactions of insufficient amplitude could be easily recovered but the precise reactions (both fast continuous and slow discontinuous) did not recover at least for half a year after the ablation. On the contrary, the fast precise escape reactions (to the shock applied to the "working" limb and eliciting its unconditioned flexion) remained essentially unchanged, i. a. the ability to stop movement in the correct (previously learnt) position persisted. The ability to fix position of the flexed limb retained but in was less perfect and did not improve. The ability to overcome unconditioned flexion (in order to perform discontinuous extensor escape reaction) was severely and continuously (for a year) decreased. Visually guided placings of the forepaw on a held out hand of an experimenter recovered essentially spontaneously and almost completely during a month.


Hepatoblastoma presenting as precocious puberty: a case report.
Hepatoblastoma (HB), a primary liver tumor in childhood, is often accompanied by alpha-fetoprotein (AFP) secretion, and sometimes by β-human chorionic gonadotropin hormone (β-hCG) secretion, and this can cause peripheral precocious puberty (PPP). We describe a case of PPP associated with HB. Laboratory tests showed an increase in AFP, β-hCG and testosterone values, and suppression of follicle-stimulating hormone and luteinizing hormone levels. After chemotherapy and surgery, AFP, β-hCG and testosterone levels normalized and signs of virilization did not progress further. The child did not show evidence for tumor recurrence after 16 months of follow-up. New therapeutic approaches and early diagnosis may ensure a better prognosis of virilizing HB, than reported in the past. Assessment of PPP should always take into account the possibility of a tumoral source.


Fried meat intake is a risk factor for lung adenocarcinoma in a prospective cohort of Chinese men and women in Singapore.
Probable human carcinogens are generated during Chinese-style high-temperature cooking of meat and have been detected in the ambient air and on the meat surface. Although the inhalation of these compounds is an established risk factor for lung cancer, exposure via fried meat consumption has not yet been prospectively evaluated as a risk factor. The relationship between fried meat intake and lung cancer risk was investigated using data from a prospective cohort study among Chinese in Singapore. Lung cancer cases (n = 1130) were identified from 61 321 men and women, 70% of whom were lifetime never smokers. Proportional hazards regression methods were used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). Overall, there was no association between fried meat intake and risk of all lung cancers combined. For lung adenocarcinoma, fried meat intake had a statistically significant association with increased risk. The association between fried meat intake and risk of lung adenocarcinoma became stronger when analyses were restricted to lifetime never smokers. Compared with the lowest tertile of fried meat intake, the HRs (95% CIs) for the second and third tertiles were 1.43 (0.98, 2.08) and 1.51 (1.03, 2.22), respectively (P for trend = 0.04). The positive association was present among both men and women. There was no association between fried meat intake and risk of non-adenocarcinomas of the lung. Our prospective results for fried meat intake support consumption as an important route of exposure to compounds from Chinese-style high-temperature cooking for the development of lung adenocarcinoma.


Evaluating three treatments for borderline personality disorder: a multiwave study.
The authors examined three yearlong outpatient treatments for borderline personality disorder: dialectical behavior therapy, transference-focused psychotherapy, and a dynamic supportive treatment. Ninety patients who were diagnosed with borderline personality disorder were randomly assigned to transference-focused psychotherapy, dialectical behavior therapy, or supportive treatment and received medication when indicated. Prior to treatment and at 4-month intervals during a 1-year period, blind raters assessed the domains of suicidal behavior, aggression, impulsivity, anxiety, depression, and social adjustment in a multiwave study design. Individual growth curve analysis revealed that patients in all three treatment groups showed significant positive change in depression, anxiety, global functioning, and social adjustment across 1 year of treatment. Both transference-focused psychotherapy and dialectical behavior therapy were significantly associated with improvement in suicidality. Only transference-focused psychotherapy and supportive treatment were associated with improvement in anger. Transference-focused psychotherapy and supportive treatment were each associated with improvement in facets of impulsivity. Only transference-focused psychotherapy was significantly predictive of change in irritability and verbal and direct assault. Patients with borderline personality disorder respond to structured treatments in an outpatient setting with change in multiple domains of outcome. A structured dynamic treatment, transference-focused psychotherapy was associated with change in multiple constructs across six domains; dialectical behavior therapy and supportive treatment were associated with fewer changes. Future research is needed to examine the specific mechanisms of change in these treatments beyond common structures.


Towards understanding sparse filtering: A theoretical perspective.
In this paper we present a theoretical analysis to understand sparse filtering, a recent and effective algorithm for unsupervised learning. The aim of this research is not to show whether or how well sparse filtering works, but to understand why and when sparse filtering does work. We provide a thorough theoretical analysis of sparse filtering and its properties, and further offer an experimental validation of the main outcomes of our theoretical analysis. We show that sparse filtering works by explicitly maximizing the entropy of the learned representations through the maximization of the proxy of sparsity, and by implicitly preserving mutual information between original and learned representations through the constraint of preserving a structure of the data. Specifically, we show that the sparse filtering algorithm implemented using an absolute-value non-linearity determines the preservation of a data structure defined by relations of neighborhoodness under the cosine distance. Furthermore, we empirically validate our theoretical results with artificial and real data sets, and we apply our theoretical understanding to explain the success of sparse filtering on real-world problems. Our work provides a strong theoretical basis for understanding sparse filtering: it highlights assumptions and conditions for success behind this feature distribution learning algorithm, and provides insights for developing new feature distribution learning algorithms.


Expression of genes involved in symbiotic carbon and nitrogen transport in Pinus taeda mycorrhizal roots exposed to CO2 enrichment and nitrogen fertilization.
As atmospheric carbon dioxide (CO(2)) concentrations rise, one important mechanism by which plants can gain greater access to necessary soil nutrients is through greater investment in their mycorrhizal symbionts. In this study, we tested the hypotheses that (1) plants increase C allocation to ectomycorrhizal fungi (EMF) under elevated CO(2) conditions, (2) N fertilization decreases C allocation to EMF, and (3) EMF activity at the site of symbiotic C and nutrient exchange is enhanced with CO(2) enrichment. To test these hypotheses, we examined expression levels of Pinus taeda genes encoding monosaccharide transport (MST) and ammonium transport (AMT) proteins thought to be involved in symbiotic C and N movement, respectively, from mycorrhizal root tips exposed to CO(2) and N fertilization. We also examined EMF ribosomal RNA expression (18S rRNA) to determine EMF activity. There was a trend toward lower relative MST expression with increased CO(2). AMT expression levels showed no significant differences between control and treatment plots. EMF 18S rRNA expression was increased in CO(2)-enriched plots and there was a marginally significant positive interactive effect of CO(2) and N fertilization on expression (p = 0.09 and 0.10, respectively). These results are consistent with greater C allocation to EMF and greater EMF metabolic activity under elevated CO(2) conditions, although selective allocation of C to particular EMF species and greater fungal biomass on roots are plausible alternative hypotheses.


Head kidney-derived macrophages of common carp (Cyprinus carpio L.) show plasticity and functional polarization upon differential stimulation.
Cells from the myeloid lineage are pluripotent. To investigate the potential of myeloid cell polarization in a primitive vertebrate species, we phenotypically and functionally characterized myeloid cells of common carp (Cyprinus carpio L.) during culture. Flow cytometric analysis, Ab labeling of cell surface markers, and light microscopy showed the presence of a major population of heterogeneous macrophages after culture. These head kidney-derived macrophages can be considered the fish equivalent of bone marrow-derived macrophages and show the ability to phagocytose, produce radicals, and polarize into innate activated or alternatively activated macrophages. Macrophage polarization was based on differential activity of inducible NO synthase and arginase for innate and alternative activation, respectively. Correspondingly, gene expression profiling after stimulation with LPS or cAMP showed differential expression for most of the immune genes presently described for carp. The recently described novel Ig-like transcript 1 (NILT1) and the CXCR1 and CXCR2 chemokine receptors were up-regulated after stimulation with cAMP, an inducer of alternative activation in carp macrophages. Up-regulation of NILT1 was also seen during the later phase of a Trypanosoma carassii infection, where macrophages are primarily alternatively activated. However, NILT1 could not be up-regulated during a Trypanoplasma borreli infection, a model for innate activation. Our data suggest that NILT1, CXCR1, and CXCR2 could be considered markers for alternatively activated macrophages in fish.


MultiBacMam Bimolecular Fluorescence Complementation (BiFC) tool-kit identifies new small-molecule inhibitors of the CDK5-p25 protein-protein interaction (PPI).
Protein-protein interactions (PPIs) are at the core of virtually all biological processes in cells. Consequently, targeting PPIs is emerging at the forefront of drug discovery. Cellular assays which closely recapitulate native conditions in vivo are instrumental to understand how small molecule drugs can modulate such interactions. We have integrated MultiBacMam, a baculovirus-based mammalian gene delivery tool we developed, with bimolecular fluorescence complementation (BiFC), giving rise to a highly efficient system for assay development, identification and characterization of PPI modulators. We used our system to analyze compounds impacting on CDK5-p25 PPI, which is implicated in numerous diseases including Alzheimer's. We evaluated our tool-kit with the known inhibitor p5T, and we established a mini-screen to identify compounds that modulate this PPI in dose-response experiments. Finally, we discovered several compounds disrupting CDK5-p25 PPI, which had not been identified by other screening or structure-based methods before.


Should embolectomy be performed in late acute lower extremity arterial occlusions?
We analyzed the embolectomy results and complications of patients who were operated on after a diagnosis of late acute arterial occlusion of lower extremities. A total of 122 patients operated on in our clinic between 2004 and 2009 for late acute arterial occlusion were included in the study. Late arterial occlusion was defined as occlusion occuring 72 hours after initial manifestation of the patient complaints related to the affected lower extremity. Average age of the 122 patients (71 male, 51 female) was 54.2 +/- 16.8 years. In this cohort, 64.75% of patients had cardiac pathologies, while 28.68% had extracardiac causes; 1.64% patients had cathetherization, 0.81% patient had malignancy, and 2.46% patients had a history of trauma. In 1.64% of the cases, no reason for thromboembolysis could be found. Thirty-one patients (25.40%) had additional surgical operations, 14 (11.47%) had fasciotomy, and 9 (7.37%) had amputation. Re-embolectomy was performed on 37 patients (30.32%) who had ongoing ischemia after an operation. Additional surgical operations were performed on 31 patients (25.40%) with ongoing ischemia. In 14 of these cases (11.47%), patients were treated with fasciotomy due to development of compartment syndrome. Amputation was performed on a total of 9 patients. Early in the postoperative phase, mortality was observed in 11 patients (9.01%). We believe that late embolectomies of acute late leg ischemia increases blood flow in the extremity and reduces the number of amputations required.


The diagnosis and management of idiosyncratic drug-induced liver injury.
Drug-induced liver injury (DILI) is an uncommon but important cause of liver disease that can arise after exposure to a multitude of drugs and herbal and dietary supplements. The severity of idiosyncratic DILI varies from mild serum aminotransferase elevations to the development of severe liver injury that can progress to acute liver failure resulting in death or liver transplantation within days of DILI onset. Chronic liver injury that persists for more than 6 months after DILI onset is also becoming increasingly recognized in up to 20% of DILI patients. Host demographic (age, gender, race), clinical and laboratory features at DILI onset have been associated with the severity and outcome of liver injury in DILI patients. In addition to cessation of the suspect drug, other medical interventions including the use of N-acetylcysteine and corticosteroids in selected patients have shown some clinical benefit, but additional prospective studies are needed. A number of promising diagnostic, prognostic and mechanistic serum and genetic biomarkers may help improve our understanding of the pathogenesis and treatment of idiosyncratic DILI.


The impact of approaches in improving male partner involvement in the prevention of mother-to-child transmission of HIV on the uptake of maternal antiretroviral therapy among HIV-seropositive pregnant women in sub-Saharan Africa: a systematic review and meta-analysis.
To identify the approaches that are used in improving on male partner involvement in the prevention of mother-to-child transmission (PMTCT) of HIV and their impact on the uptake maternal antiretroviral therapy (ART) in sub-Saharan Africa (SSA). This was a systematic review and meta-analysis of published studies carried out in SSA at all levels of healthcare (primary, secondary, tertiary and community). The participants of the studies included were HIV-positive pregnant women and breastfeeding mothers with their male partners. Studies were included if they were conducted in SSA and mentioned an approach used in improving male partner involvement with data on the impact on the uptake of maternal ART uptake. In the protocol, maternal ART uptake, infant prophylaxis, safe infant feeding options, condom use and family planning were envisaged. However, only maternal ART has been reported here due to limitations on the word count. From an initial 2316 non-duplicate articles, 17 articles were included in the systematic review and meta-analysis. In the combined model, the ORs for complex community interventions, enhanced psychosocial interventions, verbal encouragement and invitation letters were 4.22 (95% CI 2.27 to 7.77), 2.29 (95% CI 1.42 to 7.69), 2.39 (95% CI 1.26 to 4.53) and 1.21 (95% CI 0.89 to 1.63), respectively, whereas in the model using adjusted ORs, enhanced psychosocial interventions had a higher effect than any other intervention. The heterogeneity was moderate using adjusted ORs. Enhanced psychosocial interventions and complex community interventions increase male partner involvement and the uptake of PMTCT services more than any other intervention. Invitation letters had no effect. More randomised trials and observational studies (that have adjusted for potential confounders) are needed in the future. 42016032673.


When Nursing Care and Clinical Trials Coincide: A Qualitative Study of the Views of Nordic Oncology and Hematology Nurses on Ethical Work Challenges.
This study investigated the kinds of ethical challenges experienced by nurses in oncology and hematology when nursing care and research overlap in clinical trials, and how the nurses handle such challenges. Individual interviews with 39 nurses from Sweden, Denmark, and Finland indicated that all nurses were positive about research, considering it essential for developing the best care. Ethical challenges exist, however; the most difficult were associated with the end-of-life patients, no longer responsive to standard therapy, who eagerly volunteer for cutting-edge drug trials in the hope of gaining therapeutic benefit. Many nurses lacked systematic strategies for addressing such challenges but found support from their nursing colleagues and relied on the research protocols to guide them.


Student Intervention Against Homophobic Name-Calling: The Role of Peers, Teachers, and Inclusive Curricula.
Encouraging bystander intervention is an effective strategy to prevent episodes of bullying victimization at school. Yet there remains a paucity of evidence on this behavior in situations of homophobic name-calling, a form of peer victimization aimed at mocking individuals based on their actual or perceived sexual orientation. The existing research has focused on intentionality rather than actual student intervention behaviors, and, of note, no previous studies have taken into consideration contextual factors at the classroom and school levels. The present study examined whether students' observations of teacher and peer interventions against homophobic name-calling and perceptions of the representation of lesbian, gay, bisexual, and transgender (LGBT) issues in class are associated with student intervention behaviors against homophobic name-calling. A three-level multilevel approach was used to account for the nested nature of students' experiences in classrooms and schools. The sample included 1,296 students (43.57% girls) recruited from 84 classrooms of 22 Italian public high schools. Preliminary analyses showed that the variability in students' reports had more to do with which classrooms versus which schools students attend. Results from multilevel regressions indicated that students who observe teachers intervening during episodes of homophobic name-calling, and who perceive the representation of LGBT issues in class as positive, were more likely to intervene against homophobic name-calling and to observe other classmates intervene as well. Also, participants who observed other students intervening were more likely to intervene. These findings highlight the importance of the role of teachers in modeling classroom norms to encourage bystander interventions. Teachers can do so indirectly such as when providing a positive representation of LGBT issues in class, or directly when intervening to condemn episodes of homophobic name-calling. In addition, our results affirm the importance of peer influence in encouraging bystander interventions during episodes of homophobic name-calling.


FIA Score: a simple risk index for predicting fatality in aviation crashes.
Previous studies have identified a variety of risk factors for occupant fatality in aviation crashes. A simple composite index measuring the risk of fatality in a given crash, however, is lacking. The FIA Score is a four-point (0-3) index based on the number of three risk factors for occupant fatality present in a given aviation crash: fire, instrument meteorological condition, and being away from airport. We assessed the validity of this risk index using aviation crash investigation data from the National Transportation Safety Board for the years 1983 to 2005. Sensitivity, specificity, and area under the receiver operating characteristic curve according to the type of flight operations were computed. The analysis was first limited to pilot-in-command fatality and then replicated to any fatality. The study sample consisted of 44,828 aviation crashes, in which 7,889 (18%) pilots-in-command were fatally injured. The pilot crash fatality rate was 3%, 18%, 62%, and 89% for FIA Scores of 0 (none of the 3 risk factors present), 1, 2, and 3 (all 3 risk factors present), respectively. The FIA Score performed consistently well in predicting pilot fatality in crashes involving different types of flight operations. The area under receiver operating characteristic curve was 0.86 (95% confidence interval [CI]: 0.78-0.95) for major airline crashes, 0.83 (95% CI: 0.80-0.85) for commuter and air taxi crashes, and 0.81 (95% CI: 0.81-0.82) for general aviation crashes. The results were similar when the outcome was measured by whether or not the crash resulted in any fatality. The FIA Score appears to be a valid tool for measuring fatality risk in aviation crashes. Given its simplicity, the FIA risk index should be readily applicable to trauma research and prevention.


Metastatic Ductal Eccrine Adenocarcinoma with Excellent Response to Immunotherapy.
Eccrine carcinoma, a subtype of which is ductal eccrine adenocarcinoma (DEA), is a rare cutaneous malignancy. For metastatic eccrine carcinoma, there are very limited data to guide treatment. Conventional chemotherapy is of limited benefit and there is only a small body of evidence for the use of immunotherapy in non-DEA eccrine carcinomas. We report the first case of metastatic DEA treated with a multimodality approach including surgery, radiotherapy, and immunotherapy, with an excellent prolonged response to pembrolizumab, and provide a review of the literature on pathological and management aspects for this rare tumour subtype. A 60-year-old male with a history of pT1N0M0 left scalp DEA, managed 2 years prior with excision and adjuvant radiotherapy, represented with a symptomatic right pontine metastasis. Imaging demonstrated intracranial, pulmonary, and hilar disease; biopsy of the cranial and lung lesions showed metastatic adenocarcinoma, morphologically similar to the previously resected scalp DEA. The patient was treated with stereotactic resections of his pontine metastases and adjuvant cranial radiotherapy, then commenced on immunotherapy with pembrolizumab. The patient has completed 21 months of pembrolizumab with a significant radiological response of the pulmonary and hilar disease and nil evidence of intracranial recurrence or further metastases. In this case report, we provide the first evidence of efficacy of immunotherapy in metastatic DEA, demonstrating an excellent and prolonged response of metastatic DEA to pembrolizumab. Further research is required to better establish the role of immunotherapy within the management protocol for this uncommon but aggressive tumour subtype.


Steric self-assembly of laterally confined organic semiconductor molecule analogues.
Self-assembly of planar molecules can be a critical route to control morphology in organic optoelectronic systems. In this study, Monte Carlo simulations were performed with polygonal disc analogues to planar semiconducting molecules under confinement. By examining statistically the molecular density and configurations of such analogues, we have observed that the symmetry of the confining medium can have a greater impact on the final densified particle configurations than the intramolecular interactions. Using the steric frustration imparted by confinement, novel self-assembled (partially) ordered phases are available. Our Monte Carlo simulations suggest new avenues to control ordering and morphology of planar molecules, which are critical for high-performance organic optoelectronic devices.


A developmental fMRI study of self-regulatory control in Tourette's syndrome.
Disturbances in the maturation of neural systems that mediate self-regulatory processes may contribute to the development of Tourette's syndrome by releasing motor and vocal tics from regulatory control. The purpose of this study was to examine the age correlates of functional activity in neural circuits that subserve self-regulatory control in children and adults with Tourette's syndrome. The participants were 136 children and adults, which included 66 Tourette's syndrome patients and 70 healthy comparison subjects. During performance of the Stroop interference task, the authors compared the functional magnetic resonance imaging (fMRI) blood-oxygen-level dependent response in patients with Tourette's syndrome with that of healthy comparison subjects. General linear modeling of Stroop-related activations was used to compare the differential effects of age and behavioral performance on changes in self-regulatory control between the two diagnostic groups. Although the correlations of age with behavioral performance on the Stroop task were similar between patients with Tourette's syndrome and healthy comparison subjects, the two groups differed significantly in their correlations of age with the magnitude of regional brain activation during the task. Interactions of age with diagnosis were detected in the ventral prefrontal (Brodmann's areas 10 and 24) and posterior cingulate cortices (Brodmann's area 31), and post hoc analyses indicated that subjects with Tourette's syndrome deactivated these regions less with advancing age. Greater activation of bilateral frontostriatal regions (Brodmann's areas 9/46, 45/46; lenticular nucleus; and thalamus) accompanied poorer performance in the patient group, which-in the presence of normal behavioral performance on the Stroop task-suggests that greater activation of the frontostriatal systems helps to maintain task performance in individuals with Tourette's syndrome. Normative developmental correlates of activity in frontostriatal circuits that subserve self-regulatory control are disturbed in persons with Tourette's syndrome. These aberrant developmental correlates are likely a consequence of greater anatomical and functional disturbances in these circuits in adults with Tourette's syndrome, which leads to impaired regulation of tic behaviors. Reduced default-mode processing in ventral prefrontal and posterior cingulate cortices in adults with Tourette's syndrome suggests the presence of greater difficulty in engaging mental processes that become active when freed from the demands of more challenging cognitive tasks. However, individuals with Tourette's syndrome appear to co-opt normal developmental processes in circuits that subserve age-related improvement in self-regulatory control while presumably struggling to maintain adequate task performance.


Anti-aging effect of fullerenol on skin aging through derived stem cells in a mouse model.
Fullerenol is similar to graphite in terms of structure. In the present study, the anti-aging effect of fullerenol on skin through derived stem cells in a mouse model was assessed and the potential mechanism of fullerenol was investigated. The anti-aging effect of fullerenol effectively inhibited the retention rate of transplanted adipose-derived stem cells and increased the thickness of the dermal portion of skin and collagen ratio in mice. The effect of fullerenol on the proliferation of stem cells was observed. Treatment with fullerenol effectively promoted the mRNA expression of Runt-related transcription factor 2, alkaline phosphatase and osteocalcin in a mouse model of skin aging induced by D-galactose. However, fullerenol treatment effectively suppressed the protein expression of peroxisome proliferator-activated receptor-γ (PPAR-γ) and increased forkhead box protein O1 (FoxO1) protein expression in the mice model of skin aging induced by D-galactose. These results demonstrate that the anti-aging effect of fullerenol on skin through derived stem cells may be mediated in mice via the PPAR-γ/FoxO1 signaling pathway.


Optimization of mass spectrometry-compatible surfactants for shotgun proteomics.
An optimization and comparison of trypsin digestion strategies for peptide/protein identifications by microLC-MS/MS with or without MS compatible detergents in mixed organic-aqueous and aqueous systems was carried out in this study. We determine that adding MS-compatible detergents to proteolytic digestion protocols dramatically increases peptide and protein identifications in complex protein mixtures by shotgun proteomics. Protein solubilization and proteolytic efficiency are increased by including MS-compatible detergents in trypsin digestion buffers. A modified trypsin digestion protocol incorporating the MS compatible detergents consistently identifies over 300 proteins from 5 microg of pancreatic cell lysates and generates a greater number of peptide identifications than trypsin digestion with urea when using LC-MS/MS. Furthermore, over 700 proteins were identified by merging protein identifications from trypsin digestion with three different MS-compatible detergents. We also observe that the use of mixed aqueous and organic solvent systems can influence protein identifications in combinations with different MS-compatible detergents. Peptide mixtures generated from different MS-compatible detergents and buffer combinations show a significant difference in hydrophobicity. Our results show that protein digestion schemes incorporating MS-compatible detergents generate quantitative as well as qualitative changes in observed peptide identifications, which lead to increased protein identifications overall and potentially increased identification of low-abundance proteins.


Association of personality traits with elder self-neglect in a community-dwelling population.
Elder self-neglect is an important public health issue. However, little is known about the association between personality traits and risk of elder self-neglect among community-dwelling populations. The objectives of this study are as follows: 1) to examine the association of personality traits with elder self-neglect and 2) to examine the association of personality traits with elder self-neglect severity. Population-based study conducted from 1993 to 2005 of community-dwelling older adults (N = 9,056) participating in the Chicago Health Aging Project (CHAP). Subsets of the CHAP participants (N = 1,820) were identified for suspected self-neglect by social services agency, which assessed the severity. Personality traits assessed included neuroticism, extraversion, rigidity, and information processing. Logistic and linear regressions were used to assess these associations. In the bivariate analyses, personality traits (neuroticism, extraversion, information processing, and rigidity) were significantly associated with increased risk of elder self-neglect. However, after adjusting for potential confounders, the above associations were no longer statistically significant. In addition, personality traits were not associated with increased risk of greater self-neglect severity. Furthermore, interaction term analyses of personality traits with health and psychosocial factors were not statistically significant with elder self-neglect outcomes. Neuroticism, extraversion, rigidity, and information processing were not associated with significantly increased risk of elder self-neglect after consideration of potential confounders.


Effect of sesame oil on the inhibition of experimental autoimmune encephalomyelitis in C57BL/6 mice.
Sesame oil was evaluated in the treatment of in C57BL/6 mice. It has profound anti-inflammatory activity and been traditionally used to treat inflammatory disorders. EAE was induced by immunization of 6-8 week old mice with MOG(35-55) with complete Freunds adjuvant. Therapy with sesame oil was started on day 3 before the immunization. Total Antioxidant Capacity (TAC) was assessed by Ferric Reducing-antioxidant Power (FRAP) method. Nitric Oxide (NO) production was also estimated by Griess reaction. For histological analysis, mice brain was harvested and sections were stained with Hematoxylin-Eosin. After daily intraperitoneal dosage the sesame oil significantly reduced the clinical symptoms in C57BL/6 mice with EAE. Also, treated mice displayed a significantly delayed disease onset compared with control mice. Sesame oil significantly increased TAC, but it's effect on serum nitrite production was not significant. Typical brain leukocyte infiltration was observed in control mice compared with treated mice. Present results suggest for the first time that sesame oil therapy may be effective in the prevention of symptomatic EAE. This resistance to encephalomyelitis may be associated with inhibition of oxidative stress.


Eat, Sleep, Console Approach or Usual Care for Neonatal Opioid Withdrawal.
Although clinicians have traditionally used the Finnegan Neonatal Abstinence Scoring Tool to assess the severity of neonatal opioid withdrawal, a newer function-based approach - the Eat, Sleep, Console care approach - is increasing in use. Whether the new approach can safely reduce the time until infants are medically ready for discharge when it is applied broadly across diverse sites is unknown. In this cluster-randomized, controlled trial at 26 U.S. hospitals, we enrolled infants with neonatal opioid withdrawal syndrome who had been born at 36 weeks' gestation or more. At a randomly assigned time, hospitals transitioned from usual care that used the Finnegan tool to the Eat, Sleep, Console approach. During a 3-month transition period, staff members at each hospital were trained to use the new approach. The primary outcome was the time from birth until medical readiness for discharge as defined by the trial. Composite safety outcomes that were assessed during the first 3 months of postnatal age included in-hospital safety, unscheduled health care visits, and nonaccidental trauma or death. A total of 1305 infants were enrolled. In an intention-to-treat analysis that included 837 infants who met the trial definition for medical readiness for discharge, the number of days from birth until readiness for hospital discharge was 8.2 in the Eat, Sleep, Console group and 14.9 in the usual-care group (adjusted mean difference, 6.7 days; 95% confidence interval [CI], 4.7 to 8.8), for a rate ratio of 0.55 (95% CI, 0.46 to 0.65; P<0.001). The incidence of adverse outcomes was similar in the two groups. As compared with usual care, use of the Eat, Sleep, Console care approach significantly decreased the number of days until infants with neonatal opioid withdrawal syndrome were medically ready for discharge, without increasing specified adverse outcomes. (Funded by the Helping End Addiction Long-term (HEAL) Initiative of the National Institutes of Health; ESC-NOW ClinicalTrials.gov number, NCT04057820.).


Identification of the phytosphingosine metabolic pathway leading to odd-numbered fatty acids.
The long-chain base phytosphingosine is a component of sphingolipids and exists in yeast, plants and some mammalian tissues. Phytosphingosine is unique in that it possesses an additional hydroxyl group compared with other long-chain bases. However, its metabolism is unknown. Here we show that phytosphingosine is metabolized to odd-numbered fatty acids and is incorporated into glycerophospholipids both in yeast and mammalian cells. Disruption of the yeast gene encoding long-chain base 1-phosphate lyase, which catalyzes the committed step in the metabolism of phytosphingosine to glycerophospholipids, causes an ~40% reduction in the level of phosphatidylcholines that contain a C15 fatty acid. We also find that 2-hydroxypalmitic acid is an intermediate of the phytosphingosine metabolic pathway. Furthermore, we show that the yeast MPO1 gene, whose product belongs to a large, conserved protein family of unknown function, is involved in phytosphingosine metabolism. Our findings provide insights into fatty acid diversity and identify a pathway by which hydroxyl group-containing lipids are metabolized.


[Argon laser trabeculoplasty. Initial results of a prospective study].
This paper presents the results of a prospective study on argon laser trabeculoplasty with clinical application in 166 cases up to now. So far, patients have been followed up for between 2 and 12 months. Low-intensity coagulation was performed over 360 degrees of the trabecular meshwork. The coagulation site within the trabecular meshwork was chosen according to the outflow facility as measured by tonography. In eyes with high outflow facility (C greater than 0.08) the unpigmented, so-called nonfunctioning trabecular meshwork was coagulated. Where the outflow facility was lower (C less than 0.03), a pigmented area of the trabecular meshwork was aimed at. Where the facility was intermediate (0.08 greater than C greater than 0.03) the border area between pigmented and nonpigmented meshwork was coagulated. Three groups of patients were treated: (1) older patients with insufficient compliance; (2) patients whose intraocular pressure (IOP) was poorly controlled by drugs and was under 35 mm Hg; (3) patients suffering from glaucoma in aphakia or status post trabeculectomy and poor control of IOP. Applying these criteria , IOP was controlled in 26.8% without additional drugs and in 68% in combination with local medication after 6 weeks. Very few complications were seen (8 cases), and they did not lead to deterioration or loss of vision. In the light of theoretical considerations and initial histopathologic findings in human eyes, the authors assume that low-intensity coagulation causes a denaturation and shrinkage of the trabecular collagen, leading to stretching of the surrounding trabecular structures.(ABSTRACT TRUNCATED AT 250 WORDS)


[Effect of caffeine on the Ca2+-transport function of sarcoplasmic reticulum vesicles in the rat myocardium].
The effects of caffeine on active transport of Ca2 by heavy and light fractions of rat myocardial microsomes were investigated with the use of a Ca2+-selective electrode and nephelometry. It was found that under the effect of caffeine (5 mM) the rate of Ca2 transport in the presence of oxalate decreased by 30 to 40%. The caffeine-induced inhibition was prevented by ruthenium and tetracaine, thus suggesting the inhibitor specificity. Since caffeine is a specific blocker of Ca2 transport to the terminal cisterns of the skeletal muscle sarcoplasmic reticulum, it is assumed that the microsomal fraction of rat myocardium contains terminal cistern fragments.


[Presence and viability of Giardia spp. and Cryptosporidium spp. in drinking water and wastewater in the high basin of Bogotá river].
Faecal contamination in wastewater and drinking water is linked to the dissemination of water related diseases. The bacteria, virus and parasites present in drinking water are responsible for substantial morbidity and mortality, especially among infants. Giardia spp. and Cryptosporidium spp. were the organisms selected as parasite contamination indicators. Their presence serves as a useful tool for evaluating water quality and determining sanitary risk. At present, in Colombia, concentration and occurrence of these parasites is unknown and an immediate assessment was considered necessary. Protozoan presence was determined in five sampling stations in the Bogotá river upper basin and in two drinking water plants near the same area. The techniques applied for counting encysted forms consisted of inorganic flocculation for wastewater or filtration for drinking water. Fluorogenic vital dyes tested for viability. The presence of Cryptosporidium spp. was confirmed in two of the sampled stations and at two of the drinking water plants. Giardia spp. was found at two of the drinking water plants but not at the sampled stations. Viable cysts were found for Cryptosporidium spp. in one of the samples from the Bogotá river, but only inviable exemplars were obtained from the drinking water plants. The results revealed protozoan presence in drinking and residual water implying the presence of a potential sanitary hazard.


Midtrimester abortion induced by serial intramuscular injections of 15(S)-15-methyl-prostaglandin F2alpha.
Midtrimester abortion was successfully induced in 35 patients by serial intramuscular injections of 15(S)-15-methyl-prostaglandin F2alpha. The dose schedule in this series was an initial injection of 250 mug of 15-ME-PGF2alpha followed by another 250 mug in 2 hours, then 500 mug every 2 hours up to 24 hours; in patients who did not abort within 24 hours the dose was raised to 750 mug every 2 hours until abortion. The mean abortion time was 15.98 hours in this series and 86 per cent of the patients aborted in under 24 hours. Parous patients aborted faster (mean 14.81 hours) than nulliparous patients (mean 17.02 hours) and patients with lower gestational age, 13 to 16 weeks, aborted more quickly (mean 13.98 hours) than patients with gestational age 17 to 20 weeks (mean 16.35). These differences in this series, however, were not statistically significant. Gastrointestinal side effects occurred in 32 of the 35 patients and eight patients had a temperature elevation of more than 1 degree F. during the treatment period. The mean estimated blood loss was 137 plus or minus 42 ml. Thirty patients passed the fetal-placental unit intact, the placenta was removed by sponge forceps in three patients, and by surgical intervention in two patients. There were no failures of technique in this study and none of the patients developed endometritis.


Sudden unexpected death resulting from previously nonsymptomatic subependymoma.
A 34-year-old, previously healthy man died suddenly and unexpectedly. The autopsy showed brain and pulmonary edema, numerous small meningeal meningiomas, bilateral and symmetrical juxtaventricular meningiomas, and a well-demarcated gray tan tumor in the medulla oblongata and upper cervical spinal cord. The latter tumor was a subependymoma with features of ependymoma in places. The authors describe and discuss the characteristics of this rare central nervous system tumor, its histogenesis, and its coexistence with other intracranial tumors. The possible mechanisms of death in the present case include compression of vital centers and acute obstruction of the cerebrospinal fluid flow.


Treatment of FIGO stage IV ovarian carcinoma: results of primary surgery or interval surgery after neoadjuvant chemotherapy: a retrospective study.
The objective of the study is to determine whether surgery influences the outcome of stage IV ovarian cancer. The study design is as follows: From May 1995 to December 2000, 129 patients with FIGO stage IV ovarian cancer, recruited in 42 centers, were prospectively included in GINECO first-line randomized studies of platinum-based regimens with paclitaxel administered simultaneously or sequentially. In all, 109 were eligible for this study. Standard peritoneal cytoreductive surgery was defined as a procedure including at least total hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and peritoneal debulking. Surgery was considered optimal if residual lesions were smaller than 1 cm. The Kaplan-Meier method was used to compare survival. Initial abdominopelvic cytoreductive surgery was considered standard in 55 (54%) patients. Abdominopelvic surgery was optimal in 29 patients and nonoptimal in 26. Twenty-two (22%) patients had a simple biopsy, and 25 (24%) patients underwent substandard surgery. Twenty-two of these 47 patients without initial standard surgery underwent a second surgical procedure, and 17 of the 22 patients completed standard surgery. The median overall survival time in the entire population was 24.3 months (95% confidence interval [CI], 19.5-29.1 months). Patients treated without a cytoreductive surgical procedure had significantly worse median survival (15.1 months; 95% CI, 5.4-24.9 months) than patients who had optimal primary surgery (22.9 months; 95% CI, 15.6-30.1 months), nonoptimal primary surgery (27.1 months; 95% CI, 21.2-32.9 months), or neoadjuvant chemotherapy followed by surgery (45.5 months; 95% CI, 23.5-67.5 months) (P= .001). In conclusion, this study shows a significant benefit of debulking surgery in stage IV ovarian cancer patients who responded to neoadjuvant chemotherapy. Neoadjuvant chemotherapy can help to select patients for surgery.


Management of pulmonary arterial hypertension associated with congenital systemic-to-pulmonary shunts and Eisenmenger's syndrome.
A large proportion of patients with congenital heart disease (CHD), in particular those with relevant systemic-to-pulmonary shunts, will develop pulmonary arterial hypertension (PAH) if left untreated. Persistent exposure of the pulmonary vasculature to increased blood flow, as well as increased pressure, may result in pulmonary obstructive arteriopathy, which leads to increased pulmonary vascular resistance that, if it approaches or exceeds systemic resistance, will result in shunt reversal. Eisenmenger's syndrome, the most advanced form of PAH associated with CHD, is defined as CHD with an initial large systemic-to-pulmonary shunt that induces severe pulmonary vascular disease and PAH, with resultant reversal of the shunt and central cyanosis. The histopathological and pathobiological changes seen in patients with PAH associated with congenital systemic-to-pulmonary shunts, such as endothelial dysfunction of the pulmonary vasculature, are considered similar to those observed in idiopathic or other associated forms of PAH. A pathological and pathophysiological classification of CHD with systemic-to-pulmonary shunt leading to PAH has been developed that includes specific characteristics, such as the type, dimensions and direction of the shunt, extracardiac abnormalities and repair status. A clinically oriented classification has also been proposed. The prevalence of PAH associated with congenital systemic-to-pulmonary shunts in Western countries has been estimated to range between 1.6 and 12.5 cases per million adults, with 25-50% of this population affected by Eisenmenger's syndrome. Clinically, Eisenmenger's syndrome presents with multiple organ involvement, with progressive deterioration of function over time. The signs and symptoms of Eisenmenger's syndrome in the advanced stages include central cyanosis, dyspnoea, fatigue, haemoptysis, syncope and right-sided heart failure. Survival of patients with Eisenmenger's syndrome is clearly less than that of the general population, but appears to be better than that of patients with idiopathic PAH in a comparable functional class. The treatment strategy for patients with PAH associated with congenital systemic-to-pulmonary shunts and, in particular, those with Eisenmenger's syndrome is based mainly on clinical experience rather than being evidence based. General measures include recommendations for physical activity, pregnancy, infections, air travel, exposure to high altitudes and elective surgery, and that psychological assistance be provided as necessary. Phlebotomies are required only when hyperviscosity of the blood is evident, usually when the haematocrit is >65%. The use of supplemental oxygen therapy is controversial and it should be used only in patients in whom it produces a consistent increase in arterial oxygen saturation. Oral anticoagulant treatment with warfarin can be initiated in patients with pulmonary artery thrombosis and absent, or only mild, haemoptysis. The following three classes of drugs targeting the correction of abnormalities in endothelial dysfunction have been approved recently for the treatment of PAH: (i) prostanoids; (ii) endothelin receptor antagonists; and (iii) phosphodiesterase-5 inhibitors. The efficacy and safety of these compounds have been confirmed in uncontrolled studies in patients with PAH associated with corrected and uncorrected congenital systemic-to-pulmonary shunts, as well as in patients with Eisenmenger's syndrome. One randomized controlled trial reported favourable short- and long-term outcomes of treatment with the orally active dual endothelin receptor antagonist bosentan in patients with Eisenmenger's syndrome. Lung transplantation with repair of the cardiac defect or combined heart-lung transplantation are options for Eisenmenger's syndrome patients with a poor prognosis. A treatment algorithm based on the one used in the treatment of PAH patients is proposed for patients with PAH associated with corrected and uncorrected congenital systemic-to-pulmonary shunts and Eisenmenger's syndrome.


Centrosome and retroviruses: the dangerous liaisons.
Centrosomes are the major microtubule organizing structures in vertebrate cells. They localize in close proximity to the nucleus for the duration of interphase and play major roles in numerous cell functions. Consequently, any deficiency in centrosome function or number may lead to genetic instability. Several viruses including retroviruses such as, Foamy Virus, HIV-1, JSRV, M-PMV and HTLV-1 have been shown to hamper centrosome functions for their own profit, but the outcomes are very different. Foamy viruses, HIV-1, JSRV, M-PMV and HTLV-1 use the cellular machinery to traffic towards the centrosome during early and/or late stages of the infection. In addition HIV-1 Vpr protein alters the cell-cycle regulation by hijacking centrosome functions. Enthrallingly, HTLV-1 Tax expression also targets the functions of the centrosome, and this event is correlated with centrosome amplification, aneuploidy and transformation.


Complementary therapies in inflammatory bowel diseases.
Complementary and alternative therapies (CAM) are defined as therapies that are presently not considered part of conventional medical practice. They are termed "complementary" when used in addition to conventional therapies and termed "alternative" when used instead of conventional therapies. CAM includes many different practices, for example Ayurveda, acupuncture or traditional Chinese medicine (TCM), phytotherapy, homeopathy, probiotics and dietary supplements. While some evidence of benefit exists regarding some therapies, for most of these therapeutic approaches, the therapeutic efficacy and safety have not been proven in well-designed scientific studies. However, the use of complementary and alternative medicine among IBD patients is common, and physicians are frequently confronted with questions about their use. As most of the reported studies contain methodological problems, it is often difficult for physicians to inform their patients adequately. Nevertheless, the widespread use of CAM needs to be recognized. Some of these agents exert plausible biological effects in IBD patients and warrant further investigation. Controlled trials in IBD are warranted to show therapeutic benefits and safety of CAM. This review aims to give a brief overview on the current use of various complementary and alternative treatment options in IBD patients.


Characterization of p96h2bk: immunoreaction with an anti-Erk(extracellular-signal-regulated kinase) peptide antibody and activity in Xenopus oocytes and eggs.
We have shown previously that oncogenic Ras induces cell cycle arrest in activated Xenopus egg extracts [Pan, Chen and Lin (1994) J. Biol. Chem. 269, 5968-5975]. The cell cycle arrest correlates with the stimulation of a protein kinase activity that phosphorylates histone H2b in vitro (designated p96(h2bk)) [Chen and Pan (1994) J. Biol. Chem. 269, 28034-28043]. We report here that p96(h2bk) is likely to be p96(ram), a protein of approx. 96 kDa that immunoreacts with a monoclonal antibody (Mk-1) raised against a synthetic peptide derived from a sequence highly conserved in Erk1/Erk2 (where Erk is extracellular-signal-regulated kinase). This is supported by two lines of evidence. First, activation/inactivation of p96(h2bk) correlates with upward/downward bandshifts of p96(ram) in polyacrylamide gels. Secondly, both p96(h2bk) and p96(ram) can be immunoprecipitated by antibody Mk-1. We also studied the activity of p96(h2bk)/p96(ram) in Xenopus oocytes and eggs. p96(h2bk)/p96(ram) was inactive in stage 6 oocytes, was active in unfertilized eggs, and became inactive again in eggs after fertilization. Since stage 6 oocytes are at G2-phase of the cell cycle, unfertilized eggs arrest at M-phase and eggs exit M-phase arrest after fertilization, the results thus indicate that p96(h2bk)/p96(ram) activity is cell cycle dependent. Moreover, microinjection of oncogenic Ras into fertilized eggs at the one-cell stage arrests the embryos at the two-cell stage, and this induced arrest is correlated with an inappropriate activation of p96(h2bk)/p96(ram). The data are consistent with the concept that inappropriate activation of p96(h2bk)/p96(ram) plays a role in the cell cycle arrest induced by oncogenic Ras.


Ultrastructural distribution of DNA and RNA within the nucleolus of human Sertoli cells as seen by molecular immunocytochemistry.
The precise distribution of DNA and RNA within the human Sertoli cell nucleolus has been investigated, at the ultrastructural level, by cytochemical and molecular immunocytochemical techniques. In Sertoli cells, the nucleolar components show a typical spatial distribution. The fibrillar centres are not surrounded by a layer of dense fibrillar component, but come in contact only with strands of dense fibrillar component. These fibrillar parts of strands are the extensions of granular strands connected to a large granular mass. These strands delimit numerous nucleolar interstices in which chromatin fibres are clearly obvious. Using the in situ terminal deoxynucleotidyl transferase/immunogold procedure for detecting DNA, we find evident label exclusively over the chromatin fibres enclosed in the nucleolar interstices and over the fibrillar centres, and no significant label over the dense fibrillar component and granular component of the nucleolus. Furthermore, using the polyadenylate nucleotidyl transferase/immunogold procedure for detecting RNA, we show that label is deposited not only over the granular component and dense fibrillar component, as expected, but also quite obviously over the fibrillar centres. No label is seen over the interstices containing chromatin.


Support, don't punish: Drug decriminalization is harm reduction.
Despite large investments in and policy support for harm reduction including naloxone, syringes, and medications for opioid use disorder, people who use drugs continue to experience unprecedented rates of mortality from overdose and morbidity from infectious diseases. The criminalization of drug use has disproportionately exacerbated these drug-related harms and imposed short- and long-term burdens on already marginalized and vulnerable populations. Pharmacy professionals and students are not immune to the effects of drug criminalization, where one conviction can lead to the loss of their license, employment, or educational progress. Communities become less healthy and stagnate in punitive criminalization systems, further reducing opportunities for growth. Decriminalization of drug use and possession is an urgently needed and effective approach to drug use that shifts resources from punishment to public health, thereby reducing the negative impacts of drug use and keeping communities safe and healthy. Pharmacists play essential roles in the prevention and management of drug misuse and use disorders. As policy makers consider and implement drug decriminalization, pharmacists must actively advocate for these policies and educate community and organizational partners on the individual, professional, and community benefits of this harm reduction strategy.


1,2,4-triazol-3-yl-thiopropyl-tetrahydrobenzazepines: a series of potent and selective dopamine D(3) receptor antagonists.
The discovery of new highly potent and selective dopamine D3 receptor antagonists has recently permitted characterization of the role of the dopamine D3 receptor in a wide range of preclinical animal models. A novel series of 1,2,4-triazol-3-yl-thiopropyl-tetrahydrobenzazepines demonstrating a high level of D3 affinity and selectivity with an excellent pharmacokinetic profile is reported here. In particular, the pyrazolyl derivative 35 showed good oral bioavailability and brain penetration associated with high potency and selectivity in vitro. In vivo characterization of 35 confirmed that this compound blocks the expression of nicotine- and cocaine-conditioned place preference in the rat, prevents nicotine-triggered reinstatement of nicotine-seeking behavior in the rat, reduces oral operant alcohol self-administration in the mouse, increases extracellular levels of acetylcholine in the rat medial prefrontal cortex, and potentiates the amplitude of the relative cerebral blood volume response to d-amphetamine in a regionally specific manner in the rat brain.


Controlling outbreak of vancomycin-resistant Enterococcus faecium among infants caused by an endemic strain in adult inpatients.
Vancomycin-resistant Enterococcus faecium (VREfm) is commonly associated with hospital outbreaks and has been found to be associated with increased morbidity, mortality, length of stay, and health care costs. We sought to investigate and control an outbreak of VREfm in the neonatal intensive care unit (NICU) of a public academic hospital with a level III NICU. The index case was an infant in the NICU incidentally identified with urinary colonization with VREfm. Aggressive control measures were initiated promptly. Investigation included active surveillance cultures in infants, parents of colonized infants, and birth mothers of newborn admitted to NICU; molecular strain typing of available isolates of VREfm including adult inpatients; and medical record review. After identification of index case, 13 additional infants were identified with VREfm colonization. Age at culture was 6 to 87 days; birth weight was 1,070 to 2,834 g. VREfm isolated from majority of infants (12/14 [85.7%]), the birth mother of a pair of colonized twins, and a pulse oximeter device used in adult inpatients belonged to a single strain. Outbreak control measures were successful in the NICU. The outbreak-causing strain was found to be endemic among adult inpatients. Adult patients with the outbreak-causing strain of VREfm were more likely to have received previous therapy with meropenem (Mann-Whitney 2-tailed P value = .038). VRE colonization was identified in 0.3% (1/310) of birth mothers with newborn admitted to NICU. An endemic strain of VREfm among adult inpatients was responsible for a subsequently controlled outbreak in the NICU.


X-ray structure analysis of the iron-dependent superoxide dismutase from Mycobacterium tuberculosis at 2.0 Angstroms resolution reveals novel dimer-dimer interactions.
The X-ray structure of the tetrameric iron-dependent superoxide dismutase from Mycobacterium tuberculosis has been refined to an R-factor of 0.167 and a correlation coefficient of 0.954 at 2.0 A resolution. The crystals are monoclinic P2(1) and have four subunits related by strong non-crystallographic 222 (or D2) symmetry in the asymmetric unit. 198 of the 207 amino acids of each subunit are defined by the electron density which shows that they adopt the conserved fold of other iron- or manganese-dependent SODs. The structure can be divided into two domains, the N-terminal domain involving an extended region followed by two projecting antiparallel alpha-helices, and the C-terminal domain containing four more helical segments with a three-stranded antiparallel beta-sheet inserted sequentially between the fourth and fifth helices. The catalytic iron is co-ordinated by five ligands: three histidines (residues 28, 76 and 164), one aspartate (160) and a solvent molecule. The inferred positions of protons at the active site are consistent with the solvent ligand being a hydroxide ion. This ligand interacts with His145 in the Mycobacterium tuberculosis SOD. In the highly homologous Mycobacterium leprae Mn-SOD, the histidine is replaced by glutamine, this being the only significant residue difference within 10 A of the Fe3+. The nature of the amino acid at this position may influence the metal ion specificity of these enzymes. The subunits of the Mycobacterium tuberculosis SOD associate by polar contacts to form dimers, which closely resemble those of other dimeric or tetrameric Fe- or Mn-SODs. However, the dimer-dimer interactions within the tetramer are novel, being dominated by dimerisation of the 144 to 152 loop regions which connect the outer two beta-strands of the three-membered beta-sheet. This contrasts strongly with the other tetrameric Fe- or Mn-SODs where the dimer-dimer association is dominated by the projecting alpha alpha-turn in the N-terminal domain.


Poverty transitions in severe mental illness: longitudinal analysis of social drift in China, 1994-2015.
Although poverty associated with severe mental illness (SMI) has been documented in many studies, little long-term evidence of social drift exists. This study aimed to unravel the poverty transitions among persons with SMI in a fast change community in China. Two mental health surveys, using the International Classification of Disease (ICD-10), were conducted in the same six townships of Xinjin county, Chengdu, China in 1994 and 2015. A total of 308 persons with SMI identified in 1994 were followed up in 2015. The profiles of poverty transitions were identified and regression modelling methods were applied to determine the predictive factors of poverty transitions. The poverty rate of persons with SMI increased from 39.9% to 49.4% in 1994 and 2015. A larger proportion of them had fallen into poverty (27.3%) rather than moved out of it (17.8%). Those persons with SMI who had lost work ability, had physical illness and more severe mental disabilities in 1994, as well as those who had experienced negative changes on these factors were more likely to live in persistent poverty or fall into poverty. Higher education level and medical treatment were major protective factors of falling into poverty. This study shows long-term evidence on the social drift of persons with SMI during the period of rapid social development in China. Further targeted poverty alleviation interventions should be crucial for improving treatment and mental recovery and alleviating poverty related to SMI.


Organochlorines, perfluoroalkyl substances, mercury, and egg incubation temperature in an Arctic seabird: Insights from data loggers.
In birds, incubation-related behaviors and brood patch formation are influenced by hormonal regulation such as prolactin secretion. Brood patch provides efficient heat transfer between the incubating parent and the developing embryo in the egg. Importantly, several environmental contaminants are already known to have adverse effects on avian reproduction. However, relatively little is known about the effect of contaminants on incubation temperature (Tinc ) in wild birds. By using temperature thermistors placed into artificial eggs, we investigated whether the most contaminated parent birds are less able to provide appropriate egg warming and thus less committed to incubating their clutch. Specifically, we investigated the relationships among 3 groups of contaminants (organochlorines, perfluoroalkyl substances [PFASs], and mercury [Hg]) with Tinc and also with prolactin concentrations and brood patch size in incubating Arctic black-legged kittiwakes (Rissa tridactyla). Our results reveal that among the organochlorines considered, only blood levels of oxychlordane, the main metabolite of chlordane, a banned pesticide, were negatively related to the minimum incubation temperature in male kittiwakes. Levels of PFASs and Hg were unrelated to Tinc in kittiwakes. Moreover, our study suggests a possible underlying mechanism: since we reported a significant and negative association between blood oxychlordane concentrations and the size of the brood patch in males. Finally, this reduced Tinc in the most oxychlordane-contaminated kittiwakes was associated with a lower egg hatching probability. Environ Toxicol Chem 2018;37:2881-2894. © 2018 SETAC.


Ocular manifestations of Blau syndrome.
This article summarizes the systemic and ocular manifestations of Blau syndrome, its genetic basis, and reviews recently published literature. A large multicenter prospective case series is underway, with 3-year preliminary results indicating the prevalence of uveitis, clinical characteristics and early data on its visual prognosis. Case reports have demonstrated the successful use of newer biologic agents. Blau syndrome is an exceedingly rare autoinflammatory disorder with skin, joint and eye manifestations. It is caused by autosomal dominant mutations of the NOD2 protein. Eye involvement is typically a chronic bilateral granulomatous iridocyclitis, often with multifocal choroiditis in the posterior segment. Treatment starts with topical and systemic steroids and often requires antimetabolites or biologic agents.