The molecular underpinnings of totipotency.
Embryonic stem (ES) cells are characterized by their functional potency and capacity to self-renew in culture. Historically, ES cells have been defined as pluripotent, able to make the embryonic but not the extraembryonic lineages (such as the yolk sac and the placenta). The functional capacity of ES cells has been judged based on their ability to contribute to all somatic lineages when they are introduced into an embryo. However, a number of recent reports have suggested that under certain conditions, ES cells, and other reprogrammed cell lines, can also contribute to the extraembryonic lineages and, therefore, can be said to be totipotent. Here, we consider the molecular basis for this totipotent state, its transcriptional signature and the signalling pathways that define it.


Flat-panel conebeam CT in the clinic: history and current state.
Research into conebeam CT concepts began as soon as the first clinical single-slice CT scanner was conceived. Early implementations of conebeam CT in the 1980s focused on high-contrast applications where concurrent high resolution ( < 200 μ m ), for visualization of small contrast-filled vessels, bones, or teeth, was an imaging requirement that could not be met by the contemporaneous CT scanners. However, the use of nonlinear imagers, e.g., x-ray image intensifiers, limited the clinical utility of the earliest diagnostic conebeam CT systems. The development of consumer-electronics large-area displays provided a technical foundation that was leveraged in the 1990s to first produce large-area digital x-ray detectors for use in radiography and then compact flat panels suitable for high-resolution and high-frame-rate conebeam CT. In this review, we show the concurrent evolution of digital flat panel (DFP) technology and clinical conebeam CT. We give a brief summary of conebeam CT reconstruction, followed by a brief review of the correction approaches for DFP-specific artifacts. The historical development and current status of flat-panel conebeam CT in four clinical areas-breast, fixed C-arm, image-guided radiation therapy, and extremity/head-is presented. Advances in DFP technology over the past two decades have led to improved visualization of high-contrast, high-resolution clinical tasks, and image quality now approaches the soft-tissue contrast resolution that is the standard in clinical CT. Future technical developments in DFPs will enable an even broader range of clinical applications; research in the arena of flat-panel CT shows no signs of slowing down.


Effects of Influenza Vaccination on the Response to BNT162b2 Messenger RNA COVID-19 Vaccine in Healthcare Workers.
Vaccine-induced immunity is at present the main strategy to stop the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Recent evidences suggested a protective effect of influenza vaccination against coronavirus disease 2019 (COVID-19) severity, while impact on the immune response to BNT162b2 messenger RNA (mRNA) vaccine is under investigation. We aimed to evaluate this aspect in a cohort of 297 healthcare workers (108 males, 189 females) after seasonal influenza vaccination compared to no-flu-vaccination. VAX+ (165 individuals; 63 males and 102 females) had tetravalent influenza vaccine, and VAX- (132 individuals; 45 males and 87 females) had no flu vaccination. Anti-spike-receptor binding domain (RBD) level was tested 15 - 70 days after BNT162b2 second inoculum. Increased antibody response was observed in total VAX+ compared to VAX- (2,047.4 vs. 1,494.2 binding antibody unit (BAU)/mL, P = 0.0039), independently from gender and body mass index (BMI). Younger total individuals (< 35 years) showed significant increase of the level of binding antibodies (2,184.8 vs. 1,590.9 BAU/mL, P = 0.0038) compared to ≥ 35 years; young/old difference was lost restricting to VAX+ subgroup. Flu vaccinations appear associated to better antibody response in older individuals (P = 0.027, ≥ 35 years VAX+ vs. VAX-). A decreasing trend during time was observed for both VAX+ and VAX-, except for < 35 years VAX- individuals. Early response was higher in VAX+ compared to VAX-; however a more rapid waning was observed in VAX+ subjects. Our data showed better antibody response to SARS-CoV-2 vaccine in subjects already vaccinated against seasonal influenza; this may represent one of the mechanisms underlying the cross-protective effects of influenza vaccination against heterologous infections reported in recent epidemiological studies.


[Epidemiological study and clinical analysis of 931 children with hand foot and mouth disease in Yantai].
To discuss the epidemiological and clinical characteristics of the hospitalized children with hand foot and mouth disease (HFMD) in Yantai area. Epidemiological and clinical data of HFMD children from 2009 to 2010 were summarized and analyzed retrospectively. Most of the infected (94.6%) were under 5 years old and the ratio between male and female was 1.5: 1. Oral mucosal pox or ulcer as well as hand and foot rashes were observed in all 931 patients. Fever and neurological disorders occurred in 840 (90.2%) and 121 (13.0%) patients respectively. The incidence was positively correlated with air temperature (r = 0.887, P < 0.001), with a peak in April to September (88.9%). The ratio of children from countryside, total duration of fever, serum concentration of c-reacting protein (CRP) and fasting blood glucose (FBG) were significantly higher in severe cases than in those mild ones. Multivariate analysis showed longer mean duration of fever( Odds ratio [OR], 1.491; 95% confidence interval [ CI] 1.170-1.901; P = 0.001) and hyperglycemia (OR, 1.124; 95% CI 1.016-1.245; P = 0.024) were independent risk factors of severity. Children younger than 5 years old are susceptible to HFMD and most cases occur in April to September. The monthly incidence is positively correlated with temperature of that month. Longer duration of fever and hyperglycemia are independent risk factors for severity. Most cases could have a favorable prognosis after timely diagnosis and proper intervention.


A novel method for live imaging of human airway cilia using wheat germ agglutinin.
Multiciliated epithelial cells in the airway are essential for mucociliary clearance. Their function relies on coordinated, metachronal and directional ciliary beating, appropriate mucus secretion and airway surface hydration. However, current conventional methods for observing human airway ciliary movement require ciliated cells to be detached from airway tissues. Determining the directionality of cilia is difficult. We developed a novel method to stain airway epithelial cilia to observe their movement without releasing ciliated cells. Human tracheae were obtained from patients (n = 13) who underwent laryngectomies to treat malignancies or swallowing disorders. The tracheae were treated with fluorescently labeled wheat germ agglutinin, which interacts with the acidic mucopolysaccharides present on the cilia. Epithelial surfaces were observed using an epi-fluorescence microscope equipped with a water-immersion objective lens and a high-speed camera. Ciliary movement was observable at 125 fps (13/13 samples). Ciliated cells in close proximity mostly exhibited well-coordinated ciliary beats with similar directionalities. These findings indicated that wheat germ agglutinin renders ciliary beats visible, which is valuable for observing human airway ciliary movements in situ.


A molecular signature in blood identifies early Parkinson's disease.
The search for biomarkers in Parkinson's disease (PD) is crucial to identify the disease early and monitor the effectiveness of neuroprotective therapies. We aim to assess whether a gene signature could be detected in blood from early/mild PD patients that could support the diagnosis of early PD, focusing on genes found particularly altered in the substantia nigra of sporadic PD. The transcriptional expression of seven selected genes was examined in blood samples from 62 early stage PD patients and 64 healthy age-matched controls. Stepwise multivariate logistic regression analysis identified five genes as optimal predictors of PD: p19 S-phase kinase-associated protein 1A (odds ratio [OR] 0.73; 95% confidence interval [CI] 0.60-0.90), huntingtin interacting protein-2 (OR 1.32; CI 1.08-1.61), aldehyde dehydrogenase family 1 subfamily A1 (OR 0.86; 95% CI 0.75-0.99), 19 S proteasomal protein PSMC4 (OR 0.73; 95% CI 0.60-0.89) and heat shock 70-kDa protein 8 (OR 1.39; 95% CI 1.14-1.70). At a 0.5 cut-off the gene panel yielded a sensitivity and specificity in detecting PD of 90.3 and 89.1 respectively and the area under the receiving operating curve (ROC AUC) was 0.96. The performance of the five-gene classifier on the de novo PD individuals alone composing the early PD cohort (n = 38), resulted in a similar ROC with an AUC of 0.95, indicating the stability of the model and also, that patient medication had no significant effect on the predictive probability (PP) of the classifier for PD risk. The predictive ability of the model was validated in an independent cohort of 30 patients at advanced stage of PD, classifying correctly all cases as PD (100% sensitivity). Notably, the nominal average value of the PP for PD (0.95 (SD = 0.09)) in this cohort was higher than that of the early PD group (0.83 (SD = 0.22)), suggesting a potential for the model to assess disease severity. Lastly, the gene panel fully discriminated between PD and Alzheimer's disease (n = 29). The findings provide evidence on the ability of a five-gene panel to diagnose early/mild PD, with a possible diagnostic value for detection of asymptomatic PD before overt expression of the disorder.


Nanoscale range finding of subsurface structures by measuring the absolute phase lag of thermal wave.
The need for a subsurface imaging technique to locate and characterize subsurface defects in multidimensional micro- and nanoengineered devices has been growing rapidly. We show that a subsurface heater can be located accurately using the phase lag of a thermal wave. We deduce that the absolute phase lag is composed of four components. Among the four components, we isolate the component directly related to the position and the structure of the periodic heat source. We demonstrate that the position of the heater can be estimated accurately from the isolated phase lag component.


Craniovertebral junction: normal anatomy, craniometry, and congenital anomalies.
The craniovertebral junction (CVJ) comprises the occiput, atlas, and axis and is visible in most magnetic resonance (MR) imaging studies of the brain. Craniometric measurements used in radiologic assessment of CVJ anomalies include the Chamberlain line, Wackenheim clivus baseline, Welcher basal angle, and atlantooccipital joint axis angle. Most anomalies of the occiput are associated with decreased skull base height and basilar invagination, the latter being a primary developmental anomaly in which the vertebral column is abnormally high and prolapsed into the skull base. Occiput anomalies include condylus tertius, condylar hypoplasia, basiocciput hypoplasia, and atlanto-occipital assimilation. Most atlas anomalies produce no abnormal CVJ relationships and are not associated with basilar invagination. These anomalies include aplasias, hypoplasias, and clefts of the atlas arches and "split atlas" (ie, posterior arch rachischisis associated with anterior arch rachischisis). Except for fusion anomalies, abnormalities of the axis are primarily confined to the odontoid process and are not associated with basilar invagination. These anomalies include persistent ossiculum terminale, odontoid aplasia, and os odontoideum. With the widespread availability of MR imaging, which is well suited for evaluating the CVJ because of its direct sagittal imaging capabilities, renewed understanding of CVJ anatomy and anomalies is important for all radiologists.


Synergism between atracurium and mivacurium compared with that between vecuronium and mivacurium.
Synergism exists between some combinations of nondepolarizing muscle relaxants. To test the possibility of synergism between mivacurium and atracurium or vecuronium, 60 children anesthetized with propofol-alfentanil-N2O-O2 were randomized to one of five groups. Three groups of 10 patients each received an ED50 dose of a parent drug atracurium (A), vecuronium (V), or mivacurium (M), respectively, and two other groups of 15 patients each received a single-dose combination of atracurium with mivacurium (cAM) or vecuronium with mivacurium (cVM). Dose combinations constituted 0.5 times an ED50 dose of each drug. Neuromuscular response was monitored by adductor pollicis electromyogram (EMG). Maximum neuromuscular block (NMB) established by a single parent drug did not differ between the groups or from 50% NMB. It averaged 5.03 +/- 0.12 probits (51.2% NMB). On the contrary, maximum NMB established by the two-dose combinations, cAM or cVM, was significantly more than NMB produced by either single parent drug of the particular combination (cAM vs A or M; P = 0.0035, and cVM vs V or M; P = 0.0004) without a statistically significant difference between groups cAM and cVM. Maximum NMB established by combinations averaged 6.15 +/- 0.21 probits (87.5% NMB). The onset of maximum NMB for mivacurium was significantly faster compared to that for atracurium or for vecuronium (2.8 +/- 0.3 vs 5.7 +/- 0.4 or 4.0 +/- 0.3 min, respectively; P = 0.0001). Our results indicate that both drug combinations are synergistic even though only vecuronium is markedly different in its molecular structure from mivacurium.


[Development of technologies of population health management in Kazakhstan based on an integrated assessment of the combined exposure to environmental factors].
At present there is overdue necessity of an integral approach to the assessment of health status and the impact of environmental factors on it, in the development of science-based management decisions and programs on improvement of the health status of the population of Kazakhstan and in the increase in life expectancy from the birth and healthy life expectancy. The purpose of the proposed program--improving health and increasing life expectancy from the birth and healthy life expectancy of the population of Kazakhstan. Based on a meta-analysis to justify the target age group in which an implementation of complex of preventive measures will increase both the life expectancy from the birth and healthy life expectancy, to perform a comprehensive health screening for the basic classes of diseases and behavioral characteristics of the target group in the course of a multicentre studies to give a comprehensive hygienic characteristics of the ecological status of the studied regions and to develop the Health Passport of the region, to develop a model of the combined effects of environmental factors on health; to create a theoretical model for the calculation of life expectancy from the birth and healthy life expectancy, taking into account the limits of modifiability of factors that affect them, and justify a comprehensive program of management decisions on modification of factors, to carry out pilot studies on the development and validation technological (managemental) solutions to control modifiable factors that affect life expectancy from the birth and healthy life expectancy.


Novel AlkB dioxygenases--alternative models for in silico and in vivo studies.
ALKBH proteins, the homologs of Escherichia coli AlkB dioxygenase, constitute a direct, single-protein repair system, protecting cellular DNA and RNA against the cytotoxic and mutagenic activity of alkylating agents, chemicals significantly contributing to tumor formation and used in cancer therapy. In silico analysis and in vivo studies have shown the existence of AlkB homologs in almost all organisms. Nine AlkB homologs (ALKBH1-8 and FTO) have been identified in humans. High ALKBH levels have been found to encourage tumor development, questioning the use of alkylating agents in chemotherapy. The aim of this work was to assign biological significance to multiple AlkB homologs by characterizing their activity in the repair of nucleic acids in prokaryotes and their subcellular localization in eukaryotes. Bioinformatic analysis of protein sequence databases identified 1943 AlkB sequences with eight new AlkB subfamilies. Since Cyanobacteria and Arabidopsis thaliana contain multiple AlkB homologs, they were selected as model organisms for in vivo research. Using E. coli alkB(-) mutant and plasmids expressing cyanobacterial AlkBs, we studied the repair of methyl methanesulfonate (MMS) and chloroacetaldehyde (CAA) induced lesions in ssDNA, ssRNA, and genomic DNA. On the basis of GFP fusions, we investigated the subcellular localization of ALKBHs in A. thaliana and established its mostly nucleo-cytoplasmic distribution. Some of the ALKBH proteins were found to change their localization upon MMS treatment. Our in vivo studies showed highly specific activity of cyanobacterial AlkB proteins towards lesions and nucleic acid type. Subcellular localization and translocation of ALKBHs in A. thaliana indicates a possible role for these proteins in the repair of alkyl lesions. We hypothesize that the multiplicity of ALKBHs is due to their involvement in the metabolism of nucleo-protein complexes; we find their repair by ALKBH proteins to be economical and effective alternative to degradation and de novo synthesis.


Biochemical characterization and distribution of glutathione S-transferases in leaping mullet (Liza saliens).
In this study, feral leaping mullet (Liza saliens) liver cytosolic glutathione S-transferases (GSTs) were investigated and characterized using 1-chloro-2,4-dinitrobenzene (CDNB) and ethacrynic acid (EA) as substrates. The average GST activities towards CDNB and EA were found to be 1365 +/- 41 and 140 +/- 20 nmol/min per mg protein, respectively. The effects of cytosolic protein amount and temperature ranging from 4 to 70 degrees C on enzyme activities were examined. While both activities towards CDNB and EA showed similar dependence on protein amount, temperature optima were found as 37 and 42 degrees C, respectively. In addition, the effects of pH on GST-CDNB and -EA activities were studied and different pH activity profiles were observed. For both substrates, GST activities were found to obey Michaelis-Menten kinetics with apparent V(max) and K(m) values of 1661 nmol/min per mg protein and 0.24 mM and 157 nmol/min per mg protein and 0.056 mM for CDNB and EA, respectively. Distribution of GST in Liza saliens tissues was investigated and compared with other fish species. Very high GST activities were measured in tissues from Liza saliens such as liver, kidney, testis, proximal intestine, and gills. Moreover, our results suggested that GST activities from Liza saliens would be a valuable biomarker for aquatic pollution.


Analysis of paediatric medical cases admitted to Children's Clinic Benin City.
Until the Paediatric Ward at the University of Benin Teaching Hospital was commissioned in August, 1973, the Children's Clinic of the Specialist Hospital, Benin City was the only unit for specialised treatment of sick children. From June 1972 when the Clinic was opened to May 1973 (12 month period)--56,000 children aged from a few days to 15 years were treated. 4720 (8.5%) of the total seen were admitted and 212 (4.5%) of total admission died. The average age for both children admitted and those who died was 2 years. While the average for in-patient care was 4 days, that for children who died was 2 days. So called tropical diseases except malarial infection and sickle cell anaemia were not common. The three commonest diagnoses were Enteritis, Respiratory infections and malaria.


Cerebral vasculitis--recognition, diagnosis and management.
Cerebral vasculitis is a serious but uncommon condition which presents considerable difficulties in recognition, diagnosis and treatment. We studied eight consecutive patients in whom this diagnosis was made. Despite the great diversity of symptoms and signs, we noted three clinical patterns: (i) acute or sub-acute encephalopathy, (ii) a picture with some similarities to multiple sclerosis ('MS-plus'), and (iii) features of a rapidly progressive space-occupying lesion. The identification of these patterns may help recognition of cerebral vasculitis. The diagnostic value of four investigative procedures not previously studied in cerebral vasculitis was assessed: ophthalmological examination using low-dose fluorescein angiography with slit-lamp video microscopy of the anterior segment (abnormal in 4/5 patients); spinal fluid oligoclonal band analysis (abnormal in 3/6 patients); anti-neutrophil cytoplasmic antibody assay (abnormal in 3/8 patients); and indium-labelled white-cell cerebral imaging (positive in only one patient). Treatment was with steroid alone (n = 2) or steroid with cyclophosphamide (n = 6). Seven patients responded clinically.


A New Microwave Shield Preparation for Super High Frequency Range: Occupational Approach to Radiation Protection.
Widespread use of X-band frequency (a part of the super high frequency microwave) in the various workplaces would contribute to occupational exposure with potential of adverse health effects. According to limited study on microwave shielding for the workplace, this study tried to prepare a new microwave shielding for this purpose. We used EI-403 epoxy thermosetting resin as a matrix and nickel oxide nanoparticle with the diameter of 15-35 nm as filler. The Epoxy/ Nickel oxide composites with 5, 7, 9 and 11 wt% were made in three different thicknesses (2, 4 and 6 mm). According to transmission / reflection method, shielding effectiveness (SE) in the X-band frequency range (8-12.5 GHz) was measured by scattering parameters directly given by the 2-port Vector Network Analyzer. The fabricated composites characterized by X-ray Diffraction and Field Emission Scanning Electron Microscope. The best average of shielding effectiveness in each thickness of fabricated composites obtained by 11%-2 mm, 7%-4 mm and 7%-6 mm composites with SE values of 46.80%, 66.72% and 64.52%, respectively. In addition, the 11%-6 mm, 5%-6 mm and 11%-4 mm-fabricated composites were able to attenuate extremely the incident microwave energy at 8.01, 8.51 and 8.53 GHz by SE of 84.14%, 83.57 and 81.30%, respectively. The 7%-4mm composite could be introduced as a suitable alternative microwave shield in radiation protection topics in order to its proper SE and other preferable properties such as low cost and weight, resistance to corrosion etc. It is necessary to develop and investigate the efficacy of the fabricated composites in the fields by future studies.


Do footedness and strength asymmetry relate to the dominant stance in swimming track start?
This study explored the relationship between lower limb asymmetry and stance preference in the swimming track start. Track start performances and asymmetry measures were collected from 11 male and 11 female competitive age group swimmers. The track start performance was defined as the time taken to reach the 5-m mark. Asymmetry measures included assessment of footedness using the revised version of the Waterloo Footedness Questionnaire and assessment of performance asymmetry in the one-legged countermovement jump. Participants performed five trials on each side of both the one-legged countermovement jump and the track start, and the best three trials of each were compared. Asymmetry was declared when at least two trials from one side were better than the contralateral side. While the majority of the participants produced better performances using the preferred track start stance, it was not related to footedness or the dominant limb for the one-legged countermovement jump. Further investigation is required to identify factors that predict the lateralised behaviour of the track start, and determine whether changing the stance would provide significant advantage.


Recurrence of cutaneous Mycobacterium chelonae infection: A case report.
Mycobacterium chelonae is a species of mycobacteria that can be found ubiquitously in the environment. It can be found in soil, water, and in aquatic animals. Infections with this pathogen usually involve the soft tissues, eyes, bones, and skin. We present the case of a recurrence of a sporotrichoid cutaneous infection by M. chelonae in an immunocompromised 31-year-old woman with systemic lupus erythematosus. The patient originally developed a swelling of her right foot followed by a sporotrichoid pattern of infection on her right lower leg. A susceptibility profile was established, and treatment with linezolid and clarithromycin was administered for 8 months, in accordance with guidelines from the American Thoracic Society. The patient was clear of new lesions for approximately 1 month before noting a re-emergence. Treatment with linezolid and clarithromycin was re-initiated with subsequent improvement. This case underlines the need for prolonged treatment of this infection in patients with an immunocompromised status.


Reactive oxygen species-responsive mitochondria-targeted liposomal quercetin attenuates retinal ischemia-reperfusion injury via regulating SIRT1/FOXO3A and p38 MAPK signaling pathways.
Retinal ischemia-reperfusion (RIR) injury is involved in the pathogenesis of various vision-threatening diseases. The overproduction of reactive oxygen species (ROS) is thought to be the main cause of RIR injury. A variety of natural products, including quercetin (Que), exhibit potent antioxidant activity. However, the lack of an efficient delivery system for hydrophobic Que and the presence of various intraocular barriers limit the effective retinal delivery of Que in clinical settings. In this study, we encapsulated Que into ROS-responsive mitochondria-targeted liposomes (abbreviated to Que@TPP-ROS-Lips) to achieve the sustained delivery of Que to the retina. The intracellular uptake, lysosome escape ability, and mitochondria targeting ability of Que@TPP-ROS-Lips were evaluated in R28 retinal cells. Treating R28 cells with Que@TPP-ROS-Lips significantly ameliorated the decrease in ATP content, ROS generation, and increase in the release of lactate dehydrogenase in an in vitro oxygen-glucose deprivation (OGD) model of retinal ischemia. In a rat model, the intravitreal injection of Que@TPP-ROS-Lips 24 h after inducing retinal ischemia significantly enhanced retinal electrophysiological recovery and reduced neuroinflammation, oxidative stress, and apoptosis. Que@TPP-ROS-Lips were taken up by retina for at least 14 days after intravitreal administration. Molecular docking and functional biological experiments revealed that Que targets FOXO3A to inhibit oxidative stress and inflammation. Que@TPP-ROS-Lips also partially inhibited the p38 MAPK signaling pathway, which contributes to oxidative stress and inflammation. In conclusion, our new platform for ROS-responsive and mitochondria-targeted drug release shows promise for the treatment of RIR injury and promotes the clinical application of hydrophobic natural products.


Modulating electronic structure of metal-organic frameworks by introducing atomically dispersed Ru for efficient hydrogen evolution.
Developing high-performance electrocatalysts toward hydrogen evolution reaction is important for clean and sustainable hydrogen energy, yet still challenging. Herein, we report a single-atom strategy to construct excellent metal-organic frameworks (MOFs) hydrogen evolution reaction electrocatalyst (NiRu0.13-BDC) by introducing atomically dispersed Ru. Significantly, the obtained NiRu0.13-BDC exhibits outstanding hydrogen evolution activity in all pH, especially with a low overpotential of 36 mV at a current density of 10 mA cm-2 in 1 M phosphate buffered saline solution, which is comparable to commercial Pt/C. X-ray absorption fine structures and the density functional theory calculations reveal that introducing Ru single-atom can modulate electronic structure of metal center in the MOF, leading to the optimization of binding strength for H2O and H*, and the enhancement of HER performance. This work establishes single-atom strategy as an efficient approach to modulate electronic structure of MOFs for catalyst design.


Kinetic and spectroscopic properties of the YZ* radical in Ca2+- and Cl--depleted photosystem II preparations.
Depletion of Ca2+ and/or Cl- ions from PSII membranes blocks the electron-transfer reactions that precede O2 evolution on the oxidizing side of the enzyme. Illumination of these inhibited preparations at 273 K generates a paramagnetic species that is detectable by low-temperature (T < 20 K) EPR as a signal in the g = 2 region, 90-230 G wide, depending on the treatment that PSII has undergone. This signal has recently been assigned to YZ* in magnetic interaction with the manganese cluster in its S2 state [Gilchrist et al. (1995) Proc. Natl. Acad. Sci. U.S.A. 92, 9545-9549]. This view, however, is not universal, owing, in part, to the fact that its spectroscopic properties depend on the preparation and the experimental conditions used for its study and, in part, to uncertainties as to the room temperature behavior of YZ* in inhibited preparations. Here, we report time-resolved and conventional EPR data showing that, at room temperature and at 273 K, YZ* can be accumulated in its 20 G form in high yields in both Ca2+-depleted and acetate-inhibited preparations, and that the kinetics of its decay match the decay kinetics of the low-temperature signal generated in corresponding samples. The properties of the YZ* signal, however, are shown to depend on the polypeptide content, the temperature, and the electron donors and acceptors present in the sample under examination. Our results support assignment of the EPR signal in inhibited preparations to S2 YZ* and demonstrate a protective role of the 17 and 23 kDa extrinsic polypeptides for the manganese cluster against externally added reductants.


Determination of average glandular dose with modern mammography units for two large groups of patients.
Until recently, for mammography Mo anode-Mo filter x-ray tube assemblies were almost exclusively used. Modern mammography units provide the possibility to employ a variety of anode-filter combinations with the aim of adapting the x-ray spectrum to compressed breast thickness and composition. The present contribution provides information on the radiation exposure of two large groups of patients (one of 1678 and one of 945 women) who were mammographed with modern x-ray equipment, and on the dosimetry necessary for the evaluation. For dosimetric purposes spectral information is essential. X-ray spectra have been determined for various anode-filter combinations from measurements with a Ge detector. Based on these spectra, conversion factors from air kerma free in air to average glandular dose (g factors) have been calculated for different anode-filter combinations, compressed breast thickness ranging from 2 to 9 cm and breast compositions varying from 0 to 100% glandular tissue. Determinations of various quantities, including entrance surface air kerma (ESAK), tube output, tube loading (TL), fraction of glandular tissue (FGL) and compressed breast thickness, were made during actual mammography. Average glandular dose (AGD) was determined using g factors corrected for tissue composition as well as g values for standard breast composition, i.e. 50% adipose tissue and 50% glandular tissue by mass. It is shown that, on average, the influence of the actual breast composition causes variations of the order of about 15%. For group 1 and group 2, the mean values of average glandular dose (using g factors corrected for tissue composition) were 1.59 and 2.07 mGy respectively. The number of exposures per woman was on average 3.4 and 3.6 respectively. The mean value of compressed breast thickness was 55.9 and 50.8 mm respectively. The mean age of group 1 was 53.6 years (for group 2 the age was not recorded). The fraction by mass of glandular tissue FGL decrease with increasing compressed breast thickness and age of patient (from 75% at 25 mm to 20% at 80 mm, and from 65% at 20 years to 30% at 75 years). For a medium-sized breast, i.e. a compressed breast thickness of 55 mm, FGL is about 35%, indicating that the standard mix (FGL = 50%) might need some modification, particularly because of additional evidence from another investigation with similar results on FGL.


Changes in medical education: the community perspective.
The societal and economic forces driving change in medical education are affecting communities as well as universities. Each of the four authors of this paper is deeply involved in one of the components of their locale's well-developed community-based medical educational system, and each describes how change is influencing his role in that system, whether the role be managing a community hospital, directing a local Area Health Education Center, participating as a family medicine faculty member, or being a community preceptor. They agree on some common themes: (1) that it is good that medical students' education is moving into the community (e.g., this validates the importance of the community hospital to medical education, is an acknowledgment of the importance of generalism, and provides students invaluable learning experiences); (2) that educating medical students in the community is expensive, and more funding and resources are needed so that the area's hospitals, community faculty, preceptors, and support services can be fairly compensated for their commitment; and (3) that their community-based education system can no longer absorb the costs of training more medical students. This is not a criticism of academic medical centers, which are under tremendous financial pressures themselves, but is simply to state the community perspective and to urge fairness in the distribution of resources for medical education. Community institutions and academic medical centers will work individually to create their own integrated health care systems but must work together to create a better, more cost-effective system for educating medical students.


[The role of mitochondrial calcium overload and energy deficiency in pathogenesis of arterial hypertension].
The author proceeds that increased arterial blood (BP) pressure, reflecting the shift of the threshold blood pressure controlling system, is conditioned by underlying energy deficiency at the cellular level, caused by a decrease of the mitochondrial energy generating function. Elevation of systemic BP in hyperthyroidism resultant from oxidation-phosphorylation uncoupling, leading to decrease of ATP production by mitochondria, is an example of energy dependence of the hypertension phenomenon. In primary hypertension (essential hypertension in humans and spontaneous hypertension in rats) one can speak about genetically determined characteristics of cell membranes (so-called membrane defect) leading to insufficient regulation of intracellular calcium and increased concentrations of free calcium in the cytosol under physiological actions on cell calcium homeostasis mechanisms. Elevation of BP mediated by increased efferent sympathetic activity occurs as far as the excess of the cytosolic calcium accumulates in the mitochondria and their energy generating function decreases, which results in alteration of the ion transporting function of cell membranes. Hence, increased systemic BP in primary hypertension should be considered as an inherent feature of circulation corresponding to altered cell energetics.


Temporal Evolution of Multiday, Epileptic Functional Networks Prior to Seizure Occurrence.
Epilepsy is one of the most common neurological disorders, characterized by the occurrence of repeated seizures. Given that epilepsy is considered a network disorder, tools derived from network neuroscience may confer the valuable ability to quantify the properties of epileptic brain networks. In this study, we use well-established brain network metrics (i.e., mean strength, variance of strength, eigenvector centrality, betweenness centrality) to characterize the temporal evolution of epileptic functional networks over several days prior to seizure occurrence. We infer the networks using long-term electroencephalographic recordings from 12 people with epilepsy. We found that brain network metrics are variable across days and show a circadian periodicity. In addition, we found that in 9 out of 12 patients the distribution of the variance of strength in the day (or even two last days) prior to seizure occurrence is significantly different compared to the corresponding distributions on all previous days. Our results suggest that brain network metrics computed fromelectroencephalographic recordings could potentially be used to characterize brain network changes that occur prior to seizures, and ultimately contribute to seizure warning systems.


A systematic review and dose-response meta-analysis of exposure to environmental selenium and the risk of type 2 diabetes in nonexperimental studies.
Accumulating evidence from both experimental and nonexperimental human studies in the last 15 years indicates that exposure to high levels of the trace element selenium increases the risk of type 2 diabetes. However, the relation of dose to effect is not well understood because randomized controlled trials used only one dose (200 μg/day) of selenium supplementation. While no new trial on this topic has been published since 2018, several nonexperimental studies have appeared. We therefore updated a previous meta-analysis to include recently published observational studies, and incorporated the recently developed one-stage random-effects model to display the dose-response relation between selenium and type 2 diabetes. We retrieved 34 potentially eligible nonexperimental studies on selenium and diabetes risk up to April 15, 2021. The bulk of the evidence indicates a direct relation between blood, dietary and urinary levels of selenium and risk of diabetes, but not with nail selenium, which may be considered a less reliable biomarker. The association was nonlinear, with risk increasing above 80 μg/day of dietary selenium. Whole blood/plasma/serum selenium concentrations of 160 μg/L corresponded to a risk ratio of 1.96 (95% CI 1.27-3.03) compared with a concentration of 90 μg/L (approximately 60 μg of daily selenium intake). The cohort studies, which are less susceptible to reverse causation bias, indicated increased risk for both blood and urine selenium levels and dietary selenium intake, whereas no such pattern emerged from studies relying on nail selenium content. Overall, the nonexperimental studies agree with findings from randomized controlled trials, indicating that moderate to high levels of selenium exposure are associated with increased risk for type 2 diabetes.


Surface phonons, elastic response, and conformal invariance in twisted kagome lattices.
Model lattices consisting of balls connected by central-force springs provide much of our understanding of mechanical response and phonon structure of real materials. Their stability depends critically on their coordination number z. d-dimensional lattices with z = 2d are at the threshold of mechanical stability and are isostatic. Lattices with z < 2d exhibit zero-frequency "floppy" modes that provide avenues for lattice collapse. The physics of systems as diverse as architectural structures, network glasses, randomly packed spheres, and biopolymer networks is strongly influenced by a nearby isostatic lattice. We explore elasticity and phonons of a special class of two-dimensional isostatic lattices constructed by distorting the kagome lattice. We show that the phonon structure of these lattices, characterized by vanishing bulk moduli and thus negative Poisson ratios (equivalently, auxetic elasticity), depends sensitively on boundary conditions and on the nature of the kagome distortions. We construct lattices that under free boundary conditions exhibit surface floppy modes only or a combination of both surface and bulk floppy modes; and we show that bulk floppy modes present under free boundary conditions are also present under periodic boundary conditions but that surface modes are not. In the long-wavelength limit, the elastic theory of all these lattices is a conformally invariant field theory with holographic properties (characteristics of the bulk are encoded on the sample boundary), and the surface waves are Rayleigh waves. We discuss our results in relation to recent work on jammed systems. Our results highlight the importance of network architecture in determining floppy-mode structure.


[The effect of inactivity-induced osteoporosis on the scintigraphic image of bone lesions of the wrist].
In addition to its established oncological indications the sensitivity of bone scintigraphy is of steadily increasing significance in traumatology. Inactivity-induced osteoporosis plays a major role during the immobilization period in the plaster cast. In the region of the joints remodelling intensity may reach such a high level that the non-injured bone shows a higher rate of accumulation than the fracture. This process already begins between the third and fourth week of immobilization. The highest uptake is found after fracture of the scaphoid bone at the end of twelve weeks of immobilization. Control scintigraphies at intervals of several days are indicated to differentiate between various clinical conditions (pseudoarthrosis, activated osteoarthrosis, algodystrophy in case of doubtful x-ray results).


Prospective study of the serum Aspergillus-specific IgG, IgA and IgM assays for chronic pulmonary aspergillosis diagnosis.
Chronic pulmonary aspergillosis (CPA) is an underdiagnosed and misdiagnosed disease and now increasingly recognised. However, the diagnosis of CPA remains challenging. In this study, we aimed to investigate the diagnostic values of serum Aspergillus-specific IgG, IgA and IgM antibodies in patients with CPA. The prospective study was performed at Chinese People's Liberation Army General Hospital in Beijing, from January 2017 to December 2017. Adult patients with lung lesions presented as cavity, nodule, mass, bronchiectasis or severe fibrotic destruction with at least two lobes in CT imaging were enrolled. One hundred healthy persons were also enrolled as additional controls. The serum levels of Aspergillus-specific IgG, IgA and IgM antibodies and galactomannan (GM) levels were measured simultaneously by plate ELISA kit. A total of 202 patients were enrolled in this study, including 42 CPA patients, 60 non-CPA patients and 100 healthy persons. The most common underlying lung diseases in CPA patients were bronchiectasis (28.6%) and COPD (19.0%). The most common symptoms in the CPA patients were cough (76.2%), sputum (71.4%), and fever (45.2%); chest pain (4.8%) was infrequent. Receiver operating characteristic (ROC) curve analysis revealed that the optimal CPA diagnostic cut-off of Aspergillus-specific IgG, IgA and IgM assays and GM test were 89.3 AU/mL, 8.2 U/mL, 73.3 AU/mL and 0.5μg/L, respectively. The serum levels of Aspergillus-specific IgG and IgA in CPA patients were higher than these in non-CPA patients or healthy persons. The sensitivities and specificities of Aspergillus-specific IgG, IgA, IgM tests and GM test were 78.6 and 94.4%, 64.3 and 89.4%, 50.0 and 53.7% and 71.4 and 58.1%, respectively. The sensitivity and specificity of serum Aspergillus-specific IgG assay are satisfactory for diagnosing CPA, while the performance of Aspergillus-specific IgA assay is moderate. Aspergillus-specific IgM assay and serum GM test have limited value for CPA diagnosis. NCT03027089 . Registered 20 January 2017.


Modality specific functional interaction in sensorimotor synchronization.
Movement execution strongly relies on precise sensorimotor synchronization. In a finger-tapping task that requires subjects to synchronize their finger taps to regular pacing signal synchronization accuracy varies with respect to pacing signal's modality. This study aimed at elucidating functional brain dynamics associated with modality specific behavioral synchronization accuracy. To this end, 10 right-handed subjects performed a finger-tapping task with respect to regular auditory and visual pacing, respectively, whereas neuromagnetic activity was recorded using a 122-channel whole-head neuromagnetometer. Visual pacing was associated with significantly reduced tap-to-pacer asynchrony and increased intertap variability as compared to auditory pacing. The brain dynamics associated with task execution were analyzed using the frequency domain beamformer approach dynamic imaging of coherent sources (DICS). Both tasks were shown to be associated with comparable networks. However, during visual pacing involvement of the ventral premotor cortex (PMv) was shown, whereas during auditory pacing the dorsal premotor cortex (PMd) was concerned with task execution. Synchronization with respect to visual pacing was associated with significantly increased functional interaction between thalamus and PMv at beta frequency as compared to functional interplay between thalamus and PMd during auditory pacing. Auditory synchronization was associated with increased functional interaction between left superior temporal gyrus and PMd at alpha frequency. Furthermore, functional interaction between thalamus and premotor cortex at beta frequency was significantly correlated with synchronization accuracy. All in all the present data suggest that modality specific synchronization differences are associated with frequency and connectivity specific changes of functional interaction in distinct brain networks.


The Added Value of Dynamic 18F-Florbetapir PET in the Assessment of Dementia With Lewy Bodies.
Dementia with Lewy bodies (DLB) is the most common cause of dementia after Alzheimer disease. It is often underdiagnosed because of the overlapping with Alzheimer disease symptoms. We report the F-FDG and F-florbetapir dynamic PET images (early and delay phases) of an 83-year-old woman with cognitive impairment associated with visual hallucinations and parkinsonism due to probable DLB. This image highlights that the early phases of F-florbetapir may reflect regional cerebral perfusion with a pattern very similar to that of regional glucose metabolism in DLB.


Interleukin-10 controls the protective effects of circulating microparticles from patients with septic shock on tissue-engineered vascular media.
During sepsis, inflammation can be orchestrated by the interaction between circulating and vascular cells that, under activation, release MPs (microparticles). Previously, we reported that increased circulating MPs in patients with sepsis play a pivotal role in ex vivo vascular function suggesting that they are protective against vascular hyporeactivity. The present study was designed to investigate the effects of MPs from patients with sepsis on the contractile response of TEVM (tissue-engineered vascular media). TEVM that were composed only of a media layer were produced by tissue engineering from human arterial SMCs (smooth muscle cells) isolated from umbilical cords. TEVM was incubated with MPs isolated from whole blood of 16 patients with sepsis. TEVM were incubated for 24 h with MPs and used for the study of vascular contraction, direct measurements of NO and O2- (superoxide anion) production by EPR and quantification of mRNA cytokine expression. MPs from patients with sepsis increased contraction induced by histamine in TEVM. This effect was not associated with inflammation, neither linked to the activation of NF-κB (nuclear factor κB) pathway nor to the increase in iNOS (inducible NO synthase) and COX (cyclo-oxygenase)-2 expression. In contrast, mRNA expression of IL (interleukin)-10 was enhanced. Then, we investigated the effect of IL-10 on vascular hyporeactivity induced by LPS (lipopolysaccharide). Although IL-10 treatment did not modify the contractile response in TEVM by itself, this interleukin restored contraction in LPS-treated TEVM. In addition, IL-10 treatment both prevented vascular hyporeactivity induced by LPS injection in mice and improved survival of LPS-injected mice. These findings show an association between the capacity of MPs from patients with sepsis to restore vascular hyporeactivity induced by LPS and their ability to increase IL-10 in the tissue-engineered blood vessel model.


Occurrence and distribution of yellow grub trematodes (Clinostomum complanatum) infection in Taiwan.
Digenetic trematodes of the genus Clinostomum are widely distributed in many species of freshwater fish and are known to cause the zoonotic disease Halzoun. Humans may become accidental hosts if they ingest raw freshwater fish containing metacercaria of Clinostomum complanatum, which causes pharyngitis or laryngitis. The yellow grub parasitizing cultivated ayu (Plecoglossus altivelis) and loach (Misgurnus anguillicaudatus) was one of the most serious problems in fish farms from 1977 to 1979 in Taiwan. The present study revealed, for the first time, frequent occurrence of C. complanatum metacercaria in various fish species in a natural environment, the Dahan River, in Taiwan. We examined 1503 fish specimens belonging to four families and 162 snails representing six species. C. complanatum metacercaria was mainly from the fish family Cyprinidae, and only cercaria from the snail Radix swinhoei was recovered. The prevalence and mean intensity of metacercaria were 9.8% and 9.35 parasites/infected fish, respectively. The prevalence of cercaria was low, 0.62%, in snails. Acrossocheilus paradoxus, Zacco barbata, Zacco pachycephalus, Zacco platypus, Onychostoma barbatula, and Hemibarbus labeo are new host records. Metacercariae were primarily found in the operculum, mandible, muscle, and oral cavity of fish. Morphological description and molecular analysis with 18S rDNA sequencing allowed for rapidly identifying C. complanatum. Encysted and excysted metacercariae cultivated at 22 °C in physiological saline died within 60 h. The mean intensity of infection increased with an increasing length of Z. pachycephalus. We found no association between monthly parasite prevalence and mean intensity at each sampling location. No C. complanatum metacercaria survived after 8 h of salting. The Dahan River has suitable conditions and hosts (snails, fish, and fish-eating birds) for maintaining the life cycle of C. complanatum.


Purinergic GPCR-integrin interactions drive pancreatic cancer cell invasion.
Pancreatic ductal adenocarcinoma (PDAC) continues to show no improvement in survival rates. One aspect of PDAC is elevated ATP levels, pointing to the purinergic axis as a potential attractive therapeutic target. Mediated in part by highly druggable extracellular proteins, this axis plays essential roles in fibrosis, inflammation response, and immune function. Analyzing the main members of the PDAC extracellular purinome using publicly available databases discerned which members may impact patient survival. P2RY2 presents as the purinergic gene with the strongest association with hypoxia, the highest cancer cell-specific expression, and the strongest impact on overall survival. Invasion assays using a 3D spheroid model revealed P2Y2 to be critical in facilitating invasion driven by extracellular ATP. Using genetic modification and pharmacological strategies, we demonstrate mechanistically that this ATP-driven invasion requires direct protein-protein interactions between P2Y2 and αV integrins. DNA-PAINT super-resolution fluorescence microscopy reveals that P2Y2 regulates the amount and distribution of integrin αV in the plasma membrane. Moreover, receptor-integrin interactions were required for effective downstream signaling, leading to cancer cell invasion. This work elucidates a novel GPCR-integrin interaction in cancer invasion, highlighting its potential for therapeutic targeting.


Design and evaluation of a prosthesis control system based on the concept of extended physiological proprioception.
This paper describes the design and evaluation of an experimental prosthesis-control system based on the concept of extended physiological proprioception (EPP). It was originally hypothesized that EPP control effected by residual shoulder motion could be effectively applied in multifunctional prostheses for shoulder disarticulation amputees. The experimental system developed for this study utilized a force-driven control scheme and a shoulder motion transduction system in which direct cable linkages to the prosthesis components were used to implement EPP position-servo relationships between shoulder elevation-depression and prosthesis elbow flexion, and between shoulder protraction-retraction and prosthesis wrist rotation. The results of experiments performed with this prosthesis (and with an experimental velocity-controlled prosthesis implemented for comparison purposes) clearly demonstrated the superior performance provided by EPP control of prosthesis function.


The role of self-efficacy, recovery self-efficacy, and preparatory planning in predicting short-term smoking relapse.
This study aims to identify the role of self-efficacy, recovery self-efficacy, and preparatory planning with regard to short-term smoking relapse. We also assessed whether the importance of these variables differed for smokers quitting individually and without help (self-quitters) and smokers quitting with the help of a smoking cessation course (group quitters). A longitudinal quasi-experimental study with follow-ups at 1 and 3 months after the quit attempt was conducted in order to assess the role of baseline self-efficacy, recovery self-efficacy, and preparatory planning on short-term relapse. The recruitment included adult daily smokers (N= 121), quitting in a smoking cessation course (N= 57) and self-quitters (N= 64). Respondents received internet-based questionnaires 2 weeks before quitting (baseline) and 1 and 3 months after the quit attempt. Predictors of relapse were analysed using logistic regression analyses. Relapse at 1 and 3 months after the quit attempt was predicted by low levels of baseline self-efficacy. Simple slope analyses revealed that less preparatory planning significantly predicted relapse at 1 month after the quit attempt among group quitters, but not among self-quitters. Recovery self-efficacy was only predictive of relapse after 1 month when self-efficacy was excluded from the analyses. Moreover, among group quitters, the results indicated a borderline significant curved relation between recovery self-efficacy and relapse after 1 month. Our results suggest that more research is needed on the role of preparatory planning and recovery self-efficacy. Moreover, we recommend incorporating self-efficacy increasing techniques in relapse-prevention interventions.


Australian parents' use of universal child and family health services: A consumer survey.
This study aimed to explore Australian parents' use of universally available well-child health services. It used an online survey of 719 parents of children aged from birth to 5 years in all states and territories to examine patterns of service use and consumer preferences. In Australia, several health professional groups provide advice to pregnant women, infants, children, and parents, offering health promotion, developmental screening, parenting support, and referral to specialist health services if required. The survey examined parents' use of different child and family health providers, and their preferences for support with several common parenting issues. The study indicated that families with young children obtain primary healthcare from a range of service providers, often more than one, depending on children's ages and needs. Parents frequently visit general practitioners for immunisation and medical concerns. They attend dedicated child and family health nurses for parenting advice and well-child checks and prefer them as an information source for many health issues. However, a substantial proportion of parents (44.1%) do not currently visit a child and family health nurse, often because they not only do not perceive a need but also sometimes because these services are unknown, inaccessible, or considered unsuitable. They may seek advice from less qualified sources. There is potential for increased collaboration between child and family health providers to ensure effective resource use and consistency of parenting information and advice. Nursing services may need to address accessibility and appropriateness of care.


Association of SLC6A12 variants with aspirin-intolerant asthma in a Korean population.
Aspirin-intolerant asthma (AIA) occurs from asthma exacerbation after exposure to aspirin. However, the underlying mechanisms of AIA occurrence are still unclear. The critical role of the solute carrier family 6 (neurotransmitter transporter, betaine/GABA) member 12 (SLC6A12) gene in GABAergic transmission, which is associated with mucus production in asthma, makes it a candidate gene for AIA association study. Eight single nucleotide polymorphisms (SNPs) in SLC6A12 were genotyped in 163 aspirin-intolerant asthma (AIA) and 429 aspirin-tolerant asthma (ATA) patients of Korean ethnicity. Associations between polymorphisms of SLC6A12 and AIA were analysed using multivariate logistic analysis. Results showed that two polymorphisms and a haplotype in SLC6A12, rs499368 (P= 0.005; P(corr)= 0.03), rs557881 (non-synonymous C10R, P= 0.007; P(corr)= 0.04), and SLC6A12_BL1_ht1 (P= 0.009; P(corr)= 0.05) respectively, were significantly associated with AIA after multiple testing corrections. In addition, SNPs of SLC6A12 were significantly associated with the fall rate of FEV(1) by aspirin provocation suggesting that SLC6A12 could affect reversibility of lung function abnormalities in AIA patients. Although these results are preliminary and future replications are needed to confirm these findings, this study showed evidence of association between variants in SLC6A12 and AIA occurrence among asthmatics in a Korean population.


CtsR, a novel regulator of stress and heat shock response, controls clp and molecular chaperone gene expression in gram-positive bacteria.
clpP and clpC of Bacillus subtillis encode subunits of the Clp ATP-dependent protease and are required for stress survival, including growth at high temperature. They play essential roles in stationary phase adaptive responses such as the competence and sporulation developmental pathways, and belong to the so-called class III group of heat shock genes, whose mode of regulation is unknown and whose expression is induced by heat shock or general stress conditions. The product of ctsR, the first gene of the clpC operon, has now been shown to act as a repressor of both clpP and clpC, as well as clpE, which encodes a novel member of the Hsp100 Clp ATPase family. The CtsR protein was purified and shown to bind specifically to the promoter regions of all three clp genes. Random mutagenesis, DNasel footprinting and DNA sequence deletions and comparisons were used to define a consensus CtsR recognition sequence as a directly repeated heptad upstream from the three clp genes. This target sequence was also found upstream from clp and other heat shock genes of several Gram-positive bacteria, including Listeria monocytogenes, Streptococcus salivarius, S. pneumoniae, S. pyogenes, S. thermophilus, Enterococcus faecalis, Staphylococcus aureus, Leuconostoc oenos, Lactobacillus sake, Lactococcus lactis and Clostridium acetobutylicum. CtsR homologues were also identified in several of these bacteria, indicating that heat shock regulation by CtsR is highly conserved in Gram-positive bacteria.


Anticonvulsant drugs and bone metabolism.
The influence of chronic antiepileptic treatment on bone metabolism has been investigated in 52 adult epileptics, who had normal dietary intake, sunlight exposure and daily living activities. None of the patients had symptoms or signs suggestive of osteomalacia. Serum phosphate levels were significantly decreased and serum alkaline phosphatase levels were significantly increased in the patients compared with matched controls. Calcitonin values and bone mineral content, measured by single photon absorptiometry, were significantly lower among anticonvulsant users. Calcium metabolism impairment grossly correlated to the number of drugs concurrently used by the patient but not to the types, to the relative plasma concentrations or to the overall duration of the treatment. Our findings indicate that in ambulatory patients with adequate diet and outdoor activities in Italy present with clinically irrelevant impairment of bone metabolism.


Statins: Pharmacokinetics, Pharmacodynamics and Cost-Effectiveness Analysis.
Cardiovascular diseases secondary to atherosclerosis are the primary causes of early death and disability worldwide and dyslipidaemia represents one of the most important modifiable risk factors. Among lipid abnormalities that define it, low-density lipoprotein cholesterol (LDL-C) is the primary target of therapy, since multiple randomized controlled trials have shown the positive impact of its reduction on atherosclerosis development. For their ability to lower LDL-C levels, statins are the most studied drugs in cardiovascular disease prevention, of proven utility in slowing the progression or even determining regression of atherosclerosis. In addition, they have ancillary proprieties, with positive effects on the mechanisms involved in the development of atherosclerosis and cardiovascular morbidity and mortality, the so-called "pleiotropic mechanisms". Although sharing the same mechanism of action, the different chemical and pharmacological characteristics of each kind of statins affect their absorption, bioavailability, plasma protein binding properties, excretion and solubility. In this overview, we analysed pharmacokinetic and pharmacodynamic mechanisms of this class of drugs, specifying the differences among the molecules, along with the economic aspects. Detailed knowledge of characteristics and differences of each kind of available statin could help the physician in the correct choice, based also on patient's clinical profile, of this essential tool with a demonstrated high cost-effectiveness both in primary than in the secondary prevention of cardiovascular disease.


Drug cue induced overshadowing: selective disruption of natural reward processing by cigarette cues amongst abstinent but not satiated smokers.
Addicts show both reward processing deficits and increased salience attribution to drug cues. However, no study to date has demonstrated that salience attribution to drug cues can directly modulate inferences of reward value to non-drug cues. Associative learning depends on salience: a more salient predictor of an outcome will 'overshadow' a less salient predictor of the same outcome. Similarly, blocking, a demonstration that learning depends on prediction error, can be influenced by the salience of the cues employed. This study investigated whether salient drug cues might interact with neutral cues predicting financial reward in an associative learning task indexing blocking and overshadowing in satiated smokers (n=24), abstaining smokers (n=24) and non-smoking controls (n=24). Attentional bias towards drug cues, craving and expired CO were also indexed. Abstaining smokers showed drug cue induced overshadowing, attributing higher reward value to drug cues than to neutral cues that were equally predictive of reward. Overshadowing was positively correlated with expired CO levels, which, in turn, were correlated with craving in abstainers. An automatic attentional bias towards cigarette cues was found in abstainers only. These findings provide the first evidence that drug cues interact with reward processing in a drug dependent population.


Hepatotoxicity associated with statins.
Treatment with statins is known all over the world. They are generally considered safe at therapeutic doses. Nevertheless, clinical trials are not enough to assess their scarce adverse effects such as idiosyncratic drug induced liver injury (DILI). Due to some conditions, such as concomitant usage (drug-drug interaction using an identical metabolising enzyme) and genetic polymorphisms, there is an increasing concern about their safety. Hepatotoxicity and rhabdomyolysis have begun to appear in published studies. Most of investigations have focused on both these adverse effects and mechanisms of drug induced toxicity. The present review has attempted to compile almost all of the existing studies on the hepatotoxicity of statins but not rhabdomyolysis. The aim of our study is to provide an overview of the studies on the statin-associated hepatotoxicity and to discuss the published studies. The researchers are of the opinion that the research on this topic is incomplete but extremely necessary.


Direct evidence of trophic interactions among apex predators in the Late Triassic of western North America.
Hypotheses of feeding behaviors and community structure are testable with rare direct evidence of trophic interactions in the fossil record (e.g., bite marks). We present evidence of four predation, scavenging, and/or interspecific fighting events involving two large paracrocodylomorphs (='rauisuchians') from the Upper Triassic Chinle Formation (∼220-210 Ma). The larger femur preserves a rare history of interactions with multiple actors prior to and after death of this ∼8-9-m individual. A large embedded tooth crown and punctures, all of which display reaction tissue formed through healing, record evidence of a failed attack on this individual. The second paracrocodylomorph femur exhibits four unhealed bite marks, indicating the animal either did not survive the attack or was scavenged soon after death. The combination of character states observed (e.g., morphology of the embedded tooth, 'D'-shaped punctures, evidence of bicarination of the marking teeth, spacing of potentially serial marks) indicates that large phytosaurs were actors in both cases. Our analysis of these specimens demonstrates phytosaurs targeted large paracrocodylomorphs in these Late Triassic ecosystems. Previous distinctions between 'aquatic' and 'terrestrial' Late Triassic trophic structures were overly simplistic and built upon mistaken paleoecological assumptions; we show they were intimately connected at the highest trophic levels. Our data also support that size cannot be the sole factor in determining trophic status. Furthermore, these marks provide an opportunity to start exploring the seemingly unbalanced terrestrial ecosystems from the Late Triassic of North America, in which large carnivores far outnumber herbivores in terms of both abundance and diversity.


The effect of response biases on resolution thresholds of Sloan letters in central and paracentral vision.
Sloan letters are one of the most commonly used optotypes in clinical practice. Sloan letters have different relative legibility which could be due to three factors: perceivability, response bias, and similarity. Similarities between Sloan letters are known to be the major source of errors in threshold determination. However, little is known about the effect of response biases on the resolution thresholds. The aim of the present study was to investigate the effect of response bias and similarity on resolution thresholds of Sloan letters in central and paracentral vision. Eight subjects with normal ocular health participated in this study. Using the method of constant stimuli, we measured resolution thresholds for the Sloan letters set at 0° (central) and ± 3° eccentricity along the vertical meridian of the visual field. We calculated thresholds from data pooled across the 10 Sloan letters (pooled threshold). For further analysis we also calculated thresholds for each of the 10 Sloan letters (individual threshold). Response biases and letter similarities were determined using Luce's choice model. Results showed statistically significant differences between the mean individual thresholds of Sloan letters at the central and the upper visual field, but not at the lower visual field. For equally-sized letters at pooled threshold, unlike letter similarity, response biases showed statistically significant correlations to the differences in individual thresholds at the central, upper and lower visual field locations. For equally legible letters at individual thresholds, response biases and similarities showed no significant correlations to the differences in individual thresholds at the central, the upper and the lower visual field locations. These results suggest that, for equally-sized letters at pooled threshold, the response biases may lead to an underestimation of the pooled threshold, i.e. an overestimation of visual acuity measurements when using Sloan letters.


Growth and body composition of Meishan and Yorkshire barrows and gilts.
Five barrows and five gilts of each of two breeds (Meishan [Ms] and Yorkshire [Y]) were slaughtered at birth and at 41, 71, 123, and 171 d of age and five gilts of each breed were slaughtered at 260 d of age. Major organ and visceral weights were obtained immediately postmortem (PM), whereas carcass characteristics, carcass composition, femur measurements, and two individual muscle weights were obtained 24 h PM. Linear and quadratic regression coefficients on age differed between the two breeds, in favor of Y barrows and gilts, for live weight, carcass weight, longissimus muscle area (LMA), liver, heart, spleen, and kidney weights, and femur cross-sectional, medullary, and cortical areas (P < .001), leaf fat weight, and percentage of body fat and protein. In contrast to somatic tissue, Ms gilts had uteri and ovaries that grew faster than those of Y gilts from birth to 260 d of age (P < .05), although the uterus and ovary weights were similar for both breeds by 260 d of age (P < .05). Regression coefficients differed (P < .05) between the two sexes for live, carcass, liver, lung and trachea, stomach and esophagus and leaf fat weights, dressing percentage, percentage of body protein, 10th rib backfat (TRBF) thickness (P < .001), and small intestine, kidney (P < .01), heart, and spleen weights (P < .05). Breed differences in regression coefficients differed between the two sexes for percentage of body protein and leaf fat weights (P < .05). Yorkshire pigs were larger, later-maturing pigs that grew faster from birth to 171 d of age. Yorkshire pigs slaughtered at 171 d of age had heavier total wholesale cut (WC), trimmed cut (TC), and boneless cut (BC) weights than did Ms pigs of the same age (P < .001).


Effects of Omega-3 Fatty Acid Supplementation on Serum Biomarkers, Inflammatory Agents, and Quality of Life of Patients on Hemodialysis.
Patients on long-term hemodialysis are at a higher risk of cardiovascular disease and premature mortality. It is generally believed that omega-3 supplementation can prevent cardiovascular events due to its anti-inflammatory and anti-atherosclerotic effects. Fifty-two hemodialysis patients were divided into 2 groups to receive omega-3 and placebo for 6 six months. Serum biomarkers and inflammatory agents were measured in both groups before and after the intervention. Quality of life was also assessed before and after the trial using the Kidney Disease Quality of Life-Short Form questionnaire. Patients who received omega-3 showed an increase in serum calcium level (P = .005), a decrease in vascular cell adhesion molecule (P = .04), and an increase in the high-density lipoprotein cholesterol level (P < .001), while such changes were not documented in the control group. However, omega-3 administration did not have a significant effect on serum levels of albumin, low-density lipoprotein cholesterol, or triglyceride. Quality of life scores were improved after treatment with omega-3 in both scopes of general and kidney-specific assessment (P = .37 and P = .20, respectively), while no similar changes were seen in the control group. Our data showed beneficial effects of omega-3 supplementation during chronic hemodialysis on inflammatory processes and also quality of life. We suggest administration of omega-3 in the hemodialysis community in a preventive manner for improvement of cardiovascular events and quality of life.


Rapid-high, syncytium-inducing isolates of human immunodeficiency virus type 1 induce cytopathicity in the human thymus of the SCID-hu mouse.
Clinical deterioration in human immunodeficiency virus type 1 (HIV-1) disease is associated with an increased viral burden in the peripheral blood and a loss of circulating CD4+ T cells. HIV-1 isolates obtained prior to this stage of disease often have a "slow-low," non-syncytium-inducing (NSI) phenotype, whereas those obtained afterwards are often characterized as "rapid-high" and syncytium inducing (SI). Paired NSI and SI isolates from two different patients were inoculated into the human thymus implants of SCID-hu mice. The two slow-low, NSI isolates replicated to minimal levels in the grafts and did not induce thymocyte depletion. In contrast, the two SI isolates from the same patients showed high levels of viral replication and induced a marked degree of thymocyte depletion, accompanied by evidence of programmed cell death. These observations reveal a correlation between the replicative and cytopathic patterns of HIV-1 isolates in vitro and in the SCID-hu mouse in vivo and provide direct evidence that the biological phenotype of HIV-1 switch may be a causal and not a derivative correlate of HIV-1 disease progression.


Antioxidant vitamin supplementation in Crohn's disease decreases oxidative stress. a randomized controlled trial.
We showed previously that patients with Crohn's disease (CD) had increased oxidative stress and lower antioxidant vitamins compared with healthy controls. This is despite inactive or mildly active disease and maintenance therapy. The aim of this study was to evaluate in these patients the effects of antioxidant vitamin supplementation on oxidative stress. This is a randomized controlled trial where stable but oxidatively stressed CD subjects (n = 57) were supplemented with vitamins E (800 IU) and C (1000 mg) or their placebo for 4 wk. Oxidative stress measured by breath pentane and ethane output, plasma lipid peroxides, and F2-isoprostane was assessed at baseline and at 4 wk. Disease activity was also monitored by measuring CD activity index and plasma orosomucoid. During supplementation, plasma vitamin C and alpha-tocopherol increased and all indices of oxidative stress decreased significantly. Disease activity remained stable. In this population, vitamin E and C supplementation resulted in a significant reduction in oxidative stress. This suggests that patients with inactive or mildly active CD can be oxidatively stressed and have increased requirement in antioxidant vitamins.


The Incidence of Abortion in Nigeria.
Because of Nigeria's low contraceptive prevalence, a substantial number of women have unintended pregnancies, many of which are resolved through clandestine abortion, despite the country's restrictive abortion law. Up-to-date estimates of abortion incidence are needed. A widely used indirect methodology was used to estimate the incidence of abortion and unintended pregnancy in Nigeria in 2012. Data on provision of abortion and postabortion care were collected from a nationally representative sample of 772 health facilities, and estimates of the likelihood that women who have unsafe abortions experience complications and obtain treatment were collected from 194 health care professionals with a broad understanding of the abortion context in Nigeria. An estimated 1.25 million induced abortions occurred in Nigeria in 2012, equivalent to a rate of 33 abortions per 1,000 women aged 15-49. The estimated unintended pregnancy rate was 59 per 1,000 women aged 15-49. Fifty-six percent of unintended pregnancies were resolved by abortion. About 212,000 women were treated for complications of unsafe abortion, representing a treatment rate of 5.6 per 1,000 women of reproductive age, and an additional 285,000 experienced serious health consequences but did not receive the treatment they needed. Levels of unintended pregnancy and unsafe abortion continue to be high in Nigeria. Improvements in access to contraceptive services and in the provision of safe abortion and postabortion care services (as permitted by law) may help reduce maternal morbidity and mortality.


Intereye Asymmetry in Eyes With Keratoconus and High Ammetropia: Scheimpflug Imaging Analysis.
To evaluate intereye asymmetry using several parameters obtained from Scheimpflug imaging to discriminate between normal eyes, high-ammetropic eyes with very early keratoconus (VEKC), and keratoconus eyes in all stages. This prospective comparative study includes 685 patients (1370 eyes), of which 294 patients had bilateral keratoconus, 50 patients had high ammetropia, and 341 patients were normal. These patients were studied from July 2012 to July 2014. Thirty parameters, which were obtained from Scheimpflug imaging (Oculus GmBH) and derived from pachymetry, curvature, anterior and posterior elevation, asphericity, and others, were analyzed. Asymmetry was determined by subtracting the right eye value from the left eye value for each variable and by considering the absolute value of the result. Receiver operating characteristic curves and logistic regression analysis were used. In the hyperopic astigmatism group, the mean intereye asymmetries in maximum keratometry, maximum posterior elevation, and maximum anterior elevation were 0.35 diopters (D), 4.67 μm, and 2.5 μm, respectively. In the myopic astigmatism group the asymmetries were 0.33 D, 5.38 μm, and 2.13 μm, respectively. In the astigmatism group the asymmetries were 0.18 D, 3.33 μm, and 1.66 μm, respectively. In the VEKC group the asymmetries were 0.96 D, 10.76 μm, and 4.95 μm, respectively. A mixed model that includes the asymmetry and the nonasymmetry values shows an AUROC value of 0.9957, discriminating between normal and VEKC eyes. Specific asymmetry values derived from the Scheimpflug analysis effectively discriminate between patients with VEKC and normal patients. Patients with VEKC showed higher asymmetry values than those presented in high-ammetropic groups.


Surfactant-thermal syntheses, structures, and magnetic properties of Mn-Ge-sulfides/selenides.
Although either surfactants or amines have been investigated to direct the crystal growth of metal chalcogenides, the synergic effect of organic amines and surfactants to control the crystal growth has not been explored. In this report, several organic bases (hydrazine monohydrate, ethylenediamine (en), 1,2-propanediamine (1,2-dap), and 1,3-propanediamine (1,3-dap)) have been employed as structure-directing agents (SDAs) to prepare four novel chalcogenides (Mn3Ge2S7(NH3)4 (1), [Mn(en)2(H2O)][Mn(en)2MnGe3Se9] (2), (1,2-dapH)2{[Mn(1,2-dap)2]Ge2Se7} (3), and (1,3-dapH)(puH)MnGeSe4(4) (pu = propyleneurea) under surfactant media (PEG-400). These as-prepared new crystalline materials provide diverse metal coordination geometries, including MnS3N tetrahedra, MnGe2Se7 trimer, and MnGe3Se10 T2 cluster. Compounds 1-3 have been fully characterized by single-crystal X-ray diffraction (XRD), powder XRD, UV-vis spectra, Fourier transform infrared spectroscopy, and thermogravimetric analysis. Moreover, magnetic measurements for compound 1 showed an obvious antiferromagnetic transition at ~9 K. Our research not only enriches the structural chemistry of the transitional-metal/14/16 chalcogenides but also allows us to better understand the synergic effect of organic amines and surfactants on the crystallization of metal chalcogenides.


Prevalence of the Wish to be of the Opposite Gender in Adolescents and Adults with Autism Spectrum Disorder.
Several studies have suggested an overrepresentation of (symptoms of) autism spectrum disorder (ASD) among individuals with gender dysphoria. Three studies have taken the inverse approach in children with ASD and showed increased parent report of the wish to be of the opposite gender in this group. This study compared the self-reported wish to be of the opposite gender (one item of the Youth Self-Report [YSR] and the Adult Self-Report [ASR]) of 573 adolescents (469 assigned boys and 104 assigned girls) and 807 adults (616 assigned males and 191 assigned females) with ASD to 1016 adolescents and 846 adults from the general population. Emotional and behavioral problems were measured by the DSM-oriented scales of the YSR and ASR. In addition, the Children's Social Behavior Questionnaire and the Adult Social Behavior Questionnaire were used to measure specific subdomains of the ASD spectrum to test whether specific subdomains of ASD were particularly involved. Significantly more adolescents (6.5%) and adults (11.4%) with ASD endorsed this item as compared to the general population (3-5%). In adolescents, assigned girls endorsed this item more than assigned boys. No significant gender differences were found in the adults with ASD. In addition, on all DSM-oriented scales of both the YSR and ASR, adolescents and adults with ASD who endorsed the gender item had significantly higher scores compared to those without. There were no significant associations between endorsement of the gender item and any specific subdomain of ASD, providing no evidence for a sole role of one of the ASD subdomains and endorsement of the wish to be the opposite gender.


Role of urokinase plasminogen activator and plasminogen activator inhibitor mRNA expression as prognostic factors in molecular subtypes of breast cancer.
Protein levels of urokinase plasminogen activator (uPA) and its inhibitor (PAI-1) determined by enzyme-linked immunosorbent assay from fresh-frozen tumor tissue have been evaluated as prognostic factors in prospectively randomized trials in breast cancer. However, the role of uPA and PAI-1 in the context of breast cancer subtypes and for mRNA expression of these factors is less clear. We evaluated uPA and PAI-1 mRNA expression using the Affymetrix HG-U 133A array within molecular subgroups of breast cancer in cohorts of patients with systemic treatment (cohort A, n=362) and without systemic treatment (cohort B, n=200). We validated mRNA expression in a cohort of HER2-positive breast cancer patients (cohort C, n=290). Luminal, triple-negative, and HER2-positive subcohorts were defined by ESR1 and ERBB2 mRNA expression using predefined cutoffs. In the entire cohort A, elevated PAI-1 but not uPA mRNA expression was associated with shorter disease-free survival (P=0.007 for PAI and 0.069 for uPA). Regarding different molecular subgroups, 67% (n=244) of tumors were luminal, 14% (n=49) were HER2-positive, and 19% (n=69) were triple-negative. Elevated PAI-1 mRNA expression was associated with shorter disease-free survival only in the HER2-positive subgroup (P=0.031). The same disease-free survival results were found for uPA in HER2-positive patients (P=0.011). In contrast, no association between either marker and survival was observed in the luminal or triple-negative subgroups. In the HER2-positive validation cohort C, elevated uPA and PAI-1 mRNA expression also showed strong associations with shorter disease-free survival (P=0.014 for PAI-1, P<0.001 for uPA). In this study, the prognostic impact of uPA and PAI-1 expression was mainly observed in patients with HER2-positive tumors.


Electrophysiological and morphological properties of neurons in layer 5 of the rat postrhinal cortex.
The postrhinal (POR) cortex of the rat is homologous to the parahippocampal cortex of the primate based on connections and other criteria. POR provides the major visual and visuospatial input to the hippocampal formation, both directly to CA1 and indirectly through connections with the medial entorhinal cortex. Although the cortical and hippocampal connections of the POR cortex are well described, the physiology of POR neurons has not been studied. Here, we examined the electrical and morphological characteristics of layer 5 neurons from POR cortex of 14- to 16-day-old rats using an in vitro slice preparation. Neurons were subjectively classified as regular-spiking (RS), fast-spiking (FS), or low-threshold spiking (LTS) based on their electrophysiological properties and similarities with neurons in other regions of neocortex. Cells stained with biocytin included pyramidal cells and interneurons with bitufted or multipolar dendritic patterns. Similarity analysis using only physiological data yielded three clusters that corresponded to FS, LTS, and RS classes. The cluster corresponding to the FS class was composed entirely of multipolar nonpyramidal cells, and the cluster corresponding to the RS class was composed entirely of pyramidal cells. The third cluster, corresponding to the LTS class, was heterogeneous and included both multipolar and bitufted dendritic arbors as well as one pyramidal cell. We did not observe any intrinsically bursting pyramidal cells, which is similar to entorhinal cortex but unlike perirhinal cortex. We conclude that POR includes at least two major classes of neocortical inhibitory interneurons, but has a functionally restricted cohort of pyramidal cells.


Probiotics as antifungal agents: Experimental confirmation and future prospects.
Fungal burden throughout the world is very high and it keeps escalating due to increasing numbers of immunocompromised individuals. In contrast, the drugs used in management of fungal infections are so few some with high toxicity. Furthermore, highly resistant fungal pathogens are emerging for example Candida auris, Candida glabrata, Candida gullemondii and Aspergillus species among others. Thus now, more than ever, there is a need for combined efforts and an all round search for possible solutions to curb these problems. Therefore, the role of probiotics in management of fungal infections is indispensable. In fact, the antimicrobial activity of probiotics has been screened with promising results against microbial pathogens. Although, recent reports indicated that probiotics may also contribute to protect against fungal infections, the research done in checking antifungal activity of probiotics has used varied technology. This calls for harmonization of the methods used to screen and confirm the antimicrobial activity of probiotics and other candidate microorganisms. We therefore sought to address issues of disparity in probiotic research and their outcomes. Thus this paper is in order as it comprehensively reviews' publications, provides a summary of the methods and future prospects of probiotics as antifungal agents.


Secular trends in muscular fitness among Finnish adolescents.
To investigate secular change over time in health-related muscular fitness and how leisure time physical activity (LTPA), sport club participation, and body mass index are associated with muscular fitness in adolescents. Two cross-sectional samples of Finnish 13-16-year-old adolescents were studied in 1976 (n = 643; 312 boys and 331 girls) and in 2001 (n = 579; 308 boys and 271 girls). Muscular fitness index was calculated as the sum of age- and sex-specific z-scores of four tests measuring muscular fitness and agility. Height and weight were also measured. Self-reported weekly frequency of LTPA of at least 30-min duration and regularity of participation in organised sport were obtained by questionnaire. Identical methods were used in 1976 and 2001. Muscular fitness index was higher in 2001 than in 1976 in both boys (by 0.77 points, p = 0.008, effect size d = 0.17, small difference) and girls (1.01 points, p = 0.004, d = 0.20, small difference). Sport club participation, body mass index, and participation in LTPA together explained more of the muscular fitness index variance in 2001 than in 1976 in both boys (coefficient of determination from 0.10 to 0.24) and girls (from 0.25 to 0.40). The muscular fitness of 13-16-year old adolescents slightly improved over time. Organised LTPA showed a stronger association with muscular fitness in 2001 than in 1976. Due to increased polarisation in fitness, in health promotion more attention should be paid on adolescents' health-related fitness and its association to LTPA.


Direct and Indirect Harassment Experiences and Burnout among Academic Faculty in Japan.
The purpose of this study is three-fold: (1) to compare harassment (sexual, gender, and academic harassment both directly and indirectly experienced - i.e. "directly harassed" and "have seen or heard of someone who experienced harassment", respectively) experienced by males and females, (2) to investigate whether such experiences correlate with burnout, and (3) to explore whether social support might mitigate any such relationship between harassment and burnout. This cross-sectional study was conducted at a private university in Japan in February 2014 and is based on a work-life balance survey obtained from 330 academic faculty members. We investigated the association between each of the six subcategories of harassment (direct and indirect forms of each of the three types) and burnout using general linear regression models; we then evaluated interactions between harassment and social support in these models. The prevalence of direct and indirect experiences of harassment was higher in females than in males for all three types of harassment. Males showed higher burnout scores if they had direct experiences of harassment. There were significant interactions between social support and the direct experience of harassment; high social support mitigated the effect size of direct harassment on burnout among males. Females showed higher burnout scores if they had indirect experiences of harassment. However, the same buffering effect of social support on burnout as observed in males was not observed in females. Direct harassment experiences increased the risk of burnout in males, and indirect harassment experiences increased burnout in females.


Potassium channel conductance as a control mechanism in hair follicles.
The opening of intracellular potassium channels is a common mechanism of action for a set of anti-hypertensive drugs that includes the hair-growth-inducing agent minoxidil. Recent work suggests potassium channel openers (PCOs) also influence hair growth. Correlative studies demonstrate that a series of PCOs including minoxidil, pinacidil, P-1075, an active pinacidil analog, RP-49,356, cromakalim, and nicorandil maintain hair growth in cultured vibrissa follicles. Studies using balding stumptail macaques verify that minoxidil, P-1075, and cromakalim but not RP-49,356 stimulate hair growth. The definition of potassium channels and documentation of drug effects on these channels is classically done using electrophysiologic techniques. Such studies require the identification and isolation of target cells. Both these are among the unsolved problems in the area of hair biology. Estimating K+ flux using 86Rb+ as a K+ tracer is an accepted method of assessing potassium channel conductance in other organ systems. Both pinacidil and RP-49,356 induce measurable Rb+ flux in isolated vibrissa follicles and a hair epithelial cell line whereas neither minoxidil nor minoxidil sulfate had measurable effects. Potassium channels have been studied successfully in other organ systems using specific pharmacologic blockers for the various channel subtypes. Blockers including glyburide, tetraethylammonium, and procaine failed to inhibit minoxidil stimulation of cultured follicles. The current explosion of knowledge on potassium channel biology, cloning of channels, and continued progress in hair biology promise to clarify the role of K+ ions in the control of hair follicles.


DNMT3A mutations are associated with inferior overall and leukemia-free survival in chronic myelomonocytic leukemia.
DNMT3A mutations are seen in ∼5% of patients with chronic myelomonocytic leukemia (CMML) and thus far, have had an indeterminate prognostic impact on survival. We carried out this study to assess the prognostic impact of DNMT3A mutations on a larger informative cohort of CMML patients (n = 261). DNMT3A mutations were seen in 6% (n = 16); 56% (n = 9) male, with a median age of 64 years. Eighty-one % of DNMT3A mutations were missense, with the Arg882 mutational hot spot accounting for 63% of all changes. Five (31%) patients had an abnormal karyotype whereas concurrent gene mutations (SF3B1/SRSF2/U2AF1-56%, TET2-50%, and ASXL1-25%) were seen in all patients. Apart from a higher frequency of SF3B1 (P = 0.0001) and PTPN11 (P = 0.005) mutations and a lower frequency of SRSF2 (P = 0.004) mutations, there were no significant differences between DNMT3A mutated patients and their wildtype counterparts. In univariate analysis, survival was shorter in DNMT3A mutated (median 8 months) versus wildtype (median 27 months) patients (P = 0.0007; HR 2.9, 95% CI 1.5-5.7); with other variables of significance including lower hemoglobin (P = 0.002), higher leukocyte count (P = 0.0009), higher monocyte count (P = 0.0012), circulating blast % (P = 0.001), circulating immature myeloid cells (P = 0.01), bone marrow blast % (P = 0.045), abnormal karyotype (P = 0.02), and ASXL1 (P = 0.01) mutations. In a multivariable model that included the aforementioned variables, when both DNMT3A and ASXL1 mutations were added, only DNMT3A (P < 0.0001) and ASXL1 (P = 0.004) mutations remained significant. DNMT3A mutations were also predictive of a shortened leukemia-free survival. These findings warrant inclusion of DNMT3A mutations in molecularly integrated CMML prognostic models. Am. J. Hematol. 92:56-61, 2017. © 2016 Wiley Periodicals, Inc.


Determination of zygosity by questionnaire and physical features comparison in Chinese adult twins.
This study reports on the determination of zygosity in Chinese adult twins by simple questionnaire and physical features comparison. The subjects were 511 twin pairs from two cities and their town areas, consisting of 371 monozygotic (MZ) and 140 same-sex dizygotic (DZ) pairs, identified by ABO blood group and multiplex polymerase chain reaction of several polymorphic short tandem repeat markers. The twins themselves responded to 8 questionnaire items, 4 items on twin similarity, and 4 items on the frequency of mistaking one twin for another by parents, relatives, teachers and strangers when they were 6 to 13 years old. Research assistants responded to 20 items regarding twins' physical features at the moment of interview. A parsimonious model established using stepwise logistic regression analysis of the 28 items showed that the total accuracy of zygosity diagnosis was 90.1%. The accuracy was 89.2% when using only the items dealing with the confusion of twins and 85.4% using only similarity. In the questionnaire, 'facial appearance', 'mistaken by teachers' and 'mistaken by strangers' had stronger discriminating power between MZ and DZ twins. Two physical features--'eyelid' and 'middigital hair'--were informative to some extent. There was no statistically significant sex and area difference in the validity of such questionnaire and physical features comparison-based classification. In conclusion, questionnaire-based zygosity assessment in this Chinese adult twin sample could still be regarded as a valid and valuable classification method. Physical features comparison, however, could only provide limited information for zygosity determination.


Meta-analysis of endovascular vs open repair for traumatic descending thoracic aortic rupture.
Traumatic thoracic aortic injuries are associated with high mortality and morbidity. These patients often have multiple injuries, and delayed aortic repair is frequently used. Endoluminal grafts offer an alternative to open surgical repair. We performed a meta-analysis of comparative studies evaluating endovascular vs open repair of these injuries. A systematic search of studies reporting treatment of traumatic aortic injury was performed using the following databases: Medline/PubMed, CINAHL, Proquest, Up to Date, Database of Abstracts of Reviews of Effects (DARE), ClinicalTrials.gov, the Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Reviews. Search terms were thoracic aortic trauma, traumatic thoracic aortic injury, traumatic aortic rupture, stent graft repair, and endovascular repair. Outcomes analyzed were procedure-related mortality, overall 30-day mortality, and paraplegia/paraparesis rate using odds ratios (OR) and 95% confidence intervals (CI). Publication bias was investigated using funnel plots. Assessment of homogeneity was performed using the Q test; statistical heterogeneity was considered present at P < .05. Weighted averages of age, interval to repair, and injury severity score were compared with the Welch t test; P < .05 was considered statistically significant. Seventeen retrospective cohort studies from 2003 to 2007 were included. All were nonrandomized; no prospective randomized trials were found. These studies reported on 589 patients; 369 were treated with open repair, and 220 underwent thoracic stent graft placement. There was no significant difference in age (mean 38.8 years for both) or interval to repair (mean 1.5 days for endoluminal repair; 1 day for open repair). Injury severity score was higher for patients undergoing endoluminal repair (mean, 42.4 vs 37.4 for open repair, P < .001). Procedure-related mortality was significantly lower with endoluminal repair (OR, 0.31; 95% CI, 0.15-0.66; P = .002). Overall 30-day mortality was also lower after endoluminal repair (OR, 0.44; 95% CI, 0.25-0.78; P = .005). Sixteen studies reported data for postoperative paraplegia; 215 patients were treated with endograft placement and 333 with open repair. The risk of postoperative paraplegia was significantly less with endoluminal repair (OR, 0.32; 95% CI, 0.1-0.93; P = .037). The Q test did not indicate significant heterogeneity for the outcomes of interest; publication bias was limited. Meta-analysis of retrospective cohort studies indicates that endovascular treatment of descending thoracic aortic trauma is an alternative to open repair and is associated with lower postoperative mortality and ischemic spinal cord complication rates.