Calcaneal quantitative ultrasound and phalangeal radiographic absorptiometry alone or in combination in a triage approach for assessment of osteoporosis: a study of older women with a high prevalence of falls.
The objective of this study was to investigate if application of United Kingdom National Osteoporosis Society (UK-NOS) triage approach, using calcaneal quantitative ultrasound (QUS), phalangeal radiographic absorptiometry (RA), or both methods in combination, for identification of women with osteoporosis, would reduce the percentage of women who need further assessment with Dual Energy X-ray Absorptiometry (DXA) among older women with a high prevalence of falls. We assessed 286 women with DXA of hip and spine (Hologic Discovery) of whom 221 were assessed with calcaneal QUS (Achilles Lunar), 245 were assessed with phalangeal RA (Aleris Metriscan), and 202 were assessed with all three methods. Receiver operator characteristics (ROC) curve for QUS, RA, and both methods in combination predicting osteoporosis defined by central DXA were performed. We identified cutoffs at different sensitivity and specificity values and applied the triage approach recommended by UK-NOS. The percentage of women who would not need further examination with DXA was calculated. Median age was 80 years (interquartile range [IQR]) [75-85], range 65-98. 66.8% reported at least one fall within the last 12 months. Prevalence of osteoporosis was 44.4%. Area under the ROC-curve (AUC) (95% confidence interval (CI)) was 0.808 (0.748-0.867) for QUS, 0.800 (0.738-0.863) for RA, and 0.848 (0.796-0.900) for RA and QUS in combination. At 90% certainty levels, UK-NOS triage approach would reduce the percentage of women who need further assessment with DXA by 60% for QUS, and 43% for RA. The false negative and false positive rates ranged from 4% to 5% for QUS and RA respectively. For the combined approach using 90% certainty level the proportion of DXAs saved was 22%, the false negative rate was 0% and false positive rate was 0.5%. Using 85% certainty level for the combined approach the proportion of DXAs saved increased to 41%, but false negative and false positive values remained low (0.5%, and 0.5% respectively). In a two-step, triage approach calcaneal QUS and phalangeal RA perform well, reducing the number of women who would need assessment with central DXA. Combining RA and QUS reduces misclassifications whilst still reducing the need for DXAs.


Anxiety, Depression, and Satisfaction With Life Among College Students in China: Nine Months After Initiation of the Outbreak of COVID-19.
Mental health problems are common among college students. This study sought to assess the prevalence and risk factors of depressive and anxiety symptoms and well-being among Chinese college students 9 months after initiation of the outbreak of COVID-19. A cross-sectional study (N = 3,951, mean age = 19.58) was conducted from October to December 2020. An online survey was used to collect socio-demographic data, and the symptoms of depression and anxiety and satisfaction with life using Disorder 7-Item Scale (GAD-7), the Patient Health Questionnaire 9-Item Scale (PHQ-9), and the 5-items Satisfaction with Life Scale (SWLS). The prevalence of depressive and anxiety symptoms was 59.35 and 54.34%, respectively, and the score of satisfaction with life was 20.51 ± 6.42 among Chinese college students during the pandemic. After controlling for covariates, students in urban areas (AOR = 0.73, 95% CI = 0.61-0.87), with good family economic levels (AOR = 0.77, 95% CI = 0.66-0.91), and having psychological counseling (AOR = 0.55, 95% CI = 0.42-0.73) were positively associated with depression symptoms; meanwhile, higher anxiety symptoms were observed among medical students (AOR = 0.81, 95% CI = 0.69-0.95). Besides, healthy lifestyle such as regular physical activity and diet was associated with depression and anxiety symptoms. Multiple linear models revealed that medical students (β = 0.479, P = 0.031), those with good family economic level by self-evaluation (β = 1.283, P < 0.001 for good; β = 3.013, P < 0.001 for general), good academic performance by self-evaluation (β = 1.786, P < 0.001 for good; β = 3.386, P < 0.001 for general), learning burden (β = 1.607, P < 0.001 for general; β = 2.117, P < 0.001 for light), regular physical activity (β = 0.859, P < 0.001), daily routine (β = 1.289, P < 0.001), diet (β = 1.714, P < 0.001), and sufficient sleep (β = 1.408, P < 0.001) had more score of SWLS (all β > 0, P < 0.05), while senior students (β = -1.053, P=0.009), students having psychological counseling (β = -1.753, P < 0.001), and drinking (β = -0.743, P = 0.012) had lower satisfaction with life. These findings suggest that more attention should be paid to psychological health among college students, especially during and after the COVID-19 outbreak. Policy makers and educators should help college students develop a healthy lifestyle with regular diet and exercise to promote the psychological health of college students.


A systems life cycle approach to managing the radiology profession: an Australian perspective.
Although the medical system has expanded considerably over the past two decades in almost all countries, so too has the demand for health care. The radiology specialisation may be an early system indicator, being especially sensitive to changes in supply and demand in both rural and urban environments. The question is whether the new policies of increasing the number of radiologists can be a proper long-term solution for the imbalance of workforce supply and demand or not. Using system dynamics modelling, we present our integrated descriptive models for the supply and demand of Australian radiologists to find the actual gap. Followed by this, we pose a prescriptive model for the supply in order to lessen the identified imbalance between supply and demand. Our system dynamics models compare the demand and supply of Australian radiologists over 40 years between 2010 and 2050. The descriptive model shows that even if the radiology training program grows at a higher rate than the medical training growth rate and its own historical growth, the system will never be able to meet demand. The prescriptive model also indicates that although changing some influential factors (e.g the intake rate) reduces the level of imbalance, the system will still stay unstable during the study period. We posit that Australia may need to design a new system of radiology provision to meet future demands for high-quality medical radiation services. We also suggest some strategies, such as greater development of radiographers' role, are critical for enabling sustainable change over time. What is known about the topic? Long-term workforce planning for medical services at the national level has been very challenging for policy makers of the 21st century. The current demographic imbalance in the supply and demand of the Australian radiologist workforce makes it difficult to plan the effects of extra inflow of radiology students over time.


Effect of mechanical stimulus spread across glabrous skin of raccoon and squirrel monkey hand on tactile primary afferent fiber discharge.
The role of spread of skin deformation in activating cutaneous mechanoreceptors at a distance from their threshold receptive fields (RFs) was examined in glabrous skin of the North American raccoon and the squirrel monkey. One feedback-controlled mechanical stimulus probe was used to indent the skin to a controlled depth at a constant velocity, at varying distances from a second probe, which was used to monitor vertical displacement depth and velocity at this distant site. In many instances, the monitor probe was positioned over the RF of a cutaneous mechanoreceptor, and single-unit action potentials were simultaneously recorded from individual fibers of the median or ulnar nerve. With distance from the site of stimulation, there was a systematic, monotonic decline in indentation depth and velocity; velocity fell off with distance more rapidly than depth. The degree of diminution with distance varied with the size, shape, and curvature of the digital or palm pad stimulated. Spread of indentation was more restricted on digital than on palm pads, and was more restricted across monkey skin than across raccoon skin. Spread was less with higher-velocity than with lower-velocity indentations, but was seemingly unaffected by indentation depth. As expected from the findings noted above, the number of spikes discharged by slowly adapting mechanoreceptive afferent fibers declined more rapidly with distance between stimulus site and RF for digital than for palmar RFs, in squirrel monkey than in raccoon skin, and with higher-velocity than with lower-velocity stimuli. Furthermore, the number of spikes occurring during either ramp or early static indentation phases of stimulation dropped to zero more rapidly with distance than did either vertical indentation depth or velocity. Decreases with distance in both indentation depth and velocity acted to restrict the size of suprathreshold RFs. For most units, horizontal components of mechanical stimulation subtracted from the effects of vertical components. It is suggested, on the basis of this and other studies, that many neural and perceptual phenomena usually attributed to central mechanisms of afferent inhibition may be attributable, at least in part, to mechanical properties of the skin. In addition, the present data suggest that regional variations in the two-point limen may be associated with variations in spread of mechanical deformation. The conclusion that glabrous skin and subjacent soft tissues act as a low-pass filter system provides a mechanical basis for the relative efficacy of high-frequency vibratory stimuli in tactile pattern perception.(ABSTRACT TRUNCATED AT 400 WORDS)


Impact of an evidence-based guideline on the management of community-acquired bacterial meningitis: a prospective cohort study.
To study the impact of an evidence-based guideline on the management of community-acquired bacterial meningitis. We performed an interrupted time series analysis in a prospective nationwide cohort study from 2006 to 2015. The guideline stresses the importance of cranial imaging before lumbar puncture (LP) in selected patients based on clinical criteria, and early treatment with amoxicillin and a third-generation cephalosporin for adults with suspected community-acquired bacterial meningitis. The guideline was published in April 2013. We included 1326 episodes before and 210 episodes after guideline introduction. Cranial imaging was performed before LP in 497 (84%) of 591 episodes with clinical criteria warranting computed tomography (CT). The guideline did not improve this (increase of 2%; 95% confidence interval (CI), -15 to 19). Without these criteria, imaging before LP occurred in 606 (67%) of 900 episodes, also without effect of the guideline (increase of 1%; 95% CI, -25 to 28). The estimate of effect of the guideline for treatment with the recommended antibiotic regimen was an increase of 19.5% (95% CI, 13.5 to 25.5), and there was a trend towards more frequent initiation of treatment before CT. There was no association between delay in antibiotic treatment due to imaging before LP and unfavourable outcome (odds ratio, 1.14; 95% CI 0.86 to 1.52). Cranial imaging is performed before LP in the majority of patients with bacterial meningitis, irrespective of guideline indications. The guideline introduction was associated with a trend towards early initiation of treatment before imaging and with increased adherence to antibiotic policy.


[Effects of erlong zuoci pills and its effective disassembled prescriptions on gentamycin induced hair cell apoptosis].
To investigate the effects of erlong zuoci (ELZC) pills and its disassembled prescriptions (Shudi-huang-Zexie group and Zexie group) on the enzymatic activity and protein expression changes of the key apoptosis molecules in the gentamycin injured hair cells. The model of gentamycin induced ototoxicity in mice cochlear primary cultures was copied. Cochlear organotypic cultures of postnatal day 3-5 (P3-P5) mice were treated with gentamycin alone or in combination with ELZC pills, Shudihuang-Zexie group or Zexie group respectively. The enzymatic activity of Caspase-9 and Caspase-3 was determined by means of fluorescence staining in situ. The protein expression of Bcl-2 and Bax in the hair cell area was examined by immunofluorescence in normal and treated specimens. Average optical density analysis indicated that, compared to the normal group, 0.03 mmol x L(-1) gentamycin could significantly activate Caspase-9 and Caspase-3, downregulate the ratio of Bcl-2 and Bax protein expression. Compared to the gentamycin model group, ELZC pills significantly inhibited the enzymatic activity of Caspase-9 and upregulated the ratio of Bcl-2 and Bax protein expression, showing inhibition trend toward the enzymatic activity of Caspase-3. Both Shudihuang-Zexie group and Zexie group could effectively inhibit the enzymatic activity of Caspase-9 and Caspase-3, upregulate the ratio of Bcl-2 and Bax protein expression. ELZC pills, Shudihuang-Zexie group and Zexie group can effectively protect hair cells from gentamycin by correcting the abnormal changes of the mitochondrion-dependent signal transduction pathway.


Effect of energy intake on the postpartum interval in beef cows and the adequacy of the cow's milk production for calf growth.
Lactating Hereford and Hereford X Angus cows, 2 to 6 yr old, and their calves were used in two trials to study the effects of energy intake on the postpartum interval (PPI) and the adequacy of the cow's milk production for calf growth. In trial 1, 23 cows were fed either 120 (high energy, HE) or 100% (adequate energy, AE) of National Research Council energy recommendations. Cow weights, calf weights and milk production were determined 1 wk after calving and every 2 wk until 17 wk postcalving . One-half of the calves received creep feed from the start of the study, whereas the other half did not receive creep feed until their average daily gain was below .23 kg/d. In trail 2, 19 cows were fed energy levels of 100 (AE) or 85% (low energy, LE). Estimated percentage body fat ( EPBF ) was estimated twice during the study; other variables were determined as in trial 1. In trial 1, the HE cows gained more weight (P less than .01) and produced more milk (P less than .01). In trial 2, the AE cows gained more weight (P less than .01) and produced calves 17 kg heavier (P less than .01) at the end of the study than did the LE cows. Milk production was not influenced by energy treatment (P greater than .2). It required 7.5 kg of milk and 2.3 kg of creep feed to produce 1 kg of calf gain in trial 1.(ABSTRACT TRUNCATED AT 250 WORDS)


[Surgery of vesicoureteral reflux (author's transl)].
The objective of surgery of vesicureteral reflux is to block the way of urine from urinary bladder to the ureter without upsetting normal flux of urine in descending sense. Most important techniques used are described from the beginning of this surgery until nowadays and specially the Leadbetter-Politano technique, which accomplished most essential requirements for the obtention of favourable results. Finally special considerations are enumerated to keep in mind in treatment of reflux when is associated to other malformations of urinary tract like the ureteral diverticule of double ureter.


Functional morphology of the douc langur (Pygathrix spp.) scapula.
Most colobine monkeys primarily move through their arboreal environment quadrupedally. Douc langurs (Pygathrix spp.), however, are regularly observed to use suspensory behaviors at the Endangered Primate Rescue Center (EPRC) in Northern Vietnam. Previous work has linked variation in scapular morphology to different modes of primate arboreal locomotion. Here we investigate whether the shape of the Pygathrix scapula resembles obligate brachiators (gibbons) or obligate arboreal quadrupeds (other cercopithecoids). Using a MicroScribe G2X 3D digitizer, the positions of 17 landmarks were recorded on 15 different species of nonhuman primates (n = 100) from three categories of locomotor behavior: brachiator, arboreal quadruped, and unknown (Pygathrix). All analyses were conducted in the R package geomorph. A Procrustes analysis uniformly scaled the shape data and placed specimens into the same morphospace. A Principal Component Analysis was used to examine scapular shape and a Procrustes ANOVA was conducted to test for shape difference in the scapulae. A pairwise analysis was used to compare the means of the locomotor categories and identify any statistically significant differences. A phylogenetically controlled Procrustes ANOVA was also conducted using a phylogeny from 10kTrees. Results show Pygathrix scapular morphology is significantly different from both arboreal colobine quadrupeds (p < 0.01) and hylobatid brachiators (p < 0.01). It does, however, share some features with each including a long vertebral border, like other cercopithecoids, and a more laterally projecting acromion process, like the hylobatids. The principal difference segregating Pygathrix from both the arboreal quadrupeds and the brachiators is the more medially placed superior angle. These nuanced morphological characteristics associated with suspensory behaviors may be useful for inferring suspensory locomotion in the primate fossil record.


Equilibria in a two-species fishery.
In this paper, we consider a two-species fishery model where the species can have different biological interactions, namely, competitive, symbiotic or prey-predator relationships. Each species is harvested by a group of fisherpersons. We characterize and compare equilibrium harvesting strategies, steady-state stocks and total discounted utilities under different modes of play, that is, noncooperation in both groups, cooperation in each of the groups and cooperation in only one group of fisherpersons. Our main results are as follows: (i) In all scenarios, the equilibrium strategy of an agent fishing either species consists of harvesting, in each period, a proportion of the available stock. (ii) The dividend of cooperation in a given group is increasing with the number of members in that group. (iii) Coordination between agents fishing a given species may be detrimental (biologically and economically) to the other species.


Use of implantable loop recorders in the diagnosis and management of syncope.
Syncope is a common, disabling symptom. The most useful data for diagnosing and managing syncope is the recording of physical parameters such as the ECG and blood pressure during a spontaneous event. Implantable loop recorders (ILR) provide an opportunity to record ECG data from a spontaneous event. The purpose of the Eastbourne Syncope Assessment Study (EaSyAS) was to investigate the impact of ILRs on an unselected population of syncopal patients presenting acutely to our institution. All patients presenting acutely with recurrent, unexplained syncope over a 16-month period, were randomised after a basic clinical workup to receive the Reveal Plus ILR or conventional investigation. All patients were followed up for at least 6 months (mean 276+/-134 days) following randomisation. The primary outcome measure was time to ECG diagnosis. Four hundred twenty-one patients presented, 201 were eligible, median age 74 years (interquartile range 61-81 years), 54% female, with a median of three previous syncopes (IQ range 2-6). Thirty-three percent of ILR patients and 4% of conventional patients had an ECG diagnosis (hazard ratio 8.93, 95% CI 3.17-25.2, p < or = 0.0001). Introduction of ECG-directed therapy was quicker for ILR patients (hazard ratio 7.9, 95% CI 2.8-22.3, p < 0.0001). ILR patients had fewer post-randomisation investigations and fewer hospital days, resulting in a saving of costs, 406 UK pounds versus 1210 UK pounds (mean difference 809 UK pounds, 95% CI 123-2730 UK pounds). There was no difference in the number of subsequent syncopal episodes, mortality, or quality of life. LR significantly increased the rate of diagnosis in an unselected Western population with recurrent syncope. There was a significant decrease in the rates of hospitalisation and investigation in patients receiving an ILR.


Efficient targeting of conserved cryptic epitopes of infectious agents by single domain antibodies. African trypanosomes as paradigm.
Antigen variation is a successful defense system adopted by several infectious agents to evade the host immune response. The principle of this defense strategy in the African trypanosome paradigm involves a dense packing of variant surface glycoproteins (VSG) exposing only highly variable and immuno-dominant epitopes to the immune system, whereas conserved epitopes become inaccessible for large molecules. Reducing the size of binders that target the conserved, less-immunogenic, cryptic VSG epitopes forms an obvious solution to combat these parasites. This goal was achieved by introducing dromedary Heavy-chain antibodies. We found that only these unique antibodies recognize epitopes common to multiple VSG classes. After phage display of their antigen-binding repertoire, we isolated a single domain antibody fragment with high specificity for the conserved Asn-linked carbohydrate of VSG. In sharp contrast to labeled concanavalin-A that stains only the flagellar pocket where carbohydrates are accessible because of less dense VSG packing, the single domain binder stains the entire surface of viable parasites, irrespective of the VSG type expressed. This corroborates the idea that small antibody fragments, but not larger lectins or conventional antibody fragments, are able to penetrate the dense VSG coat to target their epitope. The diagnostic potential of this fluorescently labeled binder was proven by the direct, selective, and sensitive detection of parasites in blood smears. The employment of this binder as a molecular recognition unit in immuno-toxins designed for trypanosomosis therapy becomes feasible as well. This was illustrated by the specific trypanolysis induced by an antibody::beta-lactamase fusion activating a prodrug.


Long non-coding RNA NEAT1 regulates ferroptosis sensitivity in non-small-cell lung cancer.
Ferroptosis is caused by iron-dependent lipid peroxide accumulation, the sensitivity of which might be regulated by acyl-CoA synthetase long chain family member 4 (ACSL4). Non-small-cell lung cancer (NSCLC) can resist oxidative stress and reduce the sensitivity of tumor cells to ferroptosis by changing the expression of some proteins. Mechanisms involving ferroptosis sensitivity in NSCLC are not fully understood. A dual-luciferase reporter assay was used to confirm a targeting relationship between long non-coding (lnc)RNA NEAT1 and ACSL4. Overexpression and silencing assays of NEAT1 function were used to determine its roles in cell death (by TUNEL staining) and lipid peroxidation (by malondialdehyde levels). Expression of ferroptosis-related proteins (SLCA11, GPX4, and TFR4) was evaluated by western blot in NSCLC cells treated or not with the ferroptosis inducer erastin. Erastin-induced cell death was positively correlated with ACSL4 level. NEAT1 regulated levels of ACSL4 and proteins related to the ferroptosis and classical apoptosis pathways. Levels of ACSL4, SLC7A11, and GPX4 were decreased more by NEAT1 silencing plus erastin than by erastin alone. NEAT1 regulates ferroptosis and ferroptosis sensitivity, with the latter depending on ACSL4, suggesting that targeting NEAT1 or ACSL4 may be a viable therapeutic approach to the treatment of NSCLC.


Cytokeratin autoantibodies: useful serologic markers for toluene diisocyanate-induced asthma.
To evaluate the clinical significance of autoantibodies to three major epithelial cytokeratins (CK)--CK8, CK18, and CK19--we compared 66 patients with toluene diisocyanate (TDI)-induced asthma (group I) with three control groups: 169 asymptomatic exposed subjects (group II), 64 patients with allergic asthma (group III), and 123 unexposed healthy subjects (group IV). Serum IgG, specific for human recombinant CKs, were measured by ELISA (enzyme linked immunosorbent assay), and ELISA inhibition tests were performed. The existence of these antibodies was confirmed by IgG immunoblot analysis. Anti-TDI-HSA (human serum albumin) IgE and IgG antibodies were measured by ELISA in the same set of the patients. The prevalence of CK8, CK18, and CK19 auotantibodies in group I was significantly higher than in the other three groups. Results of the ELISA inhibition test showed significant inhibition with the addition of three CKs in a dose-dependent manner. No significant association was found between CK autoantibodies and the prevalence of anti- TDI-HSA IgG and IgE antibodies. These results suggest that autoantibodies to CK18 and CK19 can be used as serologic markers for identifying patients with TDI-induced asthma among exposed workers.


Estimating disease rates from a diagnostic test.
Incidence and remission rates are often estimated from studies that employ a diagnostic test to indicate the presence of disease. The apparent rates that result from a simple study design with one test given at two time points will be substantially different from the true rates, even if the error rates of the test are low. Estimation of the true rates requires extra assumptions or extended designs with more tests or more time points. The authors illustrate their points with the use of two examples, the second of which compares the estimates obtained to actual data from a study of onchocerciasis (river blindness) in Guatemala.


Pneumonia, Aspiration Pneumonia, or Frailty-Associated Pneumonia?
Pneumonia is a common reason for admission afflicting frail older adults. Those who are the frailest are more likely to be provided with a diagnosis of aspiration pneumonia. This diagnosis has no clear definition and no clinical consensus. It is therefore time to stop attempting to differentiate between pneumonia type and use the term frailty-associated pneumonia.


Slowly Reducible Genetically Encoded Green Fluorescent Indicator for In Vivo and Ex Vivo Visualization of Hydrogen Peroxide.
Hydrogen peroxide (H2O2) plays an important role in modulating cell signaling and homeostasis in live organisms. The HyPer family of genetically encoded indicators allows the visualization of H2O2 dynamics in live cells within a limited field of view. The visualization of H2O2 within a whole organism with a single cell resolution would benefit from a slowly reducible fluorescent indicator that integrates the H2O2 concentration over desired time scales. This would enable post hoc optical readouts in chemically fixed samples. Herein, we report the development and characterization of NeonOxIrr, a genetically encoded green fluorescent indicator, which rapidly increases fluorescence brightness upon reaction with H2O2, but has a low reduction rate. NeonOxIrr is composed of circularly permutated mNeonGreen fluorescent protein fused to the truncated OxyR transcription factor isolated from E. coli. When compared in vitro to a standard in the field, HyPer3 indicator, NeonOxIrr showed 5.9-fold higher brightness, 15-fold faster oxidation rate, 5.9-fold faster chromophore maturation, similar intensiometric contrast (2.8-fold), 2-fold lower photostability, and significantly higher pH stability both in reduced (pKa of 5.9 vs. ≥7.6) and oxidized states (pKa of 5.9 vs.≥ 7.9). When expressed in the cytosol of HEK293T cells, NeonOxIrr demonstrated a 2.3-fold dynamic range in response to H2O2 and a 44 min reduction half-time, which were 1.4-fold lower and 7.6-fold longer than those for HyPer3. We also demonstrated and characterized the NeonOxIrr response to H2O2 when the sensor was targeted to the matrix and intermembrane space of the mitochondria, nucleus, cell membranes, peroxisomes, Golgi complex, and endoplasmic reticulum of HEK293T cells. NeonOxIrr could reveal endogenous reactive oxygen species (ROS) production in HeLa cells induced with staurosporine but not with thapsigargin or epidermal growth factor. In contrast to HyPer3, NeonOxIrr could visualize optogenetically produced ROS in HEK293T cells. In neuronal cultures, NeonOxIrr preserved its high 3.2-fold dynamic range to H2O2 and slow 198 min reduction half-time. We also demonstrated in HeLa cells that NeonOxIrr preserves a 1.7-fold ex vivo dynamic range to H2O2 upon alkylation with N-ethylmaleimide followed by paraformaldehyde fixation. The same alkylation-fixation procedure in the presence of NP-40 detergent allowed ex vivo detection of H2O2 with 1.5-fold contrast in neuronal cultures and in the cortex of the mouse brain. The slowly reducible H2O2 indicator NeonOxIrr can be used for both the in vivo and ex vivo visualization of ROS. Expanding the family of fixable indicators may be a promising strategy to visualize biological processes at a single cell resolution within an entire organism.


Standardized feeding regimen for reducing necrotizing enterocolitis in preterm infants: an updated systematic review.
A systematic review (2005) of observational studies has reported 87% reduction in the incidence of necrotizing enterocolitis (NEC) after introducing standardized feeding regimen (SFR) in preterm infants. Considering the many new studies in this field since 2005 and the continued health burden of NEC, we aimed to systematically review the incidence of NEC in preterm infants 'before' vs 'after' implementing a SFR. PubMed, EMBASE, CINAHL and E-abstracts from the Pediatric Academic Society meetings and other pediatric and neonatal conference proceedings were searched in May 2016. Observational studies reporting incidence of NEC before and after implementing a SFR were included. Relevant data were extracted independently by two reviewers. Meta-analysis was conducted using random effects model (REM) and results rechecked with fixed effects model. Pooled results from 15 observational studies (N=18 160) using REM showed that SFR significantly reduced the incidence of NEC (risk ratio 0.22; 95% confidence interval 0.13 to 0.36; P<0.00001; I2=74%). The results remained significant after comparing studies in two epochs (1978 to 2003 vs 2004 to 2016). SFR continues to be an important tool in prevention of NEC in preterm infants.


Meal patterns and the quality of breakfast and snacks in relation to adolescents' dental health in southeast of Iran.
Aim: The objective was to determine the frequency pattern and nutritional quality of breakfast and snacks in Iranian adolescents and to investigate these dietary habits in relation to tooth decay and tooth erosion. Methods: A multistage cluster random sampling method was adopted to recruit 600 adolescents with equal sex distribution in the city of Kerman/southeast of Iran. Decayed, Missing and Filled Teeth (DMFT) and Tooth Wear Index (TWI) were recorded for each subject. Snacking and breakfast quality, frequency of snacking and regular/irregular use of main meals were also recorded. Poisson regression and Firth's bias-reduced penalized-likelihood logistic regression were used for data analysis. Results: DMFT score of adolescents who consumed low-quality snacks were 1.13 times more than those who consumed high-quality snacks. Regular use of all three main meals was associated with a lower DMFT score. DMFT score of adolescents who did not have regular use of breakfast was 1.19 times more than those who consumed breakfast on a regular basis. Also, regarding adolescents who had an irregular use of lunch, the DMFT score was 1.3 times more than those who had a regular lunch schedule. In addition, participants with irregular dinner consumption had 1.24 times more DMFT scores compared to those with a regular dinner schedule. Conclusions: Regular breakfast consumption, decreased snacking occasions, use of higher nutritional quality snacks, and increased nutritional education are important in order to prevent a higher chance of dental caries and promote dental health status.


Workplace bullying and post-traumatic stress symptoms among family physicians in Lithuania: an occupation and region specific approach.
The study investigated associations between workplace bullying and post-traumatic stress symptoms as compared to and controlled for associations between the latter and other psychosocial stress factors at work and in everyday life. The study employed a representative sample of Lithuanian family physicians, hence investigated a particularly resourceful occupational group in a geographical region earlier found to have a high risk context for exposure to bullying at work. With a response rate of 89.2%, a total of 323 family physicians filled in an anonymous questionnaire on workplace bullying, post-traumatic symptomatology (IES-R), other psychosocial stressors at work and in everyday life, personal health resources (sense of coherence), behavioral characteristics and demographic variables. The statistical software SPSS 14.0, Windows was used in the analysis. Associations were tested using a multivariate logistic regression analysis. A high prevalence of bullying was found among family physicians in Lithuania, with 13% of them experiencing severe workplace bullying and 17.3% experiencing more occasional incidents of bullying. The prevalence of post-traumatic stress symptoms was also high with 15.8% scoring above the standardized cut-off thresholds for post-traumatic stress disorder. The odds ratio (OR) of severe bullying for post-traumatic stress after adjustment for age and gender was 8.05 (95% confidence intervals (CI): 3.80-17.04). In the fully adjusted model it increased to 13.88 (95% CI: 4.68-41.13) indicating cumulative effects of all the investigated stressors. Workplace bullying is particularly prevalent among Lithuanian family physicians, as are the symptoms of post-traumatic distress. Strong associations between post-traumatic stress and exposure to severe bullying indicate that bullying is a significant source of mental health.


Stress Distribution in All-Ceramic Posterior 4-Unit Fixed Dental Prostheses Supported in Different Ways: Finite Element Analysis.
The purpose of this finite element analysis (FEA) was to complement results of previously published studies that investigated the influence of abutment resilience on the load-bearing capacity of zirconia posterior 4-unit fixed dental prostheses (FDPs) with static load tests. Duplicates of 3 different physical specimens were modeled for FEA. The first virtual specimen was supported by teeth with periodontal resilience, the second by the combination of tooth and implant, and the third by implants only. The center of the FDP was loaded, vertically to the occlusal plane. The highest maximum principal stresses (MPSs) were computed. The highest MPS in each model occurred in the basal region of the middle framework connector. Comparison between the 3 models showed that the tensile stresses were lower when the support of the FDP was more rigid. Numerically determined highest MPSs in the FDPs correlated well with experimentally observed load-bearing capacities. The FEA is well suited to confirm the in vitro study mentioned and complement the results with stress distributions in all-ceramic posterior 4-unit FDP.


Ultrastructure of the hepatocytes after application of azithromycin (Sumamed).
Azithromycin (Sumamed, PLIVA Cracow) was administered intragastrically to rats in doses 10 times and 100 times bigger than the therapeutic dose (according to the indications for a 5-day treatment). Ultrastructural examinations of the liver were performed. Changes observed in the morphology of hepatocytes and Browicz-Kupffer cells (swelling of mitochondria, more numerous lysosomes, weaker RER content and granular material inside biliary canaliculi) may indicate temporary violation of the functional equilibrium in the liver due to the application of azithromycin.


Ultrafast dynamics of the excited states of the uranyl ion in solutions.
We have investigated the relaxation dynamics of the higher excited states of the uranyl ion in aqueous and methanolic solutions following photoexcitation to the S(1)((1)Phi(g)) state using 400 nm light. Although the time-resolved spectra are significantly different in these two solvents, the temporal dynamics studied in the entire wavelength region clearly suggest the involvement of three excited state processes in both solvents. The S(1)((1)Phi(g)) state undergoes ultrafast intersystem crossing (tau(ISC) approximately <100 fs) to the higher vibrational levels of the T(2)((3)Delta(g)) state, followed by the intramolecular vibrational relaxation (IVR) process in the later electronic state (tau(IVR) approximately 0.85 and 1 ps in aqueous and methanolic solutions, respectively). Subsequently, the T(2)((3)Delta(g)) state undergoes an internal conversion (IC) process (tau(IC) approximately l.6 and 4.5 ps in aqueous and methanol solutions, respectively) to the long-lived T(1)((3)Phi(g)) state, which is responsible for the luminescent properties of the uranyl ion. In neat methanol, because of stronger interaction between the excited triplet, T(1)((3)Phi(g)), state and the solvent via solvent to uranyl charge transfer, the U(VI) ion undergoes partial reduction to U(V) and the energy level of this state possibly lies lower than that of (UO(2)(2+))*, which is the transient species existing in aqueous solution, and hence increasing the energy gap between the T(2) and T(1) states in methanol solution. These facts possibly explain different spectral characteristics of the transient species produced in methanol and aqueous solutions as well as the longer lifetime of the IC process in methanol solution.


Effects of solar UV-B radiation on aquatic ecosystems.
Solar UV degrades dissolved organic carbon photolytically so that they can readily be taken up by bacterioplankton. On the other hand solar UV radiation inhibits bacterioplankton activity. Bacterioplankton productivity is far greater than previously thought and is comparable to phytoplankton primary productivity. According to the "microbial loop hypothesis," bacterioplankton is seen in the center of a food web, having a similar function to phytoplankton and protists. The penetration of UV and PAR into the water column can be measured. Marine waters show large temporal and regional differences in their concentrations of dissolved and particulate absorbing substances. A network of dosimeters (ELDONET) has been installed in Europe ranging from Abisko in Northern Sweden to Gran Canaria. Cyanobacteria are capable of fixing atmospheric nitrogen which is then made available to higher plants. The agricultural potential of cyanobacteria has been recognized as a biological fertilizer for wet soils such as in rice paddies. UV-B is known to impair processes such as growth, survival, pigmentation, motility, as well as the enzymes of nitrogen metabolism and CO2 fixation. The marine phytoplankton represents the single most important ecosystem on our planet and produces about the same biomass as all terrestrial ecosystems taken together. It is the base of the aquatic food chain and any changes in the size and composition of phytoplankton communities will directly affect food production for humans from marine sources. Another important role of marine phytoplankton is to serve as a sink for atmospheric carbon dioxide. Recent investigations have shown a large sensitivity of most phytoplankton organisms toward solar short-wavelength ultraviolet radiation (UV-B); even at ambient levels of UV-B radiation many organisms seem to be under UV stress. Because of their requirement for solar energy, the phytoplankton dwell in the top layers of the water column. In this near-surface position phytoplankton will be exposed to solar ultraviolet radiation. This radiation has been shown to affect growth, photosynthesis, nitrogen incorporation and enzyme activity. Other targets of solar UV irradiation are proteins and pigments involved in photosynthesis. Whether or not screening pigments can be induced in phytoplankton to effectively shield the organisms from excessive UV irradiation needs to be determined. Macroalgae show a distinct pattern of vertical distribution in their habitat. They have developed mechanisms to regulate their photosynthetic activity to adapt to the changing light regime and protect themselves from excessive radiation. A broad survey was carried out to understand photosynthesis in aquatic ecosystems and the different adaptation strategies to solar radiation of ecologically important species of green, red and brown algae from the North Sea, Baltic Sea, Mediterranean, Atlantic, polar and tropical oceans. Photoinhibition was quantified by oxygen exchange and by PAM (pulse amplitude modulated) fluorescence measurements based on transient changes of chlorophyll fluorescence.


Phosphoinositides in New Spaces.
Phosphoinositides (PIs) are phospholipids derived from phosphatidylinositol. PIs are regulated via reversible phosphorylation, which is directed by the opposing actions of PI kinases and phosphatases. PIs constitute a minor fraction of the total cellular lipid pool but play pleiotropic roles in multiple aspects of cell biology. Genetic mutations of PI regulatory enzymes have been identified in rare congenital developmental syndromes, including ciliopathies, and in numerous human diseases, such as cancer and metabolic and neurological disorders. Accordingly, PI regulatory enzymes have been targeted in the design of potential therapeutic interventions for human diseases. Recent advances place PIs as central regulators of membrane dynamics within functionally distinct subcellular compartments. This brief review focuses on the emerging role PIs play in regulating cell signaling within the primary cilium and in directing transfer of molecules at interorganelle membrane contact sites and identifies new roles for PIs in subcellular spaces.


Clinical management of brain metastasis.
Brain metastasis is a common complication occurring in about 15-20% of all cancer patients. For the initial management, distinguishing between three types of presentation is essential: de novo brain metastasis, simultaneous presentation of both brain metastasis and the primary tumour (usually lung carcinoma), and the presentation of a patient known to have systemic cancer developing a brain metastasis. For de novo brain metastasis, surgery is required, and detecting the primary tumour is of limited value. For simultaneous presentation, both a craniotomy and a thoracotomy may be indicated and may lead to cure in a number of cases. For a sequential presentation, the outcome is determined by a number of independent prognostic factors: age, performance status, and the extent of metastatic disease. In relatively young patients with a single brain metastasis, good performance status and no progression of systemic disease, treatment by either surgery or radiosurgery in combination with whole brain radiation therapy is indicated. Otherwise, as in multiple brain metastases, radiation therapy only is the main treatment. For symptomatic therapy of brain oedema or increased intracranial pressure, dexamethasone is administered. The standard doses of dexamethasone may vary between 4 and 16 mg/day, depending on the severity of symptoms.


Preventive service utilization among low-income cancer survivors.
Adequate access to and utilization of preventive services are vital among cancer survivors. This study examined preventive service utilization of cancer survivors compared to matched patients with no history of cancer among patients seeking care at community health centers (CHCs). We utilized electronic health record data from the OCHIN network between 2014 and 2017. Cancer survivors (N = 20,538) ages ≥ 18 years were propensity score matched to three individuals with no history of cancer (N = 61,617) by age, sex, region, urban/rural, ethnicity, race, BMI, and Charlson Comorbidity Index. Preventive screenings included cancer, mental health and substance abuse, cardiovascular, and infectious disease screenings, and vaccinations. Patient-level preventive service indices were calculated for each screening as the total person-time covered divided by the total person-time eligible. Preventive service rate ratios comparing cancer survivors to patients with no history of cancer were estimated using negative binomial regression. Cancer survivors had higher overall preventive service utilization (incidence rate ratio = 1.11, 95% confidence interval = 1.09-1.13) and higher rates of cancer screenings (IRR = 1.16, 95% CI = 1.12-1.20). There was no difference between the two groups in mental health screenings. Cancer survivors were more likely to be up-to-date with preventive care than their matched counterparts. However, mental health and substance abuse screenings were low in both groups, despite reports of increased mental health conditions among cancer survivors. With the growing number of cancer survivors in the USA, efforts are needed to ensure their access to and utilization of preventive services, especially related to behavioral and mental healthcare.


The role of oral methotrexate as a steroid sparing agent in refractory eosinophilic asthma.
The use of oral methotrexate for refractory eosinophilic asthma in a tertiary asthma referral centre, Glenfield Hospital, Leicester, was evaluated between January 2006 and December 2014. The patients ( n = 61) were carefully phenotyped at baseline with markers of airway inflammation. In addition, a structured oral methotrexate proforma was utilized to evaluate response to therapy and adverse events. Oral steroid withdrawal was attempted 3 months after commencing treatment. Several outcomes were evaluated at 12 months, including both efficacy and adverse effects; 15% ( n = 9/61) responded by achieving a decrease in daily oral corticosteroid dose (mean 8.43 (±8.76) mg), although we were unable to identify factors that predicted a treatment response. There were no other significant changes in any other clinical outcome measures. There was a high rate of adverse events (19/61 (31%)), primarily gastrointestinal/hepatitis. Our findings support the use of biological agents in preference to using oral methotrexate as a steroid sparing agent at the first instance. In the event of failure of these agents, oral methotrexate remains a therapeutic option, which can be considered in highly specialist severe asthma centres.


Pearls in the management of macular holes.
We studied the efficacy of removing the retinal pigment epithelium (RPE) from the base of the macular hole to treat 124 eyes of 118 patients with stage 2 (n = 38), stage 3 (n = 52), or stage 4 (n = 34) macular hole. The patients ranged in age from 42 to 81 years (mean = 66.7 years), and the duration of symptoms preoperatively ranged from 1 to 140 months (average = 16.8 months). During vitrectomy for the macular hole, the RPE at the base of the hole was gently aspirated with either a silicone-tipped extrusion needle or a blunt-tipped 27-gauge needle. The follow-up period averaged 18.6 months (range = 3 to 48 months). The holes resolved in 112 (90%) of the 124 eyes after one surgical procedure. In 107 eyes with a follow-up period of 6 months or longer, 91 (85.0%) showed improved visual acuity of at least 2 lines of Snellen equivalent. The final visual acuity was 20/25 or better in 34 (31.8%) and 20/40 or better in 80 (74.8%) of the 107 eyes. A complication peculiar to RPE removal is the hypertrophy of the RPE. This complication was observed in 15 (14.0%) of the 107 eyes that were followed for 6 months or longer. From these results, I conclude that RPE removal will improve the anatomical and the visual results in selected macular hole cases.


β-caryophyllene emitted from a transgenic Arabidopsis or chemical dispenser repels Diaphorina citri, vector of Candidatus Liberibacters.
Production of citrus, the main fruit tree crop worldwide, is severely threatened by Huanglongbing (HLB), for which as yet a cure is not available. Spread of this bacterial disease in America and Asia is intimately connected with dispersal and feeding of the insect vector Diaphorina citri, oligophagous on rutaceous host plants. Effective control of this psyllid is an important component in successful HLB management programs. Volatiles released from the non-host guava have been shown to be repellent to the psyllid and to inhibit its response to citrus odour. By analysing VOC emission from guava we identified one volatile compound, (E)-β-caryophyllene, which at certain doses exerts a repellent effect on D. citri. Non-host plant rejection mediated by (E)-β-caryophyllene is demonstrated here by using Arabidopsis over-expression and knock-out lines. For the first time, results indicate that genetically engineered Arabidopsis plants with modified emission of VOCs can alter the behaviour of D. citri. This study shows that transgenic plants with an inherent ability to release (E)-β-caryophyllene can potentially be used in new protection strategies of citrus trees against HLB.


Single amino acid substitutions at the N-terminus of a recombinant cytotoxic ribonuclease markedly influence biochemical and biological properties.
Onconase is a cytotoxic ribonuclease with antitumor properties. A semisynthetic gene encoding the entire protein sequence was constructed by fusing oligonucleotides coding for the first 15 and the last 6 of the 104 amino acids to a genomic clone that encoded the remaining amino acid residues [Newton, D. L., et al. (1997) Protein Eng. 10, 463-470]. The resulting protein product expressed in Escherichia coli exhibited little enzymatic or cytotoxic activity due to the unprocessed N-terminal Met amino acid residue. In this study, we demonstrate that modification of the 5'-region of the gene to encode [Met-(-1)]Ser or [Met-(-1)]Tyr instead of the native pyroglutamate results in recombinant onconase derivatives with restored activities. [Met-(-1)]rOnc(E1S) was more active than [Met-(-1)]rOnc(E1Y) in all assays tested. Consistent with the action of native onconase, [Met-(-1)]rOnc(E1S) was a potent inhibitor of protein synthesis in the cell-free rabbit reticulocyte lysate assay, degrading tRNA at concentrations that correlated with inhibition of protein synthesis. An interesting difference between the recombinant onconase derivatives and the native protein was their susceptibility to inhibition by the major intracellular RNase inhibitor, PRI (onconase is refractory to PRI inhibition). [Met-(-1)]rOnc(E1S) and [Met-(-1)]rOnc(E1Y) inhibited protein synthesis in intact SF539 neuroblastoma cells with IC50's very similar to that of onconase (IC50 3.5, 10, and 10 microg/mL after 1 day and 0.16, 0.35, and 2.5 microg/mL after 5 days for onconase, [Met-(-1)]rOnc(E1S), and [Met-(-1)]rOnc(E1Y), respectively). Similar to that of onconase, cytotoxic activity of the recombinant derivatives was potentiated by monensin, NH4Cl, and retinoic acid. Brefeldin A completely blocked the enhancement of cytotoxicity caused by retinoic acid with all three proteins. Thus, drug-induced alterations of the intracellular trafficking of the recombinant derivatives also resembles that of onconase. Stability studies as assessed in serum-containing medium in the presence or absence of cells at 37 degreesC showed that the recombinant proteins were as stable to temperature and cell culture conditions as the native protein. Therefore, exchanging the Glu amino acid residue at the amino terminus of onconase with an amino acid residue containing a hydroxyl group produces recombinant proteins with ribonuclease and cytotoxic properties similar to native onconase.


High pressure liquid chromatographic determination of saccharin in alcoholic products.
After preliminary cleanup, sodium saccharin can be quantitatively determined in wines and proprietary drugs by using high pressure liquid chromatography. The preliminary cleanup removes materials that cause column deterioration, loss of baseline stability, and interfering peaks. The average experimental error found in analyses of 6 wines for sodium saccharin content was 2.3% and the standard deviation was 0.01. In the analysis of 10 cough medicines and vitamin preparations, the difference between declared and experimental values for sodium saccharin averaged 5.7%. The recovery for the extraction process ranged from 97.8 to 101.6%.


Localization with Graph Diffusion Property.
Node localization is an essential issue in wireless sensor networks (WSNs). Many range-free localization methods have been proposed to satisfy the requirement of low-system cost. However, some range-free methods only depend on network connectivity, and others only utilize the proximity information attached in neighborhood ordering. To employ the strength of the above two aspects, this paper introduces a new metric system called Combined and Weighted Diffusion Distance (CWDD). CWDD is designed to obtain the relative distance among nodes based on both graph diffusion property and neighbor information. We implement our design by embedding CWDD into two well-known localization algorithms and evaluate it by extensive simulations. Results show that our design improves the localization performance in large scale and non-uniform sensor networks, which reduces positioning errors by as much as 26%.


Morphological and flow cytofluorometrical analyses of regenerated rat thymus after irradiation.
Reconstituted rat thymuses were studied by immunohistochemistry, transmission electron microscopy (TEM) and flow cytofluorometry on days 0, 1, 2, 3, 5, and 7 after whole-body sublethal irradiation (6 Gy). One day after irradiation, numerous apoptotic cells were seen in the cortical thymus; the percentage of the sub-G1 peak representing apoptotic cells was 8.9% in the DNA content histogram of cytofluorometry. On day 3, the thymic structure had been destroyed and no distinction was drawn between the cortex and medulla. In this stage, few thymocytes but many macrophages were present, and the percentage of the sub-G1 peak reached a peak at 13.0%. Bromodeoxyuridine (BrdU) incorporated cells gradually increased after irradiation, and immunohistochemically numerous apoptotic cells were found primarily in the cortex on day 7. These thymocytes showed some levels of electron density of the nucleus as revealed by TEM. The percentage of S phase cells did not change markedly (20-30%) based on one-color DNA content histograms, but the percentage of early S and S phase cells was extremely high on day 7 (70%). These data indicate that a part of DNA synthetic cells may result in apoptosis. The combination of immunohistochemistry, TEM and flow cytofluorometry to analyze DNA content and BrdU incorporation proved a useful tool for investigating the reconstituted thymus.


Scalable micromesh-digital spatial light modulators.
Digital spatial light modulators (SLMs) with small pitch comparable to the wavelength of illuminating light and large physical dimension comparable to consumer displays are highly demanding for realizing realistic digital holography but are impractical due to various technical issues. Previously we proposed the way to overcome these hurdles by scalable SLM-micromesh (μM) heterostructures utilizing large scale consumer displays and passive binary amplitude μMs (AMs). However, a few drawbacks with these heterostructures are identified such as their low power efficiency due to the blocking of light beam diffracted from the SLM by the opaque part of the AM and the brightest zeroth order diffraction beam causing the lower power efficiency at higher diffraction orders. Thus in this paper, we employed scalable binary phase micromeshes (PMs) instead of AMs in the scalable heterostructures. This is able to minimize the power loss and to diminish the zeroth order diffraction beam simultaneously without requiring any time consuming steps. As a result, this allows full utilization of large scale consumer displays for scalable digital holography by employing scalable SLM-μM heterostructures with negligible power loss.


The bird's nest inferior vena cava filter: progress report.
The bird's nest inferior vena cava filter, in clinical trial since 1982, has been placed in 568 patients at risk for pulmonary embolism. Of the 481 patients in whom the filter had been in place for 6 months or more, 440 were followed up clinically. The prevalence of clinically suspected recurrent pulmonary thromboembolism was 2.7% (12 patients) and that of inferior vena cava filter occlusion was 2.9% (13 patients). With the initial filter design, filter migration occurred in five patients. No migrations have occurred in the 147 patients treated with the filter after its modification to improve the anchoring system for greater stability. The bird's nest filter has proved safe and effective in the prevention of pulmonary embolism.


Child effects and child care: Implications for risk and adjustment.
Evocative effects of child characteristics on the quality and quantity of child care were assessed in two studies using longitudinal data from the NICHD Study of Early Child Care. We focus on the influence of child characteristics on two important aspects of the child care experience: language stimulation provided by caregivers and quantity of care. In Study 1, associations between the developmental status of children aged 15 to 54 months and the language stimulation provided by their caregivers were examined using path models, and longitudinal child effects were detected across the earliest time points of the study. In Study 2, the associations among child behavior, temperament, development, and time in care were examined. Little evidence was found for such child effects on time in care. The results are discussed in terms of the effects of child care on child development and implications for developmental processes, particularly for children at greatest risk for developmental delay or psychopathology.


Solution Combustion Synthesis: Low-Temperature Processing for p-Type Cu:NiO Thin Films for Transparent Electronics.
Low-temperature solution processing opens a new window for the fabrication of oxide semiconductors due to its simple, low cost, and large-area uniformity. Herein, by using solution combustion synthesis (SCS), p-type Cu-doped NiO (Cu:NiO) thin films are fabricated at a temperature lower than 150 °C. The light doping of Cu substitutes the Ni site and disperses the valence band of the NiO matrix, leading to an enhanced p-type conductivity. Their integration into thin-film transistors (TFTs) demonstrates typical p-type semiconducting behavior. The optimized Cu5% NiO TFT exhibits outstanding electrical performance with a hole mobility of 1.5 cm2 V-1 s-1 , a large on/off current ratio of ≈104 , and clear switching characteristics under dynamic measurements. The employment of a high-k ZrO2 gate dielectric enables a low operating voltage (≤2 V) of the TFTs, which is critical for portable and battery-driven devices. The construction of a light-emitting-diode driving circuit demonstrates the high current control capability of the resultant TFTs. The achievement of the low-temperature-processed Cu:NiO thin films via SCS not only provides a feasible approach for low-cost flexible p-type oxide electronics but also represents a significant step toward the development of complementary metal-oxide semiconductor circuits.


Oxidation state of the XRCC1 N-terminal domain regulates DNA polymerase beta binding affinity.
Formation of a complex between the XRCC1 N-terminal domain (NTD) and DNA polymerase beta (Pol beta) is central to base excision repair of damaged DNA. Two crystal forms of XRCC1-NTD complexed with Pol beta have been solved, revealing that the XRCC1-NTD is able to adopt a redox-dependent alternate fold, characterized by a disulfide bond, and substantial variations of secondary structure, folding topology, and electrostatic surface. Although most of these structural changes occur distal to the interface, the oxidized XRCC1-NTD forms additional interactions with Pol beta, enhancing affinity by an order of magnitude. Transient disulfide bond formation is increasingly recognized as an important molecular regulatory mechanism. The results presented here suggest a paradigm in DNA repair in which the redox state of a scaffolding protein plays an active role in organizing the repair complex.


Internal audit consider the implications.
Internal audit can not only allay external and internal concerns about appropriateness of business operations, but also help improve efficiency and the bottom line. To get an internal audit function under way, healthcare organizations need to obtain board buy-in, form an audit committee of the board, determine resources needed, perform a risk assessment, and develop an internal audit plan.


AMELX Gene Association with Dental Caries in Iranian Adults.
Dental decay is a disease that is greatly affected by environmental components, but recently there have been an increasing number of documents supporting a genetic factor in the development of caries. The purpose of this study was to examine the association between dental caries and single-nucleotide polymorphisms in the AMELX gene. This research was carried out on 360 individuals of both sexes, who were referred to the dental school at the Shiraz University of Medical Sciences. In this research, individuals aged 20-65 years were divided into two groups: controls (decayed, missed, or filled teeth (DMFT) ≤ 5; n = 180) and cases (DMFT ≥ 14; n = 180). The tetra-primer ARMS-PCR technique was performed for genotyping the DNA extracted from blood cells. Analysis of the AMELX rs946252 polymorphism showed that the T allele of rs946252 was a significant protective factor against dental caries in Iranian adults (T vs. C: OR = 0.70, 95% CI: 0.49-0.98, P = 0.04). We demonstrated the significant differences in the genotype frequencies under two genetic models: overdominant (TC vs. TT + CC: OR 0.35, 95% CI 0.19-0.64, P = 0.0006) and recessive (CC vs. TC + TT: OR 2.57, 95% CI 1.39-4.76, P = 0.002). Our results show that the SNPs of the AMELX gene may be related with susceptibility to dental caries in Iranian adults.


Cultural consensus and intracultural diversity in ethnotaxonomy: lessons from a fishing community in Northeast Brazil.
Traditional fishing communities are strongholds of ethnobiological knowledge but establishing to what degree they harbor cultural consensus about different aspects of this knowledge has been a challenge in many ethnobiological studies. We conducted an ethnobiological study in an artisanal fishing community in northeast Brazil, where we interviewed 91 community members (49 men and 42 women) with different type of activities (fishers and non-fishers), in order to obtain free lists and salience indices of the fish they know. To establish whether there is cultural consensus in their traditional knowledge on fish, we engaged a smaller subset of 45 participants in triad tasks where they chose the most different fish out of 30 triads. We used the similarity matrices generated from the task results to detect if there is cultural consensus in the way fish were classified by them. The findings show how large is the community's knowledge of fish, with 197 ethnospecies registered, of which 33 species were detected as salient or important to the community. In general, men cited more fish than women. We also found that there was no cultural consensus in the ways fish were classified. Both free-listing and triad task methods revealed little cultural consensus in the way knowledge is structured and how fish were classified by community members. Our results suggest that it is prudent not to make assumptions that a given local community has a single cultural consensus model in classifying the organisms in their environment.


Subdiffusion of mixed origins: when ergodicity and nonergodicity coexist.
Single particle trajectories are investigated assuming the coexistence of two subdiffusive processes: diffusion on a fractal structure modeling spatial constraints on motion and heavy-tailed continuous time random walks representing energetic or chemical traps. The particles' mean squared displacement is found to depend on the way the mean is taken: temporal averaging over single-particle trajectories differs from averaging over an ensemble of particles. This is shown to stem from subordinating an ergodic anomalous process to a nonergodic one. The result is easily generalized to the subordination of any other ergodic process (i.e., fractional Brownian motion) to a nonergodic one. For certain parameters the ergodic diffusion on the underlying fractal structure dominates the transport yet displaying ergodicity breaking and aging.


Social Support and Depression After Cardiac Surgery in Elderly Patients.
Two methods of measuring social support components were compared for their ability to predict depression 6 months after cardiac surgery in older patients (N = 155). Multiple regression models were used to compare summary support measures with subtype measures. A personality inventory was also included to rule out the possibility that significant findings about relationships of depression and social support were due primarily to personality dimensions. In the summary model, only the number of network members seen regularly was associated with less depression. In the subtype model, the number of relatives seen regularly and perceived adequacy of support from friends were associated with less depression, whereas receipt of tangible support was associated with more. When examined together with personality dimensions, both the summary components and subtypes of components of social support were better predictors of depressive symptomatology than the personality dimensions. The results helped confirm the importance of social support factors to the occurrence of depression in elderly patients and suggested that measures of social support subtypes were more informative than summary measures of social support.


Nourishing the brain on deep space missions: nutritional psychiatry in promoting resilience.
The grueling psychological demands of a journey into deep space coupled with ever-increasing distances away from home pose a unique problem: how can we best take advantage of the benefits of fresh foods in a place that has none? Here, we consider the biggest challenges associated with our current spaceflight food system, highlight the importance of supporting optimal brain health on missions into deep space, and discuss evidence about food components that impact brain health. We propose a future food system that leverages the gut microbiota that can be individually tailored to best support the brain and mental health of crews on deep space long-duration missions. Working toward this goal, we will also be making investments in sustainable means to nourish the crew that remains here on spaceship Earth.


Ovarian stimulation with low-dose pure follicle-stimulating hormone in polycystic ovarian syndrome anovulatory patients: effect of long-term pretreatment with gonadotrophin-releasing hormone analogue.
A randomised clinical trial was performed to evaluate the effect of a 3-month gonadotrophin-releasing-hormone analogue (GnRH-a) in one cycle of ovulation induction with low-dose pure follicle-stimulating hormone (pFSH) in patients with polycystic ovarian syndrome (PCOS) anovulation. Twenty patients with chronic anovulation due to PCOS were randomised to ovulation induction with pFSH administered in a low-dose schedule with (10 patients) and without (10 patients) a 3-month pretreatment with GnRH-a. Ultrasound scan only monitoring of follicular growth, evaluation of plasmatic oestradiol at the day of triggering of ovulation with human chorionic gonadotrophin 5,000 IU and evaluation of plasmatic progesterone 8 days after were the main outcome measures. Ovulation occurred in 9 patients treated with pFSH and in 2 patients treated with GnRH-a plus pFSH. Five pregnancies in the pFSH group and no pregnancy in the GnRH-a group were obtained. Five cycles were stopped due to multifollicular growth in the GnRH-a group and 1 in the pFSH group. Pretreatment with a 3-month administration of a GnRH-a did not improve the ovulation rate and pregnancy rate in PCOS patient ovulation induction with low-dose pFSH.


[Diagnosis and therapy of multiple sclerosis].
The diagnosis of multiple sclerosis is still a clinical one, and depends on the occurrence of neurological symptoms due to lesions at two or more necessarily distinct sites in the white matter of the central nervous system. Up to now there exists no specific laboratory test for the diagnosis of multiple sclerosis. The cerebrospinal fluid-profile strongly supporting the diagnosis of multiple sclerosis consists of: cell count slightly elevated, total protein concentration normal or slightly elevated, in the electrophoresis distinct immunreaction without disturbance of the blood-brain-barrier, i.e. significant increase of gammaglobulins and IgG, oligoclonal pattern of the gammaglobulin subfractions. Newly developed diagnosistic possibilities are based on the determination of myelin basic protein, determination of the different glycerophosphatides and on the measurement of the activity of lipid hydrolyzing enzymes. Disturbances of lipid metabolism play an important role in the course of demyelination. Therapy of multiple sclerosis by steroids and immunsuppression will be discussed.


Nationwide survey of hospital practices when compounding parenteral nutrition solutions in latex-allergic patients.
We surveyed 100 institutions in 50 states, varying in size from 50 to 1,000 beds. The purpose of this survey was to examine the policies and techniques hospitals used in confirming latex allergy (LA) in patients and preparing parenteral nutrition (PN) for LA patients. Our survey indicated that within the institutions in our study, many inpatient pharmacists do not use any defined method for confirming LA other than what is documented in the patient profile upon admission. Most inpatient pharmacies are not aware of any institutional policy concerning parenteral medications in LA patients, and some do not identify the importance of LA in preparing PN. It is apparent from the results of this survey that uniform guidelines or practice standards for this important issue should be developed. Although the publications on LA are numerous, they mostly deal with the exposure to latex gloves or latex devices. Knowledge of preparing parenteral medications for LA patients in the literature is minimal. It is also clear that awareness and knowledge of pharmacy personnel should be enhanced. Finally, we are hoping that this survey will send a clear message to pharmacy organizations to develop guidelines or pharmacy practice standards for this issue, and for health institutions to develop policies and make them available to their personnel.


Small gap sleeve bridging can improve the accuracy of peripheral nerve selective regeneration.
The pure motor peripheral nerves animal model, obtained by ablating the dorsal root ganglions (DRGs), was used to investigate the accuracy of peripheral nerve selective regeneration using small gap sleeve bridging compared to epineurium neurorrhaphy. The results showed that the number of improperly regenerated motor axons in the distal stump and the misrouting ratio were significantly lower when the nerve transection was treated by small gap sleeve bridging. This suggests that more accurate reinnervation may be achieved by small gap sleeve bridging than by traditional epineurium neurorrhaphy.


The type III secretion system is necessary for the development of a pathogenic and endophytic interaction between Herbaspirillum rubrisubalbicans and Poaceae.
Herbaspirillum rubrisubalbicans was first identified as a bacterial plant pathogen, causing the mottled stripe disease in sugarcane. H. rubrisubalbicans can also associate with various plants of economic interest in a non pathogenic manner. A 21 kb DNA region of the H. rubrisubalbicans genome contains a cluster of 26 hrp/hrc genes encoding for the type three secretion system (T3SS) proteins. To investigate the contribution of T3SS to the plant-bacterial interaction process we generated mutant strains of H. rubrisubalbicans M1 carrying a Tn5 insertion in both the hrcN and hrpE genes. H. rubrisulbalbicans hrpE and hrcN mutant strains of the T3SS system failed to cause the mottled stripe disease in the sugarcane susceptible variety B-4362. These mutant strains also did not produce lesions on Vigna unguiculata leaves. Oryza sativa and Zea mays colonization experiments showed that mutations in hrpE and hrcN genes reduced the capacity of H. rubrisulbalbicans to colonize these plants, suggesting that hrpE and hrcN genes are involved in the endophytic colonization. Our results indicate that the T3SS of H. rubrisubalbicans is necessary for the development of the mottled stripe disease and endophytic colonization of rice.


Etanercept for refractory asthma therapy.
Asthma is a chronic disease of the airways in which inflammation causes bronchial hyper-reactivity and consequent asthma attacks triggered by various stimuli. The bronchospasm attacks are usually relieved by short-acting beta2 agonists, and inflammation and bronchial hyper-reactivity are reduced by maintenance therapy and, in particular, by inhaled corticosteroids. In milder asthma subjects, airway inflammation is dominated by eosinophils, whereas in more severe asthma increased neutrophil counts were detected. In severe/refractory asthma, TNF-alpha is known to play a role in the maintenance of neutrophilic inflammation and of bronchial hyper-responsiveness and is not influenced by corticosteroid therapy. Etanercept, a TNF-alpha-blocking agent, could represent one of the potential therapies for refractory asthma based on demonstrated safety and efficacy.


Characterization of the rate, predictors, and thrombotic complications of thrombocytosis in iron deficiency anemia.
The association of thrombocytosis with iron deficiency anemia (IDA) is well-recognized, but data describing the rate, predictors, and risk of thrombotic complications associated with IDA-related thrombocytosis are limited. We queried an institutional patient data repository containing comprehensive chart data for over 6 million patients to identify IDA patients with and without thrombocytosis and thrombotic events over a 40-year time period (1979 to 2019). Demographics, hematological parameters, thrombosis history, and other medical history were collected. Fidelity of query data was assessed via detailed manual chart review of 700 patients, including confirmation of ferritin and hematologic parameters in addition to temporal and clinical association of thrombocytosis. Our queries identified 36 327 cases of IDA of which 15 022 had thrombocytosis. Following assessment for data integrity, we observed a thrombocytosis rate of 32.6% in patients with IDA. The rate of thrombosis was calculated to be 7.8% in patients with IDA and 15.8% in patients with IDA and thrombocytosis. Platelet mass index at time of peak thrombocytosis was significantly higher than at baseline and was strongly negatively correlated with hemoglobin at peak thrombocytosis. A multivariable model demonstrated a significant predictive relationship between decreasing hemoglobin and increasing platelet count at peak thrombocytosis. In conclusion, we observed reactive thrombocytosis in one-third of IDA patients, and a 2-fold thrombosis risk in patients with IDA and thrombocytosis compared with patients with IDA alone. Given the global burden of untreated and undertreated IDA, adequate IDA treatment may reduce thrombotic complications and associated morbidity and mortality.


Newly detected liver nodules with a history of colorectal cancer: are they metastatic? Review of 2,632 cases in a single center.
The diagnosis of newly detected liver nodules in patients with colorectal cancer (CRC) is crucial for determining prognosis and treatment. Accurate identification of benign nodules can help avoid unnecessary therapy. The aim of our study was to retrospectively review patients with CRC who underwent liver resection for benign liver nodules misdiagnosed as CRC metastasis (CRLM) in our institution. We reviewed all patients with a history of CRC who underwent liver resection from January 2012 to December 2019 in our institution. We specifically focused on nodules pathologically confirmed as benign. The pathology was rechecked by an independent pathologist. The clinicopathological characteristics of these patients were collected. Preoperative imaging examinations, including ultrasound (US), magnetic resonance imaging (MRI), and positron emission tomography-computed tomography (PET-CT) were reviewed. From 2012 to 2019, a total of 2,632 patients with CRC who were preoperatively diagnosed CRLM received liver resection, among which 2,584 (98.2%) cases were proven to be malignant, and 48 (1.8%) cases were benign. Among these 48 cases, 24 were pathologically confirmed as focal nodular hyperplasia (FNH), 9 were peliosis, 10 were inflammatory lesions, and 5 were hemangioma. At least one preoperative imaging examination indicated CRLM, with a median size of 2.0 cm (range, 0.4-8.0 cm). Before liver resection, ten patients received chemotherapy after the discovery of liver nodules. It should be noted that newly detected liver nodules in patients with a history of CRC could be benign. Accurate diagnosis of liver nodules in CRC is necessary to avoid overtreatment and to identify cost-effective medication.


Abrupt weaning reduces postweaning growth and is associated with alterations in gastrointestinal markers of development in dairy calves fed an elevated plane of nutrition during the preweaning period.
The benefits of feeding elevated quantities of milk to dairy calves have been well established. However, there is a reluctance to adopt this method of feeding in commercial dairy production because of concerns around growth, health, and ruminal development during weaning. The objective of this study was to characterize the effect of an abrupt (0 d step-down) or gradual (12 d step-down) feeding scheme when calves are fed an elevated plane of nutrition (offered 1.35 kg of milk replacer/d). For this experiment, a total of 54 calves were randomly assigned to an abrupt or a gradual weaning protocol before weaning at 48 d of life. Calves were housed and sampled in individual pens for the duration of the experiment, and milk, starter, and straw intake were measured on a daily basis. Body weight was measured every 6 d, whereas blood, rumen fluid, and fecal samples were collected on d 36 (pre-step-down), 48 (preweaning), and 54 (postweaning) of the experiment. Although the growth rates of the step-down calves were lower from d 37 to weaning (0.62 ± 0.04 vs. 1.01 ± 0.04 kg/d), the postweaning average daily gain was greater compared with the group that was abruptly weaned (0.83 ± 0.06 vs. 0.22 ± 0.06 kg/d). Total ruminal volatile fatty acid was greater in the step-down group on the day of weaning (d 48; 59.80 ± 2.25 vs. 45.01 ± 2.25 mmol), whereas the fecal starch percentage was lower during postweaning compared with the abruptly weaned calves (d 54; 3.31 ± 0.76 vs. 6.34 ± 0.76%). Analysis of the digestive tract of bull calves on d 55 revealed minimal differences between gross anatomy measurements of gut compartments as well as no morphological differences in rumen papillae development, yet the total mass of rumen when full of contents was larger in the step-down calves (7.83 ± 0.78 vs. 6.02 ± 0.78 kg). Under the conditions of this study, the results showcase the benefits of a step-down feeding strategy from an overall energy balance standpoint, due to increased adaptation of the gastrointestinal tract preweaning.


Pharyngeal airway dimensions in skeletal class II: A cephalometric growth study.
This retrospective study aimed to evaluate the nasopharyngeal and oropharyngeal dimensions of individuals with skeletal class II, division 1 and division 2 patterns during the pre-peak, peak, and post-peak growth periods for comparison with a skeletal class I control group. Totally 124 lateral cephalograms (47 for skeletal class I; 45 for skeletal class II, division 1; and 32 for skeletal class II, division 2) in pre-peak, peak, and post-peak growth periods were selected from the department archives. Thirteen landmarks, 4 angular and 4 linear measurements, and 4 proportional calculations were obtained. The ANOVA and Duncan test were applied to compare the differences among the study groups during the growth periods. Statistically significant differences were found between the skeletal class II, division 2 group and other groups for the gonion-gnathion/sella-nasion angle. The sella-nasion-B-point angle was different among the groups, while the A-point-nasion-B-point angle was significantly different for all 3 groups. The nasopharyngeal airway space showed a statistically significant difference among the groups throughout the growth periods. The interaction among the growth periods and study groups was statistically significant regarding the upper oropharyngeal airway space measurement. The lower oropharyngeal airway space measurement showed a statistically significant difference among the groups, with the smallest dimension observed in the skeletal class II, division 2 group. The naso-oropharyngeal airway dimensions showed a statistically significant difference among the class II, division 1; class II, division 2; and class I groups during different growth periods.


Necrotising fasciitis in an infant with congenital insensitivity to pain syndrome.
We present a rare case of necrotising fasciitis in an infant with congenital insensitivity to pain syndrome. The aetiology, diagnosis and management of necrotising fasciitis in children are compared with those in adults. In contrast to adults, children affected by necrotising fasciitis are usually previously healthy and have no predisposing factors. Early diagnosis, intravenous antibiotics and aggressive surgical debridement are mandatory for an optimal outcome.


[Effect of Miscanthus planting on the structure and function of soil bacterial community.]
Miscanthus is a promising candidate species of second-generation energy crops. To our knowledge, the composition and function of Miscanthus rhizosphere bacterial communities has not yet been reported. In this study, rhizosphere soil samples were collected from Miscanthus (Xiangzamang No. 1) which was grown in Nanyang City for five years and bareground (as the control) to analyze the bacterial community structure and diversity using 16S rRNA gene sequencing on the Illumina MiSeq platform. PICRUSt was used to determine the metabolic and functional abilities of soil bacterial communities. Phylogenetic analysis based on 16S rRNA gene sequences showed that sol bacteria could be divided into 23 phyla and 231 genera, with high richness of the community composition. The dominant phyla were Proteobacteria, Acidobacteria, Actinobacteria, Chloroflexi, Bacteroidetes and Gemmatimonadetes. The bacterial community diversity in the rhizosphere samples of Xiangzamang No. 1 was lower than that in unplanted samples. Rhizosphere bacterial communities were affected by Miscanthus crops. Based on the PICRUSt analysis of bacterial community functions, our results revealed a wide genetic diversity of organisms involved in various essential processes,such as amino acid transport and metabolism, cell wall/membrane/envelope biogenesis, signal transduction mechanisms. Based on the 16S rRNA gene copy number of the detected phylotypes, 22 bacterial metabolic function in the rhizosphere samples of Miscanthus was higher than that in bareground. Results from N- and P-cycling gene analysis showed that Miscanthus planting altered the N- and P-cycling metabolic capacities of soil bacteria.


Investigating the Streptococcus sinensis competence regulon through a combination of transcriptome analysis and phenotypic evaluation.
Streptococcus sinensis is a recently identified member of the Mitis group of streptococci. This species has been associated with infective endocarditis; however its mechanisms of pathogenesis and virulence are not fully understood. This study aimed to investigate the influence of the competence-stimulating peptide (CSP) and the competence regulon quorum-sensing circuitry (ComABCDE) on subsequent gene transcription and expression, as well as resultant phenotypes. In this study we confirmed the native CSP identity, ascertained when endogenous CSP was produced and completed a transcriptome-wide analysis of all genes following CSP exposure. RNA sequencing analysis revealed the upregulation of genes known to be associated with competence, biofilm formation and virulence. As such, a variety of phenotypic assays were utilized to assess the correlation between increased mRNA expression and potential phenotype response, ultimately gaining insight into the effects of CSP on both gene expression and developed phenotypes. The results indicated that the addition of exogenous CSP aided in competence development and successful transformation, yielding an average transformation efficiency comparable to that of other Mitis group streptococci. Additional studies are needed to further delineate the effects of CSP exposure on biofilm formation and virulence. Overall, this study provides novel information regarding S. sinensis and provides a substantial foundation on which this species and its role in disease pathogenesis can be further investigated.


Toward Reagent-Free Discrimination of Alzheimer's Disease Using Blood Plasma Spectral Digital Biomarkers and Machine Learning.
Alzheimer's disease (AD) is the most prevalent neurodegenerative disease. The detection of early-stage AD is particularly desirable because it would allow early intervention. However, a minimally invasive, low-cost, and accurate discrimination or diagnostic method for AD is especially difficult in the earliest stage of AD. The aim of this research is to discover blood plasma spectral digital biomarkers of AD, develop a novel intelligent method for the discrimination of AD and accelerate the translation of Fourier transform infrared (FTIR) spectral-based disease discrimination methods from the laboratory to clinical practice. Since vibration spectroscopy can provide the structure and chemical composition information of biological samples at the molecular level, we investigated the potential of FTIR spectral biomarkers of blood plasma to differentiate between AD patients and healthy controls. Combined with machine learning technology, we designed a hierarchical discrimination system that provides reagent-free and accurate AD discrimination based on blood plasma spectral digital biomarkers of AD. Accurate segregation between AD patients and healthy controls was achieved with 89.3% sensitivity and 85.7% specificity for early-stage AD patients, 92.8% sensitivity and 87.5% specificity for middle-stage AD patients, and 100% sensitivity and 100% specificity for late-stage AD patients. Our results show that blood plasma spectral digital biomarkers hold great promise as discrimination markers of AD, indicating the potential for the development of an inexpensive, reagent-free, and less laborious clinical test. As a result, our research outcome will accelerate the clinical application of spectral digital biomarkers and machine learning.


A New Perspective for Infantile Hepatic Hemangioma in the Age of Propranolol: Experience at Baskent University.
Propranolol was first used in 2008 to treat hemangioma; its efficacy and safety have since changed the classical treatment indications. Infantile hepatic hemangioma presents as a spectrum of clinical conditions varying from simple asymptomatic lesions to lethal complications. Tufted hemangioma and Kaposiform hemangioendothelioma are congenital vascular tumors that lead to Kasabach-Merritt syndrome. Hemangiomas, like pure arteriovenous malformations, can cause hyperdynamic heart failure, and diffuse nodular-type hemangiomas can present with hypothyroidism. Respiratory problems and hepatic failure can be associated with diffuse nodular-type liver hemangiomas. There is a spectrum of approaches to management, varying from "watchful waiting" to liver transplant. In the age of propranolol, there has been a prominent change in the infantile hepatic hemangioma treatment algorithm. Our suggestion is early treatment with 3 mg/kg/day propranolol plus 1.0 to1.5 mg/kg/day prednisolone in all patients. This protocol is the most effective strategy for type 3 infantile hepatic hemangioma. Approximately one-third of patients with abdominal compartment syndrome in the era before propranolol treatment required liver transplant; this new treatment obviates transplant for many of these patients.


Aging: A mitochondrial DNA perspective, critical analysis and an update.
The mitochondrial theory of aging, a mainstream theory of aging which once included accumulation of mitochondrial DNA (mtDNA) damage by reactive oxygen species (ROS) as its cornerstone, has been increasingly losing ground and is undergoing extensive revision due to its inability to explain a growing body of emerging data. Concurrently, the notion of the central role for mtDNA in the aging process is being met with increased skepticism. Our progress in understanding the processes of mtDNA maintenance, repair, damage, and degradation in response to damage has largely refuted the view of mtDNA as being particularly susceptible to ROS-mediated mutagenesis due to its lack of "protective" histones and reduced complement of available DNA repair pathways. Recent research on mitochondrial ROS production has led to the appreciation that mitochondria, even in vitro, produce much less ROS than previously thought, automatically leading to a decreased expectation of physiologically achievable levels of mtDNA damage. New evidence suggests that both experimentally induced oxidative stress and radiation therapy result in very low levels of mtDNA mutagenesis. Recent advances provide evidence against the existence of the "vicious" cycle of mtDNA damage and ROS production. Meta-studies reveal no longevity benefit of increased antioxidant defenses. Simultaneously, exciting new observations from both comparative biology and experimental systems indicate that increased ROS production and oxidative damage to cellular macromolecules, including mtDNA, can be associated with extended longevity. A novel paradigm suggests that increased ROS production in aging may be the result of adaptive signaling rather than a detrimental byproduct of normal respiration that drives aging. Here, we review issues pertaining to the role of mtDNA in aging.


Two Independent HIV Epidemics in Saint Petersburg, Russia Revealed by Molecular Epidemiology.
The HIV epidemic in Russia, one of the world's fastest growing, has been concentrated mostly among people who inject drugs (PWID). We sought to explore the epidemiology of the epidemic in St. Petersburg by sampling from the highest risk groups of PWID and men who have sex with men (MSM) and use viral sequencing data to better understand the nature of the city's epidemic. Serological testing confirmed an HIV prevalence among PWID in excess of 40%. All but 1 of 110 PWID whose blood samples were tested for genetic diversity were infected by subtype A virus, specifically by the AFSU strain. The remaining person was infected with a CRF-06cpx recombinant. Analysis of pairwise genetic distance among all PWID studied revealed an average of 3.1% sequence divergence, suggesting clonal introduction of the AFSU strain and/or constraints on sequence divergence. The HIV prevalence was less than 10% among MSM. All 17 sequences from HIV-infected MSM were found to be a clade B virus with a much higher average sequence diversity of 15.7%. These findings suggest two independent epidemics with little overlap between the two highest at-risk populations, which will require different HIV prevention approaches.


Topological characterization of crystallization of gold nanoclusters.
In this study we use a new topological structure measure to analyze the local environment of 923 atom gold clusters quenched from the melt, at various quench rates, by molecular dynamics. The crystallization and geometrical rearrangements of the core atoms upon freezing can be clearly observed using our structure measure which is based on planar graphs. Our results support the hypothesis that crystallization is initiated from the surface and proceeds into the cluster core.


Impact of HbAlc on acute cardiac states.
To find out the impact of HbAlc levels on the severity and short term complications of patients with heart disease admitted to the Intensive Coronary Care Unit (ICCU). One hundred and sixty six patients admitted to ICCU in 2006 with acute cardiac states (unstable angina, acute myocardial infarction, heart failure, cardiomyopathy) were prospectively studied. Patients were divided into two groups--Group A (diabetics) and Group B (non diabetics). Patients were followed up till the time of discharge. Out of the 166 patients, 92 were diabetic (group A) and 74 were non diabetic (group B). The mean HbAlc of group A was 8.4+1.9% and that of group B was 5.7+0.6%. Risk factors like dyslipidemia, hypertension, previous history of heart disease and triple vessel disease were found more in group A than in group B. History of smoking, positive family history of heart disease, and angina as a presenting symptom were more in group B. Complications like heart failure and post infarction angina occurred significantly more in patients with diabetes. In group A, unstable angina, ST elevation myocardial infarction, cardiac failure, accelerated hypertension, dilated cardiomyopathy and triple vessel disease were seen in a significantly higher proportion of patients with poor glycemic control (HbAlc>or=7%) compared to patients with HbAlc level<7%. In group B, 72/74 (97.2%) patients had HbAlc levels>or=5%, 68.8% of whom had HbAlc levels of >or=5.6%. Severity and complications of heart disease were significantly higher in diabetics and showed a significant correlation with HbAlc. A large number of non diabetics presenting with acute cardiac states i.e. 97.2%, had HbAlc values>or=5%.


Purkinje and ventricular activation sequences of canine papillary muscle. Effects of quinidine and calcium on the Purkinje-ventricular conduction delay.
We have studied in vitro preparations of canine right and left papillary muscles to determine the excitation sequences of the Purkinje and ventricular cells, using both monopolar surface electrodes and intracellular microelectrodes. Our results show, for right papillary muscles, that the Purkinje layer covers the basal part of the muscle, and that activation from the right bundle branch propagates over all of the Purkinje layer, but directly activates the underlying ventricular layer only at specific junctional sites. Left papillary muscles have attachments to both apical and basal Purkinje strands and the Purkinje layer covers the entire muscle, but, as for right papillary muscles, activation from the Purkinje layer to the ventricular layer occurs only at basal junctional sites. Antidromic conduction in papillary muscles (propagation from the ventricular layer to the Purkinje layer) can occur at regions other than the specific sites through which the Purkinje layer activates the ventricular layer. At the identified junctional sites, the Purkinje cell action potential duration is significantly shorter than in the free-running strand, but it remains longer than that of the ventricular cells. The time delay at the junctional sites is increased by quinidine, increased calcium concentration, and increased pacing frequency.


High resolution analysis of human prostatic fluid by two-dimensional electrophoresis.
High-resolution two-dimensional electrophoresis has been used to resolve the major protein components of human prostatic fluid. Samples taken from individuals ranging in age from 19 to 74 years show ten major proteins that are consistently present in the fluids examined. Seven major proteins appear to have age-dependent patterns of synthesis and accumulation in the prostatic fluid. A major protein in the human fluid has electrophoretic properties similar to the glycosylated component of the rat ventral prostate secretory protein known as prostatic binding protein, prostatein, or estramustine binding protein. The isoelectric point/molecular weight of the human protein is 6.0/17,000 compared with 5.6/13,000 for the rat protein. Protein patterns from benign prostatic hyperplasia cases were not dramatically different from the normal patterns.


Obstetric ultrasonography: recent observations in first trimester of pregnancy.
It is possible both to accurately measure foetal size and visualize the yolk sac and the amniotic membrane by ultrasound scanning in the first trimester of pregnancy. In threatened abortion an intrauterine haematoma or a foetal size smaller than normal are ominous signs. Likewise, too small a foetal size in early diabetic pregnancy indicates an increased risk of foetal malformation.


Subarachnoid hemorrhage caused by rupture of a distal anterior inferior cerebellar artery aneurysm--three case reports.
Three female patients, two under 35 years old, presented with ruptured aneurysms of the distal anterior inferior cerebellar artery (AICA) manifesting as subarachnoid hemorrhage. The first patient had a ruptured saccular aneurysm of the meatal loop of AICA, which was treated by direct neck clipping. The second patient had a ruptured aneurysmal lesion that arose from a microvascular anomaly of the dorsolateral portion of the AICA, which was successfully treated by trapping. The third patient was dead on arrival, and autopsy revealed a ruptured saccular aneurysm in the meatal loop of the AICA. The mechanism of development of distal AICA aneurysm remains unclear, and some cases indicate a complicated causal relationship between the aneurysms and vascular anomalies. Neurosurgeons need to carefully evaluate the vascular structure around the aneurysms by preoperative angiography in each case, and select the most appropriate strategy.