Elucidating the role of D4 receptors in mediating attributions of salience to incentive stimuli on Pavlovian conditioned approach and conditioned reinforcement paradigms.
The power of drug-associated cues to instigate drug 'wanting' and consequently promote drug seeking is a corner stone of contemporary theories of addiction. Gambling disorder has recently been added to the pantheon of addictive disorders due to the phenomenological similarities between the diseases. However, the neurobiological mechanism that may mediate increased sensitivity towards conditioned stimuli in addictive disorders is unclear. We have previously demonstrated using a rodent analogue of a simple slot machine that the dopamine D4 receptor is critically engaged in controlling animals' attribution of salience to stimuli associated with reward in this paradigm, and consequently may represent a target for the treatment of gambling disorder. Here, we investigated the role of acute administration of a D4 receptor agonist on animals' responsivity to conditioned stimuli on both a Pavlovian conditioned approach (autoshaping) and a conditioned reinforcement paradigm. Following training on one of the two tasks, separate cohorts of rats (male and female) were administered a dose of PD168077 shown to be maximally effective at precipitating errors in reward expectancy on the rat slot machine task (10mg/kg). However, augmenting the activity of the D4 receptors in this manner did not alter behaviour on either task. These data therefore provide novel evidence that the D4 receptor does not alter incentive motivation in response to cues on simple behavioural tasks.


Antioxidant combinations are no more beneficial than individual components in combating ram sperm oxidative stress during storage at 5°C.
The unfrozen storage of ram semen for 2-4 days is an important goal for the acceptance of artificial insemination in sheep breeding programmes. The objective was to investigate the benefits of antioxidant supplementation on the production of hydrogen peroxide (H(2)O(2)) by ram spermatozoa stored at 5°C over 3 days. Ejaculates from 9 rams were split between two defined diluents, INRA-96 and RSD-1, and cooled slowly to 5°C for storage. Four different additives (vitamin E phosphate 6-100 μmol/L, catalase 500 IU+superoxide dismutase 9-150 μmol/L, and glutathione peroxidase, 20 IU) were investigated both separately and in combination. The amount of H(2)O(2) generated was assessed by use of a 1-step fluorometric micro-plate assay. Sperm viability, acrosome integrity and membrane fluidity were assessed by flow cytometry. H(2)O(2) production in INRA-96- compared with RSD-1-diluted spermatozoa increased approximately 2-3-fold after 24h in storage at 5°C and then declined up to 72 h, while that in RSD-1 showed no change over 72 h; this had no effect on the sperm characteristics. Addition of antioxidants singly reduced H(2)O(2) production in INRA-96, regardless of concentration. Optimal concentrations were vitamin E phosphate 12.5 μmol/L, catalase 500 IU, superoxide dismutase 37 μmol/L, and glutathione peroxidase, 20 IU. In any combination, none was more effective than others. Viability was reduced but acrosomal integrity protected by the antioxidants in INRA-96 but not in RSD-1; membrane fluidity was not affected. Based on this study, there were no combinations more efficient at combating oxidative stress than any one alone.


Acute myocarditis associated with Shigella sonnei gastroenteritis.
We describe two patients with acute myocarditis temporally associated with an acute Shigella sonnei gastroenteritis. This association has not been described in children and should be considered in children with shigellosis who do not respond to rehydration therapies.


Elastic properties of the human chest during cardiopulmonary resuscitation.
Sternal displacement during CPR was measured in 11 adults and 2 manikins (Recording Resusci Anne) while the chest was compressed with variable maximum pulse compression force at a rate of 60/min with compression duration of 0.5-0.6 sec. In 10 patients, the pulsatile sternal elastic characteristic can be satisfactorily described with a 2nd degree polynomial F = beta Ds + gamma D2s, where beta = 54.9 +/- 29.4 (mean +/- SD) N/cm is the pulsatile initial elasticity and gamma = 10.8 +/- 4.1 N/cm2 is the posterior resiliency. The sternal characteristics of manikins were linear F = kDs with high elasticity constants, k = 131 and 142 N/cm. Therefore, the manikins tested differ significantly in elasticity characteristics from the human chest during resuscitation. In general, the manikin: (1) has markedly greater stiffness at the onset of compression, and (2) maintains a linear stiffness throughout the usual range of displacement, rather than becoming stiffer with greater chest displacement.


The influence of dysbiosis on kidney stones that risk up renal cell carcinoma (RCC).
Kidney stone is a common urological condition, the prevalence and incidence of which has escalated in the last few years due to dietary habits and other related medical conditions such as obesity and diabetes mellitus. It is a chronic disease which leads to loss of kidney function(s) and nephrectomy. Chronic kidney stone disease has been shown to be associated with transitional cell carcinoma (TCC) or renal cell carcinoma (RCC) and kidney tumors have been found to be more frequent among patients with kidney stones. Although hyperoxaluria is mainly responsible for kidney stone formation, dysbiosis of the gut and urinary tract microbiome may in part contribute to kidney stone disease. Dysbiosis of the gut and urinary tract microbiome have been linked to kidney stone diseases with both gain and loss of function. The review provides a detailed study of how the variations in the microbiome of the human gut and urinary tract result in the chronic kidney stone diseases which are associated with increased papillary RCC risks.


Hexose metabolism in pancreatic islets. Galactose transport, phosphorylation and oxidation.
In rat pancreatic islets, the apparent space of distribution of galactose is not different from that of other hexoses. In homogenates of islets or tumoral insulin-producing cells, galactose is phosphorylated at a very low rate relative to either glucose phosphorylation in the same tissues or galactose phosphorylation by liver homogenates. In intact islets, galactose increases modestly the glucose 6-phosphate content and is oxidized at a much lower rate than glucose. Galactose slightly increases insulin output in the presence of a stimulatory concentration of glucose but fails to provoke insulin release in the absence of glucose, whether in islets removed from rats fed a normal or galactose-rich diet. The low rate of galactose oxidation and its poor insulinotropic capacity appear attributable to the weak activity of galactokinase in pancreatic islets.


Colour flow Doppler mapping in the assessment of prosthetic valve regurgitation.
Two hundred Carpentier-Edwards, Björk-Shiley, and Starr-Edwards prostheses in 173 patients were examined. Sixteen (16%) in the aortic and 24 (25%) in the mitral position were associated with clinical signs of regurgitation. A phased array system (Hewlett-Packard A77020A) with a 2.5 MHz duplex and 1.9 MHz continuous wave transducer was used. Colour flow mapping showed trivial transvalvar regurgitation in 23 (53%) metal aortic prosthesis, and only nine (20%) metal mitral prostheses. This difference was probably attributable to shielding of the left atrium by the metal components. Colour mapping confirmed abnormal regurgitation in all aortic prostheses with early diastolic numbers, but regurgitation was also shown in 25 (29%) with no diastolic murmur. Abnormal mitral regurgitation was found in 13 (54%) patients with a pansystolic murmur, but also in six (8%) with no systolic murmur. Two patients, thought on clinical grounds to have mild mitral regurgitation, had unexpectedly large jets on colour flow mapping. About one in three prostheses had paraprosthetic leaks, 65 (79%) of which were small with a jet area less than 20% of the area of the receiving chamber. The development of new paraprosthetic leaks led to the diagnosis of bacterial endocarditis in two patients. In eight patients regurgitation was first diagnosed with continuous wave Doppler, but was afterwards shown with colour mapping and in a further 10 regurgitation could only be shown by continuous wave Doppler. Colour flow mapping was less sensitive than continuous wave Doppler in detecting regurgitation,but seemed able to distinguish normal transvalvar from paraprosthetic regurgitation. Further studies in the natural course of paraprosthetic leaks and a comparison of the transoesophageal and transthoracic approaches in the assessment of mitral prostheses are needed.


Lack of an association between candidate gene loci and idiopathic generalized epilepsy in Kuwaiti Arab children.
Idiopathic generalized epilepsies (IGEs) are the most common types of epilepsy in childhood and adolescence. A variety of data suggest that IGEs have a predominant genetic etiology. Recently, a number of gene mutations have been found to be associated with various types of epilepsy in mainly the Caucasian populations. The objective of this study was to investigate the association of three different candidate genes with IGE in Kuwaiti Arab children. This study includes 123 Kuwaiti patients with a confirmed diagnosis of epilepsy. Most of the patients have had a diagnostic EEG with generalized spike-wave discharges (GSWs). All patients were evaluated by using a validated seizure questionnaire. The clinical type of epilepsy was determined by a trained neurologist/pediatrician. The study also include 100 controls, the control subjects were children which did not have any history of neurological disorders. Blood samples were collected from all patients and control subjects after taking informed consent. DNA was isolated and analyzed by molecular methods. A FokI polymorphism in neuronal nicotinic acetylcholine receptor alpha-4 subunit (CHRNA4) gene was detected by PCR-RFLP method. A missense mutation (Ser248Phe) in CHRNA4 gene was analyzed by PCR-RFLP using HpaII. A C121W mutation in sodium-channel beta-1 subunit (SCN1B) gene was screened by a PCR-RFLP method using HinPI. A 2-bp deletion in Cystatin B gene was detected by PCR-RFLP using XcmI. The incidence of three FokI polymorphism genotypes in Kuwaiti IGE patients was 1,1 (85%), 1,2 (14%) and 2,2 (1%) respectively. The missense mutation Ser248Phe of CHRNA4 gene was not detected at all in Kuwaiti IGE patients. The C387G transversion resulting in C121W change in third exon of the SCN1B gene was detected in 3/123 patients (2%). The patients carrying this mutation also exhibited febrile seizures. The incidence of 2 bp deletion in the cystatin B gene was found to be 4% (5/123 IGE patients). The data obtained from molecular analysis show a lack of association between three candidate genes and clinical expression of IGE in Kuwaiti Arab children. This is completely different from the findings reported from Caucasian populations of France, Australia and USA in which case a strong association has been reported between IGE and these genes.


Enhanced interleukin 1 (IL-1) production mediated by mouse serum amyloid P component.
Purified serum amyloid P component (SAP), the major acute-phase reactant of mice, induces enhanced interleukin 1 (IL-1) production by elicited monocytes/macrophages in vitro. SAP also enhanced IL-1 elaboration by macrophages from lipopolysaccharide (LPS)-low responder mice and in the presence of polymyxin B, indicating that the small amounts of LPS present in the SAP preparation did not augment IL-1 production. Concentrations of SAP of 0.1 to 10.0 micrograms/ml enhanced IL-1 production by elicited and bacillus Calmette-Guerin (BCG)-activated peritoneal macrophages, but not by resident peritoneal macrophages. The inflammation-induced monocyte/macrophage population displayed selective binding of SAP. The mouse macrophage line P388D1, also could bind SAP and display enhanced IL-1 production in response to SAP. SAP did not bind to the macrophage cell line RAW264.7 nor did it enhance IL-1 secretion by this line. The results suggest that this acute-phase reactant has the potential to enhance inflammatory and immunological events mediated by IL-1.


Synthetic biology-driven customization of functional feed resources.
To constantly supply functional feed resources (FFRs) toward meeting the rapidly growing meat demand, an efficient process alternative to traditional farming is required. Fermentation of synthetic microorganisms serves as an emerging solution, necessitating the coordination of (i) microorganism customization, (ii) product processing, and (iii) effect evaluation using animal experiments.


Prevalence of multimorbidity and its associations with hospitalisation or death in Japan 2014-2019: a retrospective cohort study using nationwide medical claims data in the middle-aged generation.
To describe the prevalence of multimorbidity and its associations with clinical outcomes across age groups. Retrospective cohort study using nationwide medical claims data. Carried out in Japan between April 2014 and March 2019. N=246 671 Japanese individuals aged 20-74 enrolled in the health insurance were included into the baseline data set for fiscal year (FY) 2014. Of those, N=181 959 individuals were included into the cohort data set spanning FY2014-FY2018. Multimorbidity was defined as having ≥2 of 15 chronic conditions according to the International Classification of Diseases 10th Revision codes of the Charlson Comorbidity Index. Primary outcome: the standardised prevalence of multimorbidity across age groups was evaluated using data from FY2014 and extrapolated to the Japanese total population. hospitalisation or death events were traced by month using medical claims data and insurer enrolment data. Associations between multimorbidity and 5-year hospitalisation and/or death events across age groups were analysed using a Cox regression model. The standardised prevalence rate of multimorbidity in the nationwide Japanese total population was estimated to 26.1%. The prevalence rate with age was increased, approximately 5% (ages 20-29), 10% (30-39), 20% (40-49), 30% (50-59), 50% (60-69) and 60% (70-74). Compared with individuals aged 20-39 without multimorbidity, those with multimorbidity had a higher incidence of clinical events in any age group (HR=2.43 (95% CI 2.30 to 2.56) in ages 20-39, HR=2.55 (95% CI 2.47 to 2.63) in ages 40-59 and HR=3.41 (95% CI 3.23 to 3.53) in ages ≥60). The difference in the incidence of clinical events between multimorbidity and no multimorbidity was larger than that between age groups. Multimorbidity is already prevalent in the middle-aged generation and is associated with poor clinical outcomes. These findings underscore the significance of multimorbidity and highlight the urgent need for preventive intervention at the public healthcare level.


Supplemental fermented plant product ('Manda Koso') reduces succinate and deoxycholate, as well as elevates IgA and mucin levels, in rats fed a high-fat diet.
'Manda Koso' is a commercial fermented plant product (FPP) made from 53 types of fruits and vegetables that have been fermented for >3 years and 3 months. We hypothesized that FPP intake improves the luminal environment of rats fed a high-fat diet. Thus, the present study examined the effects of consumption of 5% FPP diet for 3 weeks on colonic luminal parameters in rats fed a 30% beef tallow diet. Food intake and body weight gain were unaffected. Consumption of the FPP diet did not influence the proportions of Bifidobacterium, Lactobacillus, Bacteroides, Prevotella or Clostridium in cecal contents. However, the FPP diet caused a significant reduction (-88%) in the level of cecal succinate, a putative inflammatory signal (P<0.01), but did not affect the levels of n-butyrate, propionate, acetate and lactate. The fecal levels of deoxycholate and hyodeoxycholate, which are toxic bile acids, were also significantly reduced by the FPP diet (P<0.05). The FPP diet significantly increased fecal immunoglobulin A and mucins responsible for intestinal immune and barrier functions (P<0.05). The results suggest that the consumption of FPP is beneficial for the colonic luminal environment in rats fed a high-fat diet.


Efficacy and safety of human umbilical cord-derived mesenchymal stem cells (hUC-MSC PLEB001) for the treatment of grade II-IV steroid-refractory acute graft-versus-host disease: a study protocol for a multicenter, randomized, double-blind, placebo-controlled, phase II trial.
Systemic corticosteroid therapy failure is quite common in patients with newly diagnosed acute graft-versus-host disease (aGVHD). Growing evidence has suggested that mesenchymal stem cell (MSC) therapy could be a promising treatment option for aGVHD due to its distinctive immunomodulating functions. However, there is a lack of randomized well-controlled clinical trials. This is a clinical trial protocol for a multicenter, randomized, double-blind, placebo-controlled phase II study. The aim of the trial is to evaluate the efficacy and safety of the administration of the human umbilical cord-derived MSC product hUC-MSC PLEB001 in patients with grade II-IV, steroid-refractory aGVHD. A total of 96 patients will be randomized 1:1 to receive MSC or placebo treatment twice per week for 4 weeks, in addition to second-line therapy according to institutional standards. Patients who achieve partial response (PR) at day 28 will be eligible to receive further infusions twice per week for an additional 4 weeks. This study will evaluate the efficacy and safety of MSC therapy in patients who have failed first-line steroid treatment for grade II-IV aGVHD. Chinese Clinical Trial Registry (ChiCTR), ChiCTR2000035740. Registered on 16 August 2020.


Maternal immunosuppression and cytomegalovirus infection of the fetus.
Prenatal cytomegalovirus (CMV) infection associated with severe brain damage was detected in an infant whose mother had been treated with prednisolone and azathioprine for systemic lupus erythematosus (SLE). Serology showed that maternal CMV infection had been acquired at least four months before pregnancy. Screening for CMV infection in pregnant women receiving immunosuppressive drugs is recommended.


[Study of the audiospinal effect on the H-reflex].
Studies of the audiospinal effect on the H-reflex demonstrated that in normal test subjects and in patients with injuries to the spinal cord coupled with parapareses and in part of patients with paraplegia of the lower limbs, there was a sound-induced 30-70% increase in the amplitude of the H-reflex. As the interval between the conditioning sound and testing electric stimulations was raised, two maxima of the increment of the H-reflex amplitude within 30-40 ms and 80-100 ms were revealed. The increased H-response within these intervals seems likely to be connected with the conduction of excitation from the brain cortex via the pyramidal tract and the reticulospinal tract. Part of the patients with spinal cord injuries and paraplegia of the lower limbs did not manifest any sound-induced increase in the H-reflex. Apparently, such lack of increase is either a consequence of the functional blockade of the afferent conduction tract or that of their anatomical disturbance. The method of the audiospinal effect on the H-reflexes may be used for diagnostic purposes, namely for the determination of the conduction via the afferent cerebrospinal tract.


The diagnostic value of tau protein, beta-amyloid (1-42) and their ratio for the discrimination of alcohol-related cognitive disorders from Alzheimer's disease in the early stages.
Chronic and heavy alcohol abuse or dependence may result in impaired cognition and dementia. The increased risk of Alzheimer's disease (AD) in older individuals interferes with the differential diagnosis, especially when dealing with elderly patients with a long history of alcohol abuse. The aim of the present study was to evaluate the diagnostic value of the putative cerebrospinal fluid (CSF) biomarkers tau, beta-amyloid 1-42 (Abeta42) and their ratio in differentiating alcohol related cognitive disorder (ARCD) from AD. Double-sandwich ELISA (Innotest htau antigen and beta-Amyloid (1-42), Innogenetics) were used to quantify the above markers in a total of 20 patients with ARCD, 33 AD patients with mild to moderate dementia and 50 mentally intact subjects. Tau protein successfully differentiated AD from normal ageing with 96% specificity and 93.9% sensitivity and from ARCD with 95% specificity, and 87.9% sensitivity. Abeta42 alone had a specificity of 88% and a sensitivity of 69.7% in differentiating AD from normal ageing, while the corresponding values for differentiating AD from ARCD were 80% and 84.8% respectively. The tau/Abeta42 ratio was better than tau alone for differentiating AD from normal ageing (specificity 94%, sensitivity 97%) and better than any of the candidate markers alone, for differentiating AD from ARCD (specificity 100%, sensitivity 97%). The combined use of CSF tau and Abeta42 may be a useful tool in the differential diagnosis of ARCD from AD, especially in the early stages, where diagnostic uncertainty is greater.


Molecular Identification of Fasciola Isolated from the Liver of Meat Animals in Fars Province, Iran.
Fasciola hepatica and Fasciola gigantica are flatworms that infect animals and humans. Fasciola is the parasite of the liver or bile ducts and intestines of mammals, where such animals are known as their "definite hosts." The study aims to detect the genotype of Fasciola spp. from the livers of meat animals by using RFLP-PCR in samples collected from Fars province. Sixty Fasciola spp. samples were collected from infected slaughtered animals in three counties of Fars province, Iran (Jahrom, Nourabad Mamasani, and Kazeroun).Genomic DNA was extracted by the conventional phenol-chloroform method. For the study, PCR-RFLP and sequence analysis of the first nuclear ribosomal internal transcribed spacer (ITS1) region from Fasciola species were used to conduct the study. The fragment of about 700 bp in all the Fasciola samples was amplified. In total, 43 samples of Fasciola gigantica and 17 samples of Fasciola hepatica were identified. The dominant Fasciola species in this region is Fasciola gigantica. Hence, it seems that hygienic policies should be developed to prevent and control fascioliasis because of the dominant species, Fasciola gigantica.


Toll-like receptor 3 neuroimmune signaling and behavior change: A strain comparison between Lewis and Wistar rats.
There are many unanswered questions about the interaction between the immune system and behavior change, including the contributions of individual differences. The present study modeled individual differences in the immune system by comparing inbred Lewis rats, which have dysregulated stress and immune systems, to their genetically diverse parent strain, Wistar rats. The objective was to examine the consequences of an immune challenge on behavior and neuroimmune signaling in both strains. Peripheral administration of the toll-like receptor 3 (TLR3) agonist and viral memetic polyinosinic-polycytidylic acid (poly(I:C)) induced behavior changes in both strains, reducing locomotor activity and increasing avoidance behavior (time on the dark side of the light-dark box). Furthermore, poly(I:C) induced hyperarousal and increased avoidance behavior more in female Lewis than female Wistar rats. Baseline strain differences were also observed: Lewis rats had higher avoidance behavior and lower startle response than Wistars. Lewis rats also had lower levels of peripheral inflammation, as measured by spleen weight. Finally, poly(I:C) increased expression of genes in the TLR3 pathway, cytokine genes, and CD11b, a gene associated with proinflammatory actions of microglia, in the prelimbic cortex and central amygdala, with greater expression of cytokine genes in male rats. Lewis rats had lower baseline expression of some neuroimmune genes, particularly CD11b. Overall, we found constitutive strain differences in immune profiles and baseline differences in behavior, yet poly(I:C) generally induced similar behavior changes in males while hyperarousal and avoidance behavior were heightened in female Lewis rats.


Are we overemphasizing sun avoidance in protection from melanoma?
The public health effect of melanoma in the United States is undeniable as approximately 60,000 diagnoses of invasive melanoma and 8,000 deaths from melanoma are expected in 2007. Due to the poor outcomes associated with treating advanced cases of melanoma, substantial public health resources have been devoted to prevention efforts. Of the various factors involved in the pathogenesis of melanoma, including genetic predisposition, immunosuppression, and UV radiation, decreasing UV exposure has attracted the most attention for decreasing the public health effect of melanoma. Although sun avoidance may be an important measure for reducing the public health effect of melanocytic and keratinocytic malignancies, educational and media campaigns to encourage sun avoidance have failed to achieve the desired behavior changes in young people, have had limited effect on elderly patients who have already experienced decades of damaging sun exposure, and most importantly have failed to decrease the incidence of melanoma. We believe the best method to reduce deaths from melanoma is to emphasize early detection and treatment of suspicious lesions through combined efforts of both patients and providers.


Use of a Behavioural Pain Scale to assess pain in ventilated, unconscious and/or sedated patients.
Current empirical evidence supports claims that pain in sedated, unconscious Intensive Care Unit (ICU) patients is underrated and under-treated. Given the severity of ICU patients' illness pain management, whilst important, may not be considered a priority and therefore can be easily overlooked. The aim of this study was to validate the Behavioural Pain Scale (BPS) for the assessment of pain in critically ill patients by evaluating facial expressions, upper limb movements and compliance with mechanical ventilation. A prospective, descriptive repeated measures study design was used to assess the validity and reliability of the BPS for assessing pain in critically ill patients undergoing routine painful (repositioning) and non-painful (eye care) procedures. An average of 73% of BPS scores increased (indicating pain) after patients were repositioned, as opposed to 14% after eye care. This increase was statistically significant for repositioning (p < 0.003) but not for eye care (p > 0.3). The odds of an increase in BPS between pre- and post-procedure assessments was more than 25 times higher for repositioning compared with eye care (p < 0.0001), after controlling for analgesics and sedatives. The BPS was found to be a valid and reliable tool in the assessment of pain in the unconscious sedated patient. Results also highlighted that traditional pain indicators, such as fluctuations in haemodynamic parameters, are not always an accurate measure for the assessment of pain in unconscious patients and as such more objective pain assessment measures are essential. Finally, further validation of the BPS and identification of other painful routine procedures is needed to enhance pain management delivery for unconscious patients.


Homogenization with heat treatment: A cost effective alternative to nucleic acid extraction for herpes simplex virus real-time PCR from viral swabs.
Most laboratories use expensive commercial kits to purify nucleic acids and remove PCR inhibitors that may be present in clinical specimens. In this study a simple homogenization with heat treatment of herpes simplex virus types 1 and 2 (HSV-1/2) was shown to be equivalent to commercial kit-based nucleic acid extraction methods. With a cost of less than $1 USD per extraction, this method provides an economical, rapid, and effective method to recover HSV-1/2 DNA from swabs suitable for real-time HSV PCR.


Aerobic exercise increases sprouting angiogenesis in the male rat motor cortex.
Exercise is beneficial to brain health, and historically, the advantageous effects of exercise on the brain have been attributed to neuronal plasticity. However, it has also become clear that the brain vascular system also exhibits plasticity in response to exercise. This plasticity occurs in areas involved in movement, such as the motor cortex. This experiment aimed to further characterize the effects of exercise on structural vascular plasticity in the male rat motor cortex, by specifically identifying whether features of angiogenesis, the growth of new capillaries, or changes in vessel diameter were present. Male rats in the exercise group engaged in a 5-week bout of voluntary wheel running, while a second group of rats remained sedentary. After the exercise regimen, vascular corrosion casts, resin replicas of the brain vasculature, were made for all animals and imaged using a scanning electron microscope. Results indicate sprouting angiogenesis was the primary form of structural vascular plasticity detected in the motor cortex under these aerobic exercise parameters. Additionally, exercised rats displayed a slight increase in capillary diameter and expanded endothelial cell nuclei diameters in this region.


nuScore: a web-interface for nucleosome positioning predictions.
Sequence-directed mapping of nucleosome positions is of major biological interest. Here, we present a web-interface for estimation of the affinity of the histone core to DNA and prediction of nucleosome arrangement on a given sequence. Our approach is based on assessment of the energy cost of imposing the deformations required to wrap DNA around the histone surface. The interface allows the user to specify a number of options such as selecting from several structural templates for threading calculations and adding random sequences to the analysis. The nuScore interface is freely available for use at http://compbio.med.harvard.edu/nuScore. email@example.com; firstname.lastname@example.com The site contains user manual, description of the methodology and examples.


Warmer ambient air temperatures reduce nasal turbinate and brain infection, but increase lung inflammation in the K18-hACE2 mouse model of COVID-19.
Warmer climatic conditions have been associated with fewer COVID-19 cases. Herein we infected K18-hACE2 mice housed at the standard animal house temperature of ∼22 °C, or at ∼31 °C, which is considered to be thermoneutral for mice. On day 2 post infection, RNA-Seq analyses showed no significant differential gene expression lung in lungs of mice housed at the two temperatures, with almost identical viral loads and type I interferon responses. There was also no significant difference in viral loads in lungs on day 5, but RNA-Seq and histology analyses showed clearly elevated inflammatory signatures and infiltrates. Thermoneutrality thus promoted lung inflammation. On day 2 post infection mice housed at 31 °C showed reduced viral loads in nasal turbinates, consistent with increased mucociliary clearance at the warmer ambient temperature. These mice also had reduced virus levels in the brain, and an ensuing amelioration of weight loss and a delay in mortality. Warmer air temperatures may thus reduce infection of the upper respiratory track and the olfactory epithelium, resulting in reduced brain infection. Potential relevance for anosmia and neurological sequelae in COVID-19 patients is discussed.


Relational graph convolutional networks for predicting blood-brain barrier penetration of drug molecules.
Evaluating the blood-brain barrier (BBB) permeability of drug molecules is a critical step in brain drug development. Traditional methods for the evaluation require complicated in vitro or in vivo testing. Alternatively, in silico predictions based on machine learning have proved to be a cost-efficient way to complement the in vitro and in vivo methods. However, the performance of the established models has been limited by their incapability of dealing with the interactions between drugs and proteins, which play an important role in the mechanism behind the BBB penetrating behaviors. To address this limitation, we employed the relational graph convolutional network (RGCN) to handle the drug-protein interactions as well as the properties of each individual drug. The RGCN model achieved an overall accuracy of 0.872, an area under the receiver operating characteristic (AUROC) of 0.919 and an area under the precision-recall curve (AUPRC) of 0.838 for the testing dataset with the drug-protein interactions and the Mordred descriptors as the input. Introducing drug-drug similarity to connect structurally similar drugs in the data graph further improved the testing results, giving an overall accuracy of 0.876, an AUROC of 0.926 and an AUPRC of 0.865. In particular, the RGCN model was found to greatly outperform the LightGBM base model when evaluated with the drugs whose BBB penetration was dependent on drug-protein interactions. Our model is expected to provide high-confidence predictions of BBB permeability for drug prioritization in the experimental screening of BBB-penetrating drugs. The data and the codes are freely available at https://github.com/dingyan20/BBB-Penetration-Prediction. Supplementary data are available at Bioinformatics online.


Occupational exposure to environmental tobacco smoke.
To measure occupational exposures to environmental tobacco smoke in diverse settings, including offices and production areas, and to evaluate the effectiveness of policies that restrict or ban smoking in the workplace. Survey. The average weekly concentration of environmental tobacco smoke was measured with passive monitors that sample nicotine. Approximately 25 samples were placed in each worksite for 1 week. Twenty-five Massachusetts worksites, including fire stations, newspaper publishers, textile dyeing plants, and manufacturers of valves, fiberoptics, flight instruments, batteries, adhesives, semiconductor equipment, filters, and tools and dies. Samples were collected in offices and production areas. The distribution of nicotine concentrations in various work settings as a function of company smoking policy. These data were interpreted with three approaches: comparing measured concentrations with a published risk assessment; comparing occupational exposures with home exposures; and evaluating the "cigarette equivalents" to which workers were exposed. Worksite smoking policy had a major effect on the nicotine concentrations, which fell from a median of 8.6 micrograms/m3 in the open offices at worksites that allowed smoking to 1.3 micrograms/m3 in sites that restricted smoking, and to 0.3 microgram/m3 in worksites that banned smoking. The nonoffice workspaces were affected similarly, with median concentrations of 2.3, 0.7, and 0.2 microgram/m3 at worksites that allowed, restricted, and banned smoking, respectively. All three evaluation methods indicated that occupational exposure to environmental tobacco smoke presents a substantial risk to workers in the absence of a policy restricting or banning smoking.


Microheterogeneity in the recognition of a HLA-DR2-restricted T cell epitope from a meningococcal outer membrane protein.
The trimolecular interaction of T cell receptor (TcR), antigen and major histocompatibility complex (MHC) class II was analyzed using a panel of HLA-DR2-restricted T cell clones recognizing the 49-61 region of a meningococcal class I outer membrane protein (OMP). The clones, all CD3+CD4+CD8-TcR alpha/beta+, were selected by restimulation with the synthetic peptide OMP(49-61), which contains an immunodominant T helper determinant. Using a series of peptides that were sequentially truncated from the N or C terminus, four different epitope fine-specificity patterns were identified. Furthermore, each clone was found to exhibit a distinct recognition pattern for a panel of 20 single-residue substitution analogues of the minimal epitope OMP(50-58). Most substitutions that were not tolerated in the nonamer were allowed when the analogues were prepared departing from the native peptide OMP(49-61). Obviously, the residues outside the minimal epitope contribute to stabilization of the trimolecular complex. These findings suggest that defining the minimal size of T cell determinants may be of limited value. By performing proliferation competition assays putative MHC and TcR contact residues were identified in the peptide. Most likely, Ile 51 and Phe 54 act as MHC-anchoring residues, whereas Asp 53 represents a critical TcR contact residue for all of the clones. MHC anchoring may be provided by other residues as well, since Ile 51 and Phe 54 can be substituted by conservative residues [as OMP(50-58) and OMP(49-61) analogues] and with Ala [as OMP(49-61) analogues only]. Some evidence was found for interaction of particular side chains at other positions with TcR molecules, but this contribution was not equally important for all clones. Apparently, the clonotypic TcR can see a single epitope in different ways in the context of the same MHC restriction element. Since most clones use different V alpha and V beta genes (which encompass the putative MHC-binding regions first and second complementarity-determining regions, CDR1 and CDR2) different modes of interaction with the HLA-DR2 molecule indeed are likely to occur.


Global Prevalence of Meeting Screen Time Guidelines Among Children 5 Years and Younger: A Systematic Review and Meta-analysis.
Pediatric guidelines suggest that infants younger than 2 years avoid screen time altogether, while children aged 2 to 5 years receive no more than 1 hour per day. Although these guidelines have been adopted around the world, substantial variability exists in adherence to the guidelines, and precise estimates are needed to inform public health and policy initiatives. To derive the pooled prevalence via meta-analytic methods of children younger than 2 years and children aged 2 to 5 years who are meeting guidelines about screen time. Searches were conducted in MEDLINE, PsycINFO, and Embase up to March 2020. Studies were included if participants were 5 years and younger and the prevalence of meeting (or exceeding) screen time guidelines was reported. Data extraction followed Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Two independent reviewers extracted all relevant data. Random-effects meta-analyses were used to derive the mean prevalence rates. Prevalence of meeting screen time guidelines. From 63 studies, 95 nonoverlapping samples with a total of 89 163 participants were included. For children younger than 2 years, the pooled prevalence of meeting the screen time guideline (0 h/d) was 24.7% (95% CI, 19.0%-31.5%). Moderator analyses revealed that prevalence of meeting screen time guidelines varied as a function of year of data collection (increased over time), measurement method (higher when questionnaires compared with interview), and type of device use (higher when a combination of screen use activities compared with television/movies only). For children aged 2 to 5 years, the mean prevalence of meeting the screen time guideline (1 h/d) was 35.6% (95% CI, 30.6%-40.9%). Moderator analyses revealed that the prevalence of meeting screen time guidelines varied as a function of type of device use (higher when screen time was television/movies only compared with a combination of screen use activities). The findings of this meta-analysis indicate that only a minority of children 5 years and younger are meeting screen time guidelines. This highlights the need to provide support and resources to families to best fit evidence-based recommendations into their lives.


[Effects of experimental hypovolaemic shock on platelets in the pig (author's transl)].
The effects of standardized blood loss on the platelets, as well as on coagulation, fibrinolysis and complement parameters were studied in the pig. A simultaneous fall in arterial and venous platelet counts was demonstrated during the initial phase of blood loss, with a concomitat rise in pulmonary vascular resistance. After exsanguination to the extent of about 40% of the blood volume, the arterial platelet counts increased significantly, whilst the pulmonary vascular resistance, which was negatively correlated with the arterial platelet counts throughout the experiment, fell. Venous platelet counts, on the other hand, remained low during this experimental period and were correlated with cardiac output, but not with pulmonary vascular resistance.


A cross-sectional analysis of self-reported scholarly publications among United States pharmacy practice faculty.
The objectives of this study were to provide an estimate of self-reported peer-reviewed publications and evaluate characteristics associated with publication rates among pharmacy practice faculty within United States (US)-based colleges and schools of pharmacy. An online survey instrument was distributed to pharmacy practice faculty via email listserv. Information regarding faculty members' publication histories, faculty position, institutional characteristics, and faculty demographic characteristics was gathered. Descriptive statistics were used to characterize participants, and t-tests and analysis of variance were used for comparisons among groups. Two hundred and nine pharmacy practice faculty were included. The majority were female (67%), white (81%), and from public institutions (66%). Academic ranks were well-represented. Reporting higher percent time spent in research, employment at public institutions, and having earned a doctor of philosophy (PhD) degree were all significantly associated with higher total number of publications and a higher annualized publication rate. Tenure track faculty who were not yet tenured had higher annual publication rates than faculty who were tenured or in non-tenure track positions. The overall annual publication rate was 2.0 ± 2.1 publications per year. Characteristics such as being in a tenure track position, holding a PhD, spending more time in research, and employment within a public institution were all associated with a higher publication rate. These self-reported data from pharmacy practice faculty also indicate an increase in the average number of scholarly publications per year from previously reported estimates.


Early ethnic difference in insulin-like growth factor-1 is associated with African genetic admixture.
IGF-1 is a growth-promoting hormone. Numerous studies have reported higher systemic concentrations of IGF-1 among African Americans (AA) compared with European Americans (EA) before puberty. We conducted this cross-sectional analysis to determine whether African ancestral genetic background, dietary factors, energy expenditure, adiposity, and socioeconomic status contribute to this difference. Children were prepubertal, AA and EA males and females. Genetic admixture was assessed from approximately 20 ancestry informative genetic markers. Body composition was determined by dual-energy x-ray absorptiometry; intake of energy, carbohydrate, protein, and fat by 24-h dietary recall; activity-related energy expenditure by doubly labeled water and indirect calorimetry; and socioeconomic status (SES) according to the Hollingshead scale. IGF-1 and IGF binding protein-3 (IGFBP-3) were measured using immunoradiometric assays. AA children had significantly greater IGF-1 compared with EA children (p < 0.01). In addition, AA children had lower SES and greater protein intake relative to EAs (p < 0.05 for both). Multiple linear regression analysis revealed that the only significant independent predictors of IGF-1 were IGFBP-3 and African admixture (p < 0.01 for both). Thus, our data suggest that the greater IGF-1 of AA relative to EA children could have a genetic basis.


Trainee-led research using an integrated knowledge translation or other research partnership approaches: a scoping reviews.
There are increasing expectations for researchers and knowledge users in the health system to use a research partnership approach, such as integrated knowledge translation, to increase the relevance and use of research findings in health practice, programmes and policies. However, little is known about how health research trainees engage in research partnership approaches such as IKT. In response, the purpose of this scoping review was to map and characterize the evidence related to using an IKT or other research partnership approach from the perspective of health research trainees in thesis and/or postdoctoral work. We conducted this scoping review following the Joanna Briggs Institute methodology and Arksey and O'Malley's framework. We searched the following databases in June 2020: MEDLINE, Embase, CINAHL and PsycINFO. We also searched sources of unpublished studies and grey literature. We reported our findings in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews. We included 74 records that described trainees' experiences using an IKT or other research partnership approach to health research. The majority of studies involved collaboration with knowledge users in the research question development, recruitment and data collection stages of the research process. Intersecting barriers to IKT or other research partnerships at the individual, interpersonal and organizational levels were reported, including lack of skills in partnership research, competing priorities and trainees' "outsider" status. We also identified studies that evaluated their IKT approach and reported impacts on partnership formation, such as valuing different perspectives, and enhanced relevance of research. Our review provides insights for trainees interested in IKT or other research partnership approaches and offers guidance on how to apply an IKT approach to their research. The review findings can serve as a basis for future reviews and primary research focused on IKT principles, strategies and evaluation. The findings can also inform IKT training efforts such as guideline development and academic programme development.


A quantitative analysis of stereotyped gnawing induced by apomorphine.
An apparatus was designed and constructed to enable a quantitative analysis of the stereotyped gnawing produced by the dopamine agonist apomorphine. Using this apparatus it was discovered that increasing the subcutaneous dose of apomorphine increased (1) the number of animals that gnawed, and (2) the duration of gnawing in those animals that gnawed at all doses. Other aspects of apomorphine-induced gnawing, in particular the latency to respond and the frequency and duration of individual gnaws, were relatively unaffected. Likely properties of the system responsible for the organization of sterotyped gnawing are discussed.


Assessing the relationship between routine and schizophrenia symptoms with passively sensed measures of behavioral stability.
Increased stability in one's daily routine is associated with well-being in the general population and often a goal of behavioral interventions for people with serious mental illnesses like schizophrenia. Assessing behavioral stability has been limited in clinical research by the use of retrospective scales, which are susceptible to reporting biases and memory inaccuracies. Mobile passive sensors, which are less susceptible to these sources of error, have emerged as tools to assess behavioral patterns in a range of populations. The present study developed and examined a metric of behavioral stability from data generated by a passive sensing system carried by 61 individuals with schizophrenia for one year. This metric-the Stability Index-appeared orthogonal from existing measures drawn from passive sensors and matched the predictive performance of state-of-the-art features. Specifically, greater stability in social activity (e.g., calls and messages) were associated with lower symptoms, and greater stability in physical activity (e.g., being still) appeared associated with elevated symptoms. This study provides additional support for the predictive value of individualized over population-level data in psychiatric populations. The Stability Index offers also a promising tool for generating insights about the impact of behavioral stability in schizophrenia-spectrum disorders.


Estrogen treatment to ovariectomized rats modifies morphine-induced behavior.
Two weeks after surgery, ovariectomized (OVX) rats were treated for 3 days with either 17 beta-estradiol (10 or 100 micrograms/kg, SC, per day) or the oil vehicle. They were then tested for morphine-induced hyperactivity (4 mg/kg, IP), analgesia and catalepsy (15 and 20 mg/kg, IP) 24 or 72 hr after the last steroid or oil injection. Estradiol treatment did not affect the locomotion or the sensitivity to nociceptive stimuli of OVX rats and did not induce a cataleptic state in animals. Estradiol- (100 micrograms/kg) treated OVX rats exhibited attenuated morphine-induced hyperlocomotion regardless of the time that had elapsed after estradiol treatment cessation, attenuated morphine-induced catalepsy at 24 hr after estradiol treatment and unaltered morphine-induced analgesia. OVX rats treated with a lower estradiol dose (10 micrograms/kg) exhibited significantly increased morphine-induced analgesia and slightly increased catalepsy. The results show that the sensitivity of brain opiate systems controlling some of the behavioral effects of morphine is modified following estradiol treatment to OVX rats.


Disseminated tuberculosis mimicking abdominal metastatic carcinoma: A case report.
Extra-pulmonary tuberculosis (TB) has long been a diagnostic challenge for clinicians, often requiring extensive workup and invasive procedures, with the risk of significant complications. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a minimally invasive and highly accurate diagnostic modality for the evaluation of mediastinal and abdominal lymphadenopathy and masses. Several reports on the utility of EUS-FNA as a favorable method for diagnosing extrapulmonary TB have been published. A 54-year-old man complained of intermittent melena. 18 fluorine-fluorodeoxyglucose positron emission tomography/computed tomography revealed suspected carcinoma metastasis. EUS-FNA did not reveal any evidence of malignancy. Laparoscopy was performed, and frozen section pathology during surgery showed granulomas with focal necrosis. Mycobacterium tuberculosis polymerase chain reaction was positive, but acid-fast bacilli staining was negative. Anti-TB treatment was initiated, and the patient was advised to visit the local TB dispensary regularly. The presence of atypical inflammation of inadequate material or non-representative samples of extra-pulmonary TB was observed on EUS-FNA cytology. Mycobacterium tuberculosis polymerase chain reaction and acid fast bacilli should be performed to diagnose TB because of its higher sensitivity.


Evaluation of the Pfs25-IMX313/Matrix-M malaria transmission-blocking candidate vaccine in endemic settings.
Malaria control relies heavily on the use of anti-malarial drugs and insecticides against malaria parasites and mosquito vectors. Drug and insecticide resistance threatens the effectiveness of conventional malarial interventions; alternative control approaches are, therefore, needed. The development of malaria transmission-blocking vaccines that target the sexual stages in humans or mosquito vectors is among new approaches being pursued. Here, the immunological mechanisms underlying malaria transmission blocking, status of Pfs25-based vaccines are viewed, as well as approaches and capacity for first in-human evaluation of a transmission-blocking candidate vaccine Pfs25-IMX313/Matrix-M administered to semi-immune healthy individuals in endemic settings. It is concluded that institutions in low and middle income settings should be supported to conduct first-in human vaccine trials in order to stimulate innovative research and reduce the overdependence on developed countries for research and local interventions against many diseases of public health importance.


Effect of combined maternal and infant food-allergen avoidance on development of atopy in early infancy: a randomized study.
The effect of maternal and infant avoidance of allergenic foods on food allergy was examined in a prenatally randomized, controlled trial of infants of atopic parents. The diet of the prophylactic-treated group (N = 103) included (1) maternal avoidance of cow's milk, egg, and peanut during the third trimester of pregnancy and lactation and (2) infant use of casein hydrolysate (Nutramigen) for supplementation or weaning, and avoidance of solid foods for 6 months; cow's milk, corn, soy, citrus, and wheat, for 12 months; and egg, peanut, and fish, for 24 months. In the control group (N = 185), mothers had unrestricted diets, and infants followed American Academy of Pediatrics feeding guidelines. The cumulative prevalence of atopy was lower at 12 months in the prophylactic-treated (16.2%) compared to the control (27.1%) group (p = 0.039), resulting from reduced food-associated atopic dermatitis, urticaria and/or gastrointestinal disease by 12 months (5.1% versus 16.4%; p = 0.007), and any positive food skin test by 24 months (16.5% versus 29.4%; p = 0.019), caused primarily by fewer positive milk skin tests (1% versus 12.4%; p = 0.001). The prevalences of allergic rhinitis, asthma, and inhalant skin tests were unaffected. Serum IgE levels in the prophylactic-treated group were marginally lower only at 4 months. Thus, reduced exposure of infants to allergenic foods appeared to reduce food sensitization and allergy primarily during the first year of life.


A mixed-methods study of the disease experience in hematopoietic stem cell transplantation survivors: the contribution of text analysis.
Few studies have detected qualitative and quantitative aspects of patients who underwent HSCT during childhood. The aims of this study are to explore the most recurrent narrative themes of HSCT experience in families five years after the procedure, and to observe statistical correlations between meaning attributed to the experience and defined variables. Thirty-five families of pediatric HSCT survivors participated in the research. Both survivors and their families were asked to write a brief composition about their disease experiences. Qualitative analysis of the texts was performed using the T-LAB software. Information about medical aspects and psychological problems in HSCT survivors were collected with interviews and administering the Child Behavior Checklist 6-18. HSCT survivor families that reported the presence of externalizing and internalizing symptoms focused on thematic areas concerning broken families with separation between parents and the affected child versus healthy children. Long term psychological problems seem to be connected to the perception of family disruption. Specifically, family relationships seem to be the factor that protects from or enhances the risk of psychopathology in HSCT survivors. Moreover, the use of metaphoric terms to refer to HSCT presents higher associations with psychopathology. On the contrary, the possibility of referring directly to the transplantation is associated with psychological well-being. It is important to consider the family as a group in order to improve care.


Fabrication of 3D Scaffolds with Nano-Hydroxyapatite for Improving the Preosteoblast Cell-Biological Performance.
Three-dimensional (3D) scaffolds fabricated by rapid prototyping techniques have many merits for tissue engineering applications, due to its controllable properties such as porosity, pore size and structural shape. Nonetheless, low cell seeding efficiency remains drawback. In this study, poly-caprolactone (PCL) composite 3D extruded scaffolds were modified with nano hydroxyapatite (n-HAp). PCL/n-HAp 3D scaffold surface was treated with oxygen plasma to improve the preosteoblast cell seeding efficiency and proliferation. The results indicate that oxygen plasma is useful technique to improve the cell affinity.


[Merkel cell carcinoma: a new radiation-induced cancer?].
Merkel cell carcinoma (MCC), a rare and aggressive neuroendocrine tumour, appears primarily on sun-exposed areas in light-skinned elderly subjects. UV exposure and profound immunosuppression (particularly in a setting of solid organ transplantation, haematological malignancies, HIV) constitute the principal risk factors. The aetiopathogenesis of this cancer is not known, although a polyomavirus involved in the oncogenic process was recently discovered. The carcinogenic effect of ionizing radiation, while not clearly established, has been suspected in rare cases involving the onset of MCC in irradiated zones. We report a new case of case of MCC in a patient previously undergoing radiotherapy. A 59-year-old-man underwent radiotherapy for a Darier-Ferrand dermatofibrosarcoma on the left shoulder and developed MCC at the same site 38 years later. The time between radiotherapy and diagnosis of MCC, its site within the radiation field (radio-dermatitis), the description of similar cases in the literature concerning the onset of MCC in irradiated areas, and the known carcinogenic effects of ionizing radiation all militate strongly in favour of the radiation-induced nature of MCC.


Targeting thioredoxin reductase by micheliolide contributes to radiosensitizing and inducing apoptosis of HeLa cells.
Inhibition of thioredoxin reductase (TrxR) is a crucial strategy for the discovery of antineoplastic drugs and radiosensitizers. As an anticancer candidate derived from Michelia, micheliolide (MCL) is converted readily from parthenolide (PTL), and has better stability and solubility than PTL. However, the anticancer mechanism of MCL has not been fully dissected. We present here for the first time that MCL-targeted inhibition of TrxR not only promotes oxidative stress-mediated HeLa cell apoptosis but also sensitizes ionizing radiation (IR) treatment. Further mechanistic studies demonstrate that MCL covalently binds to Sec at position 498 of TrxR to restrain the biological function of TrxR. It exhibits the inhibition of TrxR activity, enhancement of oxidized Trx, and sensitization of IR in the cellular environment, accompanied by the accumulation of reactive oxygen species (ROS) and the collapse of the intracellular redox balance. In addition, HeLa-shTrxR1 cells with knockdown of TrxR were more sensitive than the HeLa-shNT cells to either MCL-treated or IR-induced cytotoxicity, ROS, and apoptosis, suggesting that inhibition of TrxR by MCL is likely responsible for increased cytotoxicity and enhanced radiation response. These findings further establish the mechanistic understanding and preclinical data to support the further investigation of MCL's potential as a prospective radiosensitizer and cancer chemotherapeutic agent.


Shape critical properties of patterned Permalloy thin films.
The effects of shape and edges in magnetic elements with reduced dimensions on the magnetization reversal of cross- and framed cross-shaped Ni79Fe21 (30nm) films were studied. Remagnetization details in the stripes of the patterned structures, which had 3 μm to 30 μm widths and ~100 μm lengths, were visualized by the magneto-optical indicator film technique. The magneto-optic images revealed three different types of the domain structure formation and evolution in the samples during their magnetization reversal: (i) spin rotation with growth and annihilation of a cross-tie structure in the stripes perpendicular to the applied field, (ii) nucleation and fast motion of special boundaries, which consist of a number of coupled vortices located along both edges of the stripes parallel to the applied field, and (iii) nonuniform magnetization rotation with macrodomain nucleation and domain wall motion in the large unpatterned part of the films. It was experimentally revealed that there exists a dependence of the critical field for nucleation and motion of domain walls in the parallel-to-field stripes on their width and frame width. In particular, an inverse proportionality between this nucleation field and stripe width was found. Both experimental and simulation results show that, in cases (i) and (ii), the magnetostatic fields, which are formed on the edges of the stripes and at their intersections, play a crucial role in the formation of spin inhomogeneities and switching of the samples.


[Vitreous metastasis of malignant cutaneous melanoma during treatment with ipilimumab].
An isolated metastasis of the vitreous body from a malignant cutaneous melanoma without involvement of the choroid is an extremely rare occurrence. We report on the case of a 59-year-old female patient who presented with a vitreous body metastasis during systemic treatment with the anti-cytotoxic T lymphocyte-associated antigen (anti-CTLA 4) antibody ipilimumab. This case report underlines the diagnostic difficulties in such cases and points out the risk of metastasis in immune-privileged sites under systemic immunotherapy.


Anomalous distribution of nuclear basic proteins in round-headed human spermatozoa.
An electrophoretic analysis of nuclear proteins has been carried out in normal and in round-headed human spermatozoa. Results revealed an anomalous distribution of nuclear basic proteins in round-headed spermatozoa. They contained more histones and especially more intermediate proteins and less protamines than normal spermatozoa.


Patterns of p53, erbB-2, and EGF-r expression in premalignant lesions of the urinary bladder.
Frequent recurrences and multicentricity of bladder cancer suggest that alterations of the urothelium distant from the tumor may be relevant to prognosis. In this study immunohistochemistry and fluorescence in situ hybridization (FISH) were used to examine expression of p53, erbB-2, and epidermal growth factor receptor (EGF-r), genomic aberrations, and tumor cell proliferation (Ki67 LI) in normal and dysplastic urothelium. Biopsy specimens examined included normal urothelium (n = 40), mild dysplasia (n = 34), moderate dysplasia (n = 18) and carcinoma in situ (CIS; n = 20). Several different oncogene expression patterns were found, only some of which were associated with dysplasia. EGF-r expression was equally frequent in normal and dysplastic urothelium and showed a strong association with Ki67 LI (P < .0001). A purely superficial erbB-2 positivity was present in both normal and dysplastic biopsies. However, diffuse erbB-2 positivity and p53 overexpression were both associated with advanced dysplasia (P < .0001 each). FISH analysis showed erbB-2 gene amplification and p53 deletions in selected CIS, as well as a marked chromosome 17 copy number heterogeneity in all six CIS examined. These findings indicate a considerable genomic instability in bladder CIS. They show that both erbB-2 and p53 are altered during malignant transformation. Detectable oncogene expression alone, however, is not diagnostic of malignancy in bladder urothelium.


Double-blind and placebo-controlled study to assess efficacy and safety of a modified allergen extract of Dermatophagoides pteronyssinus in allergic asthma.
A randomized double-blind, placebo-controlled study was conducted in patients allergic asthma sensitized to Dermatophagoides pteronyssinus. To evaluate the efficacy and safety after 1-year of immunotherapy with a modified D. pteronyssinus extract compared with placebo. Fifty-five patients were randomly allocated to receive the active treatment (n = 29), or placebo (n = 26). The main outcome was the specific bronchial provocation test (BPT). Other parameters analysed were dose-response skin prick test (SPT), symptom and medication scores and asthma quality of life (AQLQ). At the end of the study, the active group showed a significant increase in the PD(20)FEV(1) compared with placebo (P = 0.0029). Nineteen patients of the active vs 10 of the placebo group needed more than twice the initial amount of allergen extract to have a positive BPT (P = 0.0293); seven patients in the placebo vs one in the active group needed less than half (P = 0.0137). In SPT, a significant improvement (P = 0.0049) was found in the active group. This group also had a median reduction of 91.5% in symptom scores, whereas the placebo group increased by 86%. Medication scores decreased in both groups (56% in the active and 11.4% in the placebo). In AQLQ, the differences between both groups were significant (P = 0.0234) at the end of the study. After 1 year of treatment, the modified extract of D. pteronyssinus demonstrated to be safe and efficacious to treat patients with asthma and allergic rhinoconjunctivitis sensitized to this mite.


Genetic evidence of shared ancestry among diverse ethno-linguistic human populations of Himachal Pradesh.
In Indian montane system, human populations often exhibit an unparallel social organization where inter-caste marriages are still not common. This attribute affects the demography and population genetic structure of the resident populations. Further, human populations residing in the mountains in India are poorly studied for their genetic make-up and allele distribution patterns. In the present study, we genotyped 594 unrelated individuals using PowerPlex® 21 System (Promega, USA) from eight different populations belonging to 12 districts of Himachal Pradesh which differed in ethnicity, language, geography and social organization. Altogether, we obtained 1415 alleles with a mean of 8.84 ± 0.26 alleles per locus and 0.80 mean observed heterozygosity. Locus Penta E showed the highest combined power of discrimination and was found most informative for forensic purposes. Interestingly, phylogenetic analysis grouped the populations of Rajputs, Scheduled castes and Brahmins into one cluster, which indicated a deep genetic admixture in the ancestral populations. This study documents the first-ever report on the population genetic assignment of various castes in Himachal Pradesh and unveils the facts of cryptic gene flow among the diverse castes in the northern hilly state of India. Our results showed a genetic relationship among the various ethno-linguistically diverse populations of India.


Taurolidine-Citrate Line Locks Prevent Recurrent Central Line-Associated Bloodstream Infection in Pediatric Patients.
This study describes a successful, targeted intervention in central venous access device routine care to decrease central line-associated bloodstream infection. Taurolidine-citrate locks significantly reduced the rate of central line-associated bloodstream infection, particularly Gram-negative organisms without adverse events.


A case of Cushing's syndrome due to ACTH-independent bilateral macronodular hyperplasia associated with excessive secretion of mineralocorticoids.
A 74-year-old man developed Cushing's syndrome and hypokalemia due to ACTH-independent bilateral macronodular adrenocortical hyperplasia (AIMAH) with excessive secretion of mineralocorticoid hormones. Plasma concentrations of weak mineralocorticoids were high. The increase in plasma cortisol did not have a diurnal rhythm, and was not suppressed by a high dose of dexamethasone. Plasma ACTH was undetectable, but plasma cortisol was increased by ACTH administration. The concentrations of mineralocorticoids, especially deoxycorticosterone and corticosterone were increased, and augmented the response to ACTH administration. Plasma renin activity and aldosterone concentrations were rather suppressed. Both adrenal glands, with a total weight of 110 g, were enlarged and contained several macronodules. These nodules were composed of hyperplasia of small cortical cells and usual clear cells. This is a rare case of ACTH-independent bilateral macronodular adrenocortical hyperplasia because there were excessive secretion of mineralocorticoid and hypokalemia.


Fitness and strength responses to distinct exercise modes in twins: Studies of Twin Responses to Understand Exercise as a THerapy (STRUETH) study.
Exercise is considered medicine; however, the individual degree of responsiveness to a standardized dose of exercise is idiosyncratic. Individual responsiveness between distinct exercise modalities and the genetic/environmental contributions to exercise response are not well understood. In this novel randomized cross-over design study, monozygotic and dizygotic twins, as pairs, underwent 3 months of resistance and endurance training, separated by a 3 month washout period, aiming to assess training responses in strength and fitness outcomes to dichotomous training modalities, as well as the genetic/environmental contributions to exercise response. Our findings indicate that (i) individual responsiveness differs between exercise modalities; (ii) low-responders to one mode may be 'rescued' by switching to an alternate mode of exercise; and (iii) genes may not play as large a role, as previously estimated from cross-sectional data, for exercise training adaptation. The present study has implications for those charged with optimizing the benefits of exercise by means of individualizing the exercise prescription. Exercise response is idiosyncratic, although the degree of responsiveness, concordance in response between modalities and genetic contribution to responsiveness are not well understood. We investigated this using a novel randomized cross-over design of dichotomous exercise interventions in mono-(MZ) and di-zygotic (DZ) twin pairs. We studied strength (1RM) and fitness ( V̇O2max ) responses in 84 same-sex untrained twins (30 MZ, 12 DZ pairs; 24.9 ± 5.4 years). Twins, as pairs, underwent 3 months of resistance (RES) and endurance (END) training, separated by a 3 month washout period. Training responses and genetic/environmental contributions to responses were assessed. Leg strength 1RM increased following RES but not END (△47 ± 29 vs. 3 ± 26 kg; P < 0.001), whereas V̇O2max increased following END but not RES (△0.25 ± 0.26 vs. 0.04 ± 0.25 L min-1 ; P < 0.001). A higher percentage of individuals responded to RES for strength and to END for V̇O2max (P < 0.0001). Within-individual responses to each mode were not correlated (P > 0.05). Cross-sectional intraclass correlations were higher for MZ than DZ pairs for all variables, largely as a result of shared environment. Following training, MZ, but not DZ pairs, were significantly correlated for strength change to RES (rMZ = 0.62, P = 0.002) and END (rMZ = 0.36, P = 0.04), and for V̇O2max change to END (L min-1 , rMZ = 0.45, P = 0.02) with a mixture of unshared/shared environmental contributions. Our findings indicate that individual responsiveness differs between modalities and low-responders to one mode may be 'rescued' by switching to an alternate mode. Additionally, genes may not play as large a role as previously estimated from cross-sectional data for training adaptation, and/or cross-sectional data do not reflect longitudinal training effects. The present study has implications for optimizing the individualization of exercise prescription.


Chronic recurrent abdominal pain.
Chronic recurrent abdominal pain remains a common medical and surgical problem, frequently dismissed as functional. Instead, these patients should be approached systematically, based on the pattern of recurrent abdominal pain. It is vital to seek out the potential cause of this type of chronic pain because specific and often curative treatment is available.


Mikulicz Disease Mimicking Intraorbital Tumors.
We report a case of Mikulicz disease (MD), an immunoglobulin G4 (IgG4)-related disease that affects the lacrimal and salivary glands. IgG4-related disease is a relatively new clinical entity and is not commonly encountered by neurosurgeons. MD sometimes mimics intraorbital tumors such as malignant lymphoma but responds well to corticosteroid treatment. Thus it is important to recognize the clinical and radiographic features of MD.


Filling-in with colour: different modes of surface completion.
We investigated the figural dynamics of filling-in processes in figures with more than one possible figure-ground organisation. Using a central disk and two concentric rings as well as similar stimuli consisting of three nested squares or parallel stripes, we tested for filling-in with different equiluminant colour combinations. We observed four modes of filling-in: First, in most of the cases, the inner ring assumed the colour of the central disk and outer ring (M1). Second, the central disk became filled-in with the colour of the inner ring, without any colour change on the outer ring (M2). Third, in a first step, the colour of the inner ring spread onto the central disk; then, in a second step, the colour of the outer ring spread over the whole stimulus (M3). This two step filling-in process has not been reported so far. Fourth, a mode (M4) was sometimes observed that was characterised by the central disk and outer ring assuming the colour of the inner ring. Thus, colour filling-in or colour spreading proceeded both in a centripetal (periphery to fovea) as well as a centrifugal direction. The colours red and yellow proved to be stronger inducers than blue and green. Conversely, the latter colours became filled-in more easily than the former. The filled-in colour was always that of the inducing stimulus, i.e., there was no colour mixture. This suggests a long-range, neural process underlying filling-in under these conditions.


Loads of continuous mechanics for uprighting the second molar on the second molar and premolar.
This paper aims to evaluate the effect of tube height on uprighting a mandibular second molar with a continuous arch, specifically the main effects on the molar tube and the side effects on the second premolar bracket. Slot brackets (0.18-in) and tubes were passively bonded from the left second molar to the right second premolar of the patient's cast and fixed to an orthodontic force tester. A mesially tipped second molar along with its tube was positioned at 5 different heights in relation to the bracket slots of the remaining appliance: 2 mm below (group -2), 1 mm below (group -1), leveled (group 0), 1 mm above (group 1) and 2 mm above (group 2). Each group had 10 different 0.016 × 0.022-in superelastic nickel-titanium wires tied one at a time to the appliance to register the vertical forces (Fz) and tipping moments (Mx) produced at the molar tube and the premolar bracket, statistically. Analysis of variance was used to identify differences of load among the groups for wire response to the position of the tube in relation to the other brackets' slots. As the molar tube was positioned more occlusally, Fz and Mx decreased at the molar tube from 1.31 N to 0.75 N and 13.98 N.mm to 11.84 N.mm, respectively, whereas at the premolar bracket, Fz and Mx decreased from 1.52 N to 0.88 N and 8.77 N.mm to 1.05 N.mm, respectively. In all groups, the load system at the molar tube (the main effects) registered a distal tipping moment and an extrusive force, whereas at the premolar bracket, the load system (side effects) included a distal tipping moment and an intrusive force. As the tube moved occlusally, the extrusive force and the uprighting moment decreased, along with the side effects at the premolar bracket. Attempting to bond the molar tube more occlusally (within reasonable intraoral dimensions) when trying to upright a molar does not appear to be sufficient to keep a molar from extruding.


Improved surface-enhanced Raman scattering on optimum electrochemically roughened silver substrates.
In this work, the effects of preparation conditions used in roughening silver substrates by electrochemical triangular-wave oxidation-reduction cycles (ORC) on surface-enhanced Raman scattering (SERS) were first investigated. The optimum roughening conditions for obtaining strongest SERS of Rhodamine 6G (R6G) are as follows. Ag electrodes were cycled in deoxygenated aqueous solutions containing 0.1 M NaCl from -0.3 to +0.2 V versus Ag/AgCl at 25 mV s(-1) for five scans. The SERS of R6G adsorbed on this optimum procedure-prepared roughened Ag substrate exhibits a higher intensity by one order of magnitude, as compared with that of R6G adsorbed on a normally roughened Ag substrate.


Loss-of-function mutations in the ERF96 gene enhance iron-deficient tolerance in Arabidopsis.
Iron is an essential micronutrient for plant growth and development. Here we provide evidence for a role of ERF96 in iron-deficiency response in Arabidopsis thaliana. The ERF96-loss-of-function mutants were found to be more tolerant to iron-deficiency stress than wild type (WT) and to have higher iron and chlorophyll content. Further studies showed that the transcriptional levels of iron-uptake related genes IRT1, FRO2, AHA2, FIT and bHLH38 in mutants were significantly higher than in WT under iron deficiency. Comparative transcriptome analysis suggested that the differentially expressed genes (DEGs) between ERF96-loss-of-function mutant and WT under iron deficiency were mainly enriched in iron uptake and chlorophyll degradation. According to the specific analysis of these two kinds of DEGs, the expression of iron uptake and transport related genes in ERF96-loss-of-function mutant was higher and the expression of chlorophyll degradation related genes was lower under iron deficiency. Furthermore, loss-of-function of ERF96 influenced the plant hormone, especially auxin and ethylene signal transduction. Altogether, our results demonstrate that loss-of-function of ERF96 increased Fe uptake and chlorophyll level through ethylene and auxin signal pathway in the regulation of iron-deficiency response in Arabidopsis.


A rare case on anomalous pulmonary venous drainage in congenital cardiovascular disease.
Anomalous pulmonary veins drain into the right side of the left atrium is an uncommon variety of anomalous pulmonary venous return. Rarely, anomalous pulmonary venous drainage combined with cor triatriatum and atrial septal defect. We presented the imaging findings of a male patient who had anomalous pulmonary venous drainage which has not previously been described.


Identification and functional characterization of the Neisseria gonorrhoeae lbpB gene product.
We cloned lbpB, encoding a predicted 80-kDa lipoprotein, upstream of lbpA. A nonpolar mutant (LbpB- LbpA+) had normal lactoferrin (LF) binding and grew normally with LF as an iron source, whereas LbpB- LbpA- and LbpB+ LbpA- strains had reduced binding of LF and did not grow with LF as an iron source. LbpB bound LF directly in an affinity purification, suggesting that LbpB might play a still-uncharacterized role in the LF iron utilization.


Gabapentin: pharmacology and its use in pain management.
Although its exact mode of action is not known, gabapentin appears to have a unique effect on voltage-dependent calcium ion channels at the postsynaptic dorsal horns and may, therefore, interrupt the series of events that possibly leads to the experience of a neuropathic pain sensation. Gabapentin is especially effective at relieving allodynia and hyperalgesia in animal models. It has been shown to be efficacious in numerous small clinical studies and case reports in a wide variety of pain syndromes. Gabapentin has been clearly demonstrated to be effective for the treatment of neuropathic pain in diabetic neuropathy and postherpetic neuralgia. This evidence, combined with its favourable side-effect profile in various patient groups (including the elderly) and lack of drug interactions, makes it an attractive agent. Therefore, gabapentin should be considered an important drug in the management of neuropathic pain syndromes.


Suberoylanilide hydroxamic acid induces apoptosis and sub-G1 arrest of 320 HSR colon cancer cells.
Histone deacetylases and histone acetyl transferases covalently modify histone proteins, consequentially altering chromatin architecture and gene expression. The effects of suberoylanilide hydroxamic acid, a HDAC inhibitor, on 320 HSR colon cells were assessed in 320 HSR colon cancer cells. Concentration and time-dependent inhibition of 320 HSR cell proliferation was observed. Treatment of 320 HSR cells with 5 μM SAHA for 72 h significantly inhibited their growth by 50% as compared to that of the control. Fluorescence-activated cell sorting analysis demonstrated significant inhibition of cell cycle progression (sub-G1 arrest) and induction of apoptosis upon various SAHA concentrations after 48 h. In addition, the anti-apoptosis proteins, survivin and Bcl-xL, were significantly inhibited by SAHA after 72 h of treatment. Immunocytochemistry analysis revealed that SAHA-resistant cells were positive for cyclin A (85%), ki-67 (100%), p53 (100%), survivin (100%), and p21 (90%) expression. Furthermore, a significant increase cyclin A-, Ki-67-, p53-, survivin-, and p21-positive cells were noted in SAHA-resistant tumor cells. Our results demonstrated for the first time in 320 HSR colon adenocarcinoma cells that SAHA might be considered as an adjuvant therapy for colon adenocarcinoma.


Establishing a histologic basis for false-negative mammograms.
In order to explore the histology of false-negative mammograms, 264 consecutive patients with breast cancer were retrospectively reviewed until 100 patients with palpable cancers were identified. These patients were imaged by a dedicated mammographer within 6 months prior to biopsy. Nine of the 100 patients had "negative" readings originally, with 6 of the 9 still regarded as negative when re-examined after full knowledge of the tumor location. Histologic review of these six tumors showed a diffusely infiltrative pattern in five patients (three with invasive lobular carcinomas and two with multifocal, invasive ductal carcinomas). Although background breast density always serves in a critical relationship with tumor density on film, only one of these six patients showed a severe degree of mammographic breast density. Diffuse histology should be recognized as a principal cause of false-negative mammograms. Since mammography is based solely on anatomic contrasts, diffuse histology could easily prevent the perfection of this modality, calling attention to the need for improved adjunct imaging techniques.


Characterization of the "viable but nonculturable" (VBNC) state in the wine spoilage yeast Brettanomyces.
Although the viable but not culturable (VBNC) state has been studied in detail in bacteria, it has been suggested that maintenance of viability with loss of culturability also exists in eukaryotic cells, such as in the wine spoilage yeast Brettanomyces. To provide conclusive evidence for the existence of a VBNC state in this yeast, we investigated its capacity to become viable and nonculturable after sulfite stress, and its ability to recover culturability after stressor removal. Sulfite addition induced loss of culturability but maintenance of viability. Increasing the medium pH to decrease the concentration of toxic SO(2) allowed yeast cells to become culturable again, thus demonstrating the occurrence of a VBNC state in Brettanomyces upon SO(2) exposure. Relative to culturable Brettanomyces, VBNC yeast cells were found to display a 22% decrease in size on the basis of laser granulometry. Assays for 4-ethylguaiacol and 4-ethylphenol, volatile phenols produced by Brettanomyces, indicated that spoilage compound production could persist in VBNC cells. These morphological and physiological changes in VBNC Brettanomyces were coupled to extensive protein pattern modifications, as inferred by comparative two-dimensional electrophoresis and mass spectrometric analyses. Upon identification of 53 proteins out of the 168 spots whose abundance was significantly modified in treated cells relative to control, we propose that the SO(2)-induced VBNC state in Brettanomyces is characterized by a reduced glycolytic flux coupled to changes in redox homeostatis/protein turnover-related processes. This study points out the existence of common mechanisms between yeast and bacteria upon entry to the VBNC state.


Routine use of transrectal ultrasound in rectal carcinoma: results of a prospective multicenter study.
Preoperative transrectal ultrasound (TRUS) can establish the depth of penetration of a tumor, and thus provide important information for decisions about further management. In the literature, this method is reported to have a high level of sensitivity and specificity. Our investigation aimed at establishing the quality of the diagnostic procedure and treatment of colorectal carcinoma. This investigation, which covered a 1-year period, and involved 75 hospitals, was conducted in the form of a prospective multicenter study and included a total of 3756 patients. For rectal carcinomas, all endosonographically determined uT categories were compared with histologically established T categories (pT). At 49 hospitals a total of 499 TRUS examinations in 1463 rectal carcinomas (34.1 %) were performed. A comparison of uT with pT category was possible for 422 TRUS examinations. Agreement between the preoperative endosonographic diagnosis with the histological diagnosis was found in 63.3 % (n = 267) of cases (95 % confidence interval 58.5 % - 67.9 %). The diagnostic accuracy was 50.8 % for pT1 carcinomas, 58.3 % for pT2 lesions, 73.5 % for pT3 tumors, and 44.4 % for pT4 carcinomas. Overstaging was observed in 23.9 %, overall, and understaging in 12.8 %. Understaging was significantly less common than overstaging (P < 0.05, s.). The accuracy of transrectal ultrasound used as a routine clinical examination in rectal carcinoma patients was clearly lower than that reported in the literature. We conclude that TRUS may aid decisions relevant to treatment only when used by well-trained investigators with a large case load of rectal carcinoma patients. Centralization of transrectal ultrasonography service is mandatory if a high level of quality is to be achieved with this method.


Structural, vibrational, electronic properties, hirshfeld surface analysis topological and molecular docking studies of N-[2-(diethylamino)ethyl]-2-methoxy-5-methylsulfonylbenzamide.
The theoretical (Freebase, Cationic species) and experimental investigations on the molecular structural, spectroscopic characterization, and electronic properties of N2M5MB are reported. The most stable structure of the N2M5MB was analysed by employing Density Functional Theory (DFT) at different functional such as B3LYP, PBEPBE, TPSSTPSS and IEF-PCM (Freebase) and Cationic (B3LYP, IEF-PCM)/ 6-311++G (d,p) basis set level. The Potential Energy Scan (PES) analysis has been employed to investigate the conformational preference of the title molecule. The optimized molecular geometry, vibrational assignments (FT-IR, FT-Raman) of wavenumbers have been performed for freebase, cationic species (Gas, PCM) for the individual modes of vibration. The experimental UV-Vis absorption spectrum was obtained and compared with the simulated (Freebase, Cationic species) Time-Dependent (TD-DFT-M062X) method. The FMO's, electron-hole distributions, HOMA, FLU, Hirshfeld surface analysis, Electrostatic potential surface (ESP), Fukui functions, and topological parameters were discussed. Molecular docking studies were performed for the N2M5MB (ligand) into the active site of targeted proteins (1H22, 4DTL, 5OV9) which belong to AChE inhibitors with the minimum binding energy was detected.


Complete Genome Sequence of Lacticaseibacillus rhamnosus DM065, Isolated from the Human Oral Cavity.
The 3.0-Mb complete genome of Lacticaseibacillus rhamnosus strain DM065, which was isolated from the oral cavity of healthy volunteers in South Korea, was sequenced using a combination of PacBio and Illumina technologies. The genome consists of one circular chromosome and two plasmids and lacks antimicrobial resistance genes.


Placental angiopoietin-1 and angiopoietin-2 expression and correlation with birth weight in twins.
To study the expression of angiopoietin 1 (Ang1) and angiopoietin 2 (Ang2) in human placentas of dizygotic dichorionic twins in relation to fetal growth. Placentas from dizygotic-dichorionic twins (n=14) obtained from normal uncomplicated pregnancies were collected immediately after delivery. A quantitative assessment of the placental expression of Ang1 and Ang2 was done using quantitative PCR. Birth weight and anthropometric parameters were measured. Statistical analysis was preformed. Ang1 and Ang2 were expressed in the placentas. We found a significant positive correlation between birth weight and expression of both Ang1 and Ang2 (p<0.009, p<0.011, respectively). In addition, there was a significant positive correlation between skin fold, BMI and Ang1 expression (p<0.0001 and p<0.01, respectively). A positive correlation between twin birth weight and placental angiogenesis was found. We suggest that placental expression of Ang1 and Ang2 may have an important role in fetal growth in twin pregnancy.


Leak detection and localization in water distribution networks using conditional deep convolutional generative adversarial networks.
This paper explores the use of 'conditional convolutional generative adversarial networks' (CDCGAN) for image-based leak detection and localization (LD&L) in water distribution networks (WDNs). The method employs pressure measurements and is based on four pillars: (1) hydraulic model-based generation of leak-free training data by taking into account the demand uncertainty, (2) conversion of hydraulic model input demand-output pressure pairs into images using kriging interpolation, (3) training of a CDCGAN model for image-to-image translation, and (4) using the structural similarity (SSIM) index for LD&L. SSIM, computed over the entire pressure distribution image is used for leak detection, and a local estimate of SSIM is employed for leak localization. The CDCGAN model employed in this paper is based on the pix2pix architecture. The effectiveness of the proposed methodology is demonstrated on leakage datasets under various scenarios. Results show that the method has an accuracy of approximately 70% for real-time leak detection. The proposed method is well-suited for real-time applications due to the low computational cost of CDCGAN predictions compared to WDN hydraulic models, is robust in presence of uncertainty due to the nature of generative adversarial networks, and scales well to large and variable-sized monitoring data due to the use of an image-based approach.


It's in Your Hands: An Educational Initiative to Improve Parent/Family Hand Hygiene Compliance.
Health care-associated infections contribute to increased morbidity and mortality, increased resource use, higher costs, and extended hospitalizations. Proper hand hygiene (HH) is essential to health care-associated infection prevention. Low compliance among parents in our neonatal intensive care unit (NICU) was identified and prompted development of an HH initiative. The objective of this quality improvement project was to improve parent HH practices with the ultimate goal of achieving 100% compliance with parent HH. Between December 2011 and November 2014, our NICU Infection Prevention Committee developed and implemented the parent/family HH initiative entitled "It's in Your Hands" and created learning materials based on the World Health Organization and Centers for Disease Control and Prevention recommendations. Materials included information sheets, posters, stickers, and checklists. Audits, based on the World Health Organization's Five Moments for Hand Hygiene, were performed several times per week to monitor compliance. Before the intervention, only 71% (n = 1143) of all observed parents and family members performed proper HH. After the intervention, proper HH increased to 89% (n = 939). An average compliance of 89% was maintained throughout the intervention phase. This initiative led to sustained improvements in HH compliance among NICU parents. It has empowered parents to speak up and request proper HH from health care providers when interacting with their child. This initiative has been adopted as a hospital-wide standard of care.


Effect of Foliar Spray Application of Zinc Oxide Nanoparticles on Quantitative, Nutritional, and Physiological Parameters of Foxtail Millet (Setaria italica L.) under Field Conditions.
It has been shown that the foliar application of inorganic nano-materials on cereal plants during their growth cycle enhances the rate of plant productivity by providing a micro-nutrient source. We therefore studied the effects of foliarly applied ZnO nanoparticles (ZnO NPs) on Setaria italica L. foxtail millet's quantitative, nutritional, and physiological parameters. Scanning electron microscopy showed that the ZnO NPs have an average particle size under 20 nm and dominant spherically shaped morphology. Energy dispersive X-ray spectrometry then confirmed ZnO NP homogeneity, and X-ray diffraction verified their high crystalline and wurtzite-structure symmetry. Although plant height, thousand grain weight, and grain yield quantitative parameters did not differ statistically between ZnO NP-treated and untreated plants, the ZnO NP-treated plant grains had significantly higher oil and total nitrogen contents and significantly lower crop water stress index (CWSI). This highlights that the slow-releasing nano-fertilizer improves plant physiological properties and various grain nutritional parameters, and its application is therefore especially beneficial for progressive nanomaterial-based industries.


Enantioselective assembly of substituted dihydropyrones via organocatalytic reaction in water media.
The diarylprolinol ether/HOAc-catalyzed cascade Michael addition and cyclization of aldehydes and alpha-keto-alpha,beta-unsaturated esters proceeds smoothly in water to afford cyclic hemiacetals, which are oxidized to furnish highly functionalized 3,4,5,6-tetrasubstituted dihydropyrones with excellent enantioselectivities.


Mast4 knockout shows the regulation of spermatogonial stem cell self-renewal via the FGF2/ERM pathway.
Spermatogenesis is an important cellular differentiation process that produces the male gametes and remains active throughout the individual's lifespan. Sertoli cell-only syndrome (SCO) refers to the dysfunction of the male reproductive system, including infertility. Accurate self-renewal of spermatogonial stem cells (SSCs) is essential to prevent SCO syndrome. This study investigated the role of microtubule-associated serine/threonine kinase family member 4 (MAST4) in spermatogenesis in mice. MAST4 was localized in Sertoli cells before puberty, providing a somatic niche for spermatogenesis in mice and MAST4 expression shifted to Leydig cells and spermatids throughout puberty. Mast4 knockout (KO) testes were reduced in size compared to wild-type testes, and germ cell depletion associated with an increase in apoptosis and subsequent loss of tubular structure were similar to the SCO phenotype. In addition, MAST4 phosphorylated the Ets-related molecule (ERM), specifically the serine 367 residue. The phosphorylation of ERM ultimately controls the transcription of ERM target genes related to SSC self-renewal. The expression of spermatogenesis-associated proteins was significantly decreased whereas Sertoli cell markers were increased in Mast4 KO testes, which was well-founded by RNA-sequencing analysis. Therefore, MAST4 is associated with the fibroblast growth factor 2 (FGF2)/ERM pathway and this association helps us explore the capacity of SSCs to maintain a vertebrate stem cell niche.


Vasopressin messenger ribonucleic acid in supraoptic and suprachiasmatic nuclei: appearance and circadian regulation during development.
The developmental appearance and regulation of hypothalamic vasopressin (prepropressophysin) mRNA was studied using quantitated in situ hybridization techniques. Vasopressin mRNA levels in the supraoptic nuclei were reliably detected on day 16 of gestation, while mRNA in the suprachiasmatic nuclei (SCN) was detectable on day 21. These developmental patterns correlate well with the immunohistochemical appearance of prepropressophysin translation products previously reported in these nuclei. A prominent day-night rhythm of vasopressin mRNA levels was evident in the SCN on day 21 of gestation; the rhythm was also present on postnatal days 2 and 11. No such rhythm was present in the supraoptic nuclei at any developmental stage examined. These results demonstrate regulated expression of the vasopressin gene during fetal life. Vasopressin mRNA levels in the SCN are already under specific circadian control when the nuclei are morphologically immature and lacking many of the connections found in adult animals.


Human herpes viruses in non-melanoma skin cancers.
We examined the possible involvement of human herpes viruses in sporadic non-melanoma skin cancer of Greek patients. Polymerase chain reaction (PCR) based detection assays were utilized for the detection of viral cytomegalovirus (CMV), herpes simplex virus (HSV) and Epstein-Barr virus (EBV) genomes in 24 squamous cell carcinomas (SCC), five Bowen's disease, 72 basal cell carcinomas (BCC) specimens and eight premalignant lesions. Forty-two of 109 (38.5%) skin lesions were found positive for CMV DNA. The highest incidence was 6/8 (75%) observed in specimens with premalignant lesions. The incidence was 37.5% (27/72) in BCC, 33% (8/24) in SCC and 20% (1/5) in extragenital Bowen's disease. All samples were negative for HSV-1/2 and EBV DNA as assessed by our PCR based assay. The CMV infection showed no statistically significant correlation with the histological type, age, site of lesion or sex. Our results give a strong indication of the possible involvement of CMV in non-melanoma skin cancer development.