Review of microbiota gut brain axis and innate immunity in inflammatory and infective diseases.
The microbiota gut brain (MGB) axis has been shown to play a significant role in the regulation of inflammatory and infective diseases. Exploring the structure and communication mode of MGB axis is crucial for understanding its role in diseases, and studying the signaling pathways and regulatory methods of MGB axis regulation in diseases is also of profound significance for future clinical research. This article reviews the composition, communication mechanism of MGB axis and its role in inflammatory and infective diseases, including Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), autism spectrum disorder (ASD), depression, psoriasis, irritable bowel syndrome (IBS), and inflammatory bowel diseases (IBD). In addition, our investigation delved into the regulatory functions of the inflammasome, IFN-I, NF-κB, and PARK7/DJ-1 innate immune signaling pathway in the context of inflammatory and infective diseases. Ultimately, we discussed the efficacy of various interventions, including fecal microbiota transplantation (FMT), antibiotics, probiotics, prebiotics, synbiotics, and postbiotics, in the management of inflammatory and infective diseases. Understanding the role and mechanism of the MGB axis might make positive effects in the treatment of inflammatory and infective diseases.


Effect of fasting on mucosal blood flow in antrum and corpus of the stomach.
Gastric mucosal blood flow in the rat was determined by the indicator fractionation technique 86RbCl. Antral and corpus flow rates were determined after increasing periods of fasting, and the effect of vagotomy was assessed. The physiological stimulus of food in the stomach markedly increased antral as well as corpus blood flow, and after vagotomy lower flow rates were recorded in all parts of the stomach. With progressive starvation, the antral:corpus flow ratio decreased. The findings suggest that the antrum plays an active role in response to a physiological stimulus and may, as has been suggested by others, contribute to the control of parietal cell blood flow and secretion.


Monotone and partially monotone neural networks.
In many classification and prediction problems it is known that the response variable depends on certain explanatory variables. Monotone neural networks can be used as powerful tools to build monotone models with better accuracy and lower variance compared to ordinary nonmonotone models. Monotonicity is usually obtained by putting constraints on the parameters of the network. In this paper, we will clarify some of the theoretical results on monotone neural networks with positive weights, issues that are sometimes misunderstood in the neural network literature. Furthermore, we will generalize some of the results obtained by Sill for the so-called min-max networks to the case of partially monotone problems. The method is illustrated in practical case studies.


Effects of kanamycin administration to poultry on the interspecies transmission of drug-resistant Salmonella.
Three experiments were conducted to assess the relationship between antibiotic administration to poultry and the transmission of drug-resistant Salmonella through a simulated food chain. Poults were inoculated per os with either multiply drug-resistant Escherichia coli and drug-sensitive S. typhimurium or with multiply drug-resistant S. typhimurium. One-half of the poults inoculated with drug-sensitive S. typhimurium and all poults given drug-resistant S. typhimurium received kanamycin in their drinking water. Liver tissue from these poults was incorporated into diets fed to rats, half of which were treated with kanamycin. Antibiotic administration to the poults was associated with a significantly (P less than .05) higher frequency of transmission of drug-resistant S. typhimurium to the rats through the simulated food chain. S. typhimurium was isolated only from rats treated with kanamycin. The highest frequency of isolation of drug-resistant S. typhimurium from rats (40%) was observed in kanamycin-treated rats fed a diet containing liver from kanamycin-treated poults. Results of this experiment indicate that antibiotic administration can increase the frequency of transmission of drug-resistant Salmonella through the food chain.


[Practical comments on the use of immunoglobulins].
The paper contains basic information relating to treatment with immunoglobulin. Presented indications for their use, among others: primary immunodeficiency, Kawasaki disease, Guillain-Barre syndrome, chronic lymphocytic leukemia, primary thrombocytopenia. The factors to consider when choosing a preparation: the content of IgG, IgA, method of administration (intravenous or subcutaneous). The most frequent side effects, depending on the organ localization. Presented at risk (obesity, diabetes, renal failure, hypovolemia) in which these symptoms may occur especially frequently, which should be taken into account in the conduct of therapy (adequate hydration, low-dose, slow infusion).


Timing of Surgery for Hip Fracture in Patients on Direct Oral Anti-coagulants: A Population-Based Cohort Study.
In patients with hip fracture on direct oral anti-coagulants (DOACs), timely surgery is important in optimising outcomes but the safety of early surgery is unclear. This study aims to evaluate the timing of surgery on peri- and post-operative outcomes in patients with hip fracture on DOAC therapy. Single-centre, retrospective, population-based cohort study of patients on DOAC therapy compared to standard care with low-molecular-weight heparin (LMWH) undergoing surgery for hip fracture. Data obtained: patient demographics, fracture classification, American Society of Anaesthesiologists (ASA) classification, time to surgery, procedure performed, type of DOAC, timing of last DOAC dose, use of reversal agents or pro-coagulants and length of stay. Outcomes assessed: pre- and post-operative haemoglobin levels, incidence of blood transfusion, major haemorrhage, venous thromboembolism (VTE) and death within 30 days of surgery. A total of 755 patients were included. Compared to standard treatment, DOAC use was associated with a similar change in pre- and post-operative haemoglobin levels (P = .90), risk of blood transfusion (RR: 1.04, 95% CI: .70-1.54, P = .84), haemorrhage (RR: 1.51, 95% CI: .53-4.28, P = .44), VTE (RR: .92, 95% CI: .12-7.20, P = .94) and mortality (RR: 1.85, 95% CI: .89-3.84, P = .10), all of which were independent of the timing of surgery. This study builds on growing evidence that surgery for hip fracture in patients on DOAC therapy is not associated with an excessive risk of haemorrhage, irrespective of the timing of surgery. Timely surgical fixation of the hip fracture in this population is indicated in the absence of other risk factors for haemorrhage.


Dietary lysolecithin supplementation improves growth performance of weaned piglets via improving nutrients absorption, lipid metabolism, and redox status.
Lysolecithin is widely used as emulsifier to improve the digestibility and retention of fat. The current study aimed to investigate the effects of dietary lysolecithin supplementation on growth performance, nutrients absorption, lipid metabolism, and redox status of weaned pigs. A total of 60 weaned piglets were assigned into 2 dietary treatments in a randomized complete block design, receiving basal diet with 0 or 1,000 mg/kg lysolecithin for a period of 28 d. Each dietary treatment had 10 replicates with 3 piglets per replicate. Growth performance and fecal score were monitored during trial. Samples of blood, ileum, and liver tissues were collected and analyzed for serology, intestinal histomorphology, and lipid metabolism-related gene and protein expressions. Dietary lysolecithin supplementation increased average daily gain (+15%, P < 0.05) and tended to increase average daily feed intake (+14%, P = 0.08) in overall experimental period. At final, the average body weight of piglets in lysolecithin group was 10% greater than that of control group (P = 0.09). In addition, dietary lysolecithin supplementation improved the ability of nutrients absorption as indicated by the higher d-xylose level in plasma (P < 0.05). Moreover, piglets from lysolecithin group had higher concentration of high-density lipoprotein (P < 0.05), but lower triglyceride (P < 0.05) in plasma. The inclusion of lysolecithin in diet increased the level of reduced glutathione (GSH) and GSH to oxidized glutathione (GSSG) ratio in plasma and liver (P < 0.05), but attenuated the levels of malondialdehyde and GSSG in ileum (P < 0.05). The upregulation of lipogenesis-related genes (FAS and ACC), downregulation of lipolysis (PNPLA2 and PABP1), and lipid mobilization (PGC-1α and SRIT1) genes were observed in lysolecithin relative to control piglets. Compared with control group, dietary lysolecithin supplementation upregulated protein expressions of GPX4, SREBP1, and LPL in liver and LPL in ileum (P < 0.05). Collectively, our study indicates that dietary lysolecithin supplementation improved growth performance of weaned piglets, which may be associated with the improved nutrients absorption, redox status, and lipid metabolism.


Hypo-echogenic pseudolesions of the liver examined by CT.
Successive hypo-echogenic focal lesions of the liver tentatively interpreted sonographically as benign were collected over a 3-year period and analyzed. All of these patients had undergone a CT examination and had been followed up. Lesions ranging in size from 2 to 13 cm were seen in about 0.1% of the patients. None of the 16 homogeneous hypo-echogenic nonexpansive and well-demarcated lesions bordering upon anatomic structures with a partly straight or concave contour turned out to be malignant. CT was able to give little additional information.


Association between insulin-like growth factor I (IGF-I) polymorphisms, circulating IGF-I, and pre- and postnatal growth in two European small for gestational age populations.
The purpose of this study was to assess the association of IGF-I and birth size by studying small for gestational age (SGA) subphenotypes and undertaking more detailed analysis of IGF-I genetic markers. SGA subjects from Haguenau, France (n = 113), and Gothenburg, Sweden (n = 174), were studied. The Swedish subjects were subphenotyped according to postnatal growth (114 short SGA and 60 SGA catch-up). IGF-I dinucleotide repeat and single nucleotide polymorphism (SNP) markers were studied, and haplotypes were generated in the Swedish short SGA group by identity of state. Association analysis was undertaken using the Monte Carlo method of association analysis of multiallelic markers for dinucleotide repeat markers, by exact chi(2) analysis for SNPs and by ANOVA for serum IGF-I levels. IGF-I genotype was associated with the SGA phenotype, in particular with symmetrical SGA and low birth weight, and with IGF-I levels in SGA subjects. Association with postnatal growth was different in the two populations, which may reflect the power of the smaller subphenotype groups. Haplotype analysis in the Swedish short SGA subjects showed that the region of association lay between the promoter and intron 2 of the IGF-I gene. These studies validate the association of the IGF-I gene with birth size and refine the region of association in Swedish short SGA subjects.


Senescent sperm performance in old male birds.
Senescence is the deterioration of the phenotype with age caused by negative effects of mutations acting late in life or the physiological deterioration of vital processes. Birds have traditionally been assumed to senescence slowly despite their high metabolic rates, high blood sugar levels and high body temperature. Here we investigate the patterns of age-related performance of sperm of a long distance migrant, the barn swallow Hirundo rustica, varying in age from 1 to 6 years, analysed by the computer-assisted sperm analysis equipment. Sperm showed deteriorating performance in terms of linear movement, track velocity, straight line velocity and reduced proportions of rapidly moving, progressive and motile sperm with age. In a second series of experiments, we assessed performance of sperm from the same males in neutral medium and in medium derived from the reproductive tract of females in an attempt to test if sperm of old males performed relatively better in female medium, as expected from extra-pair paternity being negatively related to male age, but not to female age. Older males showed consistently better performance in female medium than in neutral medium in terms of track velocity, straight line velocity and reduced proportions of rapidly moving, progressive and motile sperm, whereas young males showed better performance in neutral medium. These results provide evidence of declining sperm performance for important reproductive variables not only with age, but also with the sperm of old males performing differentially better in female medium than young males.


Ontogeny of gamma-glutamyltransferase in the rat lung.
gamma-Glutamyltransferase (gamma-GT) is a key enzyme in the metabolism of glutathione and glutathione-substituted molecules. The gamma-GT gene is expressed in two epithelial cells of the adult lung, the bronchiolar Clara cell and the alveolar type II cell. Because pulmonary glutathione metabolism may be important in the perinatal period, we studied gamma-GT ontogeny in the developing rat lung. In the late fetal and early postnatal lung, gamma-GT mRNA was below detectable limits on Northern blots. Pulmonary gamma-GT protein and enzyme activity were present at low levels after fetal day 18. gamma-GT protein appeared as a high-molecular-mass band (>95 kDa), with small amounts of enzymatically active gamma-GT heterodimer. Between the 2nd and 3rd postnatal wk, pulmonary gamma-GT mRNA expression increased in association with an increase in gamma-GT protein and enzyme activity that reached adult lung levels. At this time, gamma-GT protein appeared predominantly in the heterodimeric form with small amounts of the >95-kDa protein. Immunocytochemistry revealed that, in the fetal and early postnatal lung, gamma-GT was expressed only in the alveolar type II cell, whereas the Clara cell became the major site of gamma-GT mRNA and protein expression by 2-3 wk and in the adult. Type II cells isolated from the fetal lung express gamma-GT mRNA and synthesize the >95-kDa form of gamma-GT in excess of the heterodimer. These studies demonstrate that the alveolar type II cell is the only cell producing gamma-GT in the newborn lung and that it synthesizes a form of gamma-GT that appears to differ from that produced at a later time point by the Clara cell.


Lower limb revascularization in diabetics.
Treatment of critical lower limb ischemia in diabetics is often a complex clinical problem for the diabetics' general condition and the local condition of the territory to be revascularized. For these reasons, often the only treatment for diabetics with ischemic-necrotic lesions is amputation. In the symptomatology of arterial disease in diabetics there are three stages: claudication, rest pain, ulcerative-necrotic lesions and two treatment modalities: conservative treatment and revascularization. Conservation is based on the optimization of metabolic control, correction of anemia, control of risk factors, removal of necrotic areas, specific antibiotic treatment based on culture tests. No healing of ulcerative-necrotic lesions after a reasonable period of optimum therapy, quantified in 6 weeks, is suggestive for the presence of absolute or relative ischemia and diagnostic angiography is suitable for the indication for intravascular or surgical revascularization. The latter, in case of diabetics with ischemic complications of the foot, is performed in specialized centers with inverted saphenous veins or in situ in the supragenicular and subgenicular district. Recently intravascular revascularization with balloons, atherotomes, stents, less invasive and less traumatic than bypass revascularization, have become available. At present, with peripheral revascularization, limb salvage at 5-years is feasible in 92% of diabetics with critical lower extremity ischemia.


Nuclear localization signal in a cancer-related transcriptional regulator protein NAC1.
Nucleus accumbens-associated protein 1 (NAC1) might have potential oncogenic properties and participate in regulatory networks for pluripotency. Although NAC1 is described as a transcriptional regulator, the nuclear import machinery of NAC1 remains unclear. We found, using a point mutant, that dimer formation was not committed to the nuclear localization of NAC1 and, using deletion mutants, that the amino-terminal half of NAC1 harbored a potential nuclear localization signal (NLS). Wild type, but not mutants of this region, alone was sufficient to drive the importation of green fluorescent protein (GFP) into the nucleus. Bimax1, a synthetic peptide that blocks the importin α/β pathway, impaired nuclear localization of NAC1 in cells. We also used the binding properties of importin to demonstrate that this region is an NLS. Furthermore, the transcriptional regulator function of NAC1 was dependent on its nuclear localization activity in cells. Taken together, these results show that the region with a bipartite motif constitutes a functional nuclear import sequence in NAC1 that is independent of NAC1 dimer formation. The identification of an NAC1 NLS thus clarifies the mechanism through which NAC1 translocates to the nucleus to regulate the transcription of genes involved in oncogenicity and pluripotency.


Development of a Portable Tool for Screening Neuromotor Sequelae From Repetitive Low-Level Blast Exposure.
Blast exposure is a prevalent cause of mild traumatic brain injury (mTBI) in military personnel in combat. However, it is more common for a service member to be exposed to a low-level blast (LLB) that does not result in a clinically diagnosable mTBI. Recent research suggests that repetitive LLB exposure can result in symptomology similar to symptoms observed after mTBI. This manuscript reports on the use of an Android-based smartphone application (AccWalker app) to capture changes in neuromotor functioning after blast exposure. Active duty U.S. Navy personnel (N = 59) performed a stepping-in-place task before repetitive LLB exposure (heavy weapons training), and again immediately after, 24 hours after, and 72 to 96 hours after the completion of the training. The AccWalker app revealed that there are changes in neuromotor functioning after LLB exposure (slower self-selected movement pace and increased stride time variability) in participants who experienced neurocognitive decline. These data suggest that neurocognitive and neuromotor decline can occur after repeated LLB exposure.


Eukaryotic operon-like transcription of functionally related genes in Drosophila.
Complex biological processes require coordinated function of many genes. One evolutionary solution to the problem of coordinately expressing functionally related genes in bacteria and nematodes is organization of genes in operons. Surprisingly, eukaryotic operons are considered rare outside the nematode lineage. In Drosophila melanogaster, we found lounge lizard (llz), which encodes a degenerin/ENaC cation channel, cotranscribed with CheB42a, a nonhomologous gene of unknown function residing <100 bp upstream. These two genes were transcribed from a single promoter as one primary transcript and were processed posttranscriptionally to generate individual mRNAs. The mechanism did not involve alternative splicing, and it differed from the trans splicing used in nematode operons. Both genes were expressed in the same tissues, and previous work suggested that both may be involved in courtship behavior. A bioinformatic approach identified numerous additional loci as potential Drosophila operons. These data reveal eukaryotic operon-like transcription of functionally related genes in Drosophila. The results also suggest that operon-based transcription may be more common in eukaryotes than previously appreciated.


Technology-Based Educational Approaches to Address Opioid Use Management by Advanced Practice Registered Nurses.
Opioid overdose remains the leading cause of accidental death, with 64,000 deaths attributable to opioid-related overdoses in 2016 and a 20% increase in mortality since 2015. Advanced practice registered nurses (APRNs) are now eligible to prescribe buprenorphine. The purpose of this project was to develop educational training materials regarding opioid use management; widely disseminate these materials; monitor reach and intervention efficacy in precipitating practice change; and to evaluate barriers and facilitators of buprenorphine prescribing. The authors developed a three-webinar series pertaining to opioid use management. A broad marketing and dissemination approach was utilized. Demographic data was collected when individuals registered to participate in the webinar series. Follow-up data was collected post-webinar and sought to assess practice change, and barriers to and facilitators of buprenorphine prescribing. Of the 670 individuals that viewed one or more of the live webinars, 218 (32.5%) completed a portion of one or both of the follow-up surveys (at 3- and 6-months post-webinar). Of the respondents, 39 (18%) had obtained the DATA 2000 (buprenorphine) waiver since viewing the webinar series, and 11 (5.1%) were in the process of obtaining the DATA 2000 waiver. Barriers to buprenorphine prescribing included regulatory factors, patient-specific factors, and provider-specific factors. Facilitators to buprenorphine prescribing included institutional support and mentorship, collaboration with professional organizations, increased community awareness, and patient outcomes. APRNs should be abreast of best practices in the management of opioid use disorders. Barriers to and facilitators of buprenorphine prescribing must be understood and addressed.


Diabetic myonecrosis in a previously healthy woman and review of a 25-year Mayo Clinic experience.
To describe a case of diabetic myonecrosis, an unusual complication of diabetes mellitus, and to provide an overview of an institutional experience with this condition. We report the clinical, laboratory, and imaging findings in a 50-year-old woman with no history of diabetes, who was hospitalized because of weakness in her left lower extremity and an infection in her right hand. A morbidly obese woman had sustained several falls attributable to left leg weakness, which had resulted in repetitive trauma to, and subsequent infection of, her right hand. Laboratory studies showed a fasting blood glucose level of 204 mg/dL, a glycated hemoglobin of 12.8%, and a calculated hemoglobin Alc of 10.6%. Results of evaluations for retinopathy and nephropathy were negative. Electromyography of the left leg suggested the presence of a diabetic plexopathy. Two weeks after admission of the patient, severe left lower extremity pain and swelling developed abruptly. Ultrasound evaluation of the leg was negative for deep venous thrombosis. Laboratory data revealed a leukocyte count of 7.1 x 10(3)/mL and a creatine kinase level of 26 U/L. Magnetic resonance imaging of the left leg demonstrated extensive muscle edema and collections of fluid surrounding the femur and posterior compartment of the thigh and extending into the left calf. Gram stain and cultures of aspirated fluid were negative. The patient was managed with supportive care, including strict glycemic control, periodic analgesia, and physical therapy. A review of medical records for a 25-year period at the Mayo Clinic disclosed only five patients with the diagnosis of diabetic myonecrosis. All five patients had insulin-treated diabetes and severe end-organ disease. The current case is the first report of myonecrosis as the initial manifestation of diabetes. This case also demonstrates that myonecrosis, although typically involving the thigh, can extend abruptly to the calf. Diabetic myonecrosis should be included in the differential diagnosis of an acutely painful lower extremity mass in patients with diabetes.


[Effects of sublingual immunotherapy on serum IL-17 and IL-35 levels in children with allergic rhinitis or asthma].
To study the clinical effect and mechanisms of specific sublingual immunotherapy (SLIT) for the treatment of allergic rhinitis or asthma in children. Thirty children suffering from Dermatophagoides farinae-allergic rhinitis or asthma (case group) and 30 healthy children (control group) were enrolled in this study. The case group accepted SLIT between January and December 2011. The ratio of forced expiratory volume in one second (FEV1) and its expected value, the ratio of airway resistance and its expected value, peripheral blood eosinophil (Eos) count and serum levels of IL-17 and IL-35 were measured before treatment and one and two years after treatment. The rhinitis or asthma symptom scores were rated and the level of asthma control was monitored. Serum IL-17 level in the case group was significantly higher than in the control group before treatment and one year after treatment (P<0.01). Furthermore, serum IL-17 level in the case group gradually decreased from before treatment to 1 year to 2 years after treatment (P<0.01). By two years of treatment, there was no significant difference in serum IL-17 level between the case and control groups (P>0.05). The changes of serum IL-35 level after treatment were opposite to serum IL-17 in the case group. The ratio of FEV1 and its expected value gradually increased from before treatment to 1 year to 2 years after treatment (P<0.01) in the case group. In contrast, the change of the ratio of airway resistance and its expected value and Eos count gradually decreased from before treatment to 1 year to 2 years after treatment (P<0.01) in the case group. More patients achieved improved rhinitis or asthma symptom scores two years after treatment than one year after treatment in the case group (P<0.01). SLIT was effective in 85% of children with allergic rhinitis one after treatment vs 100% two years after treatment. Asthma control was observed in 76% of the asthmatic patients one after treatment vs 92% two years after treatment. SLIT is effective for allergic rhinitis and asthma in children, and the treatment period of two years seems to be superior to one year. The mechanism of action of SLIT for the treatment of allergic rhinitis and asthma may be associated with inhibition of IL-17 expression and promotion of IL-35 expression.


Prophylaxis of upper gastrointestinal bleeding with cimetidine in patients undergoing partial hepatectomy.
The aim of this study was to evaluate the effect of cimetidine on prophylaxis of upper gastrointestinal (GI) bleeding from acute mucosal lesions or stress ulcers of the stomach and duodenum after partial hepatectomy. Five (27.8%) of 18 control patients had upper GI bleeding v.s. only two (5.9%) of 34 cimetidine treated patients (P less than 0.05). The result showed that cimetidine therapy is an effective modality to prevent upper GI bleeding after liver resection but there was a trend that it may induce postoperative liver failure and hepatitis. A further study is necessary to elucidate whether cimetidine therapy is really safe following major hepatic resection.


Decationized polyplexes for gene delivery.
Gene therapy has received much attention in the field of drug delivery. Synthetic, nonviral gene delivery systems have gained increasing attention as vectors for gene therapy mainly due to a favorable immunogenicity profile and ease of manufacturing as compared to viral vectors. The great majority of these formulations are based on polycationic structures, due to their ability to interact with negatively charged nucleic acids to spontaneously form nanoparticles. In recent years, several polycationic systems have demonstrated high transfection in vitro. However, progress toward clinical applications has been slow, mainly because the cationic nature of these systems leads to intolerable toxicity levels, inappropriate biodistribution and unsatisfactory efficiency in vivo, particularly after systemic administration. Decationized polyplexes are a new class of gene delivery systems that have been developed as an alternative for conventional polycation-based systems. The major innovation introduced by decationized polyplexes is that these systems are based on neutral polymers, without any detrimental effect on the physicochemical stability or encapsulation ability, due to the transient presence of cationic charge and disulfide cross-links between the polymer chains by which the nucleic acids are physically entrapped in the particles. This editorial summarizes the most important features of decationized polyplexes and discusses potential implications for the development of new safe and efficient gene delivery systems.


Survival analysis of orthodontic retainers.
Retainers play a critical role in the long-term success of orthodontic treatment. The aims of this study were to evaluate the survival time of different retainers and to investigate the potential predictors of the retainer failures. A total of 591 retainers from 309 patients (between 2003 and 2014) were included in the study, including Hawley retainers (n = 199), vacuum-formed retainers (n = 34), lingual fixed retainers (n = 278), and the COMBO (a combination of two different retainers in the same arch; n = 80). Patient's demographics, retention procedures, time to failure (survival time), and reasons for failures were extracted from patient files. Failure of retainer was defined as any events after which the retainers needed to be replaced or repaired; loss of retainer was treated as a failure because the retainer could not fulfil its role. Survival analyses were performed to compare the survival time between different retainer groups. The survival time was the longest for lingual fixed retainers (median 1604 days) and Hawley retainers (1529 days), followed by COMBO (258 days) and vacuum-formed retainers (105 days; overall P < 0.001). No statistical significance of survival time of lingual fixed retainers was found between maxilla (1497 days) and mandible (1604 days; P = 0.341), nor between different types of the COMBO (overall P = 0.078). These results were unchanged before and after adjusting for the age, gender, and socioeconomic status (SES) of the patients. The reasons for failures varied among different retainers: most failures of the Hawley retainers were 'lost' (52.0%), most failures of the lingual fixed retainers were debond (63.5%), and fracture was the most common cause of failure for both vacuum-formed retainers (43.5%) and the COMBO (41.9%). Lingual fixed retainers and Hawley retainers had the longest survival times, followed by the COMBO retainers and vacuum-formed retainers. The reasons of failure were mainly mechanical (debond and fracture) and patient-related (loss).


A study of the so-called neurotization of nevi.
Fourteen nevi with neuroid zones were examined and compared with nine nevi without neuroid structures. At light microscopic level, nevus cells from the neuroid nevi and the control nevi show the same staining pattern with polyclonal antibodies against S-100 protein. Around the cells of the neuroid zones is a more intensive immunoreactivity with monoclonal antibodies against laminin and collagen type IV than around the nevus cells in the upper dermis and the nevus cells in the control nevi. Also, the Gordon-Sweet stain for reticulin shows a dense network around the cells of the neuroid zones. No immunoreactivity in the neuroid zones was found with monoclonal antibodies against myelin-basic protein, myelin-associated protein, and glial fibrillary acidic protein. At the electron microscopic level, nevus cells from the neuroid zones show stacks of elongated cytoplasmic processes surrounded by basal lamina material. This pattern explains the presence of the abundant cytoplasm seen at light microscopy. Because no features of neural or neurolemmal differentiation could be found, the exactitude of the term neurotization can be questioned.


Time-to-turbidity model for non-protective type B Clostridium botulinum.
A model to predict the time for growth to turbidity from spores of non-proteolytic type B strains of Clostridium botulinum was developed in broth media with varying temperatures (4-28 degrees C), pH values (5-7), NaCl additions (0-4%) and total spores (10(1)-10(5)). The model estimates the probability that a sample will have growth on a given day for up to 90 days of storage. The parameters of the model include the probability of growth after 90 days (Pmax) and the mean time of growth (tau) for those that showed growth. The 95% confidence interval (CI95%) for tau was also determined. The tau decreased with increasing temperature and pH, but NaCl levels below 3% had little effect. Decreasing the number of spores in a sample increased both tau and the confidence intervals about tau, reflecting the increasing uncertainty about the estimation of growth times for low spore numbers.


Laser frequency noise induced error in resonant fiber optic gyro due to an intermodulation effect.
For the first time, a significant noise source in the resonant fiber optic gyroscope (RFOG) called intermodulation induced error is proposed and deeply analyzed in this paper. The intermodulation error is produced by the laser frequency noise at even multiples of the modulation frequency due to an intermodulation effect, which will seriously limit the random noise performance of the RFOG. Experiments are designed and conducted to verify and measure the intermodulation induced error in the RFOG. The experimental results confirm the existence of intermodulation error, and fit well with the theory. As for the design of the RFOG, light sources with a narrow intrinsic linewidth and a high modulation frequency are preferable to achieve a high rotation-rate sensitivity.


Morphological effects of itraconazole on murine macrophage.
Morphological effects of itraconazole (ITCZ) on murine macrophages were examined by light microscopy (LM), scanning electron microscopy (SEM) and transmission electron microscopy (TEM), and compared with the effects of other antifungal agents. Thioglycolate-induced peritoneal macrophages were prepared from C3H/He J mice and cultured for 20 h in the presence of the antifungal azoles econazole, fluconazole, miconazole, ketoconazole, ITCZ, hydroxy-itraconazole (ITCZ-OH), and a polyene antibiotic amphotericin B (AMPH). Among these reagents, only ITCZ and its derivative ITCZ-OH were effective in causing morphological changes of murine macrophage as determined by LM and SEM. Macrophages treated with 2 microg/ml ITCZ or ITCZ-OH were stretched out bidirectionally, their surface was smooth and their 'ruffles' decreased. TEM observation showed that the bundles of the filamentous structure existed along the cell shape in the cytoplasm. These findings suggest that ITCZ and ITCZ-OH affect the morphology of macrophages.


[Clinical characteristics and prognostic analysis of sudden sensorineural hearing loss with metabolic syndrome].
Objective:To analyze the clinical characteristics and prognosis of sudden sensorineural hearing loss (SSNHL) with metabolic syndrome (MetS).Method:Records of 212 patients with SSNHL treated in our department were retrospectively reviewed, including gender, age,course of the disease, concomitant time of tinnitus and vertigo, concomitant rate of hypertension and diabetes mellitus, BMI, systolic pressure, diastolic pressure, HDL-C, TG, fasting plasma glucose level, severity of hearing loss and audiograms. All patients were divided into two groups, the MetS group and the Non-MetS group, and the clinical characteristics and prognosis between two groups were compared.Result:In the MetS group, the BMI, systolic pressure, TG, fasting plasma glucose level were higher than that in the Non-MetS group, while the HDL-C level was lower than that in Non-MetS group (P<0.01), and the rates of profound hearing loss, flat audiogram and total deafness audiogram were higher than that in the Non-MetS group (P<0.05). In the MetS group, the overall recovery rate, complete recovery rate and marked recovery rate were 57.8%,6.0% and 14.5%, respectively, which was lower than that in the Non-MetS group (79.8%,19.4% and 27.9%, P<0.05 ).Conclusion:SSNHL patients with MetS suffered a severer hearing loss, the most audiograms were flat and total deafness, and the prognosis of SSNHL patients with MetS was poorer.


Nephron-sparing surgery for renal tumours using selective renal parenchymal clamping.
To describe a technical modification that facilitates nephron-sparing surgery (NSS) for renal tumours, without clamping the renal pedicle or promoting renal surface hypothermia. Seventeen patients with renal tumours had NSS using the selective renal-parenchymal clamping technique. In 11 patients the tumour was polar and in six it was central. The mean (range) size of the tumours was 3.6 (2-6) cm. The technique was performed using one or two large Satinsky vascular clamps. Time was not limited as there was no clamping of the renal pedicle, or renal hypothermia. The mean (range) operative duration was 190 (120-300) min. Only one patient needed a blood transfusion. There were no complications in 13 patients after NSS. The mean (range) hospital stay was 5 (3-12) days. The pathological examination detected malignant tumours in 13 patients, and a microscopic examination showed adequate surgical margins in all. The mean (range) follow-up was 24.5 (4-60) months. No patients required haemodialysis immediately after surgery or later. Selective renal parenchymal clamping is a simple and efficient technical manoeuvre that facilitates NSS without dissection or clamping of the renal pedicle. Time is not limited as the ischaemia is limited to the tissue surrounding the tumour. The operative duration and blood loss are acceptable and the complications similar to those with the conventional technique. The size and position of the tumour could be limiting factors to this technique.


Lifestyle habits, health indicators and sociodemographic factors associated with health-related quality of life and self-esteem in adolescents.
Mental health is defined as a state of emotional, psychological, and social well-being, and has been shown to be positively associated with self-esteem and quality of life. It is important to note that mental health is dynamic and influenced by a wide range of social, biological, and behavioral factors. Therefore, the aim this study was to describe the health-related quality of life and self-esteem in adolescents, examining their relationship with various health indicators, lifestyle habits, and sociodemographic variables. A cross-sectional study was conducted with a representative sample of 761 students (14.51 ± 1.63 years). Health-related quality of life, self-esteem, satisfaction with body image, adherence to the Mediterranean diet, physical activity practice, hours of nightly sleep, maximum oxygen consumption, body mass index, academic performance, and various sociodemographic factors of all participants were analyzed. Regression analysis showed that body satisfaction and academic performance were associated of both health-related quality of life and self-esteem. Additionally, physical activity, age, and favourable settings for physical activity engagement were also found to be related to health-related quality of life, whilst adherence to the Mediterranean diet, hours of nightly sleep, maximum oxygen consumption and socioeconomic status were associated with self-esteem. Given the associations found between health-related quality of life and self-esteem with lifestyle habits and sociodemographic indicators, there is an urgent need to develop interdisciplinary and cross-cutting promotion strategies to improve the mental health of adolescents.


Multispectral illumination and image processing techniques for active millimeter-wave concealed object detection.
Active millimeter-wave imaging systems for concealed object detection offer the possibility of much higher image contrast than passive systems, especially in indoor applications. By studying active millimeter-wave images of different test objects derived in the W band, we show that multispectral illumination is critical to the detectability of targets. We also propose to use image change detection techniques, including image differencing, normalized difference vegetation index, and principle component analysis to process the multispectral millimeter-wave images. The results demonstrate that multispectral illumination can significantly reveal the object features hidden by image artifacts and improve the appearance of the objects.


Coupling photocatalysis and redox biocatalysis toward biocatalyzed artificial photosynthesis.
In green plants, solar-energy utilization is accomplished through a cascade of photoinduced electron transfer, which remains a target model for realizing artificial photosynthesis. We introduce the concept of biocatalyzed artificial photosynthesis through coupling redox biocatalysis with photocatalysis to mimic natural photosynthesis based on visible-light-driven regeneration of enzyme cofactors. Key design principles for reaction components, such as electron donors, photosensitizers, and electron mediators, are described for artificial photosynthesis involving biocatalytic assemblies. Recent research outcomes that serve as a proof of the concept are summarized and current issues are discussed to provide a future perspective.


Treatment Outcomes of Multidrug-Resistant Tuberculosis Patients in East Java, Indonesia: A Retrospective Cohort Analysis.
The drug regimen for the treatment of multidrug-resistant tuberculosis (MDR-TB) has lower potency, is more costly, and has a greater risk of adverse effects than first-line anti-TB drugs. We aimed to compare the treatment outcomes of patients using standard shorter regimen (STR regimen) versus bedaquiline (BDQ)-containing individual regimen in a high TB-burden setting. This was a retrospective cohort study using secondary data from the medical records in the hospital. The study population were patients with MDR-TB who started treatment in 2016-2018. Treatment outcomes were classified as successful (cured/completed treatment) or unsuccessful (failure/death/loss to follow-up/not evaluated). Categorical data were presented as frequencies and percentage, whereas continuous data were presented as mean± standard deviations. Risk ratio (RR) was obtained by using the Chi-square statistical test with 95% confidence interval (CI) and P < 0.05 set as a significant result. We included 99 patients out of 444 registered patients in 2016-2018. The overall success proportion was 41.4%. Success was more likely in patients who received BDQ regimen than those receiving STR regimen (52.9% vs. 35.4%, RR: 1.496, 95% CI: 0.948-2.362). Factors that influenced the treatment outcomes were smear status and sputum culture status. The success rate of the STR regimen and the BDQ regimen in this study is still below the national and global figures due to the high rate of lost to follow-up. The success was higher in the BDQ regimen, although not statistically significant. Further research is needed on adverse effects, quality of life, and costs during treatment.


Analysis of MMP-2-735C/T (rs2285053) and MMP-9-1562C/T (rs3918242) Polymorphisms in the Risk Assessment of Developing Lung Cancer.
Matrix metalloproteinase (MMP)-2 and -9 are gelatinases which are capable of degrading type IV collagen and have been linked to cancer invasion and metastatic development. MMP-2 and MMP-9 gene polymorphisms may affect their biological function, and thus their role in cancer development and progression. We analyzed the association of the polymorphism frequencies of MMP-2-735C/T and MMP-9-1562C/T with MMP-2 and MMP-9 serum concentrations, as well as their potential effects in lung cancer patients. We conducted a retrospective, case-control study consisting of 112 lung cancer patients and 100 healthy individuals from a Caucasian population in Poland. Polymerase chain reaction with restriction fragment length polymorphism (PCR/RFLP) and electrophoresis was used to genotype genomic DNA from whole blood samples. MMP-2 and MMP-9 serum concentrations were then determined using ELISA. For statistical analysis, Statistica version 13 from TIBCO Software Inc. was utilized with a significance level <0.05. Logistic regression analysis revealed that MMP-2-735CC (OR = 5.39; 95% CI = 0.62-47.17; p = 0.238504) and -735CT genotype (OR = 7.22; 95% CI = 0.78-67.14; p = 0.072836), as well as MMP-9-1562CC (OR = 1.45; 95% CI = 0.31-6.70; p = 0.757914) and -1562CT genotype (OR = 1.60; 95% CI = 0.33-7.83; p = 0.548801) were associated with a higher risk of lung cancer. There were statistically significant differences observed in the MMP-2 concentration between individuals with the -735CC genotype and the -735CT genotype (non-smoking control: 204.04 ng/mL vs. 237.00 ng/mL, respectively, p = 0.041479; adenocarcinoma patients: 157.69 ng/mL vs. 126.37 ng/mL, respectively, p = 0.013222), as well as differences in the MMP-9 concentration between individuals with the -1562CC genotype and the -1562CT genotype (smoking control: 385.67 ng/mL vs. 562.80 ng/mL, respectively, p = 0.000936; patients with other lung neoplasms: 821.64 ng/mL vs. 928.88 ng/mL, respectively p = 0.023315). The role of MMP-2-735C/T and MMP-9 -1562C/T polymorphisms in an increased risk of lung cancer cannot be dismissed. Specific genotypes affect MMP-2 and MMP-9 concentrations in both lung cancer patients and healthy controls, which may thereby increase lung cancer risk, disease aggressiveness, and patient survival outcomes.


[The place of Isaac Israeli in medieval medicine].
Despite the fact that some few studies have been made of Isaac Israeli, his personality remains relatively obscure to the medical historian. He is regarded as a neoplatonic philosopher. He departed Egypt for Kairouan at the beginning of the 10th Century, leaving a series of medical treatises in Arabic, on fever, diets and urine showing great originality. Constantine the African, a native of Tunisia, translated most of his work into Latin, a century later, thus ensuring their enduring success. In order to determine the originality of this author, we will analyse what Pierre de Saint-Flour and Jacques Despars, respectively of the 14th and the 15th Century withheld about him. Both these physicians exhibit vast erudition in the way they deal with the works of Isaac Israeli heritage enabling us to have a better understanding of them.


Hepatoprotective and Immunosuppressive Effect of Synedrella nodiflora L. on Carbon Tetrachloride (CCl4)-Intoxicated Rats.
Synedrella nodiflora is a medicinal plant that is used by the natives of Sabah, Malaysia to treat rheumatism and several other ailments. This study aims to evaluate the ability of the crude aqueous extract of S. nodiflora leaves to protect against carbon tetrachloride (CCl4)-mediated hepatic injury in rats. S. nodiflora aqueous extract was orally administered to adult Sprague Dawley rats once daily for 14 days (150 and 300 mg/kg body weight [b.w.]) before CCl4 oral treatment (1.0 mL/kg b.w.) on the 13th and 14th days. Serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), hepatic antioxidant enzymes, and malondialdehyde (MDA) levels were estimated. Immunohistochemistry was performed for oxidative stress markers (4-hydroxynonenal [HNE], 8-hydroxy-deoxyguanosine [8-OHdG]) and proinflammatory markers (tumor necrosis factor-α, interleukin-6, prostaglandin E2). Biochemical, immunohistochemical, histological, and ultrastructural findings were in agreement to support the hepatoprotective effect of S. nodiflora against CCl4-mediated oxidative hepatic damage. Hepatoprotective effects of S. nodiflora might be attributable to the presence of phenolic antioxidants and their free radical scavenging property.


Effects of the Saline Flush on High-pitch CT Coronary Angiography on Third-generation Dual-source CT System.
Objective To preliminarily investigate and optimize the saline flush effects to the image quality (IQ)and effective scan rate of high-pitch CT coronary angiography (CCTA)using ultra-low contrast media (CM)protocols on third-generation dual-source CT (DCST). Methods Sixty-eight consecutive patients with suspected or known coronary artery disease (CAD)were recruited and underwent prospective high-pitch CCTA on third-generation DSCT with automatic tube voltage selection (70-80 kV)based ultra-low CM protocols:18 ml(3.0 ml/s) for 70 kV and 21 ml (3.0 ml/s) for 80 kV. All the patients were randomly divided in to two groups:Group A(n=31)with the saline flush of 3.0 ml/s(40 ml) and Group B (n=37)with the saline flush of 4.0 ml/s(40 ml). The baseline data,risk factors,quantitative image quality (IQ),qualitative IQ results,and effective dose (ED)were evaluated and compared. Results There was no significant difference in ED between two groups [(0.36±0.12)mSv vs. (0.37±0.13)mSv;t=-0.40,P=0.70]. The average ED in all patients was (0.43±0.28)mSv. However,the contrast to noise ratio (CNR) of right coronary artery distal segment in Group A was significantly higher than that in Group B(76.04±62.46 vs. 43.96±26.94;t=2.67,P=0.01) and the CNR of left circumflex artery proximal segment in Group A was significantly higher than that in Group B(69.60±43.13 vs. 44.08±24.08;t=2.96,P=0.01). No other significant difference was found in terms of baseline characteristics,and objective image quality (all P>0.05). Subjective IQ showed no significant difference between these two groups (χ2=2.53,P=0.47). Conclusion Under high-pitch CCTA using ultra-low CM protocols [18-21 ml (3.0 ml/s)]on third-generation DCST,the saline flush at a flow rate of 3.0 ml/s can achieve satisfactory IQ and effective scan rate.


Perinatal exposure to organohalogen pollutants decreases vasopressin content and its mRNA expression in magnocellular neuroendocrine cells activated by osmotic stress in adult rats.
Polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are environmental pollutants that produce neurotoxicity and neuroendocrine disruption. They affect the vasopressinergic system but their disruptive mechanisms are not well understood. Our group reported that rats perinatally exposed to Aroclor-1254 (A1254) and DE-71 (commercial mixtures of PCBs and PBDEs) decrease somatodendritic vasopressin (AVP) release while increasing plasma AVP responses to osmotic activation, potentially emptying AVP reserves required for body-water balance. The aim of this research was to evaluate the effects of perinatal exposure to A1254 or DE-71 (30mgkg/day) on AVP transcription and protein content in the paraventricular and supraoptic hypothalamic nuclei, of male and female rats, by in situ hybridization and immunohistochemistry. cFOS mRNA expression was evaluated in order to determine neuroendocrine cells activation due to osmotic stimulation. Animal groups were: vehicle (control); exposed to either A1254 or DE-71; both, control and exposed, subjected to osmotic challenge. The results confirmed a physiological increase in AVP-immunoreactivity (AVP-IR) and gene expression in response to osmotic challenge as reported elsewhere. In contrast, the exposed groups did not show this response to osmotic activation, they showed significant reduction in AVP-IR neurons, and AVP mRNA expression as compared to the hyperosmotic controls. cFOS mRNA expression increased in A1254 dehydrated groups, suggesting that the AVP-IR decrease was not due to a lack of the response to the osmotic activation. Therefore, A1254 may interfere with the activation of AVP mRNA transcript levels and protein, causing a central dysfunction of vasopressinergic system.


Habitual suppression relates to difficulty in regulating emotion with cognitive reappraisal.
One common strategy to cope with the difficulties of daily life is suppression. Habitual users of suppression tend to suppress their feelings rather than expressing them. Although this strategy may reduce outward response to emotion, it is not thought to lessen induced negative affect. Moreover, it remains unclear whether people with high suppression scores can reduce negative affect through cognitive reappraisal. In the present study, twenty-nine healthy participants differing in suppression scores were directed to reappraise aversive stimuli during functional magnetic resonance imaging (fMRI). Results showed that higher suppression scores correlated with decreased response of dorsomedial prefrontal cortex (dmPFC) during cognitive reappraisal. Further, high suppression scores related to enhanced negative affect to stimuli with greater negative affect correlating with decreased dmPFC response during cognitive reappraisal. This study suggests that people with high suppression scores experience difficulty in reducing negative affect through cognitive reappraisal and implicates neurobiological processes that may underlie this difficulty.


Olive oil and its phenolic constituent tyrosol attenuates dioxin-induced toxicity in peripheral blood mononuclear cells via an antioxidant-dependent mechanism.
Olive oil (OO) and its phenolic compounds are reported to possess many potential biological effects, which are ascribed to its powerful antioxidant property. In this study, we have assessed whether OO and its phenolic compound tyrosol (TY) could mitigate 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced oxidative damages in peripheral blood mononuclear cells (PBMC). The results showed that exposure of PBMC to 10 nM TCDD caused significant cell death and elevated cellular concentrations of reactive oxygen species and lipid peroxidation. Comet assay indicated that OO and TY protected DNA damage against dioxin toxicity. In addition, alterations in levels of antioxidant enzymes were substantially prevented by OO and TY. TCDD-induced CYP1A1 activity and loss of mitochondrial membrane potential were significantly reduced by the administration of OO and TY. The results suggested that dietary modifications incorporating diets rich in OO and associated phenolics could prove beneficial in protecting individuals against toxicity induced by dioxins.


Prevalence estimates of overweight and obesity in Cree preschool children in northern Quebec according to international and US reference criteria.
We estimated the prevalence of overweight and obesity in Cree Canadian children aged 5 years (n=1044) using international and US growth references and examined the longitudinal tracking of weight categories between ages 2 and 5 years (n=562). Weight categories based on body mass index (calculated from measured heights and weights) were derived from the International Obesity Task Force (IOTF) and the Centers for Disease Control and Prevention (CDC) references. According to the IOTF reference, 52.9% of children were overweight (31.6%) or obese (21.3%) whereas with the CDC reference, 64.9% were overweight (27.5%) or obese (37.4%). The IOTF and CDC references provided dissimilar tracking of weight categories. Based on the IOTF reference, 4.9% of the children who were normal weight at age 2 years were obese at age 5 years. Based on the CDC reference, 14.9% of children categorized as normal weight at age 2 years were obese at age 5 years. The IOTF reference provided more conservative estimates of obesity than the CDC reference, and longitudinal analyses showed dissimilar tracking of weight categories with the 2 references. Public health responses to obesity prevalence estimates should be made with awareness of methodological limitations.


Electrospray ionization of nucleic acid aptamer/small molecule complexes for screening aptamer selectivity.
Molecular recognition of small molecule ligands by the nucleic acid aptamers for tobramycin, ATP, and FMN has been examined using electrospray ionization mass spectrometry (ESI-MS). Mass spectrometric data for binding stoichiometry and relative binding affinity correlated well with solution data for tobramycin aptamer complexes, in which aptamer/ligand interactions are mediated by hydrogen bonds. For the ATP and FMN aptamers, where ligand interactions involve both hydrogen bonding and significant pi-stacking, the relative binding affinities determined by MS did not fully correlate with results obtained from solution experiments. Some high-affinity aptamer/ligand complexes appeared to be destabilized in the gas phase by internal Coulombic repulsion. In CAD experiments, complexes with a greater number of intermolecular hydrogen bonds exhibited greater gas-phase stability even in cases when solution binding affinities were equivalent. These results indicate that in at least some cases, mass spectrometric data on aptamer/ligand binding affinities should be used in conjunction with complementary techniques to fully assess aptamer molecular recognition properties.


Integrative review of nurse-led follow-up after discharge from the ICU.
To analyse and synthesise the structure, content, types of outcome variables and advantages of nurse-led follow-up of adult patients after discharge from intensive care units. Follow-up service after discharge from the intensive care unit has been suggested as a way of supporting recovery of patients. Nevertheless, varieties exist in the understanding and content of nurse-led follow-up. An integrative review of nurse-led follow-up inspired by the framework of Whittemore and Knafl. An integrative method merged with the recommendations of the PRISMA statement was used to structure the review and findings. Online databases PubMed, CINAHL, ScienceDirect and Scopus were searched from the years 2003-2014. The retrieved articles were independently assessed by two reviewers. Critical appraisal was conducted using check lists from Johanna Briggs Institute. Emerging patterns were validated by all the authors throughout the entire process of analysis. Seventeen papers were included. Three patterns of nurse-led follow-up were identified: (1) Ward visits--in the immediate time after discharge from intensive care unit, (2) Ward visits and appointment(s) to an intensive care unit follow-up clinic and (3) follow-up visit to an intensive care unit and phone call(s) after discharge. Content of short-term nurse-led follow-up (1) ranged from clinical assessment to supporting patients in articulating their subjective health concerns. Long-term nurse-led follow-up (2, 3) included appointments, phone call(s) or information on where advice could be sought. Types of outcome variables were primarily descriptive. There were strong implications for patients' satisfaction with nurse-led follow-up up to six months after discharge. Nurse-led follow-up might promote patients' health and enable use of adequate resources. The findings of this review could be used to design, and test, future interventions and their implementation.


[Usefulness of nuclear medicine in Erdheim-Chester disease: A Lille experience].
Erdheim-Chester disease is a rare form of non-langerhans histiocytosis and its etiology is still not well established. The aims of the study were to assess the value of the bone scintigraphy and the 18F-FDG PET/CT for the diagnostic and for the latter in the therapeutic evaluation. We retrospectively reviewed 49 patients suspected of Erdheim-Chester disease between 2004 and 2016. Bone scintigraphy was compared with histopathology and PET-CT to conventional morphological examinations and bone scintigraphy. For therapeutic evaluation, thresholds similar to PERCIST 1.0 were used. Forty-nine bone scintigraphy were evaluated with a sensitivity of 100%, a specificity 97%, a positive predictive value 90% and a negative predictive value of 100%. Eight patients had at least an initial PET-CT. The sensitivity compared to conventional morphological examinations differed from the location but was excellent for orbital, bone and vascular involvements. Specificity was comparable between the different examinations. Six patients treated with interferon® and three with vemurafenib® were followed by PET-CT. PET-CT, in agreement to clinicobiological data, identified 4 partial responses and one complete response with interferon® et two partial responses and one complete response with vemurafenib®. Our retrospective study suggests that bone scintigraphy and 18F-FDG PET/CT could be useful in the initial assessment of Erdheim-Chester disease but also for the latter in the therapeutic evaluation.


Primary Culture of Porcine Retinal Pigment Epithelial Cells.
The retinal pigment epithelium (RPE) is a monolayer of polarized pigmented epithelial cells, located between the choroid and neuroretina in the retina. Multiple functions, including phagocytosis, nutrient/metabolite transportation, vitamin A metabolism, etc., are conducted by the RPE on a daily basis. RPE cells are terminally differentiated epithelial cells with little or no regenerative capacity. Loss of RPE cells results in multiple eye diseases leading to visual impairment, such as age-related macular degeneration. Therefore, the establishment of an in vitro culture model of primary RPE cells, which more closely resembles the RPE in vivo than cell lines, is critical for the characteristic and mechanistic studies of RPE cells. Considering the fact that the source of human eyeballs is limited, we create a protocol to culture primary porcine RPE cells. By using this protocol, RPE cells can be easily dissociated from adult porcine eyeballs. Subsequently, these dissociated cells attach to culture dishes/inserts, proliferate to form a confluent monolayer, and quickly re-establish key features of epithelial tissue in vivo within 2 wks. By qRT-PCR, it is demonstrated that primary porcine RPE cells express multiple signature genes at comparable levels with native RPE tissue, while the expressions of most of these genes are lost/highly reduced in human RPE-like cells, ARPE-19. Moreover, the immunofluorescence staining shows the distribution of tight junction, tissue polarity, and cytoskeleton proteins, as well as the presence of RPE65, an isomerase critical for vitamin A metabolism, in cultured primary cells. Altogether, we have developed an easy-to-follow approach to culture primary porcine RPE cells with high purity and native RPE features, which could serve as a good model to understand RPE physiology, study cell toxicities, and facilitate drug screenings.


Dexamethasone treatment of post-MI rats attenuates sympathetic innervation of the infarct region.
Sympathetic fiber innervation of the damaged region following injury represents a conserved event of wound healing. The present study tested the hypothesis that impaired scar healing in post-myocardial infarction (post-MI) rats was associated with a reduction of sympathetic fibers innervating the infarct region. In 1-wk post-MI rats, neurofilament-M-immunoreactive fibers (1,116 +/- 250 microm(2)/mm(2)) were detected innervating the infarct region and observed in close proximity to a modest number of endothelial nitric oxide synthase-immunoreactive scar-residing vessels. Dexamethasone (Dex) treatment (6 days) of post-MI rats led to a significant reduction of scar weight (Dex + MI 38 +/- 4 mg vs. MI 63 +/- 2 mg) and a disproportionate nonsignificant decrease of scar surface area (Dex + MI 0.54 +/- 0.06 cm(2) vs. MI 0.68 +/- 0.06 cm(2)). In Dex-treated post-MI rats, the density of neurofilament-M-immunoreactive fibers (125 +/- 47 microm(2)/mm(2)) innervating the infarct region was significantly reduced and associated with a decreased expression of nerve growth factor (NGF) mRNA (Dex + MI 0.80 +/- 0.07 vs. MI 1.11 +/- 0.08; P < 0.05 vs. MI). Previous studies have demonstrated that scar myofibroblasts synthesize NGF and may represent a cellular target of Dex. The exposure of 1st passage scar myofibroblasts to Dex led to a dose-dependent suppression of [(3)H]thymidine uptake and a concomitant attenuation of NGF mRNA expression (untreated 3.47 +/- 0.35 vs. Dex treated 2.28 +/- 0.40; P < 0.05 vs. untreated). Thus the present study has demonstrated that impaired scar healing in Dex-treated post-MI rats was associated with a reduction of neurofilament-M-immunoreactive fibers innervating the infarct region. The attenuation of scar myofibroblast proliferation and NGF mRNA expression may represent underlying mechanisms contributing to the diminished neural response in the infarct region of Dex-treated post-MI rats.


Intravenous digital subtraction angiography of the precerebral and cerebral arteries in patients with TIA. A comparison with conventional angiography.
A study of the diagnostic utility of both intravenous digital subtraction angiography (IV-DSA) and conventional angiography of precerebral and cerebral arteries is presented. The series comprised 60 patients with TIA, who underwent the two procedures with a mean interval of 16 days. Conventional angiography was generally superior to IV-DSA, and this was particularly marked in the siphons and cerebral arteries. Only the excellent IV-DSA examinations obtained in a few patients with TIA could be accepted as final pre-operative procedures. Accurate imaging of the lesions and collateral flow pattern usually required intra-arterial injections, and intra-arterial DSA is now usually preferred.


Isolation by electrofocusing of two lymphocyte mitogens produced by Staphylococcus aureus.
Staphylococcus aureus strain DA352, grown in a diffusate of Todd-Hewitt broth, produced two extracellular nondialyzable lymphocyte mitogens having isoelectric points of 5.5 to 5.7 and 8.6 to 9.0. The mitogens were separable from one another by isoelectric focusing and could be isolated free of detectable amounts of other staphylococcal products by ethanol precipitation followed by isoelectric focusing. Dose-response curves with both mitogens showed a maximum per cent transformation in the range (90%+) obtained with phytohemagglutinin (PHA), a decrease of transformation with excess mitogen, and, with decreasing concentrations, a slope somewhat less steep than that obtained with PHA. Incubation with undigested or pepsin-digested pooled human gamma globulin enhanced the activity of the basic mitogen.


Nanosecond Laser-Fabricated Monolayer of Gold Nanoparticles on ITO for Bioelectrocatalysis.
Redox enzymes can be envisioned as biocatalysts in various electrocatalytic-based devices. Among factors that play roles in bioelectrochemistry limitations, the effect of enzyme-enzyme neighboring interaction on electrocatalysis has rarely been investigated, although critical in vivo. We report in this work an in-depth study of gold nanoparticles prepared by laser ablation in the ultimate goal of determining the relationship between activity and enzyme density on electrodes. Nanosecond laser interaction with nanometric gold films deposited on indium tin oxide support was used to generate in situ gold nanoparticles (AuNPs) free from any stabilizers. A comprehensive analysis of AuNP size and coverage, as well as total geometric surface vs. electroactive surface is provided as a function of the thickness of the treated gold layer. Using microscopy and electrochemistry, the long-term stability of AuNP-based electrodes in the atmosphere and in the electrolyte is demonstrated. AuNPs formed by laser treatment are then modified by thiol chemistry and their electrochemical behavior is tested with a redox probe. Finally, enzyme adsorption and bioelectrocatalysis are evaluated in the case of two enzymes, i.e., the Myrothecium verrucaria bilirubin oxidase and the Thermus thermophilus laccase. Behaving differently on charged surfaces, they allow demonstrating the validity of laser treated AuNPs for bioelectrocatalysis.


Effect of chemotherapy on the mutation frequency of ovarian cancer cells at the HPRT locus.
Resistance to chemotherapy in ovarian cancers is a difficult problem. Our objective was to demonstrate the effect of chemotherapeutic agents, used in the treatment of ovarian cancer, on the mutation frequency of ovarian cancer cells at the HPRT locus. Single cell clones were isolated from a recently established ovarian cancer cell line. The cells were then exposed to sublethal doses of cisplatin, paclitaxel or topotecan. After recovering from the cytotoxic effect of these agents, mutation frequencies of the treated and control cells were determined in 6-thioguanine. Recovery from chemotherapeutic agents was variable among clones. Cisplatin had 5/8 clones showing an enhancement in the induced mutation frequency. Paclitaxel had only 1/7 clones showing a positive increase in the induced mutation frequency, the parent line. Finally topotecan had 3/8 colonies showing an accelerated induced mutation frequency. A total of 9/23 clones with an accelerated induced mutation frequency were identified following various chemotherapeutic agents. We demonstrated that, in a limited number of colonies from an ovarian cancer, there was an ability to increase the mutation frequency at the HPRT locus after exposure to common chemotheraputics used in the treatment of this disease. This induction of more mutations by chemotherapy may help explain the developing chemoresistance of this disease during or following treatment.


Preparation and biodegradation of sugar-containing poly(vinyl acetate) emulsions.
To accelerate the biodegradability of poly(vinyl acetate)-based emulsions, emulsion copolymerizations of vinyl sugars, including triacetylated N-acetyl-D-glucosamine (GlcNAc)-substituted 2-hydroxyethyl methacrylate (GlcNAc(Ac)3-substituted HEMA), glucose-substituted HEMA (GEMA) and 6-O-vinyladipoyl-D-glucose (6-O-VAG) with vinyl acetate (VAc), were carried out using poly(vinyl alcohol) as an emulsifying agent in the presence of poly[(butylene succinate)-co-(butylene adipate)] [poly(BS-co-BA)]. Copolymerization with GEMA produced a stable emulsion and that with 6-O-VAG also produced a homogeneous emulsion. Their biodegradation tests indicated that PVAc main chain scission was accelerated by copolymerization with vinyl sugars.


Thermodynamics of bovine spleen galectin-1 binding to disaccharides: correlation with structure and its effect on oligomerization at the denaturation temperature.
Isothermal titration calorimetry (ITC) measurements of the binding 1-beta carbohydrate-substituted galactopyranoside derivatives to galectin-1 from bovine spleen, a dimer with one binding site per subunit, were performed at 283-285 and 298 K. The disaccharides were lactose, methyl beta-lactoside, lactulose, 4-O-beta-D-galactopyranosyl-D-mannopyranoside, 3-O-beta-D-galactopyranosyl-D-arabinose, 2'-O-methyllactose, lacto-N-biose, N-acetyllactosamine, and thiodigalactopyranoside. The site binding enthalpies, DeltaHb, are the same at both temperatures and range from -42.2 +/- 3.3 kJ mol-1 for thiodigalactopyranoside to -24.5 +/- 0.5 kJ mol-1 for lacto-N-biose, and the site binding constants range from 4.86 +/- 0.78 x 10(3) M-1 for methyl beta-lactoside at 297.8 K to 6.54 +/- 0.97 x 10(4) M-1 for N-acetyllactosamine at 281.3 K. The binding reactions are enthalpically driven, exhibit enthalpy-entropy compensation, and, with the exception of N-acetyllactosamine, follow a van't Hoff dependence of the binding constant on temperature. The number of contacts at distances <4.0 A between the disaccharide and galectin was determined from the energy-minimized conformation of the complex derived from the X-ray crystallographic structure of the galectin-N-acetyllactosamine complex determined by Liao et al. [Liao, D. I., Kapadia, G., Ahmed, H., Vasta, G. R., and Herzberg, O. (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 1428-1432]. The binding enthalpies calculated from changes in the solvent-accessible surface areas of the galectin binding site upon binding of the disaccharide were in close agreement with the experimental values for lactose, lactulose, lacto-N-biose, and N-acetyllactosamine, all of which exhibit binding enthalpies >-36 kJ mol-1. Differential scanning calorimetry measurements on solutions of galectin and its disaccharide complexes show that the galectin dimer does not dissociate upon denaturation in contrast to the legume lectins. At the denaturation temperature, the galectin in the absence of sugar exists as a tetramer, and the extent of this association is substantially reduced in the presence of a disaccharide.


Influence of Interleukin-6 (174G/C) Gene Polymorphism on Obesity in Egyptian Children.
Obesity is a multi-factorial chronic disorder. A considerable number of studies have been performed to figure out whether there is an association between obesity and polymorphisms of gene IL-6 (174G/C), but the results are equivocal. This study aimed to find out whether the IL-6 (174G/C) gene was associated with the risk of developing obesity in Egyptian children. The study included 149 children and adolescents with age ranged between 9.5 - 18 years. Eighty-five of them were obese which BMIZ-score is > 2, and sixty-four children with BMIZ-score ≤ 2 served as control group. Serum level of IL-6 and genetic analysis for IL-6 (174G/C) gene polymorphism were done. Obese children had significantly higher serum levels of IL-6 as compared to those of control children (P = 0.003). A high percentage of IL-6 polymorphism GC was found in obese subjects (93.7%), while the control group had a higher percentage of IL-6 polymorphism GG (70.6 %). Our study showed that carriers of the C allele for the IL-6 (174G/C) polymorphism have higher BMI. As the G174C polymorphism is likely to affect IL-6 expression and its physiological regulation; consequently this polymorphism may affect adiposity.


Impact of alternate Mn doping in ternary nanocomposites on their structural, optical and antimicrobial properties: Comparative analysis of photocatalytic degradation and antibacterial activity.
The present study was done to investigate and compare the photocatalytic and antibacterial activity of two in situ Manganese doped ternary nanocomposites. The dual ternary hybrid systems comprised Mn-doped Ag2WO4 coupled with MoS2-GO and Mn-doped MoS2 coupled with Ag2WO4-GO. Both hierarchical alternate Mn-doped ternary heterojunctions formed efficient plasmonic catalysts for wastewater treatment. The novel nanocomposites were well-characterized using XRD, FTIR, SEM-EDS, HR-TEM, XPS, UV-VIS DRS, and PL techniques confirming the successful insertion of Mn+2 ions in respective host substrates. The bandgap of the ternary nanocomposites evaluated by the tauc plot showed them visible light-active nanocomposites. The photocatalytic ability of both Mn-doped coupled nanocomposites was investigated against the dye methylene blue. Both ternary nanocomposites showed excellent sunlight harvesting ability for dye degradation in 60 min. The maximum catalytic efficiency of both photocatalysts was obtained at a solution pH value of 8, photocatalyst dose and oxidant dose of 30 mg/100 mL and 1 mM for Mn-Ag2WO4/MoS2-GO, 50 mg/100 mL, 3 mM for Mn-MoS2/Ag2WO4-GO keeping IDC of 10 ppm for all photocatalysts. The nanocomposites showed excellent photocatalytic stability after five successive cycles. The response surface methodology was used as a statistical tool for the evaluation of the photocatalytic response of several interacting parameters for dye degradation by ternary composites. The antibacterial activity was determined by the inactivation of gram-positive (Staphylococcus aureus) and gram-negative (Escherichia coli) bacteria by support-based doped ternary hybrids.


[Characteristics of Clostridium difficile infection in a high complexity hospital and report of the circulation of the NAP1/027 hypervirulent strain in Colombia].
Clostridium difficile is the main pathogen related to healthcare-associated diarrhea and it is the cause of 20 to 30% of diarrhea cases caused by antibiotics. In Colombia and Latin America, the knowledge about the epidemiological behavior of this infection is limited. To describe the characteristics of a series of patients with C. difficile infection. We performed a descriptive case series study of patients with C. difficile infection hospitalized in the Fundación Clínica Shaio from January, 2012, to November, 2015. We analyzed 36 patients. The average age was 65 years. The risk factors associated with the infection were: previous use of antibiotics (94.4%), prior hospitalization in the last three months (66.7%) and use of proton pump inhibitors (50%). The most common comorbidities were chronic kidney disease (41.7%) and diabetes mellitus (30.6%). The most frequent symptoms were more than three loose stools per day (97.1%) and abdominal pain (42.9%). According to the severity of the disease, 44.4% of cases were classified as mild to moderate, 38.9% as severe, and 11.1% as complicated or severe. The detection of the toxin by PCR (GeneXpert) was the most common diagnostic procedure (63.8%). Global mortality during hospitalization was 8%. We identified four strains with serotype NAP1/027 and nine samples positive for binary toxin. Clostridium difficile infection should be suspected in patients with diarrhea and traditional risk factors associated with this disease. We report the circulation of the hypervirulent strain serotype NAP1/027 in Colombia, which should be countered with epidemiological surveillance and a prompt diagnosis.


Age of initiation of smokeless tobacco use among young adults: Findings from the population assessment of tobacco and health (PATH) study, 2013-2017.
Smokeless tobacco (SLT) use, across all age groups, is most prevalent among young adults in the US. A study estimating the age of initiation of SLT use among young adults is needed amid the changing landscape of tobacco products. Secondary analyses of PATH young adults across waves 1-4 were conducted. A total of 10595 young adults who were never SLT users at their first wave of adult participation in PATH (waves 1-3) were included in the analysis. Age of initiation outcomes of ever, past 30-day, and fairly regular SLT use, were assessed prospectively in waves 2-4. Interval censoring Cox regression models were used to assess differences in the age of initiation of each outcome by sex and race/ethnicity, adjusting for other tobacco product use. By the age of 27 years, 4.9%, 3.0%, and 1.9% of young adults reported initiating ever, past 30-day, and fairly regular SLT use, respectively. After controlling for demographic factors and other tobacco use, males initiated each of the SLT outcomes at earlier ages than females; non-Hispanic Blacks initiated each of the SLT use at later ages than non-Hispanic Whites; and Hispanic and non-Hispanic others initiated ever use at later ages than non-Hispanic Whites. These data suggest that three young adult groups are more likely to initiate use of SLT at earlier ages: males, non-Hispanic Whites, and poly-tobacco users. Knowing the age of SLT initiation outcomes among young adults will educate the public domain, inform SLT use prevention campaigns, and provide a baseline to measure the success of the Tobacco 21 legislation from December 2019.


An EM Induction Hi-Speed Rotation Angular Rate Sensor.
A hi-speed rotation angular rate sensor based on an electromagnetic induction signal is proposed to provide a possibility of wide range measurement of high angular rates. An angular rate sensor is designed that works on the principle of electromagnetism (EM) induction. In addition to a zero-phase detection technique, this sensor uses the feedback principle of magnetic induction coils in response to a rotating magnetic field. It solves the challenge of designing an angular rate sensor that is suitable for both low and high rotating rates. The sensor was examined for angular rate measurement accuracy in simulation tests using a rotary table. The results show that it is capable of measuring angular rates ranging from 1 rps to 100 rps, with an error within 1.8‰ of the full scale (FS). The proposed sensor is suitable to measurement applications where the rotation angular rate is widely varied, and it contributes to design technology advancements of real-time sensors measuring angular acceleration, angular rate, and angular displacement of hi-speed rotary objects.


Positive stereotypes, negative outcomes: Reminders of the positive components of complementary gender stereotypes impair performance in counter-stereotypical tasks.
Gender stereotypes are complementary: Women are perceived to be communal but not agentic, whereas men are perceived to be agentic but not communal. The present research tested whether exposure to reminders of the positive components of these gender stereotypes can lead to stereotype threat and subsequent performance deficits on the complementary dimension. Study 1 (N = 116 female participants) revealed that compared to a control/no-stereotype condition, exposure to reminders of the stereotype about women's communality (but not to reminders of the stereotype about women's beauty) impaired women's math performance. In Study 2 (N = 86 male participants), reminders of the stereotype about men's agency (vs. a control/no-stereotype condition) impaired men's performance in a test of socio-emotional abilities. Consistent with previous research on stereotype threat, in both studies the effect was evident among participants with high domain identification. These findings extend our understanding of the potentially adverse implications of seemingly positive gender stereotypes.


Genome-wide operon prediction in Staphylococcus aureus.
Identification of operon structure is critical to understanding gene regulation and function, and pathogenesis, and for identifying targets towards the development of new antibiotics in bacteria. Recently, the complete genome sequences of a large number of important human bacterial pathogens have become available for computational analysis, including the major human Gram-positive pathogen Staphylococcus aureus. By annotating the predicted operon structure of the S.aureus genome, we hope to facilitate the exploration of the unique biology of this organism as well as the comparative genomics across a broad range of bacteria. We have integrated several operon prediction methods and developed a consensus approach to score the likelihood of each adjacent gene pair to be co-transcribed. Gene pairs were separated into distinct operons when scores were equal to or below an empirical threshold. Using this approach, we have generated a S.aureus genome map with scores annotated at the intersections of every adjacent gene pair. This approach predicted about 864 monocistronic transcripts and 533 polycistronic operons from the protein-encoding genes in the S.aureus strain Mu50 genome. When compared with a set of experimentally determined S.aureus operons from literature sources, this method successfully predicted at least 91% of gene pairs. At the transcription unit level, this approach correctly identified at least 92% of complete operons in this dataset. This consensus approach has enabled us to predict operons with high accuracy from a genome where limited experimental evidence for operon structure is available.


An Assessment of the Robustness of the COSHH-Essentials (C-E) Target Airborne Concentration Ranges 15 Years on, and Their Usefulness for Determining Control Measures.
The Health and Safety Executive (HSE) in Great Britain (GB), in association with its stakeholders, developed the Control of Substances Hazardous to Health (COSHH)-Essentials (C-E) control banding tool in 1998. The objective was to provide a simple tool for employers, particularly small and medium-sized enterprises (SMEs), to help select and apply appropriate measures for the adequate control of exposure to hazardous substances. The tool used hazard classification information (R-phrases) to assign substances to one of five health hazard groups, each with its respective 'target airborne concentration range'. The validity of the allocation of substances to a target airborne concentration range was demonstrated at the time using 111 substances that had a current health-based Occupational Exposure Limit (OEL) in GB. The C-E control banding approach remains an important tool to complement exposure assessment/monitoring and the selection and use of suitable control measures for hazardous substances. These include engineering controls and personal protective equipment (PPE). The C-E based control banding approach has been adopted around the world. This paper extends the original validation exercise, using a greater number of chemical substances, to establish whether the target airborne concentration ranges remain appropriate. This is of particular interest in light of the introduction of the Globally Harmonized System (GHS) for classification, in which R-phrases have now been replaced by hazard-statements (H-statements). The validation exercise includes substances with OELs published by nine bodies internationally; and the Derived No-Effect Levels (DNELs) assigned by registrants under the European Union-Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) Regulations. When compared against 8-hour TWA OELs for 850 substances drawn from nine bodies and a limited number of DNELS, the C-E target airborne concentration ranges remain valid. This comparative work also informs a wider consideration around the practicality and the applicability of the C-E generic approach to facilitate the implementation of good practice control for a wide range of substances (more than 95%) which do not have any recognized OEL.


Chromosomes 22q11 deletion syndrome: an update and review for the primary pediatrician.
Chromosome 22q11 deletion syndrome is a relatively newly described syndrome that encompasses the majority of patients previously felt to have velo-cardio-facial syndrome, DiGeorge syndrome, and conotruncal anomaly face syndrome. The disorder is characterized by a deletion of band 11 on the long arm of chromosome 22 most often recognized by fluorescent in situ hybridization (FISH) techniques. Extensive laboratory investigations are currently ongoing to uncover the specific genes involved and their functions. Phenotypically, individuals present with congenital heart disease, palatal abnormalities, facial dysmorphism, and developmental delay, as well as variable degrees of immunodeficiency, hypocalcemia, and endocrine abnormalities. The primary care physician has an important role in caring for these patients and their families. We review the current state of knowledge regarding chromosome 22q11 deletion syndrome, with an emphasis on the clinical presentation and on prevention and treatment of the known complications associated with this multisystem disorder. Chromosome 22q11 deletion syndrome can be inherited in an autosomal dominant fashion or result from a de novo deletion or translocation. Hence, this syndrome may have significant reproductive risks to affected individuals and families.


Optical Surface Tension Measurement of Two-Dimensionally Confined Liquid Surfaces.
Surface tension measurement based on spontaneous capillary wave resonance in confined micrometer-sized liquid interfaces was demonstrated. A single-beam quasi-elastic laser scattering method was used to detect the resonance. Characteristic resonant modes were observed on a 44-μm-sized circular water surface. The frequencies of the peaks agreed well with those simulated by assuming planar resonance, and the relationship was further confirmed for triangular, square, and pentagonal water surfaces. Then, the applicability of the method was successfully demonstrated by surface tension measurements of aqueous solutions of sodium dodecyl sulfate. The sensitive detection of capillary resonance opens new possibilities for the chemical and biochemical analysis of liquid interfaces.


Exogenous α-synuclein hinders synaptic communication in cultured cortical primary rat neurons.
Amyloid aggregates of the protein α-synuclein (αS) called Lewy Bodies (LB) and Lewy Neurites (LN) are the pathological hallmark of Parkinson's disease (PD) and other synucleinopathies. We have previously shown that high extracellular αS concentrations can be toxic to cells and that neurons take up αS. Here we aimed to get more insight into the toxicity mechanism associated with high extracellular αS concentrations (50-100 μM). High extracellular αS concentrations resulted in a reduction of the firing rate of the neuronal network by disrupting synaptic transmission, while the neuronal ability to fire action potentials was still intact. Furthermore, many cells developed αS deposits larger than 500 nm within five days, but otherwise appeared healthy. Synaptic dysfunction clearly occurred before the establishment of large intracellular deposits and neuronal death, suggesting that an excessive extracellular αS concentration caused synaptic failure and which later possibly contributed to neuronal death.


[Single nuclear polymorphisms in exon 3 of POMC gene and the association with growth traits in Hu sheep and East Friesian x Hu crossbred sheep].
Pro-opiomelancortin (POMC) plays important roles in the regulation of food intake and energy expenditure. The sheep exon 3 of gene POMC was amplified and sequenced by screening the DNA pools to select single nuclear polymorphisms and analyze the association with the growth traits. Two silent SNP mutations (g.273 T/C and g.456 G/A) in Hu sheep were identified. PCR-restriction fragment length polymorphism (RFLP) was used to test the g.273 T/C and the association between the g.273 T/C polymorphism and some growth traits was analyzed in Hu sheep (n = 162) and East Friesian x Hu crossbred sheep (n=130). The results showed that three genotypes, TT, TC and CC, were detected in Hu sheep with the frequencies of 0.469, 0.438 and 0.093, respectively. Two genotypes, TT and TC, were detected in East Friesian x Hu crossbred sheep with the frequencies of 0.754 and 0.246, respectively. The association analysis showed that in Hu sheep the two-month weaning weight, four-month rump height of genotype CC and the four-month body length, cannon circumference of genotype TC were significantly higher than those of genotype TT (P < 0.05); the four- and six-month weight of genotype CC were significantly higher than those of genotypes TT and TC (P < 0.01); the four-month body height and body length of genotype CC were significantly higher than those of genotypes TT (P < 0.01) and TC (P < 0.05); the four-month cannon circumference of CC genotype was significantly higher than that of TT genotype (P < 0.01). In East Friesian x Hu crossbred sheep the two-month weaning weight, four-month weight, body height, body length, chest depth and cannon circumference of genotype TC were significantly higher than those of genotype TT (P < 0.05); the six-month weight of genotype TC was significantly higher than that of genotype CC (P < 0.01). In conclusion, the exon 3 of gene POMC was associated with growth traits, and C allele was beneficial to the increase of body weight and body size traits of sheep, which potentially afford a good foundation for further study on POMC gene as aided breeding markers for growth traits in sheep.


Treatment strategies for Hodgkin's disease.
Over the past 2 decades, treatment of Hodgkin's disease has evolved considerably through innovations in the management of various stages. The impact of various treatments on the 5-, 10-, and 15-year results is being balanced against delayed morbidity, such as organ damage and second malignancies, produced by the intensity of therapy or the prolonged delivery of given drugs. The results of clinical trials performed during the past decade have allowed us to reconsider the various prognostic variables that can be used in the treatment strategy. The major unfavorable prognostic factors are represented by bulky disease, multiple extranodal sites, systemic B symptoms, age greater than 60 years, lymphocyte-depleted histology, male sex, and progressive disease during chemotherapy. In patients with early disease after surgical staging, the aim of current therapy is to provide a high cure rate within a short period and with limited morbidity. In patients with advanced Hodgkin's disease, the treatment strategy is to achieve durable complete remission in most cases through effective, full-dose, multidrug regimens at the expense of acceptable morbidity. Subtotal or total nodal radiotherapy (RT) induces a 10-year cure rate ranging from 70% to 85% in stages I and II with no bulky lymphoma. In patients with bulky disease and all three systemic symptoms, comparable results can be achieved with primary chemotherapy followed by RT. Currently, stages IIIA and IIIB disease are often managed with combined treatment modalities, although comparable results can be obtained with intensive chemotherapy alone.(ABSTRACT TRUNCATED AT 250 WORDS)


Characteristics of adenosine triphosphate [corrected] release from porcine and human normal bladder.
Although the sensory and motor roles of the purinergic system in the bladder are well proven in animal species, there is increasing evidence that it may have an important role in humans. In addition, it may be important in the pathophysiology of bladder dysfunction. We established the level of adenosine triphosphate (ATP) release from porcine and normal human bladders. Bladder strips from patients with a urodynamically proven stable bladder undergoing surgery for stress incontinence and those undergoing cystectomy for cancer with no lower urinary tract symptoms were subjected to varying degrees of stretch (up to 50%) and electric field stimulation (10 to 40 Hz). A luciferase assay was used to quantify ATP release. Significantly increased ATP release over baseline was induced by mechanical and electrical stimulation (each p <0.05). Mean ATP release +/- SE from porcine bladders (38.2 +/- 1.9 pM/gm tissue following stretch and 19.9 +/- 6.5 pM/gm following electrical stimulation) was comparable to the release from human bladders (26.1 +/- 2.4 pM/gm tissue following stretch and 29.9 +/- 1.0 pM/gm following electrical stimulation). The main source of ATP release was the urothelium and not the muscle (p <0.05). This ATP release following stretch was not tetrodotoxin sensitive. The characteristics of ATP release from porcine and human bladders are similar and, therefore, the pig is a good model for humans. The main source of ATP release is urothelium from predominantly nonneuronal sources. This study supports a sensory role for ATP. An increased role for this purinergic neurotransmission may result in functional motor as well as sensory bladder disorders.


Management of Women at High Risk for Breast Cancer.
Primary care clinicians screen for breast cancer risk factors and assess the risk level of their patients. Women at high risk for breast cancer (eg, 5-year risk of at least 3% or lifetime risk of ≥20%) are eligible for enhanced screening and/or chemoprophylaxis. However, many clinicians do not identify women at high risk and offer appropriate referrals, screening, or chemoprophylaxis. We reviewed a sample of 200 charts of women ages 35 to 50 years old with a family history of breast cancer. We identified factors that contribute to their risk for breast cancer and used the Tyrer-Cuzick Risk Assessment Calculator to determine their personal lifetime risk. We then assessed whether these patients received counseling for chemoprophylaxis, referrals, or screening. We also looked for correlations between combinations of risk factors and increased lifetime risk. Out of 200 charts reviewed, 71 women were identified as high risk for breast cancer (lifetime risk of ≥20%). Of those 71 women, just 17 were referred to a high-risk clinic for enhanced screening and/or chemoprophylaxis. Three risk factors, mammographic breast density of category C or D, first degree relatives with breast cancer, and age first given birth if after 30 years old had a significant impact on lifetime risk for breast cancer. Primary care clinicians can use these independent risk factors as cues to pursue a more formal calculation of a woman's lifetime risk for breast cancer and make appropriate referrals for enhanced screening and chemoprophylaxis counseling if indicated.


Effect of topical ophthalmic dorzolamide(2%)-timolol(0.5%) solution and ointment on intraocular pressure in normal horses.
To compare the effect of commercially available solution and compounded ointment formulations of dorzolamide(2%)-timolol(0.5%) on intraocular pressure (IOP) of normal horses. Eighteen clinically normal horses. A randomized, masked prospective design was used with horses divided into two equal groups. One eye of each horse was selected for topical ophthalmic treatment with either 0.2 mL of dorzolamide(2%)-timolol(0.5%) solution or 0.2 g of dorzolamide(2%)-timolol(0.5%) ointment every 12 h for 5 days. The contralateral eye of horses in both groups was untreated. Rebound tonometry was performed every 6 h starting 2 days prior to and ending 2 days after the treatment period. The mean IOP reduction in eyes treated with the solution or ointment formulations was 13%. Untreated eyes in both groups experienced a lesser but still statistically significant reduction in IOP. The IOP values did not return to baseline within 48 h of the last treatment. The commercially available solution and compounded ointment formulations of ophthalmic dorzolamide(2%)-timolol(0.5%) had similar effects on IOP in normal horses. Persistent IOP reduction following cessation of treatment may indicate prolonged drug effect or acclimation of horses to tonometry.


Tumor-specific overexpression of histone gene, H3C14 in gastric cancer is mediated through EGFR-FOXC1 axis.
Incorporation of different H3 histone isoforms/variants have been reported to differentially regulate gene expression via alteration in chromatin organization during diverse cellular processes. However, the differential expression of highly conserved histone H3.2 genes, H3C14 and H3C13 in human cancer has not been delineated. In this study, we investigated the expression of H3.2 genes in primary human gastric, brain, breast, colon, liver, and head and neck cancer tissues and tumor cell lines. The data showed overexpression of H3.2 transcripts in tumor samples and cell lines with respect to normal counterparts. Furthermore, TCGA data of individual and TCGA PANCAN cohort also showed significant up-regulation of H3.2 genes. Further, overexpressed H3C14 gene coding for H3.2 protein was regulated by FOXC1 transcription factor and G4-cassette in gastric cancer cell lines. Elevated expression of FOXC1 protein and transcripts were also observed in human gastric cancer samples and cell lines. Further, FOXC1 protein was predominantly localized in the nuclei of neoplastic gastric cells compared to normal counterpart. In continuation, studies with EGF induction, FOXC1 knockdown, and ChIP-qPCR for the first time identified a novel axis, EGFR-FOXC1-H3C14 for regulation of H3C14 gene overexpression in gastric cancer. Therefore, the changes the epigenomic landscape due to incorporation of differential expression H3 variant contributes to change in gene expression pattern and thereby contributing to pathogenesis of cancer.