[Action of ketotifen on the mitogen-evoked proliferative response of human mononuclear cells].
Ketotifen at low concentrations (5 and 50 microns) potentiated and at high ones (250 and 500 microM) blocked the proliferative response of human peripheral blood mononuclear cells ( NNC ) induced by PHA. The proliferative response was evaluated by 3H-thymidine incorporation into the cells. At doses inhibiting proliferative response to PHA ketotifen blocked both Con A-induced and Pokeweed mitogen-induced proliferations of MNC. At tested concentrations ketotifen inhibited and at the highest concentration (250 microM) blocked PHA-induced increase of protein synthesis in MNC evaluated by incorporation of 14C-L-leucine into the cells. The presented data showed that ketotifen acted not on the inductive step of the proliferative response but on the steps preceding the cell shift into S-phase.


[Benzoyl peroxide in the treatment of decubitus ulcers].
We communicate a case of pressure sore (decubitus ulcer) treated with 20% topic benzoyl peroxide in O/W emulsion with very satisfactory results. This substance feeds hyperbaric oxygen. Benzoyl peroxide also has antimicrobial, antipruriginous and antifungal properties all of them contributing to shorten the evolution of the lesions.


Shifts in KDIGO CKD risk groups with empagliflozin: Kidney-protection from SGLT2 inhibition across the spectrum of risk.
T2D is a well-established risk factor for development and progression of CKD. KDIGO recommends categorization of risk by likelihood of progression to ESKD. Compared to placebo, empagliflozin decreases likelihood of worsening (OR 0.70, 95 % CI 0.62-0.78) and increases likelihood of improvement (OR 1.56, 95 % CI 1.30-1.86) in KDIGO risk category.


[Manual handling of loads in the hotel trade: the experience of the ASL (Local Health Unit) Milan].
There are over 400 hotels in Milan with a guest capacity of about 62,000 and employing more than 10,000 workers. In 2008/09 the Occupational Health and Safety Service of A.S.L. Milano (Local Health Unit) carried out research into the hotel trade to ascertain the development of this commercial sector, also in view of EXPO 2015. The aim of the project was to improve hygiene and safety conditions and carry out preventive measures. A specific purpose was to study manual handling of loads and repetitive movements risk. The study covered 30 hotels and 7 temporary staff cooperatives. We acquired the Risk Evaluation Document, the Health Surveillance Programme and Registers of Labour Accidents to analyze manual handling of loads and repetitive movements. In the investigations and assessments on hotels we used currently available scientific tools--NIOSH Lifting Index, Push and Pulling Analysis, OC.R.A. Check-List--to study risks related to handling loads and upper limb mechanical overload, which revealed a specific occupational risk that requires a fresh approach to prevention and safety in the entire sector. Chambermaid: LI (Range): 0.57-2.75; Push and Pulling Actions: Fi 0.66-Fm 1.5 and Fi 0.76-Fm 1.33 respectively; OC.R.A. Check-List: 21. Porter: LI (Range): 0.77-3.75. Maintenance staff LI (Range): 0.57-2.75. The study highlighted the presence of risk due to manual handling of loads and repetitive movements in porters, maintenance personnel and particularly in chambermaids that up to now have been poorly assessed by safety experts. Analysis of the information contained in the registers of labour accidents suggests that a significant number of accidents can be related to muscular-skeletal disorders that affect especially cleaning, portering and kitchen staff


icMRCI+Q Study of the Spectroscopic Properties of the 14 Λ-S and 49 Ω States of the SiN- Anion in the Gas Phase.
This paper calculates the potential energy curves of the 14 Λ-S and 49 Ω states, which come from the first three dissociation channels of the SiN- anion. These calculations are conducted using the valence internally contracted multireference configuration interaction and the Davidson correction approach. Core-valence correlation and scalar relativistic corrections are taken into account. The potential energies are extrapolated to the complete basis set limit. The spin-orbit coupling is computed using the state interaction approach with the Breit-Pauli Hamiltonian. We found that the X¹Σ⁺ (υ'' = 0-23) and a³Σ⁺ (υ' = 0-2) states of SiN- are stable at the computed adiabatic electron affinity value of 23,262.27 cm-1 for SiN. Based on the calculated potential energy curves, the spectroscopic parameters and vibrational levels were determined for all stable and metastable Λ-S and Ω states. The computed adiabatic electron affinity of SiN and the spectroscopic constants of SiN- (X¹Σ⁺) are all in agreement with the available experimental data. The d³Σ⁺, 2⁵Σ⁺, 1⁵Δ, and 1⁵Σ- quasi-bound states caused by avoided crossings were found. Calculations of the transition dipole moment of a³Σ⁺₁ to X¹Σ⁺0+ are shown. Franck-Condon factors, Einstein coefficients, and radiative lifetimes of the transition from the a³Σ⁺₁ (υ' = 0-2) to the X¹Σ⁺0+ state are evaluated.


Single nucleotide polymorphisms of the chicken insulin-like factor binding protein 2 gene associated with chicken growth and carcass traits.
Five single nucleotide polymorphisms (SNP) of the chicken insulin-like factor binding protein 2 (IGFBP2) gene were selected to genotype a F2 designed population with restriction fragment length polymorphisms and single stranded-conformation polymorphisms. The associations of the SNP and their haplotypes with chicken growth and carcass traits were analyzed. Results showed that the difference induced by the haplotypes derived from the 5 SNP was more significant than that by the single SNP in the genotype-phenotype association analysis. The haplotypes were associated with BW at hatch and at 21, 28, 42, 49, 56, and 90 d of age, as well as eviscerated weight with giblets (EWG), eviscerated weight (EW), and weights of heart, liver, and gizzard (HLGW) (P < or = 0.01). The haplotypes were also related to BW at 7, 14, and 35 d of age, breast depth, carcass weight, and breast muscle weight (P < or = 0.05). Significant and suggestive dominant effects of H1H5 diplotype were detected for BW at 7, 14, 21, 28, and 90 d of age, as well as breast depth, carcass weight, eviscerated weight with giblets, eviscerated weight, breast muscle weight, leg muscle weight, and weights of heart, liver, and gizzard. It was concluded that H1H5 was the most advantageous diplotype, and H4H10 was the negative diplotype for growth and carcass traits.


Comparison between newly developed scanning peripheral anterior chamber depth analyzer and conventional methods of evaluating anterior chamber configuration.
To compare the newly developed scanning peripheral anterior chamber depth analyzer (SPAC) with the Van Herick technique, the Shaffer grading system, and ultrasound biomicroscopy (UBM), in terms of accuracy of measurement of peripheral anterior chamber depth (ACD). The subjects were well-controlled glaucoma patients who were being treated at the University of Yamanashi Hospital. Ten eyes from each of the 4 groups classified as Shaffer grades 1 to 4 were evaluated by SPAC, the Van Herick technique, and UBM. All measurements were performed independently on the temporal side in a masked fashion. SPAC evaluated ACD consecutively from the pupil center to the limbus at 0.4 mm intervals. UBM measurements were carried out at a depth of 500 mum (angle-opening distance 500) from the scleral spur. A dummy eye was used for evaluating SPAC measurement accuracy. The results of SPAC measurement were well correlated with those of the Van Herick technique and the Shaffer grading system. The SPAC measurement results were also significantly correlated with angle-opening distance 500. The correlation coefficients at distances of 2, 4, 4.8, and 5.6 mm from the pupil center were r=0.68, 0.69, 0.69, and 0.61, respectively, and the P values of all the correlations were less than 0.0001. Study of the dummy eye revealed that SPAC has high accuracy for measuring ACD and that the coefficient variances were less than 1.0% at all measured points. The results of SPAC measurement correlate well with those of the conventional methods.


Perception and attitude of medical doctors in Dhaka, Bangladesh, with regard to Ayurvedic medicine.
The World Health Organization (WHO) Traditional Medicine Strategy (2014-2023) aimed to help member states promote the safe and effective use of traditional medicine. While economic conditions have markedly improved in Bangladesh, the country is experiencing significant public health problems. Because of limited medical resources, there is a strong incentive to enhance complementary and alternative medicine usage in Bangladesh. Therefore, this study aimed to confirm the perceptions and attitudes of medical doctors (MDs) in Dhaka, Bangladesh, with regard to Ayurvedic medicine (AM). A total number of 159 MDs in Dhaka were interviewed by face-to-face between February and June 2015. The study revealed that 62.0% of MDs had treated patients with AM and 55.3% believed that AM should be regarded as its own specialty, whereas 39.7% of MDs believed that AM should be part of the conventional medical curriculum and 32.7% thought that AM did not seem scientific. In terms of gender, 45.3% of male MDs agreed or strongly agreed that AM only had a placebo effect. On the other hand, 65.8% of female MDs disagreed or strongly disagreed it. In terms of age, 77.0% of MDs aged 36 or elder (elder MDs) believed they were more likely to recommend AM use and 80.3% of elder MDs believed that the government should encourage more initiatives to promote AM. To enhance AM use, scientifically robust information on the efficacy, safety and scientific basis of AM should be more effectively conveyed to male MDs.


Analysis of wear, wear particles, and reduced inflammatory potential of vitamin E ultrahigh-molecular-weight polyethylene for use in total joint replacement.
Vitamin E (VE) has been added to ultrahigh-molecular-weight polyethylene (UHMWPE) acetabular cups and tibial trays primarily to reduce oxidative damage to the polymer. The aim of this study was to investigate the relative wear rates of UHMWPE-containing VE compared with virgin UHMWPE. The ability of VE to reduce the amount of inflammatory cytokines produced from stimulated peripheral blood mononuclear cells (PBMNCs) was also investigated. Stimulation was achieved by exposure of PBMNCs to either lipoplysaccharide (LPS) or VE-containing UHMWPE (VE-UHMWPE). In the present study, results showed that the wear rates of UHMWPE with or without VE were not significantly different. Particles generated by UHMWPE with and without VE were not significantly different in size distribution. The production of osteolytic mediators, tumor necrosis factor-alpha, interleukin 1β (IL-β), IL-6, and IL-8 were significantly reduced in (PBMNCs) stimulated with either LPS + VE compared with LPS or VE-UHMWPE particles compared to virgin UHMWPE particles. This trend was also observed when VE was added as a liquid to UHMWPE wear particle-stimulated PBMNCs. The exact mechanism of how VE affects the release of inflammatory mediators from particle-stimulated macrophages is not yet understood. It is likely to involve the anti-inflammatory and/or antioxidant effects of VE.


[Abdominal secondary aorto-enteric fistulae complicating aortic graft replacement: postoperative and long-term outcomes in 32 patients].
Management of patients with abdominal secondary aorto-entericfistulae (SAEF) complicating aortic graft replacement is controversial. We retrospectively analyzed the postope- rative and long-term outcomes of all consecutive patients operated on for SAEF betwveen 2002 and2012. All were managed by in situ replacement with a cryopreserved allograft and treatment of the affected digestive tract. Thirty-two patients (median age 65 years) underwent aortic replacement for SAEFa median of 5 years after initial aortic surgery. The fistulae were located in the duodenum (n = 20), small bowel (n = 6), colon (n = 5) or stomach (n = 1). Treatment of the digestive tract included suture (n = 16), resection with anastomosis (n = 12) covered by a defunctioning stoma (n = 1), and Hartmann's procedure (n = 3). Omentoplasty was performed in 18 patients (56 %), and 17 patients (53 %) had afeedingjejunostomy. Eight patients (25 %) died post-operatively, 3 with a recurrent aorto-enteric fistula. Fifteen (62.5 %) of the remaining patients developed 27 complications, including 6 patients (19 %) with severe morbidity (Dindo III-IV). The reoperation rate was 21 %. The median hospital stay was 33 days. During follow-up (median 15 months), no further patients had a recurrent aorto-enteric fistula. We conclude that surgery for SAEF is a major procedure associated with high mortality and morbidity. Good long-term results can be obtained by excision of the prosthetic graft with cryopreserved allograft replacement, and by management in a tertialy referral center with expertise in both vascular and digestive surgery.


Occupational exposure to urban pollutants and plasma insulin.
The aim of this study was to investigate whether traffic police of a big city who are exposed to urban pollutants are at risk to alterations in plasma insulin concentrations compared with controls. The class of workers examined in this study were employees of the municipal police in Rome, Italy. The study was carried out during the period March-April 2001. Traffic police were matched with a control group, where gender, age, working life and drinking habit were noted. A total of 246 traffic police (128 men and 118 women) with outdoor activity and exposure to urban pollutants and 242 subjects (128 men and 114 women) with indoor activity were included in the study. The levels of plasma insulin were significantly lower in traffic police compared to the control group of both gender. Plasma insulin level was altered in traffic police who are exposed to chemical and physical stressors.


PRO-RESOLUTION POTENCY OF RESOLVINS D1, D2 AND E1 ON NEUTROPHIL MIGRATION AND IN DERMAL WOUND HEALING.
An exuberant inflammatory response may exacerbate the primary tissue damage caused by injuries to the skin due to burns, surgery, excessive pressure, and other etiologies, thus increasing the time to heal. We hypothesized that application of factors that decrease inflammation would allow the skin to more quickly restore its barrier function, and promote the return to homeostasis. Resolvins are endogenous, pro-resolving lipid mediators derived from omega-3 fatty acids that serve to inhibit neutrophil migration and enhance macrophage phagocytosis, thus promoting the resolution of inflammation and the beginning of the proliferative phase of wound healing. Resolvins are derived either from docosahexaenoic (D-series) or eicosapentaenoic (E-series) acid. Herein, we compare the effects of resolvins D1 (RvD1), D2 (RvD2) and E1 (RvE1) on their abilities to inhibit neutrophil migration in vitro and to promote wound healing in vivo. In Transwell experiments, all resolvins inhibited neutrophil migration, with RvE1 being the most effective at a 2000nM concentration. In an in vivo murine excisional wound (1cm × 1cm) healing model, topically applied resolvins accelerated wound closure. RvE1-treated wounds healed by 19.4 ± 1.5 days post-wounding, which was significantly shorter than the RvD2-treated and RvD1-treated groups (p<0.05), which closed by an average of 22.8 ± 1.8 and 24.4 ± 2.2 days, respectively. Furthermore, all resolvin-treated groups healed faster than vehicle controls (p<0.05), which closed at 28.6 ± 1.5 days. There was a strong linear correlation (R2=0.9384) between each resolvin's potency in inhibiting neutrophil migration in vitro versus accelerating wound healing in vivo. Furthermore, upon histological analysis, the RvE1-treated group exhibited more mature collagen organization and reepithelialization.


Sensory and Physico-Psychological Metaphor Comprehension in Children with ASD: A Preliminary Study on the Outcomes of a Treatment.
Recent research into difficulties in figurative language in children with ASD highlighted that it is possible to devise training interventions to overcome these difficulties by teaching specific strategies. This study describes how children with ASD can improve their capability to explain metaphors with a treatment. Two types of metaphors, in the "X is Y" form, were addressed: sensory and physico-psychological. To face the difficulties posed by these metaphors, the adult taught two strategies: inserting the connective "is like" between "X" and "Y", which transforms the metaphor into a simile; comparing "X" and "Y" by means of thinking maps. Two tests of metaphor comprehension were used, one based on sensory and the other on physico-psychological metaphors. Sixteen 10 year-old children participated into the study, including an experimental group formed by 8 children with ASD (n = 4) which had received the treatment, and a control group (n = 4) which had not, and 8 typically-developing (TD) children. At the post-test, the experimental group significantly outperformed the controls in explaining both types of metaphors, but only in the sensory metaphors did their performances reach TD children's levels. These results illuminate how clinical treatment can positively influence the developmental trajectories of metaphor comprehension.


Contrasting Photo-Switching Rates in Azobenzene Derivatives: How the Nature of the Substituent Plays a Role.
A molecular design approach was used to create asymmetrical visible light-triggered azo-derivatives that can be good candidates for polymer functionalization. The specific electron-donor substituted molecules were characterized and studied by means of NMR analyses and UV-visible spectroscopy, comparing the results with Time Dependent Density Functional (TD-DFT) calculations. A slow rate of isomerization (ki = 1.5 × 10-4 s-1) was discovered for 4-((2-hydroxy-5methylphenyl) diazenyl)-3-methoxybenzoic acid (AZO1). By methylating this moiety, it was possible to unlock the isomerization mechanism for the second molecule, methyl 3-methoxy-4-((2-methoxy-5-methylphenyl) diazenyl)benzoate (AZO2), reaching promising isomerization rates with visible light irradiation in different solvents. It was discovered that this rate was heightened by one order of magnitude (ki = 3.1 × 10-3 s-1) for AZO2. A computational analysis using density functional (DFT/PBE0) and wavefunction (QD-NEVPT2) methodologies provided insight into the photodynamics of these systems. Both molecules require excitation to the second (S2) excited state situated in the visible region to initiate the isomerization. Two classic mechanisms were considered, namely rotation and inversion, with the former being energetically more favorable. These azo-derivatives show potential that paves the way for future applications as building blocks of functional polymers. Likewise, they could be really effective for the modification of existing commercial polymers, thus transferring their stimuli responsive properties to polymeric bulky structures, converting them into smart materials.


Epidemiology, Prevention, and Potential Future Treatments of Sexually Transmitted Zika Virus Infection.
While mosquitoes have been primarily responsible for outbreaks of Zika virus worldwide, most prominently in the Americas during 2015 and 2016, there has been increased recognition of the importance of sexual transmission. We review human reports and animal model studies of Zika sexual transmission and summarize potential therapeutic candidates. Male-to-female, male-to-male, and female-to-male transmission has been reported, among unprotected sexual contacts of returning travelers. Human studies have shown the potential importance of long-term persistence of Zika virus in semen while animal models have begun to yield important insights into pathogenesis of Zika infection of the genital tract. Adherence to federal and global guidelines for prevention of sexual transmission of Zika virus from travelers to their sexual partners represents the best strategy for reducing the risk of transmission outside of endemic areas. Active research on potential treatments may soon yield candidates for clinical trials.


Detection of minor populations of drug-resistant HIV-1 in acute seroconverters.
The transmission of drug-resistant HIV-1 is a major health concern. To date, most clinical studies have relied on sequencing techniques for genotypic analyses which do not allow quantification of minority viral populations below 25%. As minor populations of drug-resistant HIV-1 could impact the efficiency of antiretroviral therapy, this study was performed to determine the prevalence of minor populations of drug-resistant HIV-1 in acute seroconverters. Forty-nine acute seroconverters from two clinical centers in Germany were included in the study. Individuals were identified between June 1999 and March 2003, and none had received antiretroviral therapy prior to sampling. Minor populations of drug-resistant variants were detected by quantitative real-time polymerase chain reaction using allele-discriminating oligonucleotides for three key resistance mutations: L90M (protease), K103N and M184V (reverse transcriptase). The approximate discriminative power was between 0.01 and 0.2%. Drug-resistant variants were detected in 10 of 49 patients (20.4%). The L90M mutation was found in one of 49 (2%), the K103N mutation in five of 49 (10.2%) and the M184V mutation in six of 49 (12.2%) patients, respectively. In five of the 10 individuals with detectable drug-resistant virus (50%), the detected population represented a minor viral quasi-species (< 25% of viruses) and was not detected by direct sequencing. The prevalence of minor populations of drug-resistant HIV-1 in acute seroconverters can be frequently detected and may impact the success of antiretroviral therapy.


Mycobacterium tuberculosis Pili promote adhesion to and invasion of THP-1 macrophages.
Central to the paradigm of the pathogenesis of Mycobacterium tuberculosis is its ability to attach to, enter, and subsequently survive in host macrophages. However, little is known regarding the bacterial adhesins and invasins involved in this interaction with host macrophages. Pili are cell-surface structures produced by certain bacteria and have been implicated in adhesion to and invasion of phagocytes in several species. M. tuberculosis pili (MTP) are encoded by the Rv3312A (mtp) gene. In the present study, we assessed the ability of a Δmtp mutant and an mtp-complemented clinical strain to adhere to and invade THP-1 macrophages in comparison with the parental strain by determining colony-forming units. Both adhesion to and invasion of macrophages, although not reaching significance, were markedly reduced by 42.16% (P = 0.107) and 69.02% (P = 0.052), respectively, in the pili-deficient Δmtp mutant as compared with the wild-type. The pili-overexpressing complemented strain showed significantly higher levels of THP-1 macrophage adhesion (P = 0.000) and invasion (P = 0.040) than the mutant. We, thus, identified a novel adhesin and invasin of M. tuberculosis involved in adhesion to and invasion of macrophages.


Expression of HIV-1 nef in yeast: the 27 kDa Nef protein is myristylated and fractionates with the nucleus.
The nef gene of human immunodeficiency virus type 1 (HIV-1) has been expressed in the yeast Saccharomyces cerevisiae to produce native Nef proteins. The proteins of M(r) 27 kDa and 25 kDa, produced by translation from the first and second start codons of the nef gene react with human HIV-1 antisera. Under low-level steady-state expression conditions, Nef27 undergoes myristylation and is targeted to the nuclear fraction while Nef25 is not myristylated and not nuclear localized. When produced rapidly and to high levels, Nef27 is initially present in the cytoplasm as a soluble myristylated protein that later fractionates with the nucleus.


A Korean family with RHD*DNT only detectable after anti-D alloimmunization.
Identification of DNT, a rare partial D, can be challenging, as it is difficult to distinguish from D+. This study aimed to identify DNT individuals by analyzing the DNT proband's family members, characterize DNT, and propose management strategies. Family members of the first Korean DNT proband were recruited. RHD genotyping was conducted, and weak D tests were carried out using several anti-D reagents. Three DNT individuals were identified among 6 family members, including 1 with an anti-D alloantibody. As DNT red cells exhibited strong reactivity with all anti-D clones, DNT was serologically indistinguishable from D+. Moreover, unusual serologic findings in DNT individuals only became apparent after anti-D alloimmunization. We recommend DNT individuals as candidates for Rh immune globulin prophylaxis during the perinatal period and transfusions with D- blood components. An anticipatory RHD genotyping is suggested for partial D family members to prevent potential partial D individuals from becoming alloimmunized.


Clinical significance and distinctiveness of purging disorder and binge eating disorder.
In the DSM-IV, individuals with binge eating disorder (BED) and those with purging disorder (PD) receive a diagnosis of eating disorder not otherwise specified (EDNOS), suggesting no meaningful differences between clinical presentations. This article compares PD and BED on eating disorder severity and comorbid disorders. Individuals with PD (n = 33), DSM-IV BED (n = 23 with BMI >30 kg/m(2) , and n = 18 with BMI between 18.5 and 26.5 kg/m(2) ), and noneating disorder controls (n = 35) completed SCID-I interviews and questionnaires. Eating disorder groups reported significantly greater depression, body dissatisfaction, and dietary restraint and more Axis I disorders compared with controls. Compared with both the obese and normal weight BED groups, PD reported significantly greater dietary restraint and body dissatisfaction. Compared with obese BED, PD reported lower prevalence of impulse control disorders. Findings support differentiating among EDNOS based on behavioral presentation in both research and future nosological schemes such as the DSM-V.


Activation of RAGE/STAT3 pathway by methylglyoxal contributes to spinal central sensitization and persistent pain induced by bortezomib.
Bortezomib is a first-line chemotherapeutic drug widely used for multiple myeloma and other nonsolid malignancies. Although bortezomib-induced persistent pain is easily diagnosed in clinic, the pathogenic mechanism remains unclear. Here, we studied this issue with use of a rat model of systemic intraperitoneal administration of bortezomib for consecutive 5days. Consisted with our previous study, we found that bortezomib treatment markedly induced mechanical allodynia in rats. Furthermore, we first found that bortezomib treatment significantly induced the upregulation of methylglyoxal in spinal dorsal horn of rats. Spinal local application of methylglyoxal also induced mechanical allodynia and central sensitization in normal rats. Moreover, administration of bortezomib upregulated the expression of receptors for advanced glycation end products (RAGE) and phosphorylated STAT3 (p-STAT3) in dorsal horn. Importantly, intrathecal injection of metformin, a known scavenger of methylglyoxal, significantly attenuated the upregulation of methylglyoxal and RAGE in dorsal horn, central sensitization and mechanical allodynia induced by bortezomib treatment, and blockage of RAGE also prevented the upregulation of p-STAT3, central sensitization and mechanical allodynia induced by bortezomib treatment. In addition, inhibition of STAT3 activity by S3I-201 attenuated bortezomib-induced mechanical allodynia and central sensitization. Local knockdown of STAT3 also ameliorated the mechanical allodynia induced by bortezomib administration. Our results suggest that accumulation of methylglyoxal may activate the RAGE/STAT3 signaling pathway in dorsal horn, and contributes to the spinal central sensitization and persistent pain induced by bortezomib treatment.


[Meckel's diverticulum in childhood. The authors' own experience].
Meckel's diverticulum occurs in approximately 2 percent of the population and may present at any age. Although Meckel's diverticulum may produce an intestinal obstruction or perforation, simulating an appendicitis, hemorrhage is its most important clinical presentation. From 1989 to 1994, Meckel's diverticulum was discovered in ten children at laparotomy. Three cases were asymptomatic, representing an incidental finding at laparotomy. Of the seven symptomatic patients, four presented with bowel obstruction (intussusception), three had rectal bleeding one of whom had diverticulitis. Contrast studies--in gastrointestinal hemorrhage--were not helpful in establishing the diagnosis; colonoscopy and gastroscopy ruled out other causes of bleeding. Five of seven symptomatic patients had an intestinal resection while two a diverticulectomy after assessment that the ulcer did not require resection. No postoperative morbidity and mortality is reported in either groups. A Meckel's diverticulum found incidentally at laparotomy should be always resected as the risk of complication is high and that of resection low.


Prolactin-induced activation of tuberoinfundibular dopaminergic neurons: evidence for both a rapid 'tonic' and a delayed 'induction' component.
Results of previous studies have revealed that prolactin causes a delayed (12-16 h) increase in the rate of synthesis and turnover of dopamine (DA) in terminals of tuberoinfundibular (TI) neurons in the median eminence. Attempts to demonstrate a rapid in vivo action of prolactin on these neurons has been frustrated because pharmacological manipulations needed to make the biochemical measurements of TIDA neuronal activity (i.e., administration of alpha-methyltyrosine or NSD 1015) inhibit DA synthesis and thereby remove the tonic inhibitory control of DA on prolactin secretion. Thus, 'control' rates of synthesis and turnover of DA in terminals of TIDA neurons are actually values obtained in the presence of high circulating concentrations of prolactin. Results of the present in vivo studies demonstrate that there are two components to the activation of TIDA neurons by prolactin: a rapid 'tonic' component, which is responsive to acute changes in prolactin concentrations, and a delayed 'induction' component, which is activated by long-term changes in prolactin concentrations. Experimental observations which support this proposal are described below. Hypophysectomy or treatment with bromocriptine (a DA agonist) reduce circulating levels of prolactin and reduce the rate of DA synthesis in the median eminence. Intracerebroventricular (i.c.v.) administration of prolactin to these animals increases the rate of DA synthesis in the median eminence within 4 h (rapid 'tonic' component) and then causes a further increase after 12 h (delayed 'induction' component); only the latter component is blocked by treatment with cycloheximide, indicating the involvement in protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)


Oxidative stress in children with bacterial meningitis.
Bacterial meningitis is a common cause of morbidity and mortality in children. The oxidative stress in bacterial meningitis is barely determined. Forty children with bacterial meningitis were studied for their oxidants and antioxidants status in serum and cerebrospinal fluid. Fever (95%) was commonest presentation followed by seizure and vomiting. Neck rigidity and Kernig's sign were present in 37.5% and 27.5% cases, respectively. Plasma and cerebrospinal fluid malondialdehyde, protein carbonyl and nitrite levels were significantly raised in cases (p < 0.001). Plasma and cerebrospinal fluid ascorbic acid, glutathione and superoxide dismutase levels were significantly decreased in children with septic meningitis (p < 0.001). Significantly elevated malondialdehyde, nitrite and protein carbonyl levels reflect increased oxidative stress, whereas decreased concentrations of glutathione, ascorbic acid and superoxide dismutase indicates utilization of the antioxidants in septic meningitis. Thus, changes in oxidants and antioxidants observed suggest production of reactive oxygen species and their possible role in pathogenesis of septic meningitis.


Posttraumatic Stress Disorder Symptom Clusters and Perpetration of Intimate Partner Violence: Findings From a U.S. Nationally Representative Sample.
Associations between posttraumatic stress disorder (PTSD) and perpetration of intimate partner violence (IPV) have not been extensively studied in nonveteran samples. Secondary analysis was conducted using a nationally representative U.S. sample and limited to those who reported being in a relationship in the past year (N = 25,652). This sample was mostly White (72.0%), the majority had completed high school/ general educational development (GED; 87.8%), about half were female (49.2%), and the mean age was 46.44 years (SD = 15.92). We hypothesized that a diagnosis of PTSD in the past year would be associated with greater perpetration of IPV and that the arousal/reactivity and intrusion symptom clusters would evidence the strongest associations with IPV. Consistent with expectations, a PTSD diagnosis in the past year was associated with greater perpetration of IPV, OR = 2.07, 95% CI [1.89, 2.26]. Among those with a PTSD diagnosis in the past year (n = 1,742), arousal/reactivity symptom cluster scores were associated with greater perpetration of IPV for both men and women, AOR = 1.27, 95% CI [1.11, 1.44]; intrusion symptom cluster scores were associated with perpetration of IPV for men only, AOR = 1.56, 95% CI [1.20, 2.04]; whereas negative cognitions/mood symptom cluster scores were only significant among women, AOR = 1.12, 95% CI [1.01, 1.24]. Results suggested that theoretical and empirical work linking PTSD and perpetration of IPV in military samples extends to the general population.


Improvement in deployment of MRI of the sacroiliac joints in patients suspected for spondyloarthritis using a targeted intervention: a case study.
To assess characteristics of deployment of MRI of the SI joints (MR-SI) in patients with suspected axial spondyloarthritis (SpA) before and after a targeted intervention. In a retrospective chart review study, all MR-SI performed in the period 1 April 2004 to 31 December 2010 were collected. Inclusion criteria were complete patient data and MR-SI ordered by a rheumatologist for suspicion of axial SpA. MR-SI reports were graded as normal, suspected sacroiliitis or sacroiliitis. In April 2007 an intervention was made to improve deployment. Rheumatologists were provided with data on ordering behaviour, patient characteristics and MRI outcomes. An introduction on the effect of pretest chance on positive and negative predictive value was given; the burden for patients and costs was illustrated. An alternative behavioural strategy was offered in the form of a simple diagnostic algorithm. Percentages of MRIs and positive MRI for sacroiliitis were compared before and after intervention. From April 2004 to April 2007, 198 MR-SIs were performed, of which 166 (83.9%) were normal, 5 (2.5%) were suspicious and 27 (13.6%) were positive. After the intervention, patients displayed significantly more SpA features. More optimal patient selection resulted in 79 MR-SI requests, a decrease of 60.1%. Fifty-seven (72.2%) reports were normal, 0 were suspicious and 22 (27.8%) were positive. A simple, one-time, five-step feedback intervention resulted in a 60% reduction in MR-SI requests with a doubling of the percentage of MR-SI positive for sacroiliitis. This approach may benefit future research in areas with diagnostic uncertainty and suboptimal testing.


Isolation and characterization of Magnetospirillum sp. strain 15-1 as a representative anaerobic toluene-degrader from a constructed wetland model.
Previously, Planted Fixed-Bed Reactors (PFRs) have been used to investigate microbial toluene removal in the rhizosphere of constructed wetlands. Aerobic toluene degradation was predominant in these model systems although bulk redox conditions were hypoxic to anoxic. However, culture-independent approaches indicated also that microbes capable of anaerobic toluene degradation were abundant. Therefore, we aimed at isolating anaerobic-toluene degraders from one of these PFRs. From the obtained colonies which consisted of spirilli-shaped bacteria, a strain designated 15-1 was selected for further investigations. Analysis of its 16S rRNA gene revealed greatest similarity (99%) with toluene-degrading Magnetospirillum sp. TS-6. Isolate 15-1 grew with up to 0.5 mM of toluene under nitrate-reducing conditions. Cells reacted to higher concentrations of toluene by an increase in the degree of saturation of their membrane fatty acids. Strain 15-1 contained key genes for the anaerobic degradation of toluene via benzylsuccinate and subsequently the benzoyl-CoA pathway, namely bssA, encoding for the alpha subunit of benzylsuccinate synthase, bcrC for subunit C of benzoyl-CoA reductase and bamA for 6-oxocyclohex-1-ene-1-carbonyl-CoA hydrolase. Finally, most members of a clone library of bssA generated from the PFR had highest similarity to bssA from strain 15-1. Our study provides insights about the physiological capacities of a strain of Magnetospirillum isolated from a planted system where active rhizoremediation of toluene is taking place.


The effect of mismatching for HLA-DR in recipients of renal allografts sharing one HLA-ABC haplotype with related donors.
The effects of mismatching for DR antigens on renal allograft survival rates have largely been restricted to analyses of cadaver transplant results. Analyses of HLA matching in recipients of transplants from related donors have focused on the number of haplotypes shared between the recipients without regard to DR, or on the total number of HLA antigens mismatched, or on the degree of MLC responsiveness of the recipient to the donor. Most related donor-recipient pairs sharing only one HLA haplotype will be mismatched for DR at the other haplotype, but because there are a limited number of DR alleles, sharing of DR antigens on the mismatched haplotypes occurs relatively frequently. To determine the influence of mismatching for DR on the fate of renal allografts from related donors, we analyzed the results of 172 kidney transplants from related donors who shared one HLA-ABC haplotype with the recipient. There were 156 primary grafts and 16 retransplants; 147 donor-recipient pairs were satisfactory typed for DR antigens. Because genotyping was not usually done, we performed two analyses under two different assumptions. The first assumption was that individuals expressing less than or equal to 1 DR antigen had null antigens, or were homozygous for DR; the alternative assumption was that blanks were true antigens and individuals with blanks were heterozygous. The first assumption is more likely to be correct, and is the assumption used in most analyses of the effect of DR antigen mismatches on the results of cadaveric transplantation. Under the first assumption, of the 147 related donor-recipient pairs in whom DR typing was satisfactory, 33% were mismatched for 0, 64% for 1, and 3% for 2 DR antigens. The one-year absolute graft survival rates in recipients of kidneys from donors with 0 mismatches for DR was 92% (n = 49); in those with one mismatch for DR it was 82% (n = 94); and from those with two mismatches it was 50% (n = 4). The one-year graft survival rate in 25 donor-recipient pairs in which one or both members could not be satisfactorily DR typed was 76%. Differences in graft survival rates between the 0 and 1 and the 1 and 2 DR-mismatched groups were not statistically significant.(ABSTRACT TRUNCATED AT 400 WORDS)


Acute Dietary Restriction Acts via TOR, PP2A, and Myc Signaling to Boost Innate Immunity in Drosophila.
Dietary restriction promotes health and longevity across taxa through mechanisms that are largely unknown. Here, we show that acute yeast restriction significantly improves the ability of adult female Drosophila melanogaster to resist pathogenic bacterial infections through an immune pathway involving downregulation of target of rapamycin (TOR) signaling, which stabilizes the transcription factor Myc by increasing the steady-state level of its phosphorylated forms through decreased activity of protein phosphatase 2A. Upregulation of Myc through genetic and pharmacological means mimicked the effects of yeast restriction in fully fed flies, identifying Myc as a pro-immune molecule. Short-term dietary or pharmacological interventions that modulate TOR-PP2A-Myc signaling may provide an effective method to enhance immunity in vulnerable human populations.


[Rubella virus IgG and IgM antibody levels in 17-20 year old female students using ELISA and fluorescent antibody tests].
In this study Rubella virus antibody levels were investigated by using ELISA and IFAT in 94 sera obtained from girl students in Gülhane Military Medical Academy nursing college. We have propagated Rubella virus in BHK-21 cell line for production Rubella virus antigen in order to use IFAT. 81 sera IgG (86.2%) and 29 sera IgM (30.9%) were found positive in ELISA. However 76 sera (80.9%) IgG and 27 sera (28.7%) were positive in IFAT. On the other hand we have obtained suspected results in 8 sera (8.5%) with 1/10 dilution in IgG ELISA and in 3 sera (3.2%) with the same dilution in IgM ELISA. One of 29 sera which are ELISA IgM positive have established 80 IU/ml RF. We can say that ELISA is more reliable sensitive and practical than IFAT. It may be considered 29 student who have Rubella IgM antibody may be infected or reinfected by Rubella virus with in the last six months. On the other hand they may also infected with Parvovirus or some other viruses. We believe that the causes of false positive Rubella IgM antibody results should be investigated well enough.


Fatty acid oxidation and isoprostanes: oxidative strain and oxidative stress.
Oxidative stress is implicated as one of the key causes underlying many diseases. Free radicals are important constituents of basal physiology. Assessment of free radicals or the end products of their action has proved to be difficult. Consequently, authentication of the contribution of free radicals to physiology and pathology has usually been equivocal. Isoprostanes are biosynthesized in vivo, predominantly through free radical attack on arachidonic acid and are now regarded as robust biomarkers of oxidative stress in vivo. Isoprostanes are associated with many human diseases, and their concentration is altered over the course of normal human pregnancy, but their (patho)physiological roles have not yet been clearly defined. Measurement of F(2)-isoprostanes in body fluids could offer a unique analytical opportunity to study the role of free radicals in physiology and pathophysiology in order to comprehend both oxidative strain and oxidative stress.


HOX-7 suppresses body weight gain and adipogenesis-related gene expression in high-fat-diet-induced obese mice.
HOX-7 is a newly developed dietary formula composed of traditional oriental herbal medicines. The formula was developed with the aim of improving weight control. We investigated the anti-obesity effect of HOX-7 on high-fat-diet (HFD)-induced obesity in C57BL/6 mice. The mice were divided into four groups and were fed a normal diet (ND), HFD, or HFD with oral administration of HOX-7 at 100 or 200 mg/kg/day for 12 weeks. Body and fat weight, histological changes of fat tissue, and the expression of key adipogenic transcription factors were investigated. The body weight of mice fed the HFD with HOX-7 was significantly decreased compared to the HFD group. There were no obvious differences in weekly food intake among the 4 groups. The weight of the epididymal and total fat pads was reduced in mice fed the HFD with HOX-7. Treatment with HOX-7 also substantially attenuated the expression of key adipogenic transcription factors, including peroxisome proliferator-activated receptor γ, CCAAT/enhancer binding protein α, sterol regulatory element binding protein 1c, adipocyte P2, liver X receptor, and lipoprotein lipase in the epididymal adipose tissue. Overall, this study highlighted the anti-obesity effects of HOX-7, a finding that could contribute to the development of natural anti-obesity herbal medicines.


Inhibitory effects of estrogen and progesterone on several parameters of pulsatile LH release in the ovariectomized rat.
Recent reports on the effects of progesterone on the frequency of pulsatile LH release in several species have compelled a reevaluation of the regulation of pulsatile LH secretion by gonadal steroids in the rat. Long-term ovariectomized (OVX) adult rats were given Silastic implants filled with estradiol-17 beta in oil, and blood samples were taken every 5 min for 3 h, either 1 or 2 days later. Compared with the control group (empty Silastic capsules), estrogen-treated animals had significantly lower mean plasma LH concentrations, because of a significant increase in the time between pulses, pulse amplitude not being significantly affected. In a second experiment, it was determined that progesterone alone had no significant effect on pulse amplitude, frequency or mean plasma LH concentrations. In a third experiment, OVX animals received estrogen-filled (or empty) capsules on 1 day followed by progesterone-filled (or empty) capsules on the next day, and frequent blood samples were taken on the following day. Two-way analysis of variance showed significant inhibitory effects of estrogen on mean LH levels, pulse amplitude and pulse frequency. Progesterone lowered the pulse amplitude significantly, but had no effect on pulse frequency, unlike its reported effects in other species. There were no significant interactions between estrogen and progesterone on any parameter tested, indicating that there is no synergism between the two steroids under these conditions. We conclude that estrogen is the principal ovarian hormone restraining LH secretion in the long-term OVX rat and that progesterone has only a modest effect, even in the presence of estrogen.


Aicardi Syndrome: Key Fetal MRI Features and Prenatal Differential Diagnosis.
This study was aimed to investigate the prenatal findings in Aicardi syndrome (AIC) by intrauterine magnetic resonance imaging (iuMRI) suggesting possible diagnostic criteria and differential diagnosis. The iuMRI features of nine AIC confirmed cases were described and then compared with those of postnatal MRI. Furthermore, all iuMRI cases with both corpus callosum (CC) agenesis-dysgenesis and cortical malformation (AIC mimickers) were retrospectively reviewed and compared with iuMRI AIC cases, in order to identify possible neuroradiological predictors of AIC syndrome. For this purpose, Chi-square statistic and binary logistic regression analysis were performed. In all AIC cases, iuMRI was able to detect CC agenesis-dysgenesis and cortical development anomalies. Postnatal MRI revealed some additional findings mainly including further cystic lesions and in two cases small coloboma. A statistically significant difference between AIC and AIC mimicker were found regarding sex, nodular heterotopias, posterior fossa abnormalities, coloboma, and cortical gyration abnormalities. The most predictive variables in the logistic regression model were cortical gyration abnormalities, coloboma, and sex. The iuMRI findings may suggest prenatal diagnosis of AIC syndrome with significant impact on parental counseling. Among possible differential diagnoses, tubulinopathies emerged.


Automatic identification of pavement cracks in public roads using an optimized deep convolutional neural network model.
The current study aims to improve the efficiency of automatic identification of pavement distress and improve the status quo of difficult identification and detection of pavement distress. First, the identification method of pavement distress and the types of pavement distress are analysed. Then, the design concept of deep learning in pavement distress recognition is described. Finally, the mask region-based convolutional neural network (Mask R-CNN) model is designed and applied in the recognition of road crack distress. The results show that in the evaluation of the model's comprehensive recognition performance, the highest accuracy is 99%, and the lowest accuracy is 95% after the test and evaluation of the designed model in different datasets. In the evaluation of different crack identification and detection methods, the highest accuracy of transverse crack detection is 98% and the lowest accuracy is 95%. In longitudinal crack detection, the highest accuracy is 98% and the lowest accuracy is 92%. In mesh crack detection, the highest accuracy is 98% and the lowest accuracy is 92%. This work not only provides an in-depth reference for the application of deep CNNs in pavement distress recognition but also promotes the improvement of road traffic conditions, thus contributing to the progression of smart cities in the future. This article is part of the theme issue 'Artificial intelligence in failure analysis of transportation infrastructure and materials'.


[Microsurgical blood vessel reconstruction in kidney transplantation].
Of 214 donor kidney transplants, 14.5% exhibited multiple arterial supply, 2.8%, injuries to vessels, and 1.8%, severance of the polar vessel. Microsurgical procedures were used on 14 of these kidneys; 11 functioned immediately, so that the patients could be discharged. Techniques of anastomosis using an operating microscope or magnifying spectacles are described.


[The role of permeability in histological staining].
Ionic stain-binding is influenced by number of acid and basic groups, their dissociation equilibrium coefficient and isoelectric point of proteins, respectively, and by permeability, on tissue side and acid and basic character, respectively, ionic volume, isochronic and succedaneous way of application, respectively, and hydrogene ion concentration of solution on side of stain. With joint or sequent use of acid stains of different ionic volume, permeability order of certain tissue elements, their relative permeability can be determined.


Effects of smoke inhalation on alveolar surfactant subtypes in mice.
The effects of smoke inhalation on alveolar surfactant subtypes were examined in mice exposed for 30 minutes to smoke generated from the burning of a flexible polyurethane foam. At 4 or 12 hours after the exposure, three surfactant pellets, P10, P60, and P100, and a supernatant, S100, were prepared by sequential centrifugation of lavage fluids at 10,000 g for 30 minutes (P10), 60,000 g for 60 minutes (P60), and 100,000 g for 15 hours (P100 and S100). Phospholipid analysis and electron microscopy were performed on each fraction. Smoke exposure dramatically altered the normal distributions of these fractions: it significantly increased the phospholipid content of the heavier subtype, P10, which is thought to represent newly secreted surfactant; had no effect on the intermediate form, P60; and dramatically increased the phospholipid content (approximately fivefold) of the lighter subtypes, P100 and S100, which are believed to represent catabolic end-products of alveolar surfactant. Only P100 was structurally altered by the smoke. These results represent alterations of the normal metabolic processing of alveolar surfactant. Whereas the mechanism is yet to be defined, it seems to involve a small but significant increase in the newly secreted surfactant, as well as an excessively high accumulation of the structurally altered catabolic forms of the secreted surfactant.


[Infections of the sternum after cardiac surgery].
Methods of treatment of suppurative mediastinitis in cardiosurgical operations applied at the clinic are analysed. These methods are: debridment with closure of the sternum with irrigation of the substernal space, debridment with bandage of open wound and healing per secundam, debridment with bandage of open wound and its closure by myocutaneous layers. It has been concluded that these infections are very complex etiopathogenetically because of which it is very important to know all relevant risk factors aiming to prevent development of this complication in cardiosurgical operations. Its early recognition is necessary.


Using Natural Language Processing Techniques to Detect Adverse Events From Progress Notes Due to Chemotherapy.
In recent years, natural language processing (NLP) techniques have progressed, and their application in the medical field has been tested. However, the use of NLP to detect symptoms from medical progress notes written in Japanese, remains limited. We aimed to detect 2 gastrointestinal symptoms that interfere with the continuation of chemotherapy-nausea/vomiting and diarrhea-from progress notes using NLP, and then to analyze factors affecting NLP. In this study, 200 patients were randomly selected from 5277 patients who received intravenous injections of cytotoxic anticancer drugs at Kagawa University Hospital, Japan, between January 2011 and December 2018. We aimed to detect the first occurrence of nausea/vomiting (Group A) and diarrhea (Group B) using NLP. The NLP performance was evaluated by the concordance with a review of the physicians' progress notes used as the gold standard. Both groups showed high concordance: 83.5% (95% confidence interval [CI] 74.1-90.1) in Group A and 97.7% (95% CI 91.3-99.9) in Group B. However, the concordance was significantly better in Group B (P = .0027). There were significantly more misdetection cases in Group A than in Group B (15.3% in Group A; 1.2% in Group B, P = .0012) due to negative findings or past history. We detected occurrences of nausea/vomiting and diarrhea accurately using NLP. However, there were more misdetection cases in Group A due to negative findings or past history, which may have been influenced by the physicians' more frequent documentation of nausea/vomiting.


A congenic strain (F344.OLETF-Imfm) displays the existence of intramuscular fat accumulation QTL on rat chromosome 1.
A genomic region between D1Wox8 and D1Rat90 on rat chromosome 1 was previously shown to be linked to intramuscular fat accumulation by quantitative trait locus (QTL) analysis using a F2 population derived from the Otsuka Long-Evans Tokushima Fatty (OLETF) rat, which exhibits an increase in the levels of intramuscular fat content in Musculus longissimus, and the F344 rat. There exist two regions showing major and minor lod peaks for linkage to intramuscular fat accumulation, in the chromosomal region. We constructed a congenic strain introgressing the OLETF allele on the minor but not the major lod peak region in the F344 rat strain. The congenic strain had higher levels of intramuscular fat content in Musculus longissimus than the inbred partner F344 rat, thereby proving the existence of a QTL, designated Imfm (for Intramuscular fat-minor), responsible for the intramuscular fat accumulation in the congenic region of the minor lod peak region of about 10 cM. The F344.OLETF-Imfm congenic strain might provide a refined tool for the analysis of the gene causing intramuscular fat accumulation.


Prognostic value of chemotherapy-induced leukopenia in small-cell lung cancer.
Chemotherapy is the standard treatment for small-cell lung cancer (SCLC), and leukopenia is a common side effect. This study assesses whether chemotherapy-induced leukopenia is a predictor of efficacy and whether it is associated with the survival of SCLC patients. A retrospective analysis was conducted on data from 445 patients with SCLC who received standard chemotherapy for 4 to 10 cycles. The World Health Organization grading system classifies leukopenia during chemotherapy as follows: absent (grade 0), mild (grades 1 and 2), or severe (grades 3 and 4). The primary endpoint is overall survival (OS). The association between chemotherapy-induced leukopenia and OS was assessed. According to a multivariate Cox model with time-varying covariates, the hazard ratio of death was significantly lower among patients with mild leukopenia than among patients with severe leukopenia at 0.687 (0.506 to 0.943) and 1.414 (1.147 to 1.744), respectively. The median survival was 13 months (95% CI: 11 to 15 months) for patients who did not experience leukopenia, 17 months (95% CI: 14 to 18 months) for those with mild leukopenia, and 14 months (95% CI: 13 to 16 months) for those with severe leukopenia (absent vs. mild vs. severe leukopenia, P=0.047). Leukopenia during chemotherapy is associated with the survival of SCLC patients. Mild leukopenia is strongly associated with longer survival time.


XG-102 administered to healthy male volunteers as a single intravenous infusion: a randomized, double-blind, placebo-controlled, dose-escalating study.
The aim of the study is to evaluate the safety, tolerability and pharmacokinetics (PK) of the JNK inhibitor XG-102 in a randomized, double blind, placebo controlled, sequential ascending dose parallel group Phase 1 Study. Three groups of male subjects received as randomly assigned ascending single XG-102 doses (10, 40, and 80 μg/kg; 6 subjects per dose) or placebo (2 subjects per dose) as an intravenous (IV) infusion over 60 min. Safety and tolerability were assessed by physical examination, vital signs, electrocardiography, eye examination, clinical laboratory tests and adverse events (AEs). PK was analyzed using noncompartmental methods. All reported AEs were mild to moderate and neither their number nor their distribution by System Organ Class suggest a dose relationship. Only headache and fatigue were considered probably or possibly study drug related. Headache frequency was similar for active and placebo, consequently this was not considered to be drug related but probably to study conditions. The other examinations did not show clinically relevant deviations or trends suggesting a XG-102 relationship. Geometric mean half-life was similar among doses, ranging from 0.36 to 0.65 h. Geometric mean XG-102 AUC0-last increased more than linearly with dose, 90% confidence intervals (CIs) did not overlap for the two highest doses. Geometric mean dose normalized C max values suggest a more than linear increase with dose but 90% CIs overlap. It may be concluded that XG-102 single IV doses of 10-80 μg/kg administered over 1 h to healthy male subjects were safe and well tolerated.


Vitamin A supplementation is effective for improving the clinical symptoms of urinary tract infections and reducing renal scarring in girls with acute pyelonephritis: a randomized, double-blind placebo-controlled, clinical trial study.
It is believed that tubulointerstitial inflammation plays a role in the formation of renal scarring secondary to acute pyelonephritis (APN). Vitamin A is an anti-inflammatory agent that is involved in the re-epithelialization of damaged mucosal surfaces. The aim of this study was to evaluate the efficacy of vitamin A supplementation in combination with antibiotics for improving urinary tract infections (UTIs) symptoms and preventing renal scarring in girls with APN. This randomized, double-blind, placebo-controlled clinical trial was conducted on 90 girls aged 2 to 12 years old between 2015 and 2017. Patients with UTIs and first episode of APN diagnosed based on 99 mTc-DMSA scintigraphy (uptake defect) were assessed for eligibility. Patients were randomly divided into two groups that either received 10 days of oral vitamin A (intervention group) or 10 days of placebo (control group) in addition to antibiotics during the acute phase of infection. The clinical response was considered as the primary outcome [duration (positive days) of UTI symptoms during trial treatment period] and secondary outcomes (no change, improving and or worsening of 99 mTc-DMSA scan results 6 months after treatment from baseline). P < 0.05 was considered to be statistically significant. Seventy-four patients (vitamin A group: 36 patients, placebo: 38 patients) were included in the analysis. The mean age was 5.25 ± 1 year old. Three patients (7.89%) in the placebo group and 2 patients (5.55%) in the vitamin A group had vesicoureteral reflux (VUR) (p = 0.114). Duration of fever (vitamin A group: 1.8 days, placebo: 3.1 days, p = 0.0026), urinary frequency (1.3 days vs. 2.8 days, p = 0.003) and poor feeding (2.3 days vs. 4.2 days, p = 0.005) were significantly lower in the vitamin A group. Following the second 99 mTc-DMSA scan, worsening of lesions was observed among 8 (22.2%) and 17 (44.7%) patients in the vitamin A and placebo groups, respectively (p = 0.003). 63.8% (23 patients) of the vitamin A group and 21% (8 patients) of placebo group showed lesion improving in the photopenic region. (P < 0.0001) There was no evidence of vitamin A intolerance. Our results show the efficacy of vitamin A supplementation on reducing renal scarring secondary to APN and on fever, urinary frequency and poor feeding duration in girls with APN. Vitamin A supplementation is effective for improving the clinical symptoms of UTI and reducing renal injury and scarring following APN in girls with first APN. However, larger randomized clinical trials (RCTs) with longer follow up are needed to confirm these effects.


Efficacy of mistletoe for chemical pleurodesis in rats without malignancy.
Chemical pleurodesis is an effective treatment modality to reduce recurrence of malignant effusion. Several agents have been used in chemical pleurodesis but, it is not yet clear which is better. Eighteen Sprague-Dawley rats were used and classified into three groups: a group intrapleurally injected normal saline (group A, n=6), 400mg/kg talc (group B, n=6), and 9mg/kg mistletoe extraction (ME) (group C, n=6). Autopsy was performed to evaluate the pleural adhesion, pathologic examination of pleura and lung and bronchoalveolar lavage fluid analysis 4 weeks after pleurodesis. Both group B and C showed an obvious pleural adhesion and there was no significant difference in grade of pleural adhesion between two groups (p=0.58). The parietal pleural thickness in talc group than ME group was significantly thicker (p=0.002) and the visceral pleura of talc group showed marked foreign body reaction with fibrosis and many multinucleated giant cells associated with talc crystal. This study suggests that pleurodesis using ME in condition without malignancy has comparable effect to pleurodesis using talc. However, additional experimental study in large animal or clinical trials would be required to prove a safety and an efficacy of pleurodesis using ME.


Abnormal plasma sodium concentrations in patients treated with desmopressin for cranial diabetes insipidus: results of a long-term retrospective study.
Patients with cranial diabetes insipidus (CDI) are at risk of developing both hypernatraemia and hyponatraemia, due to the condition itself or secondary to treatment with vasopressin-analogues or during administration of i.v. fluids. We aimed to assess the frequency and impact of dysnatraemias in the inpatient (INPT) and outpatient (OPT) setting in desmopressin-treated CDI, comparing those with normal thirst with those with abnormal thirst. The study included 192 patients with cranial diabetes, who were identified from the Beaumont Pituitary Database, a tertiary referral centre. Retrospective case note audit was performed and the clinical and biochemical information of 147 patients with CDI were available for analysis. A total of 4142 plasma sodium measurements for 137 patients with normal thirst, and 385 plasma sodium measurements for ten patients with abnormal thirst were analysed. In those with normal thirst, the most common OPT abnormality was mild hyponatraemia (pNa(+) 131-134 mmol/l) in 27%, while 14.6% had more significant hyponatraemia (pNa(+) ≤130 mmol/l). Of those patients with normal thirst, 5.8% were admitted due to complications directly related to hyponatraemia. Compared with patients with normal thirst, those with abnormal thirst were more likely to develop significant OPT hypernatraemia (20% vs 1.4%, P=0.02) and significant INPT hyponatraemia (50% vs 11.1%, P 0.02). OPT management of CDI is complicated by a significant incidence of hyponatraemia. In contrast, OPT hypernatraemia is almost exclusively a complication seen in adipsic CDI, who also had more frequent INPT hyponatraemia. CDI associated with thirst disorder requires increased physician attention and patient awareness of potential complications.


What types of sex-role behavior should behavior modifiers promote?
Rekers and Lovaas (1974) reported a study using reinforcement procedures aimed at modifying the behavior of a 5-yr-old who engaged in cross-gender behavior. The use of traditional sex-role concepts in forming target behaviors is criticized and androgynous behavior is suggested as an empirically based alternative. The pathological nature of the behavior that the study was designed to prevent is also questioned, as is the ability to predict sex-role behavior from a 5-yr-old child's current behavior. These issues are raised in the context of the more general question, whom should the therapist serve?


VSL#3 can prevent ulcerative colitis-associated carcinogenesis in mice.
To investigate the effects of VSL#3 on tumor formation, and fecal and intestinal mucosal microbiota in azoxymethane/dextran sulfate sodium (AOM/DSS) induced mice model. C57BL/6 mice were administered AOM/DSS to develop the ulcerative colitis (UC) carcinogenesis model. Mice were treated with 5-ASA (75 mg/kg/d), VSL#3 (1.5 × 109 CFU/d), or 5-ASA combined with VSL#3 by gavage from the day of AOM injection for three months (five days/week). The tumor load was compared in each group, and tumor necrosis factor (TNF-α) and interleukin (IL)-6 levels were evaluated in colon tissue. The stool and intestinal mucosa samples were collected to analyze the differences in the intestinal microbiota by 16s rDNA sequencing method. VSL#3 significantly reduced the tumor load in AOM/DSS-induced mice model and decreased the level of TNF-α and IL-6 in colon tissue. The model group had a lower level of Lactobacillus and higher level of Oscillibacter and Lachnoclostridium in fecal microbiota than the control group. After the intervention with 5-ASA and VSL#3, Bacillus and Lactococcus were increased, while Lachnoclostridium and Oscillibacter were reduced. 5-ASA combined with VSL#3 increased the Lactobacillus and decreased the Oscillibacter. The intestinal mucosal microbiota analysis showed a lower level of Bifidobacterium and Ruminococcaceae_UCG-014 and higher level of Alloprevotella in the model group as compared to the control group. After supplementation with VSL#3, Bifidobacterium was increased. 5-ASA combined with VSL#3 increased the level of both Lachnoclostridium and Bifidobacterium. VSL#3 can prevent UC-associated carcinogenesis in mice, reduce the colonic mucosal inflammation levels, and rebalance the fecal and mucosal intestinal microbiota.


Alexithymia as a Mediator Between Childhood Maltreatment and Impulsivity.
Impulsivity, specifically negative urgency, is associated with diverse health risk behaviours, yet relatively little research has examined factors contributing to negative urgency. The purpose of this study was to examine the relationship between childhood maltreatment, alexithymia and negative urgency. The sample was comprised of 410 undergraduate students who completed measures online. A series of regression analyses tested whether alexithymia mediated the association between childhood maltreatment and negative urgency. Results supported the hypothesized mediation model. Subsequent analyses examined effects of specific subtypes of maltreatment and alexithymia subscales. These analyses indicated that growing up in a punishing environment (e.g. being hit or beat; expected to follow a strict code of behaviour) was indirectly associated with negative urgency via difficulty identifying feelings, suggesting that excessive use of punishment during childhood may reduce the development of the ability to identify and label feeling states. This difficulty in emotional processing may in turn lead to acting rashly when emotionally aroused.


Nucleolar exit of RNF8 and BRCA1 in response to DNA damage.
The induction of DNA double-strand breaks (DSBs) elicits a plethora of responses that redirect many cellular functions to the vital task of repairing the injury, collectively known as the DNA damage response (DDR). We have found that, in the absence of DNA damage, the DSB repair factors RNF8 and BRCA1 are associated with the nucleolus. Shortly after exposure of cells to γ-radiation, RNF8 and BRCA1 translocated from the nucleolus to damage foci, a traffic that was reverted several hours after the damage. RNF8 interacted through its FHA domain with the ribosomal protein RPSA, and knockdown of RPSA caused a depletion of nucleolar RNF8 and BRCA1, suggesting that the interaction of RNF8 with RPSA is critical for the nucleolar localization of these DDR factors. Knockdown of RPSA or RNF8 impaired bulk protein translation, as did γ-irradiation, the latter being partially countered by overexpression of exogenous RNF8. Our results suggest that RNF8 and BRCA1 are anchored to the nucleolus through reversible interactions with RPSA and that, in addition to its known functions in DDR, RNF8 may play a role in protein synthesis, possibly linking the nucleolar exit of this factor to the attenuation of protein synthesis in response to DNA damage.


Urokinase (u-PA) is produced by collecting duct principal cells and is post-transcriptionally regulated by SV40 large-T, arginine vasopressin, and epidermal growth factor.
We have analyzed the expression and regulation of plasminogen activators (PA) in principal cells of the renal collecting duct. We used a rabbit principal cell line (RC.SVtsA58) infected with the temperature-sensitive SV40 strain tsA58. Transformed cells cultured at permissive temperature (33 degrees C) produced only tissue-type plasminogen activator (t-PA). Shifting the cells to nonpermissive temperature (39.5 degrees C) induced their differentiation and a marked increase in total fibrinolytic activity due to the induction of urokinase-type plasminogen activator (u-PA) synthesis and secretion. The effect on u-PA was post-transcriptional and it could be attributed to large-T inactivation at 39.5 degrees C since it was abolished by re-infecting the cells with wild-type SV40. Run-on assay and real-time RT-PCR of u-PA transcripts indicated that large-T altered post-transcriptional regulation. u-PA was also produced by primary cultures of collecting duct cells and was present in the rabbit urine. In the kidney, u-PA and its receptor (u-PAR) were almost exclusively expressed at the apex of collecting duct cells. We then analyzed the regulation of u-PA by arginine vasopressin (AVP) and epidermal growth factor (EGF), two key regulators of principal cell functions. We found that AVP and EGF, which have opposite hydro-osmotic effects in the collecting duct, also exhibited contrasted effects on u-PA synthesis in differentiated RC.SVtsA58 cells. EGF increased but AVP suppressed u-PA activity and protein, and these regulations occurred at post-transcriptional level. These results point to a physiological role of u-PA in principal cells of the renal collecting duct.


Structural and functional insight into an unexpectedly selective N-methyltransferase involved in plantazolicin biosynthesis.
Plantazolicin (PZN), a polyheterocyclic, N(α),N(α)-dimethylarginine-containing antibiotic, harbors remarkably specific bactericidal activity toward strains of Bacillus anthracis, the causative agent of anthrax. Previous studies demonstrated that genetic deletion of the S-adenosyl-L-methionine-dependent methyltransferase from the PZN biosynthetic gene cluster results in the formation of desmethylPZN, which is devoid of antibiotic activity. Here we describe the in vitro reconstitution, mutational analysis, and X-ray crystallographic structure of the PZN methyltransferase. Unlike all other known small molecule methyltransferases, which act upon diverse substrates in vitro, the PZN methyltransferase is uncharacteristically limited in substrate scope and functions only on desmethylPZN and close derivatives. The crystal structures of two related PZN methyltransferases, solved to 1.75 Å (Bacillus amyloliquefaciens) and 2.0 Å (Bacillus pumilus), reveal a deep, narrow cavity, putatively functioning as the binding site for desmethylPZN. The narrowness of this cavity provides a framework for understanding the molecular basis of the extreme substrate selectivity. Analysis of a panel of point mutations to the methyltransferase from B. amyloliquefaciens allowed the identification of residues of structural and catalytic importance. These findings further our understanding of one set of orthologous enzymes involved in thiazole/oxazole-modified microcin biosynthesis, a rapidly growing sector of natural products research.


Differentiation of HL-60 myeloid leukemia cells induced by all-trans retinoic acid is enhanced in combination with caffeic acid.
We investigated a possible enhancement of all-trans retinoic acid (ATRA)-induced differentiation of HL-60 human myeloid leukemia cells by caffeic acid (CA), a widely distributed plant phenolic compound. Our results showed that CA, in the concentration of 13 or 52 micro M, had no or minimal influence on cell differentiation, whereas the differentiating activity of ATRA was potentiated by CA treatment. We proved, using flow cytometric detection of the CD66b surface molecule, a synergistic effect of CA: at day 10, 18.3% of CD66b-positive cells were detected after treatment with ATRA only, and 33% when CA and ATRA were combined together. NBT-assay confirmed that this additive effect of CA on ATRA-induced differentiation. Proliferating activity as assessed by MTT-assay was generally not affected by CA at given concentrations. However, cell proliferation was significantly reduced by 52 micro M CA at 96-h intervals. This effect was markedly enhanced when CA, at both concentrations, and ATRA were combined. The possibility to enhance the differentiation potential of ATRA by CA may improve outcomes in the therapy of acute promyelocytic leukemia.


Improved survival with splenic autotransplantation and fibronectin therapy following endotoxin administration in rats.
The risk of overwhelming infections is greatly increased after splenectomy. In this experimental study in rats, we investigated whether the administration of fibronectinrich cryoprecipitate can improve the survival rate of splenectomized autotransplanted rats subjected to an intravenous challenge with endotoxin. Inbred Lewis rats were divided into four groups: A, splenectomy; B, splenectomy + splenic autotransplantation; C, splenectomy, splenic autotransplantation + fibronectin treatment, and D, sham. Five months after surgery, rats were challenged intravenously with Escherichia coli endotoxin. Immunoglobulin (IgG, IgM, IgA), complement and fibronectin levels were measured before surgery and endotoxin challenge, and 48 h after endotoxin challenge. The survival rate of splenectomized rats was not significantly improved by autotransplantation of splenic tissue, but was significantly (p less than 0.05) improved by autotransplantation and fibronectin treatment. The levels of fibronectin, immunoglobulins and/or complements were significantly decreased after endotoxin challenge in control and in autotransplanted fibronectin-treated rats. The survival improvement of autotransplanted rats treated by fibronectin is probably due to increased endotoxin phagocytosis and clearance.


Frequency Of Common Bacteria And Their Antibiotic Sensitivity Pattern In Diabetics Presenting With Foot Ulcer.
Foot ulcers are one of the most important complications of diabetes mellitus and often lead to lower limb amputation. Diabetic foot ulcers are susceptible to infection. The objective of this study was to determine the frequency of common bacteria infecting these ulcers and their antibiotic sensitivity pattern. This descriptive cross-sectional study was performed in the Departments of Medicine and Surgery, Khyber Teaching Hospital, Peshawar from April, 2011 to February, 2012. Specimens collected from ulcers of 131 patients were inoculated on Blood Agar and MacConkey Agar, and antibiotic sensitivity was tested using standard disc diffusion method. Out of 131, specimens from 120 patients yielded 176 bacteria. Sixty-six patients had monomicrobial infection while polymicrobial growth was obtained in 54 patients. Overall, Staphylococcus aureus (38.6%) was the most common isolate followed by Pseudomonas aeruginosa (27.3%). Staphylococcus aureus was most often sensitive to Moxifloxacin, Imipenem/Meropenem, Vancomycin and Linezolid while it showed varying sensitivity to Penicillins and Cephalosporins. 47.1% isolates of Staphylococcus aureus were resistant to Methicillin. Most of the gram negative rods were sensitive to Imipenem/Meropenem, Piperacillin-Tazobactam and Ticarcillin-Clavulanate. Majority of gram negative bacteria were found resistant to Cephalosporins and Moxifloxacin except Pseudomonas which showed variable sensitivity to Ceftriaxone, Ceftazidime and Moxifloxacin. Majority of isolates were found resistant to the commonly used antibiotics. Most commonly isolated bacterium, Staphylococcus aureus was most often sensitive to Moxifloxacin, Imipenem/Meropenem, Vancomycin and Linezolid, while majority isolated gram negative rods were sensitive to Imipenem/Meropenem, Piperacillin-Tazobactam and Ticarcillin-Clavulanate.


[Effects of Genipin on the expression of uncoupling protein 1 in brown adipose and white adipose tissues in mice].
To investigate the effects of genipin on promoting brown adipose tissue activation and white adipose tissue browning. The male C57BL/6J mice were divided into three groups: normal control group, genipin group and cold-stimulus group.Genipin group were treated consecutively with genipin at a dose of 15 mg/kg once a day for 9 days, normal control group were treated with the saline.The mice with cold-stimulus were exposed to 4℃ environment for 5 days.Daily food amount and body weight were measured.Morphological changes were observed in the subscapular region, inguinal region and epididymis around the adipose tissue.The expression of uncoupling protein 1 (UCP1) was determined by real-time PCR and Western blot respectively. The wet weight of white fat in genipin-treated mice was decreased by 16% , and 28% in that of cold-stimulus mice, compared with the normal control group (P<0.05).After treatments of genipin and cold-stimulus, the color of white adipose tissues was darker, and the size of lipid droplets in adipocytes was smaller, whereas the number was increased.Compared with the normal control group, UCP1 expression was increased obviously in fat tissues, including the subcutaneous and visceral white adipose tissues, and brown adipose tissue after treated with genipin and cold-stimulus (P<0.05). Genipin promoted activation of brown adipose tissue and browning of white adipose tissue by upregulating UCP1 expression, which could contribute to the loss of body weight against obesity.


Emergency care in 59 low- and middle-income countries: a systematic review.
To conduct a systematic review of emergency care in low- and middle-income countries (LMICs). We searched PubMed, CINAHL and World Health Organization (WHO) databases for reports describing facility-based emergency care and obtained unpublished data from a network of clinicians and researchers. We screened articles for inclusion based on their titles and abstracts in English or French. We extracted data on patient outcomes and demographics as well as facility and provider characteristics. Analyses were restricted to reports published from 1990 onwards. We identified 195 reports concerning 192 facilities in 59 countries. Most were academically-affiliated hospitals in urban areas. The median mortality within emergency departments was 1.8% (interquartile range, IQR: 0.2-5.1%). Mortality was relatively high in paediatric facilities (median: 4.8%; IQR: 2.3-8.4%) and in sub-Saharan Africa (median: 3.4%; IQR: 0.5-6.3%). The median number of patients was 30 000 per year (IQR: 10 296-60 000), most of whom were young (median age: 35 years; IQR: 6.9-41.0) and male (median: 55.7%; IQR: 50.0-59.2%). Most facilities were staffed either by physicians-in-training or by physicians whose level of training was unspecified. Very few of these providers had specialist training in emergency care. Available data on emergency care in LMICs indicate high patient loads and mortality, particularly in sub-Saharan Africa, where a substantial proportion of all deaths may occur in emergency departments. The combination of high volume and the urgency of treatment make emergency care an important area of focus for interventions aimed at reducing mortality in these settings.


Neurosurgical endoscopic training via a realistic 3-dimensional model with pathology.
Training in intraventricular endoscopy is particularly challenging because the volume of cases is relatively small and the techniques involved are unlike those usually used in conventional neurosurgery. Present training models are inadequate for various reasons. Using 3-dimensional (3D) printing techniques, models with pathology can be created using actual patient's imaging data. This technical article introduces a new training model based on a patient with hydrocephalus secondary to a pineal tumour, enabling the models to be used to simulate third ventriculostomies and pineal biopsies. Multiple models of the head of a patient with hydrocephalus were created using 3D rapid prototyping technique. These models were modified to allow for a fluid-filled ventricular system under appropriate tension. The models were qualitatively assessed in the various steps involved in an endoscopic third ventriculostomy and intraventricular biopsy procedure, initially by 3 independent neurosurgeons and subsequently by 12 participants of an intraventricular endoscopy workshop. All 3 surgeons agreed on the ease and usefulness of these models in the teaching of endoscopic third ventriculostomy, performing endoscopic biopsies, and the integration of navigation to ventriculoscopy. Their overall score for the ventricular model realism was above average. The 12 participants of the intraventricular endoscopy workshop averaged between a score of 4.0 to 4.6 of 5 for every individual step of the procedure. Neurosurgical endoscopic training currently is a long process of stepwise training. These 3D printed models provide a realistic simulation environment for a neuroendoscopy procedure that allows safe and effective teaching of navigation and endoscopy in a standardized and repetitive fashion.


Metabolic Myopathies: Experience of a Reference Center of Inherited Metabolic Diseases.
Metabolic myopathies (MM) are a heterogeneous group of genetic disorders affecting metabolic pathways involved in energy production during rest, exercise and physiologic stress (fever, fasting, …). Impairments in the pathways of glycolysis/ glycogenolysis, fatty acid transport/oxidation or in the mitochondrial respiratory chain present primarily with exercise intolerance, myalgias, weakness, cramps, or rhabdomyolysis. Depending on aetiology, the diagnosis can be made through neonatal screening, pre-symptomatic or in the set of clinical manifestations for which a high level of suspicion is important. Retrospective descriptive study of the clinical, biochemical, and molecular features of patients with a confirmed diagnosis of MM followed by the multidisciplinary team of the Reference Center of Inherited Metabolic Diseases of Centro Hospitalar Universitário de Lisboa Central from 2009 to 2022. Twenty-three patients with MM were included: 9 (39%) glycogen storage diseases (7 McArdle and 2 Pompe), 7 (30%) fatty acid oxidation disorders (3 CPT2, 3 LCHAD and 1 MAD deficiencies), 6 (26%) mitochondrial disease with significant muscle involvement (2 Pearson, 1 Kearns Sayre, 1 VARS2, 1 SUCLA2 and 1 MT-TL1 deficiencies), and 1 myoadenylate deaminase deficiency. Ages varied from 15 months to 35 years. Eighteen (78%) patients were diagnosed by clinical symptoms, 3 by newborn screening (LCHAD) and 2 were asymptomatic (1 Pompe and 1 McArdle). Frequent symptoms were rhabdomyolysis triggered by illness or exercise 12 (52%), fatigue 11 (48%), exercise intolerance 10 (43%), and myalgia 9 (43%). Eight (35%) patients (LCHAD and mitochondrial) had multisystemic involvement. In 20 (87%) patients, the diagnosis was confirmed by biochemical and/or genetic analysis and 3 (McArdle) by muscle biopsy. MM are a heterogeneous set of disorders, but a careful history may guide the differential diagnosis among biochemical pathways and other etiologies. Nowadays, molecular testing has become a powerful tool for diagnosis confirmation, surpassing muscular biopsy in most cases. Accurate diagnosis is important to identify who may benefit from specific therapeutic options, such as enzyme replacement therapy, restricted diets, emergency regime and cofactors. All patients benefit from adequate lifestyle modifications, individualized exercise prescription, nutritional intervention, and genetic counselling.


Distortion dependent intersystem crossing: A femtosecond time-resolved photoelectron spectroscopy study of benzene, toluene, and p-xylene.
The competition between ultrafast intersystem crossing and internal conversion in benzene, toluene, and p-xylene is investigated with time-resolved photoelectron spectroscopy and quantum chemical calculations. By exciting to S2 out-of-plane symmetry breaking, distortions are activated at early times whereupon spin-forbidden intersystem crossing becomes (partly) allowed. Natural bond orbital analysis suggests that the pinnacle carbon atoms distorting from the aromatic plane change hybridization between the planar Franck-Condon geometry and the deformed (boat-shaped) S2 equilibrium geometry. The effect is observed to increase in the presence of methyl-groups on the pinnacle carbon-atoms, where largest extents of σ and π orbital-mixing are observed. This is fully consistent with the time-resolved spectroscopy data: Toluene and p-xylene show evidence for ultrafast triplet formation competing with internal conversion, while benzene appears to only decay via internal conversion within the singlet manifold. For toluene and p-xylene, internal conversion to S1 and intersystem crossing to T3 occur within the time-resolution of our instrument. The receiver triplet state (T3) is found to undergo internal conversion in the triplet manifold within ≈100-150 fs (toluene) or ≈180-200 fs (p-xylene) as demonstrated by matching rise and decay components of upper and lower triplet states. Overall, the effect of methylation is found to both increase the intersystem crossing probability and direct the molecular axis of the excited state dynamics.


Cross-cultural application of the Korean version of Ureteral Stent Symptoms Questionnaire.
We validated the Korean version of the Ureteral Stent Symptoms Questionnaire (USSQ) in patients with an indwelling ureteral stent. Linguistic validation of the original USSQ was performed through a standard process including translation, back translation, and pilot study. A total of 65 patients who underwent ureteroscopic surgery were asked to complete the Korean USSQ as well as EuroQOL (male and female), the International Prostate Symptom Score (male), and Urogenital Distress Inventory-6 (female). Patients were evaluated at weeks 1 and 2 after stent placement and at week 4 after removal. Sixty-four healthy subjects without a ureteral stent were also asked to complete the Korean USSQ once. The psychometric properties of the questionnaire were analyzed. Internal consistencies (Cronbach α coefficients: 0.73-0.83) and test-retest reliability (Spearman correlation coefficient: ≥0.6) were satisfactory for urinary symptom, body pain, general health, and work performance domains. Most USSQ domains showed moderate correlations with each other. Convergent validity determined by correlation between other instruments and corresponding USSQ domain was satisfactory. Sensitivity to change and discriminant validity were also good in most domains (P<0.01). Only a small proportion of the study population had an active sexual life, with the stent in situ, limiting its analysis. The Korean version of the USSQ is a reliable and valid instrument that can be self-administered by Korean patients with a ureteral stent in the clinical and research settings. Further clinical studies in the Korean settings would be useful to provide robust data on sensitivity to change.


The functional output of the mesolimbic dopamine system.
In summary, the nucleus accumbens, located at the interface of the limbic projections from the amygdala, hippocampus, and cingulate cortex, and receiving extrapyramidal fibers from midbrain DA-containing nuclei, is well situated to form neural circuitry that mediates the behaviorally activating properties of several stimulants. Efferent GABAergic fibers projecting from the nucleus accumbens to the ventral pallidum translate integrated limbic and extrapyramidal information to lower motor circuitry; some of this information appears to be carried by ventral pallidal efferent fibers projecting to the dorsomedial nucleus of the thalamus. It seems very possible that activation of this circuitry by positive reinforcing environmental stimuli, through the release of endogenous DA or opiate compounds, might contribute to motivated behavior. Indeed, environmentally generated locomotor activity can be blocked by disruption of this circuitry following destruction of N. Acc. DA terminals. It is also tempting to speculate that pathological changes in activity within this system might disrupt normal reinforcement contingencies, and contribute to the affective components of both psychiatric and neurologic disease states.


Two-hit model of schizophrenia induced by neonatal immune activation and peripubertal stress in rats: Study of sex differences and brain oxidative alterations.
Schizophrenia is considered to be a developmental disorder with distinctive sex differences. Aiming to simulate the vulnerability of the third trimester of human pregnancy to the developmental course of schizophrenia, an animal model was developed, using neonatal poly(I:C) as a first-hit, and peripubertal stress as a second-hit, i.e. a two-hit model. Since, to date, there have been no references to sex differences in the two-hit model, our study sought to determine sex influences on the development of behavior and brain oxidative change in adult rats submitted to neonatal exposure to poly(I:C) on postnatal days 5-7 as well as peripubertal unpredictable stress (PUS). Our results showed that adult two-hit rats present sex-specific behavioral alterations, with females showing more pronounced deficits in prepulse inhibition of the startle reflex and hyperlocomotion, while males showing more deficits in social interaction. Male and female animals exhibited similar working memory deficits. The levels of the endogenous antioxidant, reduced glutathione, were decreased in the prefrontal cortex (PFC) of both male and female animals exposed to both poly(I:C) and poly(I:C)+PUS. Only females presented decrements in GSH levels in the striatum. Nitrite levels were increased in the PFC of male and in the striatum of female poly(I:C)+PUS rats. Increased lipid peroxidation was observed in the PFC of females and in the striatum of males and females exposed to poly(I:C) and poly(I:C)+PUS. Thus, the present study presents evidence for sex differences in behavior and oxidative brain change induced by a two-hit model of schizophrenia.


Phosphorylated Pullulan Coating Enhances Titanium Implant Osseointegration in a Pig Model.
To investigate the effect of coating a titanium implant surface with a phosphorylated exopolysaccharide, pullulan, on the peri-implant bone formation and implant osseointegration. Implants were placed in the skull bone of 12 domestic pigs and healed for 1 or 3 months. Osseointegration of (un)coated implants was evaluated by quantitative histology (peri-implant bone fraction [BF] and bone-to-implant-contact [BIC]). The Wilcoxon-Mann-Whitney test with α = .05 was used to statistically compare BF and BIC of the coated and uncoated implants. Significantly more BF was observed surrounding pullulan-coated implants compared with uncoated implants (P < .05) and for both healing periods (P < .05). BIC was positively affected by the exopolysaccharide coating, with significantly more BIC after the 3-month healing period compared with the uncoated implant (P < .05). Furthermore, BIC remained stable over time for the coated implants, while it significantly decreased for the uncoated ones (P < .05). These findings reveal the capacity of functionalizing the titanium implant surface with phosphorylated pullulan to improve the mineralization of the implant-bone interface.


Dextrothyroxine treatment of phosphorylase-kinase deficiency glycogenosis in four boys.
Four boys, aged 2 years 5 months to 3 years 7 months, with large hepatomegaly due to phosphorylase-kinase deficiency glycogenosis, were given a trial of sodium dextrothyroxine (D-T4) at a mean dose of 0.165 mg/kg/day for an average period of 6 months. Phosphorylase-kinase was undetectable in the haemolysates of erythrocytes (3 patients) or in the liver (one patient) before, and still undetectable in the haemolysates of the four patients during treatment, thus pointing to X-linked phosphorylase-kinase deficiency glycogen storage disease (GSD IXb). D-T4 administration resulted in complete normalization of liver size, decrease of serum GOT (p less than 0.02), GPT (p less than 0.05) and triglycerides (p less than 0.01) to normal values, as well as correction of mild asymptomatic hypoglycemia (p less than 0.01). As long as the outcome of type IXb glycogenosis in adult life remains undefined, dextrothyroxine therapy seems an effective means of reducing liver size and correcting part of the biochemical abnormalities of the disease.


Exploring textile-based electrode materials for electromyography smart garments.
In recent years, electromyography (EMG) has been increasingly studied for wearable applications. Conventional gel electrodes for electrophysiological recordings have limited use in everyday applications such as prosthetic control or muscular therapy at home. This study investigates the efficacy and feasibility of dry-contact electrode materials employed in smart textiles for EMG recordings. Dry-contact electrode materials were selected and implemented on textile substrates. Using these electrodes, EMG was recorded from the forearm of able-bodied subjects. 25% and 50% isometric maximum voluntary contractions were captured. A comparative investigation was performed against gel electrodes, assessing the effect of material properties on signal fidelity and strength compared. When isolating for electrode surface area and pressure, 31 of the 40 materials demonstrated strong positive correlations in their mean PSD with gel electrodes (r > 95, p < 0.001). The inclusion of ionic liquids in the material composition, and using raised or flat electrodes, did not demonstrate a significant effect in signal quality. For EMG dry-contact electrodes, comparing the performance against gel electrodes for the application with the selected material is important. Other factors recommended to be studied are electrodes' durability and long-term stability.


Plural cells organize thyroid follicles through aggregation and linkage in collagen gel culture of porcine follicle cells.
Some follicle cells organize thyroid follicles through proliferation of single cells in collagen gel culture. The aim of this study was to clarify whether two or more (plural) cells can form follicles through aggregation and linkage in this culture system. To address this question, we performed collagen gel culture of porcine follicle cells, using cell labeling with PKH 2 dye. A mixture of dye-labeled and nonlabeled cells was cultured in collagen gel. Organized follicles consisted of both dyed and nondyed cells. This suggested that plural cells reconstructed follicles through aggregation and linkage. To further confirm this finding, cells embedded in collagen gel were cultured in inhibition of cell proliferation with 2 micrograms/ml aphidicolin. Forty to 60 percent of the cells formed follicles, which did not grow larger. Electron microscopy showed that intracytoplasmic cavities appeared in the cells. In contrast, 20-30% of the embedded cells developed into cavity-embracing single cells, which remained signet rings. These results indicate that follicle cells organize follicles in collagen gel culture by two means: through cell division of cavity-embracing single cells and through aggregation and linkage of plural cells.


Molecular cloning and characterisation of the methionine sulphoxide reductase A (msrA) gene locus in Campylobacter lari organisms.
The methionine sulphoxide reductase A (msrA) gene and its adjacent genetic loci from urease-negative (UN) Campylobacter lari RM2100 and urease-positive thermophilic Campylobacter (UPTC)CF89-12 strains appear to be composed of a msrA structure gene (507 base pairs [bp]) and another five-gene cluster (approximately 6300 bp) in the same strand and direction. A primer pair (F1/R4-msrA) for polymerase chain reaction (PCR) amplification was designed to generate a product of approximately 900 bp of the msrA gene, including its adjacent genetic loci for the thermophilic Campylobacter organisms and generate an amplicon with 16 C. lari isolates (n = 4 for UN C. lari; n = 12 for UPTC). Following direct nucleotide sequencing, sequence analysis and nucleotide sequence alignment analysis, the putative full-length msrA gene from the 16 C. lari isolates showed high nucleotide sequence similarities (91.8-100%) to each other and relatively low similarity (69.3-71.8%) to three reference C. jejuni and C. coli strains. In addition, the msrA gene was transcribed in both the UPTC CF89-12 and NCTC12893 cells using reverse transcription PCR. An immunoreactively positive signal was identified in the UPTC CF89-12 and NCTC12893 cells with anti-UPTC MsrA synthetic peptide antibodies.