A search for differences in size perception of near objects in young myopes corrected by either spectacles or contact lenses.
Accommodation and convergence demands are lower for a spectacle-corrected myope than for the same individual when corrected with contact lenses. Thus the impact of accommodative/convergence micropsia ought to be lower with the spectacle correction. A size-matching experiment which required myopic subjects (corrections up to -12.25 D) to match the sizes of each of four standard targets with a variable comparison target was therefore conducted. The standard targets were placed at four viewing distances: 3 m, I m, 0.5 m and 0.25 m. All standard targets subtended 2 degrees at the eye. The variable comparison target was situated at a fixed distance of 2 m and was generated on a visual display unit. Each of the eight subjects was shown one standard target at a time under binocular viewing conditions and was told to adjust the size of the comparison target until he/she felt that both targets were equal in linear size. Two sets of readings were taken: one when the subject's myopia was corrected with spectacles and one when corrected with contact lenses. No systematic difference in size perception was found between the spectacle and contact lens corrected cases, implying that the relatively small differences in accommodation and convergence demand did not significantly influence the size judgements.


Use of Joint Commission International standards to evaluate and improve pediatric oncology nursing care in Guatemala.
Inadequate nursing care is a major impediment to development of effective programs for treatment of childhood cancer in low-income countries. When the International Outreach Program at St. Jude Children's Research Hospital established partner sites in low-income countries, few nurses had pediatric oncology skills or experience. A comprehensive nursing program was developed to promote the provision of quality nursing care, and in this manuscript we describe the program's impact on 20 selected Joint Commission International (JCI) quality standards at the National Pediatric Oncology Unit in Guatemala. We utilized JCI standards to focus the nursing evaluation and implementation of improvements. These standards were developed to assess public hospitals in low-income countries and are recognized as the gold standard of international quality evaluation. We compared the number of JCI standards met before and after the nursing program was implemented using direct observation of nursing care; review of medical records, policies, procedures, and job descriptions; and interviews with staff. In 2006, only 1 of the 20 standards was met fully, 2 partially, and 17 not met. In 2009, 16 were met fully, 1 partially, and 3 not met. Several factors contributed to the improvement. The pre-program quality evaluation provided objective and credible findings and an organizational framework for implementing change. The medical, administrative, and nursing staff worked together to improve nursing standards. A systematic approach and involvement of all hospital disciplines led to significant improvement in nursing care that was reflected by fully meeting 16 of 20 standards.


Application of the indirect fluorescent antibody test for diagnosis of Theileria hirci infection of sheep: using cell culture schizont antigen.
The indirect fluorescent antibody test was applied for detection of circulating antibodies in sheep as a result of Theileria hirci infections. A schizont antigen was prepared from an in vitro culture suspension of lymphoid cells infected with T. hirci macroschizonts. The peak antibody titre of 1/8, 192 was reached 24 days after the initial antibody rise in the sheep experimentally infected by means of Hyalomma anatolicum anatolicum ticks.


DERM/MIS update. The Dermatology Management and Information System of the American Academy of Dermatology.
The Dermatology Management and Information System (DERM/MIS) was created by the Task Force on Biomedical Communications of the American Academy of Dermatology. The concept of such a System was conceived as part of the National Program for Dermatology and has been actively pursued since. The purpose of this report is to review the current status of DERM/OMS (Dermatology Office Management System); DERM/LIT (Dermatology Literature); DERM/RX (Dermatology treatment); DERM/DDX (Dermatology Differential Diagnosis); DERM/PATH (Dermatopathology). Other components of the DERM/MIS system are currently being planned. Predictions indicate that by the end of this decade a substantial percent of dermatologic offices will have access to some form of computerized programs. The DERM/MIS system has been designed specifically to meet the needs of the practicing dermatologist in the office setting.


Policy and socio-cultural differences between cantons in Switzerland with high and low adolescent vaccination coverage for hepatitis B and HPV.
Vaccination recommendations in Switzerland are national, but vaccine coverage varies greatly from one canton to another, particularly for vaccinations recommended in adolescence. To explain these differences, we studied vaccination practices and socio-cultural views from the vantage points of policy makers, healthcare providers and community adolescents and parents in 4 cantons with low (LVC) and 4 cantons with high (HVC) vaccination coverage for hepatitis B (HBV) and human papillomavirus (HPV) vaccines. In-depth semi-structured interviews were administered to a policy maker, a private practitioner and 4 to 7 community members (adolescents and parents of adolescents) from each of the 8 cantons. LVCs were notable for less government involvement in vaccination issues, more autonomy of municipalities for school health, lower density of pediatricians, less information about these vaccines, greater emphasis on individual rather than government responsibility for vaccinations and for anticipated community hesitancy. Doctors in HVCs more actively advocated for vaccines. Community views in HVCs were more collectivistic and reliant on schools as a source of information than in LVCs. In both groups, hesitancy and concerns about efficacy were greater for HPV than for HBV vaccine. Findings suggest more systematic involvement of health and school authorities will be appreciated by adolescents and their parents, and will improve vaccination coverage. Interventions focused only on community awareness and hesitancy are likely to be inadequate without efforts to reach policy makers and doctors.


Fuzzy classifier model to know the sustainability of aquatic organisms and to forecast the aqua farmers.
This research work focuses to develop a fuzzy classifier model, to know the sustainability of aquatic animals and/or plants by assessing the aqua pond water quality. This model categorizes the water quality of aqua pond into four levels like as normal, acceptable, abnormal, and dangerous based on the numerical values of physical limits. The developed model is useful to forecast the pond water quality by the aqua farmers to keep up within the acceptable limits at the earliest. Data collected from five ponds are used to develop the fuzzy classifier model. The output of this model is validated using a known set of sample data. This model yields high classification performance against variation in aqua pond water quality parameters and also provides the status of pond water continuously along with a remedy to keep up the water quality.


Epicatechin treatment generates resilience to chronic mild stress-induced depression in a murine model.
Several studies have proposed that cocoa products-enriched in flavonoids reduce anxiety and depressive symptoms. (-)-Epicatechin (Epi), a flavonoid present in high concentration in cocoa, has been associated with many dark chocolate effects and has been postulated as an exercise mimetic. Physical exercise is used as an adjuvant treatment for many depressive patients. This study aimed to evaluate the impact of Epi on resilience in depression-like behavior in a murine model. Male mice were randomly selected and divided into four groups (n = 8/group). Beginning at the age of 8-9 weeks, the mice were subjected to Chronic Mild Stress (CMS) and/or treatment Epi for five weeks. Epi was administered by oral gavage twice daily/5 weeks. The control group was housed in conditions without stress and Epi treatment. Depressive behavior was evaluated by sucrose preference and open field tests. Interestingly, Epi reduced anhedonia and anxiogenic behavior in the murine stress model. These results suggest that Epi induces resilience to stress-induced depression. Furthermore, our findings propose that muscles respond to Epi treatment according to their type of metabolism and that kynurenine aminotransferases (KATs) could play a role in modulating this response.


Reproductive toxicity of environmental levels of triphenyltin to the marine rotifer, Brachionus plicatilis.
Triphenyltin (TPT) is a representative organotin often used in marine antifouling coatings, herbicides, and pesticides. However, leaching of TPT into water may be toxic to aquatic life. In this study, environmental concentrations of TPT were used to explore reproductive toxicity of TPT to Brachionus plicatilis, a representative marine rotifer. Toxicity was examined at individual, biochemical, and molecular levels and via phenotypic traits. Rotifers exposed to 10 ng/L TPT group showed increased population size, improved reproductive rate, and a higher weekly growth rate. At 100 ng/L TPT group, the greatest degree of oxidative damage was seen. Exposure to 200 ng/L TPT group shorten generation time, delayed reproduction, and obscured the reproductive peak. Expression of the Vasa gene associated with reproduction was increased after exposure to 10 and 200 ng/L TPT group and decreased at 100 ng/L TPT group. High concentrations of TPT reduced rotifer body length and width and slowed swimming speed. Findings provide a better understanding of the adverse effects of changing TPT concentrations on marine rotifer, by the life cycle parameters, oxidative stress defense mechanisms, expression of a gene related to reproduction, and phenotypic traits. This paper firstly analyzed the reproductive toxicity of environmental levels of organotin compounds to zooplankton, which provided new data support for the comprehensive evaluation of its marine ecological toxicity.


Phenome-wide genetic-correlation analysis and genetically informed causal inference of amyotrophic lateral sclerosis.
Leveraging genome-wide association statistics generated from a large study of amyotrophic lateral sclerosis (ALS; 29,612 cases and 122,656 controls) and UK Biobank (UKB; 4,024 phenotypes, up to 361,194 participants), we conducted a phenome-wide analysis of ALS genetic liability and identified 46 genetically correlated traits, such as fluid intelligence score (rg = - 0.21, p = 1.74 × 10-6), "spending time in pub or social club" (rg = 0.24, p = 2.77 × 10-6), non-work related walking (rg = - 0.25, p = 1.95 × 10-6), college education (rg = - 0.15, p = 7.08 × 10-5), "ever diagnosed with panic attacks (rg = 0.39, p = 4.24 × 10-5), and "self-reported other gastritis including duodenitis" (rg = 0.28, p = 1.4 × 10-3). To assess the putative directionality of these genetic correlations, we conducted a latent causal variable analysis, identifying significant genetic causality proportions (gĉp) linking ALS genetic liability to seven traits. While the genetic component of "self-reported other gastritis including duodenitis" showed a causal effect on ALS (gĉp = 0.50, p = 1.26 × 10-29), the genetic liability to ALS is potentially causal for multiple traits, also including an effect on "ever being diagnosed with panic attacks" (gĉp = 0.79, p = 5.011 × 10-15) and inverse effects on "other leisure/social group activities" (gĉp = 0.66, p = 1 × 10-4) and prospective memory result (gĉp = 0.35, p = 0.005). Our subsequent Mendelian randomization analysis indicated that some of these associations may be due to bidirectional effects. In conclusion, this phenome-wide investigation of ALS polygenic architecture highlights the widespread pleiotropy linking this disorder with several health domains.


Stillbirths, mummies, abortions, and early embryonic death.
Stillbirths, mummies, abortions, and early embryonic death have a substantial impact on the profitability of a farm in both endemic and epidemic conditions. Fetal death is highly dependent on stage of gestation. Implantation occurs around day 14 postmating in sows, and fetal death of an entire litter at this time usually results in a regular return to service. If more than four embryos remain alive, the sow may go on to farrow normally. If fetal death occurs after implantation but before calcification (around 35 days gestation), the sow will either return to estrus at an irregular interval or will farrow a normal litter of reduced size. Although fetuses are normally resorbed prior to calcification, fetal death after that stage of development leads to mummification. Abortions are more directly related to maternal control of pregnancy than fetal failure. Stillbirths are those pigs that appear normal at birth but have lungs that do not float in water. Causes of fetal death can be divided into infectious and noninfectious categories. Infectious causes perhaps are overemphasized but are certainly important in epidemic situations. Some infectious causes of fetal death are primarily systemic maternal pathogens, whereas others may attack the fetus and/or placenta, directly such as PPV, PEV, PRV, SIRS virus, and Leptospira sp. Several other infectious agents have been associated with fetal death. Noninfectious causes of stillborns, mummies, abortions, and early embryonic death are most common in endemic situations. Most stillbirths are due to difficulty at or around parturition, primarily extended duration causing fetal anoxia. Environmental factors such as increased ambient temperature and seasonal infertility affect death rates, as do specific individual sow characteristics, nutritional factors, and toxicities. The causes of stillborns, mummies, abortions, and early embryonic death are often difficult to ascertain, but the potential rewards make investigation efforts worthwhile.


Hurricane Katrina: addictive behavior trends and predictors.
Post-disaster trends in alcohol consumption and cigarette smoking, as well as their predictors, were identified. Methods. Data from cross-sectional and panel surveys of African American adults in New Orleans, Louisiana, were used from before (2004: n = 1,867; 2005: n = 879) and after (2006a: n = 500; 2006b: n = 500) Hurricane Katrina. Alcohol consumption increased significantly from pre- to post-Hurricane Katrina, while cigarette smoking remained constant. In 2006, posttraumatic stress disorder (PTSD) was associated with cigarette smoking, whereas "news attention" and "provided social support" were inversely associated with cigarette smoking. "News attention" was also inversely associated with cigarette smoking frequency, while "neighborliness" was associated with alcohol consumption. In addition, the effects of PTSD on alcohol consumption were moderated by "neighborliness." In the wake of Hurricane Katrina, there were complex predictive processes of addictive behaviors involving PTSD, news information, and social capital-related measures.


Roseimicrobium gellanilyticum gen. nov., sp. nov., a new member of the class Verrucomicrobiae.
The taxonomic properties of strain DC2a-G7(T), a Gram-negative, ovoid to rod-shaped, gellan gum-lysing bacterium, were examined. The 16S rRNA gene sequence similarity showed that DC2a-G7(T) is a member of the phylum Verrucomicrobia and the closest type strain of a species with a validly published name is Verrucomicrobium spinosum DSM 4136(T), with a sequence similarity of 91.2%. In addition to this similarity value lower than 95%, the absence of prostheca, the orangey-red colony colour and the compositions of the major menaquinones and polar lipids also supported the differentiation of this bacterium from the genus Verrucomicrobium. Here, we propose the name Roseimicrobium gellanilyticum gen. nov., sp. nov. for the isolate. The type strain of Roseimicrobium gellanilyticum is DC2a-G7(T) (=NBRC 108606(T)=DSM 25532(T)).


Comparative studies of structure and dynamics of caprine, leporine, ovine, and equine serum albumins.
Serum albumin (SA) is the most prevalent protein found in blood. Human albumin was used as an albumin substitute in hypoalbuminemia pets due to high sequence similarity. SAs from furry animals were also reported to be the major indoor allergens. Sensitizing to one of SAs coupled with high sequence identity can lead to cross-reactive antibodies in allergic individuals. Thus, understanding the structural and dynamic characters of SAs is crucial for not only albumin substitution but also allergen therapy. Herein, Molecular dynamics (MD) simulations were performed to elucidate the structural and dynamic dissimilarity and similarity of economic animals [equine (ESA), caprine (CASA), ovine (OSA), and leporine (LSA)] to albumins from human (HSA), bovine (BSA), porcine (PSA), and pets [cat (FSA) and dog (CSA)]. The aim is to explore the feasibility of HSA substitution and understand how albumins cause the cross-reactivity. Generally, all albumins studied here show the scissoring motion like other mammalian albumins. The uniqueness of each albumin is defined by different sequence identity of domain I. Also, the drug binding affinity of studied albumins differs from HSA, CSA, FSA, BSA, and PSA. Especially, LSA displays the most deviated behavior from the group. So, such albumin may not be suitable for albumin therapy for pets and humans. CASA, OSA, and ESA share similar characteristics, therefore it is possible to use them to monitor the osmotic pressure among their species, but the allergenic response must be seriously considered. An insight obtained here can be useful to develop albumin therapy and understand clinical allergy.Communicated by Ramaswamy H. Sarma.


Purification and properties of glutamyl aminopeptidase from chicken egg-white.
Hydrolytic activities characteristic for different aminopeptidases were detected in the egg-white of unfertilized chicken eggs, and one aminopeptidase was isolated in an electrophoretically homogeneous form. The isolated aminopeptidase preferentially hydrolyzed bonds of alpha-glutamyl residue at the NH(2)-end of synthetic substrates and peptides. The enzyme is a dimer with an M(r) of 320,000 and pI of 4.2. Its optimal pH and temperature are 7.6 and 60 degrees C, respectively. EDTA, amastatin, and N-bromosuccinimide are inhibitors, while Ca2++ and Mn2+ are activators of the enzyme Ca2+ also stabilizes the enzyme. According to the observed properties, the isolated chicken egg-white aminopeptidase belongs to the glutamyl aminopeptidases.


The surgery of middle cerebral artery aneurysms.
Aneurysms of the middle cerebral bifurcation represent an interesting entity among intracranial saccular aneurysms. Their shape, size, situation, and in particular their relation to the middle cerebral trunk and its branches show wide variations. Topographical analysis of the angiograms offers a great deal of interest in planning surgery. Our experience with 289 patients with middle cerebral artery aneurysms operated on since 1977 are presented. Factors such as number of previous haemorrhages, timing of surgery, preoperative condition, major intraoperative bleeding or brain oedema and delayed postoperative deterioration play a major role in the outcome. Others such as severity of the subarachnoid bleed, age, size of the sac seem to have much less influence.


Alkylphenolic contaminants in the diet: Sparus aurata juveniles hepatic response.
A wide range of endocrine disrupter chemicals can mimic steroid hormones causing adverse health effects. Nonylphenol (NP) and t-octhylphenol (t-OP) are man-made alkylphenolic environmental contaminants possessing controversial endocrine disruption properties. This study has investigated the effects of NP and t-OP enriched diets on hepatic tissue and biotransformation activities in the liver. To this aim, sea bream juveniles were fed with commercial diet enriched with three different doses of NP (NP1: 5mg/kg bw, NP2: 50mg/kg bw and NP3: 100mg/kg bw) or t-OP (t-OP1: 5mg/kg bw, t-OP2: 50mg/kg bw and t-OP3: 100mg/kg bw) for 21 days. A significant increase of the hepatosomatic index was observed in NP1 and t-OP1. Alteration of liver morphology was observed in both NP and t-OP exposed juveniles although the most altered endpoints were observed in t-OP2 with 100% of tissue degeneration. Ethoxyresorufin-O-deethylase activity was significantly inhibited by NP and t-OP (p<0.05), while catalase activity was significantly induced, at both doses. A different pattern of protein expression of different isoforms of both vitellogenin and zona radiata protein was evidenced within the treatments. In addition, a significant increase in the abundance of the stress induced heat shock protein 70 gene in the liver of t-OP2 fish and a significant increase in the abundance of the estrogen induced cathepsin D gene in the liver of NP1 and t-OP2 fish, were observed. Finally, estradiol-17β (E2) and testosterone (T) plasma levels and E2/T showed significantly different patterns in NP and t-OP exposed against control fish.


Significance of Lung Weight in Cellular Ex Vivo Lung Perfusion.
Currently, pulmonary edema is evaluated via surgical inspection and palpation in donor lungs, and there is no quantitative standard diagnostic tool for evaluating pulmonary edema in donor procurement and ex vivo lung perfusion (EVLP). The purpose of this study was to investigate the significance of lung weight at the donor hospital and lung weight during EVLP as a complementary parameter of transplant suitability in EVLP. Twenty-one of rejected human lungs were perfused in cellular EVLP. Transplant suitability was evaluated at 2 h as per standard criteria of Lund-protocol EVLP. Lung weight at donor hospital was significantly correlated with PaO2/FiO2 (P/F) ratio in EVLP (r = -0.44). There was a significant difference in lung weight at donor hospital between suitable cases (n = 13) and nonsuitable cases (n = 8). Light lung group (lung weight at donor hospital < 1280 g; n = 17) was suitable for transplant in 76%, whereas none of heavy lung group (lung weight at donor hospital ≥ 1280 g; n = 4) was suitable (P < 0.05). Lung weight at 2 h and lung weight change during EVLP were significantly associated with P/F ratio at 2 h and transplant suitability (P < 0.05, each). Our findings demonstrate that lung weight at donor hospital, lung weight change, and lung weight at 2 h of EVLP might be a predictor of P/F ratio and transplant suitability in cellular EVLP.


The inhibition mechanism of the texture deterioration of tilapia fillets during partial freezing after treatment with polyphenols.
The inhibition mechanism of the texture deterioration of tilapia fillets after treatment with polyphenols during partial freezing for 49 days was studied. Carnosic acid (CA), procyanidin (PA), quercetin (QE), and resveratrol (RSV) treatments had significantly higher hardness values (over 230 g) than the control group (183 g) on day 49 (P < 0.05). Polyphenol treatments were effective in delaying the protein degradation, lipid oxidation and spoilage microbe growth. Moreover, the kinetic model showed that the predicted shelf life of tilapia fillets treated with PA (102 d) was extended by 25 d compared to the control group (77 d). It was the proposed possible mechanism that polyphenols comprehensively maintained the protein conformation (increased hydrogen bonds and decreased disulfide bonds) and retarded protein denaturation and degradation, protecting the texture of the fillets. Therefore, polyphenols can be used to maintain texture and extend the shelf life of tilapia fillets during partial freezing.


Clinical features, treatment methods, and evolution of birdshot chorioretinopathy in 5 different families.
To report familial cases of birdshot chorioretinopathy (BSCR). Retrospective, observational case series. Five families with 2 members in each (10 patients) with BSCR were included in this case series from a cohort of 225 patients followed up for BSCR. A review of medical and angiographic records of familial cases of BSCR was performed. We described and compared in each family the histocompatibility leukocyte antigen (HLA) typing, age at onset, ethnic group, clinical features, fluorescein and indocyanine green angiography results, evolution of disease, and treatment used with efficiency. HLA-A29 and HLA-B44 results were positive in 100% of patients tested. Mean age at onset was 46.5 years. All patients were White. Corticosteroids were required in 7 patients, and 3 patients had no treatment because of mild or moderate lesions. Cyclosporine A was administered in 2 patients from the same family. Period of follow-up ranged from 1 to 32 years (median, 7 years). Familial forms of BSCR remain rare and do not justify systematic examination in relatives of patients with BSCR.


Effects of soil amendments on fractions and stability of soil organic matter in saline-alkaline paddy.
Soil amelioration is an effective practice to alleviate the adverse effects of soil salinization. However, increasing the fertility of salt-affected soils has been challenging, particularly in coastal saline-alkaline paddy soils. Here, we carried out a 45-day incubation experiment to evaluate the impacts of soil amendments on fractions and stability of soil organic matter (SOM) in a saline-alkaline paddy. The experiment simulates the flooding-draining practice and consists of CaCO3, gypsum and biochar amendments using different fertility soils. We measured dissolved organic carbon (DOC) and nitrogen (DON) in supernatant liquids, water-soluble cations, water extractable organic carbon (WEOC) and nitrogen (WEON), and microbial biomass carbon (MBC) and nitrogen (MBN) in soils after the incubation. Results showed that water soluble sodium (Na+) was significantly decreased under all amendments (by 17%-32%), except in high fertility soil. We found a significant decrease in DOC (by 36%-47%) under gypsum treatment, but in DON (by 18%-59%) under biochar treatment. However, there was no significant effect on DOC or DON under CaCO3 treatment. Gypsum treatment led to decreased WEOC content (by 0.067%-5.4%), but increased MBC (by 0.16%-44%) and MBN (by 8.3%-37%) in all soils. Biochar treatment caused a decrease in the ratios of WEOC to soil organic carbon (SOC) and WEON to total nitrogen (TN), and an increase in MBC:SOC and MBN:TN ratios. These results suggest that gypsum and biochar amendments can enhance SOM stability in the saline-alkaline paddy. However, SOM stability was not enhanced under CaCO3 treatment, probably due to the presence of a large amount of Na+ in these soils. Our study highlights that soil amelioration has different effects on soil carbon and nitrogen cycles in the saline-alkaline paddy soils, which is associated with water-logged condition.


Chronic exposure to submicromolar arsenite promotes the migration of human esophageal Het1A cells induced by heparin-binding EGF-like growth factor.
Chronic arsenic exposure causes cancers in multiple organs in humans. However, the mechanisms underlying arsenic-induced carcinogenesis remain obscure. Here, we examined whether chronic arsenite (As(III)) exposure promotes cell migration induced by heparin-binding EGF-like growth factor (HB-EGF) in human esophageal immortalized Het1A cells. When Het1A cells were exposed to 0.5 μM As(III) for 4 months, HB-EGF-induced migration was enhanced in As(III)-exposed Het1A cells compared to controls. To elucidate the mechanisms underlying the promotion of HB-EGF-induced migration by chronic exposure to As(III), we compared ERK phosphorylation between As(III)-exposed and control Het1A cells and found that HB-EGF-induced ERK phosphorylation was enhanced in the As(III)-exposed cells. We next measured mRNA levels of 88 genes related to cell cycle regulation. The results showed elevated cyclin D1 mRNA levels in As(III)-exposed Het1A cells. The inhibitors of ERK and cyclin D/Cdk4 markedly suppressed HB-EGF-induced upregulation of cyclin D1 and the migration of Het1A cells, respectively, suggesting that cyclin D1 is located downstream of ERK and is required for HB-EGF-induced migration of Het1A cells. Collectively, these findings indicate that the promotion of HB-EGF-induced migration of Het1A cells chronically exposed to submicromolar As(III) might be caused by increased expression of cyclin D1 mediated by enhanced activation of the ERK pathway.


(5R)-5-hydroxytriptolide (LLDT-8), a novel triptolide derivative, prevents experimental autoimmune encephalomyelitis via inhibiting T cell activation.
A novel triptolide derivative (5R)-5-hydroxytriptolide (LLDT-8) has been shown to have potent immunosuppressive activities. Here LLDT-8 was evaluated in experimental autoimmune encephalomyelitis (EAE), the model of multiple sclerosis (MS). LLDT-8 reduced the incidence and severity of EAE, which was associated with the inhibition of the MOG 35-55 lymphocyte recall response, anti-MOG 35-55 T cell responses, interleukin (IL)-2 and interferon (IFN)-gamma production. In vitro, LLDT-8 inhibited primary T cells proliferation, division, IL-2 and IFN-gamma production stimulated with anti-CD3/28. These findings highlight the fact that LLDT-8 prevents EAE by suppressing T cell proliferation and activation, with a potential for treatment of MS.


How minimally interrupted direct oral anticoagulants affect intraprocedural anticoagulation during atrial fibrillation ablation? Insights from a Japanese single-center retrospective study.
Data are still lacking regarding the effects of minimally interrupted direct oral anticoagulants (MID) on the intensity of intraprocedural anticoagulation of atrial fibrillation (AF) ablation. A total of consecutive 269 patients who undergone AF ablation were eligible for the study. All oral anticoagulants (OACs) were discontinued just one dose before the procedure except warfarin. We assessed the total required dose of UFH and time-to-target ACT > 300 seconds (TTA) for each of direct oral anticoagulant (DOAC) groups compared with the uninterrupted warfarin group. DOACs were used in 86% of the patients in the present study (dabigatran group (DG)-17%, rivaroxaban group (RG)-30%, apixaban group (AG)-29%, and edoxaban group (EG)-10%). DG and EG used comparable dose of total UFH to WG (WG vs DG; 206 ± 53 U/kg vs 231 ± 63 U/kg; P = .664, vs EG; 239 ± 67 U/kg; P = .335), while RG and AG required higher total UFH (WG vs RG; 206 ± 53 U/kg vs 270 ± 63 U/kg; P < .001, vs AG; 263 ± 62 U/kg; P < .001). TTA was significantly longer in RG (RG:73 ± 28 minutes vs WG:51 ± 25 minutes; P = .001), AG (AG:64 ± 26 minutes vs WG:51 ± 25 minutes; P = .02), and EG (EG:67 ± 34 minutes vs WG:51 ± 25 minutes; P = .02) than WG, whereas DG was comparable to WG (DG:51 ± 29 minutes vs WG:51 ± 25 minutes; P = NS). Especially, only RG demonstrated significantly slower increase in ACT than WG (P = .013). In the multivariate analysis, warfarin or dabigatran use, age > 75 years, and body weight < 60 kg are clinical predictors for achieving TTA within 60 minutes (TTA-60). MID-dabigatran was comparable to uninterrupted warfarin, whereas MID-factor Xa inhibitors were not. MID is a feasible protocol; however, we should be aware of its effect on the intraprocedural anticoagulation and differences among DOACs in the responsiveness to heparin.


Toxicity of triorganotin compounds: comparative in vivo studies with a series of trialkyltin compounds and triphenyltin chloride in male rats.
In 2-week feeding studies, a series of trialkyltin chlorides and triphenyltin chloride were fed to male weanling rats at different dietary concentrations to evaluate their toxic effects, especially on the brains and the lymphoid organs, thymus and spleen. The lower trialkyltin homologs, trimethyltin chloride (TMTC) and triethyltin chloride (TETC), were neurotoxic, causing neuronal degradation and cerebral edema, respectively, at dietary concentrations of 15 ppm. The intermediate homologs, tri-n-propyltin chloride (TPTC) and tri-n-butyltin chloride (TBTC), and the aromatic compound, triphenyltin chloride (TPhTC), caused a dose-related reduction of thymus weight. At a dietary concentration of 150 ppm decreases in thymus weight to 53, 39, and 81% of controls were found following treatment with TPTC, TBTC, and TPhTC, respectively. Microscopically, thymus atrophy was associated with a lymphocyte depletion in the thymic cortex. Only 16% of the total number of nucleated thymocytes could be isolated from rats fed 150 ppm TBTC. These effects were completely reversed within 2 weeks. Slight thymus atrophy was observed after feeding a relatively high dose of 150 mg tri-n-hexyltin chloride (THTC)/kg diet, whereas tri-n-octyltin chloride (TOTC) was ineffective. A dose-related decrease in spleen weight was noticed after 2 weeks feeding of TPTC, TBTC, and TPhTC. Liver weights were increased in rats fed TBTC, THTC, and TPhTC for 2 weeks. Nevertheless, no enlarged livers and normal spleen weights were found upon feeding 100 ppm TPTC or TBTC for 4 weeks, whereas thymus weight was severely decreased. Therefore, atrophy of the thymus was considered to be the predominant effect of the intermediate trialkyltins (TPTC, TBTC). From this study it is concluded that the lower trialkyltins (TMTC, TETC) are essentially neurotoxic, the intermediate trialkytins (TPTC, TBTC) and triphenyltin are primarily immunotoxic, and the higher homologs (THTC, TOTC) are only slightly toxic or not toxic at all.


Global analysis of steady-state polarized fluorescence spectra using trilinear curve resolution.
Global analysis using trilinear curve resolution is described and shown to be a powerful method for the resolution of polarized fluorescence data arrays, in which the measured fluorescence intensity is a separable function of polarization orientation, excitation wavelength, and emission wavelength. This methodology is applicable to mixtures the components of which have linearly independent excitation and emission spectra and distinct anisotropies. Normalized excitation and emission spectra of individual components can be uniquely determined without prior assumptions concerning spectral shapes (e.g., sum of Gaussians) and without the uncertainties inherent in bilinear techniques such as principal component analysis or factor analysis. The normalized excitation and emission vectors are combined with the total absorption spectrum of the multicomponent mixture to compute absolute absorption and emission spectra. The precision of this methodology is evaluated as a function of noise, overlap, relative intensity, and anisotropy difference between components using simulated mixtures of the DNA bases. The ability of this method to extract individual spectra from steady-state fluorescence data arrays is illustrated for mixtures containing two and three components.


Ribosomal Protein S27/Metallopanstimulin-1 (RPS27) in Glioma-A New Disease Biomarker?
Despite its significant overexpression in several malignant neoplasms, the expression of RPS27 in the central nervous system (CNS) is widely unknown. We identified the cell types expressing RPS27 in the CNS under normal and disease conditions. We acquired specimens of healthy brain (NB), adult pilocytic astrocytoma (PA) World Health Organization (WHO) grade I, anaplastic PA WHO grade III, gliomas WHO grade II/III with or without isocitrate dehydrogenase (IDH) mutation, and glioblastoma multiforme (GBM). RPS27 protein expression was examined by immunohistochemistry and double-fluorescence staining and its mRNA expression quantified by RT-PCR. Patients' clinical and tumor characteristics were collected retrospectively. RPS27 protein was specifically expressed in tumor cells and neurons, but not in healthy astrocytes. In tumor tissue, most macrophages were positive, while this was rarely the case in inflamed tissue. Compared to NB, RPS27 mRNA was in mean 6.2- and 8.8-fold enhanced in gliomas WHO grade II/III with (p < 0.01) and without IDH mutation (p = 0.01), respectively. GBM displayed a 4.6-fold increased mean expression (p = 0.02). Although RPS27 expression levels did not affect the patients' survival, their association with tumor cells and tumor-associated macrophages provides a rationale for a future investigation of a potential function during gliomagenesis and tumor immune response.


Systemic lupus erythematosus associated with ANCA-associated vasculitis: an overlapping syndrome?
Systemic lupus erythematosus (SLE) and small-sized vessel vasculitis are usually two distinguishable autoimmune diseases. However, a vasculitis may be found in the course SLE but rarely corresponds to an ANCA-associated vasculitis (AAV). We report four cases of de novo SLE associated with AAV, our aim being to discuss the clinical significance of this association. We included four patients fulfilling the criteria for both SLE and AAV and followed in two different university hospitals between 1996 and 2009. In light of a 20-year literature review (25 described clinical cases), we discussed the etiopathogeny of such an association. All patients presented a severe renal involvement (creatininemia ranging from 120 to 370 μmol/l) and thrombopenia (ranging from 45,000 to 137,000 platelets/mm(3)). The other main clinical symptoms were arthritis (n = 3), serositis (n = 2) and intra-alveolar hemorrhage (n = 2). An inflammatory syndrome was noticed at diagnosis in all cases. ANCAs were MPO-ANCAs in all cases. Two out of these four patients were also diagnosed with antiphospholipid syndrome. The frequency of this association seems not fortuitous. Although the etiopathogenic mechanisms of such an association remain to be more precisely described, several clinical, histological and immunological features support the hypothesis of the existence of a SLE-AAV overlapping syndrome. Moreover, clinicians must be aware of such an overlapping syndrome, notably because its initial presentation can be very severe.


Requirement for nerve growth factor in the development of myelinated nociceptors in vivo.
In adult animals, sensory neurons innervating the skin are phenotypically diverse. We have now investigated whether nerve growth factor (NGF) has a physiological role in the development of this diversity. We gave antisera against NGF to rats from postnatal day 1 (PND 1) to adulthood (5 weeks). We found a virtually complete depletion of high threshold mechanoreceptors conducting in the A delta range (2-13 ms-1) in the sural nerve. This afferent type, normally present in large numbers, appeared to have been replaced by D-hair afferents, sensitive mechanoreceptors which normally are relatively rare. NGF deprivation had this effect only in early postnatal life; treatment from postnatal day 14 to adulthood had no effect. We conclude that the presence of NGF postnatally in skin is necessary for the proper phenotypic development of A delta cutaneous nociceptors.


Neuro-glial degeneration in Status Epilepticus: Exploring the role of serum levels of Neurofilament light chains and S100B as prognostic biomarkers for short-term functional outcome.
The last ILAE definition of Status Epilepticus (SE) highlights that the persistence of the epileptic activity per se could determine irreversible brain damages that could be responsible for long-term consequences. The measurement of neuro-glial injury biomarkers could help in the identification of those patients who will eventually develop short- and long-term consequences of SE. At present none of the already studied biomarkers has been validated to be used in everyday clinical practice. In this study, we explore the role of NfL and S100B as a prognostic biomarkers to identify patients who will develop short-term disability after an episode of SE. This is a retrospective assessment of the serum levels of both NfL and S100B in a cohort of 87 adult patients with SE prospectively collected in our SE registry (Modena Status Epilepticus Registry - MoSER -) at Baggiovara Civil Hospital (Modena, Italy). All samples were acquired during SE within 72 hours of SE diagnosis. The comparison groups were: healthy controls (HC, n = 27) and patients with epilepsy (PWE, n = 30). Demographic, clinical, and therapeutical information and thirty-days follow-up information regarding disability development were acquired for every included patient and analyzed in relation to NfL and S100B values. Serum levels of NfL were significantly higher in SE compared to those of PWE (median 7.35 pg/ml, IQR 6.4, p < 0.001) and HC (median 6.57 pg/ml, IQR 9.1, p < 0.001); S100B serum levels were higher in SE (median 0.11 ug/L, IQR 0.18) compared to PWE (median 0.03 ug/L, IQR 0.03, p < 0.001) and HC (median 0.02 ug/L, IQR 0.008, p < 0.001). However, only NfL serum levels were found to be an independent predictor of 30 days functional outcome whereas S100B levels did not. Our results suggest that NfL measurement in serum during SE could help predict the short-term functional outcome. This paper was presented at the 8th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures held in September 2022.


The way toward adulthood for females with nonclassic congenital adrenal hyperplasia.
Females with NC21OHD may present as asymptomatic or develop a wide range of androgen excess expression. Clinical manifestations may become evident in childhood and adolescence and include premature pubarche, precocious puberty, acne, hirsutism, and menstrual disorders or present later in life as oligo-ovulation and infertility. Glucocorticoids have been the mainstay of treatment as they regulate excess androgen expression by dampening ACTH activation. Their use requires a careful dose monitoring to avoid overtreatment and subsequently the risk of obesity, type 2 diabetes, dyslipidemia, hypertension, and osteoporosis. Women with NC21OHD need regular follow up throughout their life in order to overcome the physical and psychological burden of hyperandrogenism.


Triptolide reduces prostate size and androgen level on testosterone-induced benign prostatic hyperplasia in Sprague Dawley rats.
Benign prostatic hyperplasia (BPH) is an age-related disease of unknown etiology, characterized by prostatic enlargement coincident with distinct alterations in tissue histology. In the present study, we investigated whether triptolide can prevent testosterone-induced prostatic hyperplasia in rats. Castration was performed via the scrotal route after urethane aesthesia. BPH was induced in experimental groups by daily subcutaneous injections of testosterone propionate (TP) for two weeks. Triptolide was administered daily by oral gavage at a dose of 100 and 50 μg·kg-1 for 2 weeks, along with the TP injections. On day 14, the animals were humanely killed by cervical dislocation after aesthesia. Prostates were excised, weighed, and used for histological studies. Testosterone and dihydrotestosterone (DHT) levels in serum and prostate were measured. The results showed that triptolide significantly reduced the prostate weight, and the testosterone and DHT levels in both the serum and prostate. Histopathological examination also showed that triptolide treatment suppressed TP-induced prostatic hyperplasia. In conclusion, triptolide effectively inhibits the development of BPH induced by testosterone in a rat model.


The interaction of ASIC1a and ERS mediates nerve cell apoptosis induced by insulin deficiency.
Diabetes-related brain complications are the most serious complications of terminal diabetes. The increasing evidence have showed that the predisposing factor is not only hyperglycemia, but also insulin deficiency. In this study, we demonstrated that insulin deficiency was involved in the apoptosis of nerve cells, and it was related to the interaction between acid-sensitive ion channel 1a (ASIC1a) and endoplasmic reticulum stress (ERS). By silencing C/EBP homologous protein (CHOP) and ASIC1a, the pro-apoptotic effect of insulin deficiency on NS20y cells was relieved. Further research found that the binding of CHOP and C/EBPα was increased in the nucleus of cells cultured without insulin, and C/EBPα was competitively inhibited as a negative regulator of ASIC1a, which further increased the ERS and lead to neuronal apoptosis. In summary, ERS and ASIC1a play an important role in neurological damage caused by insulin deficiency. Our finding may lead to new ideas and treatment of diabetes-related brain complications.


Intermittent coronary sinus occlusion complicating coronary sinus cannulation during coronary artery bypass operation.
Coronary sinus (CS) thrombosis is a rare event, usually complicating invasive procedures that cause trauma to the CS. Based on anecdotal case reports, this pathology is frequently associated with serious complications and is commonly fatal. We describe a case of intermittent CS thrombosis resulting from CS cannulation during coronary artery bypass grafting operation. This complication was further complicated by myocardial infarction, left ventricular free wall rupture, and pseudoaneurysm formation. The characteristic echocardiographic findings and a review of the literature on this rare complication are presented.


Clinical and biochemical short-term effects of hyperbaric oxygen therapy on SARS-Cov-2+ hospitalized patients with hypoxemic respiratory failure.
Hyperbaric oxygen therapy (HBOT) has been proposed to address COVID-19- associated respiratory failure. However, its biochemical effects are poorly known. 50 patients with hypoxemic COVID-19 pneumonia were divided into C group (standard care) and H group (standard care plus HBOT). Blood was obtained at t = 0 and t = 5 days. Oxygen saturation (O2 Sat) was followed up. White blood cell (WC) count, lymphocytes (L) and platelets (P) and serum analysis (glucose, urea, creatinine, sodium, potassium, ferritin, D dimer, LDH and CRP) were carried out. Plasma levels of sVCAM, sICAM, sPselectin, SAA and MPO, and of cytokines (IL-1β, IL-1RA, IL-6, TNFα, IFNα, IFNγ, IL-15, VEGF, MIP1α, IL-12p70, IL-2 and IP-10) were measured by multiplex assays. Angiotensin Converting Enzyme 2 (ACE-2) levels were determined by ELISA. The average basal O2 Sat was 85 ± 3%. The days needed to reach O2 Sat >90% were: H: 3 ± 1 and C: 5 ± 1 (P < 0,01). At term, H increased WC, L and P counts (all, H vs C: P < 0,01). Also, H diminished D dimer levels (H vs C, P < 0,001) and LDH concentration (H vs C, P < 0.01]. At term, H showed lower levels of sVCAM, sPselectin and SAA than C with respect to basal values (H vs C: ΔsVCAM: P < 0,01; ΔsPselectin: P < 0,05; ΔSAA: P < 0,01). Similarly, H showed diminished levels of TNFα (ΔTNFα: P < 0,05) and increased levels of IL-1RA and VEGF than C respect to basal values (H vs C: ΔIL-1RA and ΔVEGF: P < 0,05). Patients underwent HBOT improved O2 Sat with lower levels of severity markers (WC and platelets count, D dimer, LDH, SAA). Moreover, HBOT reduced proinflammatory agents (sVCAM, sPselectin, TNFα) and increased anti-inflammatory and pro-angiogenic ones (IL-1RA and VEGF).


Calcium-activated neutral proteinase of human brain: subunit structure and enzymatic properties of multiple molecular forms.
Calcium-activated neutral proteinase (CANP) was purified 2,625-fold from postmortem human cerebral cortex by a procedure involving chromatography on diethylaminoethyl (DEAE)-cellulose, phenyl-Sepharose, Ultrogel AcA-44, and DEAE-Biogel A. The major active form of CANP exhibited a molecular weight of 94-100 kilodaltons (Kd) by gel filtration on Sephacryl 300 and consisted of 78-Kd and 27-Kd subunits. Two-dimensional gel electrophoresis resolved the small subunit into two molecular species with different isoelectric points. CANP degraded most human cytoskeletal proteins but was particularly active toward fodrin and the neurofilament protein subunits (145 Kd greater than 200 Kd greater than 70 Kd). The enzyme required 175 microM Ca2+ for half-maximal activation and 2 mM Ca2+ for optimal activity toward [methyl-14C]azocasein. Other divalent metal ions were poor activators of the enzyme, and some, including copper, lead, and zinc, strongly inhibited the enzyme. Aluminum, a neurotoxic ion that induces neurofilament accumulations in mammalian brain, inhibited the enzyme 47% at 1 mM and 100% at 5 mM. A second CANP form lacking the 27-Kd subunit was partially resolved from the 100-Kd heterodimer during DEAE-Biogel A chromatography. The 78-Kd monomer exhibited the same specific activity, calcium ion requirement, pH optimum, and specificity for cytoskeletal proteins as the 100-Kd heterodimer, suggesting that the 27-Kd subunit is not essential for the major catalytic properties of the enzyme. The rapid autolysis of the 27-Kd subunit to a 18-Kd intermediate when CANP is exposed to calcium may explain differences between our results and previous reports, which describe brain mCANP in other species as a 76-80-Kd monomer or a heterodimer containing 76-80-Kd and 17-20-Kd subunits. The similarity of the 100-Kd human brain CANP to CANPs in nonneural tissues indicates that the heterodimeric form is relatively conserved among various tissues and species.


Efficacy of six month neoadjuvant endocrine therapy in postmenopausal, hormone receptor-positive breast cancer patients--a phase II trial.
Neoadjuvant hormonal therapy (NHT) is playing an increasing role in the clinical management of breast cancer (BC) and may improve surgical outcomes for postmenopausal, oestrogen receptor (ER)-positive BC patients. However, there is currently no consensus on the optimal duration of NHT before surgery. Here, we present the outcomes of the TEAM IIA trial, a multicentre, phase II trial investigating the efficacy of six months of neoadjuvant exemestane in postmenopausal, strong ER-positive (ER+, ⩾50%) BC patients. 102 patients (stage T2-T4ac) were included in the study after exclusion of ineligible patients. Primary end-point was clinical response at 3 and 6 months as measured by palpation. Secondary end-point was radiological response as measured by magnetic resonance imaging (MRI), mammography and/or ultrasound. Linear mixed models (95% confidence interval (CI)) were used to compare changes in mean tumour size (in mm) between baseline, 3 and 6 months after the start of endocrine therapy. Conversion rates from mastectomy to breast conserving surgery (BCS) were evaluated. Median age of all patients was 72 years (range 53-88). Overall response rate by clinical palpation was 64.5% in all patients with a final palpation measurement. Four patients had clinically progressive disease. 63 patients had both 3-month and >3-month palpation measurements. Overall response was 58.7% at 3 months and 68.3% at final palpation (>3 months). Mean tumour size by clinical palpation at T=0 was 39.1mm (95% CI 34.8-43.4mm), and decreased to 23.0mm (95% CI 18.7-27.2mm) and 16.7 mm (95% CI 12.6-20.8) at T=3 and T>3 months, respectively (p=0.001). Final radiological response rates at the end of treatment for MRI (n=37), ultrasound (n=77) and mammography (n=56) were 70.3%, 41.6% and 48.2%, respectively. Feasibility of BCS improved from 61.8% to 70.6% (McNemar p=0.012). 6 months of neoadjuvant exemestane therapy helps reduce mean tumour size further in strongly ER-positive BC patients without significant side-effects compared to 3 months. Nevertheless, some patients still experience disease progression under exemestane. Feasibility of breast conservation rates improved by almost 10%.


Complications of percutaneously inserted central venous catheters in Japanese neonates.
To determine institutional policies concerning percutaneously inserted central venous catheter (PICC) utilization and also frequencies of complications such as pericardial effusion (PCE), cardiac tamponade (CT), pleural effusion, ascites, venous thrombosis, and catheter removal difficulties. Nationwide postal questionnaire survey was carried out that included institutional policies on PICC and numbers of complications recorded from January 1999 to December 2003. A total of 98 replies were received from 193 neonatal intensive care units (NICU) in Japan. As a catheter tip location, positions outside of the heart were highly preferred, while only 9% accepted a right atrial position. Twenty-eight cases of PCE or CT were reported, representing an estimated frequency of 0.07-0.11% of PICC insertions. Pleural effusion/ascites and removal difficulties (36 and 35 cases, respectively) were encountered in approximately 0.09-0.14% of insertions. Frequency of PCE/CT appeared comparable to previously reported occurrences. Also, pleural effusion/ascites and removal difficulty appeared to be rare complications.


Experimental radiotherapy of receptor-positive human prostate adenocarcinoma with 188Re-RC-160, a directly-radiolabeled somatostatin analogue.
The therapeutic potential of the somatostatin analogue RC-160 radiolabeled with 188Re was evaluated in nude mice bearing xenografts of human prostate adenocarcinoma. 188Re-RC-160 was selectively retained in both DU-145 and PC-3 tumors following direct intra-tumor injection at all time points examined (2, 6 and 24 hr post-injection). Unbound 188Re-RC-160 was rapidly excreted via the hepatobiliary system and, with the exception of the gastrointestinal tract, very little normal organ uptake was found at any time point examined. Negative control compounds, 188Re-perrhenate and 188Re-mercaptoacetyl-triglycine (188Re-MAG3), were essentially washed out of the tumor by 6 hr post-injection and were rapidly excreted through the kidneys. 131I-RC-160, used as reference compound, had a biodistribution in tumor-bearing animals similar to that of 188Re-RC-160. In PC-3 xenografts, 188Re-RC-160 gave a dose-dependent therapeutic response (stasis or regression) even in animals with relatively large tumor masses (greater than 600 mm3), whereas the macro-aggregated form of 188Re-RC-160 did not. Long-term studies with 188Re-RC-160 demonstrated a protracted reduction of tumor volume and a positive effect on animal survival. Neither RC-160 by itself nor a 188Re-labeled peptide, unrelated to somatostatin (PA-22-2, a laminin peptide), demonstrated the reduction in tumor mass observed with 188Re-RC-160. 188Re-RC-160 shows potential as a new clinical agent for treatment of somatostatin-receptor-positive cancers.


Nitric oxide synthase in chick embryo retina during development.
High levels of nitric oxide synthase were found in the early stages of developing chick embryo retina. The enzyme activity sharply decreased up to 13-day-old chick embryo retina, when the level of the last embryonic day was reached. The results show that nitric oxide is synthesized in chick embryo retina prior to synaptogenesis. The incubation of chick embryo retinas in presence of NMDA increased the synthesis of nitric oxide, thus, the appearance of nitric oxide production before the synaptogenesis in the retina as well as in the brain may be considered as signal for the development and shaping of neuronal and non-neuronal cells.


A pilot study into a possible relationship between diet and stuttering.
There are theoretical and empirical reasons to consider a potential role for copper metabolism in the brain in how it could influence stuttering. However, a link between stuttering and dietary intake has never been researched in a systematic way. This pilot study therefore aimed to explore a possible association between ingested amounts of copper and thiamine (vitamin B1) with stuttering frequency using a double blind cross-over longitudinal paradigm. 19 adults who stutter between 20 and 51 years old filled out an online survey for 9 consecutive weeks. The survey consisted of self-assessed fluency and mood state scales, as well as food journals. After 4 weeks, the participants consumed either copper or thiamine supplements for 2 weeks, followed by a 1-week washout period, and another period of two weeks taking the other supplement. Formal speech assessments were done pre/post baseline and at the end of each supplement intake. Participants were not informed about the nature of the supplements during the experiment and the investigators were blinded to the order of the supplements. The results demonstrated that copper and thiamine had no measurable effect on the amount of stuttering (self and formal assessments) but there was a moderate, significant correlation between mood state and fluency. The findings do not support notions of dietary influences of ingested copper or thiamine on stuttering but do provide modest support for a relationship between variations in stuttering and self-perceived anxiety.


Localization of knee joint cartilage pathology by multichannel vibroarthrography.
This paper proposes non-invasive techniques to localize sound or vibroarthrographic (VAG) signal sources in human knee joints. VAG signals from normal subjects, patients who subsequently underwent arthroscopy, and cadavers with arthroscopically-created lesions, obtained by stimulation with a finger tap over the mid-patella and swinging movement of the leg, were analyzed for time delays using cross-correlation functions for source localization. Correct results were obtained for 13 of the 14 subjects tested by finger stimulation, and for 11 of the 12 subjects whose VAG signals during swinging movement were analyzed. The techniques could be valuable in the diagnosis and treatment of knee pathology before and after joint surgery or drug therapy.


Volumetric evaluation of blood flow in normal renal arteries with a Doppler flow wire: a feasibility study.
To evaluate the feasibility of direct intravascular determination of renal artery (RA) blood flow with a Doppler probetipped guide wire. Potential renal donors (n = 10) with normal RAs (n = 23) underwent evaluation of RA blood flow velocity with use of a 0.018-inch, 12-MHz Doppler guide wire. The RA average peak velocity (APV) was obtained with the flow wire. RA diameter was obtained from the filmed images with magnification corrected to a known standard or by a computerized quantification program. These data were used to determine the vessel's cross-sectional area (CSA). The right and left RA APV, CSA, and blood flow differed insignificantly within the group and averaged 9.7 and 9.0 cm/sec (P = .43), 0.417 and 0.357 cm2 (P = .22), and 382 and 370 mL/min (P = .43), respectively. However, in individuals, the RA CSA and total volumetric blood flow varied by a mean of 29% (range, 4%-56%) and 50% (range, 19%-128%), respectively. This study demonstrates that direct intravascular determination of RA blood flow with a Doppler-tipped wire is both feasible and relatively uncomplicated. Results indicate that blood flow can vary significantly, both in kidneys within the same individual and from person to person. The Doppler wire may facilitate measurements of RA blood flow during endoluminal interventions and help determine an optimal endpoint for these procedures.


Identification of a new sucrose transporter in rye-grass (LpSUT2): effect of defoliation and putative fructose sensing.
Rye-grass fast regrowth after defoliation results from an efficient mobilization of C reserves which are transported as sucrose towards regrowing leaves, and which can be supported by one or several sucrose transporters (SUTs) like LpSUT1. Therefore, our objectives were to isolate, identify, characterize and immunolocalize such sucrose transporters. A protein (LpSUT2) showing a twelve spanning trans-membrane domain, extended N terminal and internal cytoplasmic loop, and kinetic properties consistent with well-known sucrose transporters, was isolated and successfully characterized. Along with LpSUT1, it was mainly localized in mesophyll cells of leaf sheaths and elongating leaf bases. These transporters were also found in parenchyma bundle sheath (PBS) cells but they were not detected in the sieve element/companion cell complex of the phloem. Unlike LpSUT1 transcript levels which increased as a response to defoliation in source and sink tissues, LpSUT2 transcript levels were unaffected by defoliation and weakly expressed. Interestingly, sucrose transport by LpSUT2 was inhibited by fructose. LpSUT1 and LpSUT2 appeared to have different functions. LpSUT1 is proposed to play a key role in C storage and mobilization by allowing sucrose transport between PBS and mesophyll cells, depending on the plant C status. LpSUT2 could be involved in sucrose/fructose sensing at sub-cellular level.


Meta-analysis and systematic review: Prevalence, graft failure, mortality, and post-operative thrombosis in liver transplant recipients with pre-operative portal vein thrombosis.
This study seeks to evaluate the association between pre-transplant portal vein thrombosis (PVT) and overall survival, graft failure, waitlist mortality, and post-operative PVT after liver transplantation. A conventional pairwise meta-analysis between patients with and without pre-transplant PVT was conducted using hazard ratios or odds ratios where appropriate. Prevalence of preoperative PVT was 11.6% (CI 9.70-13.7%). Pre-operative PVT was associated with increased overall mortality (HR 1.45, 95% CI 1.27-1.65) and graft loss (HR 1.58, 95% CI 1.34-1.85). In particular, grade 3 (HR 1.59, 95% CI 1.00-2.51) and 4 (HR 2.24, 95% CI 1.45-3.45) PVT significantly increased mortality, but not grade 1 or 2 PVT. Patients with PVT receiving living donor (HR 1.54, 95% CI 1.24-1.91) and deceased donor (HR 1.52, 95% CI 1.21-1.92) liver transplantation had increased mortality, with no significant difference between transplant types (P = .13). Furthermore, pre-transplant PVT was associated with higher occurrence of post-transplant PVT (OR 5.06, 95% CI 3.89-6.57). Waitlist mortality was not significantly increased in patients with pre-transplant PVT. Graft failure, mortality, and post-operative PVT are more common in pre-transplant PVT patients, especially in grade 3 or 4 PVT. Prophylactic anticoagulation can be considered to reduce re-thrombosis and improve survival.


[Effects of Obstetric Analgesia with Systemic Opioids on the Newborn - A Review].
Three-quarters of all women receive analgesia during labor. There are regional and systemic analgesia procedures available. In this review, we investigate the impact of obstetric analgesia using systemic opioids on neonatal outcomes. We searched the PubMed and Cochrane Library databases using the following search terms: "meptazinol", "meptide", "analgesia", "painkiller", "pain reliever", "obstetrics", "labor", "labour", "delivery", "neonate", "newborn", "child", "baby", "infant", "fetus", "fetal", "opioid" and "opiate" as well as performed an additional MeSH Terms search in PubMed. Of 355 potentially relevant studies, we included 23 studies in this review. The studies varied widely in quality, sample size, and outcome criteria. Neonatal outcome was often only a secondary endpoint. Rarely were significant differences related to neonatal outcome reported between the different systemic opioids or compared with control groups. Twelve studies compared neonatal APGAR scores between treatment groups, with ten (83%) of these studies showing no differences. In summary, we assess the evidence as limited and ambiguous as to whether systemic obstetric opioid therapy negatively affects the newborn. Studies regarding the long-term outcome of the newborns are lacking. A statement regarding the necessity of postnatal monitoring of newborns after maternal obstetric opioid therapy cannot be concluded. Further studies, ideally with a prospective study design and control group, should be considered.


Older migrants reflecting on aging through attachment to and identification with places.
With increasing numbers of older migrants adopting a transnational lifestyle or returning to their country of origin following retirement, the sense of attachment to and identification with the places they inhabit remains an under explored field of enquiry. Through an ethnographic approach, this paper seeks to raise awareness of the diversity within a group of older migrants, given the heterogeneity of affective bonds established with places. By highlighting the perspective of older Italian migrants living in Newcastle upon Tyne, UK, this paper illustrates the role of a sense of identification with the context of migration in later life. In referring to migration as a process of transformation, some older Italians re-define their identities, as these become interwoven with the characteristics of the places in which they grow older. However, older migrants' sense of attachment to places also reveals the complexity of aging in the context of migration, when a sense of identification with these is never fully achieved in older age. This paper argues that the notion of aging that these older Italian migrants uphold is not only altered by their experience of migration, but also shaped through their identification with the places they inhabit, given formal and informal practices of identification. Thus, by addressing the determinants for a positive experience of aging in the context of migration, this paper challenges the ways in which older migrant groups are conceptualized in gerontological scholarship.


How local authority services may be affected during the 2012 Olympics and how they can be maintained.
On 6th July, 2005, the International Olympic Committee awarded London the 2012 Olympic and Paralympic Games. This is the first time an event of this magnitude has been hosted in a western country since the September 11th attacks. The UK Government continues to assess the risk, and five years on, planning is well under way. With a limited amount of time remaining, those UK local authorities hosting Olympic events will be considering what they need to have in place to support command and control arrangements during the Games. This paper provides an overview of what local authorities need to be doing over the next two years to prepare.


Enzalutamide-induced severe thrombocytopenia complicated by a seizure in a 76-year-old man with castration-resistant prostate cancer.
Adverse events with enzalutamide widely used for men with castration-resistant prostate cancer are of interest. A 76-year-old man developed castration-resistant prostate cancer. He received 160 mg of enzalutamide daily. On the 13th day after treatment, severe thrombocytopenia was observed (platelet count: 1.9 × 104/μL). Normal coagulation and fibrinolytic systems suggested thrombocytopenia induced by enzalutamide. Enzalutamide was withdrawn immediately, and platelet count uneventfully recovered to 7.0 × 104/μL and 28.8 × 104/μL 9 and 30 days after discontinuation, respectively. He restarted enzalutamide therapy without thrombocytopenia recurrence. However, 81 days after restarting enzalutamide, he experienced a seizure. There were no significant findings from brain computed tomography, which suggested that the seizure was also an enzalutamide-associated adverse event. Thrombocytopenia may occur early following enzalutamide therapy, and blood analysis within 2 weeks after treatment may facilitate its management. Enzalutamide-induced thrombocytopenia, complicated by seizure, has not been reported.


Hypocholesterolemia in cancer patients may be caused by elevated LDL receptor activities in malignant cells.
Several epidemiological studies indicate an inverse relation between plasma cholesterol and the occurrence of cancer. Since we in previous studies have found that certain malignant cell types have an elevated LDL receptor activity, the aim of the present study was to further explore the possibility that an elevated LDL consumption by tumor cells causes hypocholesterolemia. The plasma cholesterol concentrations in patients with acute leukemia were inversely correlated with the rate of receptor-mediated degradation of 125I-LDL by the leukemic cells. During chemotherapy, the total plasma and the LDL cholesterol levels increased concomitantly with the reduction in the leukemic cell count in a patient whose leukemic cells exhibited a high rate at receptor-mediated degradation of 125I-LDL. In certain patients with inoperable urinary bladder carcinoma, the plasma cholesterol concentration fell as the disease progressed. Studies in breast cancer patients indicate that the number of LDL receptors in the tumor tissue may have prognostic significance. The results are in agreement with the hypothesis that an elevated LDL receptor activity in malignant cells may lead to hypocholesterolemia.


Association of catechol-O-methyltransferase variants with duloxetine response in major depressive disorder.
Single-nucleotide and diplotype associations with 17-item Hamilton Depression Rating Scale (HAMD(17)) total score changes were examined, based on catechol-O-methyltransferase (COMT) rs165599 status in duloxetine-treated, self-identified white patients with major depressive disorder. COMT rs165737 and a diplotype containing COMT rs165599 and COMT rs165737 were associated with HAMD(17) total score changes.


Medical management of the kidney transplant recipient: a practical approach for the primary care provider.
Kidney transplant recipients (KTRs) commonly present with complex medical issues that are best managed jointly by both their primary care physician and the kidney transplant center. Hypertension, diabetes, dyslipidemias, and obesity are frequently present in the KTR population and the successful management of these comorbidities is essential in achieving excellent posttransplant outcomes. Cardiovascular disease is the leading cause of mortality in KTRs, and interventions that mitigate the risk factors that contribute to these adverse outcomes are an important part of the long-term management of a KTR.


Type VIII SLAP Repair at Midterm Follow-Up: Throwers Have Greater Pain, Decreased Function, and Poorer Return to Play.
To evaluate and compare midterm outcomes and return to play (RTP) of throwers and nonthrowers who underwent type VIII SLAP repair. With 4-year minimum follow-up, stability, pain, range of motion (ROM), Kerlan-Jobe Orthopaedic Clinic (KJOC), and American Shoulder and Elbow Surgeons (ASES) scores; surgical satisfaction; and RTP were compared between throwing and nonthrowing athletes who underwent repair of type VIII SLAP lesions between 2003 and 2014. 46 patients (27 throwers and 19 nonthrowers) were included. The athletes were aged 24.2 ± 9.2 years at the time of surgery. The mean follow-up period was 6.6 ± 2.0 years. A significant improvement in stability, pain, ROM, KJOC, and ASES scores was seen after surgery in both throwers and nonthrowers (P < .05). When postoperative outcomes were compared, throwers had more pain (P = .047), decreased ROM (P = .03), lower KJOC scores (52.2 ± 24.0 in throwers vs 87.5 ± 18.8 in nonthrowers, P < .0001), and lower ASES scores (43.5 ± 7.1 in throwers vs 48.3 ± 3.0 nonthrowers, P = .02). There was no difference in stability (P = .06), surgical satisfaction (96.3% in throwers vs 100% in nonthrowers, P > .99), or overall RTP (70.4% in throwers vs 94.7% in nonthrowers, P = .06). However, throwers were less likely to RTP at their preoperative level (37.0% in throwers vs 73.7% in nonthrowers, P = .02). Surgical repair of type VIII SLAP tears led to significant improvements in stability, pain, ROM, and outcome scores at midterm follow-up. Compared with nonthrowers, throwers had significantly more pain, less ROM, and worse function. Throwers were also less likely to RTP at their preoperative level. These findings suggest that type VIII SLAP tears should be repaired in all athletes because outcomes do improve, although throwers require specific counseling and expectation management regarding their ability to RTP at their preinjury level. Level III, therapeutic case-control study.


The effect of changes in liver volume on the adjacent viscera.
A complex interrelationship exists between the liver and several intraperitoneal and extraperitoneal structures. Recognition of the radiographic effects of changes in liver size, hepatic displacement of other organs and tissues, variations in body build, and changes in the position of the patient can be most important in the differential diagnosis of many diseases.


Comparison of bovine jugular vein with pulmonary homograft conduits in children less than 2 years of age.
The optimal pulmonary valved conduit for infants and small children remains controversial. This report compares the initial insertion outcome of small caliber bovine jugular vein (BJV) (12-14 mm) with pulmonary homografts (PHs) (10-15 mm) in patients under age 2. From December 1998 to August 2009, 84 children (mean age 8.4 + or - 8.5 months) received BJV (n=51) or PH (n=32) conduits. Mean Z score for BJV was 2.2 (range: -0.8 to 3.3) and for PH 2.1 (range: 0.8-4.2; P=0.2). The two cohorts were similar with respect to age, BSA, conduit indication, bypass and cross-clamp time. Graft dysfunction is defined as right ventricular outflow tract obstruction with peak echo-Doppler gradient >40 mmHg and/or grade III/IV conduit valve regurgitation. Graft failure is defined as need for conduit replacement or need for catheter or surgical re-intervention. Follow-up was greater in number in homografts (BJV, 4.4 + or - 3.0 years vs PH, 5.9+/-3.6 years; P=0.05). Early and late mortality were similar (BJV, 80%; PH 88%; P=0.55). No death was graft related. Freedom from dysfunction was improved at 5 and 10 years with BJV (BJV, 90% at 85% vs PH, 71% and 24% P<0.05). Conduit failure trended higher in the PH cohort at 5 and 10 years (BJV, 85% and 67% vs PH, 75% and 45%; P=0.06). Freedom from explantation was significantly better for BJV patients (BJV, 85% vs PH, 47% P<0.001. Freedom from distal conduit stenosis was similar (BJV, 52% vs PH, 44% P=0.36). This study suggests that the early performance of small BJV may be more advantageous than homografts. A BJV conduit is an appropriate first choice for conduit replacement in patients less than 2 years of age.


Liver transplantation for hepatocellular carcinoma: expanding frontiers and building bridges.
Despite significant advances in nonsurgical treatments of hepatocellular carcinoma, these approaches rarely result in cure. Surgery remains the mainstay of curative therapy for hepatocellular carcinoma. Liver transplantation, in particular, has emerged as one of the most beneficial therapeutic modalities. Questions remain, however, regarding hepatocellular carcinoma surveillance, the choice of surgical resection versus transplantation, the role of chemotherapy, optimal selection criteria for transplantation, and the role of ablative therapies to halt tumor progression and downsize tumors exceeding transplant criteria.


Genetic and Clinical Profile of Chinese Patients with Autosomal Dominant Spastic Paraplegia.
Hereditary spastic paraplegia (HSP) refers to a group of neurodegenerative disorders characterized by bilateral weakness, spasticity, and hyperreflexia in the lower limbs. The autosomal dominant HSP (ADHSP) predominantly presents as the pure form, but the clinical profiles and causal genetic variants underlying ADHSP are complex, and many remain unknown. A cohort of 15 Chinese HSP pedigrees (including 35 patients and their 22 relatives) were screened by multiplex ligation-dependent probe amplification (MLPA) or whole-exome sequencing (WES). Neurological assessments were also conducted. The main subtypes of HSP above detected in our cohort were SPG4, SPG3A, and SPG6. Fifteen HSP-inducing mutations were identified, among which six were novel mutations: SPAST c.1277T>C, c.1292G>C, c.1562T>C, and c.1693A>T, NIPA1 c.748A>C, and KIDINS220 c.4448C>G. As expected, the most common presentation of the ADHSP cases was the pure form, manifesting spasticity of lower limbs and hyperreflexia, as well as pyramidal signs. Differing substantially from previous reports for KIDINS220 variants, our study family exhibited autosomal dominant inheritance, and only presented with spastic paraplegia, with no signs of intellectual disability, nystagmus, or obesity. Our work reveals a non-classical spastic paraplegia, intellectual disability, nystagmus, and obesity phenotype for a KIDINS220 mutation, which broadens both the clinical and genetic spectrum for ADHSP. Beyond underscoring the utility of using both MLPA and WES in studies of HSP, our work deepens the scientific understanding of phenotypes for ADHSP and defines new genetic variants to facilitate future diagnoses.


Metabolic evaluation of a synthetic amino acid mixture for parenteral nutrition in infants and children.
Ninety infants and children received total parenteral nutrition with a mixture of glucose, crystalline amino acids, vitamins, electrolytes, and minerals. The mixture was generally well-tolerated with a minimum of complications. The intravenous regimen produced positive nitrogen balance and weight gain in the majority of subjects. The amino acids provided maintained the protein pool in these patients as a further indication of utilization. Mild, transient, asymptomatic elevations in blood urea nitrogen occurred in a few low-birth-weight infants who probably received insufficient nonprotein calories relative to their needs. Hypophosphatemia and acidosis did not occur. It is concluded that this regimen is safe, effective method of providing total parenteral nutrition, provided that adequate nonprotein calories are provided.


Adipose-Derived Mesenchymal Stem Cells-Derived Exosomes Carry MicroRNA-671 to Alleviate Myocardial Infarction Through Inactivating the TGFBR2/Smad2 Axis.
Mesenchymal stem cells (MSCs) and their derived extracellular vesicles have been reported as promising tools for the management of heart disease. The aim of this study was to explore the function of adipose-derived MSCs (adMSCs)-derived exosomes (Exo) in the progression of myocardial infarction (MI) and the molecules involved. Mouse cardiomyocytes were treated with oxygen-glucose deprivation (OGD) to mimic an MI condition in vitro. The adMSCs-derived Exo were identified and administrated into the OGD-treated cardiomyocytes, and then the viability and apoptosis of cells, and the secretion of fibrosis- and inflammation-related cytokines in cells were determined. Differentially expressed microRNAs (miRNAs) in cells after Exo treatment were screened using a microarray analysis. The downstream molecules regulated by miR-671 were explored through bioinformatic analysis. Involvements of miR-671 and transforming growth factor beta receptor 2 (TGFBR2) in the exosome-mediated events were confirmed by rescue experiments. A murine model with MI was induced and treated with Exo for functional experiments in vivo. Compared to phosphate-buffered saline treatment, the Exo treatment significantly enhanced viability while reduced apoptosis of cardiomyocytes, and in reduced myocardial fibrosis and inflammation both in vitro and in vivo. miR-671 was significantly upregulated in cells after Exo treatment. Downregulation of miR-671 blocked the protective functions of Exo. miR-671 targeted TGFBR2 and suppressed phosphorylation of Smad2. Artificial downregulation of TGFBR2 enhanced viability of the OGD-treated cardiomyocytes. This study suggested that adMSC-derived exosomal miR-671 directly targets TGFBR2 and reduces Smad2 phosphorylation to alleviate MI-like symptoms both in vivo and in vitro.


Effect of amino acids and inducers on the activity of the microsomal mono-oxygenase system in rat liver cell culture.
In rat liver cell culture both benzanthracene and phenobarbitone induce the activity of benzypyrene hydrxylase while only phenobarbitone increases NADPH cytochrome c reductase activity. Benzpyrene hydroxylase but not NADPH cytochrome c reductase activity is dependent on the amino acid concentration of the culture medium in a similar manner to the regulation of the hepatic hydroxylase activity by dietary protein intake in the whole animal. Of all the amino acids present in the culture medium, only tryptophan induced benzpyrene hydroxylase when added singly to the medium. However, tryptophan also induced the activity of the reductase suggesting that its inducing effect is unrelated to raising the concentration of all the amino acids of the culture medium. It is proposed that tryptophan may only be an inducer because the cells have low levels of tryptophan pyrrolase activity.


Structure and Inhibitor Binding Characterization of Oncogenic MLLT1 Mutants.
Dysfunction of YEATS-domain-containing MLLT1, an acetyl/acyl-lysine dependent epigenetic reader domain, has been implicated in the development of aggressive cancers. Mutations in the YEATS domain have been recently reported as a cause of MLLT1 aberrant reader function. However, the structural basis for the reported alterations in affinity for acetylated/acylated histone has remained elusive. Here, we report the crystal structures of both insertion and substitution mutants present in cancer, revealing significant conformational changes of the YEATS-domain loop 8. Structural comparison demonstrates that not only did such alteration alter the binding interface for acetylated/acylated histones, but the sequence alterations in the loop in T1 mutant may enable dimeric assembly consistent with inducing self-association behavior. Nevertheless, we show that also the MLLT1 mutants can be targeted by developed acetyllysine mimetic inhibitors with affinities similarly to wild-type. Our report provides a structural basis for the altered behaviors and a potential strategy for targeting oncogenic MLLT1 mutants.


Mitochondrial perturbations define lymphocytes undergoing apoptotic depletion in vivo.
We have recently shown that lymphocyte apoptosis induced by dexamethasone or superantigens is accompanied by reduction of mitochondrial transmembrane potential (delta psi m) which precedes nuclear DNA fragmentation. Here, we demonstrate that fluorochromes such as 3,3' dihexyloxacarbocyanine iodide [DiOC6(3)] which measure delta psi m, or fluorochromes such as hydroethidine (HE) which measure mitochondrial superoxide anion production allow the identification of thymocytes or peripheral T lymphocytes which are eliminated by apoptosis in vivo. In mice bearing transgenic alpha/beta T cell receptor (TCR) specific for a class I-restricted male-specific peptide, the superoxide-mediated oxidation of HE into ethidium (Eth) is enhanced among thymocytes which are being deleted due to negative selection (CD4+ CD8+ cells expressing the transgenic TCR in male mice) or lack of positive selection (CD4+ CD8- thymocytes from female mice). delta psi m reduction and/or enhanced HE oxidation are also found when apoptosis is induced by a series of pathogenic agents. Thus, lethal irradiation provokes mitochondrial and nuclear signs of apoptosis, and both these alterations are absent in mice bearing a p53 null mutation, underlying the correlation between mitochondrial perturbation and nuclear apoptosis. Similarly, superantigen-triggered deletion of peripheral T cells in vivo is accompanied by enhanced HE-->Eth conversion and reduced DiOC6(3) uptake. More importantly, as compared to normal controls, CD4+ or CD8+ cells from clinically asymptomatic human immunodeficiency virus-1 (HIV-1) carriers also contain a significantly elevated percentage of cells endowed with reduced DiOC6(3) uptake. In superantigen- and HIV-induced apoptosis, the percentage of T lymphocytes with a subnormal DiOC6(3) uptake is more important than that of cells marked by enhanced HE-->Eth conversion. In conclusion, mitochondrial alterations precede and/or accompany nuclear signs of apoptosis induced by physiological and a variety of different pathogenic agents in vivo.


Altered gene transcription profiles in fibroblasts harboring either TK2 or DGUOK mutations indicate compensatory mechanisms.
Mitochondrial DNA (mtDNA) depletion syndrome (MDS) is an autosomal recessive disorder characterized by a reduced amount of mtDNA, which impairs synthesis of respiratory chain complexes. MDS has been classified into two main groups, the hepatocerebral form affecting liver and the central nervous system, and the myopathic form targeting the skeletal muscle. We have compared the molecular genetic characteristics of fibroblasts derived from two patients harboring TK2 mutations with two harboring mutations in DGUOK gene. Real-time PCR revealed mtDNA depletion in dGK-deficient fibroblasts (dGK-) but not in TK2-deficient cells (TK2-). Real-time RT-PCR and western blotting demonstrated significant differences in the expression of the human equilibrative nucleoside transporter 1 (hENT1) at the mRNA and protein levels. hENT1 transcript and protein were increased in quiescent control and TK2- fibroblasts relative to cycling cells. In contrast, hENT1 was stable in quiescent and cycling dGK- cells. Moreover, siRNA down-regulation of hENT1, but not of TK1, induced mtDNA depletion in TK2- fibroblasts indicating that hENT1 contributes to the maintenance of normal mtDNA levels in cells lacking TK2. Transcripts for thymidine phosphorylase, the mitochondrial transcription factor A (TFAM), and the polymerase gamma (Pol gamma), were reduced in dGK-, but not in TK2- cells while the mRNA expression of thymidylate synthase (TS) increased. Our results suggested differential gene expression in TK2 and dGK-deficient fibroblasts, and highlighted the importance of hENT1 as a compensatory factor in MDS disorder.


Impact of microbial genome completeness on metagenomic functional inference.
Inferring the functional capabilities of bacteria from metagenome-assembled genomes (MAGs) is becoming a central process in microbiology. Here we show that the completeness of genomes has a significant impact on the recovered functional signal, spanning all domains of metabolic functions. We identify factors that affect this relationship between genome completeness and function fullness, and provide baseline knowledge to guide efforts to correct for this overlooked bias in metagenomic functional inference.


Identification and Characterization of the PEBP Family Genes in Moso Bamboo (Phyllostachys heterocycla).
Moso bamboo is one of the economically most important plants in China. Moso bamboo is a monocarpic perennial that exhibits poor and slow germination. Thus, the flowering often causes destruction of moso bamboo forestry. However, how control of flowering and seed germination are regulated in moso bamboo is largely unclear. In this study, we identified 5 members (PhFT1-5) of the phosphatidyl ethanolamine-binding proteins (PEBP) family from moso bamboo genome that regulate flowering, flower architecture and germination, and characterized the function of these PEBP family genes further in Arabidopsis. Phylogenetic analysis revealed that 3 (PhFT1, PhFT2 and PhFT3), 1 (PhFT4) and 1 (PhFT5) members belong to the TFL1-like clade, FT-like clade, and MFT-like clade, respectively. These PEBP family genes possess all structure necessary for PEBP gene function. The ectopic overexpression of PhFT4 and PhFT5 promotes flowering time in Arabidopsis, and that of PhFT1, PhFT2 and PhFT3 suppresses it. In addition, the overexpression of PhFT5 promotes seed germination rate. Interestingly, the overexpression of PhFT1 suppressed seed germination rate in Arabidopsis. The expression of PhFT1 and PhFT5 is significantly higher in seed than in tissues including leaf and shoot apical meristem, implying their function in seed germination. Taken together, our results suggested that the PEBP family genes play important roles as regulators of flowering and seed germination in moso bamboo and thereby are necessary for the sustainability of moso bamboo forest.


[Conservative treatment of extensor tendon injuries].
Report on 35 cases of mallet finger treated conservatively: a circular plaster cast was modeled in hyperextension of the distal interphalangeal joint. The immobilisation of the whole finger form the tip to the proximal phalanx was maintained for six weeks. The reported results were good or excellent with the exception of two cases.


Safety and Efficacy of Immune Checkpoint Inhibitors in Patients With Metastatic Cancer Post Solid Organ Transplantation: A Case Report and Review of the Literature.
Immunotherapy is expanding its role in cancer therapy, and in various tumor types it has now become the frontline treatment. Though generally better tolerated than traditional chemotherapy, its mechanism of activating the immune system results in a unique set of adverse reactions that maybe disastrous in the setting of post solid organ transplantation. We herein describe a case report of a patient who was post-renal transplant, developed metastatic, relapsed, refractory renal cell carcinoma, and was successfully treated with nivolumab for 6 cycles while maintaining renal graft function. We also reviewed the published case reports of immunotherapy administered in the post-renal transplantation setting.


Maxillary osteomyelitis by mucormycosis: report of four cases.
Mucormycosis is a fungal infection commonly affecting structures in the head and neck, such as the air sinuses, orbits, and the brain. Common predisposing factors include diabetes mellitus and immunosuppression. We describe our clinical experience with four cases of mucormycosis of the maxillary antrum associated with uncontrolled diabetes mellitus managed at our centre. Early diagnosis and prompt treatment can significantly reduce the mortality and morbidity of this lethal fungal infection.


A novel antibacterial and fluorescent coating composed of polydopamine and carbon dots on the surface of orthodontic brackets.
Many kinds of antibacterial coatings have been designed to prevent the adherence of bacteria onto the surface of a fixed orthodontic device of brackets. However, the problems such as weak binding force, undetectable, drug resistance, cytotoxicity and short duration needed to be solved. Thus, it has great value in developing novel coating methods with long-term antibacterial and fluorescence properties according to the clinical application of brackets. In this study, we synthesized blue fluorescent carbon dots (HCDs) using the traditional Chinese medicinal honokiol, which could cause irreversible killing effects on both gram-positive and gram-negative bacteria through positive charges on the surface and inducing reactive oxygen species (ROS) production. Based on this, the surface of brackets was serially modified with polydopamine and HCDs, taking advantage of the strong adhesive properties as well as the negative surface charge of polydopamine particles. It is found that this coating exhibits stable antibacterial properties in 14 days with good biocompatibility, which can provide a new solution and strategy to solve the series of hazards caused by bacterial adhesion on the surface of orthodontic brackets.


Functional group chemistry at intramolecular frustrated Lewis pairs: substituent exchange at the Lewis acid site with 9-BBN.
The vicinal frustrated P/B Lewis pair (FLP) Mes(2)PCH(2)CH(2)B(C(6)F(5))(2) reacts with 9-borabicyclo[3.3.1]nonane (9-BBN) by C(6)F(5)vs. H exchange at boron to give the new [B]-H functionalized FLP Mes(2)PCH(2)CH(2)B(H)(C(6)F(5)) (4) and 9-C(6)F(5)-BBN. The latter was characterized as an isonitrile adduct by X-ray diffraction. The new FLP 4 forms an adduct with pyridine and it undergoes clean hydroboration reactions with 1-pentyne or added styrene or dimesitylvinylphosphane. The products formed stable adducts with pyridine; two such examples were also characterized by X-ray crystal structure analysis. A similar alkyl vs. hydrogen exchange was observed upon treatment of an Al/N based Lewis pair, iBu(2)Al-(Me(3)Si)C=C(H)-N(CH(2)CH(2))(2)NMe (14), with 9-BBN.


Subchronic treatment with phencyclidine in adolescence leads to impaired exploratory behavior in adult rats without altering social interaction or N-methyl-D-aspartate receptor binding levels.
Although both the onset of schizophrenia and human phencyclidine (PCP) abuse typically present within the interval from adolescence to early adulthood, the majority of preclinical research employing the PCP model of schizophrenia has been conducted on neonatal or adult animals. The present study was designed to evaluate the behavioral and neurochemical sequelae of subchronic exposure to PCP in adolescence. Male 35-42-day-old Sprague Dawley rats were subcutaneously administered either saline (10 ml · kg(-1) ) or PCP hydrochloride (10 mg · kg(-1) ) once daily for a period of 14 days (n = 6/group). The animals were allowed to withdraw from treatment for 2 weeks, and their social and exploratory behaviors were subsequently assessed in adulthood by using the social interaction test. To examine the effects of adolescent PCP administration on the regulation of N-methyl-D-aspartate receptors (NMDARs), quantitative autoradiography was performed on brain sections of adult, control and PCP-withdrawn rats by using 20 nM (3) H-MK-801. Prior subchronic exposure to PCP in adolescence had no enduring effects on the reciprocal contact and noncontact social behavior of adult rats. Spontaneous rearing in response to the novel testing arena and time spent investigating its walls and floor were reduced in PCP-withdrawn animals compared with control. The long-term behavioral effects of PCP occurred in the absence of persistent deficits in spontaneous locomotion or self-grooming activity and were not mediated by altered NMDAR density. Our results document differential effects of adolescent PCP administration on the social and exploratory behaviors of adult rats, suggesting that distinct neurobiological mechanisms are involved in mediating these behaviors.


A retrospective evaluation of direct oral anticoagulant (DOAC) management strategies in patients with cancer on active chemotherapy.
Use of direct oral anticoagulants (DOACs) in patients with cancer on active chemotherapy is challenging due to changes in renal or hepatic function, thrombocytopenia, chemotherapy-induced nausea and vomiting (CINV), and drug-drug interactions (DDIs) attributed to disease or treatment. The purpose of this retrospective cohort analysis was to characterize DOAC management through various interventions and evaluate the efficacy and safety of DOAC use in this patient population. A total of 58 patients with 97 unique index periods in which a patient was concomitantly on a DOAC and chemotherapy were identified. Several instances were observed in which an intervention should be made based on manufacturer guidance or clinical judgment. Of 37 instances attributed to changes in renal function, the following interventions were employed: dose adjustments (10/37), holding DOAC therapy until renal function improved (held 3/37, restarted 4/37), changing to an alternative anticoagulant (5/37), DOAC discontinuation (2/37), or no change (13/37). One change was made in response to decreased hepatic function (1/15). DOACs were held in the setting of platelet counts below 50 K/mm3 (8/20) and restarted when platelets improved above this threshold (5/20). In patients with CINV, DOAC therapy was continued (26/32) with few changes made. To manage DOAC-chemotherapy DDIs, changes in DOAC agents (4/6) and dose reductions in chemotherapy agents (2/6) were made. Thrombotic and bleeding events did not strongly correlate with renal or hepatic impairment, thrombocytopenia, CINV, or DDIs. Further guidance regarding the use of these agents in this patient population is warranted to address management strategies, efficacy, and safety. Use of direct oral anticoagulants (DOACs) in patients with cancer on active chemotherapy is challenging due to changes in renal or hepatic function, thrombocytopenia, chemotherapy-induced nausea and vomiting (CINV), and drug-drug interactions (DDIs) attributed to disease or treatment. The purpose of this retrospective cohort analysis was to characterize DOAC management and evaluate the efficacy and safety of DOAC use in this patient population. A total of 58 patients with 97 unique index periods in which a patient was concomitantly on a DOAC and chemotherapy were identified. Several instances were observed in which an intervention should be made based on manufacturer guidance or clinical judgment. Interventions employed are summarized graphically. Thrombotic and bleeding events did not strongly correlate with renal or hepatic impairment, thrombocytopenia, CINV, or DDIs. CINV chemotherapy-induced nausea and vomiting, DDIs drug-drug interactions, DOAC direct oral anticoagulant, OAC oral anticoagulant.


Inhibition of lymphocyte activation and function by the prenylation inhibitor L-778,123.
Prenylated Ras GTPases transduce signals from the T cell receptor, CD28 costimulatory receptor and IL-2 receptor. Since signals from these receptors mediate T cell activation, proliferation and survival, we hypothesized that the prenylation inhibitor L-778,123 would impart immunomodulation. The effect of L-778,123 on T cell activation (CD71 or CD25 surface expression) was determined by flow cytometry. Peripheral blood mononuclear cell (PBMC) proliferation in the presence of L-778,123 and/or cyclosporine (CsA) was determined by [3H]thymidine incorporation. The ability of L-778,123 to inhibit IL-2 receptor signaling was investigated by measuring IL-2 induced proliferation in CTLL-2 cells and IL-2 prevention of apoptosis in activated human PBMC. L-778,123 inhibited lectin induced expression of CD71 and CD25 with IC50's of 6.48 +/- 1.31 microM and 84.1 +/- 50.0 microM, respectively. PBMC proliferation was inhibited by L-778,123 with an IC50 of 0.92 +/- 0.23 microM, and addition of CsA did not increase the potency. L-778,123 did not inhibit IL-2 and IFN-gamma production by T cells. L-778,123 abrogated IL-2 induced proliferation of CTLL-2 cells with an IC50 of 0.81 +/- 0.44 microM. However, L-778,123 minimally reversed the prosurvival effect of IL-2 in activated lymphocytes. IL-2 ligand and receptor production during T cell activation are relatively unaffected by L-778,123. However, the activation and proliferative effects of IL-2 on T cells are potently blocked by L-778,123. These results reveal a selective blockade of the IL-2 cytokine axis distal to the IL-2 receptor by the L-778,123 and warrant evaluation of prenylation inhibitors in treating transplant rejection and autoimmune diseases.