Influence of chicken native breeds on some physical and biochemical characteristics and short-term storage of semen.
1. The major objective of this study was to examine the influence of 24-h storage of semen at low temperature on semen characteristics and fertilising ability of spermatozoa in two native breeds (Kadaknath-KN, Aseel Peela-AP) and White Leghorn (WL) chicken. 2. Various physical and biochemical properties of freshly ejaculated semen of KN and AP were investigated. Fertility was examined in freshly-ejaculated as well as 24-h-stored (3°C) semen diluted (1:3) with Beltsville Poultry Semen Extender. 3. No significant difference was observed in sperm motility among the different breeds whereas live counts were higher in WL than the native breeds. Body weight, semen volume and sperm concentration were highest in AP, followed by KN and WL. A similar trend was observed in the percentage of dead and morphologically-abnormal spermatozoa. 4. The activity of acid and alkaline phosphatase in seminal plasma were higher in WL than KN, whereas the opposite trend was recorded for glutamic oxaloacetic and pyruvic transaminases. The cholesterol content of semen was highest in AP, followed by KN and WL. Cholesterol was much lower in seminal plasma compared with whole semen but there were no differences between breeds. Mean values of the methylene blue reduction time test were higher in WL than in the native breeds. 5. Fertility and hatchability, using freshly-diluted semen, were poorer in the native breeds than in WL. The pattern of fertility deteriorated further, especially in native fowls, when the birds were inseminated with 24-h-stored semen. 6. In conclusion, variation in physical and biochemical characteristics of semen in native breeds compared to WL correlated with poor fertility after short-term storage of semen.


Cardiac adenylate cyclase activity, positive chronotropic and inotropic effects of forskolin analogs with either low, medium or high binding site affinity.
A series of in vitro studies were conducted examining the adenylate cyclase stimulation, positive chronotropic and inotropic effects of forskolin and nine analogs which exhibited a range of [3H]forskolin binding site affinities (K1) from 0.020 to 3.174 microM. A significant (P less than .001) linear correlation (r = 0.94) was found between binding site affinity and adenylate cyclase stimulation (EC50) for forskolin and the nine structural analogs. Adenylate cyclase activity was also significantly correlated with the positive chronotropic and inotropic effects of these substances on isolated guinea pig atria. Compounds with K1 values between 0.020 and 1.136 microM produced concentration-dependent increases in heart rate and contractile force in isolated spontaneous and electrically paced guinea pig atria, respectively. In contrast, an analog with a K1 of 3.174 microM caused significant (P less than .05) negative chronotropic and inotropic effects at concentrations above 10 microM. The optimal separation between positive inotropic and chronotropic activity was found with compounds displaying potent [3H]forskolin binding site affinity but moderate adenylate cyclase stimulation, i.e., K1 and EC50 values of approximately 0.05 to 0.10 and 3 microM, respectively. The results of this study show that the forskolin analog, P87-7692 [7-desacetyl-7-(O-propionyl)-hydroxyl amino-carbonyl-forskolin], has marked activity with a wide separation between positive inotropic (248 +/- 41%) and chronotropic effects (43 +/- 13%) at 6.2 microM and may serve as a prototype for a forskolin-based cardiotonic.


Complications of transhiatal esophagectomy.
A total of 23 papers published between 1981 and 1992, reporting a total of 1,353 patients, were reviewed for intraoperative and postoperative complications of transhiatal esophagectomy. Intraoperative complications included massive bleeding, tracheal injuries, cardiac arrhythmias, and incidental splenectomies. Even though the chest was not opened, the commonest postoperative complications were pulmonary. Leakage from the cervical anastomosis was seen in as many as 15% of all patients, but almost all resolved spontaneously. Postoperative benign strictures were seen in almost as many patients. Hoarseness due to recurrent laryngeal nerve injury, symptomatic gastro-esophageal reflux, chylothorax, Horner's syndrome, subphrenic abscess, hiatal hernia, and biliary cutaneous fistula were some of the other postoperative complications. An overview of these complications is presented, along with suggested methods of avoiding them and their treatment. The overall mortality for the 1,353 patients was 7.17%.


Apoptotic mechanism in pemphigus autoimmunoglobulins-induced acantholysis--possible involvement of the EGF receptor.
Pemphigus is an autoimmune cutaneous disease characterized by circulating autoantibodies that cause blistering and erosions on skin and mucous membranes. Circulating autoantibodies bind to epidermal cell membrane and cause cell-cell detachment (acantholysis), leading to epidermal tissue damage and cell death. The principal target of pemphigus vulgaris autoantibodies (PV-IgG) is desmosomal cadherin desmoglein 3 (Dsg3), a constituent of desmosomes, mediating cell-cell adhesion. Several hypotheses for the mechanisms of acantholysis induction by PV-IgG exist, but the actual mechanism is not clear as yet. We have previously reported on apoptosis induction in PV-IgG-mediated epidermal tissue and cell damage as a possible mechanism of acantholysis and cell death (Wang et al. 2004, Apoptosis, 9:131-143). In this study we investigated the involvement of the EGFR and intracellular signal transduction pathways in the PV-IgG-induced apoptosis. We show here that PV-IgG induced activation/autophosphorylation of EGFR in cultured keratinocytes in vitro. The specific tyrosine kinase inhibitor AG1478 abrogated EGFR autophosphorylation, cell death, FasL appearance and acantholysis, all induced by PV-IgG, in parallel, confirming the involvement of EGFR in this Fas apoptotic cascade. Activation of EGFR was followed by phosphorylation of its downstream substrates, MAP kinase ERK and transcription factor c-Jun, and internalization of EGFR. Pharmacological inactivation of the EGFR and ERK kinase activities, by use of specific inhibitors AG1478 and PD98059 respectively, blocked PV-IgG-induced phosphorylation of EGFR, ERK and c-Jun and cellular apoptosis, measured by flow cytometry and caspase 3 activity. Prolonged activation of EGFR by PV-IgG led to dramatic internalization of this receptor, possibly reducing the ability of the cell to perform survival signals. This suggests that activation of EGFR, followed by its internalization, is pivotal for intracellular apoptotic signal transduction via ERK/c-Jun pathways, leading to acantholysis. Our experimental data indicate that the EGFR is instrumental in transducing apoptotic/acantholytic signals in keratinocytes cultures in response to PV-IgG treatment. The acantholytic effect caused by PV-IgG binding to cell surface receptors begins with and depends on cell surface receptor (EGFR) activation of intracellular signaling pathways (ERK pathway) and apoptosis induction (FasR pathway), which later lead to major cell-cell separation (acantholysis) and cell death.


Analysis of European and north american maize inbred and hybrid lines by monolithic and perfusion reversed-phase high-performance chromatography and multivariate analysis.
Monolithic and perfusion RP-HPLC methods have been employed for the separation of maize proteins from several European and North American inbred and hybrid lines in analysis times close to 4 min for the perfusion column and close to 8 min for the monolithic column. A study of the repeatability of the protein extraction conditions and of the perfusion and monolithic RP-HPLC methods was performed, indicating low values of variance for the relative peak areas and for the retention times. On the other hand, a low inter-kernel variability of these chromatographic parameters was also found, confirming the possibility of a variety identification and classification of maize inbred and hybrid lines by using a RP-HPLC analysis of the maize proteins. A multivariate analysis of the chromatographic data was carried out in order to characterize and identify the inbred and hybrid maize lines. Cluster analysis of the data showed how far or closely related were the maize lines. Principal component analysis showed that protein chromatographic data had enough information to distinguish between the different groups of maize lines. Finally, a linear discriminant analysis enabled the correct classification of the inbred and hybrid lines according to their geographical origin showing the best percentage of cases correctly classified for monolithic RP-HPLC.


Unknown primary tumors: detection with dual-modality PET/CT--initial experience.
To retrospectively evaluate fused positron emission tomography (PET)/computed tomography (CT) in depicting the primary lesion in cancer of an unknown primary tumor, compared with PET, CT, and PET and CT side-by-side evaluation. Institutional review board approval and informed consent were obtained. Forty-five patients (26 men and 19 women) with metastatic cervical adenopathy (n = 18) or extracervical metastases (n = 27) of unknown primary tumor were included. The mean age of the patients was 57 years (range, 29-95 years). PET/CT imaging was performed in all patients 1 hour after administration of 350 MBq of fluorodeoxyglucose with a whole-body field of view. Contrast agents were administered orally and intravenously in all patients to ensure diagnostic CT data. PET/CT data sets were evaluated for the primary tumor, and imaging results were compared with those of CT, PET, and PET and CT side-by-side evaluation. Differences in diagnostic performance were assessed by using the McNemar test with Bonferroni correction, which accounts for multiple comparisons. PET/CT depicted the primary tumor in 15 (33%) of 45 patients. In 30 (67%) patients, the primary tumor site remained occult (P > .05). PET and CT side-by-side evaluation depicted 13 (29%) of 45 tumors (P > .05). PET alone revealed the primary tumor in 11 (24%) of 45 patients (P > .05), while CT alone helped in the correct diagnosis in eight (18%) of 45 patients (P > .05). There were no significant differences between the diagnostic accuracies of PET/CT and the other imaging modalities. PET/CT was able to depict more primary tumors, though not significantly, than either of the other imaging modalities, but larger patient cohorts are required to finally judge its value for revealing the primary tumor site.


New parameters for daytime wandering.
This study aimed to describe wandering using new parameters and to evaluate parameters as a function of cognitive impairment and mobility. Forty-four wanderers in long-term care settings were videotaped 12 times. Rate and duration of wandering episodes were plotted and used to derive parameters from values above and below case medians, proportion of hours wandering, and time of day. Participants wandered during 47% of observations; on average, the hourly rate was 4.3 episodes, the peak hourly rate was 18 episodes, and the peak hourly duration was 19.9 minutes. Mini-Mental State Examination (MMSE) scores was negatively correlated with overall duration and number of observations during which duration exceeded 15 minutes per hour, was positively correlated with number of observations without wandering, and was not significantly correlated with rate-related parameters. Mobility correlated positively with rate and duration parameters. Interaction of MMSE score and mobility was the strongest predictor of wandering duration. Parameters derived from repeated measures provide a new view of daytime wandering and insight into relationships between MMSE score and mobility status with specific parameters of wandering.


Disseminated toxoplasmosis after bone marrow transplantation: report of 9 cases.
Toxoplasma infection following bone marrow transplantation (BMT) is infrequently reported. We report 9 cases of disseminated Toxoplasma gondii infection in BMT recipients documented during an 11-year period at our institution. The incidence of T. gondii infection in our institution (1.14 per 100 allogeneic BMT) is higher than previously reported. The most frequently affected sites were the brain, lungs, and heart. Findings common to most patients who developed toxoplasmosis were positive pre-transplant serology, allogeneic transplant and graft-versus-host disease and its treatment, as well as BMT from matched unrelated donors. All 9 patients died and 8 were diagnosed only after autopsy. Heightened awareness of the occurrence of toxoplasmosis in marrow recipients, especially in highly endemic areas, and early diagnosis and therapy are needed for a better outcome.


Is the use of pan-computed tomography for blunt trauma justified? A prospective evaluation.
Many trauma centers use the pan-computed tomography (CT) scan (head, neck, chest, and abdomen/pelvis) for the evaluation of blunt trauma. This prospective observational study was undertaken to determine whether a more selective approach could be justified. We evaluated injuries in blunt trauma victims receiving a pan-CT scan at a level I trauma center. The primary outcome was injury needing immediate intervention. Secondary outcome was any injury. The perceived need for each scan was independently recorded by the emergency medicine and trauma surgery service before patients went to CT. A scan was unsupported if at least one of the physicians deemed it unnecessary. Between July, 1, 2007, and December, 28, 2007, 284 blunt trauma patients (average Injury Severity Score = 11) underwent a pan-CT after the survey form was completed. A total of 311 CT scans were judged to be unnecessary in 143 patients (27%), including scans of the head (62), neck (50), chest (116), and abdomen/pelvis (83). Of the 284 patients, 48 (17%) had injuries on 52 unsupported CT scans. An immediate intervention was required in 2 of the 48 patients (4%). Injuries that would have been missed included 5 of 62 unsupported head scans (8%), 2 of 50 neck scans (4%), 33 of 116 chest scans (28%), and 12 of 83 abdominal scans (14%). These missed injuries represent 5 of the 61 patients with closed head injuries (8%) in the series, 2 of the 23 with C-spine injuries (9%), 33 of the 112 with chest injuries (29%), and 12 of the 86 with abdominal injuries (14%). In 19 patients, none of the four CT scans was supported; nine of these had an injury identified, and six were admitted to the hospital (1 to the intensive care unit). Injuries that would have been missed included intraventricular and intracerebral hemorrhage (4), subarachnoid hemorrhage (2), cerebral contusion (1), C1 fracture (1), spinous and transverse process fractures (3), vertebral fracture (6), lung lacerations (1), lung contusions (14), small pneumothoraces (7), grade II-III liver and splenic lacerations (6), and perinephric or mesenteric hematomas (2). In this small sample, physicians were willing to omit 27% of scans. If this was done, two injuries requiring immediate actions would have been missed initially, and other potentially important injuries would have been missed in 17% of patients.


A Thermodynamically Favored Crystal Orientation in Mixed Formamidinium/Methylammonium Perovskite for Efficient Solar Cells.
Crystal orientation has a great impact on the properties of perovskite films and the resultant device performance. Up to now, the exquisite control of crystal orientation (the preferred crystallographic planes and the crystal stacking mode with respect to the particular planes) in mixed-cation perovskites has received limited success, and the underlying mechanism that governs device performance is still not clear. Here, a thermodynamically favored crystal orientation in formamidinium/methylammonium (FA/MA) mixed-cation perovskites is finely tuned by composition engineering. Density functional theory calculations reveal that the FA/MA ratio affects the surface energy of the mixed perovskites, leading to the variation of preferential orientation consequently. The preferable growth along the (001) crystal plane, when lying parallel to the substrates, affects their charge transportation and collection properties. Under the optimized condition, the mixed-cation perovskite (FA1- x MAx PbI2.87 Br0.13 (Cl)) solar cells deliver a champion power conversion efficiency over 21%, with a certified efficiency of 20.50 ± 0.50%. The present work not only provides a vital step in understanding the intrinsic properties of mixed-cation perovskites but also lays the foundation for further investigation and application in perovskite optoelectronics.


Therapeutic efficacy of an elemental diet for patients with crohn's disease and its association with amino acid metabolism.
We investigated the association between blood amino acid concentration changes caused by elemental diet (ED) and their relationship to its therapeutic effect. Patients with active Crohn's disease (CD) followed ED for 12 weeks. Patients not previously treated with ED were defined as new ED, and those with previous ED therapy (≥900 kcal/day) were defined as previous ED. Disease activity markers [Crohn's disease activity index (CDAI) and C-reactive protein (CRP) level], blood biochemistry test results, and plasma amino acid concentrations were measured before and after the treatment. Histidine (His), tryptophan (Trp), valine (Val), and methionine (Met) increased after the treatment in the 17 patients with clinical remission, however, no increase occurred in plasma amino acid concentrations in the 8 patients without remission. The multivariate index using AminoIndex™technology (MIAI) was correlated with the CDAI (r = 0.475,P < 0.001), and it decreased as patients' conditions improved during the treatment. All patients in the new ED group (n = 11) exhibited increases in the nutritional indices, albumin level, and body mass index after treatment, as well as increased levels of His, Trp, Val, and phenylalanine. None of these changes were observed in the previous ED group (n = 14). Plasma amino acid concentrations and MIAI may provide useful noninvasive markers for evaluating disease activity and response to treatment. ED was effective in improving disease activity, nutritional status, and plasma amino acid levels, and thus it may be particularly effective for poorly nourished patients with CD who have not previously undergone this treatment.


Melatonin Attenuates Dasatinib-Aggravated Hypoxic Pulmonary Hypertension via Inhibiting Pulmonary Vascular Remodeling.
Dasatinib treatment is approved as first-line therapy for chronic myeloid leukemia. However, pulmonary hypertension (PH) is a highly morbid and often fatal side-effect of dasatinib, characterized by progressive pulmonary vascular remodeling. Melatonin exerts strong antioxidant capacity against the progression of cardiovascular system diseases. The present work aimed to investigate the effect of melatonin on dasatinib-aggravated hypoxic PH and explore its possible mechanisms. Dasatinib-aggravated rat experimental model of hypoxic PH was established by utilizing dasatinib under hypoxia. The results indicated that melatonin could attenuate dasatinib-aggravated pulmonary pressure and vascular remodeling in rats under hypoxia. Additionally, melatonin attenuated the activity of XO, the content of MDA, the expression of NOX4, and elevated the activity of CAT, GPx, and SOD, the expression of SOD2, which were caused by dasatinib under hypoxia. In vitro, dasatinib led to decreased LDH activity and production of NO in human pulmonary microvascular endothelial cells (HPMECs), moreover increased generation of ROS, and expression of NOX4 both in HPMECs and primary rat pulmonary arterial smooth muscle cells (PASMCs) under hypoxia. Dasatinib up-regulated the expression of cleaved caspase-3 and the ratio of apoptotic cells in HPMECs, and also elevated the percentage of S phase and the expression of Cyclin D1 in primary PASMCs under hypoxia. Melatonin ameliorated dasatinib-aggravated oxidative damage and apoptosis in HPMECs, meanwhile reduced oxidative stress level, proliferation, and repressed the stability of HIF1-α protein in PASMCs under hypoxia. In conclusion, melatonin significantly attenuates dasatinib-aggravated hypoxic PH by inhibiting pulmonary vascular remodeling in rats. The possible mechanisms involved protecting endothelial cells and inhibiting abnormal proliferation of smooth muscle cells. Our findings may suggest that melatonin has potential clinical value as a therapeutic approach to alleviate dasatinib-aggravated hypoxic PH.


Stimulus parameters that produce age differences in block design performance.
Administered block designs that varied according to two parameters, Task Uncertainty and Perceptual Cohensiveness, to 83 persons 49 years of age or older. Performance was adjusted to remove motor speed differences. Performance changed significantly over the age span as a function of Task Uncertainty. From 49 years up, performance did not change as a function of Perceptual Cohesiveness. An analysis that included a group of 20 persons 30 years of age or younger yielded an interaction of Age and Perceptual Cohesiveness. From 49 years on, analytic or image segmentation processes do not seem to change, but other information processing becomes slower.


Influence of radiographic contrast media (Iodixanol and Iomeprol) on the endothelin-1 release from human arterial and venous endothelial cells cultured on an extracellular matrix.
Various radiographic contrast media (RCM) are available for visualization of blood vessels in interventional cardiology which can vary widely in their physicochemical properties thereby influencing different functions of blood cells. In the in vitro study described here the influence of two RCMs on arterial as well as on venous endothelial cells was compared to control cultures and examined under statical culture conditions, thus eliminating the influence of RCM viscosity almost completely. The supplementation of the culture medium with RCM (30% v/v) resulted in clearly different reactions of the endothelial cells exposed. Exposition to Iodixanol supplemented culture medium was followed by endothelin-1 release from venous endothelial cells which was equivalent to the endothelin-1 release from venous control cultures. Compared to control cultures, venous endothelial cells exposed to culture medium supplemented with Iomeprol displayed a completely different reaction, the increase in endothelin-1 secretion was missing completely after a 12 hours exposure. Following a 12 hours exposure to both RCMs there were no longer endothelial cells adherent, neither in venous nor in arterial endothelial cell cultures. The study showed that not the wall shear stress was responsible for the differing effects visible after 1.5 min, 5 min, and 12 hours exposure to culture media supplemented with RCM but differences in chemotoxicity of the RCM applied.


[Maternal feeding and social inclusion practices in mexican children with disabilities. Approach with focal groups].
The aim of this study was to identify the maternal feeding practices with children who have some kind of disability and its influence in their social inclusion process. Three focus groups were carried out with the participation of twelve mothers/caregivers of children with disabilities. The mothers/caregivers are in charge of their children's progress with respect to their physical health and disability. Their feeding practices contribute to their health condition, to the acquisition of nourishing learning, social behavior at the table, domestic collaboration, as well as to the development of language by means of the communicative interactions, and also the tightening of the affective bond between mother and child. Nourishing practices make possible the cultural transmission of food preferences and aversions and, additionally, generate a context that fosters the development of very diverse learning which, in the case of children with some type of disability, could contribute to the improvement of their pro-social skills and repertoires mediated by their mothers or caregivers.


[Comparison of beta-blocking agents pharmacokinetics in obese and non-obese subjects].
We compared in obese patients and normal subjects, the pharmacokinetics of three drugs with different solubility: d,l-sotalol markedly hydrophilic, d,l-propranolol highly lipophilic, d,l-bisoprolol moderately lipophilic. In obese subjects the pharmacokinetic data calculated for sotalol (total clearance (CL), volume of distribution (V beta), half-life of elimination (t1/2), were comparable with those measured in the controls. Data on bisoprolol showed that total V beta increased with excess of body weight, but V beta/kg of body weight was lower in obese subjects than in the controls, CL tended to increase and t1/2 was similar. As concerned propranolol, total V beta and V beta/kg were significantly lower in obese than in control subjects. Cl was decreased in obese patients and t1/2 was similar for both groups. It appears that in the obese the diffusion of liposoluble beta-blockers in the fatty excess weight remains limited. It is possible that a vasoconstrictive effect induced by beta-blockers in adipose tissues could restrict their tissular distribution.


Potential new applications of immunotherapy for neuroendocrine neoplasms: immune landscape, current status and future perspectives.
Neuroendocrine neoplasms (NENs) are a highly heterogeneous class of tumors arising from neuroendocrine cells and peptidergic neurons. After failure of first-line treatment, patients have poor prognosis and limited treatment options. Immune checkpoint inhibitors (ICIs) may be a powerful means of increasing therapeutic efficacy for such patients, but ICIs alone have low response rates and short disease control durations in most NENs and may be effective for only a portion of the population. ICIs combined with other immunotherapies, targeted therapies, or cytotoxic drugs have achieved some efficacy in patients with NENs and are worthy of further exploration to assess their benefits to the population. In addition, accumulating experimental and clinical evidence supports that the interaction between neuroendocrine and immune systems is essential to maintain homeostasis, and assessment of this broad neuroendocrine-immune correlation is essential for NEN treatment. In this review, we summarize the immune microenvironment characteristics, advances in immunotherapy, predictive biomarkers of ICI efficacy for NENs, and the effects of common endocrine hormones on the immune system, highlighting possible new application areas for this promising treatment in neglected NENs.


Stable Isotope and Element Profiling for Determining the Agroclimatic Origin of Cow Milk within a Tropical Country.
Information on the geographic origin of milk is important in determining quality attributes and for economic gain through building brand value associated with origin. Stable isotope signatures and trace element concentrations have been increasingly used in authentication of milk, though information on the power of such technology in verifying agroclimatic origin in small continents with diverse climatic, environmental conditions, and animal management practice is scarce. Therefore, the main objective of this study was to investigate the possibility of using a stable isotope composition of C, N, O, and H and element fingerprints to determine the agroclimatic origin of milk produced in different agroclimatic zones of Sri Lanka. Stable isotopes ratios of C, N, H, and O, and elemental fingerprints of milk samples were determined by IRMS and ICP-MS, respectively. Significant variations were observed in stable isotope ratios, especially δ18O and the mean content of Li, Al, Cr, Mn, and Sr in the bulk milk samples obtained from different agroclimatic zones. A linear discriminant analysis differentiated cow milk produced from four agroclimatic zones based on stable isotope ratios, and the inclusion of elemental ratios enhanced the discriminating ability.


Comparison of plaque- and flow cytometry-based methods for measuring dengue virus neutralization.
As dengue vaccines enter clinical trials, there is a need for rapid and quantitative assays to measure neutralization. We have developed flow-based neutralization assays which generated results similar to those generated by the established, plaque reduction neutralization test. The flow assays are an improvement, as they use human cells and allow for high-throughput screening.


Cosmetic rhinoplasty: radiological features.
The usual radiologic postoperative appearance of the bony nasal pyramid following a typical cosmetic rhinoplasty is demonstrated, and possible atypical sequelae are discussed. More specifically, the sites of the osteotomies performed as part of this surgical procedure are diagrammatically illustrated. It is believed that because of the increasing popularity of rhinoplastic operations, it is timely to acquaint radiologists with the postsurgical stigmata which, though minor, might be erroneously interpreted as resulting from accidental trauma or other pathologic processes. Beyond academic considerations, potential medicolegal implications also exist. A brief historical overview is included.


Severe complications of varicella in previously healthy children in Germany: a 1-year survey.
Varicella is a common infectious disease, usually benign and self-limited, and complications are believed to be rare. The purpose of this study was to describe the epidemiology of severe varicella complications in immunologically healthy children in Germany. Information on any admission of children with a severe complication associated with chickenpox was solicited throughout 1997 from all 485 pediatric hospitals in Germany using an established surveillance system. The case definition included nonimmunocompromised individuals who were up to 16 years of age and hospitalized with neurologic complications, bacterial superinfections, or hematologic complications. The response rate to the surveillance questionnaire during the observation period was high: 93.4%. Of the 153 reported cases, 119 met the case definition. There was a seasonal distribution of reported complications with a peak in March. The majority of complications occurred in preschool-age children with a maximum age of 4 years. No gender predominance was found with a distribution of 56 female and 63 male patients. Multiple entries for complications were allowed. The most frequent complications were neurologic, which were reported in 73 children (61.3%); cerebellitis was the leading diagnosis (n = 48), followed by encephalitis (n = 22), meningitis (n = 2), and central facial palsy (n = 1). A total of 46 (38.6%) infectious complications were identified. Superinfections of the skin were present in 31 (26.0%), pyogenic arthritis was present in 5 (4.2%), osteomyelitis was present in 4 (3.3%), necrotizing fasciitis was present in 3 (2.5%), orbital cellulitis was present in 2 (1.6%), and pneumonia was present in 1 (0.8%). Streptococcus pyogenes was the leading cause of bacterial infections (18 cases [15.1%]), with invasive disease in 6 patients (8.4%) and linked to 4 of 8 cases with defect healing. Infectious complications were reported in the majority in younger children up to 4 years of age, whereas neurologic complications occurred more frequently in an older age range. Five children experienced thrombocytopenia or severe anemia. There was no bleeding disorder, no fatality, and no case of Reye syndrome reported during the 1-year observation period. In total, 8 (6.7%) of 119 patients reported having long-term sequelae, 6 attributable to infectious complications and 2 to persistent deficits after neurologic complications. This is the first prospective nationwide study of severe complications of varicella in immunologically healthy children. Related to 14 025 867 children up to the age of 16, a crude incidence of severe chickenpox complications of 0.85/100 000 could be calculated [corrected]. The actual hospitalization rate attributable to complicated chickenpox is probably much higher, because this calculation refers to a population theoretically at risk and not the truly susceptible individuals. The results of this study demonstrate considerable morbidity with a comparatively high rate of encephalitis, osteomyelitis, and pyogenic arthritis. Although infectious complications were present in only 38.6% of the reported cases, they contributed disproportionately to the cases with chronic sequelae. Looking at these cases in more detail, S pyogenes involvement was identified as the major risk factor for invasive disease with an unfavorable long-term outcome. varicella-zoster virus, chickenpox/epidemiology, chickenpox/complications, encephalitis, cellulitis, osteomyelitis, necrotizing fasciitis, group A beta-hemolytic streptococci, Europe.


Comparing the Clinical Characteristics, Laboratory Findings, and Outcomes between Epidemic and Episodic Methanol Poisoning Referrals; a Cross-sectional Study.
Due to illegal manufacturing and sales of alcoholic beverages, epidemic outbreaks of methanol poisoning may occur. The aim of this study was to determine if there were differences in the severity, course of poisoning, and outcomes between methanol-poisoned patients admitted during an outbreak versus those who were admitted following episodic exposures. The present retrospective study was performed in a single referral poisoning center between March 2018 and March 2019 in patients with confirmed methanol poisoning. During this time, in addition to episodic cases of methanol intoxication, there were three methanol poisoning outbreaks. Outbreaks were characterized by an unexpected increase in the number of methanol-poisoned patients in a short period of time, which impacted resources and decision-making. The two groups were compared regarding their severity of poisoning, sessions of hemodialysis, and clinical outcomes. Outbreak cases had a higher level of methanol than episodic cases. Odds of being dialyzed more than once was 5.4 times higher in the cases presenting during an outbreak (95% CI 2.1-14.0; p=0.001). Mean hospital stay, intubation/mechanical ventilation, and death were similar between the two groups. An evaluation of the alcoholic beverage samples available in the Iranian black market during the outbreak showed a 7-percent methanol concentration with no ethanol content. Poisoning risk may be higher during methanol outbreaks due to the higher methanol concentrations, requiring more hemodialysis sessions for persistent metabolic acidosis. In addition to alcohol dehydrogenase blockade, careful risk assessment of all methanol poisonings can assist with stratifying the priority for, and duration of, hemodialysis to optimize outcomes.


Effects of two types of cobra venom factor on porcine complement activation and pulmonary artery pressure.
Autologous porcine plasma that has been incubated with cuprophan haemodialysis membranes causes pulmonary hypertension and peripheral leucopenia following reinfusion into swine. These effects appear to be mediated by biologically active fragments of C3 and C5 that are generated as a consequence of ex vivo activation of complement. Putatively, C5a induces the leucopenia; however, the specific contributions of products of C3 and C5 activation to the pulmonary vasoconstriction have not been elucidated. In the present study, the effects of in vivo infusion of two different types of cobra venom factor (CVF) on peripheral leucocyte count and pulmonary artery pressure in the swine are reported. The CVF from Naja n. naja (CVF(TN)) was shown to activate both porcine C3 and C5, whereas the CVF from Naja h. haje (CVF(NH)) activated only C3. Both types of CVF produced pulmonary hypertension. Significant peripheral leucopenia, however, was observed only with CVF(TN). These results suggest that activation products of C3 contribute to the pulmonary hypertension but not to the peripheral leucopenia observed during haemodialysis using dialysis membranes that activate complement.


[Quantitative analysis of regional cerebral blood flow in elderly with white matter lesions].
To observe whether the severity of white matter lesions (WML) is related to ischemia in elderly. WML were divided into 2 categories (centrum semiovale and periventricular regions) and four grades (grade 0, grade 1, grade 2 and grade 3) according to the severity of WML showing on the FLAIR sequence of MRI using modified Fazekas scale. The values of regional cerebral blood flow (rCBF) within WML and other brain regions were measured using Xenon contrast CT. Mean rCBF (ml x 100 g(-1) x min(-1)) within lesions around periventricular areas, in right and left centrum semiovale were 20.8 +/- 2.8, 22.3 +/- 1.9 and 22.2 +/- 2.1 in grade 0; 20.3 +/- 2.5, 21.3 +/- 1.0 and 21.0 +/- 1.8 in grade1; 16.3 +/- 2.0, 15.6 +/- 1.7 and 15.9 +/- 0.9 in grade 2; 14.1 +/- 2.6, 14.5 +/- 2.2 and 14.2 +/- 1.9 in grade 3 respectively. The severity of WML is associated significantly with reduction of rCBF within lesions both in centrum semiovale and periventricular regions (all P < 0.05). There was no significant difference in rCBF values between grade 0 and 1, but significant differences existed between grade 0 and grades 2 and 3, between grade 1 and grades 2 and 3 (all P < 0.05). Statistical significance also existed between the severity of white matter lesions and rCBF in bilateral temporal lobes and lentiform nucleases (P < 0.05). The severity of WML both in centrum semiovale and periventricular regions is associated significantly with reduction of rCBF within lesions.


Host miRNA-21 promotes liver dysfunction by targeting small intestinal Lactobacillus in mice.
New evidence shows that host-microbiota crosstalk can be modulated via endogenous miRNAs. We have previously reported that miR-21 ablation protects against liver injury in cholestasis. In this study, we investigated the role of miR-21 in modulating the gut microbiota during cholestasis and its effects in liver dysfunction. Mice lacking miR-21 had reduced liver damage and were protected against small intestinal injury as well as from gut microbiota dysbiosis when subjected to bile duct ligation surgery. The unique microbiota profile of miR-21KO mice was characterized by an increase in Lactobacillus, a key microbiome genus for gut homeostasis. Interestingly, in vitro incubation of synthetic miR-21 directly reduced Lactobacillus load. Moreover, supplementation with Lactobacillus reuteri revealed reduced liver fibrosis in acute bile duct-ligated mice, mimicking the protective effects in miR-21 knockout mice. D-lactate, a main product of Lactobacillus, regulates gut homeostasis that may link with reduced liver fibrosis. Altogether, our results demonstrate that miR-21 promotes liver dysfunction through direct modulation of the gut microbiota and highlight the potential therapeutic effects of Lactobacillus supplementation in gut and liver homeostasis.


S-phase checkpoints regulate Apo2 ligand/TRAIL and CPT-11-induced apoptosis of prostate cancer cells.
As S-phase checkpoints play critical roles in maintaining genomic integrity and replicating the human genome correctly, understanding the molecular mechanism by which they regulate the therapeutic response is of great interest. Previously, we reported that the cytotoxic effect of a zinc-bound form of Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL), which is currently evaluated in clinical trials, in combination with low-dose CPT-11, induces apoptosis of C4-2 human prostate cancer cells and tissues. Here, we show that apoptosis, induced synergistically by this combination treatment, was associated with accumulation of cells in early S phase, indicated by cell cycle analyses, increased proliferating cell nuclear antigen, and Chk2-Thr(68) phosphorylation in tumors xenografted in mice. The combination treatment induced an S-phase checkpoint response through activation of Chk2 and Chk1 by the ataxia telangiectasia mutated and ataxia telangiectasia mutated and Rad3 related kinases, leading to phosphorylation and decreased Cdc25A levels. Cdc25A-dependent regulation of cyclin-dependent kinase 2 (Cdk2) and changes in association of p21(WAF1/CIP1) and hSpy1 with Cdk2 resulted in inhibition of Cdk2-associated kinase activity. Knockdown of ataxia telangiectasia mutated/Chk2 and ataxia telangiectasia mutated and Rad3 related/Chk1 by small inhibitory RNAs abrogated the S-phase checkpoint and accelerated apoptosis, resulting in caspase-3 activation and poly(ADP-ribose) polymerase 1 cleavage following combination treatment. Thus, Apo2L/TRAIL + CPT-11 treatment-induced apoptosis is regulated through an S-phase checkpoint controlled by the Chk2-Cdc25A and Chk1-Cdc25A pathways and inhibition of Cdk2-associated kinase activity. Low-dose CPT-11 and aphidicolin increased the proportion of S-phase cells and sensitized cells to Apo2L/TRAIL, by inducing phosphatidylserine externalization, caspase activation, and poly(ADP-ribose) polymerase 1 cleavage. Combinations with S-phase arrest-inducing chemotherapeutic drugs may represent promising avenues for clinical development of Apo2L/TRAIL.


Changes in RNA titers and polyadenylation during oogenesis and oocyte maturation in Xenopus laevis.
The titers of over 90 sequences isolated by cDNA cloning of oocyte poly(A)+RNA were examined during oogenesis in Xenopus laevis. The relative titers of most sequences in unfertilized eggs are established in pre-lamp brush oocytes and persist throughout oogenesis. We have identified several sequences whose titers decrease significantly during the growth phase of oogenesis as well as a few sequences whose titers increase slightly during this period. Among 21 sequences analyzed by RNA gel blots, all remained unchanged in titer during oocyte maturation. A significant fraction of early oocyte RNA does not bind to oligo(dT)cellulose, but by the end of oogenesis transcripts for many RNA species examined are detected exclusively in the poly(A)+RNA fraction. During oocyte maturation a slight size shift or a broadening of the hybridizing band can be seen for many sequences, indicative of poly(A) elongation or degradation.


The association of polymorphisms in nucleotide excision repair genes with ovarian cancer susceptibility.
Nucleotide excision repair (NER), the core mechanism of DNA repair pathway, was commonly used to maintain genomic stability and prevent tumorigenesis. Previous investigations have demonstrated that single nucleotide polymorphisms (SNPs) of NER pathway genes were associated with various types of cancer. However, there was no research elucidating the genetic association of entire NER pathway with ovarian cancer susceptibility. Therefore, we conducted genotyping for 17 SNPs of six NER core genes (XPA, XPC, XPG, ERCC1, ERCC2, and ERCC4) in 89 ovarian cancer cases and 356 cancer-free controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to describe the strength of association. The result showed that both ERCC1 rs11615 and XPC rs2228000 were significantly associated with reduced risk of ovarian cancer under dominant genetic model (adjusted OR = 0.35, 95% CI = 0.20-0.61, P=0.0002 and adjusted OR = 0.49, 95% CI = 0.30-0.81, P=0.005 respectively). In addition, XPC rs2228001 and ERCC2 rs238406 had statistically significant association with the increased risk of ovarian cancer under dominant genetic model (adjusted OR = 1.72, 95% CI = 1.02-2.92, P=0.043 and adjusted OR = 2.07, 95% CI = 1.07-4.01, P=0.032 respectively). ERCC1 rs3212986 were related with the increased risk of ovarian cancer under recessive model (adjusted OR = 2.40, 95% CI = 1.30-4.44, P=0.005). In conclusion, our results indicated that ERCC1, XPC and ERCC2 might influence ovarian cancer susceptibility. Further research with large sample size is warranted to validate the reliability and accuracy of our results.


[New views on immunopathology of viral hepatitis B and C].
The interaction of non-cythopatic, hepatotropic viruses of hepatitis B and C with the host's immune system plays a critical role in determining the viral clearance and it contributes to the liver damage. The initial line of defence is antigen non-specific and is mediated by natural killer cells and macrophages. Simultaneously, virus-specific immunity is induced by professional antigen presenting cells that process and present viral antigens to T and B lymphocytes in the regional lymph nodes. Thereafter, viral specific T helper cells are activated and these cells initiate the anti-viral immune responses of B and CTL lymphocytes. Early, multispecific T cell responses are associated with viral clearance, whereas the imbalance of viral specific Th1 and Th2 lymphocytes plays a crucial role in the viral persistence. The imbalance of viral specific Th1 and Th2 lymphocytes leads to inadequate activation of antigen specific CTL cells. After recognition of viral antigens, T helper lymphocytes are differentiated to Th1 and Th2 cells according to the type of secreted cytokines. Th1 cells produce cytokines: interleukin-2, IFN-gamma, TNF-alpha, which are responsible for effective activation of CTL cells. In contrast, interleukin-4, interleukin-5 and interleukin-10 are secreted by Th2 cells, which are involved in activation of B lymphocytes and in production of neutralizing antibodies. These finding suggests that the viral clearance is associated with the early development and adequate mounting of the anti-viral multispecific immune responses of T helper and cytotoxic T lymphocytes.


Electroglotographic voice measurement analysis: normality standards for singers through Kay Pentax® CSL Program.
Analyze the measures of the fundamental frequency, electroglotographic jitter, contact quotient and periodicity of the electroglotographic waves of the singers in habitual voice. A cross-sectional observational study, which selected individuals from singing schools in the central region of the municipality of Belo Horizonte. The sample was non-probabilistic, for convenience consisted of 60 singers aged between 18 and 55 years, 30 males and 30 females. For the electroglotographic record collection, the Kay Pentax ™ CSL program, model 6103, the Electroglotographic module was used. The participants were placed in a seated position, and after cleaning the skin of the neck with 70% alcohol, two electrodes were placed on the wings of the thyroid cartilage at the level of the vocal folds. Subsequently, the participants were instructed to emit the vowel/a/sustained in a habitual way. The measurements of the fundamental frequency (f0), contact quotient (QC), electroglotographic jitter and periodicity of the electroglotographic wave were analyzed. The data were statistically analyzed using Minitab 17. The parameters analyzed were statistically significant. The fundamental frequency (f0) was higher in females (226.91Hz) when compared to males (166.54Hz). The measure of contact quotient and periodicity was also higher in women (40.46% and 15.51% respectively) when compared to men (27.45% and 7.82, respectively). The jitter parameter was higher in men when compared to women. Women presented higher values in the fundamental frequency (f0), contact quotient (QC) and periodicity of the wave compared to men. The men presented the jitter value higher than that of the women.


Bilateral periventricular nodular heterotopia in France: frequency of mutations in FLNA, phenotypic heterogeneity and spectrum of mutations.
Bilateral periventricular nodular heterotopia (BPNH) is the most common form of periventricular heterotopia. Mutations in FLNA, encoding filamin A, are responsible for the X linked dominant form of BPNH (FLNA-BPNH). Recently, atypical phenotypes including BPNH with Ehlers-Danlos syndrome (BPNH-EDS) have been recognised. A total of 44 FLNA mutations have so far been reported in this phenotype. Most of these mutations lead to a truncated protein, but few missense mutations have also been described. Here, the results of a mutation screening conducted in a series of 32 BPNH patients with the identification of 12 novel point mutations in 15 patients are reported. Nine mutations were truncating, while three were missense. Three additional patients with BPNH-EDS and a mutation in FLNA are described. No phenotype-genotype correlations could be established, but these clinical data sustain the importance of cardiovascular monitoring in FLNA-BPNH patients.


Defective infection of bovine herpesvirus 1 in non-permissive murine cells.
The defective growth of bovine herpesvirus I (BHV-1) was analyzed in non-permissive murine embryo fibroblast, BALB/3T3 A31-1-1 (A31) cells. BHV-1 was able to attach and penetrate into A31 cells at similar levels that were seen in semi-permissive cells. Once penetrated into A31 cells, BHV-1 was efficiently transported to nuclei, but the onset of expression of immediate early (IE) protein and viral DNA replication was not observed. These data suggest that the viral replication of BHV-1 in A31 cells is arrested at the point prior to the expression of IE proteins.


Amperometric biosensor for glyphosate based on the inhibition of tyrosinase conjugated to carbon nano-onions in a chitosan matrix on a screen-printed electrode.
Glyphosate [N-(phosphonomethyl)glycine] is the most frequently used herbicide to date. Due to its indiscriminate use, it has become a globally occurring pollutant of surface waters. A biosensor for glyphosate is described here that consists of a carbon nano-onion/tyrosinase conjugate immobilized in a chitosan matrix on a screen-printed electrode. The analytical principle is based on the inhibition of the enzyme tyrosinase by glyphosate. L-DOPA is used as the enzyme substrate. The presence of the carbon nano-onions has a beneficial effect on the sensitivity of the assay. Glyphosate can be amperometrically quantified in the 0.015 to 10 μM concentration range and with a 6.5 nM (1.1 μg L-1) detection limit. The biosensor is stable more than 2 months at 4 °C. It was applied to the detection of glyphosate in water and soil samples taken from irrigation of a rice field after aerial application. Results were in good agreement with data obtained by a commercial ELISA. Graphical abstract A highly sensitive amperometric biosensor for glyphosate is reported, based on the covalent immobilization of a carbon nano-onion/tyrosinase conjugate on a chitosan matrix.


Poly(N-vinylpyrrolidone)-Laponite XLG Nanocomposite Hydrogels: Characterization, Properties and Comparison with Divinyl Monomer-Crosslinked Hydrogels.
The present work investigates, for the first time, the synthesis and properties of some nanocomposite (NC) hydrogels obtained by the aqueous solution free radical polymerization of N-vinylpyrrolidone (NVP) in the presence of Laponite XLG (XLG) as a crosslinker, in comparison with the corresponding hydrogels prepared by using two conventional crosslinking divinyl monomers: N,N'-methylenebisacrylamide (MBA) and tri(ethylene glycol) divinyl ether (DVE). The structure and properties of the hydrogels were studied by FTIR, TEM, XRD, SEM, swelling and rheological and compressive mechanical measurements. The results showed that DVE and XLG are much better crosslinking agents for the synthesis of PNVP hydrogels than MBA, leading to larger gel fractions and more homogeneous network hydrogels. The hydrogels crosslinked by either DVE or XLG displayed comparable viscoelastic and compressive mechanical properties under the experimental conditions employed. The properties of the XLG-crosslinked hydrogels steadily improved as the clay content increased. The addition of XLG as a second crosslinker together with a divinyl monomer strongly enhanced the material properties in comparison with the hydrogels crosslinked by only one of the crosslinkers involved. The FTIR analyses suggested that the crosslinking of the NC hydrogels was the result of two different interactions occurring between the clay platelets and the PNVP chains. Laponite XLG displayed a uniform distribution within the NC hydrogels, the clay being mostly exfoliated. However, a small number of platelet agglomerations were still present. The PNVP hydrogels described here may find applications for water purification and in the biomedical field as drug delivery systems or wound dressings.


[From evidence-based medicine to medicine-based evidence].
Medical practice is changing due to the more efficient use of the biomedical literature in making decisions on the care of individual patients. This constitutes a new scientific paradigm: evidence-based medicine (EBM). The factors that may explain the growing interest in EBM are awareness of variability in clinical practice, the importance of the efficacy, effectiveness and efficiency of new health technologies, and ease of access to biomedical literature (especially through the Internet). The main tools of EBM in clinical practice are the increasing production of systematic reviews of health interventions (Cochrane Collaboration, Agencies for Health Technology Assessment, Clinical Practice Guidelines) and critical appraisal of scientific documents [Critical Appraisal Skills Program (CASP) and Critically Appraised Topics banks].EBM emphasizes benefit to the individual patient and its key point is efficacy, since the principal source of information are clinical trials and meta-analyses in "ideal" clinical practice. Medicine-based evidence, as the complement of EBM, emphasizes benefit to society and its key point is the effectiveness and efficiency of health interventions, since the main information sources are measures of health-related quality of life and economic analyses in "normal" clinical practice. Total quality management aims at medicine based evidence.


Cryopreservation of immature oocytes of the indigeneous Vietnamese Ban Pig.
We report the cryopreservation of oocytes from Ban miniature pigs which are endemic in Vietnam. Immature cumulus-oocyte complexes were collected from antral follicles of 7-8 mo old female cyclic Ban pigs and vitrified in micro-drops. Oocyte morphology, lipid content, post-warming survival, nuclear maturation, and embryo development were compared to those of oocytes from commercially slaughtered Landrace × Large white hybrid pigs. The size of oocytes in the two breeds was similar. However, significantly lower amounts of intracellular lipid were detected in Ban oocytes. There was no difference (p > 0.05) between Ban and Landrace × Large white oocytes in percentages of post-warming survival (93.1 ± 3.4% vs. 70.7 ± 16.7%, respectively) and nuclear maturation after in vitro maturation (80.4 ± 5.1% vs. 90.0 ± 1.3% respectively). Similarly, cleavage (30.8 ± 7.8% vs. 10.3 ± 6.1%, respectively) and blastocyst development rates (9.4 ± 5.0% vs. 0.79 ± 0.79, respectively) were not different (p > 0.05) between vitrified Ban and Landrace × Large white oocytes after in vitro fertilization and embryo culture. In conclusion, high survival and maturation rates were achieved after vitrification of immature Ban oocytes and their cryo-tolerance was similar to that of Landrace × Large white oocytes, despite the difference in lipid content. We succeeded to generate reasonable rates of blastocysts from vitrified Ban oocytes by in vitro fertilization.


Clinical characteristics of patients with exercise-induced ST-segment elevation without prior myocardial infarction.
Exercise-induced ST-segment elevation is a relatively uncommon problem and occurs more frequently in patients who have had a myocardial infarction. Data is limited on the characteristics of Taiwanese patients without prior myocardial infarction who develop exercise-induced ST-segment elevation. Exercise-induced ST-segment elevation developed in 9 of 6,147 consecutive patients without myocardial infarction who underwent treadmill exercise testing at out institution over a 4-year period. The clinical and angiographic characteristics of these patients were studied. Angiographically normal coronary arteries with coronary vasospasm were found in 5 patients, hemodynamically significant coronary stenosis was found in 3 patients, and coexisting spasm in angiographically normal coronary arteries combined with hemodynamically significant coronary stenosis in the different vessel was found in 1 patient. During a median follow-up of 71 months, 2 patients with coronary vasospasm developed recurrent angina after self-discontinuation of calcium antagonists and 2 patients (1 with coronary vasospasm and 1 with hemodynamically significant coronary stenosis) died of cardiac causes before arrival at the emergency department. Coronary vasospasm was a more common underlying pathology of exercise-induced ST-segment elevation in this Taiwanese cohort. Coronary angiography +/- intracoronary ergonovine provocation testing is necessary in these patients to identify the underlying pathology and appropriate treatment.


[Sorbitol-6-Phosphate Dehydrogenase Gene Polymorhism in Malus Mill. (Rosaceae)].
The sorbitol-6-phosphate dehydrogenase gene (S6PDH) sequences of six representatives of the genus Malus, which belong to five different taxonomic sections, were examined for the first time. The exon-intron structure and polymorphism of the nucleotide and amino acid sequences of these genes was characterized. The intraspecific polymorphism of the S6PDH gene was assessed for the first time in 40 Russian and foreign apple (Malus domestica) cultivars. It was demonstrated that the interspecific polymorphism level of the S6PDH coding sequences in the studied. representatives of the genus Malus was 4%, and the intraspecific polymorphism level of M. domestica cultivars was very low, constituting 0.96%.


Photochemical grafting of n-alkenes onto carbon surfaces: the role of photoelectron ejection.
The grafting of molecular layers to carbon-based materials provides a way to combine the high chemical and thermal stability of these materials with surface properties such as chemical recognition or reactivity. The functionalization of surfaces with ultraviolet light has emerged as a way to modify difficult-to-functionalize materials, such as diamond. We have performed a combined experimental and computational investigation of the photochemical reaction of terminal alkenes with hydrogen-terminated carbon surfaces. 1-Alkenes carrying various terminal functional groups (-NHCOCF3, -NHCOO(tert-butyl), -COOCH3, -CH3) were grafted from the neat liquids using 254 nm light. These layers were characterized using X-ray Photoelectron Spectroscopy and Infrared Reflectance Absorption Spectroscopy. Pronounced differences in reactivity were observed between the molecules: trifluoroacetamide-terminated alkenes grafted the fastest and yielded self-terminating layers after approximately 4 h. Ultraviolet photoelectron spectroscopy and photocurrent measurements show that the grafting reaction involves photoemission of electrons into the liquid. Density functional calculations show that the reactivities of the four molecules are correlated with their electron affinities, with the trifluoroacetamide group acting as the best electron acceptor and having the highest reactivity. Our results demonstrate that photoejection of electrons from the solid into the acceptor levels of the alkenes initiates the functionalization reaction and controls the overall rate. Finally, marginally reactive n-alkenes were induced to react and form dense monolayers by seeding the carbon surface with small amounts of a good electron acceptor, such as the trifluoroacetamide moiety. This study provides important new mechanistic insights into the use of ultraviolet light to initiate grafting of alkenes onto surfaces.


Can Arthroplasty Stem INfluence Outcome? (CASINO): a randomized controlled equivalence trial of 125 mm versus 150 mm Exeter V40 stems in total hip arthroplasty.
The use of shorter length femoral stems during total hip arthroplasty has been suggested to accommodate wider patient femoral geometry and offer maximal bone preservation. However, cemented short-stem designs may increase the risk of varus stem malalignment and influence patient outcomes. CASINO is a multi-centre randomised equivalence trial that will recruit 220 patients undergoing total hip arthroplasty for osteoarthritis at two NHS hospitals in Scotland. Patients will be aged 45-80, undergoing unilateral primary hip arthroplasty, with no plan for contralateral procedure within the study timeframe, and able to comply with the protocol. Participants will be randomised to receive either a short (125 mm) or a standard (150 mm) Exeter V40 stem. The Contemporary acetabular component will be used in all cases. All implants will be cemented. Patient pain, function and satisfaction will be assessed using change from baseline measurement in Oxford Hip Score, Forgotten Joint Score, EQ-5D, pain numerical rating scores, and patient satisfaction questionnaire at baseline and at 1 and 2 years following surgery. Radiographic assessment will evaluate stem position and will be appraised by independent reviewers. Patients will be blind to implant allocation. Stem length may be associated with outcome; however, we can find no randomised trial in which researchers investigated the effect of stem length on patient outcome following cemented total hip arthroplasty. The aim of this trial is to determine if the use of short cemented stems offers equivalent patient outcomes to those achieved following surgery with standard length stems. International Standard Randomised Controlled Trial Number, ISRCTN13154542 , Registered on 30 June 2017.


Serum concentrations of Levetiracetam in epileptic patients: the influence of dose and co-medication.
Levetiracetam (LEV) is a new antiepileptic drug approved as add-on therapy. Previous studies indicated that LEV has no relevant interactions with other antiepileptic drugs. The aim of this study was to investigate the influence of LEV dose, age, and co-medication on the serum concentration of LEV. In total, 363 samples of 297 inpatients who fulfilled the inclusion criteria (e.g., trough concentration, body weight available) were investigated. A patient was considered twice only if his co-medication had been changed. The LEV serum concentration in relation to LEV dose/body weight [level-to-dose ratio, LDR, (microgram/mL)/(mg/kg)] was calculated and compared for the most frequent drug combinations. Analysis of covariance (using age as covariate) carried out on the log-transformed data showed that co-medication had a highly significant (P < 0.001) effect on LEV serum concentrations. The median LDR of LEV was 0.32 for LEV + phenytoin, 0.32 for LEV + carbamazepine, 0.34 LEV + oxcarbazepine, 0.45 for LEV + lamotrigine, 0.46 for LEV + phenobarital, 0.52 for LEV monotherapy, 0.53 for LEV + valproic acid, and 0.54 LEV + valproic acid + lamotrigine. In co-medication with phenytoin (P < 0.001), carbamazepine (P < 0.001), and oxcarbazepine (P < 0.004), the LDR of LEV was significantly lower than it was with LEV monotherapy, whereas the LDR of LEV of patients on co-medication with valproic acid or lamotrigine did not differ significantly from the LDR of LEV of patients on LEV monotherapy (P > 0.05). Regression analysis including all 363 samples confirmed that other drugs (e.g., phenytoin, carbamazepine) lower LEV concentrations. In addition to co-medication, age had a significant effect on clearance of LEV. Children had lower LEV concentrations than adults on the same LEV dose per body weight. In contrast to other studies, our data point out that other enzyme-inducing antiepileptic drugs (e.g., phenytoin, carbamazepine) can moderately decrease LEV serum concentrations (by 20-30%). However, our observations should be confirmed by prospective pharmacokinetic studies.


Evaluation of soft tissue asymmetry using cone-beam computed tomography after open reduction and internal fixation of zygomaticomaxillary complex fracture.
In this study, we assessed soft tissue asymmetry that occurred after open reduction of unilateral zygomaticomaxillary complex (ZMC) fractures. We proposed a simple method to assess soft tissue asymmetry after reduction surgery by evaluating the symmetry between the affected and the unaffected sides. The factors affecting soft tissue contour after surgery were also analyzed. Subjects included patients admitted to Wonkwang University Dental Hospital from 2008 to 2013. Cone-beam computed tomography (CBCT) images of asymmetric patients who underwent open reduction at least 3 months prior were compared with healthy patients. The degree of asymmetry was measured in both the open reduction and control groups. Landmarks that showed a statistically significant difference between the two groups were zygion (1.73±0.24 mm), bucclae (1.08±0.26 mm), point of cheek (2.05±0.33 mm) and frontozygomatic point (1.30±0.31 mm). When compared with the normal group, asymmetry can occur in the affected side, which usually shows depression of overlying soft tissue and is statistically significantly different. Evaluation of soft tissue asymmetry with CBCT images after open reduction of ZMC fracture is useful.


A combinatory use of adenoviruses expressing melanoma differentiation-associated gene-7 and replication-competent adenoviruses produces synergistic effects on pancreatic carcinoma cells.
Type 5 adenoviruses expressing mda-7 gene (Ad-mda-7) induced cell death in various kinds of human tumors, but pancreatic carcinoma cells were relatively resistant to Ad-mda-7-mediated cytotoxicity. We then examined whether infection of Ad-mda-7 together with replication-competent Ad produced combinatory cytotoxic effects. We prepared replication-competent Ad, defective of the E1B55kDa gene or activated by a transcriptional regulatory region of the midkine or the survivin gene of which the expression was up-regulated in human tumors. Type 5 Ad bearing the exogenous regulatory region were further modified by replacing the fiber-knob region with that of type 35 Ad. Pancreatic carcinoma cells were infected with replication-incompetent Ad-mda-7 and the replication-competent Ad. Combinatory effects were examined with the CalcuSyn software and cell cycle analyses. Ad-mda-7 and the replication-competent Ad achieved cytotoxicity to pancreatic carcinoma. A combinatory use of Ad-mda-7 and either Ad defective of the E1B55kDa gene or Ad activated by the regulatory region produced synergistic cytotoxic effects. Cell cycle analyses demonstrated that the combination increased sub-G1 populations. These data collectively suggest that expression of MDA-7 augments cytotoxicity of replication-competent Ad and achieves adjuvant effects on Ad-mediated cell death.


Analysis of the B-cell progenitor compartment at the level of single cells.
During B-cell development in the mouse, the VH, DH and JH elements of the immunoglobulin heavy chain (IgH) locus are rearranged, firstly by DH-JH joining, and then by VH-DHJH joining. In-frame ('productive') VHDHJH joints and DHJH joints in reading frame 2 (one of the three possible DH reading frames) allow the expression of mu and truncated mu chains (D mu proteins), respectively. The expression of such molecules from one of the two IgH loci of a cell is thought to interfere with VH-DHJH recombination on the other IgH locus, and to guide the cells through further development. We have developed a gene amplification assay that permits the examination of rearranged immunoglobulin genes in single cells. Using this assay, we monitored cells bearing DHJH and/or VHDHJH joints at early stages of development: in CD43+ B-cell progenitors, subdivided into fractions A, B, C and C' by flow cytometry, and in CD43- pre-B cells (fraction D). Fraction C was enriched for cells with two non-productive VHDHJH joints. Cells containing both a DHJH joint in DH reading frame 2 and a VHDHJH joint were not seen in any fraction. All fraction D cells harbored an in-frame VHDHJH joint. Cells with two productive VHDHJH joints appear to be selected against throughout development. Cells expressing D mu proteins appear to be arrested in development as a result of inhibited VH-DHJH joining. Expression of the mu chain is required for maturation into CD43- pre-B cells; accordingly, cells carrying two non-productive VHDHJH joints accumulate in the CD43+ compartment. Such a developmental arrest may also affect cells that express self-reactive VHDHJH antibody domains. Our results indicate further that allelic exclusion at the IgH locus is already established at the pre-B cell stage.


Analysis of a cytostatic lymphokine produced by incubation of lymphocytes with tumor cells: relationship to leukoregulin and distinction from recombinant lymphotoxin, recombinant tumor necrosis factor, and natural killer cytotoxic factor.
Supernatants from the coculture of peripheral blood lymphocytes and the NK-susceptible cell line K562 were highly growth inhibitory for a variety of tumor cell lines. No correlation was observed between the susceptibility of the target cell lines to growth inhibition and to lysis by NK cells. Rather, the spectrum of cytostatic activity and the characteristics of the soluble factor were similar to those of leukoregulin, a recently described lymphokine. The supernatants of tumor-lymphocyte cultures contained only low levels of IFN-alpha and IFN-gamma, and antibodies to interferons did not affect the observed growth inhibition. The pattern of target cell susceptibility to growth inhibition by this factor was also quite distinct from that seen with purified recombinant LT or TNF. Furthermore, monoclonal antibodies to these cytokines also had no effect on the cytostasis, arguing against a requirement for, or synergistic interaction with, low levels of these cytokines. Some of the targets susceptible to the factor were only growth inhibited but not lysed, thereby distinguishing it from NKCF. Furthermore, the cytostasis was not inhibited by mannose-6-PO4 or rabbit antibodies to granule cytolysin, both of which have been reported to block NKCF. Therefore, the results show that a cytostatic factor is released in tumor-lymphocyte incubation that is quite distinct from interferons, LT, and TNF but has characteristics that resemble those of leukoregulin.


[The EHSA project: the study of spontaneous subarachnoid haemorrhages in Andalusia. Incidence and results].
To evaluate the incidence and results of spontaneous subarachnoid haemorrhages (SAH) in Andalusia. We conducted a longitudinal prospective study of the cases of SAH attended in 28 hospitals in Andalusia over a three month period in 2000. SAH was defined as cases of acute haemorrhagic strokes diagnosed by tomography. The gross incidence rate (GR) was determined from census information from the Instituto Andaluz de Estad stica. Standard rates (SR) were estimated with relation to the European population. Results were evaluated on hospital discharge according to the Glasgow Outcome Score (GOS) and at 12 months, according the Barthel index (BI). The GR per 100,000 inhabitants/year was found to be 5.7 cases and the SR was 5.8. A comparison of incidences by province or sex showed no statistically significant differences. The period of maximum risk was the age bracket between 55 74 years (GR: 14.1). The acute fatality GR and SR rose to 1.9 per 100,000 inhabitants and year. Mortality was concentrated in a statistically significant way (p< 0.01) among those over the age of 65; sex did not exert any influence, but clinical gravity (p< 0.001) and the amount of bleeding did (p< 0.005). The incidence of spontaneous SAH in Andalusia was found to be within the average rates. Unfavourable results were high, although similar to those in other series. Fatality is significantly associated with factors that cannot be modified medically (age, clinical gravity and volume of bleeding)


mTOR hyperactivation in Down Syndrome underlies deficits in autophagy induction, autophagosome formation, and mitophagy.
Down syndrome (DS), a complex genetic disorder caused by chromosome 21 trisomy, is associated with mitochondrial dysfunction leading to the accumulation of damaged mitochondria. Here we report that mitophagy, a form of selective autophagy activated to clear damaged mitochondria is deficient in primary human fibroblasts derived from individuals with DS leading to accumulation of damaged mitochondria with consequent increases in oxidative stress. We identified two molecular bases for this mitophagy deficiency: PINK1/PARKIN impairment and abnormal suppression of macroautophagy. First, strongly downregulated PARKIN and the mitophagic adaptor protein SQSTM1/p62 delays PINK1 activation to impair mitophagy induction after mitochondrial depolarization by CCCP or antimycin A plus oligomycin. Secondly, mTOR is strongly hyper-activated, which globally suppresses macroautophagy induction and the transcriptional expression of proteins critical for autophagosome formation such as ATG7, ATG3 and FOXO1. Notably, inhibition of mTOR complex 1 (mTORC1) and complex 2 (mTORC2) using AZD8055 (AZD) restores autophagy flux, PARKIN/PINK initiation of mitophagy, and the clearance of damaged mitochondria by mitophagy. These results recommend mTORC1-mTORC2 inhibition as a promising candidate therapeutic strategy for Down Syndrome.


Exploring finite temperature properties of materials with quantum computers.
Thermal properties of nanomaterials are crucial to not only improving our fundamental understanding of condensed matter systems, but also to developing novel materials for applications spanning research and industry. Since quantum effects arise at the nano-scale, these systems are difficult to simulate on classical computers. Quantum computers can efficiently simulate quantum many-body systems, yet current quantum algorithms for calculating thermal properties of these systems incur significant computational costs in that they either prepare the full thermal state on the quantum computer, or they must sample a number of pure states from a distribution that grows with system size. Canonical thermal pure quantum (TPQ) states provide a promising path to estimating thermal properties of quantum materials as they neither require preparation of the full thermal state nor require a growing number of samples with system size. Here, we present an algorithm for preparing canonical TPQ states on quantum computers. We compare three different circuit implementations for the algorithm and demonstrate their capabilities in estimating thermal properties of quantum materials. Due to its increasing accuracy with system size and flexibility in implementation, we anticipate that this method will enable finite temperature explorations of relevant quantum materials on near-term quantum computers.


Direct Observation of Methylmercury and Auranofin Binding to Selenocysteine in Thioredoxin Reductase.
Selenoenzymes, containing a selenocysteine (Sec) residue, fulfill important roles in biology. The mammalian thioredoxin reductase selenoenzymes are key regulators of antioxidant defense and redox signaling and are inhibited by methylmercury species and by the gold-containing drug auranofin. It has been proposed that such inhibition is mediated by metal binding to Sec in the enzyme. However, direct structural observations of these classes of inhibitors binding to selenoenzymes have been few to date. Here we therefore have used extended X-ray absorption fine structure as a direct structural probe to investigate binding to the selenium site in recombinant rat thioredoxin reductase 1 (TrxR1). The results demonstrate for the first time the direct and complete binding of the metal atom of the inhibitors to the selenium atom in TrxR1 for both methylmercury and auranofin, indicating that TrxR1 inhibition indeed can be attributed to such direct metal-selenium binding.


[Reduced expression and secretion of apolipoprotein M in fat-fed, streptozotocin-diabetic rats is partially reversed by an artificial ligand of PPARγ].
To investigate the effect of administration of rosiglitazone, an artificial ligand of PPARγ, on the expression and secretion of apolipoprotein (apoM) in fat-fed, streptozotocin-treated rats, an animal model for type 2-like diabetes. Healthy male SD rats were divided into 4 groups: a control group (n=7), a high-fat chow group (HF group, n=8), a diabetes mellitus group (DM group, n=7), and a diabetes mellitus group with rosiglitazone intervention group (RSG group, n=7). Fasting blood glucose (FBG), fasting insulin (FINS), triglyceride (TG) and total cholesterol (TC) were measured at the beginning of the study. The diabetic rats model was established by feeding high fat chow and intraperitoneal injection of streprozotocin. Then the randomly selected treatment group was given rosiglitazone by daily gavage for 8 weeks. All the rats were killed at the fifteenth week, at which time blood and tissues (liver, kidney, adipose) were collected and prepared. The levels of FBG, FINS, TG and TC were assayed. The level of apoM in serum was measured by enzyme-linked immunosorbent assay (ELISA). Reverse transcription polymerase chain reaction (RT-PCR) was used to determine apoM mRNA expression in liver, kidney, and adipose tissues. Compared with either control group or HF group, serum apoM concentration in the DM group was reduced significantly (P<0.05); compared with the DM group, however, serum apoM concentrations in RSG group were increased (P<0.05). The expression of apoM mRNA in liver was highest, in kidney medium, and in adipose tissue extremely low (P<0.05). ApoM mRNA expression in liver and kidney was decreased in both DM and HF groups compared to control group (P<0.05). But, as with serum apoM concentration, apoM mRNA in the liver, kidney and adipose tissues of the RSG group were all increased markedly (P<0.05). The level of serum apoM in SD rats correlated negatively with TG (r=-0.466, P=0.011), TC (r=-0.568, P= 0.001), FBS (r =-0.371, P<0.001), and FINS(r=-0.768, P= 0.048 ). These results suggest that apoM may participate in the glucose and lipid metabolism by the regulation of PPARγ.


Controllable synthesis of new polymerizable macrosurfactants via CCTP and RAFT techniques and investigation of their performance in emulsion polymerization.
We reported herein the synthesis of poly(methacrylic acid)-b-poly(butyl acrylate) (PMAA-b-PBA) block copolymers (surfmers) and their performance as novel polymerizable macrosurfactants in emulsion polymerization. The surfmers bearing terminal unsaturated carbon-carbon double bonds were first successfully designed and sythesized via catalytic chain transfer polymerization (CCTP) and radical addition-fragmentation polymerization (RAFT) techniques. The structures of surfmers were characterized by Raman spectra, nuclear magnetic resonance ((1)H NMR), and gel permeation chromatography (GPC). The critical micelle concentration of surfmers was determined. Subsequently, the surfmers were used as emulsifier to prepare polyacrylate latexes (PA-surf). The influence of the surfmer concentration as well as PMAA and PBA chain segment ratios of surfmer on their performance in emulsion polymerization was discussed thoroughly. The particle size, amount of coagulum, and stability against electrolyte solutions of the latexes were evaluated. Also, the relations between monomer conversion in emulsion polymerization, polymerization rate, emulsion particle size, surface tension, and reaction time were investigated, which showed some interesting information for the probable mechanism underlying this emulsion polymerization system. Atomic force microscopy (AFM) and attenuated total reflection Fourier transform infrared spectra (ATR FT-IR) were performed to investigate the surface morphology and component distribution of the latex films. The results show high efficiency of these surfmers in emulsion polymerization, suggesting that the resultant PMAA-b-PBA block copolymers act not only as the emulsifier but also as the stabilizer of monomer droplets as well as the so-called comonomer.


Lipoprotein(a) levels in patients with myocardial infarction treated with anistreplase: no prediction of efficacy but inverse correlation with plasminogen activation in non-patency.
The aim of this study was to investigate whether failure of thrombolytic treatment might be due to inhibition of fibrinolysis by high lipoprotein(a) levels. Fifty-eight patients with acute myocardial infarction were treated intravenously within 4 h after onset of symptoms with anistreplase (30 units) and heparin (30,000 IU/24 h). Blood samples for measurement of coagulation parameters were taken before and 1.5 h after treatment. Coronary angiography was performed after 48 h. Levels of lipoprotein(a) were measured 6 months after discharge from hospital. The patency rate was 74% (43/58). Median lipoprotein(a) levels were not different between the patients with a patent and those with a non-patent vessel (10 and 8 mg/dl, respectively), however, in patients with a non-patent infarct-related vessel, a significant inverse correlation was found between the lipoprotein(a) level and the decrease of plasminogen in the first 1.5 h after treatment. It is concluded that high lipoprotein(a) levels, although not directly associated with a poor outcome of anistreplase therapy, might contribute to insufficient fibrinolysis in patients with a non-patent infarct-related vessel.


Eye rotation and vignetting in visual instruments.
The eye can rotate to accommodate the angular position of an object and the distance of the object from it. The rotation of the eye inside its socket to align its visual axis in the direction of an off-axis image may introduce full or partial vignetting when one is looking through a visual instrument with a real exit pupil. We analyze the effects of vignetting owing to rotation of the eye in visual instruments with real exit pupils.


Size effects in reactive circular site interactions.
The complete series solution for the reactant diffusion and reaction at two diffusion-controlled chemically reactive surface sites of radii a(1) and a(2), located in an inert plane an arbitrary center-to-center distance d apart, is presented. Rigorous, analytical forms are developed to calculate the site reaction rates in terms of the dimensionless intersite distance σ[=d/(a(1) + a(2))] and the site radius ratio γ(=a(1)∕/a(2)). Numerical simulation and approximate theoretical results from the recent literature are compared to the exact site reaction rates. While general agreement was noted over the ranges of γ and σ, significant errors in the Wilemski-Fixman-Weiss site rates were found at small γ and σ < 3.


Implementing Virtual and Augmented Reality Tools for Radiology Education and Training, Communication, and Clinical Care.
Advances in virtual immersive and augmented reality technology, commercially available for the entertainment and gaming industry, hold potential for education and clinical use in medicine and the field of medical imaging. Radiology departments have begun exploring the use of these technologies to help with radiology education and clinical care. The purpose of this review article is to summarize how three institutions have explored using virtual and augmented reality for radiology.


[Effects of nitric oxide synthase inhibitor on hindlimb muscles in rats with neuropathic pain induced by unilateral peripheral nerve injury].
The purpose of this study was to examine effects of nitric oxide synthase (NOS) inhibitor on muscle weight and myofibrillar protein content of affected and unaffected hindlimb muscles in rats with neuropathic pain induced by unilateral peripheral nerve injury. Neuropathic pain was induced by ligation and cutting of the left L5 spinal nerve. Adult male Sprague-Dawley rats were randomly assigned to one of two groups: The NOSI group (n=19) had NOS inhibitor (L-NAME) injections daily for 14 days, and the Vehicle group (n=20) had vehicle injections daily for 14 days. Withdrawal threshold, body weight, food intake and activity were measured every day. At 15 days all rats were anesthetized and soleus, plantaris and gastrocnemius muscles were dissected from hindlimbs. Muscle weight and myofibrillar protein content of the dissected muscles were determined. The NOSI group showed significant increases as compared to the Vehicle group for body weight at 15 days, muscle weight and myofibrillar protein content of the unaffected soleus and gastrocnemius. The NOSI group demonstrated a higher pain threshold than the vehicle group. NOSI for 14 days attenuates unaffected soleus and gastrocnemius muscle atrophy in neuropathic pain model.


[Prognosis of triplet pregnancies].
31 triplet pregnancies (DG), treated during 1975-1989, were analysed retrospectively. 13 DG (D10) were registered up to the end of the 10th week of pregnancy, 16 (DG) (D16) were intact between the 11th and the 16th gestational week. 3 DG resulted from the reduction of high grade multiple pregnancies. 18 DG (62%) of the initial 29 DG had previously been treated for sterility. The spontaneous foetal loss (DF) in group D10, including the perinatal mortality, amounted to 26% (10 of 39 DF). In one case of this group, a previously vital DF died. In another case, a partial bi-phasic abortion occurred followed by a premature birth of the surviving 3rd DF. The mortality rate in group D16, including the perinatal mortality (4 DF), was 25% (12 of 48 DF). 30 DG were still intact after the 16th week of pregnancy. 2 DG (7%) suffered from EPH-gestosis. In 4 DG (13%) a foeto-foetal transfusion syndrome occurred. 5 DF (6%) had some of the serious malformations. 27 DG were completed. 7 DG (26%) ended before the 32nd gestational week. In 13 DG (48%), a Caesarean section was performed. The perinatal mortality amounted to 11% (9 of the 81 DF) including all the births from the 25th gestational week upwards. On comparing these results with the data in the literature, a significant improvement in the prognosis of DG in recent years can be observed. This is due to the progress in antenatal and neonatal care.


The cranium of Parapithecus grangeri, an Egyptian Oligocene anthropoidean primate.
A nearly complete skull of Parapithecus grangeri from the early Oligocene of Egypt is described. The specimen is relatively undistorted and is undoubtedly the most complete higher primate skull yet found in the African Oligocene, which also makes it the most complete Oligocene primate cranium worldwide. Belonging in superfamily Parapithecoidea, a group regarded by some as the sister group to all other Anthropoidea, this skull reveals important information about the radiation of stem anthropoideans. This cranium is about 15% larger than size estimates based on a fragmentary cranium of its contemporary and close relative Apidium phiomense. It is about the same size as that of the gray gentle lemur, Hapalemur griseus, or of platyrrhines such as the owl monkey, Aotus trivirgatus, or the titi monkey, Callicebus torquatus. Comparatively small orbits and size differences in jaws and teeth show it was both diurnal and dimorphic. This is the only specimen of the species that shows (from sockets) that there were four small upper incisors. Several mandibular specimens of the species establish that there were no permanent lower incisors and that the symphysis was fused. Like other early anthropoideans this species possessed a lower encephalization quotient and less-developed orbital frontality than later anthropoideans. There is full postorbital closure and fusion of the metopic suture, and the ectotympanic forms a rim to the auditory aperture. A probable frontal/alisphenoid contact is a potentially derived resemblance to Catarrhini. A proposed separate genus for the species P. grangeri is not sustained.


Gonadosomatic index and testis morphology of common carp (Cyprinus carpio) in rivers contaminated with estrogenic chemicals.
To study the effect of estrogenic chemicals on fish, the gonadosomatic index (GSI = [testis weight/body weight] x 100) and testis histology of mature common carp (Cyprinus carpio) from 2 contaminated sites (Ishizu and Wada rivers, Osaka) and a control site were examined between June 1998 and March 2001. The concentration of nonylphenol, bisphenol A and 17beta-estradiol in the Ishizu river was 3-4 times higher than in the Wada river. In the pre-breeding and breeding seasons, there were no significant differences in body weight among carp from the 3 sites, the body weight of Ishizu river carp being significantly lower (p<0.05) than that of Wada river fish only in the post-breeding season. The GSI and testis weight in fish from the Ishizu river were significantly lower (p<0.05) than in control fish during all phases of gonadal cycle and lower than in Wada river fish in the pre-breeding and post-breeding season. No histological abnormalities were found in the testes of the males examined. Histological observation of the testes revealed a delay in the onset of spermatogenesis in fish from the Ishizu river compared with those from the other sites. These results clearly imply that the estrogenic chemicals in the Ishizu river adversely affect the testis development of the fish.


On the relationship between spectroscopic constants of diatomic molecules: a machine learning approach.
Through a machine learning approach, we show that the equilibrium distance, harmonic vibrational frequency and binding energy of diatomic molecules are related, independently of the nature of the bond of a molecule; they depend solely on the group and period of the constituent atoms. As a result, we show that by employing the group and period of the atoms that form a molecule, the spectroscopic constants are predicted with an accuracy of <5%, whereas for the A-excited electronic state it is needed to include other atomic properties leading to an accuracy of <11%.


Event-Triggered Impulsive Control for Input-to-State Stabilization of Nonlinear Time-Delay Systems.
This article investigates the event-triggered impulsive control (ETIC) problem for a class of nonlinear time-delay systems subject to exogenous disturbances. An original event-triggered mechanism (ETM) which utilizes the information of system state and external input is constructed based on Lyapunov function approach. To achieve the input-to-state stability (ISS) of the considered system, some sufficient conditions are presented, in which the underlying relationship among ETM, exogenous input, and impulse action is established. Furthermore, the possible Zeno behavior induced by the proposed ETM is excluded simultaneously. As an application, the design criterion of ETM and impulse gain is put forward for a class of impulsive control systems with delay according to the feasibility of some linear matrix inequalities (LMIs). Finally, two examples with numerical simulations are provided to confirm the effectiveness of the developed theoretical results, where the synchronization issue of delayed Chua's circuit is considered.


Benzothiazines in organic synthesis. Stereoselectivity in the intermolecular Michael addition reactions of benzothiazines.
A study of the intermolecular Michael addition of certain benzothiazine anions demonstrated that stereoselectivity could be extremely high, though achieving control over the direction of relative stereoselectivity was in general not straightforward.


Changing financial base for dental education.
In recent years, there have been material changes in the manner in which U.S. dental schools are funded. This fact has had profound ramifications for the practices, operations, and culture of the schools. The kinds of programs supported, patients treated, and students admitted all are affected by the sources of available revenue as schools can only do that which does not jeopardize their economic viability.


GNG12 as A Novel Molecular Marker for the Diagnosis and Treatment of Glioma.
GNG12 influences a variety of tumors; however, its relationship with glioma remains unclear. The aim of this study was to comprehensively investigate the relationship between GNG12 and the clinical characteristics and prognosis of glioma patients and reveal the mechanisms causing the malignant process of GNG12. We obtained information on clinical samples from multiple databases. The expression level of GNG12 was validated using a RT-qPCR and IHC. KM curves were used to assess the correlation between the GNG12 expression and OS of glioma patients. An ROC curve was drawn to assess the predictive performance of GNG12. Univariate and multivariate Cox analyses were performed to analyze the factors affecting the prognosis of patients with glioma. GSEA and TIMER databases were used to estimate the relationship between GNG12 expression, possible molecular mechanisms, and immune cell infiltration. CMap analysis was used to screen candidate drugs for glioma. Subsequent in vitro experiments were used to validate the proliferation and migration of glioma cells and to explore the potential mechanisms by which GNG12 causes poor prognosis in gliomas. GNG12 was overexpressed in glioma patients and GNG12 expression level correlated closely with clinical features, including age and histological type, etc. Subsequently, the K-M survival analysis indicated that the expression level of GNG12 was relevant to the prognosis of glioma, and the ROC curve implied that GNG12 can predict glioma stability. Univariate and multivariate analyses showed that GNG12 represents a risk factor for glioma occurrence. GNG12 expression is closely associated with some immune cells. Additionally, several in vitro experiments demonstrated that down-regulation of GNG12 expression can inhibits the proliferation and migration capacity of glioma cells. Ultimately, the results for the GSEA and WB experiments revealed that GNG12 may promote the malignant progression of gliomas by regulating the cell adhesion molecule cell signaling pathway. In this study, we identified GNG12 as a novel oncogene elevated in gliomas. Reducing GNG12 expression inhibits the proliferation and migration of glioma cells. In summary, GNG12 can be used as a novel biomarker for the early diagnosis of human gliomas and as a potential therapeutic target.


Developmental changes in the pattern of larval beta-globin gene expression in Xenopus laevis. Identification of two early larval beta-globin mRNA sequences.
We have analysed beta-globin mRNA sequences in total RNA extracted from embryos and tadpoles of Xenopus laevis at different stages of development and we have identified the most abundantly transcribed beta-globin mRNA (beta T1). The entire nucleotide sequence of a cDNA clone corresponding to this mRNA is known. We have now identified the gene corresponding to this mRNA and we have determined the nucleotide sequences of its immediate 5'-flanking region. Using a DNA fragment from within the coding region of the cloned beta T1 cDNA we show, by primer extension analysis, that beta T1 mRNA is first detectable at stage 28-32 of development. This is the time at which the first presumptive erythropoietic tissue, the ventral blood island, becomes observable histologically. We show that two minor beta-globin genes, distinct from beta T1, are expressed during early stages of development, and that their expression ceases shortly after the beginning of the feeding stage. We term these two early larval genes beta E1 and beta E2. A third minor beta-globin gene is expressed during early development but, unlike beta E1 and beta E2, it is also expressed throughout subsequent larval development. We term this gene beta T2 and show that it corresponds to a gene previously termed beta LII. Finally, using a primer derived from the major adult beta-globin gene (beta 1), we have analysed the accumulation of the major adult beta-globin mRNA during larval development, and we show that this sequence does not accumulate to any significant level before metamorphosis.


The future of hyperthermia.
The major drawback of thermotherapy still is the poor reproducibility of clinical results. Many consider that this is mainly due to differences in body temperature. Hence a good knowledge of spatial and temporal temperature distribution is a prerequisite to any further clinical progress. In particular, this would enable us to establish dose-effect relationships for normal human tissue reactions and therefore to push heating up to near the threshold of tissue tolerance. The current clinical results are promising but time has come for controlled clinical studies, which are the only means we have to evaluate the various methods and combinations and to choose the optimum sequencing and scheduling.


Investigations on the pattern of linkage disequilibrium and selection signatures in the genomes of German Piétrain pigs.
The aim of this study was to study the population structure, to characterize the LD structure and to define core regions based on low recombination rates among SNP pairs in the genome of Piétrain pigs using data from the PorcineSNP60 BeadChip. This breed is a European sire line and was strongly selected for lean meat content during the last decades. The data were used to map signatures of selection using the REHH test. In the first step, selection signatures were searched genome-wide using only core haplotypes having a frequency above 0.25. In the second step, the results from the selection signature analysis were matched with the results from the recently conducted genome-wide association study for economical relevant traits to investigate putative overlaps of chromosomal regions. A small subdivision of the population with regard to the geographical origin of the individuals was observed. The extent of LD was determined genome-wide using r(2) values for SNP pairs with a distance ≤5 Mb and was on average 0.34. This comparable low r(2) value indicates a high genetic diversity in the Piétrain population. Six REHH values having a p-value < 0.001 were genome-wide detected. These were located on SSC1, 2, 6 and 17. Three positional candidate genes with potential biological roles were suggested, called LOC100626459, LOC100626014 and MIR1. The results imply that for genome-wide analysis especially in this population, a higher marker density and higher sample sizes are required. For a number of nine SNPs, which were successfully annotated to core regions, the REHH test was applied. However, no selection signatures were found for those regions (p-value < 0.1).