[Prevalence and antimicrobial susceptibility of Salmonella isolated from broiler whole production process in four provinces of China].
Objective: To determine the prevalence and antimicrobial susceptibility of Salmonella isolated from broiler production process in 4 provinces of China. Methods: Using convenience sampling method, 238 sample sites from broiler whole production process were chosen in Henan, Jiangsu, Heilongjiang and Shandong provinces in 2012. A total of 11 592 samples were collected and detected to analyze prevalence baseline, including 2 090 samples from breeding chicken farms and hatcheries, 1 421 samples from broiler farms, 5 610 samples from slaughterhouses and 2 471 samples from distribution and retail stores. All Salmonella strains were isolated through selective enrichment, and were serotyped according to Kauffmann-White scheme. The antimicrobial susceptibilities of selected Salmonella strains were determined by the broth microdilution method and fourteen antimicrobial agents were examined. Results: During incubation course, the average prevalence of Salmonella was 5.5% in feces of breeding hens, feces of chicks, and hatching eggs, 123 Salmonella strains were isolated. During cultivation course, the prevalence of Salmonella was 8.0% in feces from broiler farms, soil, feed, and workers, 114 Salmonella strains were isolated. During slaughter course, the prevalence of Salmonella was 24.9% in swabs pre-slaughter, dressed broiler carcasses, pre-cooled broiler carcasses, water from precooling pool, cutter and chipping boards, frozen chicken portions, and workers, 1 438 Salmonella strains were isolated. During distribution and sale course, the prevalence of Salmonella was 20.9% in transport carts, frozen chicken portions, retail chicken portions and workers, 551 Salmonella strains were isolated. The dominant Salmonella serotypes were Salmonella Enteritidis (n=1 229) and Salmonella Indiana (n=621). Among 1 231 examined strains, 97.2% Salmonella isolates were resistant to at least one antimicrobial, 69.9% Salmonella strains were multi-drug resistant isolates. Conclusion: Our findings indicated that Salmonella contamination was common and serious in commercial broiler whole production process in China, especially in the course of defeathering, precooling and selling. The environment of broiler farm is the important source of Salmonella contamination. Additionally, antibiotic resistance of Salmonella was serious for common antimicrobials and multi-drug resistant strains existed widespread, which can pose potential risk on public health and clinical therapy.


Group A Streptococcus Infections: Their Mechanisms, Epidemiology, and Current Scope of Vaccines.
Group A streptococci (GAS) are gram-positive, cocci-shaped bacteria that cause a wide variety of infections and are a cause of significant health burden, particularly in lower- and middle-income nations. The GAS genome contains a number of virulence factors such as the M-protein, hyaluronic acid, C5a peptidase, etc. Despite its significant health burden across the globe, a proper vaccine against GAS infections is not yet available. Various candidates for an effective GAS vaccine are currently being researched. These are based on various parts of the streptococcal genome. These include candidates based on the N-terminal region of the M protein, the conserved C-terminal region of the M protein, and other parts of the streptococcal genome. The development of a vaccine against GAS infections is hampered by certain challenges, such as extensive genetic heterogeneity and high protein sequence variation. This review paper sheds light on the various virulence factors of GAS, their epidemiology, the different vaccine candidates currently being researched, and the challenges associated with M-protein and non-M-protein-based vaccines. This review also sheds light on the current scenario regarding the status of vaccine development against GAS-related infections.


In vivo infection dynamics and human adaptive changes of SIVsm-derived viral siblings SIVmac239, SIVB670 and SIVhu in humanized mice as a paralog of HIV-2 genesis.
Simian immunodeficiency virus native to sooty mangabeys (SIVsm) is believed to have given rise to HIV-2 through cross-species transmission and evolution in the human. SIVmac239 and SIVB670, pathogenic to macaques, and SIVhu, isolated from an accidental human infection, also have origins in SIVsm. With their common ancestral lineage as that of HIV-2 from the progenitor SIVsm, but with different passage history in different hosts, they provide a unique opportunity to evaluate cross-species transmission to a new host and their adaptation/evolution both in terms of potential genetic and phenotypic changes. Using humanized mice with a transplanted human system, we evaluated in vivo replication kinetics, CD4+ T cell dynamics and genetic adaptive changes during serial passage with a goal to understand their evolution under human selective immune pressure. All the three viruses readily infected hu-mice causing chronic viremia. While SIVmac and SIVB670 caused CD4+ T cell depletion during sequential passaging, SIVhu with a deletion in nef gene was found to be less pathogenic. Deep sequencing of the genomes of these viruses isolated at different times revealed numerous adaptive mutations of significance that increased in frequency during sequential passages. The ability of these viruses to infect and replicate in humanized mice provides a new small animal model to study SIVs in vivo in addition to more expensive macaques. Since SIVmac and related viruses have been indispensable in many areas of HIV pathogenesis, therapeutics and cure research, availability of this small animal hu-mouse model that is susceptible to both SIV and HIV viruses is likely to open novel avenues of investigation for comparative studies using the same host.


A marriage of enhancement: fibrinolysis and conjunctive therapy.
Pharmacologic reperfusion of patients with acute ST segment elevation myocardial infarction is designed to achieve prompt high-quality reperfusion, prevent recurrent ischemia and reinfarction, maintain long-term patency, and to enhance patient survival and quality of life. Because monotherapy with fibrinolytics is by itself unable to achieve all of these objectives, antithrombotic, anti-platelet, and other novel agents are required. We discuss herein the role of unfractionated and enoxaparin, the potential added value of direct thrombin inhibitors, and the importance of aspirin. Despite the promise of glycoprotein IIb/IIIa inhibitors, risks associated with intracranial hemorrhage in the elderly have led to restraint in their application to broad populations. Facilitation of urgent percutaneous coronary intervention with combination reduced-dose fibrinolytic and glycoprotein IIb/IIIa inhibitors remains a promising potential future path. The future is likely to emphasize greater application of the already effective therapies at our disposal and the development of novel anti-platelet and anti-thrombin agents as well as those directed toward inflammation.


Lactate distribution in the blood compartments of sickle cell trait carriers during incremental exercise and recovery.
Whether or not whole blood lactate concentration is the same during a ramp exercise test in subjects with sickle cell trait (AS) as in normal subjects remains a point of controversy in the literature. Some studies have shown that the ability to produce or clear circulating lactate might differ between AS and subjects with normal haemoglobin (AA). If this is indeed so, the lactate distribution in the blood compartments should also differ. To test this hypothesis, lactate concentrations in the whole blood, plasma and red blood cells of AS and AA were compared at rest and in response to exercise. Eight AS and 8 AA performed an incremental exercise test. Whole blood, plasma and red blood cell lactate concentrations, the red blood cell : plasma lactate concentration ratio, the plasma-to-red blood cell lactate gradient, haematocrit and cardiorespiratory variables were analysed at rest and during an incremental exercise test and active recovery. Maximal oxygen uptake and ventilatory thresholds were similar in the two groups. No significant difference in whole blood, plasma or red blood cell lactate concentrations was observed between the two groups at rest, during exercise, or during the immediate recovery. Neither the red blood cell : plasma lactate concentration ratio nor the plasma-to-red blood cell lactate gradient differed between groups. Lactate distribution in the blood compartments did not differ between the two groups and this finding suggests that lactate production and/or clearance is quite similar during exercise in AS and AA.


The relationship between gestational diabetes mellitus and selenoprotein-P plasma 1 (SEPP1) gene polymorphisms.
Our aim is to demonstrate any correlation between gestational diabetes mellitus (GDM) and polymorphism of the selenoprotein P (SEPP1) gene encoding the SEPP1 protein, having a role in the insulin resistance in GDM. Forty pregnant women with GDM and 40 healthy pregnant women were included in the study. In both groups, single nucleotide polymorphisms (SNPs), specifically, rs4987017, rs13154178, rs146125471, rs28919926, and rs16872762 were studied. There was no difference between the groups in terms of polymorphism rs146125471, rs28919926, or rs16872762 (p > .05). There was a significant difference in SNP rs13154178 polymorphism between the two groups (p < .01). When rs13154178 gene polymorphism was compared with AA homozygous individuals, fasting blood glucose levels were significantly higher in carriers of either polymorphism than in those with no polymorphism (p < .001). We suggest rs13154178 gene polymorphism may lead to GDM in the Turkish society.


Impact of salvage surgery with or without reirradiation for skull base meningiomas recurring after prior radiotherapy.
Long-term follow-up of meningiomas has demonstrated recurrence rates ranging from 2.5% to 48% after 10 years, depending on histology grade. There are limited data available to guide the management of recurrent and previously irradiated skull base meningiomas, and challenges related to salvage surgery, reirradiation, and lack of clear systemic therapy strategies remain. In this study, the authors analyzed data from their experience with recurrent and previously irradiated meningiomas to assess the impact of salvage surgery and reirradiation on progression-free survival (PFS). A retrospective cohort study of 48 patients with recurrent and previously irradiated meningiomas who were treated between 1995 and 2021 was conducted. Data were extracted from medical records and included clinical, radiological, and pathologic reports. Patients were clustered according to WHO grades. The authors analyzed the complications related to reirradiation and salvage surgery and the impact of different treatment modalities on PFS using Cox proportional hazard ratios. Forty-eight patients (33 with WHO grade I, 11 with WHO grade II, and 4 with WHO grade III meningiomas) were treated for 143 recurrences after their first radiation treatment. For WHO grade I meningiomas, there was no change in tumor control rates with adjuvant repeat radiotherapy (HR 0.784, 95% CI 0.349-1.759; p = 0.55), and in terms of extent of resection (EOR), subtotal resection (STR) alone was associated with an increased risk of recurrence when compared with gross-total resection (GTR) (HR 3.38, 95% CI 1.268-9.036; p = 0.0189). For WHO grade II meningiomas, GTR did not significantly confer improved tumor control relative to STR (HR 0.42, 95% CI 0.17-1.037; p = 0.055), but adjuvant repeat radiotherapy after STR was associated with improved outcomes (HR 0.316, 95% CI 0.13-0.768; p = 0.0029). Finally, for WHO grade III meningiomas, EOR did not correlate with outcomes (HR 0.75, 95% CI 0.22-2.482; p = 0.588), but repeat radiotherapy alone was associated with a decreased odds of progression (HR 0.276, 95% CI 0.078-0.97; p = 0.0028). This study examined the impact of retreatment on PFS in a large cohort of patients with recurrent meningiomas that had been previously irradiated. At the time of recurrence, WHO grade I meningiomas exhibited improved PFS with GTR, subtotally resected WHO grade II meningiomas appeared to have improved PFS when reirradiated, and reirradiation in WHO grade III meningiomas showed improved PFS.


Long-acting beta2 agonists.
Two applications claim very closely related arylsulfonamide beta(2)-agonists. The basic generic claim is the same in both cases with subsidiary claims covering different permutations of the same Markush structure. The claimed compounds are potent beta(2)-agonists whose structures suggest that they would have a long duration of action. These applications represent part of what is now a significant chemical programme at Pfizer.


Growth hormone in combination with leuprorelin in pubertal children with idiopathic short stature.
There is a scarcity of data from randomised controlled trials on the association of growth hormone (GH) with gonadotrophin-releasing hormone agonists in idiopathic short stature (ISS), although this off-label use is common. We aimed to test whether delaying pubertal progression could increase near-adult height (NAH) in GH-treated patients with ISS. Patients with ISS at puberty onset were randomised to GH with leuprorelin (combination, n = 46) or GH alone (n = 45). NAH standard deviation score (SDS) was the primary outcome measure. The French regulatory authority requested premature discontinuation of study treatments after approximately 2.4 years; patients from France were followed for safety. Mean (s.d.) baseline height SDS was -2.5 (0.5) in both groups, increasing at 2 years to -2.3 (0.6) with combination and -1.8 (0.7) with GH alone. NAH SDS was -1.8 (0.5) with combination (n = 19) and -1.9 (0.8) with GH alone (n = 16). Treatment-emergent adverse events and bone fractures occurred more frequently with combination than GH alone. Due to premature discontinuation of treatments, statistical comparison of NAH SDS between the two cohorts was not possible. During the first 2-3 years of treatment, patients treated with the combination grew more slowly than those receiving GH alone. However, mean NAH SDS was similar in the two groups. No new GH-related safety concerns were revealed. A potentially deleterious effect of combined treatment on bone fracture incidence was identified.


Halogen-substituted thiophenol molecules on Cu(111).
Para-halosubstituted thiophenols (X-TPs, where X is Br, Cl, or F) form ordered islands and monolayers on Cu(111) at temperatures as low as 81 K. At incomplete coverages, all X-TPs adsorb with the dehydrogenated thiol group attached to the substrate and the substituted ring inclined toward the surface, as verified experimentally and theoretically. The structure of ordered islands has a pronounced dependence on the nature of the halogen substituent: while unsubstituted TP and pentafluoro-TP molecules do not self-assemble into extended ordered patterns at 81 K, X-TP molecules form a range of different structures which depend both on the size and electronegativity of the substituent, as well as on the coverage.


Efficacy and safety of inhaler steroids in COPD patients: Systematic review and meta-analysis of randomized placebo-controlled trials.
Chronic obstructive pulmonary disease (COPD) is a major health dilemma and cause of morbidity and mortality in either industrialized or developing countries and inhaled corticosteroids are widely used worldwide in these patients. In this systematic review, we aimed to analyze the effectiveness of these gents compared to placebo. Pubmed and Google Scholar literature search has been done to find randomized placebo-controlled trials investigating effectiveness of inhaled steroids in COPD patients. Finally, the data from 18 trials had been retrieved and included into a database, and analyzed using Stata ® v.9.0. Data of 12, 297 COPD subjects were analyzed. Analysis of survival of patients in the two groups showed no significant difference between those taking inhaled corticosteroids or placebo (relative risk (RR): 1.071, 95% confidence interval (CI): 0.938-1.224, P=0.309). Patients taking inhaled steroids were significantly less likely to develop an exacerbation episode (RR: 0.697, 95%CI: 0.596-0.816, p<0.001) or to have less withdrawal rate than placebo (RR: 0.882, 95%CI: 0.811-0.960; P=0.004). Because steroid inhalers represent no survival effects in COPD patients, and due to their life threatening side effects (pneumonia, candidemia, etc.), we propose to replace steroid inhalers to cheaper agents which provide patients with comparable advantages (e.g. few exacerbations) and fewer side effects. Pulmonary rehabilitations as well as anti-inflammatory drugs are recommended to be more attended in COPD patients.


[Pathomorphism of Hantavirus infection under prolonged heat stress].
to provide the morphological characteristics of experimental Hantavirus infection under heat stress conditions to identify the possibilities of its modeling in resistant laboratory animals. Experiments were carried out on outbred albino mice that were divided into 4 groups: 1) intact mice unexposed to heating; 2) those exposed to heating; 3) Hantavirus-infected animals unexposed to preheating; 4) those exposed to preheating. The animals in Groups 2-4 were long exposed to heat stress at a temperature of 30 °C for 3 hours during 3 days. Strain Aa 60343 (PM-79-95) of the Far East genovariant of Hantaan virus (the genus Hantavirus, family Bunyaviridae) from the collection of the G.P. Somov Research Institute of Epidemiology and Microbiology was used to induce infection. The animals in Groups 3 and 4 were intraperitoneally injected with 700 FFU of Hantavirus per mouse. Materials (lung, liver, kidney, and spleen) taken from Groups 2-4 animals were collected for histological examination on days 1, 3, 7 and 14 of observation. The intact albino mice in Group 1 showed no histopathological changes in the organs. After heat exposure, Group 2 animals were found to have an immunomorphological response in the interstitial tissues of the lung, liver and kidney in partial lymphoid hypoplasia of the spleen. There were no signs of inapparent infection in the presence of marked immunomorphological changes in the organs in Group 3 of hantavirus-infected animals unexposed to preheating. In Group 4, those exposed to preheating exhibited dystrophic and destructive changes in the target organs (lungs, kidneys) in the presence of immunodeficiency manifestations of manifestations that were more pronounced in dead animals. In an unresponsive model (adult albino mice), Hantavirus infection caused only obvious immunomorphological changes in the organs. Prolonged preheat stress in the hantavirus-infected animals promoted inapparent infection and morphological manifestations of induced secondary immunodeficiency that was responsible for the manifestation of an infectious process in some animals.


Basic aspects of gold nanoparticle photo-functionalization using oxides and 2D materials: Control of light confinement, heat-generation, and charge separation in nanospace.
Although the optical properties of localized surface plasmon resonance and the relaxation processes of excited hot electrons in gold nanoparticles (AuNPs) have been well understood, the phenomena that occur when AuNPs relax on solid surfaces of semiconductors or insulators remain largely unknown. Thermal energy diffusion and electron transfer are relatively simple physical processes, but the phenomena they induce are interesting because of a variety of new application developments. In this Perspective, we introduce the fundamental aspects as well as advanced applications of several new physical phenomena induced by AuNPs-based hybrid materials with oxides or 2D materials. Localized heat can induce a great force on the surrounding medium to control mass transport, and plasmon-induced charge transfer reactions are expected to have applications in photocatalysis and solar cells. We also review increasing reports on the development of nano-optical sensors, transistors, and nano-light sources based on precisely controlled device structures utilizing AuNPs.


[The treatment of complex urethral stricture greater than 8 cm long].
To evaluate the selection of different procedures and the feasibility for the treatment of long segment urethral stricture. Seventy-six patients with complex urethral stricture greater than 8 cm long underwent different procedures of urethroplasty. Of them various mucosa grafts urethral reconstruction were adopted in 42 cases (colonic mucosal graft, n = 26; buccal mucosal graft, n = 10; bladder mucosal graft, n = 6); One-stage pedicle flaps urethroplasty in 20; two-stage urethroplasty of Johanson procedure in 12; and penile urethra-prostatic urethra anastomosis, three-stage urethroplasty in 2. In early followed up (within 6 months postoperatively), 67 patients (88%) voided well and complications developed in 10. Among the 70 patients who lasted more than 1 year after operation, 51 cases were followed up. Forty-four patients voided well, and complications developed in 8. Of the 8 cases urethral restructure developed in 2 (18%) for pedicle flaps urethroplasty, 2 for colonic mucosal urethroplasty (9%), 1 for buccal mucosal graft (1/7), 1 for bladder mucosal graft (1/3); penile chordee in 2 (2/5), and one of them was accompanied by hair bearing neourethra for two-stage urethroplasty of Johanson procedure. Colonic mucosal and buccal mucosal grafts urethroplasty are feasible procedures for the treatment of long segment urethral stricture, and Colonic mucosal graft urethroplasty may be considered when more conventional procedures fail or complicated urethral strictures greater than 10 cm long.


A rapid derivatization based LC-MS/MS method for quantitation of short chain fatty acids in human plasma and urine.
Aim: Objective of this study is to develop a robust multi-matrix LC-MS/MS for the quantitation of endogenous short-chain fatty acids (SCFA) biomarkers in human plasma and urine. Methods: Developed method utilizes stable isotope-labeled internal standards, high-throughput derivatization procedure for sample preparation and LC-MS/MS analysis using multiple reaction monitoring transitions in positive electrospray ionization mode. Results: Surrogate matrix method was used for quantitation. Accuracy, precision, parallelism, curve linearity, derivatization efficiency, stability and recovery were all evaluated, and the results were well within the acceptable criteria. Conclusion: SCFA levels in human plasma and urine of inflammatory bowel disease patients versus non-disease subjects were quantified and compared by LC-MS/MS.


A semiautomatic image analyzer for cell counts in monolayers. II. Application to toxicity estimation and comparisons between two cell-viability markers, fluorescein diacetate and lactate dehydrogenase.
By using an image-analyzer system, toxicological effects of different substances on nonconfluent cells in monolayers can be assessed. The total number of cells and the number of viable cells are semiautomatically counted. Fluorescein diacetate is used as the viability marker. The method was tested by using monolayers of alveolar macrophages from rabbits exposed to manganese dioxide particles. A dose-response curve was obtained from a series of experiments in which the response at a certain dose level can be obtained from cell-counting procedures of the duration of 1 h. The method can be used as a short-term test, testing potentially toxic substances including cytostatic drugs where the viability should be determined. Another example is further given of the use of this technique. The results obtained from it are compared with estimates of the percentage of viable cells assessed by extracellular lactate dehydrogenase from nonexposed and manganese dioxide particle-exposed monolayers of rabbit alveolar macrophages. The two methods both account well for the theoretical relation when the lactate dehydrogenase activity values are corrected for an inactivation of this enzyme with time.


Combat-related PTSD and psychosocial adjustment problems among substance abusing veterans.
The purpose of this study were the following: a) to determine the prevalence of combat-related posttraumatic stress disorder (PTSD) symptoms among veterans seeking assistance at a Veterans Administration medical center substance abuse treatment facility, b) to examine the relative contribution of Vietnam war zone variables to PTSD symptom development, and c) to study psychosocial adjustment problems associated with Vietnam combat exposure and with PTSD symptoms among help-seeking substance abusing men. Of 489 male veterans presenting for treatment, 10.7% had significant Vietnam combat-related PTSD symptoms as measured by the Mississippi Scale for Combat-Related PTSD. Clinically significant PTSD symptoms occurred among 46% of the subsample of combat-exposed Vietnam veterans with substance abuse problems. Degree of combat exposure was the most important military stressor that distinguished Vietnam veterans with PTSD from those without PTSD, but the groups also differed on age of war zone duty, duration of war zone duty, and whether they were wounded. Veterans who served in Vietnam did not differ from veterans who had no war zone duty on various parameters of psychosocial adjustment. However, the subgroup of Vietnam veterans with PTSD symptoms reported significantly greater psychosocial adjustment problems than their counterparts who did not have PTSD. The deleterious effects associated with combat-related PTSD appeared to be confined to adjunctive psychiatric difficulties and unemployment and did not increase risk of arrests for antisocial conduct beyond that found for veterans without PTSD. Methodological and clinical implications of these findings are discussed.


Deficits and remedy of the standard random effects methods in meta-analysis.
The random effects model is often used in meta-analyses. A corresponding significance test based on a normal approximation has been established. Its type I error is derived in this article by theoretical considerations and computer simulations. The test can be conservative as well as unacceptably anti-conservative. The anti-conservatism increases with the increasing number of patients and the decreasing number of studies. A modification is proposed, which keeps the nominal level asymptotically as the number of patients approaches infinity. Simulations show that the modified test is often conservative, but its conservatism is small in those situations where the standard test is highly anti-conservative.


[Palliative or radical surgery for pancreatico-duodenal cancer?].
Reviewing the fate of 61 patients wih adenocarcinoma of the pancreatico-duodenal region in the context of a review of the literature leads to the following statements: 1. No radical surgery without histological confirmation. 2. Radical surgery for periampullary carcinoma, these tumors have the better prognosis than pancreatic carcinoma because of a different biological behaviour. 3. Radical surgery is the best palliation for pancreatic carcinoma, if pain is the leading symptom. 4. Palliative surgery is indicated for pancreatic carcinoma of the head with jaundice.


Time-Dependent Serum Brain-Derived Neurotrophic Factor Decline During Methamphetamine Withdrawal.
Methamphetamine (METH) is a widely abused illegal psychostimulant, which is confirmed to be neurotoxic and of great damage to human. Studies on the role of brain-derived neurotrophic factor (BDNF) in human METH addicts are limited and inconsistent. The purposes of this study are to compare the serum BDNF levels between METH addicts and healthy controls during early withdrawal, and explore the changes of serum BDNF levels during the first month after METH withdrawal.179 METH addicts and 90 age- and gender-matched healthy controls were recruited in this study. We measured serum BDNF levels at baseline (both METH addicts and healthy controls) and at 1 month after abstinence of METH (METH addicts only).Serum BDNF levels of METH addicts at baseline were significantly higher than controls (1460.28 ± 490.69 vs 1241.27 ± 335.52 pg/mL; F = 14.51, P < 0.001). The serum BDNF levels of 40 METH addicts were re-examined after 1 month of METH abstinence, which were significantly lower than that at baseline (1363.70 ± 580.59 vs 1621.41 ± 591.07 pg/mL; t = 2.26, P = .03), but showed no differences to the controls (1363.70 ± 580.59 vs 1241.27 ± 335.52 pg/mL; F = 2.29, P = 0.13).Our study demonstrated that serum BDNF levels were higher in METH addicts than controls during early withdrawal, and were time dependent decreased during the first month of abstinence. These findings may provide further evidence that increased serum BDNF levels may be associated with the pathophysiology of METH addiction and withdrawal and may be a protective response against the subsequent METH-induced neurotoxicity. Besides, these findings may also promote the development of medicine in the treatment of METH addiction and withdrawal.


[Clinical and morphologic aspects of benign bone tumors and tumorous bone lesions. Follow-up, therapy and prognosis].
In this study, a total of 1434 benign bone tumors and 384 tumor-like bone lesions that have been diagnosed from 1945 until 1974 in the Institute of Pathology of the University of Freiburg was reviewed and statistically analysed. The most frequent tumors include 720 osteochondromas, 345 enchondromas and 93 osteomas (80.8%). The remainder of 276 cases included several tumorous bone lesions with an individual share of below 5%. Our 64 osteoclastomas (4.5%) are in reality tumors of low grade of malignancy. There was an equal distribution among both sexes (737 male, 695 female). Predominate location were the bones of extremities and the skull. Most often, we have found these tumors in the lower legs, and one third was localized in hands and feet. 60% of the benign bone tumors of the hands have been enchondromas. Osteomas and hemangiomas have been localized most often in the skull, and ossifying and non-ossifying fibromas in the jaws. Main localization of osteoclastomas was the knee. Roentgenograms have always been put into consideration for diagnoses and have, together with the histological findings, facilitate an exact classification. Clinical findings have only exceptionally shown indicative symptoms (e. g. night pain in cases of osteoid osteomas); otherwise there were vague swelling, pain or disfunction. Benign bone tumors are poor of symptoms. Concerning therapy, most bone tumors have been cured by operation (curettage, excision). In some tumors (especially in chondromyxoidfibromas) recurrences have occurred. No investigated bone tumor has shown a malignant transformation.


Mutagenesis of the folC gene encoding folylpolyglutamate synthetase-dihydrofolate synthetase in Escherichia coli.
The folC gene of Escherichia coli, cloned in a pUC19 vector, was mutagenized by progressive deletions from both the 5' and the 3' ends and by TAB linker insertion. A number of 5'-deleted genes, which had the initiator ATG codon removed, produced a truncated gene product, in reduced amounts, from a secondary initiation site. The most likely position of this site at a GTG codon located 35 codons downstream of the normal start site. This product could complement the folC mutation in E. coli strain SF4 as well as a strain deleted in the folC gene. The specific activity of extracts of the mutant enzyme are 4-16% that of the wild type enzyme for the folylpolyglutamate synthetase activity and 6-19% for the dihydrofolate synthetase activity. The relative amount of protein expressed by the mutant, compared to the wild type, in maxicells was comparable to the relative specific activity, suggesting that the kcat of the mutant enzyme is similar to that of the wild type. Mutants with up to 14 amino acids deleted from the carboxy terminal could still complement the folC deletion mutant. Seven out of ten linker insertions dispersed through the coding region of the gene showed complementation of the folC mutation in strain SF4 but none of these insertion mutants were able to complement the strain containing a deleted folC gene. None of the carboxy terminal or linker insertion mutants had a specific activity greater than 0.5% that of the wild type enzyme. The dihydrofolate synthetase and folylpolyglutamate synthetase activities behaved similarly in all mutants, both retaining a large fraction of the wild type activity in the amino terminal deletions and both being very low in the carboxy terminal deletions and linker insertion mutants. These studies are consistent with a single catalytic site for the two activities catalyzed by this enzyme.


Intraoperative use of the Medtronic O-arm for deep brain stimulation procedures.
The purpose of this study was to analyze the feasibility and utility of 3D imaging to help lead positioning during a deep brain stimulation (DBS) procedure. A bilateral subthalamic DBS procedure was conducted in 2 patients for idiopathic Parkinson's disease. Subthalamic nucleus targeting was based on preoperative stereotactic MRI. We used the Medtronic O-arm to perform 2D-imaging control (frontal and lateral) as well as quick (<30 s) 3D acquisition. This allowed us to check the positioning of micro-macro electrodes and definite electrodes. 3D images were fused with postoperative CT to assess their accuracy, and with preoperative MRI to visualize the anatomical location of the electrodes. 3D imaging is a quick and safe method to ensure perioperative control of lead placement during DBS procedures.


Predicting Future Suicide: Clinician Opinion versus a Standardized Assessment Tool.
To compare the effectiveness of clinician prediction of risk to a standardized assessment of presentation status. All adult psychiatry emergency department consults in the two main hospitals in Winnipeg, Canada, were assessed using a standardized form (n = 5,376). This form includes two risk scales for a gestalt physician assessment of risk (Suicide Likelihood scale, suicide Attempt Likelihood scale) and the Columbia Classification Algorithm of Suicide Assessment (C-CASA). Regression determined whether assessments predicted future suicide attempts and deaths. The area under the curve (AUC) determined the prediction accuracy of these methods. Although the regression results were significant, the AUCs were either moderate or poor. Clinician assessment was not effective at predicting deaths (AUC = .546, .36-.73), but moderately accurate at predicting future attempts (AUC = .728, .66-.79). C-CASA assessment was moderately accurate at predicting both attempts and deaths (AUC = .666 and .678). Clinician assessment does not significantly outperform a simple assessment of the occurrence of suicidal thoughts and behaviors during presentation to the emergency department. Behavior-based standardized assessments should be further researched in this field. Assessment of suicidality at presentation using C-CASA or similar assessment should be standard for psychiatric patients assessed in the emergency department.


On differentiating auditory processing disorder (APD) from attention deficit disorder (ADD): an illustrative example using the Cattell-Horn-Carroll (CHC) model of cognitive abilities.
Objective: To clarify the distinction between Auditory Processing Disorder (APD) and Attention Deficit Disorder (ADD) using the CHC Model.Design: A cross-sectional study compared responses of caregivers about their children's behaviour to identify characteristics of APD (CHC Model) and ADD (DSM-5).Study Sample: Caregivers, mostly mothers (92%), of 149 children (M 61%; F 39%) aged from 6 to 16 years, referred for "Auditory Processing Assessment" of their child, were shown an A4 card displaying the characteristics of AP from the CHC Model on one side, and of ADD from DSM-5 on the other. Both sides were untitled. For each side, caregivers were asked if the characteristics were true of their child using a Conners-type four-point scale.Results: The majority of children were rated by caregivers as displaying characteristics of ADD, rather than an APD problem. Comparing problems with AP vs. problems with ADD gave: Wilcoxon T = 9.71; z = 4.86, p < 0.001.Conclusion: The finding that most children referred for an AP Assessment showed characteristics of ADD was surprising. Given the continuing audiological controversies about the nature of AP and about differentiating AP disorders from ADD, the CHC Model offers a different and informative perspective.


A combined IR/IR and IR/UV spectroscopy study on the proton transfer coordinate of isolated 3-hydroxychromone in the electronic ground and excited state.
In this paper the excited state proton transfer (ESPT) of isolated 3-hydroxychromone (3-HC), the prototype of the flavonols, is investigated for the first time by combined IR/UV spectroscopy in molecular beam experiments. The IR/UV investigations are performed both for the electronically excited and electronic ground state indicating a spectral overlap of transitions of the 3-HC monomer and clusters with water in the electronic ground state, whereas in the excited state only the IR frequencies of the proton-transferred monomer structure are observed. Due to the loss of isomer and species selectivity with respect to the UV excitations IR/IR techniques are applied in order to figure out the assignment of the vibrational transitions in the S0 state. In this context the quadruple resonance IR/UV/IR/UV technique (originally developed to distinguish different isomers in the electronically excited state) could be applied to identify the OH stretching vibration of the monomer in the electronic ground state. In agreement with calculations the OH stretching frequency differs significantly from the corresponding values of substituted hydroxychromones.


Partial anomalous pulmonary venous return of an uncommon type.
We report a rare case of complete anomalous venous return from the right lung to the supradiaphragmatic part of the inferior vena cava, associated with sinus venosus atrial septal defect. The defect was corrected with direct reimplantation of the anomalous venous trunk into the left atrium and direct suture of the ASD. A good operative result was obtained. As a great variety of associative patterns between partial APVR and ASD exists in literature, we outline the necessity of an accurate pre- and intra-operative diagnosis, in order to achieve the most satisfactory surgical result.


[Investigation on response of the patient-reported outcome scale of the main-symptoms of chronic obstructive pulmonary disease complicated with pulmonary heart disease].
To select appropriate descriptors for response of the patient-reported outcome (PRO) scale for the main symptoms of patients with chronic obstructive pulmonary disease (COPD) complicated with pulmonary heart disease. A cross-sectional investigation was carried out. Five equidistant ordinal descriptive words in the PRO scale of main symptoms for COPD complicated with pulmonary heart disease were selected. There were 32 alternative words in the questionnaire. Thirty respondents were required to place each descriptive word on a 10-centimeter line according to where they considered each descriptive word should be placed. Then, the line was measured by ruler; average, standard deviation and median were calculated by excel software; the authors finally chose the five equidistant words which accurately reflect the degree of main symptoms. The five most appropriate descriptive words were selected; they were "never", "seldom", "half-partly sometimes", "very often" and "always". These selected decorated words are suitable for the PRO scale for patients with COPD complicated with pulmonary heart disease.


Comparing erosion and organ accumulation rates of lead and alternative lead-free ammunition fed to captive domestic ducks.
Lead poisoning of birds of prey from ingestion of ammunition lead has been well documented. Alternative, lead-free ammunition is widely available, but the toxicokinetics of other metals in birds are poorly understood. We tested the erosion of lead, copper, zinc, iron and brass by feeding domestic Pekin ducks (Anas platyrhynchos forma domestica) defined numbers of small metal pellets. The accumulation of these metals was analysed in the breast muscle, brain, pancreas, liver and kidney. Four weeks after application, the ducks were euthanized and necropsied, internal organs tested for metal accumulation and gizzard pellets collected and weighed to record loss by erosion. Degree of erosion was highest in zinc pellets (81% mass loss), followed by iron (46%) and lead (45%) and was only marginal in copper and brass. Only lead showed highly elevated levels of accumulation in organs compared to controls.


[The effectiveness of hemopoietic growth factors in sepsis].
In this experimental study, consist of 54 Sprague-Dawley rats, we tried to observe the effectiveness of haemopoietic growth factors such as G-CSF and GM-CSF in treatment of sepsis and see if they have any effects on phagocytic activity of macrophages when are administered after establishment of sepsis. In first phase of this study, twenty one rats were randomly divided into three groups of 7 animals each. Cecal ligation and perforation were carried out in each rat and sepsis made up. The Control group received 2 x 0.2 cc %5 dextrose injection subcutaneous (s.c.).. The G-CSF group received 2 x 1 g G-CSF with 0.2 cc %5 dextrose s.c. The GM-CSF received 1 x 2 g GM-CSF with 0.2 cc %5 dextrose s.c. Seventh day survival was considered as criterion in the three groups. In second phase of this study, thirty three rats were randomly divided into three groups of 11 animals each. The same procedures were carried out also in these groups. Leukocyte counts and peripheric spread were analyzed in postoperative 24th and 72th hours, alveolar and peritoneal macrophages were Investigated in postoperative 72nd hour. There was significantly neutrophilic leukocytosis in the G-CSF group according to the control group. Nevertheless, there was no change in the phagocytic activity of alveolar and peritoneal macrophages. GM-CSF brought about positive effect of phagocytic activity of macrophages without change of leucocyte count in the sepsis, but it caused neutrophilic, monocytosis and lymphocytopenia. The seventh day survival rates in control, G-CSF, GM-CSF groups were as; 42.8%, 71.4%, 28.5% respectively. As a result, we saw that G-CSF has no effect on the phagocytic activity of macrophages, while increases the survival by enhancing the count and probably the function of neutrophils. GM-CSF fails to increase survival while effects the phagocytic activities of macrophages positively and enhances the peripheral neutrophil and monosit counts without changing the total number of leukocytes.


The mixed mating system of the sea palm kelp Postelsia palmaeformis: few costs to selfing.
Naturally isolated populations have conflicting selection pressures for successful reproduction and inbreeding avoidance. These species with limited seasonal reproductive opportunities may use selfing as a means of reproductive assurance. We quantified the frequency of selfing and the fitness consequences for inbred versus outcrossed progeny of an annual kelp, the sea palm (Postelsia palmaeformis). Using experimentally established populations and microsatellite markers to assess the extent of selfing in progeny from six founding parents, we found the frequency of selfing was higher than expected in every population, and few fitness costs were detected in selfed offspring. Despite a decline in heterozygosity of 30 per cent in the first generation of selfing, self-fertilization did not affect individual size or reproduction, and correlated only with a marginally significant decline in survival. Our results suggest both that purging of deleterious recessive alleles may have already occurred and that selfing may be key to reproductive assurance in this species with limited dispersal. Postelsia has an alteration of a free-living diploid and haploid stage, where the haploid stage may provide increased efficiency for purging the genetic load. This life history is shared by many seaweeds and may thus be an important component of mating system evolution in the sea.


A new test statistic based on shrunken sample variance for identifying differentially expressed genes in small microarray experiments.
Choosing an appropriate statistic and precisely evaluating the false discovery rate (FDR) are both essential for devising an effective method for identifying differentially expressed genes in microarray data. The t-type score proposed by Pan et al. (2003) succeeded in suppressing false positives by controlling the underestimation of variance but left the overestimation uncontrolled. For controlling the overestimation, we devised a new test statistic (variance stabilized t-type score) by placing shrunken sample variances of the James-Stein type in the denominator of the t-type score. Since the relative superiority of the mean and median FDRs was unclear in the widely adopted Significance Analysis of Microarrays (SAM), we conducted simulation studies to examine the performance of the variance stabilized t-type score and the characteristics of the two FDRs. The variance stabilized t-type score was generally better than or at least as good as the t-type score, irrespective of the sample size and proportion of differentially expressed genes. In terms of accuracy, the median FDR was superior to the mean FDR when the proportion of differentially expressed genes was large. The variance stabilized t-type score with the median FDR was applied to actual colorectal cancer data and yielded a reasonable result.


Transepithelial D-glucose and D-fructose transport across the American lobster, Homarus americanus, intestine.
Transepithelial transport of dietary D-glucose and d-fructose was examined in the lobster Homarus americanus intestine using D-[(3)H]glucose and D-[(3)H]fructose. Lobster intestines were mounted in a perfusion chamber to determine transepithelial mucosal to serosal (MS) and serosal to mucosal (SM) transport mechanisms of glucose and fructose. Both MS glucose and fructose transport, as functions of luminal sugar concentration, increased in a hyperbolic manner, suggesting the presence of mucosal transport proteins. Phloridizin inhibited the MS flux of glucose, but not that of fructose, suggesting the presence of a sodium-dependent (SGLT1)-like glucose co-transporter. Immunohistochemical analysis, using a goat anti-rabbit GLUT5 polyclonal antibody, revealed the localization of a brush border GLUT5-like fructose transport protein. MS fructose transport was decreased in the presence of mucosal phloretin in warm spring/summer animals, but the same effect was not observed in cold autumn/winter animals, suggesting a seasonal regulation of sugar transporters. Mucosal phloretin had no effect on MS glucose transport. Both SM glucose and SM fructose transport were decreased in the presence of increasing concentrations of serosal phloretin, providing evidence for the presence of a shared serosal GLUT2 transport protein for the two sugars. The transport of d-glucose and d-fructose across lobster intestine is similar to sugar uptake in mammalian intestine, suggesting evolutionarily conserved absorption processes for these solutes.


Regulation by fibrinogen and its products of intercellular adhesion molecule-1 expression in human saphenous vein endothelial cells.
It has been reported that fibrinogen may act as a bridging ligand, binding to intercellular adhesion molecule-1 (ICAM-1) on human umbilical vein endothelial cells and to Mac-1 on THP-1 cells (a monocytic cell line) to increase adhesion. In this study, we investigated whether fibrinogen altered the expression of ICAM-1 and, thus, increased the adhesion of THP-1 cells to cultured human saphenous vein endothelial cells (HSVECs). Incubation of HSVECs with 0.3 to 4 micromol/L fibrinogen caused a time- and concentration-dependent increase in ICAM-1, as determined by ELISA. The 4- to 5-fold increase in ICAM-1 protein concentration in HSVECs stimulated by 4 micromol/L fibrinogen for 6 hours was concomitant with a 4- to 5-fold increase in ICAM-1 mRNA. This fibrinogen-stimulated ICAM-1 upregulation was associated with a 2-fold increase in THP-1 cell adhesion to HSVECs. The fibrinogen-derived peptide Bbeta15-42 bound to HSVECs (K(d) 0.18 micromol/L). Preincubation of HSVECs with Bbeta15-42, a neutralizing antibody to urokinase plasminogen activator (uPA), or the F(ab)(1) fragment of a monoclonal antibody to vascular endothelial cadherin significantly attenuated the increase in ICAM-1 stimulated by fibrinogen. Capillary electrophoretic analysis indicated that anti-uPA prevented the release of any fibrinopeptide B (Bbeta1-14) in cultures of HSVECs incubated with 4 micromol/L fibrinogen for 6 hours. Moreover, incubation of HSVECs with either fibrin monomer (1 micromol/L) or monoclonal antibodies to vascular endothelial cadherin (25 microg/mL) increased ICAM-1 protein concentration 3- to 4-fold. These findings indicate that cleavage of fibrinopeptide B from fibrinogen by endothelial uPA permits the exposed Bbeta15-42 sequence of fibrinogen to bind to vascular endothelial cadherin on HSVECs and to upregulate the expression of ICAM-1.


Inhibition of IL-13 and IL-13Rα2 Expression by IL-32θ in Human Monocytic Cells Requires PKCδ and STAT3 Association.
Interleukin (IL)-32θ, a newly identified IL-32 isoform, has been reported to exert pro-inflammatory effects through the association with protein kinase C delta (PKCδ). In this study, we further examined the effects of IL-32θ on IL-13 and IL-13Rα2 expression and the related mechanism in THP-1 cells. Upon stimulating IL-32θ-expressing and non-expressing cells with phorbol 12-myristate 13-acetate (PMA), the previous microarray analysis showed that IL-13Rα2 and IL-13 mRNA expression were significantly decreased by IL-32θ. The protein expression of these factors was also confirmed to be down-regulated. The nuclear translocation of transcription factors STAT3 and STAT6, which are necessary for IL-13Rα2 and IL-13 promoter activities, was suppressed by IL-32θ. Additionally, a direct association was found between IL-32θ, PKCδ, and signal transducer and activator of transcription 3 (STAT3), but not STAT6, revealing that IL-32θ might act mainly through STAT3 and indirectly affect STAT6. Moreover, the interaction of IL-32θ with STAT3 requires PKCδ, since blocking PKCδ activity eliminated the interaction and consequently limited the inhibitory effect of IL-32θ on STAT3 activity. Interfering with STAT3 or STAT6 binding by decoy oligodeoxynucleotides (ODNs) identified that IL-32θ had additive effects with the STAT3 decoy ODN to suppress IL-13 and IL-13Rα2 mRNA expression. Taken together, our data demonstrate the intracellular interaction of IL-32θ, PKCδ, and STAT3 to regulate IL-13 and IL-13Rα2 synthesis, supporting the role of IL-32θ as an inflammatory modulator.


3-Ketoacyl thiolase delays aging of Caenorhabditis elegans and is required for lifespan extension mediated by sir-2.1.
Studies of long-lived Caenorhabditis elegans mutants have identified several genes that function to limit lifespan, i.e., loss-of-function mutations in these genes promote longevity. By contrast, little is known about genes that normally act to delay aging and that when mutated cause premature aging (progeria). To seek such genes, we performed a genetic screen for C. elegans mutants that age prematurely. We found that loss-of-function mutations of the ketoacyl thiolase gene kat-1 result in an increased accumulation of the lipofuscin-like fluorescent aging pigment, shortened lifespan, early behavioral decline, and other abnormalities characteristic of premature aging. These findings suggest that kat-1 acts to delay C. elegans aging. kat-1 encodes a conserved metabolic enzyme that catalyzes the last step of fatty acid oxidation and was previously shown to regulate fat accumulation in worms. We observed that kat-1 is required for the extension of lifespan and enhanced thermotolerance mediated by extra copies of the deacetylase gene sir-2.1. kat-1 acts independently of other known pathways that affect longevity. Our findings suggest that defects in fatty acid oxidation can limit lifespan and accelerate aging in C. elegans and that kat-1-mediated fatty acid oxidation is crucial for overexpressed sir-2.1 to delay aging.


Nasal septal turbinate: cadaveric study.
Despite the importance of its location, the functional behavior of the nasal septal turbinate (NST) is still not completely understood. Basic histological knowledge is still lacking. The aim of this study was to describe the histological features of the NST and to compare its morphometric features to those of the adjacent nasal septum and the inferior and middle turbinates. The study included 50 fresh cadavers. Excisional biopsy specimens of the NST with adjacent posterior septum were collected. In addition, mucosal and submucosal biopsy specimens were taken of the inferior and middle turbinates. Morphometric analysis was performed on five different tissue types: glandular elements, connective tissue stroma, arterial structures, and capillary or venous sinusoids. The mean proportion of venous sinusoids was statistically lower in the nasal septum and NST than in the inferior and middle turbinate. The mean proportion of glandular tissues was higher in the NST than in other regions of the nasal cavity. The mean proportion of arterial tissue was lower in the nasal septum and the NST. Significantly fewer capillary elements were found in the inferior and middle turbinates than in the nasal septum and NST. The mean proportion of connective tissues was lower in the NST than in other regions of the nasal cavity. The similar histopathological cell distribution in the middle and inferior turbinate supported a function as an erectile organ, but the findings for the NST pointed to different functional properties of this region.


Lung cancer screening: a review of available data and current guidelines.
Lung cancer is the leading cause of cancer mortality worldwide. A lack of clinical symptoms in early-stage disease frequently leads to diagnosis at a late stage, and a 15% 5-year survival rate in all patients so diagnosed. This has led to significant interest in effective screening methods to detect early-stage cancers, particularly for high-risk groups, such as current or former smokers. Early clinical trials focused on chest radiograph with or without sputum cytology and failed to show an improvement in mortality with screening. A meta-analysis also failed to show a difference in all-cause mortality. Subsequent protocols compared low-dose computed tomography (LDCT) scan with chest radiograph and documented increased detection of early-stage disease; however, they were not designed to prove a reduction in mortality. The most recent trials have focused on LDCT scans, including the National Lung Screening Trial. Data released from the National Lung Screening Trial demonstrated a statistically significant reduction in lung cancer deaths in patients screened with LDCT scans. When data from the study, including cost-effectiveness, are completely analyzed, they may lead to revision of current lung cancer screening recommendations to include LDCT scans in specific populations at high risk of developing lung cancer.


[Myocardial scintigraphy with thallium 201 in assessing revascularization procedures by aortocoronary bypass or coronary dilatation].
40 patients underwent aortocoronary bypass surgery for coronary artery disease involving a single vessel in 2 cases, 2 vessels in 10 cases, and all 3 vessels in 28 cases. Preoperative exercise Thallium 201 scanning showed one or several zones of hypofixation (80 p. 100 of maximum myocardial fixation) which were not present at rest. After surgery, exercise scanning was normal in 22 out of 24 patients with normalised or improved vascularisation on control angiography, but remained pathological in 2 cases. However, comparable areas of hypoperfusion were observed in 16 patients with no improvement or worsening of vascularisation after operation. The exercise EG remained pathological in 6 out of 24 patients with normalised or improved vascularisation and in 11 out of 16 patients with identical or worsened vascularisation. In addition, 10 of the 24 patients with improved or normalised vascularisation, and 12 of 16 patients with identical or worsened vascularisation, continued to have chest pain after operation. A zone of hypoactivity was observed in the preoperative exercise scan in 18 out of 20 patients with isolated stenosis treated by catheter dilatation. Normalised exercise scans were recorded in all patients in the month following dilatation, but the exercise ECG remained pathological in 3 patients. In conclusion, 201 Thallium scanning gives a good assessment of myocardial vascularisation after revascularisation procedures. It helps identify patients with non-anginal post-operative chest pain, and detects residual ischaemia in patients without ischaemic signs on electrocardiography.


Assessment of the Effects Exerted by Acid and Alkaline Solutions on Bone: Is Chemistry the Answer?
The treatment of corpses with extremely acid or basic liquids is sometimes performed in criminal contexts. A thorough characterization by chemical analysis may provide further help to macroscopic and microscopic analysis; 63 porcine bone samples were treated with solutions at different pH (1-14) for immersion periods up to 70 days, as well as in extremely acidic sulfuric acid solutions (9 M/18 M) and extremely basic sodium hydroxide. Inductively coupled optical emission spectrometry (ICP-OES)/plasma mass spectrometry (ICP-MS), Fourier transform infrared spectroscopy (FT-IR), energy dispersive X-ray analysis (EDX), X-ray powder diffraction (XRPD), and scanning electron microscopy (SEM) showed that only the sulfuric acid solution 18 M was able to completely dissolve the sample. In addition, chemical analysis allowed to recognize the contact between bone and substances. Hydrated calcium sulfate arose from extreme pH. The possibility of detecting the presence of human material within the residual solution was demonstrated, especially with FT-IR, ICP-OES, and EDX.


[A study of cognitive and behavioral development in pre-school and school children with high functioning pervasive developmental disorder].
It has been reported that school-aged children with high functioning pervasive developmental disorder (HFPDD) have numerous difficulties in their school class. We used three psychological tests to investigate whether there is a relationship between intelligence and cognitive, behavioral development in children with HFPDD. The three tests used were an intelligence test (WIPPSI, WISC-lll), the P-F (Picture Frustration) study, and behavioral assessment by their parents. In the P-F study, 60% of 23 children with HFPDD showed a GCR% (Group Conformity Rating) above or below the standard. There was no relationship between GCR% and IQ. In the behavioral assessment by their parents, over 50% of 40 children with HFPDD showed maladaptive behaviors. The high VIQ group showed more maladaptive behaviors than the low VIQ group. These findings suggest that school-aged children with H-FPDD need educational treatment for social deficits and maladaptive behaviors.


Discovery of shear- and side-specific mRNAs and miRNAs in human aortic valvular endothelial cells.
The role of endothelial cells (ECs) in aortic valve (AV) disease remains relatively unknown; however, disease preferentially occurs in the fibrosa. We hypothesized oscillatory shear (OS) present on the fibrosa stimulates ECs to modify mRNAs and microRNAs (miRNAs) inducing disease. Our goal was to identify mRNAs and miRNAs differentially regulated by OS and laminar shear (LS) in human AVECs (HAVECs) from the fibrosa (fHAVECs) and ventricularis (vHAVECs). HAVECs expressed EC markers as well as some smooth muscle cell markers and functionally aligned with the flow. HAVECs were exposed to OS and LS for 24 h, and total RNA was analyzed by mRNA and miRNA microarrays. We found over 700 and 300 mRNAs down- and upregulated, respectively, by OS; however, there was no side dependency. mRNA microarray results were validated for 26 of 28 tested genes. Ingenuity Pathway Analysis revealed thrombospondin 1 (Thbs1) and NF-κB inhibitor-α (Nfkbia) as highly connected, shear-sensitive genes. miRNA array analysis yielded 30 shear-sensitive miRNAs and 3 side-specific miRNAs. miRNA validation confirmed 4 of 17 shear-sensitive miRNAs and 1 of 3 side-dependent miRNAs. Using miRWalk and several filtering steps, we identified shear-sensitive mRNAs potentially targeted by shear-sensitive miRNAs. These genes and signaling pathways could act as therapeutic targets of AV disease.


Divergent Phenotypes of Human Regulatory T Cells Expressing the Receptors TIGIT and CD226.
Regulatory T cells (Tregs) play a central role in counteracting inflammation and autoimmunity. A more complete understanding of cellular heterogeneity and the potential for lineage plasticity in human Treg subsets may identify markers of disease pathogenesis and facilitate the development of optimized cellular therapeutics. To better elucidate human Treg subsets, we conducted direct transcriptional profiling of CD4(+)FOXP3(+)Helios(+) thymic-derived Tregs and CD4(+)FOXP3(+)Helios(-) T cells, followed by comparison with CD4(+)FOXP3(-)Helios(-) T conventional cells. These analyses revealed that the coinhibitory receptor T cell Ig and ITIM domain (TIGIT) was highly expressed on thymic-derived Tregs. TIGIT and the costimulatory factor CD226 bind the common ligand CD155. Thus, we analyzed the cellular distribution and suppressive activity of isolated subsets of CD4(+)CD25(+)CD127(lo/-) T cells expressing CD226 and/or TIGIT. We observed TIGIT is highly expressed and upregulated on Tregs after activation and in vitro expansion, and is associated with lineage stability and suppressive capacity. Conversely, the CD226(+)TIGIT(-) population was associated with reduced Treg purity and suppressive capacity after expansion, along with a marked increase in IL-10 and effector cytokine production. These studies provide additional markers to delineate functionally distinct Treg subsets that may help direct cellular therapies and provide important phenotypic markers for assessing the role of Tregs in health and disease.


Paediatric vesicoureteric reflux imaging: where are we? Novel ultrasound-based voiding urosonography.
Vesicoureteric reflux is an important association of paediatric urinary tract infection. Fluoroscopic micturating cystourethrography and radionuclide cystography have been employed for detecting and grading vesicoureteric reflux. However, both modalities involve ionising radiation, which can pose significant radiation risk to growing children. They also have a lower detection rate due to intermittent fluoroscopic technique in micturating cystourethrography, and lower spatial resolution in radionuclide cystography. Therefore, newer radiation-free ultrasound-based contrast-enhanced voiding urosonography has been developed in Europe for 15 years. This article aimed to summarise the current literature and discuss the first local pilot study in our institution on detection of vesicoureteric reflux by contrast-enhanced voiding urosonography. Contrast-enhanced voiding urosonography is a valid alternative to micturating cystourethrography in assessing vesicoureteric reflux, based on its superior diagnostic performance, reliability, safety, feasibility, and radiation safety for children. Therefore, it should be incorporated in the guideline for investigating paediatric urinary tract infection.


NFkappaB pathway: a good signaling paradigm and therapeutic target.
NFkappaB was identified 20 years ago (Sen, R., & Baltimore, D. (1986) Cell, 46, 705-716) as a nuclear factor that binds the kappa light chain enhancer in B-cells (and hence, the name NFkappaB) and was shown to play roles in innate and adaptive immune responses. More recently, its role in many other cellular processes has become apparent. Perhaps, not surprisingly, deregulated activity of the NFkappaB pathway has been observed and linked to the progression of several human ailments, including cancers. Research in the last two decades has identified the major mechanisms of activation of this pathway and has documented the roles of the key players. Over 200 physiological stimuli are known to activate NFkappaB. These include bacterial and viral products, cellular receptors and ligands, mitogens and growth factors and physical and biochemical stress inducers. The major cellular targets of NFkappaB are chemokines, immune receptors, adhesion molecules, stress response genes, regulators of apoptosis, transcription factors, growth factors, enzymes and cell cycle regulators. In addition, NFkappaB is known to be important for transcription of several viral promoter/enhancers (e.g. HIV-1 and CMV). Given that, such a large number of stimuli can activate NFkappaB, which in turn activates an equally large number of target genes, understanding how specificity generated within the framework of pleiotropic signaling is a major challenge. A thorough understanding of this would be instrumental in designing pathway specific inhibitors of NFkappaB for the treatment of specific human ailments.


[Programmed diagnosis of rheumatic diseases in general practice (author's transl)].
In the large number of rheumatic diseases and their often very different types - typical symptomatology is seldom complete - a reliable classification of a particular form of disease is often not easy. The "programmed diagnosis" presented here should be a signpost from the clinical picture, by way of the provisional diagnosis and the necessary diagnostic measures, to the final diagnosis.


Examination of Hivetop Incubator Efficacy for Emerging Osmia lignaria (Hymenoptera: Megachilidae) and the Impact on Apis mellifera (Hymenoptera: Apidae) Colonies.
Osmia lignaria Say is used in combination with Apis mellifera L. to pollinate U.S. orchard crops. The deployment of O. lignaria requires artificial warming to synchronize adult bee emergence with crop bloom. However, current methods for emerging bees are time consuming and inefficient; the Hivetop Incubator (HTI) invention creates a space atop an A. mellifera hive whose heat flows through the screened bottom of the HTI to incubate cocooned O. lignaria adults therein. In response to HTI heat, O. lignaria adults chew out of cocoons, find an exit hole, and fly away to nest in provided nesting sites and, thereby, pollinate a crop. Objectives for studies performed in Utah and Washington were to: 1) determine whether HTIs inhibit A. mellifera thermoregulation or colony growth, 2) compare O. lignaria emergence duration from an HTI with and without hive heat, and 3) assess whether O. lignaria females leave HTIs located at the orchard edge to nest throughout the orchard. We found no significant differences between the internal temperatures of A. mellifera colonies with and without HTIs and no impact on A. mellifera food storage or brood production. Osmia lignaria in hive-heated HTIs emerged 3× faster than bees in unheated HTIs. Heated HTIs were significantly cooler than hive temperatures but significantly warmer than HTIs atop empty hive boxes. Osmia lignaria nest distribution was not correlated to the location of HTIs at the orchard edge. Overall, HTIs were effective for timely, on-site emergence of O. lignaria for orchard pollination without negatively impacting A. mellifera colonies.


hst-1 transforming protein: expression in silkworm cells and characterization as a novel heparin-binding growth factor.
A protein encoded by an hst-1 transforming gene was expressed in silkworm-derived BmN cells and secreted into the culture medium using a recombinant baculovirus vector. The strong affinity for heparin of the secreted protein made it possible to purify the hst-1 protein to homogeneity in a two-step procedure. The purified hst-1 protein has a molecular weight of 18,000 and stimulates both DNA synthesis in NIH3T3 cells and human umbilical vein endothelial cell proliferation. In addition, morphological changes and anchorage-independent growth of NIH3T3 cells are induced by this product. These results show that the hst-1 transforming protein is a novel heparin-binding growth factor as predicted by nucleotide sequence analysis.


Expression of p53-induced apoptosis effector PERP in primary uveal melanomas: downregulation is associated with aggressive type.
Expression of PERP (p53 apoptosis effector related to PMP-22) was investigated in primary uveal melanomas and its variation was analyzed in relation to clinico-pathological and cytogenetical characteristics of these tumors. The transcriptional level of PERP gene was measured by quantitative real-time RT-PCR in 26 uveal melanomas with known chromosomes 3 and 8 status. PERP protein levels were assessed by Western blot analysis of 22 fresh-frozen tumors and by immunohistochemical analysis of 16 paraffin-embedded tumor specimens. Differential expression of PERP was identified in primary choroidal melanoma specimens, both at transcriptional and protein level. Reduced PERP mRNA level was significantly associated with monosomy 3 (two-way ANOVA and t-test, p=0.004) but not with gains in chromosome 8. Transcriptional downregulation of PERP did not present a statistically significant association with ciliary body involvement, size, PAS-positive loops or cell type. Immunoblotting and immunohistochemistry further demonstrated significantly reduced PERP protein level in monosomy 3 melanomas, as compared with disomy 3 tumors. The altered expression of PERP highlighted this apoptosis-specific target of p53 as a possible contributor to apoptosis in uveal melanoma with PERP downregulation being particularly relevant to the aggressive (monosomy 3) type of uveal melanoma. As PERP is a novel type of p53 effector that is likely to stimulate apoptosis through a mechanism distinct from that of Bcl-2-related mitochondrial effectors, further elucidation of its role in uveal melanoma pathogenesis will assist in the design of novel therapeutic approaches aimed at increasing the rate of apoptosis in this tumor.


Characterizing Protein Kinase Substrate Specificity Using the Proteomic Peptide Library (ProPeL) Approach.
Characterizing protein kinase substrate specificity motifs represents a powerful step in elucidating kinase-signaling cascades. The protocol described here uses a bacterial system to evaluate kinase specificity motifs in vivo, without the need for radioactive ATP. The human kinase of interest is cloned into a heterologous bacterial expression vector and allowed to phosphorylate E. coli proteins in vivo, consistent with its endogenous substrate preferences. The cells are lysed, and the bacterial proteins are digested into peptides and phosphoenriched using bulk TiO2 . The pooled phosphopeptides are identified by tandem mass spectrometry, and bioinformatically analyzed using the pLogo visualization tool. The ProPeL approach allows for detailed characterization of wildtype kinase specificity motifs, identification of specificity drift due to kinase mutations, and evaluation of kinase residue structure-function relationships. © 2018 by John Wiley & Sons, Inc.


Static osteogenesis does not precede dynamic osteogenesis in periosteal ossification of Pleurodeles (Caudata, Amphibia) and Pogona (Squamata, Lepidosauria).
Two successive mechanisms have been described in perichondral ossification: (1) in static osteogenesis, mesenchymal cells differentiate into stationary osteoblasts oriented randomly, which differentiate into osteocytes in the same site; (2) in dynamic osteogenesis, mesenchymal cells differentiate into osteoblasts that are all oriented in the same direction and move back as they secrete collagen fibers. This study is aimed at testing the hypothesis that the ontogenetic sequence static then dynamic osteogenesis observed in the chicken and in the rabbit is homologous and was acquired by the last common ancestor of amniotes or at a more inclusive node. For this we analyze the developmental patterns of Pleurodeles (Caudata, Amphibia) and those of the lizard Pogona (Squamata, Lepidosauria). We processed Pleurodeles larvae and Pogona embryos, prepared thin and ultrathin sections of appendicular bones, and analyzed them using light and transmission electron microscopy. We show that static osteogenesis does not precede dynamic osteogenesis in periosteal ossification of Pleurodeles and Pogona. Therefore, the null hypothesis is rejected and according to the parsimony method the ontogenetic sequence observed in the chicken and in the rabbit are convergent. In Pleurodeles and Pogona dynamic osteogenesis occur without a previous rigid mineralized framework, whereas in the chicken and in the rabbit dynamic osteogenesis seems to take place over a mineralized support whether bone (in perichondral ossification) or calcified cartilage (in endochondral ossification). Interestingly, in typical dynamic osteogenesis, osteoblasts show an axis (basal nucleus-distal endoplasmic reticulum) perpendicular to the front of secreted unmineralized bone matrix, whereas in Pleurodeles and Pogona this axis is parallel to the bone matrix.


Tetrahydrobiopterin analogues with NO-dependent pulmonary vasodilator properties.
Reduced NO levels due to the deficiency of tetrahydrobiopterin (BH(4)) contribute to impaired vasodilation in pulmonary hypertension. Due to the chemically unstable nature of BH(4), it was hypothesised that oxidatively stable analogues of BH(4) would be able to support NO synthesis to improve endothelial dysfunction in pulmonary hypertension. Two analogues of BH(4), namely 6-hydroxymethyl pterin (HMP) and 6-acetyl-7,7-dimethyl-7,8-dihydropterin (ADDP), were evaluated for vasodilator activity on precontracted rat pulmonary artery rings. ADDP was administered to pulmonary hypertensive rats, followed by measurement of pulmonary vascular resistance in perfused lungs and eNOS expression by immunohistochemistry. ADDP and HMP caused significant relaxation in vitro in rat pulmonary arteries depleted of BH(4) with a maximum relaxation at 0.3μM (both P<0.05). Vasodilator activity of ADDP and HMP was completely abolished following preincubation with the NO synthase inhibitor, L-NAME. ADDP and HMP did not alter relaxation induced by carbachol or spermine NONOate. BH(4) itself did not produce relaxation. In rats receiving ADDP 14.1mg/kg/day, pulmonary vasodilation induced by calcium ionophore A23187 was augmented and eNOS immunoreactivity was increased. In conclusion, ADDP and HMP are two analogues of BH(4), which can act as oxidatively stable alternatives to BH(4) in causing NO-mediated vasorelaxation. Chronic treatment with ADDP resulted in improvement of NO-mediated pulmonary artery dilation and enhanced expression of eNOS in the pulmonary vascular endothelium. Chemically stable analogues of BH(4) may be able to limit endothelial dysfunction in the pulmonary vasculature.


Unexpected electro-catalytic activity of the CO reduction reaction on Cr-embedded poly-phthalocyanine realized by strain engineering: a computational study.
The electrochemical conversion of carbon monoxide (CO) into value-added products is highly promising for carbon utilization and CO removal. Based on previous theoretical studies, we computationally explored the effect of strain engineering on electrocatalysis of the CO reduction reaction (CORR) by two-dimensional (2D) transition metal embedded polyphthalocyanines (MPPcs). By calculating the adsorption energy of CO and the free energies of key intermediates on the MPPcs under uniaxial and biaxial strains, it was revealed that only CrPPc under biaxial strain has the potential to exhibit significant enhancement of the catalytic performance. The free energy diagrams of the CORR catalyzed by CrPPc were plotted under specific biaxial strains, where both the optimal reaction pathway and rate-determining step are found to be evidently changed. What's more, the 5% compressive strain imposed on CrPPc results in an ultra-low limiting potential (UL = -0.09 V) with high selectivity on CH4 as the final product, indicating unexpected electro-catalytic activity. Our study clearly elucidates that moderate strain could greatly enhance the electrocatalytic performance of 2D materials in the CORR.


Postural Instability and Simulator Seasickness.
Motion sickness is a serious issue for many individuals, but the problem is particularly important among military personnel who may regularly experience unusual or extreme motion profiles as a part of their duties. As such, it is important to understand the underlying mechanisms that contribute to motion sickness, which in turn can lead to new and more effective countermeasures. The current study investigated causal etiology by examining the predictions of postural instability theory. Subjects experienced multiple motion profiles while reporting their sickness symptoms. Postural instability was directly manipulated by including both an active and passive condition. In the active condition, subjects could actively adapt their posture to the motion profile. In the passive condition, subjects had their feet affixed in place and could not effectively adapt their posture to the motion profiles. Subjects completed both conditions to control for individual differences in motion sickness susceptibility. Active condition subjects had greater postural stability as measured by sample entropy (M = 0.179 Active, M = 0.136 Passive), and sickness symptoms increased with time. Both results provide a methodological check against our manipulation. However, there were no differences in symptoms between active or passive conditions as measured by the simulator sickness questionnaire (M = 16.56 and M = 18.25, respectively), and no relationship between our measure of postural instability and symptomology. These results do not support postural instability as the primary causal factor in motion sickness; however, more research is needed to elucidate the mechanisms of motion sickness etiology.Pettijohn KA, Geyer D, Gomez J, Becker WJ, Biggs AT. Postural instability and simulator seasickness. Aerosp Med Hum Perform. 2018; 89(7):634-641.


Biodistribution of cisplatin revealed by imaging mass cytometry identifies extensive collagen binding in tumor and normal tissues.
Imaging mass cytometry was used for direct visualization of platinum localization in tissue sections from tumor and normal tissues of cisplatin-treated mice bearing pancreas cancer patient-derived xenografts. This recently-developed technology enabled simultaneous detection of multiple markers to define cell lineage, DNA damage response, cell proliferation and functional state, providing a highly detailed view of drug incorporation in tumor and normal tissues at the cellular level. A striking and unanticipated finding was the extensive binding of platinum to collagen fibers in both tumor and normal mouse tissues. Time course experiments indicated the slow release of stroma-bound platinum, although it is currently unclear if released platinum retains biological activity. Imaging mass cytometry offers a unique window into the in vivo effects of platinum compounds, and it is likely that this can be extended into the clinic in order to optimize the use of this important class of agent.


Utilizing individual fish biomass and relative abundance models to map environmental niche associations of adult and juvenile targeted fishes.
Many fishes undergo ontogenetic habitat shifts to meet their energy and resource needs as they grow. Habitat resource partitioning and patterns of habitat connectivity between conspecific fishes at different life-history stages is a significant knowledge gap. Species distribution models were used to examine patterns in the relative abundance, individual biomass estimates and environmental niche associations of different life stages of three iconic West Australian fishes. Continuous predictive maps describing the spatial distribution of abundance and individual biomass of the study species were created as well predictive hotspot maps that identify possible areas for aggregation of individuals of similar life stages of multiple species (i.e. spawning grounds, fisheries refugia or nursery areas). The models and maps indicate that processes driving the abundance patterns could be different from the body size associated demographic processes throughout an individual's life cycle. Incorporating life-history in the spatially explicit management plans can ensure that critical habitat of the vulnerable stages (e.g. juvenile fish, spawning stock) is included within proposed protected areas and can enhance connectivity between various functional areas (e.g. nursery areas and adult populations) which, in turn, can improve the abundance of targeted species as well as other fish species relying on healthy ecosystem functioning.


Methane production and solids destruction in an anaerobic solid waste reactor due to post-reactor caustic and heat treatment.
This study was undertaken to determine the feasibility of caustic and heat treatment of sludge from a dry anaerobic reactor (DAR) with respect to increased methane production and solids destruction. The DAR was operated semi-continuously at 55 degrees C on sized-reduced municipal solid waste at a solids retention time of 15 days. A respirometer was employed to monitor the extent and rate of methane production from anaerobic biodegradation of DAR sludge that was treated with caustic and heat. Results indicate that caustic and heat treatment at 50 degrees C and 175 degrees C increased methane production by 22% and 52%, respectively. Also, volatile solids destruction increased from 46% to 58% and 83%, respectively. Based on these results, economic analysis for a full-scale 10(5) kg/d facility suggests that annual project revenue for 50 degrees C and 175 degrees C treatment is estimated at $21,000 and $445,000, respectively.


Tunable Magnetic Anisotropy from Higher-Harmonics Exchange Scattering on the Surface of a Topological Insulator.
We show that higher-harmonics exchange scattering from a magnetic adatom on the surface of a three dimensional topological insulator leads to a magnetic anisotropy whose magnitude and sign may be tuned by adjusting the chemical potential of the helical surface band. As the chemical potential moves from the Dirac point towards the surface band edge, the surface normal is found to change from a magnetic easy to a hard axis. Hexagonal warping is shown to diminish the region with easy axis anisotropy, and to suppress the anisotropy altogether. This indirect contribution can be comparable in magnitude to the intrinsic term arising from crystal field splitting and atomic spin-orbit coupling, and its tunability with the chemical potential makes the two contributions experimentally discernible, and endows this source of anisotropy with potentially interesting magnetic functionality.


Magnetic Molecularly Imprinted Polymers: An Update on Their Use in the Separation of Active Compounds from Natural Products.
During the last few years, separation techniques using molecularly imprinted polymers (MIPs) have been developed, making breakthroughs using magnetic properties. Compared to conventional MIPs, magnetic molecularly imprinted polymers (MMIPs) have advantages in sample pretreatment due to their high specificity and selectivity towards analytes as a result of their larger specific surface areas and highly accessible specific binding sites. The techniques of isolation of active compounds from natural products usually require very long process times and low compound yields. When MMIPs are used in sample separation as Solid Phase Extraction (SPE) sorbents, the MMIPs are introduced into the dissolved sample and spread evenly, and they form bonds between the analyte and the MMIPs, which are then separated from the sample matrix using an external magnetic field. This process of separating analytes from the sample matrix makes the separation technique with MMIPs very simple and easy. This review discusses how to synthesize MMIPs, which factors must be considered in their synthesis, and their application in the separation of active compounds from natural products. MMIPs with magnetic core-shells made by co-precipitation can be a good choice for further development due to the high synthesis yield. Further optimization of the factors affecting the size and distribution of magnetic core-shell particles can obtain higher synthesis yields of MMIPs with higher adsorption capacity and selectivity. Thus, they can isolate target compounds from natural plants in high yields and purity.


Ruptured Aneurysm Trials: The Importance of Longer-term Outcomes and Meta-analysis for 1-year Mortality.
To assess current knowledge for the management of ruptured abdominal aortic aneurysm (AAA), based on the 1-year outcomes of 3 recent randomised trials. An individual patient data meta-analysis of three recent randomised trials of endovascular versus open repair, including 817 patients, was conducted according to a pre-specified analysis plan, report all-cause mortality and re-interventions at 1 year after the index event. Mortality across the 3 trials at 1-year was 38.6% for the EVAR or endovascular strategy patient groups and 42.8% for the open repair groups, pooled odds ratio 0.84 (95% CI 0.63-1.11), p = .209. There was no evidence of heterogeneity in the odds ratios between trials. When the patients in the endovascular strategy group of the IMPROVE trial were restricted to those with proven rupture who were anatomically suitable for endovascular repair, the pooled odds ratio reduced slightly to 0.80 (95% CI 0.56-1.16), p = .240. After 1 year there is a consistent but non-significant trend for lower mortality for EVAR or an endovascular strategy. Taken together with the recent gains in health economic outcomes demonstrated at 1 year in the IMPROVE trial, the evidence suggests that endovascular repair should be used more widely for ruptured aneurysms.


A Fluorescent Nanosensor for Silver (Ag+) and Mercury (Hg2+) Ions Using Eu (III)-Doped Carbon Dots.
Carbon dots doped with Eu3+ ions (Eu-Cdots) were prepared by a hydrothermal treatment, using citric acid and urea as precursors and Eu (NO3)3 as a europium source. The Eu3+ ions are strongly coordinated with the carboxylate groups at the surface of the Cdots and incorporated within the nanographene network in the carbon core. Vibrational spectroscopy provides evidence of such interaction with identification of bands assigned to the stretching of the Eu-O bond. Eu3+ doped Cdots have larger diameters then undoped Cdots, but they are divided into smaller domains of sp2 carbon. The UV-vis excitation spectrum provides evidence of energy transfer from the Cdots to the Eu3+. The luminescence spectrum shows the characteristic sharp peaks of Eu3+ in the red part of the visible spectrum and a broad emission of Cdots centered at 450 nm. The luminescence of the Cdots is strongly quenched by Hg2+ and Ag+, but not by other cations. The quenching mechanism differs significantly depending on the nature of the ion. Both the blue emission of Cdots and the red emission of Eu3+ are quenched in the presence of Hg2+ while only the emission of the Cdots is affected by the presence of Ag+. A ratiometric sensor can be built using the ratio of luminescence intensities of the Cdots to the Eu3+ peaks.


[The effect of smoking habit on aortic pulse wave velocity using a new method for data analysis].
We measured aortic pulse wave velocity (PWV) in 168 male adult cases of various arteriosclerotic diseases. In order to evaluate the effects of age, smoking habits, alcohol intake, and blood pressure, we applied the least median of squares (LMS) regression which was considered to be very useful for data analysis. The results showed that PWV level increased with age. Furthermore smoking was associated with increasing PWV level and this effect was also related to age. We concluded that the PWV was valuable as an index of arteriosclerosis, and instead of the classical least squares method, LMS regression was very useful for analysis of medical data.


Nicotinamide riboside alleviates exercise intolerance in ANT1-deficient mice.
Mitochondrial disorders are often characterized by muscle weakness and fatigue. Null mutations in the heart-muscle adenine nucleotide translocator isoform 1 (ANT1) of both humans and mice cause cardiomyopathy and myopathy associated with exercise intolerance and muscle weakness. Here we decipher the molecular underpinnings of ANT1-deficiency-mediated exercise intolerance. This was achieved by correlating exercise physiology, mitochondrial function and metabolomics of mice deficient in ANT1 and comparing this to control mice. We demonstrate a peripheral limitation of skeletal muscle mitochondrial respiration and a reduced complex I respiration in ANT1-deficient mice. Upon exercise, this results in a lack of NAD+ leading to a substrate limitation and stalling of the TCA cycle and mitochondrial respiration, further limiting skeletal muscle mitochondrial respiration. Treatment of ANT1-deficient mice with nicotinamide riboside increased NAD+ levels in skeletal muscle and liver, which increased the exercise capacity and the mitochondrial respiration. Increasing NAD+ levels with nicotinamide riboside can alleviate the exercise intolerance associated to ANT1-deficiency, indicating the therapeutic potential of NAD+-stimulating compounds in mitochondrial myopathies.


Criteria for Locating Temporary Shelters for Refugees of Conflicts: A Systematic Review.
We aimed to identify the indicators and criteria to locate temporary shelters for conflict refugees. This systematic review evaluated the full-text of the related articles in international electronic databases, such as Web of Science, Scopus, PubMed, Cochran, and Google Scholar from the beginning and without time limit to 1 June 2019. In addition, this search was based on a strategy developed by the researchers. The studies were selected regardless of their methods and two data extraction forms were used to extract the most relevant and important information. Among 10124 cases of primary documents, 38 articles were selected, and 25 articles were analyzed in full-text. Totally, 45 indicators were identified and classified into two main categories of physical and non-physical indicators with six subcategories of land ownership, host government, access to infrastructures, site safety, land characteristics, and economic, social, and cultural considerations. The selection of temporary shelters for the conflict refugees requires the identification of all the specific influential factors not properly addressed. The final indicators obtained in our review could be incorporated into the development of the models required in this regard.


Potential Impact of 68Ga-PSMA-11 PET/CT on the Planning of Definitive Radiation Therapy for Prostate Cancer.
Standard-of-care imaging for initial staging of prostate cancer (PCa) underestimates disease burden. Prostate-specific membrane antigen (PSMA) PET/CT detects PCa metastasis with superior accuracy, having a potential impact on the planning of definitive radiation therapy (RT) for nonmetastatic PCa. Our objectives were to determine how often definitive RT planning based on standard target volumes covers 68Ga-PSMA-11 PET/CT-defined disease and to assess the potential impact of 68Ga-PSMA-11 PET/CT on definitive RT planning. Methods: This was a post hoc analysis of an intention-to-treat population of 73 patients with localized PCa without prior local therapy who underwent 68Ga-PSMA PET/CT for initial staging as part of an investigational new drug trial. Eleven of the 73 were intermediate-risk (15%), 33 were high-risk (45%), 22 were very-high-risk (30%), and 7 were N1 (9.5%). Clinical target volumes (CTVs), which included the prostate, seminal vesicles, and (in accord with the Radiation Therapy Oncology Group consensus guidelines) pelvic lymph nodes (LNs), were contoured on the CT portion of the PET/CT images by a radiation oncologist masked to the PET findings. 68Ga-PSMA-11 PET/CT images were analyzed by a nuclear medicine physician. 68Ga-PSMA-11-positive lesions not covered by planning volumes based on the CTVs were considered to have a major potential impact on treatment planning. Results: All patients had one or more 68Ga-PSMA-11-positive primary prostate lesions. Twenty-five (34%) and 7 (9.5%) of the 73 patients had 68Ga-PSMA-11-positive pelvic LN and distant metastases, respectively. The sites of LN metastases in decreasing order of frequency were external iliac (20.5%), common iliac (13.5%), internal iliac (12.5%) obturator (12.5%), perirectal (4%), abdominal (4%), upper diaphragm (4%), and presacral (1.5%). The median size of the LN lesions was 6 mm (range, 4-24 mm). RT planning based on the CTVs covered 69 (94.5%) of the 73 primary lesions and 20 (80%) of the 25 pelvic LN lesions, on a per-patient analysis. Conclusion:68Ga-PSMA-11 PET/CT had a major impact on intended definitive RT planning for PCa in 12 (16.5%) of the 73 patients whose RT fields covered the prostate, seminal vesicles, and pelvic LNs and in 25 (37%) of the 66 patients whose RT fields covered the prostate and seminal vesicles but not the pelvic LNs.


Early protein malnutrition disrupts cerebellar development and impairs motor coordination.
Maternal malnutrition affects every aspect of fetal development. The present study asked the question whether a low-protein diet of the mother could result in motor deficits in the offspring. Further, to examine whether cerebellar pathology was correlated with motor deficits, several parameters of the postnatal development of the cerebellum were assayed. This is especially important because the development of the cerebellum is unique in that the time scale of development is protracted compared with that of the cortex or hippocampus. The most important result of the study is that animals born to protein-deficient mothers showed significant delays in motor development as assessed by rotarod and gait analysis. These animals also showed reduced cell proliferation and reduced thickness in the external granular layer. There was a reduction in the number of calbindin-positive Purkinje cells (PC) and granular cells in the internal granular layer. However, glial fibrillary acidic protein-positive population including Bergmann glia remained unaffected. We therefore conclude that the development of the granular cell layer and the PC is specifically prone to the effects of protein malnutrition potentially due to their protracted developmental period from approximately embryonic day 11 to 13 until about the third postnatal week.


A pilot study of the Carpathian ichneumonine parasitoids (Hymenopera, Ichneumonidae: Ichneumoninae) reveals eighty-eight new records for Ukraine.
Data on the subfamily Ichneumoninae Latreille, 1802 (Hymenopera: Ichneumonidae) from the Ukrainian Carpathians is summarized, with 196 species from eight tribes, of which 88 species are recorded from Ukraine for the first time. The new Ukrainian records belong to four tribes, Heresiarchini Ashmead, 1900, Ichneumonini Latreille, 1802, Phaeogenini Förster, 1869, and Platylabini Berthoumieu, 1904. Phaeogenini is the most poorly studied with 75% of species recorded for the country for the first time. High-altitude zone distribution is discussed: oak forest zone is the most species-rich (125 species), while the subalpine zone is the most poorly studied (57% of species found only in this zone are new records for Ukraine). The flying adults of Ichneumoninae were found from April until October, with a maximum number of species and genera collected in July, and with most specimens collected in May. Stenobarichneumon ridibitor Aubert, 1994 is transferred to the genus Baranisobas Heinrich, 1972 (comb. nov.).


Residues in foods. 1989.
A total of 18,798 samples of domestically produced food from all 50 states and Puerto Rico and imported food from 88 countries were analyzed for pesticide residues in 1989. Of these, 18,113 were surveillance samples, which are collected when there is no suspicion of a pesticide problem. No residues were found in 65% of domestic surveillance samples and in 67% of import surveillance samples. Less than 1% of the 18,113 surveillance samples contained residues that exceeded EPA tolerances. Findings in the 685 compliance samples reflect the fact that they are collected and analyzed when a pesticide problem is suspected. The 1989 Total Diet Study findings show that intakes of pesticide residues are generally well below standards set by FAO/WHO as well as by EPA. Results for 1989 are similar to those for 1987 and 1988 and continue to demonstrate that the levels of pesticide residues in the U.S. food supply are low.


A 40-cm Welded-Segment Lightweight Aluminum Alloy Telescope Mirror.
A 40-cm aluminum alloy, nickel plated, mirror has been made by welding together six individually cast segments. The mirror is shown to be stable to within one wave over a temperature of 58 degrees C primarily due to the use of the aluminum alloy Tenzaloy. The weldment as well as the alloy itself are now known to be capable of essentially complete stress relief by annealing. The possibilities of extending the welding technique to considerably larger telescope systems is also discussed.


Functional outcome measures for knee dysfunction assessment.
Maximizing the functional abilities of the individual is the primary objective of any therapeutic intervention. Functional outcome data are valuable to those involved in the care of the athlete because such data provides information that helps facilitate the clinical decision-making process and, therefore, helps insure a safe and efficient return to athletics. Functional outcome measures also provide useful data for assessing therapeutic intervention efficacy. The clinician/researcher must consider various factors when selecting an appropriate outcome measure, such as: the patient population, pathology, specific test parameters, psychometric properties, and practicality of the measure. The primary purpose of this paper is to provide the reader with guidelines for either assessing existing measures or developing new measures of functional outcomes for use in clinical practice and research.