Moxifloxacin-induced oral erythema multiforme: An unusual adverse effect hitherto unreported.
Moxifloxacin is a fluoroquinolone with excellent activity in community-acquired respiratory tract infections. Common adverse effects are gastrointestinal symptoms, headache, dizziness, etc., Some serious adverse effects include tendon rupture, rhabdomyolysis, peripheral neuropathy, and interstitial nephritis. Cutaneous adverse effects include allergic reactions, angioedema, Steven-Johnson syndrome, and toxic epidermal necrosis. Erythema multiforme (EM), an acute self-limiting disease, most commonly occurs due to infection and rarely due to drugs or systemic disease. EM is classified into EM major and minor, both having skin lesions. A third category of EM has also been described with only oral involvement and without any skin lesions. Oral EM itself is an uncommon entity which has been reported due to nonsteroidal anti-inflammatory drugs. Here, we are reporting a case of moxifloxacin-induced oral EM. After extensive search in PubMed-Medline database, we could not find any such co-occurrence of moxifloxacin-induced oral EM. To the best of our knowledge, this is the first reported case.


Evaluation of electric arc furnace-processed steel slag for dermal corrosion, irritation, and sensitization from dermal contact.
Electric arc furnace (EAF) steel slag is alkaline (pH of ~11-12) and contains metals, most notably chromium and nickel, and thus has potential to cause dermal irritation and sensitization at sufficient dose. Dermal contact with EAF slag occurs in many occupational and environmental settings because it is used widely in construction and other industrial sectors for various applications including asphaltic paving, road bases, construction fill, and as feed for cement kilns construction. However, no published study has characterized the potential for dermal effects associated with EAF slag. To assess dermal irritation, corrosion and sensitizing potential of EAF slag, in vitro and in vivo dermal toxicity assays were conducted based on the Organisation for Economic Co-operation and Development (OECD) guidelines. In vitro dermal corrosion and irritation testing (OECD 431 and 439) of EAF slag was conducted using the reconstructed human epidermal (RHE) tissue model. In vivo dermal toxicity and delayed contact sensitization testing (OECD 404 and 406) were conducted in rabbits and guinea pigs, respectively. EAF slag was not corrosive and not irritating in any tests. The results of the delayed contact dermal sensitization test indicate that EAF slag is not a dermal sensitizer. These findings are supported by the observation that metals in EAF slag occur as oxides of low solubility with leachates that are well below toxicity characteristic leaching procedure (TCLP) limits. Based on these results and in accordance to the OECD guidelines, EAF slag is not considered a dermal sensitizer, corrosive or irritant.


Valproic acid inhibits proliferation of EB virus-infected natural killer cells.
There is no recognized treatment for Epstein-Barr virus (EBV)-associated natural killer (NK) cell lymphoproliferative disorders (LPDs). To determine the possibility of histone deacetylase inhibitors as a therapeutic tool for such disorders, we investigated the anti-proliferative effects of valproic acid (VPA) on two EBV-infected NK cell lines (KAI3 and NKED). VPA inhibited the growth of both lines in a dose- and time-dependent manner by inducing histone hyperacetylation. G1 cell cycle arrest was induced at 24 hours and was associated with increased expression of p21(WAF1), p27(Kip1), and cyclin E and decreased expression of cyclin D2, CDK4, and c-myc. Sub-G1 fractions were not significantly changed at 24 hours, whereas cleaved caspase-3 and cleaved PARP were already detected, and the extrinsic apoptotic pathway, determined by cleaved caspase-8, was activated. Finally, sub-G1 accumulation was increased after 72 hours following stimulation. These findings indicate that VPA might be a therapeutic option for EBV-associated NK-cell LPDs.


Arsenic Fate in Peat Controlled by the pH-Dependent Role of Reduced Sulfur.
Reduced sulfur (S) has a contrasting role in the fate of arsenic (As) in peatlands. Sulfur bridges provide efficient binding of As to organic carbon (C), but the formation of aqueous As-S species, so-called thioarsenates, leads to a low to no sorption tendency to organic C functional groups. Here, we studied how pH changes the role of reduced S in desorption and retention of presorbed As in model peat. Control desorption experiments without S addition revealed that As was mobilized, predominantly as arsenite, in all treatments with relative mobilization increasing with pH (4.5 < 7.0 < 8.5). Addition of sulfide or polysulfide caused substantial As retention at acidic conditions but significantly enhanced As desorption compared to controls at neutral to alkaline pH. Thioarsenates dominated As speciation at pH 7.0 and 8.5 (maximum, 79%) and remained in solution without (re)sorption to peat. Predominance of arsenite in control experiments and no evidence of surface-bound thioarsenates at pH 7.0 suggest mobilization to proceed via arsenite desorption, reaction with dissolved or surface-bound reduced S, and formation of thioarsenates. Our results suggest that natural or management-related increases in pH or increases in reduced S in near-neutral pH environments can turn organic matter from an As sink into a source.


Correlation between Vitamin B12 and Mental Health in Children and Adolescents: A Systematic Review and Meta-analysis.
To conduct the association between vitamin B12 and mental health in children and adolescents. Five databases were searched for observational studies in any language reporting on mental health and vitamin B12 levels or intake in children and adolescents from inception to March 18, 2022. Two authors independently extracted data and assessed study quality. Qualitative and quantitative analysis of data were performed. The review was registered in the PROSPERO database (CRD42022345476). Fifty six studies containing 37,932 participants were identified in the review. Vitamin B12 levels were lower in participants with autism spectrum disorders (ASD) (standardized mean difference [SMD], -1.61; 95% confidence interval [95% CI], -2.44 to -0.79; p < 0.001), attention deficit hyperactivity disorders (SMD, -0.39; 95% CI, -0.78 to -0.00; p = 0.049) compared with control group. Vitamin B12 intake were lower in participants with ASDs (SMD, -0.86; 95% CI, -1.48 to -0.24; p = 0.006) compared with control group, but showed no difference between depression group (SMD, -0.06; 95% CI, -0.15 to 0.03; p = 0.17) and the control group. Higher vitamin B12 intake were associated with lower risk of depression (odds ratio [OR], 0.79; 95% CI, 0.63-0.98; p = 0.034) and behavioral problems (OR, 0.83; 95% CI, 0.69-0.99; p = 0.04). The vast majority of included studies supported potential positive influence of vitamin B12 on mental health, and vitamin B12 deficiency may be a reversible cause for some mental health disorders in children and adolescents.


Interactions of lymphokine-activated killer cells and A549 lung carcinoma nodules maintained in three-dimensional culture.
Lymphokine-activated killer (LAK) cells were cocultured in the presence of interleukin-2 (IL-2), with pulmonary surfactant secreting A549 lung carcinoma nodules and maintained in continuous three-dimensional culture for 2-6 days in an attempt to test the response of tumor cells which produce LAK cell inhibitory substances. The A549 nodules secrete mucus which envelops them. This mucus is also secreted inside pseudoalveolar structures characteristic of these nodules. The mucus contains the pulmonary surfactant and sialomucins, both LAK cell inhibitory substances. The spontaneous infiltration into the neoplastic tissue and the membrane contacts established between the two cell types were studied by means of histological, immunohistochemical and electron-microscopic methods. Free-floating LAK cells were allowed to sediment and adhere freely to the nodule surface. The cytostatic and cytolytic effects of LAK cells were tested using thymidine incorporation into DNA and flow cytometry. Despite the presence of a mucus envelope, LAK cells adhered to the A549 nodule surface and penetrated spontaneously into them in the presence of IL-2; they settled mainly in the pseudoalveolar structures where they became apoptotic. According to electron-microscopic observations performed on the second day of coculture, the LAK cells, which remained between the cancer cells, established mostly pinpoint contacts with the carcinoma cells, forming cytoplasmic fusions. These fusions indicate the induction of pores in both the cancer cell and the LAK cell membranes. Electron-microscopic observation also displayed LAK-cell-associated apoptotic and necrotic carcinoma cells. However, at this stage of the coculture (day 2), the DNA synthesis rate of the A549 nodules still remained unchanged; it diminished by approximately 3 times on day 4 and almost stopped on day 6: nodule disintegration was then complete. In the free-floating LAK cell component of the cocultures, DNA synthesis was already strongly inhibited (26x) by the second day. Nevertheless, their cytolytic effect remained unaltered, as was tested on A549 monolayer cells. The presence of tumor necrosis factor (TNF) in the coculture supernatant has been demonstrated, and when coculturing took place in the presence of monoclonal TNF antibody, nodule proliferation was significantly enhanced (up to 145%). Our results indicate that, despite the presence of pulmonary surfactant and sialomucins containing mucus, LAK cells were capable of killing lung carcinoma cells in three-dimensional culture at an early stage of coculture (day 2) by direct cell-to-cell contact. Total nodule disintegration, however, was complete much later (on day 6), and taking into account the low amount of LAK cells in the cancer tissue, this seemed to be the result of an indirect effect implying, in particular, the presence of soluble TNF.


Improved retinal ganglion cell survival through retinal microglia suppression by a chinese herb extract, triptolide, in the DBA/2J mouse model of glaucoma.
To investigate the changes in retinal microglia and retinal ganglion cell (RGC) survival after long-term administration of a Chinese herb extract, triptolide, in a DBA/2J mice. DBA/2J mice (n = 96) were administered triptolide (n = 48) 25 µg/kg or vehicle (n = 48) and were judged at 7, 9, 11 months of age. Long-term triptolide treatment tended to attenuate the anterior segment pathology in experimental group, though intraocular pressure was not significantly different between the two groups. In the experimental group, RGC survival was improved (7, 9, 11 months: p = 0.035, 0.004, 0.014), and microglia activation was suppressed based on a more ramified appearance (9, 11 months: p = 0.024, 0.013) and a lower total microglial cell count (7, 9, 11 months: p = 0.028, 0.025, 0.014). Double-immunofluorescence staining revealed TNF? localized to microglia, TNFR1 localized to the RGCs and nerve fiber layer. These findings indicate that long-term triptolide administration suppressed microglia activation and improved RGC survival in DBA/2J mice.


Impact of early subcultures on stemness, migration and angiogenic potential of adipose tissue-derived stem cells and their resistance to in vitro ischemic condition.
Adipose tissue-derived stem cells (ADSCs) are capable of multipotential differentiation and express several angiogenic, anti-apoptotic and immunomodulatory markers. These features make adipose tissue as a promising source of stem cells for regenerative medicine. However, for efficient translational use, culture-induced changes in the gene expression profile and resistance of the ADSCs to ischemic environment should be taken into consideration. We compared the expression of some clinically important markers between the unpassaged and third-passaged ADSCs by RT-PCR, qPCR and flow cytometry. Our results demonstrated that the embryonic stem cell (ESC)-specific markers were expressed in the unpassaged ADSCs but were downregulated after three passages. The expression of stemness-related genes, TGFB and FGF2, was upregulated while FGF4 and LIF were downregulated after three passages. The expression of angiogenic genes in the third-passaged ADSCs was higher than the unpassaged cells. Epithelial-mesenchymal transition (EMT) markers were either expressed in the third-passaged ADSCs or significantly upregulated after three passages. In contrast, cell cycle inhibitors, CDKN1A and TP53, were downregulated with early subcultures. The unpassaged and third-passaged ADSCs showed nearly similar resistance to oxidative stress, hypoxia and serum deprivation. In conclusion, the primary cultures of human adipose tissue contain a subpopulation of cells expressing ESC-specific genes and proteins, but the expression of these pluripotency markers subsides rapidly in standard mesenchymal stem cell culture medium. The expression of angiogenic and EMT markers also varies with early subcultures. Altogether, early-passaged ADSCs may be better choices for transplantation therapy of injured tissues, especially after ischemic conditions.


Parathyroid function in long-term renal transplant patients: importance of pre-transplant PTH concentrations.
Lack of resolution of hyperparathyroidism after long-term renal transplantation is common. The relative roles of the graft function attained and the degree of pre-transplant hyperparathyroidism have not been established. Intact parathyroid hormone (iPTH) and several clinical parameters were studied before and 68.6+/-26.8 months (range: 30-124) after renal transplantation in 62 patients (20 females/42 males) with good renal function (creatinine <2 mg/dl). iPTH decreased from 214+/-229 pre-transplantation to 116+/-70 pg/ml post-transplantation (P<0.01). However, only 22.6% of patients had PTH concentrations in the normal range, and values greater than twice the upper normal limit were not uncommon (27.4%). Of the many variables analysed, creatinine (r=0.43; P=0.001) and pre-transplant PTH (r=0.31; P=0.02) significantly correlated with post-transplant PTH. After selecting patients with serum creatinine <1.5 mg/dl (n=46), pre-transplant PTH emerged as the more important predictor of post-transplant PTH (r=0.58; P<0.0001). After controlling for creatinine, the partial correlation was r=0.53, P<0.0001. We concluded that spontaneous resolution of hyperparathyroidism after renal transplantation is uncommon. In addition, the magnitude of pre-transplant hyperparathyroidism and the renal function determine the long-term post-transplant parathyroid function.


Evaluation of six media for the growth of Trichomonas vaginalis from vaginal secretions.
Many media have been formulated for the growth of Trichomonas vaginalis, but the relative sensitivities of these media have not been determined. We evaluated the ability of six media, including all five media commercially available in the United States, to grow Trichomonas vaginalis from vaginal secretions. In a first experiment, we evaluated the ability of five media to grow T. vaginalis from vaginal secretions of 375 women and determined the optimal days on which to read culture tubes, by inoculating aliquots of secretions into each medium and reading the tubes 1, 2, 3, 4, and 7 days later. Sixty-five patients (17%) had a positive wet-mount examination for T. vaginalis, and all the positive results were confirmed by growth in at least one medium. Of 310 wet-mount-negative specimens, 37 (12%) grew T. vaginalis; overall, 102 women (27%) had a positive culture. Diamond and modified Diamond media (the latter being the only medium not commercially available) detected 99 (97%) and 92 (90%) isolates, respectively, compared with three formulations of Kupferberg medium, which detected 77 (75%), 50 (49%), and 43 (42%) isolates. The optimal single day to read wet-mount-negative cultures was day 7, but 4 (11%) of the 37 positive specimens were positive only before day 7. In a second study, we compared the ability of modified Diamond medium with that of a sixth medium, Lash medium, to grow T. vaginalis from 48 wet-mount-positive specimens; modified Diamond medium supported growth in all cases, whereas Lash medium supported growth in only 26 (54%) cases. We conclude that formulations of Diamond medium are superior to formulations of Kupferberg or Lash medium for growth of t. vaginalis.


Negative impact of cardiovascular risk factors on left atrial and left ventricular function related to aortic stiffness--new application of 2-dimensional speckle-tracking echocardiography.
The aim of the present study was to detect earlier the negative effect of cardiovascular risk (CVR) factors on left atrial (LA) and left ventricular (LV) function related to abdominal aortic (AAO) stiffness using 2-dimensional speckle-tracking echocardiography (2DSTE) in asymptomatic patients. One hundred and twelve patients with CVR factors and 56 healthy individuals were studied. 2DSTE data were acquired for determination of LA and LV myocardial and AAO wall deformations. LA volume index, LV mass index, ratio of early diastolic transmitral flow to mitral annular velocity (E/e')/peak systolic LA strain (S-LAs), and AAO stiffness were greater, and peak early diastolic LV longitudinal strain rate (SR-LVe) was lower in the patient group. Among the significantly correlated variables with AAO stiffness on univariate analysis, multivariate linear regression analysis identified SR-LVe and (E/e')/S-LAs in the patient group, and only age in the healthy group, as independent predictor of AAO stiffness. Structural and functional changes in the LA and LV and AAO stiffening were accelerated with CVR factors, and higher AAO stiffness was associated with deteriorated LA compliance and impaired LV relaxation in asymptomatic patients with CVR factors. 2DSTE has a potential for earlier detection of abnormal LA and LV function related to increased AAO stiffness.


Risk perception and acceptance--one process or two? The impact of aspirations on perceived risk and preferences.
The experiments discussed here are aimed at determining whether risk perception and risk acceptance are two distinct psychological processes. This study is motivated by the idea of a double-criterion model of choice. In particular, in line with risk-value (R-V) models, in which risk is treated as a primitive, it is tested whether risk is independent of aspirations and whether preferences depend on aspirations. In two experiments, 305 university students were presented with pairs of risky projects and were asked to compare their riskiness and select one. The aspiration level, defined as the target return on the project, was set through an explicit instruction. In Experiment 1, a within-subject designwas applied, and thus aspirations were set at two different levels. In Experiment 2, with a between-subject design, two different aspiration levels were set for each group. The results indicate that risk ordering is insensitive to changes in aspirations, but preferences are sensitive to those changes. This supports distinctness of risk perception and risk acceptance. The findings are discussed in terms of the CPT and SP/A models and the R-V approach. It appears that double-criterion models provide better and psychologically sounder predictions of subjects' preferences.


Factors influencing maternal healthcare utilization in Papua New Guinea: Andersen's behaviour model.
Papua New Guinea (PNG) has recorded the highest maternal mortality ratio in the Western Pacific Region and faces major challenges in achieving SDG 3. Antenatal care (ANC), skilled birth attendant (SBA) and postnatal care (PNC) services are critical components of maternal healthcare services (MHS) for reducing maternal mortality and promoting maternal health in PNG. The study sought to assess the prevalence and determinants of ANC, SBA and PNC services amongst women in PNG. The study was conducted using the 2016-2018 Papua New Guinea Demographic and Health Survey. A total of 5248 reproductive-age women were considered as the analytical sample. The outcome variables were utilisation of ANC, SBA and PNC services. Chi-square test, multivariable logistic regression and dominance analysis were conducted. Statistical significance was set at p < 0.05. The prevalence rates of ANC, SBA and PNC services were 52.3%, 58.7% and 26.6%, respectively. Women's employment, education, media exposure, distance to health facility, household wealth, region, residence and parity were determinants of MHS utilisation. ANC, SBA and PNC services utilisation were all primarily influenced by enabling factors, followed by predisposing and need factors. This study demonstrated that enabling factors such as media exposure, distance to health facility, household wealth, region and residence have the greatest impact on MHS utilisation, followed by predisposing (working, education) and need factors (parity). Therefore, enabling factors should be prioritised when developing maternal health programmes and policies. For example, transport and health infrastructure should be strengthened and women's education and vocational training should be increased, especially in Highlands region, Momase region and rural areas, to increase the utilisation of MHS.


Common E protein determinants for attenuation of glycosaminoglycan-binding variants of Japanese encephalitis and West Nile viruses.
Natural isolates and laboratory strains of West Nile virus (WNV) and Japanese encephalitis virus (JEV) were attenuated for neuroinvasiveness in mouse models for flavivirus encephalitis by serial passage in human adenocarcinoma (SW13) cells. The passage variants displayed a small-plaque phenotype, augmented affinity for heparin-Sepharose, and a marked increase in specific infectivity for SW13 cells relative to the respective parental viruses, while the specific infectivity for Vero cells was not altered. Therefore, host cell adaptation of passage variants was most likely a consequence of altered receptor usage for virus attachment-entry with the involvement of cell surface glycosaminoglycans (GAG) in this process. In vivo blood clearance kinetics of the passage variants was markedly faster and viremia was reduced relative to the parental viruses, suggesting that affinity for GAG (ubiquitously present on cell surfaces and extracellular matrices) is a key determinant for the neuroinvasiveness of encephalitic flaviviruses. A difference in pathogenesis between WNV and JEV, which was reflected in more efficient growth in the spleen and liver of the WNV parent and passage variants, accounted for a less pronounced loss of neuroinvasiveness of GAG binding variants of WNV than JEV. Single gain-of-net-positive-charge amino acid changes at E protein residue 49, 138, 306, or 389/390, putatively positioned in two clusters on the virion surface, define molecular determinants for GAG binding and concomitant virulence attenuation that are shared by the JEV serotype flaviviruses.


Argasid Ticks of Palearctic Bats: Distribution, Host Selection, and Zoonotic Importance.
The soft ticks (Ixodida: Argasidae) are ectoparasites of terrestrial vertebrates with a wide geographic distribution, occurring on all continents. These ticks are obligate blood-feeders, most of them show high degrees of host-specialization and several species in arid and tropical regions are important parasites of livestock and men. Species commonly occurring on domestic animals and man are generally well-known, with many studies focusing on their ecology, distribution or vectorial role. However, wildlife-specialist soft ticks are less studied. Nearly half of all soft tick species are bat specialists, with five species (Carios vespertilionis, Chiropterargas boueti, Chiropterargas confusus, Reticulinasus salahi, and Secretargas transgariepinus) occurring in the Western Palearctic. There is no comprehensive study on the distribution, hosts or pathogens in these soft ticks, although most species were shown to carry several viral, bacterial, or protozoan pathogens and also to occasionally infest humans. Based on a literature survey and 1,120 distinct georeferenced records, we present here the geographical range, host selection and vectorial potential for bat-specialist soft ticks occurring in the Western Palearctic (chiefly Europe, North Africa, and the Middle East). Carios vespertilionis shows the largest distribution range and was found on most host species, being ubiquitous wherever crevice-roosting bats occur. All the other species were located only in areas with Mediterranean climate, with Ch. boueti, Chiropteraragas confusus, and R. salahi are missing entirely from Europe. These three species have a host spectrum of bats roosting primarily in caves, while S. transgariepinus and Ca. vespertilionis is feeding primarily on crevice-roosting bat species. All but one of these soft tick species are known to feed on humans and may be vectors of important disease agents (Rickettsia spp., Borrelia spp., Bartonella spp., Ehrlichia spp., Babesia spp., several nairo-, and flaviviruses). As several crevice-roosting bat species show a continuous adaptation to human-altered areas, with certain species becoming common city-dwellers in the Western Palearctic, the study of bat specialist soft ticks is also important from an epidemiologic point of view.


Remifentanil to treat hypertension in overweight patients during a fentanyl-based cardiac anesthesia A case series.
Cardiac surgery is associated with intense nociceptive and autonomic stimulation especially during sternotomy and aortic root dissection and moderate-to-high dose opioids are required to blunt the hemodynamic and neuroendocrine response to this kind of procedures. However, episodes of unwanted sympathetic activation leading to intraoperative hypertension are not always preventable with a fentanyl-based anesthesia regimen and antihypertensive drugs without anesthetic properties are added to obtain hemodynamic stability. We report on five cardiac surgical cases in which intraoperative hypertension unresponsive to incremental doses of fentanyl was successfully treated adding a remifentanil target-controlled infusion instead of a non-anesthetic vasoactive drug. This approach could help to avoid the dilemma: when should we stop adding anesthetics and switch to antihypertensive drugs in cardiac surgery?


Crescentic glomerulonephritis induced in the goat by immunization with homologous or heterologous glomerular basement membrane antigen.
Crescentic glomerular changes developed in goats 16 to 46 weeks after immunization with homologous or heterologous glomerular basement membrane (GBM) antigens incorporated in Freund's complete adjuvant. Mesangial widening, accumulation of migrant cells, fibrin deposition, and GBM thickening became manifest with time. The GBM was then attenuated and ruptured at a local area. Through the ruptured GBM, the influx of fibrin and blood cells occurred in the Bowman's space (BS) accompanying proliferation of epithelial cells lining the BS. The crescent thus formed was mainly composed of the capsular epithelial cells. The visceral epithelial cells (podocytes) and migrated blood cells contributed to the crescent formation to a lesser extent. Basement menbrane-like material appeared later between the crescentic cells and the crescent underwent a fibroepithelial form. The results indicate that the crescent develops in relation to the characteristic GBM damage with a resultant severe exudative change in the BS.


[Implanting human splenic lymphocytes into severe combined immunodeficiency mice transplanted with tissue engineered skins].
The immunogenicity of tissue engineered skins is still vague, though it has been applied clinically for several years. To observe the evidence of immunologic rejection of tissue engineered skins transplanted to severe combined immunodeficiency (SCID) mice, which are implanted human splenic lymphocytes to construct human immune system. Tissue engineered skins and acellular dermic matrix were constructed in vitro. Twenty SCID mice, aging 4-6 weeks and weighing 16-17 g, were randomly divided into four groups equally (n=5). The tissue engineered skins, human foreskins from circumcision and acellular dermic matrix were transplanted to groups A, B, and C, respectively; group D was used as a control. After 2 weeks of transplanting, 3 x 10(7) human splenic lymphocytes were injected into every SCID mouse intraperitoneally. After 4 weeks, the morphology, histology, immunohistochemistry and human IgG immunofluorescence were used to observe immunologic rejection. Group A showed that transplanted tissue engineered skins had the bilayer structure of dermis and epidermis, which was similar to the normal human skin structure. Group B showed that the transplanted human foreskins still retained normal structure of human skin. Group C showed that acellular dermic matrix were located in situ and had no sign of degradation. After injecting human splenic lymphocytes into the SCID mice, no inflammatory cells infiltration were observed basically in groups A, C, and D; the inflammatory cells infiltration of group B were significantly higher than that of other 3 groups (P < 0.05). The results of anti human keratin 14 monoclonal antibody (mAb) staining and anti human type IV collagen mAb staining were positive in group A; no positive cells for CD3, CD4, and CD8 were observed in groups A, C, and D; and many positive cells for CD3, CD4, and CD8 were observed in group B. The results of IgG immunofluorescence staining was negative in group A, C, and D, and positive in the great vessel wells of group B. The immunogenicity of tissue engineered skins is very weak, and tissue engineered skins would not be rejected by host immune system after transplantation.


The prognostic impact of pretreatment anemia in patients with gastric cancer and nonhypoalbuminemia undergoing curative resection: a retrospective study.
The influence of pretreatment anemia on the prognosis of patients with advanced gastric cancer (GC) remains controversial. We retrospectively examined the impact of pretreatment anemia on the overall survival (OS) of patients with GC with nonhypoalbuminemia undergoing curative resection. The clinicopathological data of 2,916 patients with advanced GC who received a radical gastrectomy from 1994 to 2015 were analyzed. The patients were divided into two subgroups by hemoglobin level, <120 and ≥120 g/L. OS was analyzed using the Kaplan-Meier method, and a multivariate Cox proportional hazards model was used to identify the independent prognostic factor. A total of 1,099 patients were included in our study. The median follow-up duration was 43 (IQR, 24-66) months. The prevalence of anemia was 40.9%. Among these 1,099 patients, 505 (46.0%) had nonhypoalbuminemia. Kaplan-Meier survival analysis showed that patients with GC who were anemic had a poorer OS than patients who were not (5-year OS rate: 58.4% vs. 66.8%, P<0.0001). Multivariate analysis revealed that pretreatment anemia was an independent prognostic factor [hazard ratio (HR) =1.455, 95% CI, 1.013-2.09; P=0.043]. Our findings indicate that pretreatment anemia may serve as an independent prognostic factor for patients with advanced GC with nonhypoalbuminemia after radical gastrectomy, especially those with larger tumor size and pT3 disease.


Effects of flavonoids from Rosa laevigata Michx fruit against high-fat diet-induced non-alcoholic fatty liver disease in rats.
The effects and mechanisms of the total flavonoids (TFs) from Rosa laevigata Michx fruit on high-fat diet-induced non-alcoholic fatty liver disease (NAFLD) were investigated in this study. Gavage administration of the TFs significantly decreased the relative liver weight, serum AST and ALT activities, the levels of serum lipid, LDL, blood glucose and insulin, suppressed lipid accumulation in liver, and increased serum HDL level. Moreover, the natural product significantly enhanced SOD activity, increased GSH-Px and GSH contents and decreased the concentration of MDA and CYP2E1 expression as well as prevented mitochondrial membrane potential dysfunctions and ultrastructural alterations. Further mechanism investigation indicated that the TFs inhibited hepatic lipid accumulation by suppressing the expressions of some key molecules in fatty acid synthesis pathway and promoting fatty acid β-oxidation, while not by inhibiting cholesterol synthesis. On the base of these, the TFs should be developed as a new drug for treatment of NAFLD.


Spindle assembly defects leading to the formation of a monopolar mitotic apparatus.
Mitotic spindle formation in animal cells involves microtubule nucleation from two centrosomes that are positioned at opposite sides of the nucleus. Microtubules are captured by the kinetochores and stabilized. In addition, microtubules can be nucleated independently of the centrosome and stabilized by a gradient of Ran-GTP, surrounding the mitotic chromatin. Complex regulation ensures the formation of a bipolar apparatus, involving motor proteins and controlled polymerization and depolymerization of microtubule ends. The bipolar apparatus is, in turn, responsible for faithful chromosome segregation. During recent years, a variety of experiments has indicated that defects in specific motor proteins, centrosome proteins, kinases and other proteins can induce the assembly of aberrant spindles with a monopolar morphology or with poorly separated poles. Induction of monopolar spindles may be a useful strategy for cancer therapy, since ensuing aberrant mitotic exit will usually lead to cell death. In this review, we will discuss the various underlying molecular mechanisms that may be responsible for monopolar spindle formation.


Primary treatment of the prostate improves local palliation in men who ultimately develop castrate-resistant prostate cancer.
To determine whether local treatment of primary prostate cancer gives palliative benefit to men who later develop castrate-resistant prostate cancer (CRPC). Local treatments of primary prostate cancer are defined as radical retropubic prostatectomy (RRP) or external beam radiation therapy (EBRT). Patient records were reviewed in five different hospitals in Sydney, Australia, and 263 men with CRPC were identified. Eligible patients comprised men who had progressive disease during androgen deprivation therapy with castrate levels of testosterone. Clinical and pathological data were reviewed and evaluated using the chi-squared test and relative risk analysis to determine the relationship between previous local prostate treatment and complications secondary to local disease. The end-point was complications and morbidity attributed to cancer progression locally (i.e. from the prostate). Primary treatment of the prostate by either RRP or EBRT significantly reduces the incidence of local complications compared to no primary treatment (32.6% vs 54.6%; P = 0.001). RRP showed a significantly lower level of local complications compared to EBRT (20.0% vs 46.7%; P = 0.007). The most common local complications were bladder outlet obstruction (35.0%) and ureteric obstruction (15.2%). The present retrospective analysis supports the hypothesis that primary local prostatic treatment gives palliative benefit to men who later develop CRPC. RRP was associated with the lowest local complication rate experienced at the stage of metastatic disease.


Manual urine microscopy versus automated urine analyzer microscopy in patients with acute kidney injury.
To examine whether a significant difference exists between the reported ranges of granular and muddy brown casts in urine specimens using manual microscopy compared with an automated urine analyzer in a cohort of patients with acute kidney injury (AKI). Freshly voided urine specimens from 25 consecutive patients who were under evaluation by the Department of Nephrology for AKI were simultaneously examined using the iQ200 automated microscopy system and manual microscopy performed by a trained observer. We coded the results according to the number of pathological casts identified and performed a 3 × 2 Freeman-Halton extension of the Fisher exact probability test. Overall, the number of casts identified via manual microscopy differed significantly (P <.001) from the number identified via the automated microscopy system. This study provides evidence of the importance of performing a manual microscopic examination of urine sediment in patients with AKI. Further studies are needed to assess whether manual microscopy provides prognostic implications regarding renal recovery, hemodialysis dependency, and mortality.


Migration integration policies as social determinants of health for highly educated immigrants in the United States.
Highly educated immigrants are part of the growing population of immigrants who are impacted by the increasingly hostile migration policies in the U.S. This qualitative study used a phenomenological approach and inductive reasoning to explore the possible impacts of migration integration policies as social determinants of health among this group. Data was collected through 31 semi-structured interviewees with highly educated immigrants who had an intention and interest to stay in the U.S. at the time of the interview. Data were analyzed using reflexive thematic analysis and four main themes emerged: (1) a life overshadowed by silent worries, (2) living through uncertainties and forced decisions as the result of migration integration policies, (3) complexities and challenges of living on a work visa, and (4) shared recommendations by interviewees. Documented narratives as part of this study suggest high rates of stress and anxiety as well as negative mental and physical health outcomes among the participants. Results also suggest high levels of internalized vulnerabilities. Participants shared that migration policies can be enhanced in the U.S. to support highly educated immigrants' growth by creating a better and more transparent communication system, replacing random review processes for applications with systematic procedures, creating expedited pathways to citizenship based on merit, and granting access to work as a basic human right.


Peer-led HIV prevention among gay men in London: process evaluation.
A peer-led HIV prevention initiative, based on a diffusion of innovation model, was developed for gay men attending gyms in central London. Peer educators were recruited from people who used the gym regularly according to standard selection criteria. After initial training, peer educators agreed to talk to gay men at their gym about HIV prevention, focusing on sexual risk and steroid injecting behaviour. Outcome evaluation revealed that the peer education programme had no significant impact on the risk behaviours of gay men using the gyms. Process evaluation, based on interviews with peer educators, the health promotion team and gym managers threw light on this finding. While it was feasible to set up a peer education programme among gay men in central London gyms, attrition was an important factor. Only one in five potential peer educators initially identified remained with the project throughout, thus limiting the potential for diffusion. Those who did work as peer educators reported barriers to communication within the gyms further limiting the extent to which diffusion occurred. In fact, it appears that the critical mass required for diffusion was never established. This could explain why the intervention had no significant impact on gay men's risk behaviours. A person-time analysis demonstrated that the peer education programme required a substantial input from the health promotion team, equivalent to one team member devoting 2.5 days a week to recruit, train and support peer educators over 18 months. Peer education should not, therefore, be viewed as a low-cost approach to prevention. Many of the insights gained through this process evaluation can inform others planning peer education programmes in other settings.


Cluster analysis as selection and dereplication tool for the identification of new natural compounds from large sample sets.
Cluster analysis of gas-chromatographic (GC) data of ca. 500 bacterial isolates was used as an aid in detection and identification of new natural compounds. This approach reduces the number of GC/MS analysis (dereplication) and concomitantly improves the selection of samples with high probability to contain unknown natural products. Lipophilic bacterial extracts were derivatized and analyzed by GC under standardized conditions. A program was developed to convert chromatographic data into a two-dimensional matrix. Based on the results of hierarchical cluster analysis samples were selected for further investigation by GC/MS and NMR. This approach avoided unnecessary analysis of similar samples. By this method, the unusual oligoprenylsesquiterpenes 1 and 2 as well as new aromatic amides 7 and 8 were identified.


Toxicology of metals and metalloids: Promising issues for future studies in environmental health and toxicology.
The function and behavior of chemical elements in ecosystems and in human health probably comprise one of the most studied issues and a theme of great interest and fascination in science. Hot topics are emerging on an annual basis in this field. Bearing this in mind, some promising themes to explore in the field of metals and metalloids in the environment and in toxicology are highlighted and briefly discussed herein.


Deciduous tooth extraction & folkloric beliefs in the Samsun region.
This study was designed to investigate the methods of deciduous tooth extraction applied to children, and the effects of parents' educational status and place of residence on the way deciduous teeth are regarded in folklore in Samsun city and neighboring villages. Using questionnaires, this study tried to determine the type of superstitions held by parents living in the city and neighboring village. The questionnaire inquired about methods used to extract their deciduous teeth, what parents had done with them, and their preferred extraction methods. A significant relationship was established between the age at which the parent first visited the dentist and the method used to extract their child's deciduous teeth. Folk beliefs are not related to place, namely urban or rural living, but are concepts handed down through tradition; the educational status of parent is likewise irrelevant to the holding of folk beliefs among parents in this sample.


Clinical factors associated with early readmission among acutely decompensated heart failure patients.
Congestive heart failure (CHF) is a common cause of hospital readmission. A retrospective study was conducted at Harlem Hospital in New York City. Data were collected for 685 consecutive adult patients admitted for decompensated CHF from March, 2009 to December, 2012. Variables including patient demographics, comorbidities, laboratory studies, and medical therapy were compared between CHF patient admissions resulting in early CHF readmission and not resulting in early CHF readmission. Clinical factors found to be independently significant for early CHF readmission included chronic obstructive pulmonary disease (odds ratio (OR) = 6.4), HIV infection (OR = 3.4), African-American ethnicity (OR = 2.2), systolic heart failure (OR = 1.9), atrial fibrillation (OR = 2.3), renal disease with glomerular filtration rate < 30 ml/min (OR = 2.7), evidence of substance abuse (OR = 1.7), and absence of angiotensin-converting enzyme inhibitors or angiotensin receptor blocker therapy after discharge (OR = 1.8). The ORs were used to develop a scoring system regarding the risk for early readmission. Identifying patients with clinical factors associated with early CHF readmission after an index hospitalization for CHF using the proposed scoring system would allow for an early CHF readmission risk stratification protocol to target particularly high-risk patients.


Methodology for analysis of work practice with video observation.
Prior to developing and implementing health informatics systems it is essential to acquire information about the work practice. Interviews are often used but they don't always capture important details. In this project we used video cameras to observe the work practice of two medical secretaries at Department of Urology at Arhus University Hospital, Skejby. The project was carried out with a clear user influence in all phases of the project. The observation and the analysis focused on interruptions of the work processes, of which we found numerous that we categorized in three different types. The use of video and audio proved to be powerful tools for analysis of work practice, although it is very labor intensive method.


Microcystin-LR bioaccumulation and depuration kinetics in lettuce and arugula: Human health risk assessment.
Microcystin-LR (MC-LR) is one of the most toxic and common microcystins (MCs) variant found in aquatic ecosystems. Little is known about the possibility of recovering microcystins contaminated agricultural crops. The objectives of this study were to determine the bioaccumulation and depuration kinetics of MC-LR in leaf tissues of lettuce and arugula, and estimate the total daily intake (ToDI) of MC-LR via contaminated vegetables by humans. Arugula and lettuce were irrigated with contaminated water having 5 and 10μgL(-1) of MC-LR for 7days (bioaccumulation), and subsequently, with uncontaminated water for 7days (depuration). Quantification of MC-LR was performed by LC-MS/MS. The one-compartment biokinetic model was employed for MC-LR bioaccumulation and depuration data analysis. MC-LR was only accumulated in lettuce. After 7days of irrigation with uncontaminated water, over 25% of accumulated MC-LR was still retained in leaf tissues of plants treated with 10μgL(-1) MC-LR. Total daily toxin intake by adult consumers (60kg-bw) exceeded the 0.04μgMC-LRkg(-1) limit recommended by WHO. Bioaccumulation was found to be linearly proportional to the exposure concentration of the toxin, increasing over time; and estimated to become saturated after 30days of uninterrupted exposure. On the other hand, MC-LR depuration was less efficient at higher exposure concentrations. This is because biokinetic half-life calculations gave 2.9 and 3.7days for 5 and 10μgL(-1) MC-LR treatments, which means 29-37days are required to eliminate the toxin. For the first time, our results demonstrated the possibility of MC-LR decontamination of lettuce plants.


Short-term enhancement and suppression of dolphin auditory evoked responses following echolocation click emission.
Biosonar gain control mechanisms in a bottlenose dolphin were investigated by measuring the auditory steady-state response (ASSR) to an external tone while the animal echolocated. The dolphin performed an echo change-detection task that utilized electronically synthesized echoes with echo delays corresponding to 25- and 50-m target range. During the task, amplitude modulated tones with carrier frequencies from 25 to 125 kHz were continuously presented and the instantaneous electroencephalogram stored for later analysis. ASSRs were extracted from the electroencephalogram by synchronously averaging time epochs temporally aligned with the onset of the external tone modulation cycle nearest to each of the dolphin's echolocation clicks. Results showed an overall suppression of the ASSR amplitude for tones with frequencies near the click center frequencies. A larger, temporary suppression of the ASSR amplitude was also measured at frequencies above 40-50 kHz, while a temporary enhancement was observed at lower frequencies. Temporal patterns for ASSR enhancement or suppression were frequency-, level-, and range-dependent, with recovery to pre-click values occurring within the two-way travel time. Suppressive effects fit the patterns expected from forward masking by the emitted biosonar pulse, while the specific mechanisms responsible for the frequency-dependent enhancement are unknown.


Expression profile and biological function of miR-455-5p in colorectal carcinoma.
Underexpression of microRNA-455-5p (miR-455-5p) in medullary thyroid carcinoma, melanoma, gastric cancer and additional cancer types has been reported, which may be associated with carcinoma development. The present study aimed to evaluate the expression profile and biological role of miR-455-5p in colorectal carcinoma. Carcinoma tissues and adjacent tissue specimens from 40 patients with colorectal cancer were randomly collected. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis was conducted to detect the expression levels of miR-455-5p in colorectal carcinoma and adjacent normal tissues. The biological effects of miR-455-5p on selected colorectal cancer cells were assessed using bromodeoxyuridine assays, wound healing migration assays and flow cytometry. Bioinformatics analysis was implemented to predict the potential target genes of miR-455-5p in colorectal cancer. The expression levels of target genes were further validated by RT-qPCR and western blot analysis of the mRNA and protein levels. The results of the experiments demonstrated that miR-455-5p expression was downregulated in colorectal cancer tissues compared with adjacent normal tissues. In colorectal cancer cells (SW-480, HT-29 and HCT-116), miR-455-5p was observed to inhibit cell proliferation and migration while promoting cell apoptosis. Bioinformatics analysis predicted that the oncogene phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) was one of the top ranked target genes of miR-455-5p in colorectal cancer cells. This association was validated by RT-qPCR and western blotting. In vivo studies revealed that the expression level of miR-455-5p was significantly downregulated in human colorectal cancer. Further in vitro studies suggested that miR-455-5p may prevent the development of colorectal cancer by downregulating the oncogene PIK3R1. It was concluded that miR-455-5p may target and downregulate PIK3R1 in colorectal cancer.


Affinity transfer to the archaeal extremophilic Sac7d protein by insertion of a CDR.
Artificially transforming a scaffold protein into binders often consists of introducing diversity into its natural binding region by directed mutagenesis. We have previously developed the archaeal extremophilic Sac7d protein as a scaffold to derive affinity reagents (Affitins) by randomization of only a flat surface, or a flat surface and two short loops with natural lengths. Short loops are believed to contribute to stability of extremophilic proteins, and loop extension has been reported detrimental for the thermal and chemical stabilities of mesophilic proteins. In this work, we wanted to evaluate the possibility of designing target-binding proteins based on Sac7d by using a complementary determining region (CDR). To this aim, we inserted into three different loops a 10 residues CDR from the cAb-Lys3 anti-lysozyme camel antibody. The chimeras obtained were as stable as wild-type (WT) Sac7d at extreme pH and their structural integrity was supported. Chimeras were thermally stable, but with T(m)s from 60.9 to 66.3°C (cf. 91°C for Sac7d) which shows that loop extension is detrimental for thermal stability of Sac7d. The loop 3 enabled anti-lysozyme activity. These results pave the way for the use of CDR(s) from antibodies and/or extended randomized loop(s) to increase the potential of binding of Affitins.


A randomized controlled phase IIb trial of antigen-antibody immunogenic complex therapeutic vaccine in chronic hepatitis B patients.
The safety of the immune complexes composed of yeast-derived hepatitis B surface antigen (HBsAg) and antibodies (abbreviated as YIC) among healthy adults and chronic hepatitis B patients has been proved in phase I and phase IIa trial. A larger number of patients for study of dosage and efficacy are therefore needed. Two hundred forty two HBeAg-positive chronic hepatitis B patients were immunized with six injections of either 30 microg YIC, 60 microg of YIC or alum adjuvant as placebo at four-week intervals under code. HBV markers and HBV DNA were monitored during immunization and 24 weeks after the completion of immunization. The primary endpoint was defined as loss of HBeAg, or presence of anti-HBe antibody or suppression of HBV DNA, while the secondary endpoint was both HBeAg seroconversion and suppression of HBV DNA. Statistical significance was not reached in primary endpoints four weeks after the end of treatment among three groups, however, at the end of follow-up, HBeAg sero-conversion rate was 21.8% (17/78) and 9% (7/78) in the 60 microg YIC and placebo groups respectively (p = 0.03), with 95% confidence intervals at 1.5% to 24.1%. Using generalized estimating equations (GEEs) model, a significant difference of group effects was found between 60 microg YIC and the placebo groups in terms of the primary endpoint. Eleven serious adverse events occurred, which were 5.1%, 3.6%, and 5.0% in the placebo, 30 microg YIC and 60 microg YIC groups respectively (p>0.05). Though statistical differences in the preset primary and secondary endpoints among the three groups were not reached, a late and promising HBeAg seroconversion effect was shown in the 60 microg YIC immunized regimen. By increasing the number of patients and injections, the therapeutic efficacy of YIC in chronic hepatitis B patients will be further evaluated. ChiCTR.org ChiCTR-TRC-00000022.


Age differences in autobiographical memory across the adult lifespan: older adults report stronger phenomenology.
As an individual's life story evolves across adulthood, the subjective experience (phenomenology) of autobiographical memory likely changes. In addition to age at retrieval, both the recency of the memory and the age when a memory is formed may be particularly important to its phenomenology. The present work examines the effect of three temporal factors on phenomenology ratings: (a) age of the participant, (b) age at the event reported in the memory, and (c) memory age (recency). A large sample of Americans (N = 1120), stratified by chronological age, recalled and rated two meaningful memories, a Turning Point and an Early Childhood Memory. Ratings of phenomenology (e.g., vividness of turning points) were higher among older adults compared to younger adults. Memories of events from the reminiscence bump were more positive in valence than events from other time periods but did not differ on other phenomenological dimensions; recent memories had stronger phenomenology than remote memories. In contrast to phenomenology, narrative content was generally unrelated to participant age, age at the event, or memory age. Overall, the findings indicate age-related differences in how meaningful memories are re-experienced.


Development and validation of a military fear avoidance questionnaire.
Chronic pain due to musculoskeletal injury is one of the leading causes of disability and reduced combat readiness in the U.S. Army. Unidimensional pain management systems are not effective in addressing the complex phenomenon of pain-related disability. Growing evidence has supported use of the Fear Avoidance Model (FAM) as a suitable model to address pain-related disability and chronicity from a multidimensional pain neuroscience approach. While several fear avoidance measurement tools exist, one that addresses the complexity of the Army environment encouraged the authors to develop and test the reliability and validity of a military specific questionnaire. This study developed and validated an Army specific fear avoidance screening, the Return to Duty Readiness Questionnaire (RDRQ), which subsequently demonstrated good psychometric properties. Reliability coefficients demonstrate high internal consistency values both during pilot study (α = 0.96) and validation study (α = 0.94, ωt = 0.94). A Correlation Coefficient of 0.74 when compared with the Fear Avoidance Components Scale (FACS) suggests good concurrent validity. Future study should include replication in a new army population, investigation of responsiveness, test-retest reliability, structural validity and establishing severity scores with minimal clinically important differences to enhance utility.


Evolutionary diversification of insect innexins.
Phylogenetic analysis of insect innexins supported the hypothesis that six major clades of insect innexins arose by gene duplication prior to the origin of the endopterygote insects. Within one of the six clades (the Zpg Clade), two independent gene duplication events were inferred to have occurred in the lineage of Drosophila, after the most recent common ancestor of the dipteran families Culicidae and Drosophilidae. The relationships among this clades were poorly resolved, except for a sister relationship between ShakB and Ogre. Gene expression data from FlyAtlas supported the hypothesis that the latter gene duplication events gave rise to functional differentiation, with Zpg showing a high level of expression in ovary, and Inx5 and Inx6 showing a high level of expression in testis. Because unduplicated members of this clade in Bombyx mori and Anopheles gambiae showed high levels of expression in both ovary and tests, the expression patterns of the Drosophila members of this clade provide evidence of subdivision of an ancestral gene function after gene duplication.


The social and community opportunities profile social inclusion measure: Structural equivalence and differential item functioning in community mental health residents in Hong Kong and the United Kingdom.
China's future major health problem will be the management of chronic diseases - of which mental health is a major one. An instrument is needed to measure mental health inclusion outcomes for mental health services in Hong Kong and mainland China as they strive to promote a more inclusive society for their citizens and particular disadvantaged groups. To report on the analysis of structural equivalence and item differentiation in two mentally unhealthy and one healthy sample in the United Kingdom and Hong Kong. The mental health sample in Hong Kong was made up of non-governmental organisation (NGO) referrals meeting the selection/exclusion criteria (being well enough to be interviewed, having a formal psychiatric diagnosis and living in the community). A similar sample in the United Kingdom meeting the same selection criteria was obtained from a community mental health organisation, equivalent to the NGOs in Hong Kong. Exploratory factor analysis and logistic regression were conducted. The single-variable, self-rated 'overall social inclusion' differs significantly between all of the samples, in the way we would expect from previous research, with the healthy population feeling more included than the serious mental illness (SMI) groups. In the exploratory factor analysis, the first two factors explain between a third and half of the variance, and the single variable which enters into all the analyses in the first factor is having friends to visit the home. All the regression models were significant; however, in Hong Kong sample, only one-fifth of the total variance is explained. The structural findings imply that the social and community opportunities profile-Chinese version (SCOPE-C) gives similar results when applied to another culture. As only one-fifth of the variance of 'overall inclusion' was explained in the Hong Kong sample, it may be that the instrument needs to be refined using different or additional items within the structural domains of inclusion.


Association between the transcriptional levels of Htr-1a and tryptophan hydroxylase-1 in the hippocampus and the antifatigue effects of leucine on rats with postoperative fatigue.
Leucine (Leu), a branched-chain amino acid (BCAA), is widely used in clinical practice following severe burns, gastrointestinal surgery, trauma and sepsis. In the present study, the antifatigue effects of BCAAs on a postoperative fatigue (POF) rat model, induced by 70% intestinal resection, were investigated. Leu (16.5 g/l) was administered intraperitoneally at a dose of 18 ml/kg/day. The fatigue level and antifatigue effects of Leu were evaluated by open-field testing on day 1, 3, 5 and 7 after surgery. In addition, mRNA specimens were extracted and measured using a quantitative polymerase chain reaction method. The open-field test results indicated that Leu exhibited a significant antifatigue effect. The total distance travelled and the number of times the rats passed from the outermost grids of an open-top case were greatly improved in the Leu treatment group when compared with the POF model group. With the exception of the normal group, the mRNA expression levels of Htr-1a exhibited a similar trend in all other groups, reaching a climax on day 3 and 5, while being restored to a normal level on day 7. With regard to the Leu intervention group, the mRNA expression level of Htr-1a decreased significantly on day 3 and 5 following surgery. The mRNA expression levels of tryptophan hydroxylase-1 were unchanged in this short time period; however, the levels were increased gradually in the Leu treatment group. Therefore, Leu exhibited an apparent antifatigue effect on various 5-hydroxytryptamine-associated genes.


Synthesis and characterization of a spin crossover iron(II)-iron(III) mixed valence supramolecular pseudo-dimer exhibiting chiral recognition, hydrogen bonding, and pi-pi interactions.
Reaction of iron(II) and the 3 : 1 Schiff base condensate of 5-methylpyrazole-3-carboxaldehyde and tris(2-aminoethyl)amine in air gives a pseudo-dimer complex with a triple helix structure made of Delta-Delta and Lambda-Lambda pairings of spin crossover iron(II) and low spin iron(III) cations that are held together by three pi-pi and hydrogen bonding interactions.


Structure of transmembrane subunits gp47 of the foamy virus envelope glycoproteins.
The successful foamy viruses (FVs) infection includes at least two essential events, attachment to the cell surface and fusion of the viral envelope with the cell membrane. For the FVs, membrane fusion between virus and cell is mediated by envelope glycoprotein (Env) transmembrane (TM) subunit gp47. Compared with other retroviruses, FV TM subunit shares a similar but not identical structural characteristic. This paper focuses on in sillico analyses of all 15 available FV TM subunits gp47 based on their amino acid sequences. The hydrophobicity analysis revealed that the 15 FVs gp47 had two prominent hydrophobic regions, the N-terminal fusion peptide (FP) and the C-terminal region, which included a membrane-spanning domain (MSD) and a membrane proximal ectodomain region (MPER). In most FVs gp47, two heptad repeats, the coiled coils characterized by repetition of 7-amino acid-motif, were found to be correspondently located downstream of FP (named "N-HR") and the upstream of MPER (named "C-HR"). Furthermore, the solvent accessibility and secondary structure were predicted for all FVs gp47. These observations suggested that FVs gp47 possessed several fusion domains, which were necessary in the process of lipid membrane fusion between FVs and the target cells.


Inadvertent use of cornea with previous LASIK in deep lamellar keratoplasty.
To report transplantation of a post-laser in situ keratomileusis (LASIK) donor cornea in a deep anterior lamellar keratoplasty (DALK). An 18-year-old male patient with bilateral keratoconus underwent DALK in his right eye. One week postoperatively, the uncorrected visual acuity was 6/24 and the keratometry readings were 36.4/48.6 D in the operated eye. On slit-lamp examination, two interfaces were observed in the corneal stroma. An anterior segment optical coherence tomography (ASOCT; Visante) scan was performed on the operated eye. The ASOCT showed two distinct interfaces, one in the deep corneal stroma close to the Descemet membrane and another interface in the anterior corneal stroma, 225 µm below the surface of the cornea representing the LASIK flap. The central corneal thickness was 498 µm and the residual stromal thickness was between 45 and 52 µm. The records of the 57-year-old male donor who had died of a road traffic accident did not reveal any history of refractive surgery in the past. The patient was informed about the presence of a LASIK flap on his cornea. Because the patient is asymptomatic, a decision was taken to observe instead of exchanging the graft. Our case report highlights transplantation of a donor cornea with previous refractive surgery. With refractive surgery being performed commonly, a careful and specific history should be obtained from the relatives of the deceased. We recommend the incorporation of standard imaging protocols in eye banks for detection of previous refractive surgery in donor corneas.


Jaw-opening oromandibular dystonia secondary to Wilson's disease treated with botulinum toxin type A.
We have reported a case series of five patients with jaw-opening oromandibular dystonia secondary to Wilson's disease (WD), in which the patients were treated with botulinum toxin type A (BTX-A). In all cases, dystonia score was partially reduced three weeks after injections. The most common side effect was transient mild dysphagia. This preliminary study showed that jaw-opening oromandibular dystonia in WD may be partially responsive to the use of BTX-A.


'Like me': a foundation for social cognition.
Infants represent the acts of others and their own acts in commensurate terms. They can recognize cross-modal equivalences between acts they see others perform and their own felt bodily movements. This recognition of self-other equivalences in action gives rise to interpreting others as having similar psychological states such as perceptions and emotions. The 'like me' nature of others is the starting point for social cognition, not its culmination.


Mogamulizumab efficacy is underscored by its associated rash that mimics cutaneous T-cell lymphoma: a retrospective single-centre case series.
Mogamulizumab is a humanized antibody against chemokine receptor type 4. It was recently approved by the US Food and Drug Administration for relapsed or refractory mycosis fungoides (MF) and Sézary syndrome (SS). The most commonly reported adverse event in the phase III licensing trial was drug eruption (28%), now termed mogamulizumab-associated rash (MAR). Clinical recommendations about MAR and its treatment differ between the current package insert and postapproval insights reported from two single-centre studies that focused on its characterization, but less so on outcomes and clinicopathological differentiation from cutaneous T-cell lymphoma (CTCL). To describe our experience in the diagnosis of MAR and treatment of patients with CTCL with mogamulizumab. This is a single-centre retrospective case series study. We found a higher incidence of MAR in patients with CTCL (17 of 24, 68%) than previously reported. MAR development is associated with complete (11 of 17) or partial (four of 17) responses, with an overall response rate of 88%, compared with 29% (two of seven) in patients without MAR. Diagnosis of MAR may be obscured by its ability to mimic key CTCL features both clinically and histologically, but an absence of T-cell-receptor clonality and relatively decreased CD4 : CD8 ratio compared with baseline lesions strongly favour MAR over recurrent disease. MAR has the potential to create a significant management problem for patients on mogamulizumab. Misidentification of MAR as recurrent CTCL may detrimentally result in the premature discontinuation of mogamulizumab in patients whose disease is historically hard to treat. Thorough clinicopathological investigation of new lesions during treatment with mogamulizumab is required to inform ideal treatment decisions and achieve better outcomes.


Chlorophyll catabolism precedes changes in chloroplast structure and proteome during leaf senescence.
The earliest visual changes of leaf senescence occur in the chloroplast as chlorophyll is degraded and photosynthesis declines. Yet, a comprehensive understanding of the sequence of catabolic events occurring in chloroplasts during natural leaf senescence is still missing. Here, we combined confocal and electron microscopy together with proteomics and biochemistry to follow structural and molecular changes during Arabidopsis leaf senescence. We observed that initiation of chlorophyll catabolism precedes other breakdown processes. Chloroplast size, stacking of thylakoids, and efficiency of PSII remain stable until late stages of senescence, whereas the number and size of plastoglobules increase. Unlike catabolic enzymes, whose level increase, the level of most proteins decreases during senescence, and chloroplast proteins are overrepresented among these. However, the rate of their disappearance is variable, mostly uncoordinated and independent of their inherent stability during earlier developmental stages. Unexpectedly, degradation of chlorophyll-binding proteins lags behind chlorophyll catabolism. Autophagy and vacuole proteins are retained at relatively high levels, highlighting the role of extra-plastidic degradation processes especially in late stages of senescence. The observation that chlorophyll catabolism precedes all other catabolic events may suggest that this process enables or signals further catabolic processes in chloroplasts.


Retinopathy induced by drugs and herbal medicines.
Retina is the part of the eye suffering most damage from drugs. It is made up of a thin nervous membrane that covers the eye-ball internally, within the thickness of which three types of cells are ordered. In this paper we describe the drugs that are responsible for retinal side effects. Most commonly recognized drugs-induced retinopathy have a particular affinity for the retinal pigmented epithelium: antimalarials (quinine, hydroxychloroquine, mefloquine), phenothiazines, indomethacin, ethambutol, and desferrioxamine. Attention is especially focused on drugs more recently suspected of adverse reactions in the retina: vigabatrin, gabapentin, sildenafil, tamoxifen, isotretinoin, interferon, and omeprazole. Moreover, we referred some reports of retinopathy by herbal medicines and nutritional supplements (canthaxanthine, Gingko biloba L. and Glycyrrhiza glabra L.) This review is based on data published in scientific journals indexed by the PubMed and Medline databases. The last search of the literature was conducted in April 2008.


[Interaction of muscle glycogen phosphorylase B with F-actin].
The binding of rabbit muscle glycogen phosphorylase b to F-actin has been studied by sedimentation in analytical centrifuge in 10 mM Tris-acetate buffer pH 6.8 at 20 degrees C. The adsorption capacity of F-actin is equal to (7.8 +/- 0.9) X 10(-7) mole of glycogen phosphorylase b per 1 g of F-actin; the microscopic dissociation constant for the glycogen phosphorylase-F-actin complex is (5.4 +/- 0.5) X 10(-7) M. It was found that the allosteric activator, AMP, facilitates the adsorption of glycogen phosphorylase b on F-actin, whereas the substrate, Pi, and the inhibitor, ATP, cause an opposite effect.


Identifying Biomarkers of Spinal Muscular Atrophy for Further Development.
Spinal muscular atrophy (SMA) is caused by bi-allelic, recessive mutations of the survival motor neuron 1 (SMN1) gene and reduced expression levels of the survival motor neuron (SMN) protein. Degeneration of alpha motor neurons in the spinal cord causes progressive skeletal muscle weakness. The wide range of disease severities, variable rates of decline, and heterogenous clinical responses to approved disease-modifying treatment remain poorly understood and limit the ability to optimize treatment for patients. Validation of a reliable biomarker(s) with the potential to support early diagnosis, inform disease prognosis and therapeutic suitability, and/or confirm response to treatment(s) represents a significant unmet need in SMA. The SMA Multidisciplinary Biomarkers Working Group, comprising 11 experts in a variety of relevant fields, sought to determine the most promising candidate biomarker currently available, determine key knowledge gaps, and recommend next steps toward validating that biomarker for SMA. The Working Group engaged in a modified Delphi process to answer questions about candidate SMA biomarkers. Members participated in six rounds of reiterative surveys that were designed to build upon previous discussions. The Working Group reached a consensus that neurofilament (NF) is the candidate biomarker best poised for further development. Several important knowledge gaps were identified, and the next steps toward filling these gaps were proposed. NF is a promising SMA biomarker with the potential for prognostic, predictive, and pharmacodynamic capabilities. The Working Group has identified needed information to continue efforts toward the validation of NF as a biomarker for SMA.


Suitability of saliva cortisol as a biomarker for hypothalamic-pituitary-adrenal axis activation assessment, effects of feeding actions, and immunostimulatory challenges in dairy cows.
One of the most prominent physiological responses to stressors is the activation of the hypothalamic-pituitary-adrenocortical (HPA) axis, currently assessed by measuring cortisol concentration in blood plasma. To reduce animal discomfort during sampling, which negatively affects stress biomarkers, current research focuses on noninvasive sampling of media other than blood, for example, saliva. The aim of this study was to assess the suitability of saliva cortisol as a biomarker under different physiological and immunological states in dairy cows. Our objectives were to 1) evaluate the relationship between HPA axis activation and saliva cortisol concentration, 2) investigate effects of some feeding action (as influenced by feed and water consumption) on saliva cortisol concentration, and 3) evaluate the time lag between plasma and saliva cortisol during induced inflammatory conditions by intramammary lipopolysaccharide (LPS) and lipoteichoic acid (LTA) injection. During a specific activation of the HPA axis, a positive correlation ( = 0.75, < 0.0001) between saliva and blood cortisol concentrations was observed with increased ( < 0.01) plasma cortisol concentrations following ACTH administration. Saliva and blood samples were taken before, during, and after drinking, feeding, and ruminating. Only a low correlation between saliva and plasma cortisol concentrations ( = 0.03, = 0.83) but no significant effects of the different feeding actions on saliva cortisol were observed. When compared with basal concentrations, cortisol concentrations in plasma significantly increased during inflammatory responses following LPS and LTA injection. Compared with plasma cortisol, changes in saliva cortisol concentrations occurred at a much lower level within a narrow range and did not necessarily follow changes in plasma. In conclusion, the positive correlation between saliva and plasma cortisol concentration in response to ACTH and inflammation suggests the suitability of saliva cortisol measurement for the HPA axis activation assessment. However, changes in saliva cortisol concentration occur within a very narrow range. Furthermore, not only must variation among individual animals be considered but also variation within the same animal. Only with additional knowledge of the concomitant physiological status of the cow it is possible to correctly evaluate saliva and blood cortisol samples.


Circadian variations in blood pressure and their implications for the administration of antihypertensive drugs: is dosing in the evening better than in the morning?
: Blood pressure (BP) follows a circadian rhythm with a physiological decrease during the night. Studies have demonstrated that nocturnal BP as well as its dipping pattern during night-time have a significant prognostic importance for mortality and the occurrence of cardiovascular events. Therefore, hypertension management guidelines recommend to ascertain that patients treated for hypertension have well controlled BP values around the clock. To improve hypertension control during the night and eventually further reduce cardiovascular events, it has been proposed by some to prescribe at least one antihypertensive medication at bedtime. In this review, we have examined the data which could support the benefits of prescribing BP-lowering drugs at bedtime. Our conclusion is that there is no convincing evidence that the administration of BP-lowering drugs in the evening provides any significant advantage in terms of quality of BP control, prevention of target organ damage or reduction of cardiovascular events. Before changing practice for unproven benefits, it would be wise to wait for the results of the ongoing trials that are addressing this issue.


Validation of PRIMO Monte Carlo Model of Clinac®iX 6MV Photon Beam.
This study aims to model 6MV photon of Clinac®iX linear accelerator using PRIMO Monte Carlo (MC) code and to assess PRIMO as an independent MC-based dose verification and quality assurance tool. The modeling of Clinac®iX linear accelerator has been carried out by using PRIMO simulation software (Version 0.3.1.1681). The simulated beam parameters were compared against the measured beam data of the Clinac®iX machine. The PRIMO simulation model of Clinac®iX was also validated against Eclipse® Acuros XB dose calculations in the case of both homogenous and inhomogeneous mediums. The gamma analysis method with the acceptance criteria of 2%, 2 mm was used for the comparison of dose distributions. Gamma analysis shows a minimum pass percentage of 99% for depth dose curves and 95.4% for beam profiles. The beam quality index and output factors and absolute point dose show good agreement with measurements. The validation of PRIMO dose calculations, in both homogeneous and inhomogeneous medium, against Acuros® XB shows a minimum gamma analysis pass rate of 99%. This study shows that the research software PRIMO can be used as a treatment planning system-independent quality assurance and dose verification tool in daily clinical practice. Further validation will be performed with different energies, complex multileaf collimators fields, and with dynamic treatment fields.


Nonintegral form of the reciprocal relation associated with violation of the fluctuation response relation.
We extend Onsager's reciprocal relation to systems in a nonequilibrium steady state. While Onsager's reciprocal relation concerns the kinetic (Onsager) coefficient, the extended reciprocal relation concerns violation of the fluctuation response relation (FRR) for mechanical and thermal perturbations. This extended relation holds at each frequency when the extent of the FRR violation is expressed in a frequency domain. This nonintegral form distinguishes the extended relation from previous relations expressed by integration over a frequency. To obtain this relation, we consider one-particle one-dimensional systems described by an overdamped Langevin equation with a force driving the system away from equilibrium. We assume a special property of the potential in the system. From this Langevin equation, we obtain the Fokker-Planck (FP) equation describing the time evolution of the distribution function of the particle. Using the FP equation, we calculate the responses of the particle velocity and heat current by applying time-dependent perturbations of the driving force and temperature. We express the extent of the FRR violation in terms of these responses with time correlation functions and expand them in powers of the FP operator. This reciprocal relation is valid far from equilibrium. One can also confirm this reciprocal relation through experiments with systems such as colloidal suspensions because the FRR violation can be experimentally observed.


[Experimental schistosomiasis III. Observations on the infestation of Biomphalaria glabrata by a miracidium of Schistosoma mansoni].
380 B. glabrata infected with 1 miracidium of S. mansoni produced 87 positive snails (22,9%), 38 of which sending out male cercariae and 49 female cercariae. The snails belonged to 3 experimental series kept at 27 degrees and 24 degrees C for 15 weeks under continuous lighting. There was no difference between the proportions of both sexes. The survival of the positive snails was favoured by the male sex. The shedding of female cercariae was greater than shedding of male. During those 15 weeks, the cercarial shedding of both sexes showed large and recurring changes. A certain correlation seems to exist between the sex of cercariae, the abundance and the frequency of cercarial shedding, and the longevity of the parasitized snails. All those factors could take a part in the epidemiology of the schistosomiasis.


Interpretations on the Interaction between Protein Tyrosine Phosphatase and E7 Oncoproteins of High and Low-Risk HPV: A Computational Perception.
The most prevalent and common sexually transmitted infection is caused by human papillomavirus (HPV) among sexually active women. Numerous genotypes of HPV are available, among which the major oncoproteins E6 and E7 lead to the progression of cervical cancer. The E7 oncoprotein interacts with cytoplasmic tumor suppressor protein PTPN14, which is the key regulator of cellular growth control pathways effecting the reduction of steady-state level. Disrupting the interaction between the tumor suppressor and the oncoprotein is vital to cease the development of cancer. Hence, the mechanism of interaction between E7 and tumor suppressor is explored through protein-protein and protein-ligand binding along with the conformational stability studies. The obtained results state that the LXCXE domain of HPV E7 of high and low risks binds with the tumor suppressor protein. Also, the small molecules bind in the interface of E7-PTPN14 that disrupts the interaction between the tumor suppressor and oncoprotein. These results were further supported by the dynamics simulation stating the stability over the bounded complex and the energy maintained during postdocking as well as postdynamics calculations. These observations possess an avenue in the drug discovery that leads to further validation and also proposes a potent drug candidate to treat cervical cancer caused by HPV.


The soil resistome: a critical review on antibiotic resistance origins, ecology and dissemination potential in telluric bacteria.
Soil is a large reservoir of microbial diversity and the majority of antimicrobial compounds used today in human and veterinary health care have been isolated from soil microorganisms. The Darwinian hypothesis of an 'arms-shields race' between antibiotic producers and resistant strains is often cited to explain antibiotic resistance gene determinants (ARGD) origins and diversity. ARGD abundance and antibiotic molecule exposure are, however, not systematically linked, and many other factors can contribute to resistance gene emergence, selection and dissemination in the environment. Soil is a heterogeneous habitat and represents a broad spectrum of different ecological niches. Soil harbours a large genetic diversity at small spatial scale, favouring exchange of genetic materials by means of horizontal gene transfer (HGT) that will contribute to ARGD dissemination between bacteria and eventually acquisition by pathogen genomes, therefore threatening antibiotic therapies. Our current knowledge on the extent of the soil resistome abundance and diversity has been greatly enhanced since the metagenomic revolution and help of high-throughput sequencing technologies. Different ecological hypotheses explaining their high prevalence in soil and questioning their transfer rate to pathogens, in respect to these recent experimental results, will be discussed in the present review.


Amblyopia: a neuro-ophthalmic view.
Amblyopia designates monocular or binocular visual loss associated with form deprivation caused by obstruction or deformation of a light stimulus, strabismus, or uncorrected refractive error. Elegant neuroscientific studies have identified a critical period early in life in which the visual system is vulnerable to amblyopia and the site of pathology as the primary visual cortex. However, recent observations have challenged these concepts. A broader understanding of the pathophysiology of amblyopia will be critical to refining therapy for this condition.


Advances and Applications of Metal-Organic Framework Nanomaterials as Oral Delivery Carriers: A Review.
Oral administration is a commonly used, safe, and patient-compliant method of drug delivery. However, due to the multiple absorption barriers in the gastrointestinal tract (GIT), the oral bioavailability of many drugs is low, resulting in a limited range of applications for oral drug delivery. Nanodrug delivery systems have unique advantages in overcoming the multiple barriers to oral absorption and improving the oral bioavailability of encapsulated drugs. Metal-organic frameworks (MOFs) are composed of metal ions and organic linkers assembled by coordination chemistry. Unlike other nanomaterials, nanoscale metal-organic frameworks (nano-MOFs, NMOFs) are increasingly popular for drug delivery systems (DDSs) due to their tunable pore size and easily modified surfaces. This paper summarizes the literature on MOFs in pharmaceutics included in SCI for the past ten years. Then, the GIT structure and oral drug delivery systems are reviewed, and the advantages, challenges, and solution strategies possessed by oral drug delivery systems are discussed. Importantly, two major classes of MOFs suitable for oral drug delivery systems are summarized, and various representative MOFs as oral drug carriers are evaluated in the context of oral drug delivery systems. Finally, the challenges faced by DDSs in the development of MOFs, such as biostability, biosafety, and toxicity, are examined.


Partial EMT in head and neck cancer biology: a spectrum instead of a switch.
Our understanding of epithelial-to-mesenchymal transition (EMT) has slowly evolved from a simple two state, binary model to a multi-step, dynamic continuum of epithelial-to-mesenchymal plasticity, with metastable intermediate transition states that may drive cancer metastasis. Head and neck cancer is no exception, and in this review, we use head and neck as a case study for how partial-EMT (p-EMT) cell states may play an important role in cancer progression. In particular, we summarize recent in vitro and in vivo studies that uncover these intermediate transition states, which exhibit both epithelial and mesenchymal properties and appear to have distinct advantages in migration, survival in the bloodstream, and seeding and propagation within secondary metastatic sites. We then summarize the common and distinct regulators of p-EMT as well as methodologies for identifying this unique cellular subpopulation, with a specific emphasis on the role of cutting-edge technologies, such as single cell approaches. Finally, we propose strategies to target p-EMT cells, highlighting potential opportunities for therapeutic intervention to specifically target the process of metastasis. Thus, although significant challenges remain, including numerous gaps in current knowledge, a deeper understanding of EMT plasticity and a genuine identification of EMT as spectrum rather than a switch will be critical for improving patient diagnosis and treatment across oncology.


Recurrent Primary Hyperparathyroidism in Hyperparathyroid Jaw Tumor Syndrome: A Case Report.
Hyperparathyroidism occasionally develops secondary to genetic disorders, though CDC73-related diseases such as hyperparathyroid jaw tumor syndrome (HPT-JT) are among the least common. Typically, patients are identified in the third decade of life by characteristically early development of hyperparathyroidism, atypical pathology on histologic evaluation of parathyroid adenomas, or presence of concomitant tumors in the jaw, renal, or uterine anatomy. We report a case of a 60-year-old male who was identified as having hyperparathyroidism jaw tumor syndrome after presenting with recurrent hyperparathyroidism 10 years after parathyroid adenoma resection, which is likely the oldest age to date for diagnosis. We also review his clinical presentation, pathophysiology, genetic significance, and surveillance criteria relating to HPT-JT.


Papillon-Lefevre syndrome: Report of two cases in the same family.
Papillon-Lefevre syndrome is a very rare syndrome of autosomal recessive inheritance characterized by palmar-plantar hyperkeratosis and early onset of a severe destructive periodontitis, leading to premature loss of both primary and permanent dentitions. Various etiopathogenic factors are associated with the syndrome but a recent report has suggested that the condition is linked to mutations of the cathepsin C gene. Two cases of Papillon-Lefevre syndrome in the same family, having all of the characteristic features, are presented. An 11-year-old girl and a 9-year-old boy presented with the complaints of loose teeth. Both expressed hyperkeratosis of palms, soles, and knees. Severe generalized periodontal destruction, with mobility of teeth, was evident on intraoral examination; orthopantomograph examination showed severe generalized loss of alveolar bone in both the patients.


Characterization of Bromethalin and its Degradation Products in Veterinary Toxicology Samples by GC-MS-MS.
Bromethalin is a neurotoxicant with unusual instability and chromatographic behavior that make it difficult to analyze by gas chromatography (GC) in forensic examination of non-target animal deaths. Physicochemical breakdown of bromethalin produced multiple unique products with discernible mass spectra. This paper describes an investigation of the GC electron impact-mass spectrometric properties of bromethalin and its capacity to generate up to twenty heat- or light-induced breakdown products. Two principal breakdown products are isomeric with one another and involve release of both fluorine and methyl groups to develop dehydrofluorodesmethylbromethalin products. These compounds have proven to be excellent surrogate markers in screening forensic samples for bromethalin exposure, particularly in veterinary samples in which the active metabolite desmethylbromethalin has not yet accumulated to any appreciable extent, such as baits and animal stomach contents. The compounds as well as their parent bromethalin were easily monitored by GC interfaced with a tandem-quadrupole mass spectrometer using multiple-reaction monitoring (MRM) modes. Unusual gas chromatographic properties of bromethalin included: (i) specific requirements for a maximum oven temperature; (ii) non-linear increases in detector response on increased injection volumes, hypothesized to result from variable diffusion coefficients. We report here the development of GC strategies that facilitate detection of bromethalin and its breakdown products, as well as their MRM analysis by tandem-quadrupole mass spectrometry. The developed approaches are applicable to feed, baits and stomach contents as well as extracted tissue samples such as liver and kidney.


[Herpes simplex virus and cytomegalovirus in male ejaculate: herpes simplex virus is more frequently encountered in idiopathic infertility and correlates with the reduction in sperm parameters].
The present investigation was undertaken to study the detection rate of herpes simplex virus (HSV) and cytomegalovirus (CMV) in the ejaculates of males with infertility and to evaluate the impact of virus infection on the major parameters of sperm. Ejaculates from 808 patients were studied. As compared with apparently healthy individuals, the coupled males with primary infertility were found to have HSV more frequently in both the whole ejaculate (31% versus 17%; p = 0.049) and the fraction of actively motile spermatozoa (30% versus 8%; p = 0.016). Ejaculate HSV detection directly correlated with the reduced amount of actively motile spermatozoa (p = 0.0001) and the smaller proportion of morphologically normal forms of germ cells (p = 0.002). CMV was found to have no impact on the motility and morphology of spermatozoids in the ejaculate. Both HSV and CMV in the male ejaculate were significantly more frequently detectable in winter months. The findings lead to the conclusion that HSV is one of the factors for male infertility and can negatively affect the results of assisted reproductive technologies.


[Morgagni hernia. A rare form of diaphragmatic hernia].
The Morgagni hernia is the rarest form of diaphragmatic hernias. Knowledge has been accumulated over time of combinations with other congenital malformations, familial occurrence, and traumatic genesis. Morgagni hernia has been more often recordable from women, along with rising age and usually located on the right hand side. Embryonic disorder of diaphragmatic differentiation is believed to be the major aetiological factor. Vitamin deficit as well as some chemical substances, primarily active in the foetal period, have become known as additional factors of predisposition. Intensive diagnosis to rule out malignancy is absolutely essential because of the variability of symptoms of this type of hernia. Colon fragments and large omentum were found to be most often contained in the hernial sac. Contrast medium X-ray checks of the gastrointestinal tract and pneumoperitoneum are preferential methods of examination. Exploratory laparotomy is generally considered the optional therapeutic approach because of possible saving of liver veins, safe removal of the hernial sac, and the possibility of abdominal exploration. Preoperative wide-range sterile covering of the patient's body around the site of surgery is recommended to allow for possible thoractomy, as may be required.


Protein domain-domain interactions and requirements for the negative regulation of Arabidopsis CDC48/p97 by the plant ubiquitin regulatory X (UBX) domain-containing protein, PUX1.
CDC48/p97 is an essential AAA-ATPase chaperone that functions in numerous diverse cellular activities through its interaction with specific adapter proteins. The ubiquitin regulatory X (UBX)-containing protein, PUX1, functions to regulate the hexameric structure and ATPase activity of AtCDC48. To characterize the biochemical mechanism of PUX1 action on AtCDC48, we have defined domains of both PUX1 and AtCDC48 that are critical for interaction and oligomer disassembly. Binding of PUX1 to AtCDC48 was mediated through a region containing both the UBX domain and the immediate C-terminal flanking amino acids (UBX-C). Like other UBX domains, the primary binding site for the UBX-C of PUX1 is the N(a) domain of AtCDC48. Alternative plant PUX protein UBX domains also bind AtCDC48 through the N terminus but were found not to be able to substitute for the action imparted by the UBX-C of PUX1 in hexamer disassembly, suggesting unique features for the UBX-C of PUX1. We propose that the PUX1 UBX-C domain modulates a second binding site on AtCDC48 required for the N-terminal domain of PUX1 to interact with and promote dissociation of the AtCDC48 hexamer. Utilizing Atcdc48 ATP hydrolysis and binding mutants, we demonstrate that PUX1 binding was not affected but that hexamer disassembly was significantly influenced by the ATP status of AtCDC48. ATPase activity in both the D1 and the D2 domains was critical for PUX1-mediated AtCDC48 hexamer disassembly. Together these results provide new mechanistic insight into how the hexameric status and ATPase activity of AtCDC48 are modulated.


Bortezomib-Induced Ovarian Toxicity in Mice.
Cancer survivors may experience long-term adverse effects of cancer treatments such as premature ovarian failure and infertility. We aimed to investigate the potential effects and toxicity of bortezomib (BTZ) as an effective anticancer drug on ovaries, raise awareness to the negative consequences of the treatment, and help increase the quality of life after treatment. Mice were distributed into bortezomib (BTZ1, BTZ2) and saline-injected control groups (C1, C2) at a dose of 1 mg/kg twice per week for 6 weeks. We sacrificed C1, BTZ1 groups at day 1 and C2, BTZ2 groups at 4 weeks after the last injection. Ovary samples were examined using histopathological and immunohistochemical methods. Ovarian follicle impairment was detected on BTZ-treated mice and was associated with a statistically significant decreased population of primordial and antral follicles compared with control groups. In experimental groups, Caspase-3 and Ki67 expressions were increased, whereas estrogen receptor alpha (ERα) and progesterone receptor (PR) expressions were decreased in various developmental stages of follicles. BTZ specifically targets granulosa cells by inducing granulosa cell apoptosis and may have long-term effects on follicles. Bortezomib treatment may adversely affect ovarian function by accelerating ovarian reserve depletion and changing ERα and PR hormone levels that can cause fertility problems in the long term.


Robust VLC Beacon Identification for Indoor Camera-Based Localization Systems.
Several industrial indoor positioning systems utilize LEDs as beacons and cameras as sensors: The LED beacons transmit their identity, using various means of visible light communication (VLC) techniques. To avoid flickering effects, the transmission frequency is usually much higher than the sampling frequency of ordinary cameras, thus undersampling occurs. In this paper, a potential problem of undersampled protocols is highlighted: If the transmitter and receiver are not synchronized, the frequency slip between the transmitter and receiver clocks will periodically cause a burst of potential decoding errors. If the frequency slip is small (i.e., good-quality clocks are used in both the transmitter and the receiver), the time between bursts of errors is longer but at the same time the length of the bursts are also longer. An error analysis is provided as a function of protocol parameters and various error sources. Based on the results the robust-undersampled phase-shift on-off keying (UPSOOK) protocol is introduced, which guarantees the correct operation even in the presence of clock inaccuracies, as well as other error sources such as sensor noise, jitter, camera saturation, without the utilization of any error correcting codes. The properties of the proposed robust-UPSOOK protocol are demonstrated using simulations and measurements.