Ultrafast laser-induced molecular and morphological changes during spinodal demixing of water/2-butoxyethanol/KCl.
We initiated morphological and molecular level changes in the spinodal decomposition (SD) of H(2)O/2-butoxyethanol/KCl with a pulsed ir laser. Transient Raman spectra gave us a molecular level view of the early stage of this process that could be linked to later morphological events. Chemical changes during SD, such as reorganization of H bonds and forced hydrophobic interactions, ended after 1 micros; however, phase domains continued to grow with self-similarity after 30 micros. The growth of the phase domains satisfied the power law L(t) approximately t(0.55) and was consistent with the late stage of SD. The time scale for the onset of late stage SD is many orders of magnitude faster than previously reported in ionic and nonionic conditions.


Managing food insecurity through informal networks of care: an ethnography of youth practices in the North of England.
Food insecurity in the UK is a pressing concern that is associated with poor health outcomes. Research to date has focused on the challenges for adults in providing food for families. However, there is little evidence showing how children and young people experience food insecurity, particularly outside of the home and school. This paper, drawing on 14 months of ethnography in a youth club in the North of England, explores how young people manage food insecurity. In this youth club, the circulation of takeaway food is part of an informal network where boys purchase, share and receive food. This practice allows the boys to participate meaningfully within their peer groups whilst also providing stable access to food. This peer practice, however, was not available to everyone. This was a gendered practice that for the girls held little benefit due to their concerns about eating and pressure to provide for others. Instead, some girls depend on romantic relationships for food provision that is equated with affection and care. The findings will be discussed through a 'materialities of care' perspective to explore the complex ways in which food as a practice of care is part of everyday routines embedded within local places.


Differential diagnosis of malignant lymphomas by imprint cytology.
The results of a study of 214 touch imprints of benign and malignant lymphoid disorders are presented. The diagnostic criteria, including the results of special stains, are described for both benign proliferative disorders and malignant lymphomas. Imprint cytology achieved an accuracy of 99% in diagnosing both benign and malignant conditions. Specific subtyping of malignant disorders was correctly made in 83% of non-Hodgkin's lymphomas and in 66% of Hodgkin's lymphomas. It is concluded that imprint cytology is a useful adjunct to the histopathologic diagnosis of lymphoid disease.


Immunoperoxidase and immunofluorescence in lymph node biopsies: a comparative study.
A comparison study was made of staining for immunoglobulin by immunofluorescence and immunoperoxidase in 23 lymph node biopsies. Cryostat sections were stained for immunoglobulins using a direct technique while paraffin-embedded sections were stained for immunoglobulins using the peroxidase-antiperoxidase (PAP) technique. Of 23 cases studied, including seven reactive hyperplasias and 16 lymphoid cancers, there was agreement between the two techniques in 18 cases. Nine of 14 non-Hodgkin's lymphomas showed agreement of results. All reactive hyperplasias showed complete agreement and had a distinctive pattern by both immunofluorescence and immunoperoxidase. Fixation, reagent specificity, and sensitivity of the methods may account for some of the discrepancies noted. Immunoperoxidase staining may be a useful diagnostic aid, particularly when immunofluorescent staining is not possible.


Ovarian follicular growth in sows.
The resumption of ovarian follicular development during lactation and after weaning in sows is a complex process that ultimately determines rebreeding efficiency of sows. Ovarian follicular development before weaning is heterogeneous because multiple patterns of development are observed when individual sows are compared. Sows can have relatively inactive ovaries before weaning with follicles of < 2 mm in diameter. Other sows have non-ovulatory follicular waves in which follicles grow to approximately 5 mm and subsequently regress before weaning. Sows may also have preovulatory follicular development and ovulation, or may develop cystic ovaries before weaning. Weaning is a random event relative to follicular development on the ovary. Therefore, variation in the weaning to oestrus interval in sows is caused by weaning at random stages of follicular development. Most sows experience a rapid period of follicular growth after weaning and return to oestrus within 3-7 days. Delayed intervals to oestrus after weaning are associated with inactive ovaries before weaning (follicles < 2 mm in diameter) or weaning during the regression phase of a follicular wave. An integrated model for follicular growth and oestrus in weaned sows should include endocrine mechanisms (that is, individual differences in insulin, insulin-like growth factor I (IGF-I), LH and FSH), behavioural mechanisms (relationship between follicular growth and the initiation of oestrus) and morphological mechanisms (that is, timing of weaning relative to ovarian follicular development).


Thymosin enhances the production of IL-1 alpha by human peripheral blood monocytes.
Incubation of human peripheral blood monocytes (PBM) with a partially purified thymic preparation, thymosin fraction (TF5), results in a dose dependent production of an interleukin-1 (IL-1)-like factor. The biological activity of this factor can be blocked by anti-IL-1 alpha, but not by anti-IL-1 beta which neutralizes bacterial induced IL-1 activity. Studies with further purified TF5 fractions show that this activity is not due to the well-characterized peptide, thymosin alpha 1 (T alpha 1), but rather a new thymosin peptide(s) isolated from a more basic fraction. Intraperitoneal injection of TF5 also induces the expression of a membrane-bound IL-1 (mIL-1) on mouse peritoneal cells. This study provides the first evidence that TF5 can influence macrophage activity directly by enhancing IL-1 production. This observation may help explain the mechanism by which TF5 modulates immune responses. These results also point to a more selective role for thymic hormones, growth factors and cytokines which may trigger macrophages to secrete different forms of IL-1, which can then regulate either immune and/or inflammatory processes.


Sarcomatoid basal cell carcinoma--predilection for osteosarcomatous differentiation: a series of 11 cases.
Primary cutaneous carcinomas rarely show heterologous malignant mesenchymal differentiation. We report 11 cases of sarcomatoid basal cell carcinoma (BCC) with osteosarcomatous differentiation. The patients (7 men and 4 women) ranged in age from 61 to 92 years (median 75 y). The tumors presented as exophytic nodules (0.3 to 7 cm) on the head (n=6), upper limb (n=3), and lower limb (n=2). All lesions were completely excised. Seven patients were alive without evidence of disease (follow-up interval 5 to 24 mo) and 1 patient died of unrelated causes at 7 months without evidence of disease. On histology, the tumors were dermal in location with 2 cases showing focal subcutaneous involvement. Ten tumors were well-circumscribed and 1 tumor showed focally infiltrative edges. Ten tumors revealed conventional BCC associated with varying proportions of osteosarcomatous and undifferentiated sarcomatous stroma. Transition from neoplastic epithelial to mesenchymal cells was seen in 8 cases. One case showed a purely osteoclastic giant cell rich malignant mesenchyme, interpreted as representing early stages of osteosarcomatous transformation. Previously unreported in sarcomatoid BCC, the mesenchymal component of another two cases displayed predominant malignant giant cell tumor like areas and 1 further case disclosed areas reminiscent of telangiectatic osteosarcoma. Pancytokeratins (AE1/3 and MNF116) and smooth muscle actin stained occasional undifferentiated sarcomatous cells in 2 and 3 tumors, respectively. MNF116 and EMA were focally positive in osteosarcomatous tumor cells of 1 case. Although the follow-up interval is short, our data suggest an excellent prognosis for polypoid and exophytic sarcomatoid BCC after complete surgical resection.


Molecular dynamics study of dielectric response in a relaxor ferroelectric.
We use atomistic molecular dynamics simulations to study relaxor behavior in the 0.75 PbMg(1/3)Nb(2/3)O(3)-0.25 PbTiO(3) material. Even for a fairly small simulation size of 1000 atoms, the system exhibits frequency dispersion and deviation from the Curie-Weiss law typical of relaxor materials. Analysis of the time autocorrelation functions for individual atoms allows us to identify the Nb atoms with a high concentration of neighboring Ti atoms as the nucleation sites for the relaxor behavior. This is due to the higher coupling between the cation displacements induced by the presence of overbonded oxygen atoms.


Clear cell ovarian cancers with microsatellite instability: A unique subset of ovarian cancers with increased tumor-infiltrating lymphocytes and PD-1/PD-L1 expression.
Clear cell ovarian carcinoma (CCOC) represents a distinct histologic subtype of ovarian cancer associated with significantly worse prognosis across all stages and no effective therapeutic options. Here, we report a rare but clinically important cohort of CCOCs with microsatellite instability (MSI) (MSI-CCOCs), which are highly immunogenic and may thus be very responsive to immune checkpoint blockade. CCOCs with MSI exhibit a significantly higher number of CD8+ TILs, higher CD8+/CD4+ ratio, and higher PD-1+ TILs compared with microsatellite stable (MSS) CCOCs and compared with high grade serous ovarian cancers, which are the most common histologic subtype of ovarian cancer. Of note, PD-L1 expression in tumor cells or immune cells was noted in all cases of CCOCs with MSI. These observations open an alternative therapeutic avenue for a fraction of patients with CCOC and argue for the routine testing of CCOCs for MSI, a test that is not currently routinely performed.


The Effect of the Testis on the Ovary: Structure-Function Relationships in a Neonate with a Unilateral Ovotestis (Ovotesticular Disorder of Sex Development) .
To evaluate gonadal function in a newborn with suspected ovotesticular disorder of sex development (DSD). Gonadal function was evaluated at baseline and after gonadotropin-releasing hormone agonist (GnRHag) stimulation testing. A full-term 46,XX neonate with genital ambiguity produced serum testosterone and anti-Müllerian hormone (AMH) levels appropriate for males within days, while serum estradiol remained prepubertal, both spontaneously and in response to GnRHag stimulation testing. Ovotesticular DSD was diagnosed at laparoscopy: the left gonad was an ovotestis and the right gonad an ovary arrested at the primordial follicle stage of development. Mosaicism for an isochromosome of the Y short arm in 6-18% of gonadal cells was demonstrated. After ovotestis removal at 3 weeks of age, serum AMH became low within a month, but the elevated testosterone was slow to resolve, apparently from ovarian androgenic hyperfunction coincident with ovarian estrogenic hyperfunction and an adult degree of ovarian development. Ovarian morphology and function gradually normalized as neonatal minipuberty waned. In a neonate with genital ambiguity due to ovotesticular DSD, testicular AMH and testosterone production respectively appear to account for the initial arrest of ovarian development and subsequent rapid hyperfunction of the contralateral ovary after ovotestis removal. .


Emergency department crowding, part 1--concept, causes, and moral consequences.
Crowding is an increasingly common occurrence in hospital-based emergency departments (EDs) across the globe. This 2-article series offers an ethical and policy analysis of ED crowding. Part 1 begins with a discussion of terms used to describe this situation and proposes that the term "crowding" be preferred to "overcrowding." The article discusses definitions, measures, and causes of ED crowding and concludes that the inability to transfer emergency patients to inpatient beds and resultant boarding of admitted patients in the ED are among the root causes of ED crowding. Finally, the article identifies and describes a variety of adverse moral consequences of ED crowding, including increased risks of harm to patients, delays in providing needed care, compromised privacy and confidentiality, impaired communication, and diminished access to care. Part 2 of the series examines barriers to resolving the problem of ED crowding and strategies proposed to overcome those barriers.


Molecular characterization and expression analyses of the Solea senegalensis interferon-stimulated gene 15 (isg15) following NNV infections.
Interferons are essential in fish resistance to viral infections. They induce interferon-stimulated genes, such as isg15. In this study, the Senegalese sole isg15 gene (ssisg15) has been characterized. As other isg15, ssisg15 contains a 402-bp intron sited in the 5'-UTR, and the full length cDNA is 1492-bp, including a 480-bp ORF. The expression analyses revealed basal levels of isg15 transcripts, and a clear induction after poly I:C injection, that reached maximum values in brain, head kidney and gills. The ssisg15 induction patterns were similar in RGNNV- and SJNNV-inoculated fish, whereas the reassortant (RG/SJ) isolate, which has higher replication fitness, triggered delayed but higher transcript levels. Furthermore, RG/SJ infection after poly I:C treatment reduced the induction of ssisg15 transcripts, suggesting an antagonistic mechanism against interferon type I system, that might allow an efficient viral replication at the initial steps of the infective process.


Asymmetric synthesis of gem-difluoromethylenated linear triquinanes via cascade gem-difluoroalkyl radical cyclization.
An asymmetric synthesis of gem-difluoromethylenated linear triquinanes is described exploiting the synthetic utilities of PhSCF2TMS (5) as a "(•)CF2(-)'' building block. The strategy involves fluoride-catalyzed nucleophilic addition of PhSCF2TMS (5) to chiral ketocyclopentenes 6 to provide silylated adducts 9 or alcohol derivatives 10 and 11. Subsequent cascade radical cyclization of the gem-difluoroalkyl radical generated from silylated adducts 9 or alcohols 10 and 11 afforded gem-difluoromethylenated linear triquinanes 16 as an approximate 1:1 mixture of two diastereomers (16A and 16B). Alternatively, a convenient asymmetric synthesis of gem-difluoromethylenated linear triquinanes 16A can be accomplished by oxidation of 16a (R = H) to provide ketotriquinane 17 followed by a highly stereoselective nucleophilic addition to 17 employing DIBAL, NaBH4, and various Grignard reagents.


Transfer-matrix formalism for the calculation of optical response in multilayer systems: from coherent to incoherent interference.
We present a novel way to account for partially coherent interference in multilayer systems via the transfer-matrix method. The novel feature is that there is no need to use modified Fresnel coefficients or the square of their amplitudes to work in the incoherent limit. The transition from coherent to incoherent interference is achieved by introducing a random phase of increasing intensity in the propagating media. This random phase can simulate the effect of defects or impurities. This method provides a general way of dealing with optical multilayer systems, in which coherent and incoherent interference are treated on equal footing.


Electrostatic self-assembly of PEG copolymers onto porous silica nanoparticles.
A critical requirement toward the clinical use of nanocarriers in drug delivery applications is the development of optimal biointerfacial engineering procedures designed to resist biologically nonspecific adsorption events. Minimization of opsonization increases blood residence time and improves the ability to target solid tumors. We report the electrostatic self-assembly of polyethyleneimine-polyethylene glycol (PEI-PEG) copolymers onto porous silica nanoparticles. PEI-PEG copolymers were synthesized and their adsorption by self-assembly onto silica surfaces were investigated to achieve a better understanding of structure-activity relationships. Quartz-crystal microbalance (QCM) study confirmed the rapid and stable adsorption of the copolymers onto silica-coated QCM sensors driven by strong electrostatic interactions. XPS and FT-IR spectroscopy were used to analyze the coated surfaces, which indicated the presence of dense PEG layers on the silica nanoparticles. Dynamic light scattering was used to optimize the coating procedure. Monodisperse dispersions of the PEGylated nanoparticles were obtained in high yields and the thin PEG layers provided excellent colloidal stability. In vitro protein adsorption tests using 5% serum demonstrated the ability of the self-assembled copolymer layers to resist biologically nonspecific fouling and to prevent aggregation of the nanoparticles in physiological environments. These results demonstrate that the electrostatic self-assembly of PEG copolymers onto silica nanoparticles used as drug nanocarriers is a robust and efficient procedure, providing excellent control of their biointerfacial properties.


Isometric muscle strength of Chinese young males in Taiwan.
This paper represents the results of an anthropometric measurement of the isometric muscle strength of Chinese young males in Taiwan aged from 16 to 20 years. The study uses a sample of 120 male students and measures four types of muscle strength: (1) right arm strength in exerting pull, push, adduction, abduction, lift, and press directions with five elbow angles (60, 90, 120, 150 and 180 degrees) in seated posture; (2) grip strength of both hands; (3) backlift strength: and (4) chest expanding strength. The obtained data are analysed and listed. Comparisons are made between the results of this study and those from domestic and foreign studies available in the literature. In general, their pattern is similar, but values obtained in this study are relatively smaller than those obtained in western countries.


Ca2+ is required for phosphorylation of clam p82/CPEB in vitro: implications for dual and independent roles of MAP and Cdc2 kinases.
During early development gene expression is controlled principally at the translational level. Oocytes of the surf clam Spisula solidissima contain large stockpiles of maternal mRNAs which are translationally dormant or masked until meiotic maturation. Fertilisation of the oocyte leads to rapid polysomal recruitment of the abundant cyclin and ribonucleotide reductase mRNAs at about the time they undergo cytoplasmic polyadenylation. Clam p82, a 3' UTR RNA-binding protein, and a member of the CPEB (cytoplasmic polyadenylation element binding protein) family, functions as a translational masking factor in oocytes and as a polyadenylation factor in fertilised eggs. In meiotically maturing clam oocytes, p82/CPEB is rapidly phosphorylated on multiple residues to a 92-kDa apparent size, prior to its degradation during the first cell cleavage. Here we examine the protein kinase(s) that phosphorylates clam p82/CPEB using a clam oocyte activation cell-free system that responds to elevated pH, mirroring the pH rise that accompanies fertilisation. We show that p82/CPEB phosphorylation requires Ca2+ (<100 microM) in addition to raised pH. Examination of the calcium dependency combined with the use of specific inhibitors implicates the combined and independent actions of cdc2 and MAP kinases in p82/CPEB phosphorylation. Calcium is necessary for both the activation and the maintenance of MAP kinase, whose activity is transient in vitro, as in vivo. While cdc2 kinase plays a role in the maintenance of MAP kinase activity, it is not required for the activation of MAP kinase. We propose a model of clam p82/CPEB phosphorylation in which MAP kinase initially phosphorylates clam p82/CPEB, at a minor subset of sites that does not alter its migration, and cdc2 kinase is necessary for the second wave of phosphorylation that results in the large mobility size shift of clam p82/CPEB. The possible roles of phosphorylation for the function and regulation of p82/CPEB are discussed.


Cocaine-induced liver injury in mice elicits specific changes in DNA ploidy and induces programmed death of hepatocytes.
Liver injury was induced by a single dose (60 mg/kg) of cocaine in male albino Swiss mice untreated or pretreated with phenobarbital (in drinking water 1 gm/L), for 5 days before cocaine administration. One parameter of liver injury, serum isocitrate dehydrogenase activity, showed sharp increases at 24 hr of cocaine treatment; we also noted decrease hepatic levels of ATP, GSH, cytochrome P-450 and NADPH/NADP+ ratio and increases in malondialdehyde concentration. Histopathological study of liver slices showed perivenous and periportal necrosis induced by cocaine in untreated mice and mice pretreated with phenobarbital, respectively. A regenerative postnecrotic response, which peaked at 48 hr, was demonstrated by the appearance of mitotic cells. Mitotic index analysis showed that proliferative cells appear to be unevenly distributed in the hepatic acinus and were mainly located in the vicinity of the damaged acinar region. Genomic DNA ploidy and the distribution of DNA in the phases of the cell cycle were studied in nuclei of isolated hepatocytes. At 12 hr of cocaine administration, both in untreated and phenobarbital-pretreated mice, the following changes were observed: a sharp decrease in tetraploid (4N) cells (40% to 17% and 25% to 6%, respectively) and octoploid (8N) cells (5% to 2% and 2% to 1%, respectively), together with the appearance of a hypodiploid population (13% and 31%, respectively). Hypodiploid population was characterized as apoptotic cells by detection of DNA fragmentation in agarose gel. These results suggest that a significant percentage of cell death induced by cocaine occurs by means of the apoptosis death program. Comparison of the initial values of DNA ploidy with those obtained at 7 days of cocaine administration showed remarkable increases in polyploid populations (4N and 8N) and a decrease in diploid cells (2N), indicating that the process of differentiation occurs when liver restores its functionality.


Healthier central England or North-South divide? Analysis of national survey data on smoking and high-risk drinking.
This paper compares patterns of smoking and high-risk alcohol use across regions in England, and assesses the impact on these of adjusting for sociodemographic characteristics. Population survey of 53 922 adults in England aged 16+ taking part in the Alcohol and Smoking Toolkit Studies. Participants answered questions regarding their socioeconomic status (SES), gender, age, ethnicity, Government Office Region, smoking status and completed the Alcohol Use Disorders Identification Test (AUDIT). High-risk drinkers were defined as those with a score of 8 or more (7 or more for women) on the AUDIT. In unadjusted analyses, relative to the South West, those in the North of England were more likely to smoke, while those from the East of England, South East and London were less likely. After adjustment for sociodemographics, smoking prevalence was no higher in North East (RR 0.97, p>0.05), North West (RR 0.98, p>0.05) or Yorkshire and the Humber (RR 1.03, p>0.05) but was less common in the East and West Midlands (RR 0.86, p<0.001; RR 0.91, p<0.05), East of England (RR 0.86, p<0.001), South East (RR 0.92, p<0.05) and London (RR 0.85, p<0.001). High-risk drinking was more common in the North but was less common in the Midlands, London and East of England. Adjustment for sociodemographics had little effect. There was a higher prevalence in the North East (RR 1.67, p<0.001), North West (RR 1.42, p<0.001) and Yorkshire and the Humber (RR 1.35, p<0.001); lower prevalence in the East Midlands (RR 0.69, p<0.001), West Midlands (RR 0.77, p<0.001), East of England (RR 0.72, p<0.001) and London (RR 0.71, p<0.001); and a similar prevalence in the South East (RR 1.10, p>0.05) CONCLUSIONS: In adjusted analyses, smoking and high-risk drinking appear less common in 'central England' than in the rest of the country. Regional differences in smoking, but not those in high-risk drinking, appear to be explained to some extent by sociodemographic disparities.


Synthesis of 3'-halo-5'-norcarbocyclic nucleoside phosphonates as potent anti-HIV agents.
The synthesis and the antiviral evaluation of 3'-halo (iodo and fluoro) 5'-norcarbocyclic nucleoside phosphonates is described. No antiviral activity was observed against Zika virus, Dengue virus 2, HSV-1, HSV-2 and Chikungunya virus. In contrast, some of the synthesized compounds are potent inhibitors of the replication of HIV-1, comparatively to (R)-PMPA, with no concomitant cytotoxicity.


Tunable band-notched coplanar waveguide based on localized spoof surface plasmons.
This Letter proposes a simple band-notched coplanar waveguide (BNCPW), which consists of a coplanar waveguide (CPW) and an ultra-thin periodic corrugated metallic strip that supports spoof surface plasmon polaritons (SSPPs) with defect units on the back of the substrate. By introducing a defect unit or multiple defect units into the strip, a narrow stopband or multiple narrow stopbands would be generated flexibly and conveniently. The band-notch function is based on the idea that a defect mode, which exists in the bandgap between the fundamental and the first higher mode of the SSPPs, can be introduced to form a stopband. Thus, the SSPPs field is localized around the defect units, which is another form of localized spoof surface plasmons (LSSPs). By properly tuning the dimensions of each defect unit, the absorption level and center frequency of the stopband could be adjusted independently. We offer theoretical analysis and experimental results to validate our idea and design. In this framework, a variety of band-notched devices and antennas in the microwave and terahertz (THz) frequencies can be easily designed without additional band-stop filters.


ATRP/OMRP/CCT interplay in styrene polymerization mediated by iron(II) complexes: A DFT study of the α-diimine system.
A DFT study of various model systems has addressed the interference of catalytic chain transfer (CCT) as a function of the R(2) substituent in the atom-transfer radical polymerization (ATRP) of styrene catalyzed by [FeCl2 (R(1) N=C(R(2))C(R(2))=NR(1))] complexes. All model systems used R(1) =CH3 in place of the experimental Cy and tBu substituents and 1-phenylethyl in place of the polystyrene (PS) chain. A mechanistic investigation of 1) ATRP activation, 2) radical trapping in organometallic-mediated radical polymerization (OMRP), and 3) pathways to the hydride CCT intermediate was conducted with a simplified system with R(2)=H. This study suggests that CCT could occur by direct hydrogen-atom transfer without any activation barrier. Further analysis of more realistic models with R(2)=p-C6 H4 F or p-C6 H4 NMe2 suggests that the electronic effect of the aryl para substituents significantly alters the ATRP activation barrier. Conversely, the hydrogen-atom-transfer barrier is essentially unaffected. Thus, the greater ATRP catalytic activity of the p-NMe2 system makes the background CCT process less significant. The DFT study also compares the [FeCl2 (R(1) N=C(R(2))=C(R(2))=NR(1))] systems with a diaminobis(phenolato) derivative for which the CCT process shows even greater accessibility but has less incidence because of faster ATRP chain growth and interplay with a more efficient OMRP trapping. The difference between the two systems is attributed to destabilization of the Fe(II) catalyst by the geometric constraints of the tetradentate diaminobis(phenolato) ligand.


Tumor organoids: Opportunities and challenges to guide precision medicine.
Tumor organoids have been proposed as a model system for precision medicine. The ability of tumor organoids to retain characteristics of the original tumor makes them unique for cancer research on an individual patient level. Hence, the idea to use tumor organoids for clinical decision making and optimize patient outcome is tempting. In vitro responses of tumor organoids to a wide array of drugs have been positively correlated to patient responses. However, substantial challenges remain and prospective studies with large cohorts are highly needed before implementation in clinical cancer care can be considered. Because of their personalized characteristics and the immediate link with patient data, tumor organoids also have great potential in preclinical research. Here, we provide a critical overview of both clinical and preclinical advances using tumor organoids.


No more rattling: biomechanical evaluation of a hexapod ring fixator free of play.
Hexapod-ring-fixators have a characteristic rattling sound during load changes due to play in the hexapod struts. This play is perceived as unpleasant by patients and can lead to frame instability. Using slotted-ball-instead of universal-joints for the ring-strut connection could potentially resolve this problem. The purpose of the study was to clarify if the use of slotted-ball-joints reduces play and also fracture gap movement. A hexapod-fixator with slotted-ball-joints and aluminum struts (Ball-Al) was compared to universal-joint-fixators with either aluminum (Uni Al) or steel struts (Uni Steel). Six fixator frames each were loaded in tension, compression, torsion, bending and shear and mechanical performance was analyzed in terms of movement, stiffness and play. The slotted-ball-joint fixator was the only system without measurable axial play (<0.01 mm) compared to Uni-Al (1.2 ± 0.1) mm and Uni-Steel (0.6 ± 0.2) mm (p≤0.001). In both shear directions the Uni-Al had the largest play (p≤0.014). The resulting axial fracture gap movements were similar for the two aluminum frames and up to 25% smaller for the steel frame, mainly due to the highest stiffness found for the Uni-Steel in all loading scenarios (p≤0.036). However, the Uni-Steel construct was also up to 29% (450 g) heavier and had fewer usable mounting holes. In conclusion, the slotted-ball-joints of the Ball-Al fixator reduced play and minimized shear movement in the fracture while maintaining low weight of the construct. The heavier and stiffer Uni-Steel fixator compensates for existing play with a higher overall stiffness.


High-throughput titration of luciferase-expressing recombinant viruses.
Standard plaque assays to determine infectious viral titers can be time consuming, are not amenable to a high volume of samples, and cannot be done with viruses that do not form plaques. As an alternative to plaque assays, we have developed a high-throughput titration method that allows for the simultaneous titration of a high volume of samples in a single day. This approach involves infection of the samples with a Firefly luciferase tagged virus, transfer of the infected samples onto an appropriate permissive cell line, subsequent addition of luciferin, reading of plates in order to obtain luminescence readings, and finally the conversion from luminescence to viral titers. The assessment of cytotoxicity using a metabolic viability dye can be easily incorporated in the workflow in parallel and provide valuable information in the context of a drug screen. This technique provides a reliable, high-throughput method to determine viral titers as an alternative to a standard plaque assay.


Negatively charged Cu1.33S nanochains: endocytic pathway, photothermal therapy and toxic effect in vivo.
Negatively charged nanomaterials have good biocompatibility and low cytotoxicity, but the efficiency of their entry into cells is relatively low. Thus, striking a balance between cell transport efficiency and cytotoxicity is a challenging problem in the field of nanomedicine. In this work, negatively charged Cu1.33S nanochains have shown a higher cellular uptake level in 4T1 cells than Cu1.33S nanoparticles with a similar diameter and surface charge. Inhibition experiments indicate that the cellular uptake of the nanochains depends principally on the lipid-raft protein (i.e. caveolin-1) mediated pathway, although the role of clathrin cannot be ruled out. Caveolin-1 can provide short-range attraction at the membrane interface. Furthermore, by using biochemical analysis, blood routine examination and histological evaluation on healthy Sprague Dawley rats, it is found that the Cu1.33S nanochains have no obvious toxic effect. The Cu1.33S nanochains have an effective photothermal therapy effect of tumor ablation in vivo under low injection dosage and laser intensity. As for the best performing group (20 μg + 1 W cm-2), the temperature of the tumor site rapidly increases within the initial 3 min and rises to a plateau of 79 °C (ΔT = 46 °C) at 5 min. These results reveal the feasibility of the Cu1.33S nanochains as a photothermal agent.


[Preparation of nosiheptide liposomes and its inhibitory effect on hepatitics B virus in vitro].
To prepare liposomes of nosiheptide and study its ability to inhibit hepatitis B virus HBsAg and HBeAg secreted. Liposomes of nosiheptide was prepared by sodium deoxycholate dialysis and sonication. Nosheptide was determined by HPLC and partical size was determined by using laser light scattering instrument. Transmission electron microscopy (TEM) was used to examine the morphology of liposomes. Its actions to inhibit hepatitis B virus HBsAg and HBeAg secreted was studied by a HBV-transfectted cell line (HepG2 2. 2. 15 ). Encapsulation efficiency of liposomes by chloroform:methanol (2:1, v/v) was higher than that by dioxane. With the increase of the ratio of nosiheptide: PC (W/W), the encapsulation efficiency of liposomes decreased with the increase of ratio of sodium deoxycholate: PC, the liposomes partical size decreased. The liposomes kept stable at -20 degrees C after 2 years. The drug concentrations of liposomes that inhibit HBsAg secreted by (46.9 +/- 2. 6) %, (55.4 +/- 1.2) %, (65 +/- 3) % and HBeAg secreted by (15.1 +/- 2.3) %, (36.2 +/- 1.7) %, (36.8 +/- 2.5) % were 1.25, 2.5, 5.0 microg x mL(-1), respectively. Liposomes of nosheptide can be prepared by sodium deoxycholate dialysis and sonication, which ability to inhibit hepatitis B virus HBsAg and HBeAg secreted is better than nosheptide.


Meta-analysis demonstrates no association between XRCC1 Arg399Gln polymorphism and bladder cancer risk.
We examined whether the X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln polymorphism is a risk factor for bladder cancer by conducting a meta-analysis. We searched the Pubmed and Embase databases for study retrieval. This meta-analysis examined 16 case-control studies, including 892 prostate cancer cases and 1020 healthy controls. Meta-analysis results based on these studies showed no significant association between the XRCC1 Arg399Gln polymorphism and bladder cancer risk in comparisons of the glutamine (Gln) allele vs arginine (Arg) allele, Arg/Arg vs (Gln/Gln + Gln/Arg), Gln/Gln vs (Gln/Arg + Arg/Arg), Gln/Gln vs Arg/Arg, and Gln/Arg vs Arg/Arg [odds ratio (OR) = 0.96, 95% confidence interval (CI) = 0.80-1.16, P = 0.70; OR = 1.13, 95%CI = 0.70-1.82, P = 0.62; OR = 0.92, 95%CI = 0.79-1.07, P = 0.29; OR = 0.90, 95%CI = 0.69-1.16, P = 0.42; OR = 0.89, 95%CI = 0.75-1.05, P = 0.17, respectively]. In subgroup analysis by ethnicity, no association was observed between the XRCC1 Arg399Gln polymorphism and bladder cancer risk in Caucasian, Mongoloid, or black populations. We identified no association between the XRCC1 Arg399Gln polymorphism and bladder cancer risk.


Beauty parlor stroke syndrome due to a bone fragment from an osteophyte of the atlas: case report.
Beauty parlor stroke syndrome (BPSS) is a rare condition characterized by mechanical impingement of a vertebral artery (VA) during neck rotation and/or hyperextension followed by vertebrobasilar insufficiency. However, there have been no reports of BPSS in which the cause of mechanical impingement was identified and no cases for which surgical treatment was reported. The authors report the case of a 56-year-old Japanese man who presented with presyncope that occurred during cervical extension. Given the possibility of vertebrobasilar insufficiency, digital subtraction angiography and CT angiography were performed. These studies revealed that the right VA was hypoplastic and the left VA was dominant. Moreover, in the position of cervical extension, the dominant left VA showed constriction caused by a bone fragment of an osteophyte of the atlas. Removal of the bone fragment was performed. Postoperative left vertebral angiography showed improvement of blood flow in the extended position, and the presyncope completely disappeared. The pathomechanism of this case was a bone fragment compressing the left VA in the C-1 groove during neck extension. In BPSS patients with recurrent transient symptoms, the possibility of this mechanism of VA constriction by a free bone fragment should be considered.


Positive Classification Advantage: Tracing the Time Course Based on Brain Oscillation.
The present study aimed to explore the modulation of frequency bands (alpha, beta, theta) underlying the positive facial expressions classification advantage within different post-stimulus time intervals (100-200 ms, 200-300 ms, 300-400 ms). For this purpose, we recorded electroencephalogram (EEG) activity during an emotion discrimination task for happy, sad and neutral faces. The correlation between the non-phase-locked power of frequency bands and reaction times (RTs) was assessed. The results revealed that beta played a major role in positive classification advantage (PCA) within the 100-200 and 300-400 ms intervals, whereas theta was important within the 200-300 ms interval. We propose that the beta band modulated the neutral and emotional face classification process, and that the theta band modulated for happy and sad face classification.


Metal stressors consistently modulate bacterial conjugal plasmid uptake potential in a phylogenetically conserved manner.
The environmental stimulants and inhibitors of conjugal plasmid transfer in microbial communities are poorly understood. Specifically, it is not known whether exposure to stressors may cause a community to alter its plasmid uptake ability. We assessed whether metals (Cu, Cd, Ni, Zn) and one metalloid (As), at concentrations causing partial growth inhibition, modulate community permissiveness (that is, uptake ability) against a broad-host-range IncP-type plasmid (pKJK5). Cells were extracted from an agricultural soil as recipient community and a cultivation-minimal filter mating assay was conducted with an exogenous E. coli donor strain. The donor hosted a gfp-tagged pKJK5 derivative from which conjugation events could be microscopically quantified and transconjugants isolated and phylogenetically described at high resolution via FACS and 16S rRNA amplicon sequencing. Metal stress consistently decreased plasmid transfer frequencies to the community, while the transconjugal pool richness remained unaffected with OTUs belonging to 12 bacterial phyla. The taxonomic composition of the transconjugal pools was distinct from their respective recipient communities and clustered dependent on the stress type and dose. However, for certain OTUs, stress increased or decreased permissiveness by more than 1000-fold and this response was typically correlated across different metals and doses. The response to some stresses was, in addition, phylogenetically conserved. This is the first demonstration that community permissiveness is sensitive to metal(loid) stress in a manner that is both partially consistent across stressors and phylogenetically conserved.


Molecular anatomy of tyrosinase and its related proteins: beyond the histidine-bound metal catalytic center.
The structure of tyrosinase (Tyr) is reviewed from a double point of view. On the one hand, by comparison of all Tyr found throughout nature, from prokaryotic organisms to mammals and on the other, by comparison with the tyrosinase related proteins (Tyrps) that appeared late in evolution, and are only found in higher animals. Their structures are reviewed as a whole rather than focused on the histidine (His)-bound metal active site, which is the part of the molecule common to all these proteins. The availability of crystallographic data of hemocyanins and recently of sweet potato catechol oxidase has improved the model of the three-dimensional structure of the Tyr family. Accordingly, Tyr has a higher structural disorder than hemocyanins, particularly at the CuA site. The active site seems to be characterized by the formation of a hydrophobic pocket with a number of conserved aromatic residues sited close to the well-known His. Other regions specific of the mammalian enzymes, such as the cytosolic C-terminal tail, the cysteine clusters, and the N-glycosylation sequons, are also discussed. The complete understanding of the Tyr copper-binding domain and the characterization of the residues determinant of the relative substrate affinities of the Tyrps will improve the design of targeted mutagenesis experiments to understand the different catalytic capabilities of Tyr and Tyrps. This may assist future aims, from the design of more efficient bacterial Tyr for biotechnological applications to the design of inhibitors of undesirable fruit browning in vegetables or of color skin modulators in animals.


Association of Respiratory Mechanic Instability and Respiratory Parameters among Adults with Obstructive Sleep Apnea.
Respiratory mechanic instability (RMI) is derived from analysis of paradoxical thoracoabdominal movements during airway obstruction. This study aimed to evaluate RMI parameters in obstructive sleep apnea (OSA) and the correlation between RMI parameters and other parameters in polysomnography. Retrospective review. A university hospital. A retrospective chart review was performed, and data from 189 adult patients who underwent an in-laboratory sleep study and were seen in our clinic during the past 8 months. The RMI parameters were measured from thoracoabdominal bands during polysomnography. Subjects were divided into 2 groups: control (n = 67, apnea-hypopnea index [AHI] <5) and OSA (n = 122, AHI ≥5). The OSA group was divided into 3 subgroups according to AHI: mild, 5 ≤ AHI < 15; moderate, 15 ≤ AHI < 30; severe, AHI ≥30. As AHI increased, all RMI parameters showed a significant rising pattern and difference between control and subgroups. Arousal index, lowest oxygen saturation, and oxygen desaturation index ≥3% were significantly correlated with all RMI parameters. Based on cutoff values, areas under the curves of the RMI index for predicting mild, moderate, and severe OSA were >0.85. All RMI parameters were well related to respiratory parameters of polysomnography, such as arousal index, lowest oxygen saturation, and oxygen desaturation index ≥3%. The areas under the curves of all RMI parameters for predicting OSA and subgroups showed significant diagnostic performance. These parameters may be useful to identify OSA cases from control.


The suppression of enhanced bitterness intensity of macrolide dry syrup mixed with an acidic powder.
The aim of the present study was to identify a medicine which strongly enhanced the bitterness of clarithromycin dry syrup (CAMD) when administered concomitantly and to develop a method to suppress this enhanced bitterness. The bitterness enhancement was evaluated not only by gustatory sensation tests but also using pH and taste sensor measurements of the mixed sample. A remarkable bitterness enhancement was found when CAMD was mixed with the acidic powder L-carbocysteine. The acidic pH (pH 3.40) of the suspension made from these two preparations, seemed to be due to enhanced release of clarithromycin caused by the dissolution of the alkaline polymer film-coating. Several methods for preventing this bitterness enhancement were investigated. Neither increasing the volume of water taken with the mixture, nor changing the ratio of CAMD:L-carbocysteine in the mixture, were effective in reducing the bitterness intensity of the CAMD/L-carbocysteine mixture. The best way to achieve taste masking was to first administer CAMD mixed with chocolate jelly, which has a neutral pH, followed by the L-carbocysteine suspension. Similar results were obtained for the bitterness suppression of azithromycin fine granules with L-carbocysteine. The chocolate jelly will be useful for taste masking of bitter macrolide drug formulations, when they need to be administered together with acidic drug formulations.


Discrepancies between qualitative and quantitative analysis of cerebrospinal fluid IgG: densitometric comparison of nephelometry-silver versus immuno-enzymes.
Detection of local synthesis of IgG within the central nervous system is important for the diagnosis of brain inflammatory diseases such as multiple sclerosis. This is typically done by comparing the amounts of IgG in serum and parallel cerebrospinal fluid (CSF). Although there have been well-described problems with qualitative versus quantitative measurements of abnormal IgG, such as in myeloma paraproteins, similar difficulties are also found with CSF IgG. Traditional quantitative analysis of IgG by rate nephelometry was followed by separation of the IgG using isoelectric focusing and then either silver stain or immunofixation. Finally, quantitative analysis was performed by scanning densitometry using public domain software downloaded from the National Institutes of Health. We report here the major discrepancies that can occur with CSF IgG between the silver stain versus the IgG stain. We concur with the earlier recommendation that qualitative separation followed by densitometric estimation of enzyme-linked immunofixation is also more useful than simple quantitative nephelometric analysis followed by silver staining in the detection of local synthesis of IgG, analogous to the earlier work on paraproteins.


Familial Mediterranean fever: from the clinical syndrome to the cloning of the pyrin gene.
Familial Mediterranean fever (FMF) is a genetic disorder, restricted to peoples originating in the Middle East. The clinical syndrome is characterized by shortlived febrile episodes, accompanied by inflammation in one of the serous membranes, resulting in peritonitis pleuritis or synovitis. In many untreated FMF patients, systemic amyloidosis developed. The clinical presentation of amyloidosis in FMF is nephropathic, progressing from proteinuria, nephrosis to renal failure and end stage renal disease. Continuous colchicine treatment, which was introduced in 1972, prevents most febrile-inflammatory attacks of FMF, and inhibits the development of amyloidosis in this otherwise fatal disease. Recently, the gene that causes FMF was cloned. It is called the pyrin gene and encodes the pyrin protein. Five missense mutations were found so far in the gene. These give rise to 5 amino acid substitutions, all of them in the carboxyterminal part of the pyrin protein. The pyrin protein is expressed solely in neutrophiles white blood cells which are found in large numbers in the inflammatory sites during FMF attacks. It seems that the role of the wild type of the pyrin protein is to inhibit inflammation that can be provoked by a minor insult. The mutated pyrin protein in FMF is probably unable to inhibit these unnecessary inflammatory events. Preliminary studies of phenotype genotype correlation are reported.


Clinical and radiological features of invasive Klebsiella pneumoniae liver abscess syndrome.
Recently, a striking new clinical manifestation of Klebsiella pneumoniae (KP) infection referred to as invasive KP liver abscess syndrome (IKPLAS), defined by liver abscess with contemporaneous metastatic KP infections at other body sites has been documented. Until now, however, there have been relatively few reports regarding its radiologic features. To describe the clinical and radiological features of IKPLAS patients, and to compare them with those with KP liver abscess without metastatic infections to ascertain possible predictors of IKPLAS. From January 2008 to May 2010, 35 patients (26 men and 9 women; mean age, 59.4 years) with both liver abscess and metastatic KP infections were diagnosed with IKPLAS. Their clinical and radiological features were retrospectively evaluated and compared with those of 25 contemporaneous non-metastatic patients to investigate predictive factors for metastatic infections. The rate of intensive care unit admissions and overall mortality was 34.3% and 17.1% in IKPLAS patients, and was significantly higher than those of the non-metastatic group (8% and 0%, respectively). As for metastatic infections, the lung was the most common site and multiple nodules or masses (n = 9) were the most common manifestations. Univariate analysis revealed that liver abscess ≤5.8 cm, bilobar involvement of abscess and altered mentality were significantly related with IKPLAS. At multivariate analysis, liver abscess ≤5.8 cm was proven to be a significant independent predictor of IKPLAS (OR, 3.6; P = 0.038). In addition, altered mentality was present solely in IKPLAS (25.7% vs. 0%) although its P value (P = 0.052) did not reach a statistical significance at multivariate analysis. IKPLAS has significantly worse prognosis than non-metastatic KP abscess patients. In patients with KP liver abscess, liver abscess ≤5.8 cm can be used as an independent predictor of IKPLAS and altered mentality as a very specific feature in diagnosing IKPLAS.


Reduced immunogenicity of beta-lactoglobulin by conjugation with acidic oligosaccharides.
Bovine beta-lactoglobulin (beta-LG) was conjugated with the acidic oligosaccharides, alginic acid oligosaccharide (ALGO) and phosphoryl oligosaccharides (POs) by the Maillard reaction to reduce the immunogenicity of beta-LG. The molar ratios of beta-LG to ALGO and POs in the conjugates were 1:6 and 1:8. The carbohydrate-binding sites in the beta-LG-ALGO conjugate were partially identified to be (60)Lys, (77)Lys, (100)Lys, (138)Lys, and (141)Lys. The isoelectric point of each conjugate was lower than that of beta-LG. CD spectra indicated that the secondary structure of beta-LG was almost maintained after conjugation. The results of fluorescence studies indicated that the conformation around Trp had not changed in each conjugate and that the surface of each conjugate was covered with a saccharide chain. Structural analyses with monoclonal antibodies indicated that the conformation around (8)Lys-(19)Trp (beta-sheet, random coil, short helix) in the conjugates had changed, whereas the native structure was maintained around (15)Val-(29)Ile (beta-sheet) and (125)Thr-(135)Lys (alpha-helix). The beta-LG-ALGO and beta-LG-POs conjugates maintained 77 and 70% of the retinol binding activity of beta-LG. Conjugation with ALGO and POs substantially enhanced the thermal stability of beta-LG. The anti-beta-LG antibody response was markedly reduced after immunization with both conjugates in BALB/c, C57BL/6, and C3H/He mice. B cell epitopes of beta-LG and the conjugate recognized in these mice were determined with 15-mer multipin peptides, and the linear epitope profiles of the conjugates were found to be similar to those of beta-LG, whereas the antibody response to each epitope was dramatically reduced. In particular, effective reduction of the antibody response was observed in the vicinity of the carbohydrate-binding sites. Conjugation of beta-LG with these acidic oligosaccharides was effective in reducing the immunogenicity of beta-LG. The conjugates obtained in this study are edible, so they would be very useful for food application.


[Surveillance of the course of 6030 surgical wounds].
This report describes a 4-year prospective study of post-operative wound infections, utilizing a program of wound surveillance. Surgical wounds after 6030 operations of a general surgery service were surveyed by the authors and a specialist nurse, daily, and in the follow-up clinic for 30 days. The rates of infections showed a decline over the years of surveillance. On the first year there was a 6.37 per cent incidence of infections, and the fourth year, of 4.7 per cent. This represented an improvement in hospitalization days and expenses.


[Infant bone quantity measurement. --Hoping for the growth of smooth bone].
As a method for measuring the bone mass of the children, we the measurement board for the measurement is improved so that the children may can be correspond ultrasonic wave bone density measuring apparatus CM100 made by FURUNO ELECTRIC Co., and the bone density of 11,418 pupils has been measured from 4 years old to 20 (male infants of 5,939 and female infants of 5,479) . And the evaluation system in each age is completed and we could put the ultrasonic wave measuring device on CM200. Then, it is proposed in order to hoping for the growth of the smooth bone of children in the developing time, and in order to utilize these measuring method and evaluations to the school education.


Fourier transform infrared imaging spectroscopic analysis of tissue engineered cartilage: histologic and biochemical correlations.
The composition of cartilage is predictive of its in vivo performance. Therefore, the ability to assess its primary macromolecular components, proteoglycan (PG) and collagen, is of great importance. In the current study, we hypothesized that PG content and distribution in tissue engineered cartilage could be determined using Fourier-transform infrared imaging spectroscopy (FT-IRIS). The cartilage was grown from chondrocytes within a hollow fiber bioreactor (HFBR) system previously used extensively to study cartilage development. FT-IRIS analysis showed a gradient of PG content, with the highest content in the center near the nutritive fibers and the lowest near the interior surface of the HFBR. Further, we found significantly greater PG content in the region near culture medium inflow (45.0%) as compared to the outflow region (24.7%) (p<0.001). This difference paralleled the biochemically determined glycosaminoglycan difference of 42.6% versus 27.8%. In addition, FT-IRIS-determined PG content at specific positions within the tissue sections correlated with histologically determined PG content (R=0.73, p=0.007). In summary, FT-IRIS determination of PG correlates with histological determination of PG and yields quantitatively similar results to biochemical determination of glycosaminoglycan in developing cartilage.


Human Clostridium difficile infection caused by a livestock-associated PCR ribotype 237 strain in Western Australia.
Clostridium difficile infection (CDI) is a significant gastrointestinal disease in the developed world and increasingly recognised as a zoonotic infection. In North America and Europe, the PCR ribotype (RT) 078 strain of C. difficile is commonly found in production animals and as a cause of disease in humans although proof of transmission from animals is lacking. This strain is absent in Australian livestock. We report a case of human CDI caused by a strain of C. difficile belonging to known Australian livestock-associated RT 237. A young male was admitted for multiple trauma following a motor vehicle accident and placed on piperacillin/tazobactam for pneumonia. After 4 days of treatment, he developed symptoms of CDI, which was confirmed in the laboratory. His symptoms resolved after 6 days of intravenous metronidazole. The strain of C. difficile isolated was identified as RT 237, an unusual RT previously found in with several Western Australia piggeries. This case of CDI caused by an unusual livestock-associated C. difficile RT 237 supports the hypothesis of zoonotic transmission. The case highlights the potential of livestock to act as reservoir for C. difficile and the need for continued surveillance of CDI in both human and animal populations.


Measurements of prolactin and androgens in patients with prostatic diseases.
Testosterone (T), dihydrostestosterone (DHT) and prolactin (HPr) levels were determined in normal males and females, in patients with benign prostatic hypertrophy (BPH) and in clinically stable patients with prostatic carcinoma (CAP), intact and orchiectomized. CAP patients were either untreated or on different modalities of therapy. The HPr levels were higher in prostatic cancer patients, in BPH patients, and in subjects on estrogen therapy. No significant differences were found between controls or patients treated with 5-Fu plus cytoxan. The T and DHT levels were decreased in all noncontrol subjects. The levels of DHT in intact, untreated CAP patients or those receiving 5-FU plus cytoxan were significantly higher than in BPH patients. Based on these observations, it appears that HPr could be involved with T and DHT in a feedback control role, especially in BPH. The alterations in these hormone levels in CAP treated or untreated patients are in marked contrast and must be evaluated further.


Sex Sorting for Pest Control: It's Raining Men!
In the pursuit of better pest- and vector-control strategies, attention returns to an old proven technology, the sterile insect technique (SIT) and related insect population-suppression methods. A major obstacle for any of these approaches that involves the release of sterile males is the separation of males from females during the mass rearing stage, in order to improve the cost-efficiency of these methods and to prevent the release of biting and disease-vectoring females. This review describes recent sex-sorting developments in dipteran flies with an emphasis on assessing the suitability of these methods for large-scale rearing of male vectors for mass release.


Visual analysis in single case experimental design studies: brief review and guidelines.
Visual analysis of graphic displays of data is a cornerstone of studies using a single case experimental design (SCED). Data are graphed for each participant during a study with trend, level, and stability of data assessed within and between conditions. Reliable interpretations of effects of an intervention are dependent on researchers' understanding and use of systematic procedures. The purpose of this paper is to provide readers with a rationale for visual analysis of data when using a SCED, a step-by-step guide for conducting a visual analysis of graphed data, as well as to highlight considerations for persons interested in using visual analysis to evaluate an intervention, especially the importance of collecting reliability data for dependent measures and fidelity of implementation of study procedures.


Early small-bowel ischemia: dual-energy CT improves conspicuity compared with conventional CT in a swine model.
To compare dual-energy computed tomography (CT) with conventional CT for the detection of small-bowel ischemia in an experimental animal model. The study was approved by the animal care and use committee and was performed in accordance with the Guide for Care and Use of Laboratory Animals issued by the National Research Council. Ischemic bowel segments (n = 8) were created in swine (n = 4) by means of surgical occlusion of distal mesenteric arteries and veins. Contrast material-enhanced dual-energy CT and conventional single-energy CT (120 kVp) sequences were performed during the portal venous phase with a single-source fast-switching dual-energy CT scanner. Attenuation values and contrast-to-noise ratios of ischemic and perfused segments on iodine material-density, monospectral dual-energy CT (51 keV, 65 keV, and 70 keV), and conventional 120-kVp CT images were compared. Linear mixed-effects models were used for comparisons. The attenuation difference between ischemic and perfused segments was significantly greater on dual-energy 51-keV CT images than on conventional 120-kVp CT images (mean difference, 91.7 HU vs 47.6 HU; P < .0001). Conspicuity of ischemic segments was significantly greater on dual-energy iodine material-density and 51-keV CT images than on 120-kVp CT images (mean contrast-to-noise ratios, 4.9, 4.3, and 2.1, respectively; P < .0001). Although attenuation differences on dual-energy 65- and 70-keV CT images were not significantly different from those on 120-kVp images (55.0 HU, 45.8 HU, and 47.6 HU, respectively; 65 keV vs 120 kVp, P = .15; 70 keV vs 120 kVp, P = .46), the contrast-to-noise ratio was greater for the 65- and 70-keV images than for the 120-kVp images (4.4, 4.1, and 2.1 respectively; P < .0005). Dual-energy CT significantly improved the conspicuity of the ischemic bowel compared with conventional CT by increasing attenuation differences between ischemic and perfused segments on low-kiloelectron volt and iodine material density images.


Dioxins and dioxin-like compounds in composts and digestates from European countries as determined by the in vitro bioassay and chemical analysis.
Aerobic composting and anaerobic digestion plays an important role in reduction of organic waste by transforming the waste into humus, which is an excellent soil conditioner. However, applications of chemical-contaminated composts on soils may have unwanted consequences such as accumulation of persistent compounds and their transfer into food chains. The present study investigated burden of composts and digestates collected in 16 European countries (88 samples) by the compounds causing dioxin-like effects as determined by use of an in vitro transactivation assay to quantify total concentrations of aryl hydrocarbon receptor-(AhR) mediated potency. Measured concentrations of 2,3,7,8-Tetrachlorodibeno-p-dioxin (2,3,7,8-TCDD) equivalents (TEQbio) were compared to concentrations of polycyclic aromatic hydrocarbons (PAHs) and selected chlorinated compounds, including polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs), co-planar polychlorinated biphenyls (PCBs), indicator PCB congeners and organochlorine pesticides (OCPs). Median concentrations of TEQbio (dioxin-like compounds) determined by the in vitro assay in crude extracts of various types of composts ranged from 0.05 to 1.2 with a maximum 8.22μg (TEQbio)kg(-1) dry mass. Potencies were mostly associated with less persistent compounds such as PAHs because treatment with sulfuric acid removed bioactivity from most samples. The pan-European investigation of contamination by organic contaminants showed generally good quality of the composts, the majority of which were in compliance with conservative limits applied in some countries. Results demonstrate performance and added value of rapid, inexpensive, effect-based monitoring, and points out the need to derive corresponding effect-based trigger values for the risk assessment of complex contaminated matrices such as composts.


Long-term outcomes after infant lung transplantation for surfactant protein B deficiency related to other causes of respiratory failure.
To determine if the outcomes of lung transplantation for infants with surfactant protein-B (SP-B) deficiency are unique. From a prospective analysis to identify infants with genetic causes of surfactant deficiency, we identified 33 SP-B-deficient infants from 1993 to 2005, and, among those undergoing lung transplantation (n = 13), compared their survival, pulmonary function, and developmental progress with infants who underwent transplantation at <1 year of age for parenchymal lung disease (n = 13) or pulmonary vascular disease (n = 11). Five-year survival rates ( approximately 50%, P = .3) and causes of death were similar for all three groups once the infants underwent transplantation. However, significant pretransplantation mortality decreased 5-year survival from listing to approximately 30% (P = .17). Pulmonary function, development of bronchiolitis obliterans, and school readiness were similar among the three groups. We detected anti SP-B antibody in serum of 3 of 7 SP-B-deficient infants and none of 7 SP-B-sufficient infants but could not identify any associated adverse outcomes. Long-term outcomes after infant lung transplantation for SP-B-deficient infants are similar to those of infants transplanted for other indications. These outcomes are important considerations in deciding to pursue lung transplantation for infants with disorders of alveolar homeostasis.


A sequence highly similar to PNG is located on chromosome 22q12 in intron 15 of the LIMK-2 gene.
In this report we describe a sequence (PNG22) highly similar to the Phospholipase C beta3 Neighboring Gene (PNG). We also report that PNG22 is located in the q12 region on chromosome 22 between markers D22S1144 and D22S280. This finding explains that PNG probes cross hybridize to sequences on chromosome 22. Fine mapping using our sequence data and the complete sequence of a PAC clone (DJ515N1), located in this region, determined that PNG22 is located in intron 15 of the LIMK-2 gene. PNG22 is 93% homologous to PNG, however it do not have the introns described for the PNG gene, instead matching the cDNA sequence. This leads us to suggest that PNG22 probably represents a PNG pseudogene. In this report we also list the exon intron borders and the genomic structure of LIMK-2 and place it on the Sanger Center chromosome 22 Physical map. It also explains the finding that PNG probes cross hybridize to sequences on chromosome 22.


Feasibility and safety of beta irradiation in human coronary arteries.
We have developed a technique of endoluminally centred endovascular beta irradiation aimed at preventing restenosis after PTCA. The source consists of a pure metallic 90-Yttrium coil that can be positioned within the lumen at the target site by the use of a centering device and an afterloading console. Experimental evaluation of this approach showed that a dose of 18 Gy delivered at the inner arterial surface was highly effective in preventing fibrointimal hyperplasia in rabbit carotid and iliac arteries. A pilot clinical evaluation in the coronary arteries of 15 patients using the same dose demonstrated excellent feasibility and no unexpected side-effects. A dose-finding evaluation in the clinical setting is now planned.


[On the road to understanding the phenomena of pharmacological electroencephalography].
In animal studies (outbred albino rats with different types of conflict behaviour, cottontail rats, inbred mice) it was established that the anxiolytic effects of benzodiazepine and atypical tranquilizers including buspirone are associated only with EEG theta-rhythm slowing. At the same time, anxiogenic drugs caused an increase in frequency of the theta-activity and (in large doses) increase of low-frequency spindles. These EEG-changes are close to the patterns of EEG induced by stress. These results suggest that increase in the beta-activity, especially, owing to high-frequency spindles, which has been reported to be a common feature of all tranquilizers, might be connected with adaptive mechanisms of the brain preventing from lesions by psychotropic drugs. It is possible that some abnormal EEG activity of epileptic humans and animals (spike-slow wave, spindles) also is a reflection of these adaptive mechanisms of the brain.


Stimulation of chondrocyte-mediated cartilage destruction by S100A8 in experimental murine arthritis.
To investigate whether S100A8 is actively involved in matrix metalloproteinase (MMP)-mediated chondrocyte activation. S100A8 and S100A9 proteins were detected in inflamed knee joints from mice with various forms of murine arthritis, using immunolocalization. Murine chondrocyte cell line H4 was stimulated with proinflammatory cytokines or recombinant S100A8. Messenger RNA (mRNA) and protein levels were measured using reverse transcriptase-polymerase chain reaction and intracellular fluorescence-activated cell sorting (FACS). Breakdown of aggrecan on the pericellular surface of the chondrocytes was measured using VDIPEN and NITEGE antibodies and FACS, and breakdown in patellar cartilage was measured by immunolocalization. S100A8 and S100A9 proteins were abundantly expressed in and around chondrocytes in inflamed knee joints after induction of antigen-induced arthritis or onset of spontaneous arthritis in interleukin-1 (IL-1) receptor antagonist-knockout mice. Stimulation of chondrocytes by the proinflammatory cytokines tumor necrosis factor alpha, IL-1beta, IL-17, and interferon-gamma caused strong up-regulation of S100A8 mRNA and protein levels and up-regulation to a lesser extent of S100A9 levels. Stimulation of chondrocytes with S100A8 induced significant up-regulation of MMP-2, MMP-3, MMP-9, MMP-13, ADAMTS-4, and ADAMTS-5 mRNA levels (up-regulated 4, 4, 3, 16, 8, and 4 times, respectively). VDIPEN and NITEGE neoepitopes were significantly elevated in a concentration-dependent manner in chondrocytes treated with 0.2, 1, or 5 microg/ml of S100A8. (VDIPEN levels were elevated 17%, 67%, and 108%, respectively, and NITEGE levels were elevated 8%, 33%, and 67%, respectively.) S100A8 significantly increased the effect of IL-1beta on MMP-3, MMP-13, and ADAMTS-5. Mouse patellae incubated with both IL-1beta and S100A8 had elevated levels of NITEGE within the cartilage matrix when compared with patellae incubated with IL-1beta or S100A8 alone. These findings indicate that S100A8 and S100A9 are found in and around chondrocytes in experimental arthritis. S100A8 up-regulates and activates MMPs and aggrecanase-mediated pericellular matrix degradation.


Case report of culture-negative endocarditis in lupus nephritis.
Cardiovascular involvement is frequent in systemic lupus erythematosus (SLE). Valvular abnormalities are increasingly being recognized with the advent of echocardiography. We present a case of a 46-year-old lady who presented to the emergency department with upper limb ischaemia. On examination, she had poor dentition and a short systolic murmur on auscultation. A blood workup revealed a diagnosis of SLE. Further investigations showed vegetations on the mitral valve. Initially, an infective endocarditis (IE) diagnosis was made, which was treated with antibiotics. High-dose steroids and immunosuppressants were initiated due to her clinical deterioration and biopsy-proven lupus nephritis. She improved clinically before being discharged home. It can be difficult to distinguish between IE and Libman-Sacks endocarditis (LSE), especially in the setting of risk factors for both. Antibiotics and immunosuppressants might be started simultaneously in these cases. A multidisciplinary team is required to manage challenging cases of culture-negative endocarditis. Procalcitonin may have a role in differentiating bacterial endocarditis and LSE.


Role of the parasympathetic system in airway obstruction due to emphysema.
To study the relative contributions of parasympathetic and sympathetic mechanisms in airway obstruction in patients with emphysema, we gave supramaximal doses of anticholinergic and adrenergic agents in sequence and in combination. Serial doses of one agent were administered to achieve a plateau of bronchodilatation; after that the other agent was administered. The plateau achieved with the anticholinergic agent (atropine methonitrate) was significantly higher than that achieved with the adrenergic agent (salbutamol). When the adrenergic agent was given first, additional bronchodilatation was achieved with subsequent use of the anticholinergic agent. When the anticholinergic agent was given first, no additional bronchodilatation was achieved with subsequent administration of the adrenergic agent. When both agents were given simultaneously, the degree of bronchodilatation was virtually identical to that obtained with the anticholinergic agent alone. Tests sensitive to small-airway and large-airway function and lung volumes gave essentially the same results. Thus, all achievable bronchodilatation was obtained with the anticholinergic agent alone. These results suggest that the two classes of agents produce bronchodilatation through a common cholinergic pathway in emphysema, and support the concept that parasympathetic activity is the dominant reversible component of airway obstruction in this disease.


[Acceptance of Care Offers for exclusive Remote Treatment Illustrated by the Telemedical Model Project "docdirekt" with a Mixed-Methods Design].
Current telemedical services, such as the "docdirekt" project in Baden-Württemberg (BW), are evaluated for optimizing their implementation. Based on the results of this evaluation, strategies for adapting these services for exclusive remote treatment are identified that enable their integration in regular medical care. In the first part of the study, citizens from BW were individually interviewed on their expectations regarding such a project, and the advantages and barriers in the use of services for exclusive remote treatment. Determinants were explored by means of Mayring's qualitative content analysis. In the second part of the study, these determinants were prioritized by using a quantitative survey of randomly selected citizens from BW. A total of 27 subjects (mean age 51 years, min: 23 years, max: 86 years) participated in the interviews. Most importantly, they found the direct accessibility of healthcare professionals a great advantage. A "24/7" hotline was found to be beneficial, as well as the possibility to get electronic prescriptions or medical sickness certificates. Privacy and a missing physical examination were perceived as barriers. In the questionnaire, the participants (n=217, return 10.9%, mean age: 53 years, min: 19 years, max: 88 years) rated a "direct medical contact" as the most important, followed by the "possibility to get a specialist" and to receive "a first therapy suggestion". In total, n=71 (34.6%) rejected the future use of such a service. The willingness to use the service decreased with increasing age and decreasing digital skills. The study shows that there is an interest in the use of services for exclusive remote treatment. People who intend to use telemedical service prioritize the fast-initial medical assessment and the comfort aspects and, among other things, consider the inclusion of additional services as beneficial. The next step is to incorporate these determinants into the existing telemedical service.


Twenty-year progression of body mass index in a county-wide cohort of people with schizophrenia and bipolar disorder identified at their first episode of psychosis.
There is an increased prevalence of obesity in schizophrenia and bipolar disorder, leading to a disproportionate risk of adverse health conditions. Prospective, long-term weight gain data, however, are scarce. We analyzed data from the Suffolk County Mental Health Project cohort of consecutive first admissions with psychosis recruited from September 1989 to December 1995 and subsequently followed for 20 years, focusing on people with schizophrenia (n=146) and bipolar disorder (n=87). The time course of weight gain was examined using a 2 (group)×5 (time) mixed-model repeated measures ANOVA, and body mass index (BMI) scores at the first (6 months) and second (2 years) assessments were compared to examine whether early overweight predicted later obesity. There was a statistically significant effect of time (F(1,210)=68.06, P<.001) and diagnosis (F(1,210)=29.18, P<.001) on BMI, but not the interaction of time×diagnosis (F(1,210)=0.88, P=.48). Most participants had normal BMIs at the first two assessments. Early overweight was a predictor of eventual obesity for both groups. At the 20-year follow-ups, approximately 50% of the bipolar and 62% of the schizophrenia sample were obese, with a greater prevalence of obesity in schizophrenia at each assessment (all P<.02), except for years 4 (P=.12) and 20 (P=.27). Nearly two-thirds of the participants with schizophrenia and over half of those with bipolar disorder were obese 20 years after first hospitalization for psychosis, considerably higher than the rate for adults in New York State (27%). Early intervention may be required to prevent long-term consequences of obesity-related morbidity and mortality.


Low-Temperature Storage Improves the Over-Time Stability of Implantable Glucose and Lactate Biosensors.
Molecular biomarkers are very important in biology, biotechnology and even in medicine, but it is quite hard to convert biology-related signals into measurable data. For this purpose, amperometric biosensors have proven to be particularly suitable because of their specificity and sensitivity. The operation and shelf stability of the biosensor are quite important features, and storage procedures therefore play an important role in preserving the performance of the biosensors. In the present study two different designs for both glucose and lactate biosensor, differing only in regards to the containment net, represented by polyurethane or glutharaldehyde, were studied under different storage conditions (+4, -20 and -80 °C) and monitored over a period of 120 days, in order to evaluate the variations of kinetic parameters, as VMAX and KM, and LRS as the analytical parameter. Surprisingly, the storage at -80 °C yielded the best results because of an unexpected and, most of all, long-lasting increase of VMAX and LRS, denoting an interesting improvement in enzyme performances and stability over time. The present study aimed to also evaluate the impact of a short-period storage in dry ice on biosensor performances, in order to simulate a hypothetical preparation-conservation-shipment condition.


Flexible Inorganic All-Solid-State Electrochromic Devices toward Visual Energy Storage and Two-Dimensional Color Tunability.
Multicolor display has gradually become a sought-after trend for electrochromic devices due to its broadened application scope. Meanwhile, the advantages of inorganic electrochromic devices such as stable electrochemical performance and good energy storage ability also have great attraction in practical production applications. However, there are still huge challenges for inorganic electrochromic materials to achieve multicolor transformation due to their single-color hue change. Herein, we design an inorganic and multicolor electrochromic energy storage device (MEESD) exhibiting flexibility and all-solid-state merits. Prussian blue (PB) and MnO2, as the asymmetrical electrodes of this MEESD, show good pseudocapacitance property, matching charge capacity, and obvious color change. As a typical electrochromic device, the MEESD shows a fast response of 0.5 s and good coloration efficiency of 144.2 cm2/C. As an energy storage device, the MEESD presents excellent rate capability and volumetric energy/power density (84.2 mWh cm-3/23.3 W cm-3). Its energy level can be visually monitored by color contrast and optical modulation. In the charging/discharging process, its color can obviously change to various degrees of yellow, green, and blue along with 40% wide optical modulation at 710 nm. Meanwhile, the stability of the MEESD in a common and humidity environment was analyzed in detail from electrochemical, optical, and energy storage aspects. This work provides feasible thoughts to design multifunctional electrochromic devices integrated with inorganic, flexible, all-solid-state, multicolor, and energy storage properties.


Fitness in a U.K. screening sample--a comparison with the Canadian population.
Fitness measurements were compared from approximately 12,000 men and 5,000 women attending the BUPA Health Screening Centre, London, with published Canadian levels. The mean (+/- SD) predicted VO2-max values in the BUPA group were 35.1 (+/- 9.2) and 30.0 (+/- 8.4) ml/kg/min for men and women aged 15-64 years, respectively. These compare with means of 44.1 and 34.3 in men and women of the same age in Canada. A comparison of flexibility measurements showed that in all age groups the BUPA subjects were less flexible than their Canadian counterparts, on average 28.7% and 25.1% lower for men and women, respectively. Comparison of grip strength showed BUPA values to be on average 8.1% lower in men and 9.5% lower in women than the Canadian levels. Analysis of variance showed that the fitness measurements reflect the recorded physical activity in the BUPA sample, and in particular the predicted VO2-max and flexibility exhibit linear relationships with age and exercise levels.


Japanese Biliary Atresia Registry, 1989 to 1994.
The Japanese Biliary Atresia Society founded in 1980 for the aim of investigations of all aspects of biliary atresia (BA), started a nationwide registry of BA patients in 1989. A total of 626 cases were registered from 1989 to 1994. The male to female ratio was 0.58. Corrective surgery was performed in 603 patients. Regarding the type of obstruction, 63 cases were Type I, atresia of the common bile duct, 9 were Type II, atresia of the hepatic ducts, and 543 were Type III, atresia of the porta hepatis. As initial corrective procedures, original Roux-en Y, Suruga II and Roux-en Y with intestinal valve were mainly employed. Jaundice cleared in 346 patients (57%) and decreased in 131, while it persisted in 120. The 5-year-follow-up showed that 34 patients, 49% of the patients who were followed up, were alive without jaundice, while 28 (41%) are dead. Thirty five, 33% of the patients who were entered to the Registry, were lost to follow-up.


Comparison of Click and Level-Specific (LS) CE Chirp-Stimulated Auditory Brainstem Responses in Adults with Hearing Loss.
Background The CE-Chirp stimulus used in the ABR was developed to compensate for the cochlear wave delay. As a version of broadband CE-Chirp stimulus, the use of level-specific (LS) CE-Chirp stimuli, which are created with varying delay models suitable for the intensity levels at which the sound is transmitted, is becoming increasingly common. Purpose The aim of this study was to compare click auditory brainstem responses (ABRs) with LS CE-Chirp ABR thresholds in adults with sensorineural hearing loss. Research Design The research is a cross-sectional-analytical research. Study Sample Twenty-two adult patients (n = 44 ears) with bilateral sensorineural hearing loss were included in the study. Data Collection and Analysis Pure Tone Audiometry (PTA), click ABR and LS CE-Chirp ABR tests were performed on adult (13 male, 9 female) (42.86± 14.50 years) patients with bilateral sensorineural hearing loss. Click ABR and LS CE-Chirp ABR thresholds were compared in terms of proximity to behavioral hearing thresholds of 2 kHz, 4 kHz, and 2-4 kHz averages. Results: Both types of ABR stimuli were able to identify with total hearing loss (n = 6). A statistically significant difference was found between LS CE-Chirp ABR thresholds (53.81±20.28 dB nHL) and click ABR thresholds (58.81±19.11 dB nHL) in the other ears (n = 38) with hearing loss (p=0.00). When both ears were evaluated together and the right and left ears were evaluated separately, no difference was found between LS CE-Chirp ABR thresholds and 4 kHz behavioral hearing thresholds (p: 0.66, p:0.80, p: 0.69, respectively). Conclusion: We determined that in adults with hearing loss, the LS CE-Chirp provides ABR thresholds closer to the behavioral hearing thresholds of 2 kHz, 4 kHz compared to the click stimulus. Notably, there was no difference between LS CE-Chirp ABR thresholds and the 4 kHz behavioral hearing thresholds. We concluded that the LS CE-Chirp stimulus can be used effectively in the estimation of behavioral hearing thresholds in adults with hearing loss Keywords: Auditory Brainstem Response, Hearing loss, Click, Level specific CE-Chirp.


Framing life and death on YouTube: the strategic communication of organ donation messages by organ procurement organizations.
Using a sample of YouTube videos posted on the YouTube channels of organ procurement organizations, a content analysis was conducted to identify the frames used to strategically communicate prodonation messages. A total of 377 videos were coded for general characteristics, format, speaker characteristics, organs discussed, structure, problem definition, and treatment. Principal components analysis identified message frames, and k-means cluster analysis established distinct groupings of videos on the basis of the strength of their relationship to message frames. Analysis of these frames and clusters found that organ procurement organizations present multiple, and sometimes competing, video types and message frames on YouTube. This study serves as important formative research that will inform future studies to measure the effectiveness of the distinct message frames and clusters identified.


Identification and Functional Characterization of a Novel Variant in the SEMA3A Gene in a Chinese Family with Kallmann Syndrome.
Kallmann syndrome (KS) is a rare genetic disease characterized by the reproductive system and olfactory dysplasia due to the defective migration of gonadotropin-releasing hormone (GnRH) neurons. However, this disorder is clinically heterogeneous and the genotype-phenotype relationship has not been determined. The present study aimed to identify the variant causing KS in a Chinese family and evaluate the functional consequences and phenotypes associated with the novel variant. A Chinese family with KS was screened for pathogenic variants by whole-exome sequencing (WES). Bioinformatic analysis was performed to predict the consequences of the identified variant. The expression of the mutant protein was examined in vitro. A novel heterozygous variant (NM_006080.2 : c.814G > T) in SEMA3A was identified in the patient and his father, which caused the substitution of aspartic acid with tyrosine in codon 272. It was predicted to result in pathogenic significance with a high damaging score and seriously affect protein structure by bioinformatic analysis. In vitro experiments revealed this variant could significantly decrease the expression of SEMA3A. Furthermore, it may cause the disease by failing to induce the phosphorylation of focal adhesion kinase (FAK) in GnRH neurons. Identification and functional characterization of this novel variant in the SEMA3A gene in a Chinese family with Kallmann syndrome extend the genetic variant spectrum of SEMA3A and provide more data about the heterogeneity of KS, which may provide further insights into the diagnosis of KS and help patients get additional data in genetic counseling and timely treatment.


The different dosages of estrogen affect endometrial fibrosis and receptivity, but not SDF-1/CXCR4 axis in the treatment of intrauterine adhesions.
The study was to evaluate whether fibrotic markers, endometrial receptivity markers and SDF-1/CXCR4 had been changed in the treatment of intrauterine adhesions (IUAs) by different dosages of estrogen. A total of 39 patients with IUAs were treated with EV 4 mg or 9 mg randomly post-surgery. TGF-β1/MMP-9, VEGF/αvβ3 and SDF-1/CXCR4 were detected in endometrial tissue before and after treatment by real-time PCR and Western blot. TGF-β1 and MMP-9 expression significantly decreased after treatment for 3 months than before (p < .05), the falling range was larger with EV 4 mg than 9 mg in the mild-moderate degree IUAs (p < .05); Integrin avβ3 expression significantly increased after treatment for 3 months than before (p < .05), the variation range was larger with EV 4 mg than 9 mg (p < .05); CXCR4 expression had no significant change after treatment 3 months compared to that before treatment (p > .05). SDF-1 presented an upward tendency at early phase, and it came back to the level of pre-surgery. But there were no significant difference between treatment with 4 mg and 9 mg in the rate of menstrual restoration and pregnancy follow-up 3 months after the treatment. Endometrium fibrosis may be inhibited and endometrium receptivity may be improved by estrogen with moderate dosage therapy. Compared to the large one, it seems to be advantageous.


Human T-cell lymphotropic virus type 1 infection and ocular manifestations in São Paulo, Brazil.
Although human T-cell lymphotropic virus type 1 (HTLV-1)-associated uveitis has been well recognized in Japan, related studies in Brazil are scarce. We performed a serologic survey for HTLV-1 infection among patients with uveitis and investigated the ocular findings in HTLV-1-asymptomatic carriers. One hundred ninety serum samples from patients with uveitis of determined (n = 137) and undetermined origins (n = 53) being examined at the Uveitis Service, University of São Paulo, São Paulo, Brazil, underwent testing using HTLV enzyme-linked immunosorbent assay and discriminatory Western blots. One hundred five asymptomatic blood donors and/or their relatives who were seropositive for HTLV-1 (carrier group) and 105 age- and sex-paired blood donors who were seronegative for HTLV-1 (control group) underwent ocular evaluation. For the statistical analysis, chi2 test was used. Only 1 patient with uveitis was seropositive for HTLV- 1, and she belonged to the group with uveitis of undetermined origin. Results of tear films were evaluated in 52 carriers. The prevalence of a decreased tear break-up time was significantly higher in the carrier compared with the control group (P = .02). Two carriers had keratoconjunctivitis sicca. Three of the 105 carriers exhibited mild uveitis (cells in the vitreous, retinal and choroidal infiltrates, retinal vasculitis, and bilateral pars planitis). Retinal pigmentary changes were found in both groups (no statistical difference). Early tear abnormalities may be present in asymptomatic carriers, and mild uveitis may be found among them. The relatively low seroprevalence of HTLV-1 in the Brazilian population made it difficult to establish the real importance of HTLV-1-associated uveitis among our patients with uveitis.


Medical expertise, existential suffering and ending life.
In this article, I assess the position that voluntary euthanasia (VE) and physician-assisted suicide (PAS) ought not to be accepted in the cases of persons who suffer existentially but who have no medical condition, because existential questions do not fall within the domain of physicians' professional expertise. I maintain that VE and PAS based on suffering arising from medical conditions involves existential issues relevantly similar to those confronted in connection with existential suffering. On that basis I conclude that if VE and PAS based on suffering arising from medical conditions is taken to fall within the domain of medical expertise, it is not consistent to use the view that physicians' professional expertise does not extend to existential questions as a reason for denying requests for VE and PAS from persons who suffer existentially but have no medical condition.


Bone mineral status in childhood accidental fractures.
We studied the bone mineral and calcium (Ca) status of 17 children who suffered an accidental fracture in 1980. These children were matched by age and sex to a nonfractured control group. Blood was drawn for serum Ca, phosphorus, magnesium, 25-hydroxycholecalciferol ( calcidiol ), alkaline phosphatase, and albumin. Bone mineral content (BMC) was evaluated by photon absorptiometry. There were no differences in serum values between the two groups. Twelve (71%) of the 17 children in the fracture group had a lower BMC than their matched controls. The BMC of the fracture group was lower than their controls, 0.423 +/- 0.042 v 0.461 +/- 0.037 g/cm. Four of the 15 in the fracture group ingested less than 60% of the recommended dietary allowance (RDA) for Ca and P (800 mg/day), while all the controls were ingesting at least 60% of the RDA. Four children of the fracture group who were ingesting less Ca and P than those of the control group also had low BMC.


Implication of human telomerase reverse transcriptase in cervical carcinogenesis and cancer recurrence.
The objective of this study was to evaluate the implication of human telomerase reverse transcriptase (hTERT) in cervical carcinogenesis and cancer recurrence. One hundred three cases of uterine cervix, including 20 normal, 13 low-grade squamous intraepithelial lesion (LSIL), 30 high-grade squamous intraepithelial lesion (HSIL), and 40 squamous cell carcinoma (SCC) tissues, were evaluated for hTERT immunoreactivity. The expressions of hTERT in normal, LSIL, HSIL, and SCC tissues were compared by Fisher exact or Chi-square test. The relationships between hTERT and clinicopathologic variables of SCC were also assessed. Furthermore, SCC patients were subdivided into negative and positive hTERT expression subgroups, and Kaplan-Meier curves were used to plot the cumulative recurrence hazard for 5 years. There was a significant difference for hTERT expression between LSIL and HSIL subgroups (P < 0.001) but no significant difference between normal and LSIL as well as HSIL and SCC subgroups. For SCC patients, hTERT expression was positive in lymph nodes, vagina, and parametrium metastastic cases. However, it did not reach a significant difference. The cumulative recurrence hazard for 5 years was about 29% in positive hTERT expression subgroup compared to 0% in negative hTERT subgroup (P = 0.2866). In conclusion, a point stage of HSIL exists in the progression of cervical carcinogenesis when the hTERT expression increases significantly. Moreover, SCC patients with positive hTERT expression may have higher cumulative recurrence hazard.


The ICL1 gene of Pichia pastoris, transcriptional regulation and use of its promoter.
We cloned and characterized a gene encoding isocitrate lyase from the methylotrophic yeast Pichia pastoris. This gene was isolated from a P. pastoris genomic library using a homologous PCR hybridization probe, amplified with two sets of degenerate primers designed from conserved regions in yeast isocitrate lyases. The cloned gene was sequenced and consists of an open reading frame of 1563 bp encoding a protein of 551 amino acids. The molecular mass of the protein is calculated to be 60.6 kDa with high sequence similarity to isocitrate lyase from other organisms. There is a 64% identity between amino acid sequences of P. pastoris Icl and Saccharomyces cerevisiae Icl. Northern blot analyses showed that, as in S. cerevisiae, the steady-state ICL1 mRNA levels depend on the carbon source used for cell growth. Expression in P. pastoris of the dextranase gene (dexA) from Penicillium minioluteum under control of the ICL1 promoter proved that P(ICL1) is a good alternative for the expression of heterologous proteins in this methylotrophic yeast. The sequence presented here has been deposited in the EMBL data library under Accession No. AJ272040.


Auditory hair cell-specific deletion of p27Kip1 in postnatal mice promotes cell-autonomous generation of new hair cells and normal hearing.
Hearing in mammals relies upon the transduction of sound by hair cells (HCs) in the organ of Corti within the cochlea of the inner ear. Sensorineural hearing loss is a widespread and permanent disability due largely to a lack of HC regeneration in mammals. Recent studies suggest that targeting the retinoblastoma (Rb)/E2F pathway can elicit proliferation of auditory HCs. However, previous attempts to induce HC proliferation in this manner have resulted in abnormal cochlear morphology, HC death, and hearing loss. Here we show that cochlear HCs readily proliferate and survive following neonatal, HC-specific, conditional knock-out of p27(Kip1) (p27CKO), a tumor suppressor upstream of Rb. Indeed, HC-specific p27CKO results in proliferation of these cells without the upregulation of the supporting cell or progenitor cell proteins, Prox1 or Sox2, suggesting that they remain HCs. Furthermore, p27CKO leads to a significant addition of postnatally derived HCs that express characteristic synaptic and stereociliary markers and survive to adulthood, although a portion of the newly derived inner HCs exhibit cytocauds and lack VGlut3 expression. Despite this, p27CKO mice exhibit normal hearing as measured by evoked auditory brainstem responses, which suggests that the newly generated HCs may contribute to, or at least do not greatly detract from, function. These results show that p27(Kip1) actively maintains HC quiescence in postnatal mice, and suggest that inhibition of p27(Kip1) in residual HCs represents a potential strategy for cell-autonomous auditory HC regeneration.


The past, present and future of cystoscopy: the fusion of cystoscopy and novel imaging technology.
Non-muscle-invasive bladder cancer is a frequent disease with many recurrences, making it a labour-intensive and costly disease. In part, these frequent recurrences are due to inadequate diagnosis. Diagnostic reference standards to date are urinary cytology and cysto-urethroscopy, but both standards have significant limitations. Urinary cytology is specific, but the sensitivity, especially for low-grade tumours, is very low. Moreover, the reproducibility of cytology is low. However, cysto-urethroscopy misses many tumours, especially flat carcinoma in situ, causing flaws in the initial diagnosis and treatment, i.e. transurethral resection. Therefore, new techniques are necessary to improve the detection of bladder cancer. Here we review the advantage and disadvantage of conventional white-light and fluorescence-based cystoscopy, and discuss novel endoscopic imaging techniques that are in the clinical and preclinical stage of development.