Role of epigenetic alterations in the pathogenesis of Barrett's esophagus and esophageal adenocarcinoma.
Barrett's esophagus, a pre-malignant condition that can lead to esophageal adenocarcinoma, is characterized by histological changes in the normal squamous epithelium of the esophagus. Numerous molecular changes occur during the multistage conversion of Barrett's metaplasia to dysplasia and frank adenocarcinoma. Epigenetic changes, especially changes in DNA methylation are widespread during this process. Aberrant DNA methylation has been shown to occur at promoters of tumor suppressor genes, adhesion molecules and DNA repair genes during Barrett's esophagus. These epigenetic alterations can be used as molecular biomarkers for risk stratification and early detection of esophageal adenocarcinoma. We also show that genome wide analysis of methylation surprisingly reveals that global hypomethylation and not hypermethylation is the dominant change during Barrett's metaplasia. The transformation of Barrett's esophagus to frank adenocarcinoma is in turn characterized by much smaller wave of selective promoter hypermethylation. These studies reveal many novel, potential targets for new therapies and illustrate the utility of incorporating these epigenetic changes as biomarkers during endoscopic surveillance interval for patients with Barrett's esophagus.


Tailoring a dissonance-based body image intervention for adult women in a proof of concept trial: The Women's Body Initiative.
Although historically conceptualized as problems of youth, recent research indicates that women of all ages experience body dissatisfaction and eating disorder (ED) pathology. Despite this, existing body image interventions predominantly target youth. The Body Project (BP) has extensive support for reducing ED risk factors in younger women and girls. The current proof-of-concept study investigated the feasibility, acceptability, and estimates of intervention effect sizes of a modified BP for adult women, the Women's Body Initiative (WBI). Conducted in the Southwestern United States, adult women (N = 13) aged 29-70 (M = 49.1) participated in 4, 1-h weekly sessions, completing measures at baseline, post-intervention, and 3-month follow-up. Participants rated the program as highly feasible and acceptable. Within-subjects effects sizes were medium to large for primary outcomes (body dissatisfaction, ED pathology) and secondary outcomes (psychosocial impairment, negative affect, quality of life, nutritious food consumption, and sleep) through 3-months. Results suggest preliminary feasibility and acceptability of WBI for adult women, and support proceeding with a larger trial to investigate intervention efficacy.


[Analysis of the role of presynaptic adrenoreceptors in adrenergic synaptic transmission].
A mathematical model quantitatively describing the value of secreted mediator per each successive impulse in the series of presynaptic impulses is presented. The model is plotted with the account taken of the role of presynaptic adrenoreceptors regulating noradrenaline secretion. It has been shown that a decrease observed in neurophysiological experiments and further stabilization of postsynaptic responses in the series of presynaptic impulses of given frequency are not connected with a decreased content of noradrenaline in nerve endings, but may be connected with the work of presynaptic alpha and beta adrenoreceptors.


Natural flavonoids as promising 6-phosphogluconate dehydrogenase inhibitor candidates: In silico and in vitro assessments.
The primary strategy in the fight against cancer is to screen compounds that may be effective on different types of cancer. Compounds from plants seem to be a good source. The present study investigated the inhibitory effects of some flavonoids on the 6-phosphogluconate dehydrogenase (6-PGD) enzyme. We determined that quercetin, myricetin, fisetin, morin, apigenin, and baicalein exhibited powerful inhibition effects with IC50 values between 4.08 and 21.26 µM, while luteolin, kaempferol, apiin, galangin, and baicalin showed moderate effects with IC50 values between 54.15 and 138.91 µM. Quercetin competitively inhibited the binding of NADP and 6-phosphogluconate to the 6-PGD enzyme with Ki values of 0.527 ± 0.251 and 0.374 ± 0.138 µM, respectively. We calculated Ki values using the Cheng-Prusoff equation as between 0.44 and 14.88 µM. The possible interaction details of polyphenols with the active site of 6-PGD were analyzed with docking software. In silico and in vitro studies indicated that the -OH groups on the A and C ring of flavonoids bind to the enzyme's active site via hydrogen bonding, while the -OH groups on the C ring contributed significantly to the increase in the inhibitory potentials of the molecules. Molecular dynamic simulations tested the stability of the 6-PGD-quercetin complex during 100 ns. These phytochemicals were suitable for drug use when optimized with absorption, distribution, metabolism, excretion, and toxicity (ADMET) criteria. The effects of the studied compounds on cancer cell lines of potential targets were demonstrated by network analysis. In conclusion, this study suggests that flavonoids found to be potent inhibitors could serve as leading candidates to treat many cancers via 6-PGD inhibition.


Transient receptor potential vanilloid type 1 channel (TRPV1) immunolocalization in the murine enteric nervous system is affected by the targeted C-terminal epitope of the applied antibody.
The expression of transient receptor potential vanilloid type 1 channel (TRPV1) in the enteric nervous system is still the subject of debate. Although a number of studies have reported that TRPV1 is limited to extrinsic afferent fibers, other studies argue for an intrinsic expression of TRPV1. In the present study, reverse transcriptase PCR was employed to establish the expression of TRPV1 mRNA throughout the gastrointestinal tract. Using two antibodies directed against different epitopes of TRPV1, we were able to show at the protein level that the observed distribution pattern of TRPV1 is dependent on the antibody used in the immunohistochemical staining. A first antibody indeed mainly stained neuronal fibers, whereas a second antibody exclusively stained perikarya of enteric neurons throughout the mouse gastrointestinal tract. We argue that these different distribution patterns are due to the antibodies discriminating between different modulated forms of TRPV1 that influence the recognition of the targeted immunogen and as such distinguish intracellular from plasmalemmal forms of TRPV1. Our study is the first to directly compare these two antibodies within the same species and in identical conditions. Our observations underline that detailed knowledge of the epitope that is recognized by the antibodies employed in immunohistochemical procedures is a prerequisite for correctly interpreting experimental results.


Biological evaluation of both enantiomers of fluoro-thalidomide using human myeloma cell line H929 and others.
Over the last few years, thalidomide has become one of the most important anti-tumour drugs for the treatment of relapsed-refractory multiple myeloma. However, besides its undesirable teratogenic side effect, its configurational instability critically limits any further therapeutic improvements of this drug. In 1999, we developed fluoro-thalidomide which is a bioisostere of thalidomide, but, in sharp contrast to the latter, it is configurationally stable and readily available in both enantiomeric forms. The biological activity of fluoro-thalidomide however, still remains virtually unstudied, with the exception that fluoro-thalidomide is not teratogenic. Herein, we report the first biological evaluation of fluoro-thalidomide in racemic and in both (R)- and (S)-enantiomerically pure forms against (in vitro) H929 cells of multiple myeloma (MM) using an annexin V assay. We demonstrate that all fluoro-thalidomides inhibited the growth of H929 MM cells without any in-vivo activation. Furthermore, we report that the enantiomeric forms of fluoro-thalidomide display different anti-tumour activities, with the (S)-enantiomer being noticeably more potent. The angiogenesis of fluoro-thalidomides is also investigated and compared to thalidomide. The data obtained in this study paves the way towards novel pharmaceutical research on fluoro-thalidomides.


[Isolation and study of the biological properties of substances stimulating levorin biosynthesis in a mixed actinomycete and yeast culture].
Active components responsible for increased synthesis levels of levorin, a polyenic antibiotic in mixed cultures of an actinomycete and a yeast-like fungus C. tropicalis were isolated from the fermentation broth. Component I identified as succinic acid increased the levels of the antibiotic production by 40-50 per cent. Component II found to be lactic acid increased the antibiotic production levels by 20 per cent. Component III, a mixture of nonidentified substances of the amine nature stimulated biosynthesis of levorin by 20-25 per cent. Addition of a mixture of succinic acid and N-methyl glucosamine to the nutrient medium provided increase of the antibiotic activity of the fermentation broth up to 175-185 per cent as compared to the control.


[Immunological aspects of circulating immune complexes in kidney diseases in patients with chronic alcoholism].
Characterization of the content and features of circulating immune complexes (CIC) in chronic alcoholics with renal diseases. Quantitative and qualitative characteristics of CIC, RNA and DNA levels in CIC were studied in 58 patients suffering from chronic alcoholism stage II. The patients had the history of 10 and more years of alcohol abuse, exhibited symptoms of chronic renal affection with clinical picture of chronic glomerulonephritis. Glomerulonephritis in chronic alcoholics was accompanied with higher CIC, CIC IgM and IgA levels compared to healthy subjects and non-alcoholics with glomerulonephritis. Alcoholics had also higher DNA and CIC DNA. Quantitative and qualitative assessment of CIC in chronic alcoholics with renal disease provide information valuable for the disease diagnosis and prognosis.


Terrestrial discharges mediate trophic shifts and enhance methylmercury accumulation in estuarine biota.
The input of mercury (Hg) to ecosystems is estimated to have increased two- to fivefold during the industrial era, and Hg accumulates in aquatic biota as neurotoxic methylmercury (MeHg). Escalating anthropogenic land use and climate change are expected to alter the input rates of terrestrial natural organic matter (NOM) and nutrients to aquatic ecosystems. For example, climate change has been projected to induce 10 to 50% runoff increases for large coastal regions globally. A major knowledge gap is the potential effects on MeHg exposure to biota following these ecosystem changes. We monitored the fate of five enriched Hg isotope tracers added to mesocosm scale estuarine model ecosystems subjected to varying loading rates of nutrients and terrestrial NOM. We demonstrate that increased terrestrial NOM input to the pelagic zone can enhance the MeHg bioaccumulation factor in zooplankton by a factor of 2 to 7 by inducing a shift in the pelagic food web from autotrophic to heterotrophic. The terrestrial NOM input also enhanced the retention of MeHg in the water column by up to a factor of 2, resulting in further increased MeHg exposure to pelagic biota. Using mercury mass balance calculations, we predict that MeHg concentration in zooplankton can increase by a factor of 3 to 6 in coastal areas following scenarios with 15 to 30% increased terrestrial runoff. The results demonstrate the importance of incorporating the impact of climate-induced changes in food web structure on MeHg bioaccumulation in future biogeochemical cycling models and risk assessments of Hg.


Effects of combined traditional Chinese medicine therapy in patients of lower limbs injuries with osteoporosis: A retrospective paired cohort study.
Studies have confirmed that the health hazards of patients with lower limb injuries combined with osteoporosis are more obvious. This study is mainly based on the Taiwan National Health Insurance Database, and through big data analysis, it shows that the combined treatment of traditional Chinese medicine (TCM) is helpful to the health of patients with lower limb injuries combined with osteoporosis. A total of 9989 combined TCM-treated patients and 19,978 2:1 sex-, age-, and index-year-matched controls who did not receive TCM treatment were selected from the Taiwan National Health Insurance Database. Cox proportional hazards analyzes were performed to compare fracture surgery, inpatient, and all-cause mortality during a mean follow-up period of 17 years. A total of 5406/8601/2564 enrolled-subjects (14.11%/25.46%/5.53%) had fracture surgery/inpatient/all-cause mortality, including 1409/2543/552 in the combined TCM group (14.11%/25.46%/5.53%) and 3997/6058/2012 in the control group (20.01%/30.32%/10.07%). Cox proportional hazard regression analysis showed a lower rate of fracture surgery, inpatient and all-cause mortality for subjects in the combined TCM group (adjusted hazard ratios [HR] = 0.723; 95% confidence intervals [CI] = 0.604-0.810, P < .001; adjusted hazard ratios [HR] = 0.803; 95% CI = 0.712-0.950, P = .001; adjusted HR = 0.842; 95% CI = 0.731-0.953, P = .007, respectively). After 10 years of follow-up, the cumulative incidence of fracture surgery in patients combining TCM treatment seems to be half of that without combining TCM treatment those are shown in Kaplan-Meier analysis with statistically significant (log rank, P < .001, P < .001, and P = .010, respectively). This study hopes to provide clinicians with the option of combined TCM treatment for patients of lower limbs injuries combined with osteoporosis, so that such patients will be associate with a lower risk of fracture surgery, inpatient or all-cause mortality.


Force control in chronic stroke.
Force control deficits are common dysfunctions after a stroke. This review concentrates on various force control variables associated with motor impairments and suggests new approaches to quantifying force control production and modulation. Moreover, related neurophysiological mechanisms were addressed to determine variables that affect force control capabilities. Typically, post stroke force control impairments include: (a) decreased force magnitude and asymmetrical forces between hands, (b) higher task error, (c) greater force variability, (d) increased force regularity, and (e) greater time-lag between muscular forces. Recent advances in force control analyses post stroke indicated less bimanual motor synergies and impaired low-force frequency structure. Brain imaging studies demonstrate possible neurophysiological mechanisms underlying force control impairments: (a) decreased activation in motor areas of the ipsilesional hemisphere, (b) increased activation in secondary motor areas between hemispheres, (c) cerebellum involvement, and (d) relatively greater interhemispheric inhibition from the contralesional hemisphere. Consistent with identifying neurophysiological mechanisms, analyzing bimanual motor synergies as well as low-force frequency structure will advance our understanding of post stroke force control.


Risk of second primary breast cancer among cancer survivors: Implications for prevention and screening practice.
Second primary breast cancer (SPBC) is becoming one of the major obstacles to breast cancer (BC) control. This study was aimed to determine the trend of SPBC incidence over time and the risk of developing SPBC in site-specific primary cancer survivors in the United States. The Surveillance, Epidemiology, and End Results (SEER) 13 registry (1992-2015) was used to identify SPBC patients with previous malignancies. Standardized incidence ratio (SIR) was computed to compare the incidence rates of the observed cases of SPBC in cancer survivors over the expected cases in the general population. Elevated risk of SPBC was observed in women with previous BC (SIR = 1.74) or thyroid cancer (SIR = 1.17). Women with initial skin melanoma in older age (≥50 years) (SIR = 1.11), or White race (SIR = 1.11) presented an elevated incidence of SPBC than the general female population. Besides, Asian/Pacific Islander (API) women with cancer of corpus uteri, ovary, bladder, or kidney were prone to developing SPBC when compared with the general population, with SIRs of 1.61, 1.35, 1.48, and 1.70, respectively. Male BC patients showed profound risk of developing SPBC (SIR = 34.86). Male leukemia patients also presented elevated risk of developing SPBC (SIR = 2.06). Our study suggests significant increase of SPBC in both sexes in the United States. Elevated risk of SPBC exists in survivors with primary BC, female thyroid cancer, male leukemia, and API female cancer patients with primary genitourinary cancer. Our study is helpful in developing strategies for BC control and prevention on specific first primary cancer survivors with an elevated risk of SPBC.


Choroidal Patterns in Retinitis Pigmentosa: Correlation with Visual Acuity and Disease Progression.
The main aim was to identify different choroidal patterns in retinitis pigmentosa (RP) and to assess their clinical and anatomical meanings after 1 year of follow-up. Forty-five patients with RP (29 men; mean age 44.5 ± 11.7 years) and 45 healthy controls (29 men; mean age 44.2 ± 9.8 years) were recruited. Optical coherence tomography (OCT) and OCT angiography (OCTA) images were obtained. By means of structural OCT, the following three choroidal patterns were identified: normal-appearing choroid (pattern 1), reduced Haller and Sattler layers (pattern 2), and pattern 2 + choroidal caverns (pattern 3). Main outcome measures were best-corrected visual acuity (BCVA), central macular thickness (CMT), choroidal thickness (CT), vessel density, vessel tortuosity, vessel dispersion, vessel rarefaction, and choroidal stromal index (CSI). Mean BCVA was 0.27 ± 0.30 LogMAR for patients with RP and 0.0 ± 0.0 LogMAR for controls (P < 0.01). CMT, CT, CSI, and OCTA parameters were statistically different between patients with RP and controls (P < 0.01). Choroidal patterns 1, 2, and 3 were identified in 20 (44%), 15 (33%), and 10 (23%) patients with RP, respectively. Several statistically significant correlations were also found. Interestingly, after 1 year of follow-up, only the pattern 3 subgroup showed significant worsening of BCVA, CMT, and OCTA parameters (P < 0.01). Choroidal patterns were associated with different RP clinical forms as well as with different progression after 1 year. Choroidal patterns evaluation may provide useful clinical information for patients with RP.


Carbaryl, a carbamate insecticide, is a ligand for the hepatic Ah (dioxin) receptor.
The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that mediates many of the biological and toxicological actions of a variety of hydrophobic natural and synthetic chemicals, including the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin). Induction of CYP1A1 gene expression is one such response that is known to be regulated by the AhR complex. It was recently reported (Ledirac et al., Toxicol. Appl. Pharmacol. 144, 177-182, 1997) that, although carbaryl, a carbamate insecticide, can induce AhR-dependent expression of CYP1A1, it was not an AhR ligand. Since this apparent ligand-independent activation of the AhR is difficult to reconcile given what is known about the mechanism of AhR action, we have examined the ability of carbaryl to stimulate the AhR signaling pathway. Not only was dioxin responsive element-driven luciferase gene expression induced by carbaryl in stably transfected mouse, rat, guinea pig, and human cells, gel retardation analysis revealed that carbaryl stimulated AhR transformation and DNA binding in vitro and in cells in culture. Dose-response experiments revealed that carbaryl was 300,000-fold less potent that the prototypical inducer, TCDD, in both inducing luciferase gene expression and stimulating AhR transformation and DNA binding in vitro, suggesting that carbaryl itself was the inducing agent. The identification of carbaryl as an AhR ligand was demonstrated by its ability to competitively inhibit [3H]-TCDD to the guinea pig hepatic cytosolic AhR. Our results confirm that carbaryl is both a weak AhR ligand and inducer of AhR-dependent gene expression and argue against its proposed ligand-independent mechanism of AhR activation.


Early competition shapes maize whole-plant development in mixed stands.
Mixed cropping is practised widely in developing countries and is gaining increasing interest for sustainable agriculture in developed countries. Plants in intercrops grow differently from plants in single crops, due to interspecific plant interactions, but adaptive plant morphological responses to competition in mixed stands have not been studied in detail. Here the maize (Zea mays) response to mixed cultivation with wheat (Triticum aestivum) is described. Evidence is provided that early responses of maize to the modified light environment in mixed stands propagate throughout maize development, resulting in different phenotypes compared with pure stands. Photosynthetically active radiation (PAR), red:far-red ratio (R:FR), leaf development, and final organ sizes of maize grown in three cultivation systems were compared: pure maize, an intercrop with a small distance (25cm) between maize and wheat plants, and an intercop with a large distance (44cm) between the maize and the wheat. Compared with maize in pure stands, maize in the mixed stands had lower leaf and collar appearance rates, increased blade and sheath lengths at low ranks and smaller sizes at high ranks, increased blade elongation duration, and decreased R:FR and PAR at the plant base during early development. Effects were strongest in the treatment with a short distance between wheat and maize strips. The data suggest a feedback between leaf initiation and leaf emergence at the plant level and coordination between blade and sheath growth at the phytomer level. A conceptual model, based on coordination rules, is proposed to explain the development of the maize plant in pure and mixed stands.


Reaching the End of the Line: Urinary Tract Infections.
Urinary tract infections (UTIs) cause a substantial health care burden. UTIs (i) are most often caused by uropathogenic Escherichia coli (UPEC), (ii) primarily affect otherwise healthy females (50% of women will have a UTI), (iii) are associated with significant morbidity and economic impact, (iv) can become chronic, and (v) are highly recurrent. A history of UTI is a significant risk factor for a recurrent UTI (rUTI). In otherwise healthy women, an acute UTI leads to a 25 to 50% chance of rUTI within months of the initial infection. Interestingly, rUTIs are commonly caused by the same strain of E. coli that led to the initial infection, arguing that there exist host-associated reservoirs, like the gastrointestinal tract and underlying bladder tissue, that can seed rUTIs. Additionally, catheter-associated UTIs (CAUTI), caused by Enterococcus and Staphylococcus as well as UPEC, represent a major health care concern. The host's response of depositing fibrinogen at the site of infection has been found to be critical to establishing CAUTI. The Drug Resistance Index, an evaluation of antibiotic resistance, indicates that UTIs have become increasingly difficult to treat since the mid-2000s. Thus, UTIs are a "canary in the coal mine," warning of the possibility of a return to the preantibiotic era, where some common infections are untreatable with available antibiotics. Numerous alternative strategies for both the prevention and treatment of UTIs are being pursued, with a focus on the development of vaccines and small-molecule inhibitors targeting virulence factors, in the hopes of reducing the burden of urogenital tract infections in an antibiotic-sparing manner.


Discriminative Structured Dictionary Learning on Grassmann Manifolds and Its Application on Image Restoration.
Image restoration is a difficult and challenging problem in various imaging applications. However, despite of the benefits of a single overcomplete dictionary, there are still several challenges for capturing the geometric structure of image of interest. To more accurately represent the local structures of the underlying signals, we propose a new problem formulation for sparse representation with block-orthogonal constraint. There are three contributions. First, a framework for discriminative structured dictionary learning is proposed, which leads to a smooth manifold structure and quotient search spaces. Second, an alternating minimization scheme is proposed after taking both the cost function and the constraints into account. This is achieved by iteratively alternating between updating the block structure of the dictionary defined on Grassmann manifold and sparsifying the dictionary atoms automatically. Third, Riemannian conjugate gradient is considered to track local subspaces efficiently with a convergence guarantee. Extensive experiments on various datasets demonstrate that the proposed method outperforms the state-of-the-art methods on the removal of mixed Gaussian-impulse noise.


Students' and families' expenditures to attend a nursing programme in 2011-2012: a comparison of five southern European countries.
To compare students' and families' nursing education expenditures across Europe. Nursing education costs are affected by investments in public education. The remaining costs fall on the shoulders of students and their families. While remaining somewhat understudied, public and student expenditure for nursing education is becoming critical in the current crisis context. Comparative studies on education costs are inevitably affected by a currency bias. Therefore, a standard measure named the Purchasing Power Standard, which has received no attention in nursing research, has been introduced. A mixed-method study incorporating qualitative and quantitative study designs was undertaken in 2011-2012. Five nursing faculties located in the Czech Republic, Greece, Italy, Slovakia and Slovenia were included in the study. A questionnaire evaluating students' expenditures was developed in five languages and validated. Six hundred and twenty-five full-time students were recruited. A Slovakian student wishing to pursue a nursing career is required to commit an amount of money per year that corresponds to 15% of the average annual income of a Slovakian citizen. Lower percentages were required by students in Greece (10%), Italy (11%) and Slovenia (12%), while Czech students bore the lowest costs (5%). None of the countries involved was supporting nursing students through either direct or indirect financial incentives. Students in some countries were also required to buy and maintain uniforms. There is a need to develop supportive policies, especially in those countries where nursing programmes are expensive and may not be accessible to all talented and motivated students due to limited public support in education and the current economic context.


Combining Foxc2 and Connexin37 deletions in mice leads to severe defects in lymphatic vascular growth and remodeling.
Connexins (Cxs), proteins that are vital for intercellular communication in vertebrates, have recently been shown to play a critical role in lymphatic development. However, our knowledge is currently limited regarding the functional relationships of Cxs with other proteins and signaling pathways. Cell culture studies have shown that Cx37 is necessary for coordinated activation of the transcription factor NFATc1, which cooperates with Foxc2 (another transcription factor) during lymphatic endothelial development. These data suggest that Cxs, Foxc2, and NFATc1 are part of a common developmental pathway. Here, we present a detailed characterization of Foxc2(+/-)Cx37(-/-) mice, demonstrating that lymphatic network architecture and valve formation rely on the concurrent embryonic expression and function of Foxc2 and Cx37. Foxc2(+/-)Cx37(-/-) mice have lymphedema in utero, exhibit craniofacial abnormalities, show severe dilation of intestinal lymphatics, display abnormal lacteal development, lack lymphatic valves, and typically die perinatally (outcomes not seen in Foxc2(+/-) or Cx37(-/-) mice separately). We provide a rigorous, quantitative documentation of lymphatic vascular network changes that highlight the specific structural alterations that occur in Foxc2(+/-)Cx37(-/-) mice. These data provide further evidence suggesting that Foxc2 and Cx37 are elements in a common molecular pathway directing lymphangiogenesis.


Precision medicine in the diagnosis and treatment of male lower urinary tract symptoms suggestive of benign prostatic hyperplasia.
Male lower urinary tract symptoms (LUTSs) are highly prevalent in men and the incidence increases with aging. The pathophysiology of male LUTSs might be bladder outlet dysfunctions such as bladder neck (BN) dysfunction, benign prostatic obstruction, and poor relaxation of external sphincter and bladder dysfunctions such as detrusor overactivity (DO), detrusor underactivity, DO, and inadequate contractility. Male LUTSs include voiding and storage symptoms, and precision diagnosis should not be done based on the symptoms alone. Videourodynamic study provides a thorough look at the bladder and bladder outlet and can clearly demonstrate the underlying pathophysiology when the initial medication fails to relieve LUTS. Medical treatment should be given based on the underlying pathophysiology of LUTS, and surgical intervention to remove prostate should only be performed when a definite bladder outlet obstruction due to prostatic obstruction has been confirmed by invasive urodynamic study.


Genetic analysis of the insulin receptor gene in Chinese patients with extreme insulin resistance.
Many patients with extreme insulin resistance in combination with acanthosis nigricans are reported to have defective insulin receptor genes. Because acanthosis nigricans is commonly accompanied by severe hyperinsulinemia and obesity, and obesity is a major factor in insulin resistance, this study was initiated to assess the prevalence of mutations in the insulin receptor gene in Chinese patients with extreme insulin resistance defined by hyperinsulinemia, obesity and acanthosis nigricans. Exons 1-22 of the insulin receptor gene were amplified by polymerase chain reaction (PCR) by from genomic DNA from 13 young subjects with clinical and metabolic features of extreme insulin resistance. They were also screened for nucleotide variation using single-strand conformation polymorphism (SSCP) combined with nucleotide sequence analysis. Variant SSCP patterns were detected in exons 1, 3, 6, 11, 12 and 17 of the insulin receptor gene. However, sequencing of amplified DNA fragments revealed that none of the variations were mutations. The SSCP variant in exon 1 was caused by a novel intron polymorphism (G-->T at position 13, 5' intron), while the SSCP variant in exon 12 was caused by a novel silent polymorphism Thr789 (ACG-->ACA). Variants in exons 3 and 17 corresponded to known silent polymorphisms: Gln276 (CAA-->CAG) and His1068 (CAC-->CAT), respectively. Another three variants in exons 3, 6 and 11 were also identified as known polymorphisms in the flanking introns. In addition, two alterations, a silent polymorphism Gly8 (GGA-->GGG) and a polymorphism in the 3' flanking intron (T-->G at position 74), were observed in exon 1 of the insulin receptor gene. Although the prevalence of insulin receptor gene mutations in this Chinese study population might be underestimated because of the sensitivity of SSCP, these results suggest that mutations at the insulin receptor locus are uncommon in subjects with features of hyperinsulinemia, obesity and acanthosis nigricans.


Simplified bite-block immobilization of the head.
The use of bite blocks to immobilize a patient's head for therapeutic radiology usually involves the mechanical positioning of a rod protruding from the block. This position must be recorded at simulation time and preset for each treatment session. The authors describe a device which simply requires the vertical positioning of an auxiliary bar which, in turn, is attached vertically to the primary rod at simulation time.


Advancement of Metatranscriptomics towards Productive Agriculture and Sustainable Environment: A Review.
While chemical fertilisers and pesticides indeed enhance agricultural productivity, their excessive usage has been detrimental to environmental health. In addressing this matter, the use of environmental microbiomes has been greatly favoured as a 'greener' alternative to these inorganic chemicals' application. Challenged by a significant proportion of unidentified microbiomes with unknown ecological functions, advanced high throughput metatranscriptomics is prudent to overcome the technological limitations in unfolding the previously undiscovered functional profiles of the beneficial microbiomes. Under this context, this review begins by summarising (1) the evolution of next-generation sequencing and metatranscriptomics in leveraging the microbiome transcriptome profiles through whole gene expression profiling. Next, the current environmental metatranscriptomics studies are reviewed, with the discussion centred on (2) the emerging application of the beneficial microbiomes in developing fertile soils and (3) the development of disease-suppressive soils as greener alternatives against biotic stress. As sustainable agriculture focuses not only on crop productivity but also long-term environmental sustainability, the second half of the review highlights the metatranscriptomics' contribution in (4) revolutionising the pollution monitoring systems via specific bioindicators. Overall, growing knowledge on the complex microbiome functional profiles is imperative to unlock the unlimited potential of agricultural microbiome-based practices, which we believe hold the key to productive agriculture and sustainable environment.


Antispastic effect of electroacupuncture and moxibustion in stroke patients.
Spasticity is a frequently observed motor impairment that develops after stroke. The objective of this study was to evaluate the efficacy of electroacupuncture (EA) and moxibustion (Mox) on spasticity due to stroke. The subjects consisted of 35 stroke patients with elbow spasticity whose mean duration of stroke was 2.97 months. Fifteen patients were randomized to the EA group, ten to Mox, and ten to control. Every other day, 30 minutes of electrical stimulation with a frequency of 50 Hz was given through four needles on the Ch'ü-Ch'ih-San-Li (LI-11-LI-10) and Wai-Kuan-Ho-Ku (TB-5-LI-4) points of the paretic side. Direct Mox was applied to Ch'ü-Ch'ih (LI-11), San-Li (LI-10), Wai-Kuan (TB-5) and Ho-Ku (LI-4) points three times a day every other day. The control group was given only the routine acupuncture therapy for stroke and range of motion (ROM) exercise, which were also applied to the EA and Mox groups. The efficacy of treatment was measured before, immediately, 1 hour, 3 hours, 1 day, 5 days, 10 days and 15 days after the start of treatment using a modified Ashworth scale (MAS). In the EA group, spasticity was significantly reduced immediately, 1 hour and 3 hours after treatment (p < 0.05). Reductions were significant on the 5th day and thereafter (p < 0.05). In the Mox group, there was no significant change in the MAS scores after the first treatment. In the Mox and control group, there was no significant change in MAS scores. This study suggests that EA can temporarily reduce spasticity due to stroke, and if applied repeatedly it can maintain reduced spasticity.


NFATc4 is negatively regulated in miR-133a-mediated cardiomyocyte hypertrophic repression.
Activation of NFAT (nuclear factor of activated T cells)-mediated hypertrophic signaling is a major regulatory response to hypertrophic stimuli. A recent study unveiled potential regulatory roles for microRNA-133a (miR-133a) in cardiac hypertrophy. To date, however, no connection has been made between miR-133a and NFAT signaling. In this study, we determined that NFATc4, a hypertrophy-associated mediator, is negatively regulated by miR-133a. Two conserved base-pairing sites between the NFATc4 3'-untranslated region (UTR) and miR-133a were verified. Mutation of these sites in the NFATc4 3'-UTR completely blocked the negative effect of miR-133a on NFATc4, suggesting that NFATc4 is a direct target for miR-133a regulation. Using a gain-of-function approach, we demonstrate that miR-133 significantly reduces the endogenous level of, as well as the hypertrophic stimulus-mediated increase in, NFATc4 gene expression. This latter effect of miR-133a on NFATc4 gene expression was coincided with an attenuated cardiomyocyte hypertrophy induced by an alpha-adrenergic receptor agonist. Conversely, cells treated with miR-133a inhibitor resulted in an increase in NFATc4 expression level. Application of miR-133a had no apparent effect on NFATc4 nuclear localization. We conclude that the negative regulation of NFATc4 expression contributes to miR-133a-mediated hypertrophic repression.


Prognostic factors for successful surgical outcome with preoperative prism adaptation test in patients with superior oblique palsy.
This study evaluated the surgical outcome of patients managed with preoperative prism adaptation test (PAT) and investigated prognostic factors for successful motor alignment in adult patients with superior oblique palsy. Prospective study of preoperative PAT was performed. Fifty-seven patients with superior oblique palsy, aged 16 to 81 years, participated in this study. Patients were assigned to surgery with the target angle based on either the original angle or the prism compensated angle. When the amount of neutralizing prism exceeded 4delta or more compared to the original angle of deviation, the patient was defined as having prism compensation, and the target angle for surgery was based on the amount of neutralizing prism. The motor success rate was compared between the 2 groups at the 3-month postoperative follow-up. The prism responders group showed a superior outcome compared to that of the prism non-responders group (77% successful outcome compared with 46%, p = 0.0397). The presence of prism compensation and the amount of vertical deviation were significant prognostic factors for successful motor alignment. Preoperative PAT is a useful prognostic indicator of successful surgical outcome in patients with superior oblique palsy.


Myasthenia gravis in a pediatric patient with Lennox-Gastaut syndrome following responsive neurostimulation device implantation: illustrative case.
Myasthenia gravis (MG) is an autoimmune disorder in which the postsynaptic acetylcholine receptor of the neuromuscular junction is destroyed by autoantibodies. The authors report a case of MG in a pediatric patient who also suffered from Lennox-Gastaut syndrome (LGS) and is one of a limited number of pediatric patients who have undergone placement of a responsive neurostimulation (RNS) device (NeuroPace). A 17-year-old female underwent placement of an RNS device for drug-resistant epilepsy in the setting of LGS. Five months after device placement, the patient began experiencing intermittent slurred speech, fatigue, and muscle weakness. Initially, the symptoms were attributed to increased seizure activity and/or medication side effects. However, despite changing medications and RNS settings, no improvements occurred. Her antiacetylcholine receptor antibodies measured 62.50 nmol/L, consistent with a diagnosis of MG. The patient was then prescribed pyridostigmine and underwent a thymectomy, which alleviated most of her symptoms. The authors share the cautionary tale of a case of MG in a pediatric patient who was treated with RNS for intractable epilepsy associated with LGS. Although slurred speech, fatigue, muscle weakness, and other symptoms might stem from increased seizure activity and/or medication side effects, they could also be due to MG development.


Circulating levels of plasma adrenocorticotropin in polycystic ovary disease.
Excessive adrenal androgen production contributes to hyperandrogenism in polycystic ovarian disease (PCO). This study was performed to determine the concentration of basal plasma ACTH in PCO patients and normal women and correlate its level with that of circulating adrenal androgen. In PCO patients, significant increases in serum testosterone, androstenedione, and dehydroepiandrosterone sulfate were noted compared to levels in normal women. The mean circulating plasma ACTH in PCO patients (22 +/- 2 pg/ml) was not different from that in normal controls (20 +/- 2 pg/ml). The mean ratio of dehydroepiandrosterone sulfate to ACTH in individual PCO patients was significantly greater than that in normal subjects, whereas the cortisol to ACTH ratio was similar in both groups. These results suggest that increased adrenal androgen production in PCO patients is not due to abnormal ACTH secretion but arises from either altered adrenal responsiveness to ACTH or abnormal adrenal stimulation by a factor(s) other than ACTH.


Individual brain structure and modelling predict seizure propagation.
See Lytton (doi:10.1093/awx018) for a scientific commentary on this article.Neural network oscillations are a fundamental mechanism for cognition, perception and consciousness. Consequently, perturbations of network activity play an important role in the pathophysiology of brain disorders. When structural information from non-invasive brain imaging is merged with mathematical modelling, then generative brain network models constitute personalized in silico platforms for the exploration of causal mechanisms of brain function and clinical hypothesis testing. We here demonstrate with the example of drug-resistant epilepsy that patient-specific virtual brain models derived from diffusion magnetic resonance imaging have sufficient predictive power to improve diagnosis and surgery outcome. In partial epilepsy, seizures originate in a local network, the so-called epileptogenic zone, before recruiting other close or distant brain regions. We create personalized large-scale brain networks for 15 patients and simulate the individual seizure propagation patterns. Model validation is performed against the presurgical stereotactic electroencephalography data and the standard-of-care clinical evaluation. We demonstrate that the individual brain models account for the patient seizure propagation patterns, explain the variability in postsurgical success, but do not reliably augment with the use of patient-specific connectivity. Our results show that connectome-based brain network models have the capacity to explain changes in the organization of brain activity as observed in some brain disorders, thus opening up avenues towards discovery of novel clinical interventions.


The hydroclimatic and ecophysiological basis of cloud forest distributions under current and projected climates.
Tropical montane cloud forests (TMCFs) are characterized by a unique set of biological and hydroclimatic features, including frequent and/or persistent fog, cool temperatures, and high biodiversity and endemism. These forests are one of the most vulnerable ecosystems to climate change given their small geographic range, high endemism and dependence on a rare microclimatic envelope. The frequency of atmospheric water deficits for some TMCFs is likely to increase in the future, but the consequences for the integrity and distribution of these ecosystems are uncertain. In order to investigate plant and ecosystem responses to climate change, we need to know how TMCF species function in response to current climate, which factors shape function and ecology most and how these will change into the future. This review focuses on recent advances in ecophysiological research of TMCF plants to establish a link between TMCF hydrometeorological conditions and vegetation distribution, functioning and survival. The hydraulic characteristics of TMCF trees are discussed, together with the prevalence and ecological consequences of foliar uptake of fog water (FWU) in TMCFs, a key process that allows efficient acquisition of water during cloud immersion periods, minimizing water deficits and favouring survival of species prone to drought-induced hydraulic failure. Fog occurrence is the single most important microclimatic feature affecting the distribution and function of TMCF plants. Plants in TMCFs are very vulnerable to drought (possessing a small hydraulic safety margin), and the presence of fog and FWU minimizes the occurrence of tree water deficits and thus favours the survival of TMCF trees where such deficits may occur. Characterizing the interplay between microclimatic dynamics and plant water relations is key to foster more realistic projections about climate change effects on TMCF functioning and distribution.


CAAC-stabilised 9,10-diboraanthracene: an electronically and structurally flexible platform for small-molecule activation and metal complexation.
A biradical cyclic alkyl(amino)carbene-stabilised 9,10-diboraanthracene (DBA) activates small molecules such as hydrogen, phenyl azide or TEMPO (2,2,6,6-tetramethylpiperidin-1-oxyl) across its two boron atoms, while reactions with [(MeCN)3M(CO)3] (M = Cr, Mo, W) yield the first half-sandwich DBA complexes of the form [(η6-DBA)M(CO)3].


Are women more likely to wear red and pink at peak fertility? What about on cold days? Conceptual, close, and extended replications with novel clothing colour measures.
Evolutionarily minded researchers have hypothesized that women advertise their ovulatory status by wearing red or pink clothing on relatively cold days. Many of these studies have been based on samples of women who have self-reported their clothing choices, a practice that raises questions about accuracy. In two studies, we evaluated the relationship between women's fertility and their clothing choices using four methods for measuring clothing colour: self-reports; trained raters' judgements of garment coloration in outfits that women drew onto mannequins to represent what they would wear to a party with single attractive people in attendance; automated colour coding of the mannequins; and trained raters' judgements of garment coloration as evinced in photographs that women took of themselves. Using these four measures of clothing choice along with measures of women's fertility and outside temperature, we did not find compelling evidence that women are particularly inclined to wear red or pink during peak fertility, even on relatively cold days.


[Retrospective evaluation of the results of the microbiological meat examination (MFU) from calves and cows].
The microbiological meat examination (MFU), consisting of a bacteriological analysis and a testing for antibiotic residues, is one of several additional analyses used for an edibility rating of carcasses made during meat inspection. Reasons for performing a microbiological meat examination and procedures in the laboratory are defined in the Swiss ordinance for meat examination (FUV). The aim of this study was to analyze the data of 313 microbiological meat examinations from calves and 2882 microbiological meat examinations from cows carried out at the Institute for Food Safety and Hygiene during a period of 8 years. Reasons for microbiological meat examinations as reported by the meat inspectors were mainly classified to the category of "inflammation and necroses" (FUV, Annex 4, Pt 1.2; calves: 73%, cows: 48%). As declarations of the age of the pathological-anatomical changes (that influences directly the probability of detection of pathogens) were generally missing, it is not surprising that the compliance between a particular pathological-anatomical change and a specific detection of pathogens is poor (calves: 19%, cows: 18% of all MFU). About 18% (calves) and 45% (cows) of the reasons for microbiological meat examinations did not correspond to one of the reasons mentioned in the ordinance for meat examination. However, according to the data set, some reasons require a microbiological meat examination due to an often-found specific detection of pathogens. Otherwise, a remarkable number of reasons mentioned were missing the link to bacteriological etiology. Moreover, 14% (calf) and 7% (cow) of microbiological meat examinations with the declaration "no pretreatment" as well as 15% (calf) and 11% (cow) of microbiological meat examinations without declaration showed a positive result in the testing for antibiotic residues.


COMbined Physical and somatoSEnsory training after stroke: Development and description of a novel intervention to improve upper limb function.
After stroke, reach-to-grasp goal-directed movements are disrupted as a result of both residual motor and somatosensory impairments. This report describes the rationale and development of a new upper limb stroke rehabilitation intervention known as COMPoSE: "COMbined Physical and somatoSEnsory training," designed to improve somatosensory and motor deficits in the upper limb after stroke. A standardized training matrix has been developed to facilitate intervention delivery. The COMPoSE intervention was developed through the following stages: (a) Definition and operationalization of somatosensory and motor variables used in training sensation and movement after stroke; (b) development of methods to give feedback to enhance skill acquisition; and (c) Combination of somatosensory and motor variables, and feedback, into a standardized training matrix. The reporting of the COMPoSE intervention adheres to the recommendations of the Template for Intervention Description and Replication checklist to facilitate replication of the intervention in the future. The essential features of COMPoSE include combined somatosensory-motor training variables (grasp pressure, distance, object size, crushability, surface texture, and friction), feedback, and calibration using a haptic device providing measures of grasp pressure, use of anticipation trials, and high-dose repetitive task practice. Ten treatment sessions are delivered over 3 weeks, using a standardized matrix for treatment delivery. COMPoSE is a new intervention that combines somatosensory and movement training, delivered synchronously, within the same intervention, and within the same task.


Anomalous capillary filling and wettability reversal in nanochannels.
This work revisits capillary filling dynamics in the regime of nanometric to subnanometric channels. Using molecular dynamics simulations of water in carbon nanotubes, we show that for tube radii below one nanometer, both the filling velocity and the Jurin rise vary nonmonotonically with the tube radius. Strikingly, with fixed chemical surface properties, this leads to confinement-induced reversal of the tube wettability from hydrophilic to hydrophobic for specific values of the radius. By comparing with a model liquid metal, we show that these effects are not specific to water. Using complementary data from slit channels, we then show that they can be described using the disjoining pressure associated with the liquid structuring in confinement. This breakdown of the standard continuum framework is of main importance in the context of capillary effects in nanoporous media, with potential interests ranging from membrane selectivity to mechanical energy storage.


Both Ketamine and NBQX Attenuate Alcohol-Withdrawal Induced Depression in Male Rats.
The co-morbidity between heavy drinking and depression can negatively influence successful cessation of alcohol use. Since ketamine, a glutamatergic NMDA receptor antagonist, has shown promise as a quick-acting antidepressant, we studied its effects specifically on alcohol withdrawal-induced depression. We also evaluated the effects of NBQX an AMPA/kainate receptor antagonist, because some of the effects of ketamine are proposed to be indirectly mediated through these receptors. Adult male Wistar rats were exposed daily to ethanol via inhalation chambers 4 h/day for 7 days (blood alcohol concentration=160 mg%), followed by daily intraperitoneal injections of ketamine (2.5 mg/kg), NBQX (5mg/kg), alone or in combination. Eighteen hours later, open field locomotor activity (OFLA) followed by forced swim test (FST) were performed. The animals were sacrificed 2 h later for evaluation of brain-derived neurotrophic factor (BDNF) in the hippocampus. Alcohol withdrawal did not affect OFLA, but caused an increase in immobility in FST, suggesting induction of "depressive-like" helplessness. Both ketamine and NBQX normalized the swimming score in FST. The combination of the two drugs, however, cancelled each other's effect. Parallel to these behavioral observations, both ketamine and NBQX normalized the reduction in hippocampal BDNF caused by alcohol withdrawal. Here also, the combination of the two drugs cancelled each other's effect. These results suggest that either NMDA or AMPA/kainate receptor antagonists, acting at least partially through hippocampal BDNF, may be of therapeutic potential in alcohol use disorder.


Lateral approach to the canine elbow by proximal ulnar diaphyseal osteotomy.
A lateral approach to the elbow by proximal ulnar diaphyseal osteotomy was developed as an alternative to a number of currently used surgical approaches to that joint. The technique was easily performed, and it provided better visualization of the multiple joint compartments of the elbow than does any other technique. Repair of the osteotomy required a minimum of specialized equipment, and closure afforded excellent stabilization of the elbow and early return to function. In 3 cases, the versatility of the approach was demonstrated.


Shorter disease duration correlates with improved long-term deep brain stimulation outcomes in young-onset DYT1 dystonia.
Treatment with deep brain stimulation (DBS) of the globus pallidus internus in children with DYT1 primary torsion dystonia is highly effective; however, individual response to stimulation is variable, and a greater understanding of predictors of long-term outcome is needed. To report the long-term outcomes of subjects with young-onset DYT1 primary torsion dystonia treated with bilateral globus pallidus DBS. Fourteen subjects (7 male, 7 female) treated consecutively from 2000 to 2010 at our center were included in this retrospective study. The Burke-Fahn-Marsden Dystonia Rating Scale was performed at baseline and at 1, 2, and up to 6 years postoperatively. Pallidal DBS was well tolerated and highly effective, with mean Burke-Fahn-Marsden Dystonia Rating Scale movement scores improving from baseline by 61.5% (P < .001) at 1 year, 64.4% (P < .001) at 2 years, and 70.3% (P < .001) at the final follow-up visit (mean, 32 months; range, 7-77 months). Disability scores also improved significantly. Multiple linear regression analysis revealed a significant influence of duration of disease as a predictor of percent improvement in Burke-Fahn-Marsden Dystonia Rating Scale movement score at long-term follow-up (duration of disease, P < .05). Subjects with fixed orthopedic deformities (4) had less improvement in these regions. Location of the active DBS electrode used at final follow-up visit was not predictive of clinical outcome. Our findings highlight the sustained benefit from DBS and the importance of early referral for DBS in children with medically refractory DYT1 primary torsion dystonia, which can lead to improved long-term benefits.


Photon upconversion properties of Ni2+ in magnetic and nonmagnetic chloride host lattices.
Near-infrared to visible upconversion luminescence in Ni2+:CsCdCl3, Ni2+:CsMnCl3, and Ni2+:RbMnCl3 is presented and analyzed. In all three materials upconversion occurs via a sequence of ground-state absorption/excited-state absorption processes, which are both formally spin-forbidden transitions. Consequently, in the diamagnetic Ni2+:CsCdCl3 they are weak, and the efficiency of the upconversion process is relatively low. This is in clear contrast to the isostructural Ni2+:RbMnCl3 where the spin selection rule relaxes because of Ni(2+)-Mn2+ exchange interactions, leading to an intensity enhancement of the spin-flip transitions involved in the Ni2+ upconversion mechanism. This results in an exchange-induced enhancement of the upconversion rate in Ni2+:RbMnCl3 relative to Ni2+:CsCdCl3 by 2 orders of magnitude after two-color excitation into the maxima of the ground-state and excited-state absorption bands. In Ni2+:CsMnCl3 the Ni(2+)-Mn2+ exchange interaction does not play a significant role. This is due to the different Ni(2+)-Cl(-)-Mn2+ bridging geometry relative to Ni2+:RbMnCl3. In contrast to Ni2+:CsCdCl3 and Ni2+:RbMnCl3 where the upconversion luminescence occurs from Ni2+, in Ni2+:CsMnCl3 the upconverted energy is emitted from Mn2+ in the visible spectral region. This leads to an enhanced visible upconversion luminescence in Ni2+:CsMnCl3, relative to the other two samples where Ni2+ near-infrared inter-excited-state emissions compete with the visible upconversion luminescence.


Origin and molecular pathogenesis of ovarian high-grade serous carcinoma.
A new paradigm for the pathogenesis of ovarian cancer has recently been proposed which helps to explain persistent problems in describing the development and diverse morphology of these neoplasms. The paradigm incorporates recent advances in our understanding of the molecular pathogenesis of epithelial 'ovarian' cancer with new insights into the origin of these tumors. Correlated clinicopathologic and molecular genetic studies led to the development of a dualistic model that divides all the various histologic types of epithelial ovarian carcinomas into two broad categories designated 'type I' and 'type II'. The prototypic type I tumor is low-grade serous carcinoma and the prototypic type II tumor is high-grade serous carcinomas (HGSCs). As the serous tumors comprise ∼70% of all epithelial ovarian tumors and account for the majority of deaths, the serous tumors will be the subject of this review. There are marked differences between the low-grade and high-grade serous tumors. Briefly, the former are indolent, present in stage I (tumor confined to the ovary) and develop from well-established precursors, so-called 'atypical proliferative (borderline) tumors,' which are characterized by specific mutations, including KRAS, BRAF and ERBB2; they are relatively genetically stable. In contrast, HGSCs are aggressive, present in the advanced stage, and develop from intraepithelial carcinomas in the fallopian tube. They harbor TP53 mutations in over 95% of cases, but rarely harbor the mutations detected in the low-grade serous tumors. At the time of diagnosis they demonstrate marked chromosomal aberrations but over the course of the disease these changes remain relatively stable. Along with the recent advances in understanding the molecular pathogenesis of these tumors, studies have demonstrated that the long sought for precursor of ovarian HGSC appears to develop from an occult intraepithelial carcinoma in the fimbrial region of the fallopian tube designated 'serous tubal intraepithelial carcinoma (STIC)' and involves the ovary secondarily. Another possible mechanism for the development of ''ovarian'' HGSC is implantation of normal fimbrial epithelium on the denuded ovarian surface at the site of rupture when ovulation occurs. We speculate that this tubal epithelium can result in the formation of a cortical inclusion cyst (CICs) that can then undergo malignant transformation. Thus, serous tumors may develop from inclusion cysts, as has been previously proposed, but by a process of implantation of tubal (müllerian-type) tissue rather than by a process of metaplasia from ovarian surface epithelium (OSE, mesothelial). The dualistic model serves as a framework for studying ovarian cancer and can assist investigators in organizing this complex group of neoplasms. In conjunction with the recognition that the majority of 'ovarian' carcinomas originate outside the ovary, this model also facilitates the development of new and novel approaches to prevention, screening and treatment of this devastating disease.


Cycle ergometer training and resistance training similarly increase muscle strength in trained men.
The aim of this study was to compare two different maximal intensity exercise modality training protocols of similar durations on muscle strength, cardiorespiratory fitness, and lower limb composition in recreationally trained men. Twenty-five trained men (28.9 ± 5.6 years) were randomly divided into Cycle ergometer (4 sets of 30 seconds sprints) and Leg press (4 sets of 10-12 repetitions to momentary failure). Both groups trained three times a week for 5 weeks. Before and after the training period, the participants performed a 10-repetition maximum (10RM) test for knee extension, an incremental exercise test on a treadmill for time to exhaustion (TTE) and peak oxygen consumption (V˙O2peak) and underwent dual energy X-ray absorptiometry to assess lower limb composition. Knee extension 10RM and TTE increased in both groups with no statistically significant between group (p = 0.614 and p = 0.210). Only cycle ergometer group increased V˙O2peak (p = 0,012). For all lower limb composition outcomes, changes were minimal. The results suggest that 5 weeks of effort and duration matched exercise protocols using cycle ergometer training or leg press may produce similar strength adaptations.


Modelling Aspergillus fumigatus infections in racing pigeons (Columba livia domestica).
In vivo modelling of aspergillosis in birds allows the evaluation of control measures and the study of host-pathogen interactions. In this study the impact of the use of different inoculation routes and immunosuppression on the course of an infection with Aspergillus fumigatus in racing pigeons (Columba livia domestica) was examined. A. fumigatus conidia were inoculated in the thoracic air sac, lung or trachea in immunocompetent or immunosuppressed pigeon squabs. Immunosuppression was induced by three dexamethasone injections before inoculation. Mortality in the A. fumigatus-inoculated groups varied between 1/4 and 4/4. The highest and more acute mortality was seen in immunocompetent pigeons inoculated in the thoracic air sac and in pigeons inoculated in the thoracic air sac or lung after immunosuppression. Pigeons inoculated in the lung or inoculated intratracheally after immunosuppression developed an aspergillosis infection with a slower course of disease and more prominent clinical symptoms. Using microsatellite length polymorphism, it was confirmed that all mycoses were caused by the inoculated strain except for one isolate in a dexamethasone-treated pigeon. In conclusion, inoculation in the lung is selected as the preferred model for chronic aspergillosis in pigeons, and inoculation in the thoracic air sac as the preferred model for acute aspergillosis. The use of immunosuppressed birds seems to be contra-indicated due to the risk of opportunistic infections.


Adaptations of the in vitro MN assay for the genotoxicity assessment of nanomaterials.
The issue of appropriate testing strategies has been raised for the genotoxicity assessment of nanomaterials. Recently, efforts have been made to evaluate the adequacy of Organisation for Economic Co-operation and Development-standardised tests to assess the genotoxicity of nanomaterials. The aim of this review was to examine whether the current guideline for the in vitro micronucleus (MN) assay is applicable for testing nanomaterials. From a Pubmed literature search, 21 available studies were identified for analysis. We reviewed all protocols used for testing nanomaterials with the in vitro MN assay. All studies were categorised based on the particle type and size. Different aspects of the protocols were evaluated such as the exposure (duration and doses), the cytochalasin-B treatment, serum levels and cytotoxicity assessment. Sixteen of the 21 studies demonstrated increased frequencies of MN. Some recommendations regarding the protocol were formulated to maximise sensitivity and avoid false negatives. Determination of the cellular dose was advised for a better interpretation of MN frequency results. The level of serum can modulate the cellular response, therefore the serum percentage used should enable cell growth and proliferation and a maximal sensitivity of the assay. Furthermore, different types of cytochalasin-B treatment were used, co-treatment, post-treatment and delayed co-treatment. In order to avoid decreased cellular uptake as a consequence of actin inhibition, post-treatment or delayed co-treatment is suggested. Exposure during mitosis should be recommended to allow contact with the chromatin or mitotic apparatus for nanomaterials that are unable to cross the nuclear membrane. With these adaptations, the in vitro MN assay can be recommended for genotoxicity testing of nanomaterials.


The influence of left and right hemisphere brain damage on configural and featural processing of affective faces.
The literature about the lateralization of facial emotion perception according to valence (positive, negative) is conflicting; investigating the underlying processes may shed light on why some studies show right-hemisphere dominance across valence and other studies demonstrate hemispheric differences according to valence. This is the first clinical study to examine whether the use of configural and featural cues underlies hemispheric differences in affective face perception. Right brain-damaged (RBD; n = 17), left brain-damaged (LBD; n = 17) and healthy control (HC; n = 34) participants completed an affective face discrimination task that tested configural processing using whole faces and featural processing using partial faces. No group differences in expression perception according to valence or processing strategy were found. Across emotions, the RBD group was less accurate than the HC group in discriminating whole faces, whilst the RBD and LBD groups were less accurate than HCs in discriminating partial faces. This suggests that the right hemisphere processes facial expressions from configural and featural information, whereas the left hemisphere relies more heavily on featural facial information.


COVID-19 Mortality and Vaccine Coverage - Hong Kong Special Administrative Region, China, January 6, 2022-March 21, 2022.
On January 6, 2022, a cluster of COVID-19 cases* caused by the Omicron variant of SARS-CoV-2, the virus that causes COVID-19, was detected in Hong Kong Special Administrative Region, China (Hong Kong), resulting in the territory's fifth wave of COVID-19 cases (1). This wave peaked on March 4, 2022, with 8,764 COVID-19 cases per million population (2), resulting in a total of 1,049,959 cases and 5,906 COVID-19-associated deaths reported to the Hong Kong Department of Health during January 6-March 21, 2022.† Throughout this period, the COVID-19 mortality rate in Hong Kong (37.7 per million population) was among the highest reported worldwide since the COVID-19 pandemic began (3). Publicly available data on age-specific vaccination coverage in Hong Kong with a 2-dose primary vaccination series (with either Sinovac-CoronaVac [Sinovac], an inactivated COVID-19 viral vaccine, recommended for persons aged ≥3 years or BNT162b2 [Pfizer-BioNTech], an mRNA vaccine, for persons aged ≥5 years), as of December 23, 2021,§,¶ and COVID-19 mortality during January 6-March 21, 2022, were analyzed. By December 23, 2021, 67% of vaccine-eligible persons in Hong Kong had received ≥1 dose of a COVID-19 vaccine, 64% had received ≥2 doses, and 5% had received a booster dose. Among persons aged ≥60 years, these proportions were 52%, 49%, and 7%, respectively. Among those aged ≥60 years, vaccination coverage declined with age: 48% of persons aged 70-79 years had received ≥1 dose, 45% received ≥2 doses, and 7% had received a booster, and among those aged ≥80 years, 20%, 18%, and 2% had received ≥1 dose, ≥2 doses, and a booster dose, respectively. Among 5,906 COVID-19 deaths reported, 5,655 (96%) occurred in persons aged ≥60 years**; among these decedents, 3,970 (70%) were unvaccinated, 18% (1,023) had received 1 vaccine dose, and 12% (662) had received ≥2 doses. The overall rates of COVID-19-associated mortality among persons aged ≥60 years who were unvaccinated, who had received 1 COVID-19 vaccine dose, and who had received ≥2 vaccine doses were 10,076, 1,099, and 473 per million population, respectively; the risk for COVID-19-associated death among unvaccinated persons was 21.3 times that among recipients of 2-3 doses in this age group. The high overall mortality rate during the ongoing 2022 Hong Kong Omicron COVID-19 outbreak is being driven by deaths among unvaccinated persons aged ≥60 years. Efforts to identify and address gaps in age-specific vaccination coverage can help prevent high mortality from COVID-19, especially among persons aged ≥60 years.


[What is the humanistic medicine?].
At the Karolinska Institute, Stockholm's medical university, a new academic discipline was established in 1998. Humanistic medicine, or medical humanities, is a response to the need in an increasing technological medicine for a humanistic dimension in medical education and clinical practice. The mission of medical humanities is to contribute to the understanding of the scientific and ethical structure of medicine. Medical humanities should focus on clinical practice. At the Karolinska Institute, the discipline has three aspects: medical history, philosophy of medical science, and the "medical meeting", i.e. issues such as: What happens in the relation between patient and caregiver? What is the art of medicine? How is suffering and disease expressed in art and literature? Medical humanities can be a tool for critical reexamination and a radical reorientation of the ethos of medicine. After all, health care is at its very core a moral project.


Cholesterol reduction and macrophage function: role of paraoxonases.
Unregulated uptake of oxidized LDL by macrophages to form foam cells is the hallmark for atherosclerosis. The paraoxonase (PON) family of enzymes plays a critical role in attenuating atherosclerotic lesion formation by hydrolyzing lipid peroxides (LOOHs) and preventing the oxidation of LDL particles and by enhancing HDL-mediated cholesterol efflux. Findings in recent years suggest novel mechanisms by which PON isoforms interact with macrophages to regulate cholesterol metabolism and cellular function. The association of PON with HDL particles facilitates binding of the particle to macrophages and ABCA1-dependent cholesterol efflux. The hydrolysis of membrane phospholipids by PON generates lysophosphatidylcholine which is shown to regulate expression of cholesterol transport proteins. The PON family also regulates multiple aspects of macrophage function. PON attenuates inflammation and prevents induction of apoptosis via activation of a scavenger receptor class B type-1-dependent signaling mechanism. PON limits macrophage-dependent oxidant formation by preventing the activation of the membrane-associated NADPH oxidase and by stabilizing mitochondria. PON also promotes the differentiation of macrophages to an anti-inflammatory phenotype. This function appears to be independent of PON enzymatic activity and, rather, is dependent on the ability of endogenous sulfhydryls to neutralize pro-inflammatory peroxides. In recent years, the therapeutic efficacy of HDL-based therapies has been subject to dispute. Pharmacological approaches that target an increase in the expression and/or activity of PON may facilitate macrophage cholesterol metabolism and attenuate inflammatory injury.


Synergistic PXT3003 therapy uncouples neuromuscular function from dysmyelination in male Charcot-Marie-Tooth disease type 1A (CMT1A) rats.
Charcot-Marie-Tooth disease 1 A (CMT1A) is caused by an intrachromosomal duplication of the gene encoding for PMP22 leading to peripheral nerve dysmyelination, axonal loss, and progressive muscle weakness. No therapy is available. PXT3003 is a low-dose combination of baclofen, naltrexone, and sorbitol which has been shown to improve disease symptoms in Pmp22 transgenic rats, a bona fide model of CMT1A disease. However, the superiority of PXT3003 over its single components or dual combinations have not been tested. Here, we show that in a dorsal root ganglion (DRG) co-culture system derived from transgenic rats, PXT3003 induced myelination when compared to its single and dual components. Applying a clinically relevant ("translational") study design in adult male CMT1A rats for 3 months, PXT3003, but not its dual components, resulted in improved performance in behavioral motor and sensory endpoints when compared to placebo. Unexpectedly, we observed only a marginally increased number of myelinated axons in nerves from PXT3003-treated CMT1A rats. However, in electrophysiology, motor latencies correlated with increased grip strength indicating a possible effect of PXT3003 on neuromuscular junctions (NMJs) and muscle fiber pathology. Indeed, PXT3003-treated CMT1A rats displayed an increased perimeter of individual NMJs and a larger number of functional NMJs. Moreover, muscles of PXT3003 CMT1A rats displayed less neurogenic atrophy and a shift toward fast contracting muscle fibers. We suggest that ameliorated motor function in PXT3003-treated CMT1A rats result from restored NMJ function and muscle innervation, independent from myelination.


Trends in contraceptive use at one university: 1974-1978.
In a group of 2,700 women making initial visits to the contraception clinic at one university (California State University at Fullerton) between 1974 and 1978, oral contraceptives were the most frequently chosen of three prescription methods. (The others were the IUD and diaphragm.) The proportion of women choosing the pill, however, declined sharply over the period--from 89 percent of patients in 1974 to 63 percent in 1978. Choice of the diaphragm rose substantially: In 1978, 33 percent chose it, compared to six percent in 1974. The proportion of women choosing the IUD fluctuated over the four-year period, showing no clear trend, and averaging eight percent over the entire span. The decline in the proportion of women choosing the pill was sharpest among white Anglo students--down from 85 percent to 63 percent; among nonwhites and Hispanics, the proportion fell from 89 percent to 80 percent. The increase in the choice of the diaphragm was also greatest among the Anglo students. These trends of decreased choice of the pill and increased acceptance of the diaphragm are much sharper than those shown among young married women at the national level.


Neonatal purpura fulminans: a genetic disorder related to the absence of protein C in blood.
To confirm the pathogenesis and the genetic background of neonatal-onset purpura fulminans, two unrelated infants with this rare thrombotic syndrome and 47 of their asymptomatic relatives were studied. In both families, 27 subjects with hereditary partial deficiency of protein C, including both parents of each patient, were identified. The patient in whom it was possible to evaluate protein C directly showed no detectable levels of this plasma component. These findings confirm the linkage of neonatal purpura fulminans to a genetic trait with established mendelian transmission and strongly suggest that the syndrome is an expression of homozygosity for protein C deficiency. The dramatic clinical picture and the type of pathologic change that develops as a result of the lack of circulating protein C emphasize the vital role of this protein in protection from thrombin generation, mainly within the microvascular system. However, our data do not contribute to the evidence that partial familial protein C deficiency is associated with a major risk of venous thromboembolism.


Subcutaneous Migration: A Dynamic Anatomical Study of Gluteal Fat Grafting.
Recent anatomical studies have demonstrated that fat placed subjacent to the fascia of the gluteus maximus muscle can migrate deep through the muscle into the submuscular space, possibly causing tears in the gluteal veins, leading to fat embolisms. The purpose of this study was to define and to study subcutaneous migration and to determine whether fat placed in the subcutaneous space under a variety of pressures and fascial integrity scenarios can indeed migrate into the deep submuscular space. Four hemibuttocks from two cadavers were used. Proxy fat was inserted using syringes with various fascia scenarios (1: fascia intact; 2: cannula perforations; 3: 6mm fascia defects) or using expansion vibration lipofilling (4: fascia intact). Subcutaneous pressures were recorded. After injections, anatomical dissections were performed to evaluate the migration of the proxy fat for each of the scenarios. Scenario 1: pressure reached approximately 125 to 150 mmHg and then plateaued and all the proxy fat remained in the subcutaneous space. Scenario 2: pressure reached a 199-mmHg plateau and no proxy fat spread deeper into the muscle or beneath it. Scenario 3: pressure gradually rose to 50 mmHg then fell again and the submuscular space contained a significant amount of proxy fat. Scenario 4: pressure rose to a maximum of 30 mmHg and all of the proxy fat remained in the subcutaneous space. The gluteus maximus fascia is a stout wall that sets up the dangerous condition of deep intramuscular migration with subfascial injections and the protective condition of subcutaneous migration with suprafascial injections. These persuasive findings are profound enough to propose a new standard of care: no subfascial or intramuscular injection should be performed, and all injections should be performed exclusively into the subcutaneous tissue.


Mechanisms of polarity protein expression control.
Polarity is a universal feature of cells during division and often at other stages of the cell cycle or after post-mitotic differentiation. A conserved machinery, present in all animals, initiates and maintains polarity. Multi-cellular animals organize themselves with respect to the axes of symmetry of the organism through the process of planar cell polarity, but many tissues also express a cell-intrinsic form of polarity, for instance to segregate the apical and basolateral membranes of epithelial cells. Although the genes and proteins involved in apical-basal polarity have been known for many years, the regulation of their expression remains ill-defined. Maintenance of the correct expression levels is essential for normal cell lineage allocation, tissue morphogenesis and cell survival. Here we summarize what is known about the transcriptional and post-transcriptional regulation of polarity protein expression, and discuss areas that remain to be understood.


STUDIES ON ANTIBODY PRODUCTION X. MODE OF FORMATION OF PLASMOCYTES IN CELL TRANSFER EXPERIMENTS.
Cells from lymph nodes of rabbits injected repeatedly with bovine serum albumin were transferred subcutaneously to previously irradiated rabbits, and the recipients were immediately injected with bovine serum albumin. A good antibody response resulted. In a series of such animals killed on successive days, skin samples at sites of cell deposition were removed and examined by immunofluorescence and by light microscopy. In these tissues abundant plasmocytes were found to have multiplied and differentiated in a regular progression from immature, to medium, to mature plasmocytes. During the 6 days of the experiment the small plasmocytes accumulated until they reached 85 per cent of the total plasmocytic population. The mitotic index of the large and medium plasmocytes averaged 11 per cent, implying a generation time of 6.3 hours on the basis of a 1 hour mitotic time. This rate of growth is sufficiently rapid to account for all the plasmocytes on the 6th day as deriving from less than 1 per cent of the population initially transferred. This rate and the orderly progression in the evolution of the plasmocytic population, make it highly improbable that plasmocytes arise from transformation of lymphocytes, but rather indicate that they spring from specific precursors already present among the transferred cells.


Distinguishing between sea turtle foraging areas using stable isotopes from commensal barnacle shells.
Understanding the movement behaviour of marine megafauna within and between habitats is valuable for informing conservation management, particularly for threatened species. Stable isotope analyses of soft-tissues have been used to understand these parameters in sea turtles, usually relying on concurrent satellite telemetry at high cost. Barnacles that grow on sea turtles have been shown to offer a source of isotopic history that reflects the temperature and salinity of the water in which the host animal has been. We used a novel method that combines barnacle growth rates and stable isotope analysis of barnacle shells (δ18O and δ13C) as predictors of home area for foraging sea turtles. We showed high success rates in assigning turtles to foraging areas in Queensland, Australia, based on isotope ratios from the shells of the barnacles that were attached to them (86-94% when areas were separated by >400 km). This method could be used to understand foraging distribution, migration distances and the habitat use of nesting turtles throughout the world, benefiting conservation and management of these threatened species and may be applied to other taxa that carry hitchhiking barnacles through oceans or estuaries.


Open science initiatives: challenges for public health promotion.
While academic open access, open data and open science initiatives have proliferated in recent years, facilitating new research resources for health promotion, open initiatives are not one-size-fits-all. Health research particularly illustrates how open initiatives may serve various interests and ends. Open initiatives not only foster new pathways of research access; they also discipline research in new ways, especially when associated with new regimes of research use and peer review, while participating in innovation ecosystems that often perpetuate existing systemic biases toward commercial biomedicine. Currently, many open initiatives are more oriented toward biomedical research paradigms than paradigms associated with public health promotion, such as social determinants of health research. Moreover, open initiatives too often dovetail with, rather than challenge, neoliberal policy paradigms. Such initiatives are unlikely to transform existing health research landscapes and redress health inequities. In this context, attunement to social determinants of health research and community-based local knowledge is vital to orient open initiatives toward public health promotion and health equity. Such an approach calls for discourses, norms and innovation ecosystems that contest neoliberal policy frameworks and foster upstream interventions to promote health, beyond biomedical paradigms. This analysis highlights challenges and possibilities for leveraging open initiatives on behalf of a wider range of health research stakeholders, while emphasizing public health promotion, health equity and social justice as benchmarks of transformation.


Market segmentation and industry overcapacity considering input resources and environmental costs through the lens of governmental intervention.
The problems with China's regional industrial overcapacity are often influenced by local governments. This study constructs a framework that includes the resource and environmental costs to analyze overcapacity using the non-radial direction distance function and the price method to measure industrial capacity utilization and market segmentation in 29 provinces in China from 2002 to 2014. The empirical analysis of the spatial panel econometric model shows that (1) the industrial capacity utilization in China's provinces has a ladder-type distribution with a gradual decrease from east to west and there is a severe overcapacity in the traditional heavy industry areas; (2) local government intervention has serious negative effects on regional industry utilization and factor market segmentation more significantly inhibits the utilization rate of regional industry than commodity market segmentation; (3) economic openness improves the utilization rate of industrial capacity while the internet penetration rate and regional environmental management investment have no significant impact; and(4) a higher degree of openness and active private economic development have a positive spatial spillover effect, while there is a significant negative spatial spillover effect from local government intervention and industrial structure sophistication. This paper includes the impact of resources and the environment in overcapacity evaluations, which should guide sustainable development in emerging economies.


A reevaluation of the Native American mtDNA genome diversity and its bearing on the models of early colonization of Beringia.
The Americas were the last continents to be populated by humans, and their colonization represents a very interesting chapter in our species' evolution in which important issues are still contentious or largely unknown. One difficult topic concerns the details of the early peopling of Beringia, such as for how long it was colonized before people moved into the Americas and the demography of this occupation. A recent work using mitochondrial genome (mtDNA) data presented evidence for a so called "three-stage model" consisting of a very early expansion into Beringia followed by approximately 20,000 years of population stability before the final entry into the Americas. However, these results are in disagreement with other recent studies using similar data and methods. Here, we reanalyze their data to check the robustness of this model and test the ability of Native American mtDNA to discriminate details of the early colonization of Beringia. We apply the Bayesian Skyline Plot approach to recover the past demographic dynamic underpinning these events using different mtDNA data sets. Our results refute the specific details of the "three-stage model", since the early stage of expansion into Beringia followed by a long period of stasis could not be reproduced in any mtDNA data set cleaned from non-Native American haplotypes. Nevertheless, they are consistent with a moderate population bottleneck in Beringia associated with the Last Glacial Maximum followed by a strong population growth around 18,000 years ago as suggested by other recent studies. We suggest that this bottleneck erased the signals of ancient demographic history from recent Native American mtDNA pool, and conclude that the proposed early expansion and occupation of Beringia is an artifact caused by the misincorporation of non-Native American haplotypes.


The role of the st313-td gene in virulence of Salmonella Typhimurium ST313.
Multidrug-resistant Salmonella enterica serovar Typhimurium ST313 has emerged in sub-Saharan Africa causing severe infections in humans. Therefore, it has been speculated that this specific sequence type, ST313, carries factors associated with increased pathogenicity. We assessed the role in virulence of a gene with a yet unknown function, st313-td, detected in ST313 through comparative genomics. Additionally, the structure of the genomic island ST313-GI, harbouring the gene was determined. The gene st313-td was cloned into wild type S. Typhimurium 4/74 (4/74-C) as well as knocked out in S. Typhimurium ST313 02-03/002 (Δst313-td) followed by complementation (02-03/002-C). Δst313-td was less virulent in mice following i.p. challenge than the wild type and this phenotype could be partly complemented in trans, indicating that st313-td plays a role during systemic infection. The gene st313-td was shown not to affect invasion of cultured epithelial cells, while the absence of the gene significantly affects uptake and intracellular survival within macrophages. The gene st313-td was proven to be strongly associated to invasiveness, harboured by 92.5% of S. Typhimurium blood isolates (n = 82) and 100% of S. Dublin strains (n = 50) analysed. On the contrary, S. Typhimurium isolates of animal and food origin (n = 82) did not carry st313-td. Six human, non-blood isolates of S. Typhimurium from Belarus, China and Nepal harboured the gene and belonged to sequence types ST398 and ST19. Our data showed a global presence of the st313-td gene and in other sequence types than ST313. The gene st313-td was shown to be expressed during logarithmic phase of growth in 14 selected Salmonella strains carrying the gene. This study reveals that st313-td plays a role in S. Typhimurium ST313 pathogenesis and adds another chapter to understanding of the virulence of S. Typhimurium and in particular of the emerging sequence type ST313.


Single level anterior interbody fusion and fixation in the treatment of thoracolumbar fractures.
Many surgical methods are available for repairing thoracolumbar fractures including short-segment internal fixation with posterior pedicle screws and anterior decompression and reduction. However, most methods are associated with significant surgical trauma and long postoperative recovery. The purpose of this study was to describe anterior single level interbody fusion and fixation for the repair of thoracolumbar fractures which may reduce surgical trauma and help speed recovery. A group of 21 patients who underwent single level anterior interbody fusion and fixation from June 2006 to June 2011 were compared with a group of 21 patients who underwent double level anterior interbody fusion and fixation during the same period. The groups were compared with regard to operation time, intraoperative blood loss, fracture healing time, ratio of pre- to postoperative endplate height between adjacent vertebrae, Cobb angle in the sagittal plane, recovery of neural function, and internal fusion failure. The 2 groups were similar with the exception of fracture location (P=0.017). The patients who underwent the single level procedure had a shorter operation time (P < 0.001), less blood loss (P < 0.001), and shorter follow-up (P < 0.001). Both groups had significant improvement in Cobb angle at 1 week and 1 year after surgery, but there was no significant difference between the groups. Both groups also exhibited improvement in neurological function, and the difference in improvement between the groups was not significant. Single level intervertebral fusion and internal fixation for thoracolumbar fractures provides as satisfactory an outcome as the traditional approach, double level anterior interbody fusion and fixation, and reduces the degree of surgical trauma.


The cellular and molecular bases of the sponge stem cell systems underlying reproduction, homeostasis and regeneration.
The evolution of multicellular organisms is generally thought (and seems likely) to have been accompanied by the evolution of a stem cell system. Sponges, some of the early-evolved metazoans, have totipotent/pluripotent stem cells. Thus, uncovering the cellular and molecular bases of the sponge stem cells will not only be crucial for understanding the ancestral gene repertoire of animal stem cells, but will also give us clues to understanding the evolution of molecular mechanisms for maintaining multipotency (pluripotency) and differentiation ability during animal evolution. Sponges (Porifera) are a large phylum that includes an enormous number of species, whose cellular compositions and life cycles show striking variations. In the last decade, methodologies for molecular studies and sequencing resources have dramatically advanced and made it possible to clearly define stem cells in sponges in cellular and molecular terms. In this review, together with recent studies of sponges in various classes, the following issues will be discussed: i) recent findings that revealed that the previously proposed model that "archeocytes and choanocytes are the two types of stem cells" originally based on work in demosponges can be applied as a unified view of the stem cell system in sponges that have various cellular organizations, ii) the fact that sponge cells are more plastic than previously thought, as shown by recent studies of sponge regeneration both from dissociated cells and upon injury, and iii) the importance of transdifferentiation in sponge stem cell systems and regeneration.


Studies on the amino acid fermentation. Part 1. Production of L-glutamic acid by various microorganisms.
Screening tests for glutamate producing strains were carried out, with the media containing carbohydrate and ammonia source as chief ingredients. Glutamate as well as certain other amino acids was detected by paper chromatography in culture broth of many microorganisms tested. Accumulation of L-glutamate in a significant amount (at least a few mg of glutamate per ml of broth) has been demonstrated by various strains of bacteria, streptomycetes, yeasts, and fungi. The highest level of glutamate production has been obtained by a new species of Micrococcus, yielding as much as 0.25 mole of it from one mole of glucose. The courses of fermentations mainly by known strains of microorganisms are shown. The importance of the cultural condition and strain specificity for the production of amino acids are briefly described.


A three-tiered approach to differentiate Listeria monocytogenes biofilm-forming abilities.
The purpose of this research was to develop a system for cultivating and evaluating Listeria monocytogenes biofilms that produces consistent and reliable results. A three-tiered approach was used to evaluate biofilm-forming abilities of three L. monocytogenes strains that were originally associated with listeriosis outbreaks. A L. monocytogenes 'honeycomb' biofilm structure was described. L. monocytogenes strains Scott A and V7 were comparable in developing biofilm network structures and F2365 was less effective in forming biofilm. This three-tiered method can be very useful for further biofilm studies.


Defects in the synthetic pathway prevent DIF-1 mediated stalk lineage specification cascade in the non-differentiating social amoeba, Acytostelium subglobosum.
Separation of somatic cells from germ-line cells is a crucial event for multicellular organisms, but how this step was achieved during evolution remains elusive. In Dictyostelium discoideum and many other dictyostelid species, solitary amoebae gather and form a multicellular fruiting body in which germ-line spores and somatic stalk cells differentiate, whereas in Acytostelium subglobosum, acellular stalks form and all aggregated amoebae become spores. In this study, because most D. discoideum genes known to be required for stalk cell differentiation have homologs in A. subglobosum, we inferred functional variations in these genes and examined conservation of the stalk cell specification cascade of D. discoideum mediated by the polyketide differentiation-inducing factor-1 (DIF-1) in A. subglobosum. Through heterologous expression of A. subglobosum orthologs of DIF-1 biosynthesis genes in D. discoideum, we confirmed that two of the three genes were functional equivalents, while DIF-methyltransferase (As-dmtA) involved at the final step of DIF-1 synthesis was not. In fact, DIF-1 activity was undetectable in A. subglobosum lysates and amoebae of this species were not responsive to DIF-1, suggesting a lack of DIF-1 production in this species. On the other hand, the molecular function of an A. subglobosum ortholog of DIF-1 responsive transcription factor was equivalent with that of D. discoideum and inhibition of polyketide synthesis caused developmental arrest in A. subglobosum, which could not be rescued by DIF-1 addition. These results suggest that non-DIF-1 polyketide cascades involving downstream transcription factors are required for fruiting body development of A. subglobosum.


Considerations for colorblind individuals on selecting colorimetric or fluorescent dye assay outcomes.
A disadvantage of colorimetric detection in nucleic acid amplification assays is the possibility that a colorblind individual may interpret colors differently than observers with full-color vision. Using an isothermal amplification assay, the ability of colorblind individuals to distinguish between positive and negative results for four dyes was tested. Five individuals with self-reported colorblindness and four with full-color vision reported their observations of the color of the solution. Although colorblind individuals may accurately interpret assay results, they were often not accurate in reporting the color. Hydroxynaphthol blue was the most problematic dye, and both phenol red and SYBR™ green were less troublesome. Consideration for colorblind individuals is warranted when developing an assay and training staff in its performance.


Preparation and Evaluation of Artemether Liposomes for Enhanced Anti-Tumor Therapy.
The aim of the study was to design liposomes (Lips) of artemether (ARM), a plant-derived drug for treatment of metastatic tumors, for the intravenous delivery. The ARM-Lips were prepared using ethanol injection method. Based on the optimization of formulation with single-factor experiments, ARM-Lips were spherical with a uniform particle size (187.3 ± 1.83) nm and its EE and DL were (94.49 ± 1.18)% and (10.94 ± 0.10)%, respectively. The in vitro drug release characteristics of ARM-Lips possessed a sustained release characteristic, and their behavior was in accordance with the first-order kinetics equation. In vivo, after intravenous injection to mice, the t1/2β, MRT, and AUC of ARM-Lips were 8.38-, 3.38-, and 3.11-fold those of ARM solution (ARM-Sol), respectively. In the pharmacodynamics studies, the tumor doubling time, growth inhibition rate, and specific growth rate of tumor of ARM-Lips were 1.97 times, 1.54 times, and 0.51 times those of ARM-Sol, respectively, which indicated that the anti-tumor effect of ARM-Lips was significantly stronger than that of ARM-Sol. These encouraging results revealed that ARM-Lips would serve as an efficient carrier for ARM for increasing therapeutic efficacy on tumor.