[Use of antiglaucoma therapy to reduce acute intraocular pressure rise following neodymium: YAG laser iridotomy in angle-closure glaucoma patients].
To evaluate the efficacy of topical antiglaucoma therapy in reducing acute intraocular pressure (IOP) elevation after neodymium: Yag laser iridotomy. Primary angle-closure glaucoma (PACG) eyes were randomized to receive premedication with latanoprost and pilocarpine, brimonidine 0.2% and pilocarpine or only with pilocarpine before Yag laser iridotomy. Postoperative IOP changes were compared with Wilcoxon signed-ranks test using the fellow eyes in each group. Postoperative pressure spikes were significantly lower in the groups of patients with local antiglaucoma therapy with pilocarpine than in the control group. Mean elevation of IOP was less in the groups of patients with local antiglaucoma therapy with pilocarpine at 2 hours postoperatively. Local antiglaucoma therapy may reduce the acute IOP rise following Yag laser iridotomy in PACG eyes.


Micro-computed tomography: a method for the non-destructive evaluation of the three-dimensional structure of biological specimens.
The large increase in interest in micro-computed tomography (micro-CT) over the last decade reflects the+ need for a method able to non-destructively visualize the internal three-dimensional structure of an object. Thereby, the real beauty of computed tomography lies in the fact that it is available for a large range of nominal resolutions, which allows hierarchical imaging from whole bodies down to the tissue level. Although micro-CT is currently mainly used for imaging of hard tissue (i.e., bone and tooth), future developments might also allow high soft tissue contrast either using appropriate contrast agents or x-ray contrast mechanisms. This chapter aims to review the steps necessary for a successful micro-CT measurement. Although the actual measurement is often machine dependent, the chapter does not describe a specific system but rather lists all steps that eventually have to be considered to set up a measurement, run the measurement, process the image data, and get morphometric indices as a result. The chapter provides an easy understandable manual that should allow newcomers to perform successful measurements and hence to best profit from this powerful technique.


Lower adropin expression is associated with oxidative stress and severity of nonalcoholic fatty liver disease.
Adropin has been reported to be involved in metabolic disorders, including nonalcoholic fatty liver disease (NAFLD). However, the clinical relevance of adropin expression to the histological severity of NAFLD is unclear. This study aimed to investigate adropin expression in biopsy-proven NAFLD patients. This case-control study enrolled a total of 109 participants, including 15 normal histological controls, 26 nonalcoholic fatty liver (NAFL), 21 nonalcoholic steatohepatitis (NASH) subjects and B-ultrasound NAFLD-free normal controls matched to the cases based on age and sex (the case:control ratio was 1:1). Liver biopsies were obtained and histological characteristics were assessed. Primary murine hepatocytes were isolated from C57BL/6J mice and incubated with doses of palmitate to induce oxidative stress. The serum adropin level in NASH patients was 9.99 ± 5.51 ng/ml, significantly lower than that in B-ultrasound normal controls (22.70 ± 6.32 ng/ml), histological normal controls (21.93 ± 6.63 ng/ml) and NAFL patients (17.82 ± 6.90 ng/ml). Serum adropin levels were negatively correlated with the histological severity of NAFLD. The lower serum adropin level predicted NASH (area under the ROC curve: 87.1%). Adropin expression in serum and liver was also negatively associated with hepatic MDA and serum 8-iso-PGF2α levels. Furthermore, palmitate rather than oleate induced oxidative stress in a dose-dependent manner with a gradient decrease in adropin expression in primary murine hepatocytes. Adropin overexpression or treatment ameliorated palmitate-induced oxidative stress in hepatocytes. Circulating adropin was inversely associated with the oxidative stress and histological severity of NAFLD. It may play an important role in the development of NAFLD.


Ten years of stroke programmes in Poland: where did we start? Where did we get to?
Risk factors and a high stroke mortality rate are a heavy stroke burden on Central and Eastern European countries. The 1995 Helsingborg Declaration outlined the aim of the coming decade was to improve patient care. In Poland it led to the foundation of the National Stroke Prevention and Treatment Programme, (1998-2008) which later became part of the National Cardiovascular Disease Prevention and Treatment Programme. • Improve acute and postacute management • Implement innovative therapies • Develop poststroke rehabilitation, and • Monitor epidemiology. Establishing and equipping stroke units has raised their number from three to 111. Thrombolysis for stroke and carotid angioplasty and stenting procedures were supported and supervised. The needs in poststroke rehabilitation were assessed and services have improved due to the support of the programme. Continuous monitoring of patient care proved that the mortality and disability rates have decreased and the quality of treatment has improved.


Prostaglandin-based rAAV-mediated glaucoma gene therapy in Brown Norway rats.
Prostaglandin analogs are first-line treatments for open angle glaucoma and while effective at lowering intraocular pressure, they are undermined by patient non-compliance, causing atrophy of the optic nerve and severe visual impairment. Herein, we evaluate the safety and efficacy of a recombinant adeno-associated viral vector-mediated gene therapy aimed at permanently lowering intraocular pressure through de novo biosynthesis of prostaglandin F2α within the anterior chamber. This study demonstrated a dose dependent reduction in intraocular pressure in normotensive Brown Norway rats maintained over 12-months. Crucially, therapy could be temporarily halted through off-type riboswitch activation, reverting intraocular pressure to normal. Longitudinal multimodal imaging, electrophysiology, and post-mortem histology revealed the therapy was well tolerated at low and medium doses, with no major adverse effects to anterior chamber health, offering a promising alternative to current treatment strategies leading to clinically relevant reductions in intraocular pressure without the need for adherence to a daily treatment regimen.


Early and late hormonal changes following progesterone injection to patients with secondary amenorrhea.
In humans, progesterone (Po) administration has been shown capable of eliciting luteinizing hormone (LH) and prolactin surges in a good estrogenic milieu, but whether such changes induce corpus luteum function still remains controversial. We therefore proposed to explore further the second hypothesis in a placebo-controlled type of study. In patients with secondary amenorrhea and low circulating estradiol (E2) levels with or without ovaries, a 50-mg progesterone injection induced only a short and transient rise in plasma Po levels. On the other hand, a similar injection to patients with mid-to late follicular levels of circulating E2 and intact ovaries induced a surge of plasma LH and prolactin which was followed by a sustained elevation in plasma Po. Furthermore, a rise in basal body temperature accompanied by evidence of secretory endometrium was also observed in these patients. It is concluded that, in a proper endocrine milieu, progesterone administration may induce luteinization in human subjects.


Punishment and psychopathy: a case-control functional MRI investigation of reinforcement learning in violent antisocial personality disordered men.
Men with antisocial personality disorder show lifelong abnormalities in adaptive decision making guided by the weighing up of reward and punishment information. Among men with antisocial personality disorder, modification of the behaviour of those with additional diagnoses of psychopathy seems particularly resistant to punishment. We did a case-control functional MRI (fMRI) study in 50 men, of whom 12 were violent offenders with antisocial personality disorder and psychopathy, 20 were violent offenders with antisocial personality disorder but not psychopathy, and 18 were healthy non-offenders. We used fMRI to measure brain activation associated with the representation of punishment or reward information during an event-related probabilistic response-reversal task, assessed with standard general linear-model-based analysis. Offenders with antisocial personality disorder and psychopathy displayed discrete regions of increased activation in the posterior cingulate cortex and anterior insula in response to punished errors during the task reversal phase, and decreased activation to all correct rewarded responses in the superior temporal cortex. This finding was in contrast to results for offenders without psychopathy and healthy non-offenders. Punishment prediction error signalling in offenders with antisocial personality disorder and psychopathy was highly atypical. This finding challenges the widely held view that such men are simply characterised by diminished neural sensitivity to punishment. Instead, this finding indicates altered organisation of the information-processing system responsible for reinforcement learning and appropriate decision making. This difference between violent offenders with antisocial personality disorder with and without psychopathy has implications for the causes of these disorders and for treatment approaches. National Forensic Mental Health Research and Development Programme, UK Ministry of Justice, Psychiatry Research Trust, NIHR Biomedical Research Centre.


Acute visual change.
Changes in vision or loss of vision are common complaints for patients presenting to the emergency department. Such complaints may represent a simple problem related to recent trauma, early evidence of a systemic disease, or may be a vision-threatening lesion. A logical and organized approach to the history and the physical examination of the patient with eye complaints is key to the diagnosis and treatment of the more significant causes of these complaints. This article reviews an organized approach to the patient with complaint of visual loss and considers the wide differential diagnosis. It focuses specifically on the evaluation of the patient complaining of visual changes resulting from central retinal artery occlusion, central retinal vein occlusion, retinal detachment, acute angle-closure glaucoma, giant cell temporal arteritis, and retrobulbar hemorrhage.


Evaluation of drug-induced reno-renal vasomotor reflex in the dog.
1. Renal arterial infusions of endogenous vasoactive compounds were administered, and elctromagnetic flow probes were used to measure simultaneous ipsilateral and contralateral renal blood flow. 2. The expected ipsilateral renal blood flow changes resulting from infusions of acetylcholine, noradrenaline, angiotension II, bradykinin and PGE2 were observed. There were no transient, phasic or sustained contralateral renal blood flow changes. 3. These results suggest that a previously hypothesized reno-renal vasomotor reflex communication does not exist. The discrepancies between these present studies and previous ones proposing such a reflex may be due to the methods chosen for measurement of renal blood flow.


Impotence: are the newer diagnostic methods a necessity?
Until recently our evaluation of impotent men included a psychiatric evaluation, and history and physical examination by a urologist to determine whether the impotence was organic or psychogenic. After the introduction of specific laboratory methods, such as nocturnal penile tumescence monitoring and penile blood pressure studies, clinicians relied heavily on these tools. We evaluated 33 impotent patients and compared the results of the laboratory methods to the initial diagnoses of the psychiatrist and the urologist to determine if the new methods would confirm our initial impressions or uncover different diagnoses. Thirteen patients were considered to have psychogenic impotence by the clinicians and only 1 patient in this group had evidence of organicity when the laboratory tests were used. Twelve patients were considered to have organic impotence by the clinicians and this was confirmed in 75 per cent of the cases by laboratory testing. Thus, clinical evaluation predicted the outcome of laboratory methods in 92 per cent of the psychogenic group and 75 per cent of the organic group. In addition, postage stamps were used during nocturnal penile tumescence monitoring and in predicting the outcome of nocturnal tumescence monitoring the stamp test had a sensitivity and a specificity of 91 per cent. Many patients presenting with erectile impotence can be evaluated adequately by a psychiatrist and a urologist without the support of expensive laboratory tests. The postage stamp test is useful when nocturnal penile tumescence monitors are not available. Finally, the Minnesota Multiphasic Personality Inventory is of limited value as a screening device.


Antimicrobial agents in the prevention and treatment of periodontal diseases.
It has been estimated that there are more than 400 diseases affecting the oral cavity. In terms of prevalence, however, the major public health problems are caries and periodontal disease. Although these two destructive entities are completely different in many respects, they share a common denominator: the initial lesions are brought about by an aggregate of bacteria known as plaque. This article discusses chemical control of plaque in the treatment of gingivitis and antimicrobial control of subgingival plaque in the treatment of periodontitis. The authors address the use of antibiotics in the treatment of localized juvenile periodontitis, the ideal properties of antiplaque agents, and adjunctive subgingival application of antimicrobial agents.


Infection and infertility.
Asymptomatic infection appears to be a common cause of fallopian tube damage resulting in ectopic pregnancy or infertility.


[Prevalence of antibodies and vaccination against measles, mumps and rubella in Polish population].
The data according number of cases and morbidity rates of measles, mumps and rubella as well as antibody prevalence against diseases above mentioned in Polish population were shown. The impact of mass vaccination on decreasing of measles incidence and number of reported rubella congenital syndrome was observed. The possibility of elimination these diseases in the near future was discussed.


Weight gain after adenotonsillectomy is more common in young children.
Adenotonsillectomy (TA), performed for obstructive sleep apnea (OSA) or recurrent tonsillitis (RT), has been associated with weight gain after surgery. The objective of this study was to look at a large population of children undergoing TA and the demographic factors that contribute to postoperative weight gain. Case series with retrospective chart review. Tertiary, urban academic care center. Children undergoing TA at an academic center between 2008 and 2011 were included in this study. Demographic data (age, gender, race), OSA disease severity, preoperative and 3- to 6-month postoperative normalized body mass index (BMI; z-scores), and changes in z-scores were compared. Complete weight data after TA were available for 115 children, 85 of whom underwent surgery for OSA. Mean age (7.2 ± 4.3 vs 7.3 ± 4.4 years, P = .955) and gender distribution (38% female vs 50% male; P = .323) were similar for the OSA and RT groups. However, children with OSA were more likely to be black (60% vs 33%) than RT patients (P = .026). Overall, the preoperative BMI z-score increased from 0.98 ± 1.50 to 1.21 ± 1.25 (P = .0009) with no difference by surgical indication (P = .58). Multiple linear regression analysis demonstrated that only age was significantly, and negatively, associated with changes in BMI z-scores (P = .015). Similar to previous studies, children had weight gain after TA. In this analysis, younger age (≤ 6 years) was a significant predictor of postoperative weight gain. Future research should prospectively evaluate the association between weight gain and demographic factors in children undergoing TA, with special attention to the relationship with age.


Effects of cue-triggered expectation on cortical processing of taste.
Animals are not passive spectators of the sensory world in which they live. In natural conditions they often sense objects on the bases of expectations initiated by predictive cues. Expectation profoundly modulates neural activity by altering the background state of cortical networks and modulating sensory processing. The link between these two effects is not known. Here, we studied how cue-triggered expectation of stimulus availability influences processing of sensory stimuli in the gustatory cortex (GC). We found that expected tastants were coded more rapidly than unexpected stimuli. The faster onset of sensory coding related to anticipatory priming of GC by associative auditory cues. Simultaneous recordings and pharmacological manipulations of GC and basolateral amygdala revealed the role of top-down inputs in mediating the effects of anticipatory cues. Altogether, these data provide a model for how cue-triggered expectation changes the state of sensory cortices to achieve rapid processing of natural stimuli.


Building relationships between academia and the pharmaceutical industry.
'The climate is perfect for a proactive search for partners between industry and academia.'


Incidence of abnormal cervical and vaginal cytology among women over age 65 years living with human immunodeficiency virus.
Women with human immunodeficiency virus have higher rates of abnormal cervical and vaginal cytology and, subsequently, of cervical and vaginal cancers. Although professional bodies currently advocate for indefinite cytology screening for women living with human immunodeficiency virus, these recommendations are based on expert opinion, not evidence-based. In the general population, women who have never had an abnormal cytology result can cease screening at age 65 years. This is due to the relatively low incidence of dysplasia in this group and the risk of false-positive results as women age, invasive follow-up testing, and destructive treatments of lesions that are unlikely to progress to cancer. What is unclear, however, is how human immunodeficiency virus-infected women over age 65 years who have no history of abnormal cytology should be screened to maximize benefit while reducing harms of overscreening. This is a crucial question, as women over age 65 years who are living with human immunodeficiency virus comprise a rapidly growing population. To describe the incidence of abnormal cervical and vaginal cytology results in women over the age of 65 years living with human immunodeficiency virus, with the goal of providing evidence for screening recommendations. A retrospective chart review was performed, identifying 69 women who received gynecologic follow-up in a county hospital system in Houston, Texas, between 2000 and 2018 and who met study criteria. Incidence of abnormal cytology after age 65 was determined by analyzing all available cytology results after age 65. Demographic and clinical risk factors, including human immunodeficiency virus-specific clinical risk factors, were analyzed. Matched cervical and vaginal pathology results, if conducted, were also evaluated. Statistical analyses were conducted using Stata 15, including χ2 tests and Wilcoxon rank-sum tests for categorical and continuous variables, respectively. Estimates of the cumulative probability of developing an abnormal cytology result was calculated using the Kaplan-Meier method. Among 69 women with no history of abnormal cervical cytology, 12 (17%) went on to develop abnormal cytology results, including 3 (4%) showing high-grade squamous intraepithelial lesions. The incidence rate was 3.5 cases per 100 woman-years (95% confidence interval, 1.58, 7.81). No demographic or gynecologic characteristics were associated with abnormal cytology. A CD4 count of <200 at the time of human immunodeficiency virus diagnosis or at the time of cytology was associated with an abnormal Papanicolaou test result (P < .0001, P = .031). Of women with pathology results in the county hospital system (n = 8), 4 (50%) had cervical intraepithelial neoplasia 2+ or vaginal intraepithelial neoplasia 2+. No women developed invasive cancer. However, 50% of women who had an abnormal Papanicolaou test result in the study period were lost to follow-up; outcomes for these patients are unknown. Given the relatively high proportion (4%) of women with high-grade squamous intraepithelial lesions/cervical intraepithelial neoplasia 2+/vaginal intraepithelial neoplasia 2+ during the study period, we agree with current screening recommendations for continued routine Papanicolaou testing after the age of 65 years in women with human immunodeficiency virus. More evidence from larger studies is needed to solidify evidence-based screening recommendations in this unique and growing population.


Vacuolar processing enzyme is essential for mycotoxin-induced cell death in Arabidopsis thaliana.
Some compatible pathogens secrete toxins to induce host cell death and promote their growth. The toxin-induced cell death is a pathogen strategy for infection. To clarify the executioner of the toxin-induced cell death, we examined a fungal toxin (fumonisin B1 (FB1))-induced cell death of Arabidopsis plants. FB1-induced cell death was accompanied with disruption of vacuolar membrane followed by lesion formation. The features of FB1-induced cell death were completely abolished in the Arabidopsis vacuolar processing enzyme (VPE)-null mutant, which lacks all four VPE genes of the genome. Interestingly, an inhibitor of caspase-1 abolished FB1-induced lesion formation, as did a VPE inhibitor. The VPE-null mutant had no detectable activities of caspase-1 or VPE in the FB1-treated leaves, although wild-type leaves had the caspase-1 and VPE activities, both of which were inhibited by a caspase-1 inhibitor. gammaVPE is the most essential among the four VPE homologues for FB1-induced cell death in Arabidopsis leaves. Recombinant gammaVPE recognized a VPE substrate with Km = 30.3 microm and a caspase-1 substrate with Km = 44.2 microm, which is comparable with the values for mammalian caspase-1. The gammaVPE precursor was self-catalytically converted into the mature form exhibiting caspase-1 activity. These in vivo and in vitro analyses demonstrate that gammaVPE is the proteinase that exhibits a caspase-1 activity. We show that VPE exhibiting a caspase-1 activity is a key molecule in toxin-induced cell death. Our findings suggest that a susceptible response of toxin-induced cell death is caused by the VPE-mediated vacuolar mechanism similar to a resistance response of hypersensitive cell death (Hatsugai, N., Kuroyanagi, M., Yamada, K., Meshi, T., Tsuda, S., Kondo, M., Nishimura, M., and Hara-Nishimura, I. (2004) Science 305, 855-858).


Masculinizer gene controls male sex determination in the codling moth, Cydia pomonella.
The molecular mechanisms of sex determination in moths and butterflies (Lepidoptera) with female heterogamety (WZ/ZZ) are poorly understood, except in the silkworm Bombyx mori. However, the Masculinizer (Masc) gene that controls male development and dosage compensation in B. mori, appears to be conserved in Lepidoptera, as its masculinizing function was recently confirmed in several moth species. In this work, we investigated the role of the Masc gene in sex determination of the codling moth Cydia pomonella (Tortricidae), a globally important pest of pome fruits and walnuts. The gene structure of the C. pomonella Masc ortholog, CpMasc, is similar to B. mori Masc. However, unlike B. mori, we identified 14 splice variants of CpMasc in the available transcriptomes. Subsequent screening for sex specificity and genetic variation using publicly available data and RT-PCR revealed three male-specific splice variants. Then qPCR analysis of these variants revealed sex-biased expression showing a peak only in early male embryos. Knockdown of CpMasc by RNAi during early embryogenesis resulted in a shift from male-to female-specific splicing of the C. pomonella doublesex (Cpdsx) gene, its downstream effector, in ZZ embryos, leading to a strongly female-biased sex ratio. These data clearly demonstrate that CpMasc functions as a masculinizing gene in the sex-determining cascade of C. pomonella. Our study also showed that CpMasc transcripts are provided maternally, as they were detected in unfertilized eggs after oviposition and in mature eggs dissected from virgin females. This finding is unique, as maternal provision of mRNA has rarely been studied in Lepidoptera.


Alpha-synuclein and intracellular trafficking: impact on the spreading of Parkinson's disease pathology.
Parkinson's disease is characterized by intracellular proteinaceous depositions known as Lewy bodies. These largely consist of the protein α-synuclein, whose physiological function remains unclear, but mutations and overexpression of the protein have been shown to cause early onset cases of Parkinson's disease. Deregulation of α-synuclein biology causes neurodegeneration and impaired neuronal trafficking, hinting at a possible contribution to the pathological mechanism. Recent studies produced some evidence hinting at the involvement of several regulators of the transport machinery such as Rab GTPases and SNARE proteins, but also shown that α-synuclein can be propagated between cells. Here, we discuss the molecular interplay of α-synuclein with the intracellular transport machinery, its consequences, and the implications for disease mechanisms.


Alpha-asaronol promoted oligodendrocyte precursor cell differentiation and improved myelination as an activator PPARγ.
Preterm white matter injury (PWMI), characterized by oligodendrocyte precursor cell (OPC) differentiation disorder and dysmyelination, is a prevalent demyelinating disease of the central nervous system in premature infants, necessitating the development of mitigating strategies. Convincing evidence suggests that peroxisome proliferator-activated receptor γ (PPARγ) activation is a stimulative factor against the hindered process of oligodendrocyte (OL) differentiation. However, much remains unknown about its promotive mechanism. Our previous study indicated that alpha-asaronol (α-asaronol) could alleviate myelination disorder in a neonatal PWMI rat model, but the mechanism remained unclear. In this study, we demonstrated that α-asaronol attenuated cognitive deficits, repaired myelin damage, and stimulated OL differentiation in the corpus callosum of PWMI rats. Co-immunoprecipitation analysis confirmed that α-asaronol induced the binding of PPARγ with its coactivator peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), which in turn activated oligodendroglial PPARγ. This activation subsequently upregulated the expression of phosphatase and tensin homolog (PTEN) and pro-differentiation-associated genes of Cnp1 and Klk6 and downregulated the expression of Clk1. However, the benefits of α-asaronol were blocked by GW9662, an antagonist of PPARγ. Moreover, α-asaronol also promoted OPC differentiation under oxygen-glucose deprivation conditions. In conclusion, α-asaronol can promote OL differentiation and myelination and alleviate cognitive deficits in neonatal PWMI rats by activating PPARγ and modulating OL differentiation-associated gene expression. This study suggests that α-asaronol may be a potential therapeutic drug for myelination failure in PWMI.


Basal cell carcinomata: Risk factors for incomplete excision and results of re-excision.
Re-excision of incompletely excised basal cell carcinomas (BCCs) can be unsatisfactory in the absence of residual tumours. Recommended guidelines do suggest re-excision as a treatment modality; however, its value has been questioned due to low or variable residual tumour presence. We analysed the incomplete excision and re-excision rates and the presence of residual tumours over an 18-month period in a single unit. Using pathology results and case notes, 2586 primary excisions of BCCs in 1717 patients were reviewed. The incomplete excision rate was reported to be 7.1% (184/2586). Excision of a lesion by multiple excision lesion procedure was associated with a higher rate of incomplete excision when compared to single lesion excision procedure (61.5% vs. 38.5%). Of the incompletely excised BCCs, 33.6% (62/184) were re-excised, of which 62.9% (39/62) had residual tumours. Although the figures are small, most anatomical sites examined had a residual tumour presence >50%. After evaluating each patient individually, considering the high residual tumour rate, re-excision of an incompletely excised BCC would be a worthwhile procedure.


[Impairments of conditioned behavior in adult rats induced by interleukine-1beta treatment in early postnatal ontogenesis].
Impairments of cognitive functions in children and adolescents are often consequences ofperinatal pathology (natal injuries, ischemia, hypoxia, infection and allergic diseases), which are accompanied by enhanced production ofproinflammatory cytokine interleukine-1beta. In this work it was shown that treatment with interleukine-1beta during the third week of life impaired active and passive avoidance conditioning in adult rats at the age of 60-70 days.


Risk factors for hepatitis C transmission in HIV patients, Hepacam study, ANRS 12267 Cambodia.
In 2009, we conducted a case-control study to explore the routes of HCV transmission in people living with HIV/AIDS (PLHIV) in Cambodia. Cases were HCV/HIV co-infected patients (who tested RT-PCR positive for HCV-RNA or had confirmed presence of HCV antibodies) (n = 44). Controls were HIV mono-infected patients, with no HCV antibodies (n = 160). They were recruited among the PLHIV presenting at one national reference centre of HIV/AIDS. Multivariate analysis showed that factors associated with the co-infection were the age older than 50 years (OR 5.4, 95 % confidence interval (CI) 1.5-19.6), the exposure to multiple parenteral infusions before the year 2000 (OR 3.4, 95 % CI 1.5-7.6), to surgery (OR 2.6, 95 % CI 1.2-5.7) and to fibroscopy (OR 2.4, 95 % CI 1.0-5.7). These results show the need to implement HCV screening in PLHIV, to support the implementation of national infection control guidelines, and to reinforce public awareness on the risks linked to parenteral medications.


A prognostic risk model based on immune-related genes predicts overall survival of patients with hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is one of the most common heterogeneous tumors that occurs after chronic liver diseases and hepatitis virus infection. Immune-related genes (IRGs) and their ligands regulate the homeostasis of tumor microenvironment, which is essential for the treatment of HCC and its prognosis. This study aimed to investigate the clinical value of IRGs in predicting the prognosis of HCC. We downloaded RNA-seq data and clinical information from TCGA database. Samples were randomly divided into training cohort and testing cohort. The "limma" R package was performed to identify differentially expressed IRGs (DEIRGs) between HCC group and normal group. Prognostic DEIRGs (PDEIRGs) were obtained by univariate Cox analysis. LASSO and multivariate Cox analysis were used, and a prognostic risk model was constructed. In order to better demonstrate the clinical value of our model in predicting overall survival rate, a nomogram was constructed. To further investigate the molecular mechanism of our model, gene set enrichment analysis (GSEA) was performed. Compared with the low-risk group, the high-risk group had a significantly worse prognosis. Moreover, our prognostic risk model can accurately stratify tumor grade and TNM stage. Importantly, in our model, not only immune checkpoint genes were well predicted, but also human leucocyte antigen-I molecules were revealed. GSEA suggested that "MAPK signaling pathway," "mTOR signaling pathway," "NOD like receptor signaling pathway," "Toll like receptor signaling pathway," "VEGF signaling pathway," "WNT signaling pathway" had significant correlations with the high-risk group. Overall, our study showed that our prognostic risk model can be used to assess prognosis of HCC, which may provide a certain basis for the survival rate of patients with HCC.


Highly selective and ultrasensitive detection of nitrite based on fluorescent gold nanoclusters.
Near-infrared fluorescent gold nanoclusters (AuNCs) were prepared by sonochemical method and applied for the selective and sensitive detection of nitrite. The fluorescence of AuNCs could be selectively quenched by nitrite, and the mechanism was discussed in detail. The fluorescence intensity decreased linearly upon the increasing concentration of nitrite in a wide range of 2.0×10(-8) M to 5.0×10(-5) M. The detection limit was only 1.0 nM (S/N=3), which was much lower than the maximum admissible concentration of 2.2 μM required by the European Community. The proposed method was also applied for the determination of nitrite in real water samples. The present method exhibited excellent analytical performances, such as wide detection range, good selectivity, high sensitivity, and the applicability in neutral medium.


Preoperative radiation therapy and sphincter preservation by the combined abdominotranssacral technique for selected rectal cancers.
In an attempt to reduce the incidence of local recurrence and maintain normal sphincteric function in selected patients treated for rectal cancer, a clinical experience using full dose preoperative radiation therapy and a combined abdominotranssacral technique was begun in 1976. The first 24 of 55 patients treated have now been followed for 20 to 84 months, the median follow-up period being 39 months; sufficient data related to their clinical courses are available for analysis. Cancers were selected on the basis of unfavorability and location in the rectum (3- and 7-cm levels). Clinical staging of the disease was accurate and allowed selection and treatment of only those cancers considered unfavorable (stages B2 and C), thereby avoiding unnecessary radiation of more favorable tumors. One anastomotic disruption required reconstruction, but perioperative complications were otherwise unremarkable. Local recurrence in this group of highly unfavorable cancers has not been observed. Normal and sphincteric function has been preserved in each instance. Preliminary results indicate that full dose preoperative radiation therapy for selected unfavorable and low level cancers permits safe and effective sphincter preservation surgery by the combined abdominotranssacral technique. When proper precautionary measures are observed, surgery can be conducted with the expectation of normal continence and significant reduction in local recurrence.


Clinical studies on dissolution of gallstones using ursodeoxycholic acid.
Ursodeoxycholic acid (UDCA), 7beta hydroxy epimer of chenodeoxycholic acid (CDCA), has been used as a choleretica for 20 years in Japan. Recent report showing increased excretion of UDCA in bile after CDCA administration may suggest the possibility that UDCA has similar effects to CDCA on bile cholesterol unsaturation and on gallstone dissolution. The present paper describes the clinical usefulness of UDCA for gallstone patients during the past two years. Seventy-four gallstone patients with functioning gall-bladders, 19 men and 55 women with a mean age of 48 years, have been treated for 6 months or more. UDCA, supplied in tablets (Ursosan), was given 450 mg per day. The disappearance or the reduction of stone size or number, or both (dissolution effect) was recognized in 32 out of 74 patients (43%). In case of radiolucent stones, the overall effective rate was estimated for 24 of 46 patients (52%). There may be no significant difference in dissolution effect between CDCA and UDCA treatment, however, the merit of UDCA treatment seems to have its few side effects.


Protocol to generate endothelial cells, pericytes, and fibroblasts in one differentiation round from human-induced pluripotent stem cells.
Here, we present a protocol for differentiating human-induced pluripotent stem cells into three distinct mesodermal cell types: vascular endothelial cells (ECs), pericytes, and fibroblasts. We describe steps for using monolayer serum-free differentiation and isolating ECs (CD31+) and mesenchymal pre-pericytes (CD31-) from a single differentiation set. We then differentiate pericytes into fibroblasts using a commercial fibroblast culture medium. The three cell types differentiated in this protocol are useful for vasculogenesis, drug testing, and tissue engineering applications. For complete details on the use and execution of this protocol, please refer to Orlova et al. (2014).1.


Cyclo-(Phe-Tyr) reduces cerebral ischemia/reperfusion-induced blood-brain barrier dysfunction through regulation of autophagy.
Cerebral ischemia/reperfusion (I/R) injury is the result of ischemic stroke, a serious threat to public health. I/R injury can damage the blood-brain barrier (BBB), adversely affecting the brain environment and aggravating the injury. Cyclo-(Phe-Tyr) (sparganin C, SC) is a small molecule derived from the Chinese yam Dioscorea opposita Thunb. or Sparganii rhizoma. In our previous study, SC mitigates I/R injury both in vivo and in vitro through the action of JUNB and SOX5. However, the exact pharmacological effects of SC on BBB protection after an I/R injury remain unclear. We constructed a rat model of middle cerebral artery occlusion-reperfusion (MCAO/R) injury to evaluate the therapeutic actions of SC, and the integrity of the BBB was evaluated by ELISA, western blotting, and Evans blue staining. It was found that SC significantly reduced the amount of Evans blue staining in the brain, inhibited the expression of inflammatory factors IL-6, IL-1β, IL-17, IL-23, and TNF-α as well as TIPM1/MMP proteins, and promoted the expression of the tight junction proteins occludin, ZO-1, and claudin-5. SC was found to inhibit the excess autophagy induced by I/R injury to protect BBB integrity through the PI3K/AKT/mTOR pathway, and the PI3K inhibitor LY294002 significantly reduced the SC-mediated protection. Overall, this is the first demonstration of the alleviation of BBB damage caused by I/R injury by SC and suggests a potential treatment for the effects of an ischemic stroke.


[Paraneoplastic syndrome of disseminated intravascular coagulation in cardial carcinoma with multiple metastases].
A case of paraneoplastic DIC syndrome (asymptomatic carcinoma of the gastric fundus with multiple metastases) is described. Initially, differential diagnosis hesitated before thrombotic thrombocytopenic purpura (Moschowitz' syndrome), given the presence of grave microangiopathic haemolytic anaemia as a major symptom. The main characteristics of Moschowitz' syndrome and the most frequent causes of DIC are described in the discussion.


Antiparkinsonian dopamine agonists: a review of the pharmacokinetics and neuropharmacology in animals and humans.
With the intention of compensating for the deficit of endogenous dopamine (DA) in the basal ganglia of Parkinsonian patients by substitution with agents which directly stimulate central DA receptors, synthetic DA agonists have been introduced almost 20 years ago for the symptomatic treatment of Parkinson's disease. The original expectation that DA agonists would be able to completely restore extrapyramidal motor function in Parkinsonian patients has turned out as too mechanistic and simplicative. However, undoubtedly DA agonists have improved therapeutic possibilities in Parkinson's disease. Thus, clinical evidence from controlled chronic studies in patients indicates that the therapeutic results following the early application of DA agonists in combination with L-DOPA on a long-term base are superior to the respective monotherapy. However, none of the DA agonists currently employed for antiparkinsonian treatment i.e. apomorphine and the ergoline derivatives bromocriptine, lisuride and pergolide, is optimal with respect to pharmacokinetic properties (poor oral bioavailability with considerable intra- and interindividual variation) or pharmacological profiles (low selectivity for DA receptors in case of the ergot agonists). The pathophysiology underlying Parkinson's disease which turned out more complex than initially expected might provide another explanation for the limited therapeutic potential of DA agonists. Therefore, apart from summarizing the pharmacokinetics, biotransformation, neuropharmacology and neurobiochemistry of the DA agonists employed clinically, the present article also reviews physiological aspects of (a) central dopaminergic neurotransmission including the topographical distribution of DA receptor subtypes and their functional significance, (b) the intracellular signal processing in striatal output neurons and (c) the intraneuronal mechanisms which integrate the various neurotransmitter signals converging on the striatal output neuron to a demand-adjusted effector cell response via the cross-talk between the different second messenger systems. Based on these considerations, potential pharmacological approaches for the development of improved antiparkinsonian drugs are outlined. There is a therapeutic demand for more selective and better bioavailable DA agonists. In particular, selective D-1 receptor agonists are highly desirable to provide a more specific probe than SKF 38 393 for clarifying the current controversy on the disparate findings in nonprimate species and monkeys or Parkinsonian patients, respectively, regarding the functional significance of D-1 receptors for the antiparkinsonian action of DA agonists or L-DOPA. The therapeutic importance of D-2 receptor activation is generally accepted; whether DA agonists combining a balanced affinity to both D-1 and D-2 receptors within one molecule (to some extent a property of apomorphine) might be superior to subtype-specific DA agonists remains to be tested clinically.(ABSTRACT TRUNCATED AT 400 WORDS)


Too frail for surgery? A frailty index in major colorectal surgery.
Frailty is defined as increased vulnerability from accumulating morbidities in multiple organ systems. Evidence suggests frailty indices predict surgical outcomes in elderly patients. We assessed the validity of a frailty index in predicting post-operative outcomes in major colorectal surgery. A retrospective review of a prospective database was studied. Patients aged less than 65 years were excluded. Patients were assessed using a validated National Surgical Quality Improvement Program frailty index. Endpoints included intensive care unit (ICU) stay, post-operative complications and 30-day post-operative mortality, and also compared using American Society of Anesthesiologists (ASA) grade and P-Possum CR. Of the 205 patients, 43 (21%) were frail and 162 (79%) were not frail. Seven percent of frail patients required ICU stay compared with 6% non-frail patients (P > 0.05, NS). P-Possum in frail versus non-frail groups in ICU was 48% versus 8.6% (P < 0.05). Forty percent of frail and 26% non-frail patients developed post-operative complications (P > 0.05, NS) with mean P-Possum of 23% versus 12% in these groups, respectively (P < 0.05). Five percent of frail patients and 2.5% non-frail patients died within 30 days of surgery (P > 0.05, NS) with a mean P-Possum of 43% versus 7% in these groups, respectively (P > 0.05, NS). These data demonstrate that frail patients who developed complications, died within 30 days and required admission to ICU had significantly higher P-Possum CR scores. However, the P-Possum CR score is a superior predictor of post-operative outcomes than frailty index alone.


Seed germination ecology of Bidens pilosa and its implications for weed management.
It is now widely recognized that Bidens pilosa has become a problematic broadleaf weed in many ecosystems across the world and, particularly in the light of recent climate change conditions, closer management strategies are required to curtail its impact on agricultural cropping. In this investigation, experiments were conducted to evaluate the effect of environmental factors on the germination and emergence of B. pilosa, and also on the response of this weed to commonly available post-emergence herbicides in Australia. The environmental factors of particular interest to this current work were the effect of light and temperature, salinity, burial depth and moisture on B. pilosa since these are key management issues in Australian agriculture. In addition, the effects of a number of commonly used herbicides were examined, because of concerns regarding emerging herbicide resistance. In the tested light/dark regimes, germination was found to be higher at fluctuating day/night temperatures of 25/15 °C and 30/20 °C (92-93%) than at 35/25 °C (79%), whilst across the different temperature ranges, germination was higher in the light/dark regime (79-93%) than in complete darkness (22-38%). The standard five-minute temperature pretreatment required for 50% inhibition of maximum germination was found to be 160 °C, and it was further shown that no seeds germinated at temperatures higher than 240 °C. With regard to salinity, some B. pilosa seeds germinated (3%) in 200 mM sodium chloride (NaCl) but all failed to germinate at 250 mM NaCl. Germination declined from 89% to 2% as the external osmotic potential decreased from 0 to -0.6 MPa, and germination ceased at -0.8 MPa. Seeding emergence of B. pilosa was maximum (71%) for seeds placed on the soil surface and it was found that no seedlings emerged from a depth of 8 cm or greater. A depth of 3.75 cm was required to inhibit the seeds to 50% of the maximum emergence. In this study, application of glufosinate, glyphosate and paraquat provided commercially acceptable control levels (generally accepted as >90%) when applied at the four-leaf stage of B. pilosa. However, none of the herbicide treatments involved in this study provided this level of control when applied at the six-leaf stage. In summary, B. pilosa germination has been clearly shown to be stimulated by light and thus its emergence was greatest from the soil surface. This suggests that infestation from this weed will remain as a problem in no-till conservation agriculture systems, the use of which is increasing now throughout the world. It is intended that information generated from this study be used to develop more effective integrated management programs for B. pilosa and similar weeds in commercial agricultural environments which are tending toward conservation approaches.


Satisfactory Usage of a Lacerated Kidney for Transplantation: A Case Report.
Organ shortage is the main bottleneck in the wait-list for transplantation; therefore, expanding the donor pool is an effective way to solve the problem. Usage of the traumatized liver for transplantation has been applied, but the use of lacerated kidneys for transplant donor is rarely reported. We reported a successful case of donation after brain death. The donor committed suicide by jumping from a campus dormitory building. One of the donated kidneys was severely injured. Two lacerations measured 4 × 1 × 1 cm in the medial margin of the graft and 1 × 1 × 1.5 cm in the front side of the graft, respectively. After repair with continuous absorbable suture, the lacerated kidney was transplanted to a recipient. The post-transplantation renal function gradually recovered. Furthermore, serious complications, such as large amounts of hemorrhage, delayed graft function, or urinary fistula did not occur. The serum creatinine dropped from 1232 μmol/L to 120 μmol/L and maintained normal range after surgery. In addition, the daily urine output was normal. At day 12 after operation, the patient was discharged. Our case shows that the use of a lacerated donor kidney appears to be feasible, but long-term effects need further observation.


The potential lost hospital income from miscoded emergency department boarders in Ireland.
Emergency department (ED) boarders, namely patients who have been admitted under an in-patient service but remain on a trolley in the ED, have long been a problem in the Irish healthcare system. We conducted a retrospective analysis of all ED boarders in Cork University Hospital (CUH) for a 6-month period from January to July 2011. Data were obtained from the Hospital In-Patient Enquiry Office (HIPE). The income generated by the hospital for a subset of these patients (January and February attendances) was obtained from the Finance Office in the hospital, based on diagnoses as recorded on the HIPE system. A convenience sample of two-thirds of the 39 acute hospitals nationally was surveyed to ascertain whether ED boarders were coded by individual HIPE offices as hospital in-patients or as ED attendees. A total of 806 patients were admitted to an in-patient service from January to July 2011 in CUH and subsequently discharged, having completed their entire stay in the ED. The income generated by a sub-sample of 228 patients (January and February ED boarders) was determined. The hospital was remunerated by <euro>685,111 for these patients, i.e. an average income of <euro>3,098 per patient. Only 8 hospitals of the 27 surveyed hospitals coded overnight ED Boarders as in-patients and were thus able to request income for these patients appropriately. Discrepancies in coding of ED boarders may result in significant revenue losses for certain hospitals.


Care for the chronically ill: the future role of health care professionals and their patients.
In future decades the number of chronically ill will increase drastically. A function-orientated approach, substitution and transmural care would seem to be the key objectives for the necessary improvement in care. There will be significant changes in the task division of care provided by specialists, general practitioners and paramedics. At the same time, patients will be able to increase their own potential for self-care. Who will play which role in future will have to be considered against the background of the various phases in the course of a chronic disease. In the initial stages, in particular, there will be ample opportunity to involve patients more in their own care. This will have a positive influence on learning to live with a chronic disease, dependence on medical help and the course of the disease itself. Transdisciplinary collaboration, that means interactive collaboration with the necessary mutual knowledge and understanding of the working methods, should form the basis of the care in all phases of a chronic disease. Different carers are involved in each phase of care for the chronically ill, but since the general practitioner is involved in all phases, it is obvious that the necessary organization of collaboration between the various carers (including the patient) should be coordinated by the general practitioner.


Implementation of an integrated multidisciplinary Movement Disorders Clinic: applying a knowledge translation framework to improve multidisciplinary care.
To evaluate the implementation of an integrated multidisciplinary Movement Disorder Clinic using a model of knowledge translation. A mixed methods design was used to evaluate implementation outcomes. After recognising poor referral rates to allied health, Movement Disorder Clinic team-members identified implementation barriers. Team- and process-level implementation strategies were designed and tailored to address these barriers. The primary outcome measure was the change in the proportion of patients referred to allied health, determined by comparing pre- and post-implementation documentation audits. Secondary outcome measures included clinician and consumer surveys to identify ongoing implementation barriers and stakeholder satisfaction. Documentation from 90 medical records was included in the audits (post-intervention n = 45). There was a significant improvement in the referral rates to allied health from 53% to 84% (mean improvement 31%, p = 0.003, Fisher's exact test). However, documentation of disease education decreased by 38% (p = 0.000, Fisher's exact test). Movement Disorder Clinic team-members identified three main barriers to ongoing implementation: "memory and automaticity", "environmental context and resources" and "beliefs about capabilities". Thirty-seven consumer surveys were completed, showing high levels of satisfaction (86%) but ongoing educational needs (51%). Implementation of an integrated multidisciplinary Movement Disorder Clinic was facilitated by a knowledge translation framework, leading to improved allied health referral rates and high levels of staff and consumer satisfaction, but unmet educational needs of consumers. Future research in the field of multidisciplinary healthcare for people with movement disorders is needed to determine the impact of these changes on patients' healthcare outcomes.Implications for rehabilitationMultidisciplinary integrated healthcare models may lead to better outcomes in progressive diseases such as Parkinson's disease, however, can be challenging to implement.A knowledge translation framework facilitated successful implementation of an integrated multidisciplinary Movement Disorders Clinic, leading to significantly improved rates of appropriate referrals to allied health, and staff and consumer satisfaction.Team-members identified three main barriers to ongoing implementation - "memory and automaticity", "environmental context and resources," and "beliefs about capabilities" - which may impact sustainability and should be considered in future implementation efforts.


Medical management of pancreatic neuroendocrine tumors in patients with MEN 1: case report.
Multiple endocrine neoplasia type 1 (MEN-1) is a rare inherited autosomal dominant disease which manifests itself with at least one clinical scenario before 45 years of age. The value of somatostatin analogue therapy is unknown in the treatment of non-functioning pancreatic tumours and a few studies have been published in this field. We report a young patient with MEN-1 with multiple gastric and pancreatic neuroendocrine tumors that was treated with the monthly injection of Sandostatin LAR before and After Distal Pancreatectomy and partial gastrectomy. Now she is well after four years of treatment with Sandostatin LAR.


Personalized Pre-clinic Nursing Telemedicine Visit: An Efficient and Efficacious Approach for Bowel and Bladder Dysfunction in Children.
To evaluate the effectiveness and efficacy of a Registered Nurse (RN) led educational pre-clinic telephone call on compliance and outcomes in children with bowel and bladder dysfunction (BBD). A retrospective chart review of a prospectively applied protocol in a single academic institution was performed for children aged 4-17 presenting with BBD. All children underwent a pre-clinic RN telemedicine visit where they were educated on pathophysiology of BBD, provided personalized urotherapy and bowel recommendations and instructed to complete pre-clinic questionnaires and voiding diaries. Patients were evaluated by a provider 4weeks following RN call. Data collected included compliance with forms, bowel management and need for imaging/testing, medications, and biofeedback. Patients were considered to improve with urotherapy alone if they were discharged from urology without the need for medications and/or biofeedback. In total, 277 patients completed an RN call and 224 patients attended a provider visit between December 2020 and June 2022. Mean age was 9.4years (3:1 Female to Male ratio). During the RN call, 154 (56%) patients had bowel management initiated. Of the 224 patients seen by a provider, 69% (n = 154) had symptom improvement or resolution with urotherapy alone. Thirty-eight patients (17%) enrolled in biofeedback with 7 (3%) completing all 8 sessions. Thirty-two patients (14%) required medication for daytime bladder symptoms. Our novel RN-led pre-clinic telemedicine visit demonstrates excellent compliance and patient outcomes for children with BBD and can reduce the use of unnecessary imaging, medications, and time-consuming treatments such as biofeedback.


The association of cultural and contextual factors with social contact avoidance during the COVID-19 pandemic.
As a first line of defense to the COVID-19 pandemic in 2020, people reduced social contacts to avoid pathogen exposure. Using a panel of countries, this research suggests that this was amplified in societies characterized by high social support and future orientation. People reacted more strongly in dense environments; government orders had more effect in high power distance societies. Conversely, a focus on accomplishments was associated with lower changes. Understanding people's actual behaviors in response to health threats across societies is of great importance for epidemiology, public health, international business, and for the functioning of humanity as a whole.


The nonspecific binding of Fe3+ to transferrin in the absence of synergistic anions.
An obligatory role for barbonate (or other synergistic anions) in the specific binding of Fe3+ by transferrin has been a point of controversy for two decades. There are an equal number of confirmatory and negative reports of specific Fe3+-transferrin binary complexes. A criticism of previous studies is the use of only one synthetic route, and limited product testing. This study reports the development of several preparative routes aimed at the formation of a specific Fe3+-transferrin complex, and the characterization of the products by spectrophotometry and chemical reactivity. The preparative routes described include: (a) displacement of carbonate from Fe3+-transferrin-CO32- at low pH followed by removal of CO2 by several techniques; (b) addition of FeCl3 to apotransferrin under CO2-free conditions; (c) oxidation of Fe2+ in the presence of apotransferrin under CO2-free conditions; (d) reaction of apotransferrin with nonsubstituting Fe3+ complexes in the absence of CO2; and (e) attempts to displace anions from weak Fe3+-transferrin-anion complexes. The product were examined with regard to their visible spectra, and their examined with regard to their visible spectra, and their reactivity with: (a) NaHCO3, (b) Fe3+-nitrilotriacetic acid in NaHCO3, and (c) citrate. The results are compared with the characteristics of Fe3+-transferrin-anion complexes and nonspecific Fe3+, transferrin mixtures. The data indicate that in the absence of synergistic anions the affinity of the specific metal binding sites of transfe-rin for Fe3+ is so low as to not compete favorably with hydrolytic polymerization and nonspecific binding effects.


[Optimal management of primary and secondary mitral regurgitation].
While morphologic alteration of parts of the mitral valve apparatus (ventricular wall, papillary muscles, chordae tendineae, valve annulus and leaflets) may result in a loss of its functional integrity (primary mitral regurgitation, MR) mitral annulus dilatation following left ventricular enlargement or change in chamber geometry and consecutive opening of the angle between papillary muscles and valve annulus cause secondary MR. Irrespective of these etiologies MR is chronically progressive and much more than the severity of MR the grade of myocardial adaptation to the chronic volume overload is of prognostic significance. Inadequate myocardial adaptation is demonstrated by an increase of the echocardiographically determined radius (r) to wall thickness (Th) ratio (r/Th > 3.0), indicating increasing left ventricular wall stress or by an insufficient increase of the left ventricular ejection fraction (< or = 5% of resting values) under exercise conditions, e.g. with radionuclide angiocardiography (RNV). Stressecho may replace RNV in the future for this indication. Actually, stress echo is not reliable to determine changes in left ventricular ejection fraction at rest versus exercise because of systematic errors and error reproduction. There are preliminary reports on biochemical markers like noradrenaline or tumor necrosis factor alpha being helpful to determine the breakdown of myocardial adaptation mechanisms. Surgical intervention is indicated in chronic MR irrespective of the hemodynamic severity, if myocardial adaptation is inadequate. If mitral reconstruction, the surgical technique of choice, remains insufficient to restore normal valve function, mitral valve replacement with preservation of the subvalvular apparatus is unavoidable. For a deceleration of the progressive volume overload in chronic MR for which a surgical intervention is not yet indicated, a long-term afterload reducing medical therapy preferably with long acting ACE-inhibitors seem to be prognostically favorable.


Forces and moments in knee-ankle-foot orthoses while walking on irregular surfaces: a case series study.
Kinetic data provide important information about the mobility performance of individuals with lower limb impairments and their assistive devices; however, there is limited understanding of this in real-life environments. To evaluate the effect of real-life irregular surfaces on forces and moments in knee-ankle-foot orthoses. In this case series study, a load cell was used to measure the forces and moments at the knee joint of knee-ankle-foot orthoses of individuals with unilateral muscle weakness as a result of poliomyelitis while walking on different ground surfaces and at different speeds. Significantly higher shear forces and external peak knee flexion moments were found when walking on irregular surfaces. In individual cases, certain irregular ground conditions elicited large increases in peak flexion moments (>50%) when compared to walking on smooth level ground. Forces and moments were significantly higher at faster walking speeds. Higher external peak knee flexion moments during the stance phase suggest that greater demands for support and stability are placed on individuals and their assistive devices when negotiating real-life ground surfaces. Clinical relevance This study demonstrates that walking on irregular surfaces alters the loads placed on knee-ankle-foot orthoses and that the requirements for knee stabilization increase. This has important clinical implications on the design, prescription, and use of such devices given the structural and functional demands placed on them.


Changes in thyroid status in pregnant women treated with ritodrine.
In a clinical study of 17 pregnant women treated with ritodrine, a beta 2-sympathomimetic agent used for tocolysis, thyroid hormone status was assessed longitudinally. This was done in order to verify the hypothesis that an increase in T3 levels could result from adrenergic stimulation, since propranolol, a beta blocking agent, has proved to decrease T3 levels in man. Indeed, a statistically significant increase in T3 serum concentration and in T3/T4 ratio was found on the second day after the start of treatment with ritodrine (p less than 0.02 and less than 0.01 respectively). After discontinuation of treatment a decrease in T3 serum levels, compared to both treatment and pretreatment levels, was observed. The free T4 concentration showed a significant drop after the first week of treatment (p less than 0.01), but no changes were found in T4 and TSH levels. It was concluded that the beta 2-mimetic-mediated changes in thyroid status provide one more reason for restriction of the use of beta-mimetic drugs in hyperthyroidic patients and might offer an additional explanation for the undesirable chronotropic cardiac side-effects of the therapy.


Golgi apparatus studied in vitreous sections.
Cryo-electron microscopy of vitrified specimen is the method of choice to explore cellular ultrastructure at high resolution as close as possible to the native state and environment. In this study, we investigated the Golgi apparatus - the main organelle of the secretory pathway. Cultured mammalian cells were fixed by high-pressure freezing, sectioned in vitreous ice and subjected to cryo-electron microscopy and cryo-electron tomography. Although the overall morphology of Golgi stacks was comparable to well prepared and plastic-embedded samples, in detail we reached much higher resolution in terms of distinction between biological structures based on their native density. On cisternal buds and peri-Golgi vesicles--some associated with microtubules--we detected two different subtypes of COPI coats: (1) a homogenous coat and (2) an inhomogeneous spiky coat, providing an 8-9 nm regularity, clearly distinct from clathrin coat. Next, we monitored the secretion of cargo, namely, procollagen I, through the Golgi complex. Temporally correlated with fluorescence microscopy, we performed three-dimensional cryo-electron tomography analysis and detected Golgi cisternae enlarged to saccules, containing cargo and showing inter-cisternal connections. Our work provides a first step towards the high-resolution description of the secretory pathway in native vitrified samples and describes the challenges associated with this attempt.


Synthetic approaches to 2-(4-hydroxy-7-chromanyl)benzoic acids as antagonists of leukotriene B4.
Structural modification of 1 led to a series of 2-(4-hydroxy-7-chromanyl)benzoic acid LTB4 antagonists exemplified by 2 and 3. The use of an organostannane biaryl coupling, a non steroselective reduction and a chromatographic resolution limited the utility of this synthetic route. To address these issues, a new synthetic route was developed utilizing a palladium catalyzed coupling of aryl oxazolines in tandem with a stereospecific enone reduction as key synthetic steps. Resolution was achieved by fractional crystallization of a (S)-(-)-alpha-methylbenzylamine salt.


Topology Consistency of Disease-specific Differential Co-regulatory Networks.
Sets of differentially expressed genes often contain driver genes that induce disease processes. However, various methods for identifying differentially expressed genes yield quite different results. Thus, we investigated whether this affects the identification of key players in regulatory networks derived by downstream analysis from lists of differentially expressed genes. While the overlap between the sets of significant differentially expressed genes determined by DESeq, edgeR, voom and VST was only 26% in liver hepatocellular carcinoma and 28% in breast invasive carcinoma, the topologies of the regulatory networks constructed using the TFmiR webserver for the different sets of differentially expressed genes were found to be highly consistent with respect to hub-degree nodes, minimum dominating set and minimum connected dominating set. The findings suggest that key genes identified in regulatory networks derived by systematic analysis of differentially expressed genes may be a more robust basis for understanding diseases processes than simply inspecting the lists of differentially expressed genes.


[Considerations on correct diagnosis of atypical electrocardiographic T-wave findings in young subjects].
An analysis is made of the significance of the occasional observation of asymptomatic T-wave changes (inversion). The authors maintain that only an overall evaluation of the anamnestic, clinical and laboratory findings will enable the physician to make a correct diagnosis and exclude from the start, via coordinated protocols, any silent ischaemic disease, and also a series of clinical conditions that the ECG can reveal as this disease. In this connection the authors report a clinical case that is deemed interesting due to the finding of ECG anomalies in an asymptomatic young, athletic subject observed during a periodical medical examination for the purpose of certifying fitness for a specific type of work.


Current profile of cycling injuries: A retrospective analysis of a trauma centre level 1 in Queensland.
One out of 50 injury-related presentations to an ED is a transport-related cycling injury. Detailed information about the most frequent mechanism of cycling injuries, sustained injuries and patterns are under-reported. The objective of this research was to examine the pattern of injuries sustained by cyclists at a level 1 trauma centre. A retrospective review of data of injured cyclists admitted and treated at a level 1 trauma centre between 2011 and 2012 evaluated demographic data, mechanism of injury, injury pattern, economic costs and outcome. Data of 261 patients (mean age of 39 years) were reviewed, of which 88% was male patients with an average age of 38 years. Non-collision cycling injuries were reported in 55% of cases followed by collisions with other motor vehicles in 25.6% of cases. The mean injury severity score (ISS) was 9, but an ISS ≥ 12 was documented in 24%. Predominantly upper limb injuries (24.8%) were found, followed by injuries to the head and lower limb (each with 16.8%). Traumatic brain and chest injuries were equally seen in 8%. The overall length of stay was 4 days, and survival rate was 98%. This current data review reveals that non-collision traffic crashes accounted for the majority of injuries in cyclists treated in this facility, and the upper limb has replaced the head as the most injured body part. With a growing number of cyclists, this information contributes to considerations to improve road safety and trauma management.


Clinical and demographic characteristics of fatal anaphylaxis in Spain (1998-2011): A comparison between a series from the hospital system and a national forensic series.
Reports of fatal anaphylaxis remain scarce because of the rarity of the condition and the fact that information is limited to a few countries. Our objective was to investigate clinical and demographic characteristics and the causes of fatal anaphylaxis in Spain using two databases of cases of fatal anaphylaxis. We analysed fatal anaphylaxis in a series from the Spanish hospital system and a series from the National Institute of Toxicology and Forensic Sciences (Instituto Nacional de Toxicología y Ciencias Forenses [INTCF]), which predominantly comprise extrahospital deaths. Deaths from the Spanish hospital system were retrieved from among all deaths occurring during 1998-2011 using codes related to anaphylaxis. Deaths due to anaphylaxis in the INTCF database during the same period were retrieved by 2 allergists, who identified cases in which anaphylaxis was a possible cause of death. A logistic regression model was constructed to predict the characteristics of fatal anaphylaxis in each database. The incidence of death by anaphylaxis in Spain using both databases was 0.25 (95% CI, 0.24-0.26) deaths per million person-years. The most frequent causes of death in the hospital system were drugs (46.1%), unknown causes (40.0%), and foods (10.4%); in the INTCF, the most common causes of death were drugs (47.2%), insect stings (30.6%), and foods (11.1%). The logistic regression model showed that fatal anaphylaxis due to unknown causes (OR 15.2, 95% CI 1.8-129.8) was more likely in the hospital database, whereas insect stings (OR 100, 95% CI 10-833.3) and previous atopic comorbidity (OR 15.2, 95% CI 6.3-33.3) were more likely in the INTCF database. The estimated frequency of fatal anaphylaxis in Spain was among the lowest reported. Future studies of fatal anaphylaxis should use databases from different origins in order to show the considerable heterogeneity in this type of death.


Bizarre parosteal osteochondromatous proliferation: an educational review.
Bizarre parosteal osteochondromatous proliferation (BPOP) is a surface-based bone lesion belonging to the group of benign chondrogenic tumors. The aim of this review is to familiarize the readers with imaging features and differential diagnosis of BPOP, also addressing pathological presentation and treatment options. The peak of incidence of BPOP is in the third and fourth decades of life, although it can occur at any age. Hands are the most common location of BPOP (55%), followed by feet (15%) and long bones (25%). On imaging, BPOP appears as a well-marginated mass of heterotopic mineralization arising from the periosteal aspect of the bone. Typical features of BPOP are contiguity with the underlying bone and lack of cortico-medullary continuity, although cortical interruption and medullary involvement have been rarely reported. Histologically, BPOP is a benign bone surface lesion characterized by osteocartilaginous proliferation with disorganized admixture of cartilage with bizarre features, bone and spindle cells. Differential diagnosis includes both benign-such as florid reactive periostitis, osteochondroma, subungual exostosis, periosteal chondroma and myositis ossificans-and malignant lesions-such as periosteal chondrosarcoma and surface-based osteosarcoma. Treatment consists of surgical resection. Local recurrences are common and treated with re-excision.Critical relevance statement Bizarre parosteal osteochondromatous proliferation is a benign mineralized mass arising from the periosteal aspect of bone cortex. Multi-modality imaging characteristics, pathology features and differential diagnosis are here highlighted to familiarize the readers with this entity and offer optimal patient care.


Morphological changes of pituitary gonadotrophs and thyrotrophs following treatment with LH-RH or TRH in vitro.
To investigate the relationship between LH-RH and TRH and the formation of castration cells and thyroidectomy cells, pituitary glands of 14-day old female rats were cultured with LH-RH or TRH for 10 days. Observed in these glands were external and internal zones, the former containing active, healthy appearing cells, and the latter consisting of many degenerative and necrotic cells. Gonadotrophs and thyrotrophs were readily demonstrated in the external zone of the organs by immunocytochemistry. Hypertrophic gonadotrophs (castration cells) and thyrotrophs (thyroidectomy cells) were observed only in the external zone by electron microscopy. Neither the typical signet-ring gonadotrophs nor intracisternal granules of thyroidectomy cells were seen in the present study. However, the hypertrophic gonadotrophs or thyrotrophs were similar to castration cells or thyroidectomy cells observed in the pituitary gland following castration or thyroidectomy. The results indicate that LH-RH and TRH directly stimulate the secretion of hormones and alter the morphological features of pituitary target cells.


Compositions and functions of the hatching froth from ricefield eel (Monopterus albus Zuiew).
The ricefield eel (Monopterus albus) is an economic fish species in China. To improve its artificial reproduction, we studied the compositions and functions of the hatching froth secreted by ricefield eels. The froth showed a viscosity of 2.72 mPaS, composed of glycoproteins with a sugar content of 0.156 mg/ml and a protein content of 0.250 mg/ml at a ratio of 1.60. The froth proteins were identified by SDS-PAGE as four proteins with the molecular weights of 42.5, 58.6, 65.3, and 98.2 kDa respectively. Their total amino acid content was 201.88 mg/100 ml, consisting of 16 kinds of amino acids. Filed observation revealed three beneficial effects of the froth on the hatching of the eel eggs. First, the froth increased the hatching rates of fertilized eggs at a range of water temperatures. Second, the froth decreased the rates of infection of the fertilized eggs by the water mold. Finally, the froth accelerated velum breakage in the fertilized eggs. Of the different hatching methods, froth incubation achieved the highest hatching rate and larvae survival rate. These results demonstrate the indispensable function of the froth of ricefield eels, and offer practical reasons for protecting the froth during the breeding season.


Cell type-specific eQTLs in the human immune system.
A new study reports the mapping of gene expression in primary immune cell subsets, showing the presence of cell type-specific cis and trans expression quantitative trait loci (eQTLs). The identification of cell type-specific trans-regulated networks can inform functional studies of susceptibility loci identified from genome-wide association studies for human complex diseases.


Heritability as an indicator of genetical variation in fecundity.
Heritability is well known to be a poor indicator of genetical variation in fitness. We show here that it is also an inadequate measure of genetical variation in fecundity.


Target directed identification of natural bioactive compounds from filamentous fungi.
Some of the most powerful natural antimicrobial compounds originate from filamentous fungi. However, due to the diversity of compounds from plant and fungal origin, separation, isolation, and identification of bioactive constituents can be a long and tedious process. This study explores the effectiveness of thin layer chromatography (TLC) in combination with bioautography in the separation and identification of bioactive compounds from several filamentous fungi. Ultra-performance liquid chromatography coupled to photodiode array detector (UPLC-DAD) was employed to quantitatively identify phenolic composition. The total phenolic content of the selected filamentous fungi ranged from 31.85 mg g-1 to 101.77 mg g-1. Additionally, liquid chromatography mass spectrometry (LC/MS) determined the most abundant fatty acids were linoleic, palmitic, oleic, and stearic acid. Submerged cultivation of Grifola frondosa, Monascus purpureus, Lentinula edodes, Trametes versicolor and Pleurotus ostreatus proved to be an effective method to produce natural antimicrobial compounds.


Treatment of periarticular calcification after total hip arthroplasty.
Calcification after total hip arthroplasty resulting in severely impaired function requiring reoperation is rare. This is a report on one patient with wide spread calcification where the patient was treated with Indometacin and the total hip exchanged.


"What's measured gets done": a call for a European semester for cancer to improve cancer outcomes in Central and Southeastern Europe.
Cancer mortality varies widely across Europe, and survival depends on where you live. In particular, the inequality between countries in Central and South-Eastern Europe (CEE) and Western Europe (WE) is striking. The COVID-19 pandemic has brought existing inequalities into sharp focus, and the economic disruption it has caused threatens to deepen them. The Central European Cooperative Oncology Group (CECOG) has created a platform with the aim to reduce health inequalities and to improve patient access to cancer care. The subject of discussion is the value of new treatments to create willingness to invest in improving cancer outcomes while managing the budget. The platform includes various stakeholders as scientific leaders, policy makers, payers, patients and industry.


Stimulating the ventrolateral prefrontal cortex (VLPFC) modulates frustration-induced aggression: A tDCS experiment.
The prefrontal cortex is crucial for top-down regulation of aggression, but the neural underpinnings of aggression are still poorly understood. Past research showed the transcranial direct current stimulation (tDCS) over the ventrolateral prefrontal cortex (VLPFC) modulates aggression following exposure to risk factors for aggression (e.g., social exclusion, violent media). Although frustration is a key risk factor for aggression, no study to date has examined the modulatory role of tDCS on frustration-induced aggression. By exploring the VLPFC involvement in frustration-aggression link, we tested the hypothesis that the anodal tDCS over right and left VLPFC modulates frustration-induced aggression. We also explored whether tDCS interacts with gender to influence frustration-induced aggression. 90 healthy participants (45 men) were randomly assigned to receive anodal or sham tDCS over the right or left VLPFC before being frustrated by an accomplice. To increase reliability, several tasks were used to measure aggression. We found that anodal tDCS over the left VLPFC, compared to sham stimulation, increased aggression. Unexpectedly, no main effect was found following tDCS of right VLPFC. However, we also found a significant interaction between gender and tDCS, showing that males were more aggressive than females following sham stimulation, but females became as aggressive as males following active tDCS. Overall, these results shed light on the neural basis of frustration-induced aggression, providing further evidence for the involvement of VLPFC in modulating aggressive responses, and on gender differences in aggression. Future research should further investigate the role of stimulating the VLPFC on frustration-induced aggression.


Response of stomatal resistance and photosynthesis to night temperature in Populus deltoides.
Ramets from stem cuttings of three populations of Populus deltoides Bartr. from Wisconsin, Illinois, and Louisiana representing a latitudinal gradient were grown in pots outdoors at Urbana, Illinois and brought indoors for growth chamber studies. Leaf resistance and photosynthetic response to low night temperatures of 4° and 10° C were determined relative to 20° C controls for plants measured over one growing season. Plants from Louisiana, where nights are warm, reacted to cool nights of 4° and 10° C by opening their stomata slower upon illumination the following day than those from farther north where nights are cooler. The optimum night temperature for rate of opening was lower in the Wisconsin population than in populations from farther south. The Wisconsin population showed more ideal homeostasis of photosynthesis at different temperatures than the southern population which exhibited greater plasticity. No seasonal differences in these relationships were apparent other than at the time of leaf senescence.As plants approached senescence, which occurred earliest in the Wisconsin population, leaf resistance increased and photosynthesis declined, but stomata still retained their functional ability to respond to changes in night temperature. The change in leaf resistance, noted in the Wisconsin population, was related more to closure of lower-leaf surface stomata than upper. Only the Louisiana population had significantly more stomata on the lower than upper leaf surface.


B lymphocyte stimulator modulates number and function of endothelial progenitor cells in systemic lupus erythematosus.
Circulating endothelial progenitor cells (EPCs) are biologic markers of endothelial function. In patients with systemic lupus erythematosus (SLE), the numerical reduction and functional impairment of EPCs contribute to the endothelial dysfunction. Through ex vivo and in vitro studies, we aimed at evaluating the effects of B lymphocyte stimulator (BLyS) on EPC colonies and endothelial cells and also investigating BLyS receptor expression on these cells. EPCs were isolated from peripheral blood mononuclear cells (PBMC). In order to evaluate their ability to form colonies, EPCs were cultured on fibronectin-coated dishes and incubated with BlyS alone or BlyS and belimumab. Apoptosis of EPCs and endothelial cell line EA.hy926 was evaluated after 6, 12, and 24 h of incubation with BLyS and after 6 h with BLyS and belimumab. The expression of B cell activating factor-receptor (BAFF-R), B cell maturation antigen (BCMA), and transmembrane activator and calcium modulator and cyclophilin ligand (CAML) interactor (TACI) on EPCs and EA.hy926 was analyzed by cytofluorimetry. The number of EPC colonies was lower in patients than in controls. Moreover, the colonies from SLE patients were poorly organized compared to controls; the addition of belimumab restored the colony structure. Incubation with BLyS induced apoptosis of EPCs and EA.hy926 that was inhibited by the co-incubation with belimumab. BAFF-R and BCMA were expressed on both EPCs and EA.hy926, while TACI was expressed only on EPCs. EPCs and endothelial cells preferentially express BAFF-R which could be involved in the pro-apoptotic effect of BlyS. Belimumab administration seems to restore the quantitative and qualitative changes of EPC colonies both ex vivo and in vitro.


Insights from a cross-sectional binational study comparing obesity among nonimmigrant Colombians in their home country and Colombian immigrants in the U.S.
Latinos in the United States (U.S.) represent a heterogeneous minority population disproportionally impacted by obesity. Colombians in the U.S. are routinely combined with other South Americans in most obesity studies. Moreover, most studies among Latino immigrants in the U.S. solely focus on factors in the destination context, which largely ignores the prevalence of obesity and contextual factors in their country of origin, and warrant transnational investigations. Using 2013-17 data from the New York City Community Health Survey (NYC CHS, U.S.) and the National Survey of the Nutritional Situation (ENSIN, Colombia), Colombians that immigrated to the U.S. and are living in NYC (n = 503) were compared to nonimmigrant Colombians living in their home country (n = 98,829). Prevalence ratios (PR) for obesity (BMI ≥ 30 kg/m2) by place of residence were estimated using multivariable logistic regression adjusting for socio-demographic characteristics and daily consumption of sugar-sweetened beverages. The prevalence of obesity was 49% greater for immigrant Colombians living in NYC when compared to nonimmigrant Colombians living in in their home country (PR = 1.49; 95% CI 1.08, 2.07). Colombian immigrant men in NYC were 72% more likely to have obesity compared to nonimmigrant men living in their home country (PR = 1.72; 95% CI 1.03, 2.87). No significant differences were found in the adjusted models among women. Colombian immigrants in NYC exhibit a higher prevalence of obesity compared to their nonimmigrant counterparts back home and sex strengthens this relationship. More obesity research is needed to understand the immigration experience of Colombians in the U.S. and the underlying mechanisms for sex difference. Public health action focused on women in Colombia and both Colombian men and women immigrants in the U.S. is warranted to avert the long-term consequences of obesity.


BMI at different childhood age periods associated with cardiometabolic disorders in young adulthood.
The aim of this study was to investigate when the association between childhood obesity and adult cardiometabolic disorders starts to be operative. The study cohort included 811 participants who had data on blood pressure, lipid profile, fasting blood glucose, fasting insulin, or alanine aminotransferase in adulthood and had at least one measurement of BMI in childhood. Childhood BMI z score was significantly associated with increased risks of ≥1 cardiometabolic disorders, ≥2 cardiometabolic disorders, and elevated blood pressure in adulthood for age groups of 6 to 9 years, 10 to 12 years, 13 to 15 years, and 16 to 18 years, after adjustment for covariates. For low high-density lipoprotein cholesterol, significant associations were observed for age groups of 10 to 12 years, 13 to 15 years, and 16 to 18 years. For elevated triglyceride and elevated alanine aminotransferase, significant associations were observed for age groups of 13 to 15 years and 16 to 18 years. For insulin resistance, significant associations were observed for age groups of 10 to 12 years and 16 to 18 years. For elevated total cholesterol, elevated low-density lipoprotein cholesterol, or elevated fasting blood glucose, no association was observed in any age group. The association between childhood BMI and adult cardiometabolic disorders begins to be operative from early life. These results support universal screening of childhood obesity starting at an early age.


Effect of resistance exercise training on plasma neurofilaments in multiple sclerosis: a proof of concept for future designs.
Multiple sclerosis (MS) is a dysimmune and neurodegenerative disease of the central nervous system that continues to be one of the main causes of non-traumatic disability in young people despite the recent availability of highly effective drugs. Exercise-based interventions seem to have a positive impact on the course of the disease although pathophysiological mechanisms responsible for this benefit remain unclear. This is a longitudinal study to examine the effects of a short-term training program on neurofilament plasma levels, a biomarker of axonal destruction, measured using the ultrasensitive single molecule array (SiMoA). Eleven patients completed a 6-week supervised resistance-training program of 18 sessions that consisted of 3 sets of 8-10 repetitions of 7 exercises. Median plasma neurofilament levels significantly decreased from baseline (6.61 pg/ml) to 1 week after training intervention (4.44 pg/ml), and this effect was maintained after 4 weeks of detraining (4.38 pg/ml). These results suggest a neuroprotective effect of resistance training in this population and encourage us to investigate further the beneficial impact of physical exercise and to emphasize the importance of lifestyle in MS.


Methadone maintenance treatment: an update.
Available data (this review includes old major articles and recent articles) show that, although results are heterogeneous, methadone maintenance treatments (MMTs) have a real efficiency not only to reduce illicit opiate abuse (50-80% of patients under MMT did not use heroin in the preceding month) but also to reduce criminality, HIV risks and mortality, and to improve social rehabilitation, without inducing other alternative substance abuse. A minority of patients (perhaps 5-20%) stay on MMT on a very long-term basis (more than 10 years). Efficiency of MMTs are rather poorly related to patients' variables, with the exception of a moderately deleterious effect of a low age at onset of opiate dependence, a precocious or high involvement in criminality and an abuse of non-opiate drugs. On the other hand, variables related to treatment play a more important role in explaining heterogeneity of results. Optimal daily dose, high quality of medical and psycho-social services, clear orientation towards social rehabilitation and treatment retention (to allow a sufficient duration of treatment) and slow detoxification regimen of well-stabilized patients are all factors contributing to better results.


Z curve theory-based analysis of the dynamic nature of nucleosome positioning in Saccharomyces cerevisiae.
Nucleosome is the elementary structural unit of eukaryotic chromatin. Instability of nucleosome positioning plays critical roles in chromatin remodeling in differentiation and disease. In this study, we investigated nucleosome dynamics in the Saccharomyces cerevisiae genome using a geometric model based on Z curve theory. We identified 52,941 stable nucleosomes and 7607 dynamic nucleosomes, compiling them into a genome-wide nucleosome dynamic positioning map and constructing a user-friendly visualization platform (http://bioinfo.hrbmu.edu.cn/nucleosome). Our approach achieved a sensitivity of 90.31% and a specificity of 87.76% for S. cerevisiae. Analysis revealed transcription factor binding sites (TFBSs) were enriched in linkers. And among the sparse nucleosomes around TFBSs, dynamic nucleosomes were slightly preferred. Gene Ontology (GO) enrichment analysis indicated that stable and dynamic nucleosomes were enriched on genes involved in different biological processes and functions. This study provides an approach for comprehending chromatin remodeling and transcriptional regulation of genes.


Congenital diaphragmatic hernia: evaluation of prenatal diagnosis in 20 European regions.
To evaluate prenatal diagnosis of congenital diaphragmatic hernia by ultrasound in well-defined European populations. Data from 20 registries of congenital malformations in 12 European countries were included. The prenatal ultrasound screening programs in the countries ranged from no routine screening to three ultrasound investigations per patient being routinely performed. There were 187 cases with congenital diaphragmatic hernia, with an overall prenatal detection rate of 59% (110/187). There was considerable variation in prenatal detection rate between regions. There was a significant difference in the detection rate of isolated congenital diaphragmatic hernia (59/116, 51%) compared with congenital diaphragmatic hernia associated with multiple malformations, karyotype anomalies or syndromes (51/71, 72%) (P = 0.01). Termination of pregnancy was performed in 39 cases (21%) of which 14 cases were isolated congenital diaphragmatic hernia. Mean gestational age at discovery was 24.2 weeks (range, 11-38 weeks). The overall prenatal detection rate of congenital diaphragmatic hernia is high (59%) but varies significantly between European regions. The gestational age at discovery was greater than 24 weeks in half of the prenatally diagnosed cases.


Where there is no patient: an anthropological treatment of a biomedical category.
This work anthropologically applies the concept of 'personhood' to the Western biomedical patient role, and through cross-cultural comparisons with wellness-seeker roles (e.g. among the Maya of Guatemala and others) it seeks to discern the implications for global healthcare of assuming the universality of the "patient" role. Here, particular ethnographic attention is given to the presumption of the "patient" role in places and situations where, because of cultural and linguistic variation in local wellness-seeker roles and practices, there may be no "patient." It is hoped that establishing the biomedical patient role (with the clinical expectations, communicative and comportment practices that prefigure it) as acquired rather than intuitive, will help redirect cultural competence to the acquisition of patienthood, broadening it from an endless accrual of cultural inventories by physicians. Also it aims to shift existing biomedical associations of cultural variations in wellness-seeking away from a priori assessments of clinical defiance towards deeper understandings of the kinds of cultural differences that may make the difference treatment outcomes.


Polymorphisms of genes in nitric oxide-forming pathway associated with ischemic stroke in Chinese Han population.
To investigate the association of polymorphisms in four critical genes implicated in the NO-forming pathway with ischemic stroke (IS) in a Chinese Han population. DNA samples of 558 IS patients and 557 healthy controls from Chinese Han population were genotyped using the Taqman(TM) 7900HT Sequence Detection System. Six SNPs (rs841, rs1049255, rs2297518, rs1799983, rs2020744, rs4673) of the 4 related genes (eNOS, iNOS, GCH1, and CYBA) in the NO forming pathway were analyzed using the SPSS 13.0 software package for Windows. One SNP located in the intron of GCH1 (rs841) was associated with IS independent of the traditional cardiovascular risk factors in co-dominant and dominant models (P=0.003, q=0.027; P=0.00006, q=0.0108; respectively). Moreover, the combination of rs1049255 CC+CT and rs841 GA+AA genotypes was associated with significantly higher risk for IS after adjustments (OR=1.73, 95% CI: 1.27-2.35, P<0.0001, q<0.0001). The data suggest that genetic variants within the NO-forming pathway alter susceptibility to IS in Chinese Han population. Replication of the present results in other independent cohorts is warranted.


Catheters, wires, tubes and drains on postoperative radiographs of pediatric cardiac patients: the whys and wherefores.
Surgical treatment of congenital heart disease has advanced dramatically since the first intracardiac repairs in the mid-20th century. Previously inoperable lesions have become the focus of routine surgery and patients are managed successfully in intensive care units around the world. As a result, increasing numbers of postoperative images are processed by departments of radiology in children's hospitals. It is important that the radiologist accurately documents and describes the catheters, wires, tubes and drains that are present on the chest radiograph. This article reviews the reasons for the placement and positioning of perioperative equipment in children who have surgical repair of atrial septal defect, ventricular septal defect or transposition of the great arteries. Also included are a brief synopsis of each cardiac anomaly, the surgical procedure for its correction, and an in-depth discussion of the postoperative chest radiograph including illustrations of catheters, wires, tubes and drains.


A cohort study of leisure time physical activity and depression.
The objective of the study was to examine the role of leisure time physical activity on the risk of developing depression in a large longitudinal setting. A prospective cohort study was used, comprising three updated measures of leisure time physical activity and covariates and 26 years of follow-up data on 18,146 individuals from the Copenhagen City Heart Study, Denmark. The study population was linked to two Danish hospital registers for information on depression. Data were collected in three rounds, namely, 1976-1978, 1981-1983, and 1991-1994, and analyses were conducted in 2010. Compared to women with a high physical activity level, women with a moderate level had a hazard ratio of 1.07 (95% confidence interval: 0.80-1.44) for developing depression while women with a low level had a hazard ratio of 1.80 (95% confidence interval: 1.29-2.51). Compared to men with a high physical activity level, men with a moderate level had a hazard ratio of 1.11 (95% confidence interval: 0.73-1.68) for developing depression, while men with a low level had a hazard ratio of 1.39 (95% confidence interval: 0.83-2.34). Among women, a low level of physical activity was significantly associated with a greater risk of depression.


Oncogene-targeting nanoprobes for early imaging detection of tumor.
Malignant tumors have been one of the major reasons for deaths worldwide. Timely and accurate diagnosis as well as effective intervention of tumors play an essential role in the survival of patients. Genomic instability is the important foundation and feature of cancer, hence, in vivo oncogene imaging based on novel probes provides a valuable tool for the diagnosis of cancer at early-stage. However, the in vivo oncogene imaging is confronted with great challenge, due to the extremely low copies of oncogene in tumor cells. By combining with various novel activatable probes, the molecular imaging technologies provide a feasible approach to visualize oncogene in situ, and realize accurate treatment of tumor. This review aims to declare the design of nanoprobes responded to tumor associated DNA or RNA, and summarize their applications in detection and bioimaging for tumors. The significant challenges and prospective of oncogene-targeting nanoprobes towards tumors diagnosis are revealed as well.