In Vivo Voltage-Sensitive Dye Imaging of Subcortical Brain Function.
The whisker system of rodents is an excellent model to study peripherally evoked neural activity in the brain. Discrete neural modules represent each whisker in the somatosensory cortex ("barrels"), thalamus ("barreloids"), and brain stem ("barrelettes"). Stimulation of a single whisker evokes neural activity sequentially in its corresponding barrelette, barreloid, and barrel. Conventional optical imaging of functional activation in the brain is limited to surface structures such as the cerebral cortex. To access subcortical structures and image sensory-evoked neural activity, we designed a needle-based optical system using gradient-index (GRIN) rod lens. We performed voltage-sensitive dye imaging (VSDi) with GRIN rod lens to visualize neural activity evoked in the thalamic barreloids by deflection of whiskers in vivo. We stimulated several whiskers together to determine the sensitivity of our approach in differentiating between different barreloid responses. We also carried out stimulation of different whiskers at different times. Finally, we used muscimol in the barrel cortex to silence the corticothalamic inputs while imaging in the thalamus. Our results show that it is possible to obtain functional maps of the sensory periphery in deep brain structures such as the thalamic barreloids. Our approach can be broadly applicable to functional imaging of other core brain structures.


Nerve growth factor and brain-derived neurotrophic factor but not granulocyte colony-stimulating factor, nimodipine and dizocilpine, require ATP for neuroprotective activity after oxygen-glucose deprivation of primary neurons.
In previous work, we have demonstrated by radiolabeling, mass spectrometry and site-directed mutagenesis that nerve growth factor (NGF) as well as brain-derived neurotrophic factor (BDNF) and fibroblast growth factor 2 (FGF2) are capable of ATP-binding and that this binding appears to be essential for their neuroprotective activity. In this study, we attempted to shed some light on the question whether ATP is a general prerequisite for neuroprotection. Therefore, we used the non-ATP-binding granulocyte colony-stimulating factor (GCSF), the calcium antagonist nimodipine and the NMDA antagonist dizocilpine to find out whether they need ATP for neuroprotection comparable to NGF and BDNF. However, ATP was not necessary for the neuroprotective effects of GCSF, nimodipine and dizocilpine on primary cultures of rat cortical neurons damaged by oxygen-glucose deprivation whereas neuroprotection was demonstrable for NGF and BDNF only when ATP was present in the culture medium at a concentration higher than ca. 0.4nmol/l. In circular dichroism studies ATP caused changes of the secondary structure of NGF but not of GCSF. Taken together, we suggest that ATP is not a general prerequisite for neuroprotectivity but some growth factors like NGF and BDNF can stimulate their receptors only if they have bound ATP.


Galectin-1 as a novel risk factor for both gestational hypertension and preeclampsia, specifially its expression at a low level in the second trimester and a high level after onset.
Our aim was to evaluate whether the serum level of galectin-1 (Gal-1) at 18-24 and 27-31 weeks of gestation is a risk factor for predicting the later occurrence of not only preeclampsia (PE) but also gestational hypertension (GH). We measured serum levels of soluble fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (PlGF), and Gal-1 using an enzyme-linked immunosorbent assay in 81 and 73 normal pregnant women, 22 and 16 women with a later onset of GH, and 37 and 29 women with a later onset of PE at 18-24 and 27-31 weeks, respectively. We also measured Gal-1 in 33 women with GH and 78 women with PE after the onset. The levels of Gal-1 after the onset of GH, late-onset PE (onset at ⩾34 weeks), and early-onset PE (onset at <34 weeks) were significantly higher than those in normal pregnant women at 27-31 weeks. However, the low levels of Gal-1 (<8.1 ng ml-1) at 18-24 weeks, but not at 27-31 weeks, predicted the later occurrence of not only early-onset PE and late-onset PE but also GH. The low level of Gal-1 at 18-24 weeks was an independent risk factor for the later occurrence of GH and PE, after adjusting for the effects of a high BP and increased sFlt-1/PlGF ratio at 18-24 weeks. In conclusion, the serum level of Gal-1 is a novel risk factor for both GH and PE, specifically its expression at a low level in the second trimester and a high level after onset.


Association of skin autofluorescence with depressive symptoms and the severity of depressive symptoms: The prospective REACTION study.
Millions of people are afflicted by depression, a highly prevalent mental illness with increased morbidity and mortality. Advanced glycation end-products (AGEs) are potential risk factors for depression. We aimed to investigate the correlation of AGEs with depressive symptoms and the severity of depressive symptoms. This study was nested in the prospective REACTION (Risk Evaluation of cAncers in Chinese diabeTic Individuals) study and included 4420 eligible participants. skin autofluorescence (SAF) was used to measure skin AGEs. Depressive symptoms were evaluated by the Self-Rating Depression Scale (SDS). Multiple logistic regression analysis was used to assess the association of AGEs with depressive symptoms and the severity of depressive symptoms. Logistic analysis showed a significantly positive relationship between quartiles of SAF-AGEs and the risk of depressive symptoms with the OR [95% confidence interval (CI), p value] of 1.24 (95% CI: 1.03-1.50, p = 0.022), 1.39 (95% CI: 1.15-1.68, p = 0.001) and 1.57 (95% CI: 1.28-1.91, p < 0.001) for multivariable-adjusted model respectively. And SAF-AGEs were associated with the severity of depressive symptoms with the multivariable-adjusted OR (95% CI, p value) of 1.06 (95% CI:0.79-1.43, p = 0.681), 1.47 (95% CI: 1.08-1.99, p = 0.014), and 1.54 (95% CI: 1.12-2.11, p = 0.008) respectively. Stratified analyses showed that SAF-AGEs were significantly associated with the severity of depressive symptoms only in females, overweight people, individuals with hypertension, and those without diabetes and insomnia. The present study showed that a higher SAF-AGEs level was associated with depressive symptoms and the severity of depressive symptoms.


Clinical pharmacokinetics of the retinoids.
Etretinate, isotretinoin (13-cis-retinoic acid), and tretinoin (all-trans-retinoic acid) are retinoic acid analogues comprising a group of compounds known as the retinoids. However, they exhibit distinct and important differences with regard to their therapeutic and toxicological profiles. Tretinoin, due to a low oral therapeutic index, is limited almost exclusively to topical application, whereas etretinate and isotretinoin are therapeutically effective when given systemically by the oral route. Clinical doses of isotretinoin range from 0.5 to 8 mg/kg/day, with acute side effects appearing following doses of 1 mg/kg/day or greater. Plasma concentrations of isotretinoin following single and multiple doses peak between 2 to 4 hours and exhibit elimination half-lives of 10 to 20 hours. Isotretinoin blood concentration-time curves following a single- or multiple-dose regimen are well described by a linear model with biphasic disposition characteristics. Etretinate, which possesses a narrower therapeutic concentration range than isotretinoin, is used clinically at doses between 0.5 to 1.5 mg/kg/day; acute side effects appear following doses of 0.5 mg/kg/day or more. In most conditions, the retinoids produce a maximal effect in about 8 weeks (at the highest tolerated dose), with a slow recurrence of symptoms usually occurring within several weeks following cessation of treatment - except in the treatment of cystic acne with isotretinoin. Maintenance or intermittent dosing usually results in a prolongation of remission. Pharmacokinetically, the major difference between isotretinoin and etretinate is the much longer elimination half-life (120 days) of etretinate following long term administration. Recently, however, blood concentration versus time curves from day 1 to day 180 of etretinate therapy have been fitted by a single polyexponential pharmacokinetic equation without the need to invoke non-linearity in the kinetics. The observed lengthening of the elimination half-life with multiple dosing may thus be due to a lack of assay sensitivity at drug concentrations seen after single-dose administration, rather than to time-related alterations in the pharmacokinetics of etretinate.


Disseminated ecthymatous herpes varicella-zoster virus infection in patients with acquired immunodeficiency syndrome.
Herpesvirus infections are among the most common and debilitating opportunistic infections in patients with acquired immunodeficiency syndrome (AIDS), and they may have atypical clinical features. We describe the cases of three patients with AIDS in whom atypical persistent ulcerative skin lesions developed as a result of varicella-zoster virus infection. Two patients had disseminated infection without a vesicular stage; one patient had underlying asteatotic eczema. All responded well to acyclovir. One patient was treated with azidothymidine, and typical dermatomal herpes zoster subsequently developed. The profound loss of helper T cell function in AIDS may lead to multiple abnormalities in local immune response to cutaneous herpesvirus infections and may be responsible for the atypical morphology and a prolonged course.


Lumboperitoneal shunt for the treatment of hydrocephalus in premature infants.
Four premature infants weighing less than 2,500 grams underwent lumboperitoneal shunt for their communicating hydrocephalus. Using a microscope, mini-laminectomy and exact placement of the proximal end of the shunt tube into the subarachnoid space was achieved. After the lumboperitoneal shunting, hydrocephalus in all four patients was relieved without any complications. The author discusses the availability of lumboperitoneal shunt for hydrocephalus in premature infants.


Patterns of junctional communication in the early amphibian embryo.
It has long been recognized that cells in early embryos can communicate with each other via a direct cell-to-cell pathway, probably mediated by gap junctions. Low electrical resistance pathways, detected electrophysiologically, have been identified in all species examined so far. However, studies in various embryos on the transfer of molecules larger than small ions (for example, fluorescent dyes in the molecular weight range 350-500) have given conflicting results. In all these studies the ability to transfer dyes from cell to cell was determined without reference to the position of the injected cell in the embryo. In the experiments reported here, cell-cell transfer of the fluorescent dye, Lucifer yellow (molecular weight (Mr) 450) was re-examined in the early Xenopus laevis embryo by injecting the dye into identified cells, as the position of the injected cell within the embryo may be important. At the 32-cell stage, we found that dye transfer often occurred between animal pole blastomeres which were not sisters, as well as between sister cells, and also that Lucifer yellow was indeed transferred via gap junctions. The cell-cell transfer was not uniform within the animal pole; transfer was maximal near the dorsal side and minimal at the ventral side. This pattern may reflect differences in permeability or numbers of gap junctions across the embryo, and could be related to early events in development.


A Voltage-Responsive Synthetic Cl- -Channel Regulated by pH.
Transmembrane protein channels are an important inspiration for the design of artificial ion channels. Their dipolar structure helps overcome the high energy barrier to selectively translocate water and ions sharing one pathway, across the cell membrane. Herein, we report that the amino-imidazole (Imu) amphiphiles self-assemble via multiple H-bonding to form stable artificial Cl- -channels within lipid bilayers. The alignment of water/Cl- wires influences the conduction of ions, envisioned to diffuse along the hydrophilic pathways; at acidic pH, Cl- /H+ symport conducts along a partly protonated channel, while at basic pH, higher Cl- /OH- antiport translocate through a neutral channel configuration, which can be greatly activated by applying strong electric field. This voltage/pH regulated channel system represents an unexplored alternative for ion-pumping along artificial ion-channels, parallel to that of biology.


The prognostic value of biological markers in paediatric Hodgkin lymphoma.
Many biological and inflammatory markers have been proposed as having a prognostic value at diagnosis of Hodgkin lymphoma (HL), but very few have been validated in paediatric patients. We explored the significance of these markers in a large population of 769 affected children. By using the database of patients enrolled in A.I.E.O.P. (Associazione Italiana di Emato-Oncologia Pediatrica) trial LH2004 for paediatric HL, we identified 769 consecutive patients treated with curative intent from 1st June 2004 to 1st April 2014 with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), or hybrid COPP/ABV (cyclophosphamide, vincristine, prednisone, procarbazine, doxorubicin, bleomycin and vinblastine) regimens. On multivariate analysis with categorical forms, the 5-year freedom from progression survival was significantly lower in patients with stage IV or elevated value of platelets, eosinophils and ferritin at diagnosis. Furthermore, stage IV and eosinophils seem to maintain their predictive value independently of interim (after IV cycles of chemotherapy) positron emission tomography. Using the combination of four simple markers such as stage IV and elevated levels of platelets, ferritin and eosinophils, it is possible to classify the patients into subgroups with very different outcomes.


Interstitial Granulomatous Dermatitis as an Adverse Reaction to Vedolizumab.
A 61-year-old woman with a medical history of ulcerative colitis (UC) developed an erythematous, mildly pruritic, maculopapular rash that was histologically consistent with reactive granulomatous dermatitis (RGD) with interstitial granulomatous dermatitis (IGD)-type features 1 week after vedolizumab infusion. Awareness of this complication is key to enhanced recognition and appropriate management as use of this medication becomes more prevalent.


HLA antigens in schizophrenia, major depressive disorder, and schizoaffective disorder.
We carried out a study with 150 patients suffering from endogenous psychosis in order to confirm earlier findings of an association between HLA and various psychiatric syndromes. Our sample consisted of 107 schizophrenics, 25 patients with recurrent endogenous major depressive disorder, and 18 schizoaffectives. A significant excess of HLA B27 was found among schizophrenics with a family history of endogenous psychosis. This association is consistent with reported earlier studies. The preliminary data on the schizoaffective sample suggest a positive association with HLA B7. The data on patients with endogenous major depressive disorder failed to identify an association with HLA.


Functional electrical stimulation for chronic heart failure: a meta-analysis.
We conducted a meta-analysis of randomized, controlled trials of combined electrical stimulation versus conventional exercise training or placebo control in heart failure patients. A systematic search was conducted of Medline (Ovid) (1950-September 2011), Embase.com (1974-September 2011), Cochrane Central Register of Controlled Trials and CINAHL (1981-September 2011). The search strategy included a mix of MeSH and free text terms for the key concepts heart failure, exercise training and functional electrical stimulation (FES). FES produced inferior improvements in peak VO2 when compared to cycle training: mean difference (MD) -0.32 ml.kg(-1).min(-1) (95% C.I. -0.63 to -0.02 ml.kg(-1).min(-1), p=0.04), however FES elicited superior improvements in peak VO2: MD 2.30 ml.kg(-1).min(-1) (95% C.I. 1.98 to 2.62 ml.kg(-1).min(-1), p<0.00001); and six minute walk distance to sedentary care or sham FES; MD 46.9 m (95% C.I. 22.5 to 71.3m, p=0.0002). There was no difference in change in quality of life between cycling and FES, but FES elicited significantly larger improvements in Minnesota Living with Heart Failure score than placebo or sham treatment; MD 1.15 (95% C.I. 0.69 to 1.61, p<0.00001). Moreover, the total FES intervention hours were strongly correlated with change in peak VO2, (r=0.80, p=0.02). Passive or active exercise is beneficial for patients with moderate to severe heart failure, but active cycling, or other aerobic/resistance activity is preferred in patients with heart failure who are able to exercise, and FES is the preferred modality in those unable to actively exercise. The benefits of FES may however, be smaller than those observed in conventional exercise training. Aggregate hours of electrical stimulation therapy were associated with larger improvements in cardio-respiratory fitness.


Antibody blockade of Thy-1 (CD90) impairs mouse cytotoxic T lymphocyte induction by anti-CD3 monoclonal antibody.
Thy-1 (CD90) expressed by mouse T cells is known to have signal transducing properties, but the ability of Thy-1 to enhance cytotoxic T lymphocyte (CTL) development is not well understood. Here we show that stimulation of mouse T cells with monoclonal antibodies (mAb) to CD3, CD28 and Thy-1 (clone G7), which were coimmobilized on polystyrene microbeads, resulted in a greater proliferative response than stimulation with only anti-CD3 and anti-CD28 mAb, indicating that Thy-1 cross-linking enhanced T cell receptor/CD28-driven T cell activation. Consistent with this finding, Thy-1 blockade with a soluble nonactivating anti-Thy-1 mAb (clone 30-H12) inhibited anti-CD3-induced proliferation of CD4+ and CD8+ T cells, and the induction of cytotoxic effector cells in a dose-dependent fashion. Interleukin-2 synthesis and CD25 expression were also impaired by Thy-1 blockade. The inhibitory effect involved a defect at or before the level of protein kinase C activation because the addition of phorbol ester ablated the anti-Thy-1-mediated inhibition of anti-CD3-induced T cell activation. The CTL that were induced in the presence of blocking anti-Thy-1 mAb adhered to target cells but showed reduced expression of granzyme B and perforin. In contrast, Fas ligand expression and function was not affected by Thy-1 blockade. We conclude that Thy-1 signalling promotes the in vitro generation of CTL that kill in a granule-dependent fashion.


The Evans ratio for ventricular size: a calculation error.
The suggestion that the Evans ratio, the ratio of the transverse diameter of the anterior horns of the lateral ventricles to the internal diameter of the skull, was a more significant quantity than the ventricular measurement alone was based on a calculation error. The value of this ratio and other such ratios involving linear skull measurements is unproven.


Effect of denosumab versus zoledronic acid on calcium levels in cancer patients with bone metastasis: A retrospective cohort study.
To identify the incidence of hypercalcemia and hypocalcemia in zoledronic acid and denosumab groups. Secondary objective was to determine the correlation between calcium supplement and calcium level control. An observational retrospective cohort study was conducted by reviewing patient electronic records, laboratory results, and medication charts from 1 August 2015 to 31 July 2016. Adult cancer patients who were diagnosed with bone metastasis secondary to a solid tumor or multiple myeloma and who received either zoledronic acid or denosumab were included. Other indications for bone targeting agents were excluded. Data of bone targeting agents administration encounters were collected, evaluated, and analyzed. A total of 1141 encounters (for 271 patients) were included. The incidence of hypocalcemia was higher in denosumab compared to zoledronic acid group (5.5% vs. 3.1%, OR = 0.55, 95% CI [0.3-1.0]; P = 0.05). Hypercalcemia incidence was also higher in denosumab group (8.5% vs. 3.1%, OR = 2.9, 95% CI [1.68-5.03]; P < 0.0001). Breast cancer was the most common malignancy associated with hypocalcemia (27.3%) followed by ovarian cancer (25%) and multiple myeloma (22.7%). The risk of developing hypocalcemia was reduced by 16% in patients receiving calcium supplementation (RR = 0.84, 95% CI [0.55-1.20]; P = 0.39). Denosumab use was associated with higher rates of both hypercalcemia and hypocalcemia compared to zoledronic acid. Adequate supplementation with calcium substantially reduced the risk of hypocalcemia. Our results highlight the importance of taking preventative measures upon bone targeting agents initiation and during treatment including regular monitoring of calcium levels and providing supplements accordingly.


Effect of anticholinergic burden on brain activity during Working Memory and real-world functioning in patients with schizophrenia.
Cognitive impairment has been associated with poor real-world functioning in patients with Schizophrenia. Previous studies have shown that pharmacological treatment with anticholinergic properties may contribute to cognitive impairment in Schizophrenia. We investigated the effect of the anticholinergic burden (ACB) on brain activity, cognition, and real-world functioning in Schizophrenia. We hypothesized that greater ACB would be associated with altered brain activity along with poorer cognitive performance and lower real-world functioning. A sample of 100 patients with a diagnosis of schizophrenia or schizoaffective disorder was recruited in the naturalistic multicenter study of the Italian Network for Research on Psychoses (NIRP) across 7 centres. For each participant, ACB was evaluated using the Anticholinergic Cognitive Burden scale. The association of ACB with brain function was assessed using BOLD fMRI during the N-Back Working Memory (WM) task in a nested cohort (N = 31). Real-world functioning was assessed using the Specific Level of Functioning (SLOF) scale. Patients with high ACB scores (≥3) showed lower brain activity in the WM frontoparietal network (TFCE corrected alpha <0.05) and poorer cognitive performance (p = 0.05) than patients with low ACB scores (<3). Both effects were unaffected by demographic characteristics, clinical severity, and antipsychotic dosage. Moreover, patients with high ACB showed poorer real-world functioning than patients with lower ACB (p = 0.03). Our results suggest that ACB in Schizophrenia is associated with impaired WM and abnormal underlying brain function along with reduced real-world functioning. Clinical practice should consider the potential adverse cognitive effects of ACB in the treatment decision-making process.


Knowledge, attitude, and practice of body shape and fitness among university students in China.
Body shape and fitness (BSF) is critical for overall well-being, while university students in China are subjected to stress, peer pressure, performance anxiety, busy schedules, and lack of sleep, which can easily lead to poor BSF. This study aimed to explore the knowledge, attitude, and practice of BSF and related factors among university students in China. This web-based cross-sectional study was conducted on students of 15 universities in China between September 1st and November 30th, 2022. The KAP scores were evaluated using a 38-item questionnaire, including social demography, knowledge, attitude, and practice. Univariable and multivariable regression analyses were performed to identify the factors associated with KAP. A total of 995 valid questionnaires were collected. There were 431 (43.3%) males and 564 (56.7%) females. Most participants were sophomores (51.2%) and freshmen (36.3%). Most participants had a BMI of 18-24 kg/m2 (66.1%). The students scored highly on BSF-related knowledge (8.30 ± 1.49), moderately on attitude (37.20 ± 4.46), and low on practice (19.64 ± 4.62). Multivariate logistic regression analysis showed that attitude score (P = 0.001), sex (P = 0.001), grade (P = 0.011), body mass index (BMI) (P < 0.050), parent's education level (P = 0.005), monthly allowance (P < 0.050), and sleep quality and habits (P = 0.016) were independently associated with practice scores. University students in China were found to have good knowledge, moderate attitude, and poor practice toward BSF. Attitude, sex, grade, BMI, parents' education, monthly living expenses, and sleep quality and habits affected their practice. More BSF-related courses or activities are required to motivate students, especially females.


Dissection of Host Susceptibility to Bacterial Infections and Its Toxins.
Infection is one of the leading causes of human mortality and morbidity. Exposure to microbial agents is obviously required. However, also non-microbial environmental and host factors play a key role in the onset, development and outcome of infectious disease, resulting in large of clinical variability between individuals in a population infected with the same microbe. Controlled and standardized investigations of the genetics of susceptibility to infectious disease are almost impossible to perform in humans whereas mouse models allow application of powerful genomic techniques to identify and validate causative genes underlying human diseases with complex etiologies. Most of current animal models used in complex traits diseases genetic mapping have limited genetic diversity. This limitation impedes the ability to create incorporated network using genetic interactions, epigenetics, environmental factors, microbiota, and other phenotypes. A novel mouse genetic reference population for high-resolution mapping and subsequently identifying genes underlying the QTL, namely the Collaborative Cross (CC) mouse genetic reference population (GRP) was recently developed. In this chapter, we discuss a variety of approaches using CC mice for mapping genes underlying quantitative trait loci (QTL) to dissect the host response to polygenic traits, including infectious disease caused by bacterial agents and its toxins.


Arteriosclerosis: facts and fancy.
Arterial vascular diseases comprise the leading cause of death in the industrialized world. Every physician learns about the pathology of these diseases in medical school. All pathologists evaluate arterial disease in surgical pathology and/or autopsy specimens. All clinicians encounter patients with clinical manifestations of these diseases. With such a common and clinically-important group of entities one would think there would be a general understanding of the "known" information that exists. That is, physicians and scientists should be able to separate what is fact and what is fancy. This review article is intended to generate thought in this regard.


Does neighboring group participation by non-vicinal esters play a role in glycosylation reactions? Effective probes for the detection of bridging intermediates.
Neighboring group participation in glycopyranosylation reactions is probed for esters at the 3-O-axial and -equatorial, 4-O-axial and -equatorial, and 6-O-sites of a range of donors through the use tert-butoxycarbonyl esters. The anticipated intermediate cyclic dioxanyl cation is interrupted for the axial 3-O-derivative, leading to the formation of a 1,3-O-cyclic carbonate ester, with loss of a tert-butyl cation, providing convincing evidence of participation by esters at that position. However, no evidence was found for such a fragmentation of carbonate esters at the 3-O-equatorial, 4-O-axial and -equatorial, and 6-O positions, indicating that neighboring group participation from those sites does not occur under typical glycosylation conditions. Further probes employing a 4-O-(2-carboxy)benzoate ester and a 4-O-(4-methoxybenzoate) ester, the latter in conjunction with an (18)O quench designed to detect bridging intermediates, also failed to provide evidence for participation by 4-O-esters in galactopyranosylation.


Lateral flow immunoassay for sensitive detection of undeclared chicken meat in meat products.
This study presents the development of an immunochromatographic test system aimed at the detection of chicken additives in meat products. It is based on sandwich-format lateral flow immunoassay (LFIA) of immunoglobulins as a biomarker for species identification. The LFIA based on gold nanoparticles as a label for anti-species antibodies was used to determine chicken immunoglobulins and, accordingly, chicken meat in food products. Absence of cross-reactivity with mammalian species tested in the study confirmed high specificity of the determination. The test system showed good sensitivity and rapidity, allowing for the detection of as low as 0.063% (w/w) chicken meat in raw meat mixtures within 20 min. As a result of the testing of raw and cooked meat products, it was shown that the test system can reliably recognize specific immunoglobulins even after heat processing. The proposed assay can be recommended for rapid on-site screening control of the composition and quality of meat products.


Association between dating app use and unhealthy weight control behaviors and muscle enhancing behaviors in sexual minority men: a cross-sectional study.
Body image concerns are prevalent and are viewed as risk factors for engaging in unhealthy weight control behaviors (UWCBs), such as purging, fasting, and the misuse of laxatives and diet pills. Studies have also linked UWCBs to the development of eating disorders. In the United States (U.S.), sexual minority men (e.g., bisexual, gay, and men who have sex with men) are prone to UWCBs often as a result of societal pressures to achieve certain standards of appearance - of which are often perpetuated through various media platforms. A growing number of studies have explored the possible role mobile dating applications ("dating apps") play in contributing to UWCBs. To our knowledge, such studies have not explored this possible relationship between dating apps and UWCBs in sexual minority men (SMM). To fill this gap in the scientific literature, the present study assessed the association between dating app use and UWCBs and muscle enhancing behaviors among a sample of adult SMM in the U.S. 549 SMM participated in an anonymous survey from Qualtrics Survey Panels. UWCBs and muscle enhancing behaviors were assessed through items adapted from national surveys. Body image dissatisfaction was assessed using the Male Body Attitudes Scales. Participants also reported their history of dating app use. We performed descriptive statistics, chi-square tests, and student's t-tests. Multivariable logistic regression models assessed the relationship between dating app use and UWCBs and muscle enhancing behaviors. Dating app users had significantly higher body image dissatisfaction scores than non-users. Dating app users also demonstrated significantly elevated odds of engaging in four UWCBs and muscle enhancing behaviors: laxatives, diet pills, muscle-building supplements, and protein powders. This is one of the first studies to assess dating app use and its association with UWCBs and muscle enhancing behaviors in SMM. Increased surveillance and detection for such behaviors among SMM, particularly those using dating apps, are needed.


[Refinement of technique for cosmonaut's body radiation loading estimation using of orbital station dosimetric monitoring system].
Proposed is a technique for estimation of radiation loading of cosmonauts' body from the data of the space station radiation monitoring system by bringing the objective to a linear mathematical model. Resulted matrix ratios allow to work out the challenge; test calculations illustrating efficiency of the proposed technique are included.


Dissociation between decision making under ambiguity and risk in patients with juvenile myoclonic epilepsy.
Decision making (DM) is one aspect of impulsivity that can be defined by the ability to decide between two or more options in a given situation. To date, there are at least two types of DM that differ in the level of uncertainty, and how much information about consequences is provided. In this study, we aimed to evaluate the two domains of DM - under risk and ambiguous - with a comprehensive evaluation in a group of patients with juvenile myoclonic epilepsy (JME), and correlate with patients' characteristics, clinical variables, and neuropsychological evaluation for executive functions. We evaluated 35 patients with JME and 39 healthy controls using the Iowa Gambling Task for DM under ambiguity and the Game Dice Task for DM under risk. We assessed the performance in Iowa Gambling Task and Game Dice Task through net scores, safe and risky choices, besides the type of decisions across time. Patients with JME had a higher number of risky choices compared to controls in the Game Dice Task. There was no significant difference between patients and controls in the Iowa Gambling Task. However, patients with higher seizure frequency had worse scores on decks C and D (safe choices) from the Iowa Gambling Task. Patients with JME have worse performance on DM under risk. The same was not observed for DM under ambiguity. Epilepsy-related factors and the presence of psychiatric disorders, but not executive dysfunction, were associated with a lower tendency for safe choices. These findings showed a dissociation between DM processes in patients with JME and a tendency to make disadvantageous decisions with measurable risks.


Bryostatin 1 antagonizes the terminal differentiating action of 12-O-tetradecanoylphorbol-13-acetate in a human colon cancer cell.
12-O-Tetradecanoylphorbol-13-acetate (TPA), a highly active representative of the tumor-promoting phorbol esters, induces a rapid terminal differentiation of a human colon cancer cell line. Bryostatin 1, a macrocyclic lactone, completely counteracts this effect of TPA and promotes continued replication. The observed responses provide a system for identifying cellular processes which are involved in the induced terminal differentiation of human colon cancer cells.


A taxonomic revision of the tube-web spiders of the genus Ariadna (Araneae: Segestriidae) in Tasmania.
The genus Ariadna Audouin, 1826 is revised for Tasmania to include 13 species, ten of which are described as new: Ariadna abbreviata sp. nov., A. alta sp. nov., A. amabilia sp. nov., A. crypticola sp. nov., A. ferrogrisea sp. nov., A. fragilis sp. nov., A. gonzo sp. nov., A. muscosa Hickman, 1929, A. segmentata Simon, 1893, A. subnubilum sp. nov., A. thylacinus sp. nov. and A. tigrina sp. nov.. The species described in this manuscript exhibit high levels of sympatry.


Clinical impact of colonization with multidrug-resistant organisms on outcome after allogeneic stem cell transplantation in patients with acute myeloid leukemia.
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment option for patients with acute myeloid leukemia (AML). During transplantation, patients undergo a period of severe neutropenia, which puts them at high risk for infectious complications. However, the impact of patient colonization with multidrug-resistant organisms (MDRO) on overall survival remains unclear. In this retrospective, single-center study, the authors analyzed data from 264 patients with AML who underwent a first allo-HSCT between January 2006 and March 2016 at their institution. Primary endpoints were overall survival and nonrelapse-related mortality. One hundred forty-two of 264 patients (53.8%) were colonized by at least 1 MDRO, mainly with vancomycin-resistant Enterococcus faecalis/faecium (n = 122). The characteristics of colonized patients did not differ from those of MDRO-negative patients with respect to median age (53.5 vs 53 years), cytogenetic risk according to European LeukemiaNet criteria, remission status before allo-HSCT (first or second complete remission: 55.7% vs 60.7%, respectively; active disease: 44.4% vs 39.3%, respectively), donor type, or hematopoietic cell transplantation-comorbidity index (HCT-CI). Compared with noncolonized patients, MDRO-positive patients had an inferior probability of survival at 5 years (43.3% vs 65.5%; P = .002), primarily because of a higher cumulative incidence of nonrelapse-related mortality (33.9% vs 9.4%; P < .001). Death caused by infections occurred in 15.5% of colonized patients versus 4.9% of noncolonized patients. There was no difference in the cumulative incidence of relapse in MDRO-positive versus MDRO-negative patients (33.8% vs 42.1%, respectively; P = .798). The current data emphasize the importance of regular MDRO screenings and prompt further investigations into the impact of colonization with MDRO on the immune system after allo-HSCT. Cancer 2018;124:286-96. © 2017 American Cancer Society.


Long-term outcome in women who underwent anti-reflux surgery in childhood.
The purpose of ureterocystoneostomy to correct vesicoureteral reflux is to thereby prevent recurrent febrile urinary tract infections (UTIs). The objective of this study was to determine the frequency of UTI in adult women who underwent reimplantation as children, with the emphasis on infections during pregnancy. Included in the study were women over 20 years of age who underwent surgery for primary reflux between 1969 and 2004. A total of 392 patients were identified and information on their case history, surgery and follow-up was collected from the medical records. A questionnaire, requesting information on their present state of health, and occurrences of lower or upper UTI since the age of 16 and during any pregnancies, was sent to 337 of these patients. In all, 242 (84%) of the questionnaires were returned. UTIs had occurred in 42% of the women before they had any sexual activity; thereafter the frequency increased to 61%. In 113 of the 282 women, 242 pregnancies were recorded. UTI occurred during 59 pregnancies (24%): 19% lower, 5% upper. Risk factors for UTI during pregnancy were infections as adults or decreased differential renal function (< or = 30%). There is an ongoing risk of UTI in adult women after anti-reflux surgery in childhood. During pregnancy, these women represent a population at risk who should be observed very closely.


IUD use among parous women and risk of uterine perforation: a secondary analysis.
The objective of the study was to determine if delivery and lactation are risk factors for complete intrauterine device perforations. We performed a reanalysis of the European Active Surveillance Study on Intra-Uterine Devices data set using complete penetration of the myometrium as the definition for perforation. Of the 61,448 women enrolled (70% levonorgestrel, 30% copper devices), we identified 58 complete perforations, 30 of which occurred in lactating women. Incidence per 1000 insertions was 4.5 (95% confidence interval [CI]: 3.0-6.4) for lactating and 0.6 (95% CI: 0.4-0.9) for nonlactating women. Time since delivery was also associated with perforation risk. Lactation and delivery are independent cofactors for perforation. Results do not differ when restricting the definition of perforation.


The Effect of Purified Human Bone Marrow-Derived Mesenchymal Stem Cells on Rotator Cuff Tendon Healing in an Athymic Rat.
To evaluate the ability of purified human bone marrow-derived mesenchymal stem cells (MSCs) to augment healing of an acute small- to medium-sized rotator cuff repair in a small-animal model, evaluating the structure and composition of the healing tendon-bone interface with histologic and biomechanical analyses. Fifty-two athymic rats underwent unilateral detachment and transosseous repair of the supraspinatus tendon augmented with either fibrin glue (control group) or fibrin glue with 106 human MSCs (experimental group) applied at the repair site. Flow cytometry verified the stem cell phenotype of the cells as CD73+, CD90+, CD105+, CD14-, CD34-, and CD45-. Rats were killed at 2 and 4 weeks, with 10 from each group used for biomechanical testing and 3 for histologic analysis. Safranin O staining identified increased fibrocartilage formation at the repair site at 2 weeks in the human MSC group (18.6% ± 2.9% vs 9.1% ± 1.6%, P = .026). Picrosirius staining identified decreased energy (36.88 ± 4.99 J vs 54.97 ± 8.33 J, P = .04) and increased coherence in the human MSC group (26.96% ± 15.32% vs 14.53% ± 4.10%, P = .05), indicating improved collagen orientation. Biomechanical testing showed a significant increase in failure load (11.5 ± 2.4 N vs 8.5 ± 2.4 N, P = .002) and stiffness (7.1 ± 1.2 N/mm vs 5.7 ± 2.1 N/mm, P < .001) in the experimental group compared with the control group at 2 weeks. These effects dissipated by 4 weeks, with no significant differences in fibrocartilage formation (35% ± 5.0% vs 26.6% ± 0.6%, P = .172) or biomechanical load to failure (24.6 ± 7.1 N vs 21.5 ± 4.1 N, P = .361) or stiffness (13.5 ± 3.1 N/mm vs 16.1 ± 5.6 N/mm, P = .384). All failures occurred at the bone-tendon interface. Rotator cuff repair augmentation with purified human MSCs improved early histologic appearance and biomechanical strength of the repair at 2 weeks, although the effects dissipated by 4 weeks with no significant differences between groups. Human MSCs may improve early rotator cuff healing during the first 2 weeks after repair.


Topical nicotinamide compared with clindamycin gel in the treatment of inflammatory acne vulgaris.
Systemic and topical antimicrobials are effective in the treatment of inflammatory acne vulgaris; however, widespread use of these agents is becoming increasingly associated with the emergence of resistant pathogens raising concerns about microorganism resistance and highlighting the need for alternative nonantimicrobial agents for the treatment of acne. Nicotinamide gel provides potent antiinflammatory activity without the risk of inducing bacterial resistance. In our double-blind investigation, the safety and efficacy of topically applied 4% nicotinamide gel was compared to 1% clindamycin gel for the treatment of moderate inflammatory acne vulgaris. Seventy-six patients were randomly assigned to apply either 4% nicotinamide gel (n = 38) or 1% clindamycin gel (n = 38) twice daily for 8 weeks. Efficacy was evaluated at 4 and 8 weeks using a Physician's Global Evaluation, Acne Lesion Counts, and an Acne Severity Rating. After 8 weeks, both treatments produced comparable (P = 0.19) beneficial results in the Physician's Global Evaluation of Inflammatory Acne; 82% of the patients treated with nicotinamide gel and 68% treated with clindamycin gel were improved. Both treatments produced statistically similar reductions in acne lesions (papules/pustules; -60%, nicotinamide vs. -43%, clindamycin, P = 0.168), and acne severity (-52% nicotinamide group vs. -38% clindamycin group, P = 0.161). These data demonstrate that 4% nicotinamide gel is of comparable efficacy to 1% clindamycin gel in the treatment of acne vulgaris. Because topical clindamycin, like other antimicrobials, is associated with emergence of resistant microorganisms, nicotinamide gel is a desirable alternative treatment for acne vulgaris.


High-dose-rate brachytherapy as monotherapy versus as boost in unfavorable intermediate-risk localized prostate cancer: A matched-pair analysis.
High-dose-rate brachytherapy as monotherapy (HDR-M), or as a boost combined with external beam radiotherapy (HDR-B), are both suitable treatments for intermediate-risk prostate cancer. However, data directly comparing these two approaches for men with unfavorable intermediate-risk (UIR) patients are lacking. Patients with NCCN-defined UIR prostate cancer treated from 1997 to 2020 were identified in a prospectively maintained, single institution database. HDR-M and HDR-B patients were matched using three factors: age ±3 years; Gleason score (major and minor); and clinical T stage. Biochemical failure was defined as PSA nadir (nPSA) + 2. Available acute and chronic toxicities are additionally reported. A total of 247 patients were identified (170 receiving HDR-B, 77 receiving HDR-M), ultimately yielding 70 matched pairs (140 patients) for inclusion. The median followup time was 5.2 years for HDR-M compared with 9.3 years for HDR-B (p < 0.001). The two cohorts had similar calculated prostate EQD2 (HDR-B 118 Gy vs. HDR-M 115 Gy, p = 0.977). No significant differences in OS, CSS, DM, LRR, or FFBF were identified. HDR-B had an increased rate of any acute grade 2+ gastrointestinal toxicity and worse acute dysuria and diarrhea. Chronic gastrointestinal and genitourinary toxicity was similar. These data suggest that HDR brachytherapy as monotherapy is an effective treatment option for selected patients with unfavorable intermediate-risk prostate cancer and provides a more favorable gastrointestinal toxicity profile than HDR-B. Prospective trials should be conducted to refine the selection process for this heterogeneous cohort of patients.


Simulating advanced focused ion beam nanomachining: a quantitative comparison of simulation and experimental results.
A simulation study of focused ion beam (FIB) sputtering in SiO2 is presented. The basis of this study is an enhanced version of the EnvizION Monte Carlo simulation program for FIB processing, which previously was restricted to targets composed of a single atom. A Monte Carlo method is presented for the simulation of FIB sputtering in SiO2 in three-dimensions, with ion implantation, to elucidate the complex dynamics of nanoscale milling of compound targets. This method is applied to the simulation of sputtering experiments using both Ne+ and Ga+ ion beams. We compare simulations using experimentally derived 'measured' beam profiles for each ion species, and 'effective' beam profiles which are chosen to reproduce experimental results. Simulations using the 'measured' beam profiles produce vias which are narrower than experiments, while the 'effective' beam profiles for both Ne+ and Ga+ are significantly wider than the 'measured' profiles. The difference between the 'measured' and 'effective' beam profiles is attributed to widening of the milling effects of the beam beyond its static dimensions, due to platform level artifacts such as vibrations and, possibly, charging. Simulations using the 'effective' beam profiles are found to accurately reproduce the depths and overall shape of experimental FIB sputtered vias in test cases, which vary in ion species, beam energy, total dose, and raster parameters. This comparison is the most extensive validation of the EnvizION simulation against experiments to date. However, the location of implanted ions in simulations is shallower than experiments, which is attributed to the fact that implanted species are required to find nearest neighbor vacancies and not allowed to occupy interstitial positions.


Social and Policy Determinants of COVID-19 Infection Across 23 Countries: An Ecological Study.
This study aimed to identify the social and policy determinants of coronavirus disease 2019 (COVID-19) infection across 23 countries. COVID-19 indicators (incidence, mortality, and fatality) for each country were calculated by direct and indirect standardization. Multivariable regression analyses were used to identify the social and policy determinants of COVID-19 infection. A higher number of doctors per population was related to lower incidence, mortality, and fatality rates of COVID-19 in 23 countries (β=-0.672, -0.445, and -0.564, respectively). The number of nurses/midwives per population was associated with lower mortality and fatality rates of COVID-19 in 23 countries (β=-0.215 and -0.372, respectively). Strengthening of policy restriction indicators, such as restrictions of public gatherings, was related to lower COVID-19 incidence (β=-0.423). A national Bacillus Calmette-Guérin vaccination policy conducted among special groups or in the past was associated with a higher incidence of COVID-19 in 23 countries (β=0.341). The proportion of the elderly population (aged over 70 years) was related to higher mortality and fatality rates (β=0.209 and 0.350, respectively), and income support was associated with mortality and fatality rates (β=-0.362 and -0.449, respectively). These findings do not imply causality because this was a country-based correlation study. However, COVID-19 transmission can be influenced by social and policy determinants such as integrated health systems and policy responses to COVID-19. Various social and policy determinants should be considered when planning responses to COVID-19.


Airway-Centered Pleuroparenchymal Fibroelastosis Associated with Non-Necrotizing Granulomas: A Rare New Entity.
Pleuroparenchymal fibroelastosis is a rare form of upper-lobe-dominant progressive pulmonary fibrosis characterized histologically by visceral pleural thickening with collagenous fibrosis, subpleural elastosis, and intra-alveolar collagenous fibrosis. It was first described 25 years ago by Amitani et al. This report firstly describes a new variant or rare phenotype of PPFE with airway involvement, minimal pleuroparenchymal connections, and non-necrotizing granulomas.


Social media analysis reveals environmental injustices in Philadelphia urban parks.
The United Nations Sustainable Development Goal (SDG) target 11.7 calls for access to safe and inclusive green spaces for all communities. Yet, historical residential segregation in the USA has resulted in poor quality urban parks near neighborhoods with primarily disadvantaged socioeconomic status groups, and an extensive park system that addresses the needs of primarily White middle-class residents. Here we center the voices of historically marginalized urban residents by using Natural Language Processing and Geographic Information Science to analyze a large dataset (n = 143,913) of Google Map reviews from 2011 to 2022 across 285 parks in the City of Philadelphia, USA. We find that parks in neighborhoods with a high number of residents from historically disadvantaged demographic groups are likely to receive lower scores on Google Maps. Physical characteristics of these parks based on aerial and satellite images and ancillary data corroborate the public perception of park quality. Topic modeling of park reviews reveal that the diverse environmental justice needs of historically marginalized communities must be met to reduce the uneven park quality-a goal in line with achieving SDG 11 by 2030.


Loss of membranous expression of beta-catenin is associated with tumor progression in cutaneous melanoma and rarely caused by exon 3 mutations.
beta-Catenin plays a fundamental role in the regulation of the E-cadherin-catenin cell adhesion complex. It also plays a role in the Wnt signaling pathway by activating T-cell factor- and lymphoid enhancer factor-regulated gene transcription. The level of beta-catenin in cells is tightly controlled in a multiprotein complex, and mutations in the glycogen synthase kinase 3beta (GSK-3beta) phosphorylation sites of the beta-catenin gene (CTNNB1) result in nuclear and/or cytoplasmic accumulation of beta-catenin and constitutive transactivation of T-cell factor and lymphoid enhancer factor target genes, a mechanism occurring in many cancers. Melanoma cell lines may harbor beta-catenin mutations; in vivo, however, cellular accumulation of beta-catenin is rarely caused by CTNNB1 mutations. In our study, 43 primary cutaneous melanoma and 30 metastases were screened for CTNNB1 exon 3 mutations by using a denaturing gradient gel electrophoresis technique and sequencing. beta-Catenin mutations were found in 2 primary melanomas and 1 metastatic melanoma and were not correlated with nuclear accumulation of beta-catenin in these cases. Cellular expression of beta-catenin was evaluated by immunohistochemistry and by reverse polymerase chain reaction (RT-PCR) in 80 and 70 cases, respectively. Immunohistochemistry revealed a significant loss of membranous beta-catenin staining between the primary and metastatic melanomas as well as between radial and vertical growth phase. RT-PCR showed a significant inverse correlation between the amount of RNA and the proportion of cells with membranous expression of beta-catenin (P =.0015); no correlation existed between the amount of RNA and the number of cells with nuclear or cytoplasmic expression of beta-catenin. In conclusion, nuclear expression of beta-catenin is seen in cutaneous melanoma but, in contrast to the case of many other cancers, does not correlate with tumor stage or mutation status. A combination of immunohistochemistry and RT-PCR showed that down-regulation of membranous beta-catenin was associated with an increased amount of beta-catenin RNA in primary or metastatic melanoma. Our results suggest that posttranslational events, rather than CTNNB1 mutations, are responsible for the altered distribution of beta-catenin in cutaneous melanoma.


Efficacy of Cilnidipine (L/N-type Calcium Channel Blocker) in Treatment of Hypertension: A Meta-Analysis of Randomized and Non-randomized Controlled Trials.
Hypertension is one of the most common cardiovascular diseases, and the prevalence of hypertension continues to rise across the globe. National and international guidelines recommend angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs), diuretics, and beta-blockers for the management of hypertension. CCBs are among the most used antihypertensive medications and Cilnidipine is a newer dihydropyridine CCB shown to have a prolonged antihypertensive property. This meta-analysis of comparative randomized and non-randomized clinical trials evaluated the effect of Cilnidipine monotherapy or combination therapy on systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse rate (PR) over 48 weeks of therapy. PubMed (MEDLINE) and Google scholar databases were searched to identify studies designed to evaluate the effects of Cilnidipine in the treatment of hypertensive patients. The study criteria for inclusion into the meta-analysis were all prospective, randomized, and non-randomized clinical studies published till March 2021, studies published in a peer-reviewed journal, the inclusion of patients with hypertension, assessment of blood pressure and heart rate, and a follow-up of four weeks or longer. The initial search identified 82 potential articles; of these, 24 met the inclusion criteria. Studies with <4 weeks treatment period and those not having a CCB were excluded. Change in SBP, DBP, and PR from baseline at the end of therapy compared between the Cilnidipine and other CCB's. Cilnidipine caused a significant reduction (p<0.05) in SBP, DBP, and PR at end of therapy, whereas the reduction in SBP, DBP, and PR with Cilnidipine was similar to other CCB's (p>0.05). The results of this meta-analysis revealed that there were no significant differences in the efficacy in the treatment of hypertensive patients with Cilnidipine and the other therapies. Cilnidipine has similar anti-hypertensive effects compared with other first-line antihypertensive drugs commonly used in practice. We recommend Cilnidipine as a novel first-line CCB for the management of hypertension either as a monotherapy or as a combination therapy.


Synthesis and structure of the mercury chloride complex of 2,2'-(2-bromo-5-tert-butyl-1,3-phenyl-ene)bis-(1-methyl-1H-benzimidazole).
In the title mercury complex, catena-poly[[di-chlorido-mercury(II)]-μ-2,2'-(2-bromo-5-tert-butyl-1,3-phenyl-ene)bis-(1-methyl-1H-benzimidazole)-κ2N3:N3'], [HgCl2(C26H25BrN4)] n , the HgII atom is coordinated by two Cl atoms and by two N atoms from two 2,2'-(2-bromo-5-tert-butyl-1,3-phenyl-ene)bis-(1-methyl-1H-benzimidazole) ligands. The metal cation adopts a distorted tetrahedral coordination geometry with with bond angles around mercury of 100.59 (15)° [N-Hg-N] and 126.35 (7)° [Cl-Hg-Cl]. This arrangement gives rise to a zigzag helical 1-D polymer propagating along the b-axis direction.


Iron binding to alpha-tocopherol-containing phospholipid liposomes.
Tocopherols (vitamin E) located in the hydrophobic domains of biological membranes act as chain breaking antioxidants preventing the propagation of free radical reactions of lipid peroxidation. The naturally occurring form, d-alpha tocopherol is an exquisite molecule in that it is intercalated in the membrane in such a way that the hydrophobic tail anchors the molecule positioning the chromanol ring containing the hydroxyl group, which is the essence of its antioxidant function, at the polar hydrocarbon interface of phospholipid membranes. The interaction of this group with water soluble substances is not very well understood. In the present study, an investigation was made of the interaction of ascorbate and ferrous ions (Fe+2) initiators of lipid peroxidation with alpha tocopherol. The results show that tocopherol increases membrane associated iron. The formation of a tocopherol iron complex in the presence of phospholipid liposomes and ascorbate in its reduced form is indicated. These results suggest a new way in which tocopherols act to inhibit lipid peroxidation.


Extravasation. A serious complication of the split-sheath introducer technique for venous access.
The use of split-sheath introducers to place venous access catheters results in the potential for subcutaneous extravasation and tissue injury or necrosis. We present six cases that demonstrate this complication and illustrate the probable mechanism. The safe use of these catheters requires verification that blood can be aspirated from the catheter and a high index of suspicion for extravasation when symptoms develop.


Comparison of real-time PCR, conventional PCR, and galactomannan antigen detection by enzyme-linked immunosorbent assay using bronchoalveolar lavage fluid samples from hematology patients for diagnosis of invasive pulmonary aspergillosis.
An iCycler iQ real-time PCR assay targeting 18S rRNA Aspergillus-specific sequences was developed for the diagnosis of invasive pulmonary aspergillosis (IPA). Positive findings were obtained for 18 of 20 (90%) bronchoalveolar lavage (BAL) fluid specimens from patients with probable or confirmed IPA and were obtained for none of the 24 BAL samples from patients with no clinical evidence of aspergillosis. These results were concordant with those of a nested PCR assay, which detected 90% of the patients with IPA, while galactomannan ELISA revealed positivity for 100% of these patients, suggesting that combined use of methods might improve the diagnosis of IPA.


Frequency, levels, and significance of blood eosinophilia in systemic sclerosis, localized scleroderma, and eosinophilic fasciitis.
Blood eosinophilia is a common feature of eosinophilic fasciitis and is variably reported in systemic sclerosis and localized scleroderma. Since these diseases share cutaneous fibrosis as the final outcome and have other clinical and pathologic features that are difficult to differentiate, the presence of blood eosinophilia may be a further source of confusion. In this study, we examined the frequency and level of blood eosinophilia in 715 patients with systemic sclerosis, 72 patients with localized scleroderma, and 22 patients with clinically active eosinophilic fasciitis. When defined as greater than 400 cells/mm3, eosinophilia was present in 7% of patients with systemic sclerosis, 31% of patients with localized scleroderma, and 83% of patients with eosinophilic fasciitis. Greater than 1000 eosinophils/mm3 were present less frequently in systemic sclerosis (1%) and localized scleroderma (8%) than in eosinophilic fasciitis (61%). No difference in the frequency of eosinophilia was present in patients with the limited cutaneous CREST syndrome or the diffuse cutaneous variety of systemic sclerosis, and in these patients the presence of eosinophilia did not correlate with the extent of cutaneous or internal organ involvement or with other laboratory abnormalities. Among patients with localized scleroderma, eosinophilia was more common in those with linear scleroderma and generalized morphea than in those with morphea, and both the frequency and level of eosinophilia were greater in individuals with clinically active disease (p less than 0.02). Eosinophilia was a persistent feature in untreated patients with active eosinophilic fasciitis, even up to 30 months of disease duration.


The effects of oscillatory temperature on HaCaT keratinocyte behaviors.
Keratinocytes are exposed to a thermal gradient throughout epidermal layers in human skin depending on environmental temperatures. Here, the effect of cyclic temperature changes (ΔT) on HaCaT cell behaviors was explored. HaCaT cells were cultured at constant temperature (37 °C or 25 °C) or under ΔT conditions. The morphology, mechanics, cell cycle progression, proliferation, and lipid synthesis of HaCaT cells were determined. ΔT conditions led to the inhomogeneous arrangement of the cytoskeleton in HaCaT cells, which resulted in enlarged size, rounder shape, and increased stiffness. Accumulation in the G2/M phase in the cell cycle, a decreased proliferation rate, and a delayed lipogenesis were detected in HaCaT cells cultured under ΔT conditions. ΔT conditions resulted in the re-arrangement of the cytoskeleton in HaCaT cells, which showed similarity to the temperature-induced disassemble and re-assemble of cytoskeletons in keratinocyte in vivo. The altered cytoskeleton arrangement resulted in the cell enlargement and stiffening, which reflected the changes in cellular functions. The application of oscillatory temperature in the in vitro culture of keratinocytes provides a way to gain more insights into the role of skin in response to environmental stimuli and maintaining its homeostasis in vivo.


Ureaplasma urealyticum-harmless commensal or underestimated enemy of human reproduction? A review.
This article reviews the role, diagnosis and treatment of Ureaplasma infections in human reproduction.


Mitochondrial transcripts and associated heteroplasmies of Ancistrus spp. (Siluriformes: Loricariidae).
This data-set complements our paper entitled "The use of transcriptomic next-generation sequencing data to assembly mitochondrial genomes of Ancistrus spp. (Loricariidae)" [6]. Here, we present the nucleotide sequences of each transcript used for mitogenomes assembly, as well as tables presenting the location of each transcript in the mitogenomes; the frequency, location and codon position of the detected heteroplasmic sites; and the start/stop codons usage, UTR, CDS and poliA-tail length for each protein coding gene. Readers are referred to the paper cited above for data interpretation and discussion.


Switching from MAPK-dependent to MAPK-independent repression of the sodium-iodide symporter in 2D and 3D cultured normal thyroid cells.
Loss of sodium-iodide symporter (NIS) expression in thyroid tumour cells primarily caused by constitutive MAPK pathway activation is often refractory to small molecule MAPK inhibitors. Suggested mechanisms are rebound MAPK signalling and activation of alternative signalling pathways. Here we provide evidence that failure to recover down-regulated NIS by MEK inhibition is not specific to tumour cells. NIS mRNA levels remained repressed in TSH-stimulated primary thyroid cells co-treated with epidermal growth factor (EGF) and pan-MEK inhibitor U0126 in the presence of 5% fetal bovine serum or, independently of serum, in 3D cultured thyroid follicles. This led to inhibited iodide transport and iodination. In contrast, U0126 restituted thyroglobulin synthesis in EGF-treated follicular cells. Serum potentiated TSH-stimulated NIS expression in 2D culture. U0126 blocked down-regulation of NIS only in serum-starved cells with a diminished TSH response. Together, this suggests that morphogenetic signals modify the expression of NIS and recovery response to MEK inhibition.


Hepatic resection by the Cavitron Ultrasonic Surgical Aspirator increases the incidence and severity of venous air embolism.
The Cavitron Ultrasonic Surgical Aspirator (CUSA) is an innovative tool for resecting hepatic parenchyma, which reduces intraoperative blood loss and perioperative morbidity. We designed this study to compare the incidence and severity of venous air embolism (VAE) detected via transesophageal echocardiography (TEE) during hepatic resection by using either the clamp-crushing method or the CUSA method. Fifty patients scheduled for hepatic resection were randomly assigned to receive hepatic resection by the clamp-crushing method (CC group) or by CUSA (CUSA group). After the induction of anesthesia, the TEE probe was inserted into the patient's esophagus. An independent anesthesiologist graded VAE shown in the 4-chamber view of TEE. All patients in the CUSA group showed VAE during hepatic resection and 44% of the patients had air embolism filling more than half the right heart diameter. In CC group, 68% of the patients showed VAE, which filled less than half the right heart diameter. There were no significant differences in hemodynamics and end-tidal CO2 partial pressure between the two groups. In conclusion, hepatic resection by CUSA increases the incidence and severity of VAE. This study demonstrated that venous air embolism during hepatic resection was more frequent and severe when using the Cavitron Ultrasonic Surgical Aspirator. Although we found no evidence of hemodynamic compromise, increased venous air embolism may increase the risk of paradoxical embolism in patients with liver cirrhosis.


[Perforation of the skull base during nasogastric intubation].
The skull base was perforated and extensive wounds occurred in the brain during the passage of a nasogastric tube on a 48 year old woman, under general anaesthetic. The patient was treated by artificial respiration but died on the 14th day. The site of entry was the sphenoid sinus. False passage of the tube was favoured by a marked septal deviation, underdevelopment of the turbinates, and a high-grade pneumatisation of the paranasal sinus. 10 more cases of intracranial passage of a nasogastric tube were found in the literature.


Evidence suggesting that ghrelin O-acyl transferase inhibitor acts at the hypothalamus to inhibit hypothalamo-pituitary-adrenocortical axis function in the rat.
Production of n-octanoyl-modified ghrelin (GHREL), an active form of the peptide requires prohormone processing protease and GHREL O-acyltransferase (GOAT), as well as n-octanoic acid. Recently a selective GOAT antagonist (GO-CoA-Tat) was invented and this tool was used to study the possible role of endogenous GHREL in regulating HPA axis function in the rat. Administration of GOAT inhibitor (GOATi) resulted in a notable decrease in plasma ACTH, aldosterone and corticosterone concentrations at min 60 of experiment. Octanoic acid (OA) administration had no effect on levels of studied hormones. Plasma levels of unacylated and acylated GHREL remained unchanged for 60min after either GOATi or OA administration. Under experimental conditions applied, no significant changes were observed in the levels of GOAT mRNA in hypothalamus, pituitary, adrenal and stomach fundus. After GOATi injection hypothalamic CRH mRNA levels were elevated at 30 min and pituitary POMC mRNA levels at 60 min. Both GOATi and OA lowered basal, but not K(+)-stimulated CRH release by hypothalamic explants and had no effect on basal or CRH-stimulated ACTH release by pituitary slices. Neither GOATi nor OA affected corticosterone secretion by freshly isolated or cultured rat adrenocortical cells. Thus, results of our study suggest that in the rat endogenous GHREL exerts tonic stimulating effect on hypothalamic CRH release. This effect could be demonstrated by administering rats with selected inhibitor of ghrelin O-acyltransferase, the enzyme responsible for GHREL acylation, a process which is absolutely required for both GHSR-1a binding and its central endocrine activities.


[Interferon activation of the production of a factor increasing the bactericidal properties of mouse macrophages].
It has been established that the administration of homologous interferon to mice activates the production by splenocytes of a factor increasing the bactericidal properties of macrophages in the peritoneal exudate. The activation effect was dose-dependent. The maximum production was noted on day 3 after the injection of interferon, type I, or its inducers. Cell-producers of the factor are mainly lymphocytes.


Caspase-3 is required in the apoptotic disintegration of the nuclear matrix.
Apoptotic breakdown of cellular structures is largely mediated by caspases. One target of degradation is a proteinaceous framework of the nucleus termed the nuclear matrix. We compared the apoptotic changes of the nuclear matrix in staurosporine-treated caspase-3-deficient MCF-7 cells transfected with intact CASP-3 gene (MCF-7c3) or an empty vector (MCF-7v) as a control. Nuclear Mitotic Apparatus protein (NuMA), lamin A/C and lamin B were used as markers for internal nuclear matrix and peripheral nuclear lamina, respectively. In both cell lines, staurosporine induced rapid cytoplasmic shrinkage and partial chromatin condensation. MCF-7c3 cells formed apoptotic bodies, whereas MCF-7v cells did not. NuMA and lamins were actively cleaved in MCF-7c3 cells following caspase-3 activation, but only minimal or no cleavage was detected in MCF-7v cells. Interestingly, lamin B but not lamin A/C was relocated into cytoplasmic granules in apoptotic MCF-7v cells. Pancaspase inhibitor, z-VAD-fmk, prevented the apoptotic changes, while caspase-3 inhibitor, z-DEVD-fmk, induced lamin B granules in both cell lines. These results show that caspase-3 is involved in the cleavage of NuMA and lamins either directly or by activating other proteases. This may be essential for disintegration of the nuclear structure during apoptosis.


Nitrogen-enriched micro-mesoporous carbon derived from polymers organic frameworks for high-performance capacitive deionization.
Nitrogenization is an effective method for improving the capacitive deionization (CDI) performance of porous carbon materials. In particular, polymer organic frameworks with heteroatom doping, containing an ordered pore structure and excellent electrochemical stability, are ideal precursors for carbon materials for high-performance CDI. In this study, a nitrogen-enriched micro-mesoporous carbon (NMC) electrode was fabricated by carbonizing a Schiff base network-1 at 500, 600, and 700 °C. Scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, N2 adsorption-desorption, the contact angle of water, cyclic voltammetry, and electrochemical impedance spectroscopy were used to characterize the morphological structure, wettability, Brunauer-Emmett-Teller surface areas, and electrochemical performance of the NMCs. The results showed that the NMC carbonized at 600°C achieved the best specific capacitance (152.33 F/g), as well as a high electrosorption capacity (25.53 mg/g) because of its chemical composition (15.57% N) and surface area (312 m2/g). These findings prove that NMC is viable as an electrode material for desalination by high-performance CDI applications.


The organization of the brainstem and spinal cord of the mouse: relationships between monoaminergic, cholinergic, and spinal projection systems.
Information regarding the organization of the CNS in terms of neurotransmitter systems and spinal connections in the mouse is sparse, especially at the level of the brainstem. An overview is presented of monoaminergic and cholinergic systems in the brainstem and spinal cord that were visualized immunohistochemically in inbred C57BL/6 and outbred CD-1 mice. This information is complemented with data on spinal cord-projecting systems that were characterized using retrograde tracing, spinal hemisections, and double labeling techniques. Attention is given to differences in these systems related to spinal levels. The data are discussed with reference to studies in the rat, and to standardized information as provided in the atlas of the mouse brain. Although the overall organization of these systems in the mouse is largely similar to those in the rat, species differences are present in relative location, size and/or connectivity of cell groups. For example, catecholaminergic neurons in the (ventro)lateral pons (A5 and A7 cell groups) in the mouse project to the spinal cord mainly via contralateral, and not ipsilateral, pathways. The data further supplement information as provided in standardized brainstem sections of the C57BL/6 mouse [Paxinos, G., Franklin, K.B.J., 2001. The mouse brain in stereotaxic coordinates. Academic Press, San Diego], especially with respect to the size and/or location of the catecholaminergic retrorubral field (A8 group), A5, A1, and C1 cell groups, and the serotonergic B4 group, reticulotegmental nucleus (B9 group), lateral paragigantocellular nucleus and raphe magnus nucleus (B3 group). Altogether this study provides a comprehensive overview of the spatial relationships of neurochemically and anatomically defined neuronal systems in the mouse brainstem and spinal cord.


The millipede Typhloglomeriscaucasica Golovatch, 1975 found epigeically (Diplopoda, Glomerida, Glomeridellidae).
The millipede Typhloglomeriscaucasica Golovatch, hitherto considered as a troglobite confined to several caves near Sochi, western Caucasus, Russia, is recorded epigeically in the same region, and is therefore a troglophile.


The affective dimension of dyspnea improves in a dyspnea self-management program with exercise training.
The perception of dyspnea includes both sensory and affective dimensions that are shaped by emotions and psychological, social, and environmental experiences. Previous investigators have studied either measurement or strategies to decrease the affective dimension with laboratory-induced dyspnea. Few have reported the effect of a therapeutic clinical intervention on the affective dimension of dyspnea. (1) To evaluate the effects of three different versions of a dyspnea self-management program (DM) on the affective dimension of dyspnea, measured by dyspnea-related anxiety (DA) and dyspnea-related distress (DD); and (2) to determine the stability of DA and DD over two baseline incremental treadmill tests (ITTs). Participants with chronic obstructive pulmonary disease were randomly assigned to three 12 month DMs with varying doses of supervised exercise (DM, DM-Exposure, and DM-Training). The measurements of the affective dimension, DA and DD, were rated during ITTs on two baseline days and at two, six, and 12 months. Changes over time in DA and DD were analyzed using linear mixed-effects models. Participants in the DM-Training group who received 24 nurse-coached exercise sessions had significantly greater reductions in DA and DD compared with those who had four exercise sessions (DM-Exposure) or only received a home-walking program (DM). Reductions in DA and DD in the DM-Training group were only maintained through six months. There were no significant differences in ratings of DA and DD at end between the two baseline ITTs. These findings provide initial support for the positive impact of a self-management program with nurse-coached exercise on the affective dimension of dyspnea. Further investigation of interventions that target the affective dimension in addition to the sensory dimension of dyspnea should be encouraged.


Accuracy of diagnostic tests for Cushing's syndrome: a systematic review and metaanalyses.
The diagnosis of Cushing's syndrome (CS) requires the use of tests of unregulated hypercortisolism that have unclear accuracy. Our objective was to summarize evidence on the accuracy of common tests for diagnosing CS. We searched electronic databases (MEDLINE, EMBASE, Web of Science, Scopus, and citation search for key articles) from 1975 through September 2007 and sought additional references from experts. Eligible studies reported on the accuracy of urinary free cortisol (UFC), dexamethasone suppression test (DST), and midnight cortisol assays vs. reference standard in patients suspected of CS. Reviewers working in duplicate and independently extracted study characteristics and quality and data to estimate the likelihood ratio (LR) and the 95% confidence interval (CI) for each result. We found 27 eligible studies, with a high prevalence [794 (9.2%) of 8631 patients had CS] and severity of CS. The tests had similar accuracy: UFC (n = 14 studies; LR+ 10.6, CI 5.5-20.5; LR- 0.16, CI 0.08-0.33), salivary midnight cortisol (n = 4; LR+ 8.8, CI 3.5-21.8; LR- 0.07, CI 0-1.2), and the 1-mg overnight DST (n = 14; LR+ 16.4, CI 9.3-28.8; LR- 0.06, CI 0.03-0.14). Combined testing strategies (e.g. a positive result in both UFC and 1-mg overnight DST) had similar diagnostic accuracy (n = 3; LR+ 15.4, CI 0.7-358; LR- 0.11, CI 0.007-1.57). Commonly used tests to diagnose CS appear highly accurate in referral practices with samples enriched with patients with CS. Their performance in usual clinical practice remains unclear.


Real-time MRI for the dynamic assessment of fundoplication failure in patients with gastroesophageal reflux disease.
To assess the diagnostic potential of dynamic real-time MRI for fundoplication failure in patients with persistent or recurrent GERD-like (gastroesophageal reflux disease) complaints. Twenty-two consecutive patients (male n = 11; female n = 11; median age 59 years) with recurrent or persistent GERD-like symptom after fundoplication were enrolled between 2015 and 2017. Median duration of GERD-like symptoms was 21 months. Real-time MRI (3 Tesla) was performed at 40 ms temporal resolution using undersampled radial fast low-angle shot acquisitions with nonlinear inverse image reconstruction. MRI movies dynamically visualized bolus transit of pineapple juice through the gastroesophageal junction, position of the fundoplication wrap and recurring hernia or reflux during Valsalva maneuver. MRI results were compared to endoscopic findings. Real-time MRI was successfully completed in all patients without adverse events (average examination time 15 min). Morphological correlates for GERD-like symptoms were evident in 20 patients (90.1%) with gastric reflux in 19 cases. Nine patients (40.1%) had wrap disruption and recurrent gastric hernia. Wrap migration or telescoping hernia was detected in nine patients (40.1%). One patient presented with continued reflux despite intact fundoplication wrap. Esophageal dysmotility with delayed bolus passage was observed in one case. On endoscopy, gastric hernia or wrap disruption was diagnosed in seven cases, and esophagitis or Barret's metaplasia in nine cases. Real-time MRI is a fast and safe modality for dynamic imaging after fundoplication, without radiation exposure or administration of gadolinium-based contrast media. In a relevant number of cases, real-time MRI reveals correlates for GERD-like symptoms. • Real-time MRI reliably visualizes the gastroesophageal junction after fundoplication surgery. • Patients with recurring GERD-like symptoms have a high rate of morphological failure patterns that can be identified by real-time MRI. • Dynamic assessment of gastroesophageal junction by real-time MRI is a perspective diagnostic tool for detection of fundoplication failure.


Oncolytic virotherapy in lung cancer.
Lung tumors are one of the most aggressive threats affecting humans. Current therapeutic approaches have improved patients' survival; however, further efforts are required to increase effectiveness and protection against tumor relapse and metastasis. Immunotherapy presents an alternative to previous treatments that focuses on stimulating of the patient's immune system to destroy tumor cells. Viruses can be used as part of the immune therapeutic approach as agents that could selectively infect tumor cells, triggering an immune response against the infection and against the tumor cells. Some viruses have been selected for specifically infecting and destroying cancer cells, activating the immune response, enhancing access, amplifying the cytotoxicity against the tumor cells, and improving the long-term memory that can prevent tumor relapse. Oncolytic virotherapy can then be used as a strategy to target the destruction of transformed cells at the tumor site and act in locations distant from the primary targeted tumor site. Some of the current challenges in lung cancer treatment can be addressed using traditional therapies combined with oncolytic virotherapy. Defining the best combination, including the choice of the right settings will be at the next frontier in lung cancer treatment.


Analysis of microtubules in isolated axoplasm from the squid giant axon.
Biochemical specialization of cellular microtubules has emerged as a primary mechanism in specifying microtubule dynamics and function. However, study of specific subcellular populations of cytoplasmic microtubules has been limited, particularly in the nervous system. The complexity of nervous tissue makes it difficult to distinguish neuronal microtubules from glial microtubules, and axonal microtubules from dendritic and cell body microtubules. The problem is further compounded by the finding that a large fraction of neuronal tubulin is lost during standard preparations of brain tubulin, and this population of stable microtubules is enriched in axons. Here, we consider a unique biological model that provides a unique opportunity to study axonal microtubules both in situ and in vitro: isolated axoplasm from the squid giant axon. The axoplasm model represents a powerful system for addressing fundamental questions of microtubule structure and function in the axon.


Species-specific cell-matrix interactions are essential for differentiation of alveoli like structures and milk gene expression in primary mammary cells of the Cape fur seal (Arctocephalus pusillus pusillus).
Few models are in place for analysis of extreme lactation patterns such as that of the fur seals which are capable of extended down regulation of milk production in the absence of involution. During a 10-12 month lactation period, female fur seals suckle pups on shore for 2-3 days, and then undertake long foraging trips at sea for up to 28 days, resulting in the longest intersuckling bouts recorded. During this time the mammary gland down regulates milk production. We have induced Cape fur seal (Arctocephalus pusillus pusillus) mammary cells in vitro to form mammospheres up to 900 microm in diameter, larger than any of their mammalian counterparts. Mammosphere lumens were shown to form via apoptosis and cells comprising the cellular boundary stained vimentin positive. The Cape fur seal GAPDH gene was cloned and used in RT-PCR as a normalization tool to examine comparative expression of milk protein genes (alphaS2-casein, beta-lactoglobulin and lysozyme C) which were prolactin responsive. Cape fur seal mammary cells were found to be unique; they did not require Matrigel for rapid mammosphere formation and instead deposited their own matrix within 2 days of culture. When grown on Matrigel, cells exhibited branching/stellate morphogenesis highlighting the species-specific nature of cell-matrix interactions during morphological differentiation. Matrix produced in vitro by cells did not support formation of human breast cancer cell line, PMC42 mammospheres. This novel model system will help define the molecular pathways controlling the regulation of milk protein expression and species specific requirements of the extracellular matrix in the cape fur seal.


MRI abnormalities of the brain in one-year-old children with sickle cell anemia.
Sickle cell anemia (SCA) frequently results in damage to the central nervous system (CNS), but the age of onset of these effects is uncertain. We performed MRI examinations of the brain in infants with SCA, who were evaluated as part of the multicenter randomized double-blinded Pediatric Hydroxyurea Phase III Clinical Trial (BABY HUG). Determination of eligibility for enrollment in the trial originally required baseline MRI and magnetic resonance angiography (MRA) of the brain. A standardized imaging protocol was utilized across eight clinical centers. MRI/MRA exams were reviewed by a panel of three neurology/neuroradiology readers and interpretations reported to the coordinating center. Results were correlated with patient age, gender, history, WBC count, platelet count, hemoglobin (Hb), HbF level, score on the Bayley Scales of Infant Development, and velocity on transcranial Doppler ultrasonography (TCD). Twenty-three subjects with HbSS were examined at average age 13.7 months (range 10-18 months); 13 were male. Three (13%, CI: 3-34%) had silent infarcts on MRI, two in the right frontal area and one bilaterally. None had MRA abnormalities. The lesions were correlated with increased right-sided TCD velocity and low HbF level, but not with age, history, Hb level, developmental score, or left-sided velocity. Silent brain infarcts occur in a small but significant number of infants with SCA as early as a year of age. This finding indicates a need for thorough evaluation of the CNS very early in life in children with SCA in order to develop timely intervention strategies.


[Vaccination ethics: report on a workshop at the Ruher-Universität Bochum].
Important issues in vaccination ethics are: the right for equal access to basic health care, self determination and solidarity. National recommendations are the basis for equal access to prevention of severe infectious diseases by vaccination allowing for provision basic health care for all. Since the effect of vaccination programmes depends heavily on high vaccination rates solidarity with respect to getting vaccinated, despite small but not deniable risks for vaccination side effects is mandatory. Research challenges in vaccination ethics pertain to paternalism, individualism, solidarity and definition of basic health care with respect to vaccine preventable disease.


Mash Screen: high-throughput sequence containment estimation for genome discovery.
The MinHash algorithm has proven effective for rapidly estimating the resemblance of two genomes or metagenomes. However, this method cannot reliably estimate the containment of a genome within a metagenome. Here, we describe an online algorithm capable of measuring the containment of genomes and proteomes within either assembled or unassembled sequencing read sets. We describe several use cases, including contamination screening and retrospective analysis of metagenomes for novel genome discovery. Using this tool, we provide containment estimates for every NCBI RefSeq genome within every SRA metagenome and demonstrate the identification of a novel polyomavirus species from a public metagenome.


Awareness of methylmercury in fish and fish consumption among pregnant and postpartum women and women of childbearing age in the United States.
In 2004, the Food and Drug Administration (FDA) and the Environmental Protection Agency (EPA) reissued joint advice recommending that pregnant women, nursing mothers, young children, and women who may become pregnant not consume fish high in mercury such as shark, swordfish, king mackerel, and tilefish, and not consume more than 12 ounces (340.2g) of other lower mercury fish per week. These groups were encouraged to eat up to 12 ounces (340.2g) of low mercury fish per week to get the health benefits of fish. Using a survey of 1286 pregnant women, 522 postpartum women, and a control group of 1349 non-pregnant/non-postpartum women of childbearing age, this study evaluated awareness of mercury as a problem in food and examined fish consumption levels across groups using regression analysis. We also compared awareness of mercury as a problem in food to awareness of Listeria, dioxins and PCBs. We found that the majority of all 3 groups of women were aware of mercury and that nearly all women in all 3 groups limited consumption consistent with the advice; they ate less than 340.2g (12 oz) of fish per week and no high mercury fish. Compared with the control group, pregnant and postpartum women were more likely to be aware of mercury as a problem in food, and pregnant women ate less total fish and were less likely to eat fish, to eat more than 340.2g (12 oz) of fish, and to eat high mercury fish. However, all groups ate much less than the recommended 340.2g (12 oz) of low mercury fish per week for optimum health benefits. Among women who ate fish, the median intake of total fish was 51.6 g/wk (1.8 oz/wk), 71.4 g/wk (2.5 oz/wk), and 85.3 g/wk (3.0 oz/wk) for the pregnant, postpartum, and control groups, respectively. Thus, it appears that the targeted groups of women were more aware of mercury and were eating fish within the FDA/EPA guidelines, but these women may be missing the health benefits to themselves and their children of eating a sufficient amount of fish.


Direct atomic force microscopy visualization of integration host factor-induced DNA bending structure of the promoter regulatory region on the Pseudomonas TOL plasmid.
Atomic force microscopy (AFM) was used to analyze DNA bending induced by integration host factor (IHF). The direct AFM visualization of IHF-DNA complexes on the OP1 promoter regulatory regions on the Pseudomonas TOL plasmid showed that there was no intrinsic DNA bend in the OP1 promoter region, but a sharp DNA bend was induced by binding of IHF to the region between the upstream regulatory sequence and the promoter sequence. The DNA bending angles were distributed with a mean bend angle of 123 degrees. The IHF-DNA complexes were shown to bend at the IHF binding site giving rise to an asymmetric structure. These results provide direct evidence that IHF is required functionally for activation of OP1 transcription and support the DNA-loop model that the sharp DNA bend induced by binding of IHF facilitates the contact between RNA polymerase bound by the promoter sequence and XylR protein attached to the upstream sequence in the OP1 promoter.


Cytopathology of high-grade papillary thyroid carcinomas: tall-cell variant, diffuse sclerosing variant, and poorly differentiated papillary carcinoma.
Cytologic reports of the aggressive tall-cell and diffuse sclerosing variants of papillary carcinoma have emphasized features such as tall and large cells, increased nuclear size, nuclear pleomorphism, intranuclear pseudoinclusions, three-dimensional tissue fragments, squamous-like cells, and dense inflammatory background as characteristic features. However, the specificity of these features in identifying the particular variants and distinguishing them from other poorly differentiated papillary carcinomas and typical low-grade forms of papillary carcinoma has not been established. The objective of this study was to assess the predictive value of these reported cytologic features. Fourteen cases of high-grade papillary carcinoma consisting of the aggressive variants (tall-cell variant (tcv) and diffuse sclerosing variant (dsv)) and poorly differentiated papillary carcinomas (pdpc) were compared to 18 cases of low-grade papillary carcinoma. Seven cytologic features consisting of the presence of tall and large cells, architectural disorganization, nuclear enlargement, prominent intranuclear pseudoinclusions, nuclear pleomorphism, lymphocytic infiltrate, and squamoid appearance of the neoplastic cells were evaluated. Cytology samples from tcv, dsv, and pdpc consistently demonstrated 3 of the 7 cytologic features (architectural disorganization, nuclear enlargement, and pleomorphism). In contrast, only two of the samples from low-grade cases demonstrated these 3 features. The recognition of these 3 cytologic features had a positive predictive value of 88% and a negative predictive value of 100% for identifying tcv, dsv, and pdpc. The remaining cytologic features were not a consistent feature in the variants, and by cytology alone, distinction between the aggressive variants (dsv and tcv) and pdpc could not be made.


[Clear cell epithelioma of the kidney in a child. Apropos of a case].
The authors report a case of renal hypernephroma in a child. This is an uncommon tumour which is very rarely diagnosed preoperatively. Its treatment is exclusively surgical. As in adults, the prognosis depends on the stage of the tumour at the time of discovery.


The Putative RNA Helicase Dbp4p Is Required for Release of the U14 snoRNA from Preribosomes in Saccharomyces cerevisiae.
Around 70 yeast snoRNAs guide rRNA modification, frequently forming base-paired interactions predicted to be very stable at physiological temperatures. Eighteen putative RNA helicases are required for ribosome synthesis, but their actual substrates were not known. We report that depletion of the DEAD box helicase Dbp4p dramatically increased cosedimentation of the snoRNAs U14 and snR41 with preribosomes. Cosedimentation was maintained after deproteinization by proteinase K, indicating that the snoRNAs remained base paired to the pre-rRNA. Affinity purification showed that U14 was strongly accumulated in early 90S preribosomes and depleted from later pre-40S complexes. U14 is required for pre-rRNA processing, and depletion of Dbp4p caused a very similar pre-rRNA processing defect, perhaps due to the reduced pool of free U14. Point mutations in helicase motifs I and III of Dbp4p blocked release of U14 from preribosomes. We conclude that the helicase activity of Dbp4p is required to unwind U14 and snR41 from the pre-rRNA.


Quantitative analysis of gene regulation by seven clinically relevant progestins suggests a highly similar mechanism of action through progesterone receptors in T47D breast cancer cells.
Progesterone (P4) is an essential reproductive steroid hormone required for many aspects of female reproductive physiology. Progestins are compounds that demonstrate progesterone-like activity and are used in oral contraception, hormone therapy, and treatment of some reproductive disorders, but differ widely in their chemical structures, potency, and pharmacokinetics. While numerous studies have assessed progestins on specific endpoints, little is known about the activation of global gene expression by progestins. We used Affymetrix GeneChip U133A expression arrays to examine the action of P4 and six clinically relevant synthetic progestins (3-ketodesogestrel, drospirenone, levonorgestrel, medroxyprogesterone acetate, norethindrone acetate, and trimegestone) on the progesterone receptor (PR)-positive T47Dco and the PR-negative T47D-Y breast cancer cell lines. Excluding drospirenone, one or more of the progestins-regulated 329 genes, with 30 genes regulated by at least 2.0-fold by all progestins in the T47Dco cells. The synthetic progestins show a high degree of similarity in their transcriptional responses, and each progestin regulates between 77 and 91% of the genes regulated by P4. Independent quantitative RT-PCR analysis confirmed a similar regulation for S100P, PPL, IL20RA, NET1, ATP1A1, HIG2, and CXCL12 (SDF-1) by all seven progestins. Attempts to find differentially regulated genes by any progestin compared to all other treatments failed, suggesting any differences are quantitative, not qualitative. This analysis demonstrates a high degree of similarity among these progestins on PR-regulated gene expression in T47D cells, suggesting a similar and fairly specific mode of action.


Intrinsic focal variations of rabbit aortic hydrolase activities.
Normal arterial foci which take up Evans blue dye (EBD) in vivo are believed to represent atherosclerosis-prone, hemodynamically stressed foci compared to areas which exclude dye. We have used the rabbit EBD model to examine focal aortic hydrolases of blue areas versus white areas, and we report herein significant focal variations of hydrolase activities. Enzymes measured included neutral alpha-glucosidase, N-acetyl-beta-glucosaminidase, alpha-mannosidase, acid alpha-glucosidase, beta-galactosidase, beta-glucuronidase, cathepsin C, and acid cholesteryl esterase (ACE); specific activities were expressed on the basis of tissue DNA. In correlative areas of EBD uptake in normal rabbit aortic arch, ACE activity averaged 17% higher and cathepsin C activity averaged 37% lower than activities of areas free of EBD in the descending thoracic aorta (P less than 0.02). None of the glycosidases studied differed significantly between blue and white aortic areas. These findings indicate that discrete, intrinsic differences of hydrolytic enzyme activities exist in the normal rabbit aorta in areas delineated by in vivo EBD uptake, areas recognized as lesion-prone vs lesion-resistant.


Identifying Epstein-Barr virus peptide sequences associated with differential IgG antibody response.
Epstein-Barr virus (EBV) infection contributes to cancers in a fraction of seropositive individuals, but much remains to be learned about variation in EBV-directed humoral immunity in cancer-free adults. A protein microarray was used to probe serum from 175 Taiwanese and 141 Northern European adults for immunoglobulin G (IgG) antibody responses to 115 different peptide sequences, representing protein segments or protein variants, from 45 EBV proteins. It was posited that this antibody-based approach could identify EBV peptide sequences representing immunodominant regions relevant for B-cell immunity. Analyses of 45 EBV proteins with multiple protein segments or variants printed on the array identified eight EBV peptide sequences that appear to play a role in immunogenicity. This included: (1) three proteins with segments/regions associated with IgG reactivity (BALF5, LMP1, LMP2A); and (2) five proteins with sequence variants/amino acid changes associated with IgG reactivity (BDLF4, EBNA3A, EBNA3B, EBNA-LP, LF1). This examination of IgG antibody responses against 115 EBV peptide sequences in 316 cancer-free adults represents an important step toward identifying specific EBV protein sequences that play a role in generating B-cell immunity in humans.