HPV-induced recurrent laryngeal papillomatosis: rationale for adjuvant fatty acid therapy.
The course of human papilloma virus (HPV)-induced recurrent laryngeal papillomatosis (RLP) is variable and unpredictable. Some patients experience spontaneous remission, while others suffer from aggressive growth with dire consequences. Unfortunately, HPV DNA can persist in mucosa after treatment and can be reactivated under immunosuppressive conditions. For this reason, these benign tumors are notoriously recurrent. Better understanding of lipid-driven signaling pathways during tumorigenesis and immune responses in RLP patients can contribute to improve therapeutic approaches in an attempt to obviate this disease. Based on a mountain of evidence in the literature that concerns the immunomodulatory potential of certain FAs, it is clear that there is a rationale for adjuvant FA therapy (concurrent application) in the management of RLP. Of particular importance for immune surveillance is that the Th1 pathway in RLP is down-regulated and it is advocated that conjugated linoleic acid (CLA) and eicosapentaenoic acid (EPA) have the ability to restore the Th1/Th2 balance. Therefore, it is proposed that adjuvant FA therapy with CLA and EPA must be included in the therapeutical regime of RLP, since they are considered excellent anti-viral and anti-tumor agents to improve immune conditions and disease outcome. Immunocompetence plays a pivotal role in the clinical course of RLP and, hence, a new direction with adjuvant FA therapy may be the key to prevent recurrence of this disease.


Amyloid beta-peptide [1-42]-associated free radical-induced oxidative stress and neurodegeneration in Alzheimer's disease brain: mechanisms and consequences.
In addition to synapse loss, neurofibrillary tangles, and neurodegeneration, oxidative stress and amyloid beta-peptide [Abeta] deposition are hallmarks of Alzheimer's disease [AD] brain. Our laboratory coupled these two characteristics of AD into a comprehensive model to account for the synapse loss and neurodegeneration in AD brain. This model combines much of the extant studies on AD and is based on oxidative stress associated with amyloid beta-peptide. This review presents evidence in support of this model and provides insight into the molecular basis of this devastating dementing disorder.


p38 MAPK-MK2 pathway regulates the heat-stress-induced accumulation of reactive oxygen species that mediates apoptotic cell death in glial cells.
Previous studies have demonstratedf that heat stress can induce injury of the central nervous system and lead to neuronal cell apoptosis. However, the molecular mechanisms underlying these cellular changes remain unclear. In the present study, flow cytometry was used to investigate heat-stress-induced apoptosis, and caspase-3 activation was also assessed in neurons. The role of reactive oxygen species (ROS) accumulation in the heat-stress-induced apoptosis of neurons was demonstrated using the antioxidant drug manganese (III) tetrakis (4-benzoic acid)porphyrin. The present study presents evidence that heat stress induces mitogen-activated protein kinase (MAPK) activation in rat malignant glioma F98 cells. Following the inhibition of different MAPKs with a range of specific inhibitors, SB203580 (an inhibitor of p38 MAPK), but not PD98059 (an inhibitor of extracellular signal-regulated kinases) or SP600125 (an inhibitor of c-Jun N-terminal kinases), diminished the production of ROS and apoptosis, and prevented activation of the p38-downstream kinase MAPK-activated protein kinase 2 (MK2) in neurons. Inhibiting MK2 with dominant negative adenoviral constructs or a specific inhibitor significantly decreased normal and heat-stress-induced ROS accumulation and cell apoptosis, whereas inhibition of another kinase downstream of p38 MAPK, MAPK-activated protein kinase 5, by transfection with another adenoviral construct did not exert the same effects. Taken together, these findings indicate that heat stress stimulation induces p38-MK2 pathway activation, which exerts a pro-apoptotic effect by regulating ROS accumulation in neurons.


Endocrine cells in intestinal metaplasia of the stomach.
In this study we have investigated the mucin profile and the endocrine cell population in gastric endoscopic biopsies from 22 patients affected by chronic gastritis and intestinal metaplasia and in five surgical specimens of stomachs removed because of intestinal-type carcinoma (4) or peptic ulcer (1). High iron diamine-Alcian blue (HID-Ab) staining and peptide immunocytochemistry (peroxidase anti-peroxidase technique) were used. Forty-one foci of intestinal metaplasia were detected, 15 produced sulphomucins and 26 sialomucins. Of the endocrine cells investigated, gastrin and somatostatin cells were the most frequently observed, while cholecystokinin, glucose-dependent insulinotropic peptide-, secretin- and enteroglucagon-containing cells were also found in the metaplastic areas, but less frequently. No significant correlation was found between the type of mucin and the types of endocrine cells present, the latter usually resembling those normally found in the small intestine. On the basis of these results we conclude that intestinal metaplasia involves mucin- and peptide-producing cells of the stomach in a variable manner, with no correlation between the two.


MRI assessment of cardiac amyloidosis: experience of six cases with review of the current literature.
Cardiac MRI is known to be diagnostically valuable in cardiac amyloidosis. Several features are frequently found, including myocardial hypertrophy, diastolic dysfunction, a faster gadolinium blood wash out, pleural and pericardial effusions, and diffuse myocardial delayed enhancement. Cardiac MR facilitates the detection of cardiac amyloidosis and allows longitudinal assessment of myocardial function. This pictorial review focuses on cases with histologically proven systemic amyloidosis and cardiac involvement in order to illustrate typical findings.


Phospholipids containing photoactivable groups in studies of biological membranes.
Photoactivable carbene precursors, aryl diazirines and trifluorodiazopropionates, were incorporated synthetically into the omega-positions of fatty acids, which were used to synthesize phospholipids. Extensive intermolecular C--H insertion reactions were demonstrated by photolysis of liposomes prepared from the above phospholipids. Structural analysis of the cross-linked products showed that the predominant sites of cross-linking were in the expected positions within the bilayer. Studies on the topography of a number of membrane proteins using the above phospholipids were initiated. Cross-linking of the photoactivable phospholipids to membrane-embedded proteins, glycophorin A, cytochrome b5, and gramicidin A, was demonstrated.


Psychic trauma and masochism.
Three analyses are presented in which acute trauma (overwhelming internal or external stimulation so great as to preclude the patient's utilizing his usual defenses adequately) in childhood contributed to the development of masochism. The patients later attempted mastery through repetition, reversal, and erotization , and employed regression as a defense against feared oedipal wishes.


Prevention of post-stroke cognitive decline: a review focusing on lifestyle interventions.
Despite a high prevalence of post-stroke cognitive impairment, therapeutic possibilities are still limited. Stroke and dementia share the same cluster of modifiable risk factors. Thus, lifestyle interventions and strict adherence to medication may not only decrease the risk of recurrent stroke but also the risk of post-stroke cognitive decline. We performed a systematic literature search for randomized clinical trials (RCTs) targeting modifiable risk factors for the prevention of cognitive decline following stroke. We identified 25 non-pharmacological interventions and eight multiple risk factor interventions in stroke patients using cognition as outcome measure. None of the published trials investigated interventions aimed at the prevention of post-stroke cognitive decline. However, a number of ongoing trials aim at risk factor reduction and include measures on cognition. Evidence for risk factor modification for the prevention of cognitive decline after stroke is scarce and comes mainly from observational studies. There is a need for more RCTs targeting the prevention of post-stroke dementia using lifestyle interventions and a multiple risk factor approach.


Rare de novo inversion-duplication case with pure 3qter duplication syndrome including an overlap of the dup(3q) critical region: A case report.
We report here a very rare case of de novo inversion-duplication chromosomal abnormality with a pure 3qter duplication syndrome. Interestingly, the 3q duplication includes an overlap of the syndromes critical region. Although there have only been 9 cases of this syndrome reported in the past, our patient had more severe neurological abnormalities than anticipated. In this regard, we have gathered the 3q chromosomal duplication abnormalities known to cause pure 3q duplication syndrome to date as a reference for comparisons and we discuss the particulars of our case.


Biomarkers of Individual Foods, and Separation of Diets Using Untargeted LC-MS-based Plasma Metabolomics in a Randomized Controlled Trial.
Self-reported dietary intake does not represent an objective unbiased assessment. The effect of the new Nordic diet (NND) versus average Danish diet (ADD) on plasma metabolic profiles is investigated to identify biomarkers of compliance and metabolic effects. In a 26-week controlled dietary intervention study, 146 subjects followed either NND, a predominantly organic diet high in fruit, vegetables, whole grains, and fish, or ADD, a diet higher in imported and processed foods. Fasting plasma samples are analyzed with untargeted ultra-performance liquid chromatography-quadruple time-of-flight. It is demonstrated that supervised machine learning with feature selection can separate NND and ADD samples with an average test set performance of up to 0.88 area under the curve. The NND plasma metabolome is characterized by diet-related metabolites, such as pipecolic acid betaine (whole grain), trimethylamine oxide, and prolyl hydroxyproline (both fish intake), while theobromine (chocolate) and proline betaine (citrus) were associated with ADD. Amino acid (i.e., indolelactic acid and hydroxy-3-methylbutyrate) and fat metabolism (butyryl carnitine) characterize ADD whereas NND is associated with higher concentrations of polyunsaturated phosphatidylcholines. The plasma metabolite profiles are predictive of dietary patterns and reflected good compliance while indicating effects of potential health benefit, including changes in fat metabolism and glucose utilization.


The Contribution of Extracellular Nef to HIV-Induced Pathogenesis.
Nef is an accessory protein expressed exclusively in primate lentiviruses. It is devoid of enzymatic activities while interacting with several cell proteins as an adaptor/scaffold protein. Intracellular functions of Nef largely account for many pathogenic effects observed in AIDS disease. Nef, despite lacking known secretory pathways, can be detected in plasma of HIV-1-infected patients at the concentration varing from 5 to 10 ng/ml. Remarkably, the levels of Nef in plasma of HIV patients do not correlate with viral load or number of CD4(+) T lymphocytes, and persist during antiretroviral therapy. Here, we review literature data describing how Nef can be transmitted from HIV-1- infected cells to bystander ones, and the effects of extracellular Nef in different cell types. Overall, large part of experimental evidences supports the idea that extracellular Nef plays a relevant role in AIDS pathogenesis. Hence, efforts focused on the identification of Nef-inhibiting drugs would be of relevance to establish new therapeutic approaches supporting current antiretroviral therapies.


The Impact of a Knowledge Discovery-Based Psychoanalytic Intervention in the Treatment of Tuberculosis in University Students with Different Doses of Isoniazid.
Tuberculosis (TB) is an infectious disease that poses a serious threat to the health of the population in China, and TB outbreaks in universities have aroused great concern in society. Psychological emotions have a large impact on the academic lives of university students, and nowadays it is not only labour-intensive but also slow to monitor and analyse and deal with the psychology of university students' daily lives in a uniform manner. If psychological problems are not detected and given feedback in a timely manner, they can have a series of negative effects on the individual university student. In this paper, we apply the Bi-LSTM model and the CNN model neural network algorithm to learn the text data, and finally have 95.55% and 90.03% accuracy in the sentiment analysis experiment, respectively, which provides a feasible solution to solve the batch rapid analysis of the psychological changes reflected in the daily text of university students. Risk communication for TB emergencies should emphasize public participation, timely release of information about the epidemic, and good monitoring of public opinion.


Altered emotional modulation of associative memory in first episode schizophrenia: An fMRI study.
Alterations of associative memory, resulting from perturbations within the medial temporal lobe, are well established in schizophrenia. So far, all the studies having examined associative memory in schizophrenia have limited ecological validity, as people experience various emotional stimuli in their life. As such, emotion must be taken into account in order to fully understand memory. Thus, we designed an fMRI study aimed at investigating neural correlates of the effects of emotions on associative memory in schizophrenia. Twenty-four first episode schizophrenia (FES) patients and 20 matched controls were instructed to memorize 90 pairs of standardized pictures during a scanned encoding phase. Each of the 90 pairs was composed of a scene and an unrelated object. Furthermore, trials were either neutral or emotional as a function of the emotional valence of the scene comprising each pair. FES patients exhibited lower performance for both conditions than controls, with greater deficits in regard to emotional versus neutral associations. fMRI analyses revealed that these deficits were related to lower activations in mnemonic and limbic regions. This study provides evidence of altered associative memory and emotional modulation in schizophrenia, resulting from dysfunctions in the cerebral networks underlying memory, emotion, and encoding strategies. Together, our results suggest that all these dysfunctions may be targets for new therapeutic interventions known to improve cognitive deficits in schizophrenia.


Tetralogy of Fallot with discrete fibrous subaortic stenosis.
This is the first reported case of discrete fibrous subaortic stenosis in tetralogy of Fallot. Transaortic excision of the subaortic membrane was readily accomplished. To detect this and other forms of left ventricular outflow-tract obstruction in tetralogy of Fallot before surgery, routine selective left ventriculography is advocated.


Perineal abscess after prostatic urethroplasty with balloon catheter: report of a case.
A 72-year-old patient underwent uneventful prostatic urethroplasty by means of a balloon catheter. The immediate follow-up retrograde urethrogram failed to demonstrate any areas of extravasation and showed a significant increase in prostatic urethral caliber. Three weeks after the patient was discharged, computed tomography demonstrated a large perineal abscess that was attributed to either the prostatic urethroplasty or subsequent Foley catheter manipulations. The abscess was drained percutaneously, and the patient recovered uneventfully. It was concluded that the abscess was a possible isolated complication and that the procedure is warranted in an adequate clinical setting.


Open distal humerus fractures--review of the literature.
Fractures of the distal humerus can be difficult to treat due to the periarticular nature of these injuries and the complexity of the elbow joint. Although anatomic and timely repair of the distal humerus with meticulous handling of soft tissues and appropriate postoperative therapy all help to optimize results, an open fracture presents other challenges that may limit successful outcomes in spite of these measures. Open fractures have been found to affect younger males involved in high-energy injuries, as well as older, osteoporotic females involved in lower energy situations. Successful management of these injuries requires urgent and aggressive soft tissue management, skeletal stabilization, and treatment of neurovascular insult (if applicable). This article presents a review of the current literature available concerning the epidemiology, assessment and examination, treatment options, complications, and outcomes of patients with open distal humerus fractures.


EDUCATION AND IMAGING. Hepatobiliary and Pancreatic: Rapid growing cystic ovarian metastasis from pancreatic cancer.
Pancreatic cancer rarely develops cystic ovarian metastasis. We present a 63-year-old female patient with unresectable pancreas head cancer. Seven months after the introduction of the chemoradiotherapy, a giant intrapelvic cystic tumor with rapid growth was found. The tumor was resected because the patient complained of severe bloating and no other new metastatic sites could be identified. Postoperative pathological examination diagnosed it as an ovarian metastasis from the pancreas cancer.


Bubble dispenser in microfluidic devices.
This Brief Report presents experimental and computational results on bubble formation in microfluidic devices. Bubbles are generated at the right-angle intersection of four identical square microchannels. When the pressure gradient generated by the liquid flow dominates the pressure gradient generated by gas flow, the length of the produced confined bubbles follows a law based on the channel size and fluid volume fraction. This bubble production technique was used to produce monodisperse aqueous foam in two-dimensional and three-dimensional microchannels.


High resolution recording of late cortical surface potentials N1 and gamma band response (GBR).
The present investigation was conducted to help determine whether source activity of the direct recorded N1 response differed from that of the gamma band response (GBR). Auditory evoked cortical potential data from two patients with intractable epilepsy undergoing prolonged video EEG monitoring after implantation of subdural electrodes is reported in this investigation. Evoked responses were recorded to 1000-Hz tone bursts. The data were then filtered digitally to resolve the GBR. The voltage fields were subsequently viewed topographically. Although both responses originated in the supratemporal cortex, the N1 and GBR voltage field patterns differed. These results are consistent with the view that the sources of N1 and the GBR are different, suggesting that these components emanate from functionally distinct neuronal pools.


Lymphoid tissue neoplasms in the neck region - epidemiological and clinical analysis over 15 years.
Epidemiological and clinical analysis of lymphoid tissue neoplasms in the neck region over a 15-year period. There was performed retrospective analysis of 97 patients, aged 17 to 88 years, mean age of 60.3 years. The analysis included data from subjective study, physical examination, image and histopathological studies Results: Almost all cases were lymphoid neoplasms - 95 patients (98%). B cell lymphoma was the most commonly diagnosed lymphoma - 74 cases (76%), followed by Hodgkin's lymphoma- 19 cases (20%). Only two patients had T-cell lymphoma (2%). There was observed prevalence among women, K: M ratio for the whole group was 51: 46, while male predominance was reported in Hodgkin's lymphoma patients (K: M = 7: 12). Over the 15-year period, there was an increase in the number of lymphoid tumors. The most common location on the neck were lymph nodes - 71 (73.2%). Extranodal localizations (26.8%) were most often associated with salivary glands: parotid and submandibular involvement and with the dominant lymphoma of the marginal zone MALT (14 cases). In 57% of patients the fine needle aspiration biopsy (FNAB) results were false, with positive results only in 32% of patients. Tumors from lymphoid tissue in the neck region are most commonly B-cell lymphomas or Hodgkin,s lymphomas. Non-specific clinical signs and non-specific radiological images, as well as non-diagnostic results o FNAB, make it difficult to effectively differentiate lymphomas with cancer metastasis in neck lymph nodes. Histopathology results of the excised lymph nodes remains a standard for lymphoma diagnosis.


Chronic glucocorticoid exposure activates BK-NLRP1 signal involving in hippocampal neuron damage.
Neuroinflammation mediated by NLRP1 (nucleotide-binding oligomerization domain (NOD)-like receptor protein 1) inflammasome plays an important role in many neurological diseases such as Parkinson's disease (PD) and Alzheimer's disease (AD). Our previous studies showed that chronic glucocorticoid (GC) exposure increased brain inflammation via NLRP1 inflammasome and induce neurodegeneration. However, little is known about the mechanism of chronic GC exposure on NLRP1 inflammasome activation in hippocampal neurons. Hippocampal neurons damage was assessed by LDH kit and Hoechst 33258 staining. The expression of microtubule-associated protein 2 (MAP2), inflammasome complex protein (NLRP1, ASC and caspase-1), inflammatory cytokines (IL-1β), and large-conductance Ca2+ and voltage-activated K+ channel (BK channels) protein was detected by Western blot. The inflammatory cytokines (IL-1β and IL-18) were examined by ELISA kit. The mRNA levels of NLRP1, IL-1β, and BK were detected by real-time PCR. BK channel currents were recorded by whole-cell patch-clamp technology. Measurement of [K+]i was performed by ion-selective electrode (ISE) technology. Chronic dexamethasone (DEX) treatment significantly increased LDH release and neuronal apoptosis and decreased expression of MAP2. The mechanistic studies revealed that chronic DEX exposure significantly increased the expression of NLRP1, ASC, caspase-1, IL-1β, L-18, and BK protein and NLRP1, IL-1β and BK mRNA levels in hippocampal neurons. Further studies showed that DEX exposure results in the increase of BK channel currents, with the subsequent K+ efflux and a low concentration of intracellular K+, which involved in activation of NLRP1 inflammasome. Moreover, these effects of chronic DEX exposure could be blocked by specific BK channel inhibitor iberiotoxin (IbTx). Our findings suggest that chronic GC exposure may increase neuroinflammation via activation of BK-NLRP1 signal pathway and promote hippocampal neurons damage, which may be involved in the development and progression of AD.


A Randomized, Crossover Trial Evaluating Patient Handling, Preference, and Ease of Use of the Fluticasone Propionate/Formoterol Breath-Triggered Inhaler.
Appropriate inhaler selection is of fundamental importance in obstructive lung disease management. Key factors in device selection include a patient's capacity to operate a particular device and their preference for it. This randomized, open-label, two-period, crossover study (NCT01739387) compared the ability of adolescent and adult patients with obstructive lung disease to correctly handle the fluticasone propionate/formoterol fumarate (FP/FORM; Flutiform®) pressurized metered-dose inhaler (pMDI) and FP/FORM K-haler®, a novel breath-triggered inhaler (BTI), following a simple, standardized training regimen. The primary endpoint was the ability to perform all steps correctly at the first attempt. Secondary endpoints included the ability to perform all critical steps correctly at the first attempt, the requisite number of attempts to successfully use the inhaler, the ability to be trained within 15 minutes, and the ability to trigger the K-haler BTI to actuate at the first attempt. Ease of device use and device preference versus patients' usual maintenance inhalers were also assessed. At the first attempt, an identical proportion (77.2% [95% confidence interval [CI]: 72.1, 81.8]) of 307 patients performed all pMDI and K-haler BTI handling steps correctly, whereas the corresponding proportions performing all critical steps correctly were 82.4% (95% CIs: 77.7, 86.5) and 87.0% (95% CI: 82.7, 90.5), respectively. For both devices, >90% of patients required only two attempts to master device usage; >99% of patients could be trained to correctly use each device within 15 minutes. Virtually all patients (99.0% [95% CIs: 97.2, 99.8]) were able to successfully trigger the K-haler BTI's dose-release mechanism at first attempt. Ease of use and preference data for FP/FORM pMDI challenged the perceived wisdom that dry powder inhalers are necessarily simpler to use, whereas the corresponding data for FP/FORM K-haler strongly favored this novel BTI over the Turbuhaler®, Accuhaler®, and other pMDIs.


Hurricane Katrina response and guidance for health-care providers, relief workers, and shelter operators.
Hurricane Katrina struck the coastal areas of Alabama, Florida, Louisiana, and Mississippi on August 29, 2005, causing substantial numbers of deaths among both humans and animals, infrastructure damage, and flooding. Affected areas continue to experience shortages of essential services, including electricity, potable water, food, and fuel; damage to health-care and public health systems; and disrupted communications. CDC/ATSDR, local and state health departments, other federal agencies, and other partners are supporting public health and medical-care functions for persons in affected areas and those displaced as a result of the hurricane.


Evaluation of the digene hybrid capture II CT-ID test for detection of Chlamydia trachomatis in endocervical specimens.
The performance characteristics of the new signal amplification-based Hybrid Capture (HC) II CT-ID test system (Digene, Silver Spring, Md.) with endocervical specimens were compared to those of tissue culture and PCR (AMPLICOR CT PCR; Roche Molecular Systems, Branchburg, N.J.) for detection of Chlamydia trachomatis in 587 women. HC II CT-ID identified 62 of 65 confirmed C. trachomatis-positive patients (sensitivity of 95.4%) and was negative for 517 of 522 patients who were negative by culture and PCR (specificity of 99.0%). Twelve of the 65 confirmed positive patients were negative by culture but were identified by both HC II CT-ID and PCR (sensitivity of culture was 81.5% [P < 0.01]). In comparison, PCR detected 59 of 65 positive specimens (sensitivity of 90.8%) and had a specificity of 99.6% (520 of 522). These results demonstrate that the Digene HC II CT-ID test is a highly sensitive and specific assay for the detection of C. trachomatis infection in endocervical specimens.


Comparison of ovalbumin and ovalbumin epitope peptide for transdermal delivery and vaccination mediated by the photothermal effect of gold nanorods.
Transdermal protein delivery is a powerful and attractive method for protein therapy and dermal vaccination compared with other administrations. However, this delivery method is restricted by the low permeability of the stratum corneum (SC), a hydrophobic barrier that restricts the entry of hydrophilic molecules such as proteins. In this study, we developed an improved gel patch system carrying ovalbumin and ovalbumin epitope peptide, and then compared their permeability into the skin. First, the gel patch was placed on mouse skin to allow contact with the polymer coated gold nanorods and then irradiated by a continuous-wave laser. Thermal ablation of the SC improved the permeability and translocation of ovalbumin and the peptide. Fluorescence images showed the translocation was enhanced when the skin was treated with the FITC-modified ovalbumin epitope peptide. However, induction of anti-OVA IgG production after treatment with the FITC-modified ovalbumin epitope peptide was lower than that with FITC-OVA.


[Prognostic value of the ultrasound visualization of the bulging agent after endoscopic treatment of vesicouretal reflux].
The endoscopic treatment of vesicoureteral reflux constitutes an easy and simple option at the moment for its resolution in all degrees and ages. It is necessary to carry out an ECO and VCUG (vesical cystouretrography) during voiding to verify their resolution. The ultrasongraphy can detect the wheal of injected material (Teflon or Macroplastic), but it is ignored if its visualization implies its disappearance or not. To see the correspondence or not between the sonographic presence of injected material wheal and disappearance of reflux in the VCUG. It has been statistically selected a sample of convenience to calculate the sensibility and specificity of the sonographic visualization of the endoscopic injected material wheal. We have studied 115 ureters with all the reflux degrees and ages, chosen randomly among patients treated endoscopically of vesicoureteral reflux, independently of the injected material, polytetrafluoroethylene (Teflon) or polydimethylsiloxane (Macroplastic). Refluxes due to duplex systems and those in which there were doubts of their correct installation during endoscopy were rejected. Cases with two or more injections were rejected too. The ECO and corresponding cystographies were revised in the first control after treatment (three months later). With this data, a chart of 2X2 was built comparing the presence or not of wheal in the ECO with the presence or not of reflux in the VCUG. We calculate sensibility, specificity, PPV (positive predictive value) and NPV (negative predictive value) as well as the degree of agreement of both tests with the kappa index. In 115 ureteral units we visualized with ECO the wheal of injected material in 97 and not in 18 (16%). In those cases with visualized wheal, reflux disappeared in 59 (61%), and in 38 not (39%). In those cases where the wheal was not visualized, reflux disappeared in 13 and persisted in other 5 (28%). The degree of sensibility was 12%, the specificity 82%, the PPV 22% and the NPV 61%. Attending to the low specificity and predictive values, the sonographic presence of material wheal doesn't indicate that the reflux has been corrected, as well as its absence doesn't reflect the presence of the same one, being always necessary to carry out a cystography for its diagnosis.


Age- and sex-specific incidence of childhood leukemia by immunophenotype in the Nordic countries.
Studies from various countries have found an increasing incidence of childhood leukemia in recent decades. To characterize time trends in the age- and sex-specific incidence of childhood acute leukemia during the last 20 years in the Nordic countries, we analyzed a large set of population-based data from the Nordic Society of Paediatric Haematology and Oncology (NOPHO) in their acute leukemia database covering a population of approximately 5 million children aged 0-14 years. Temporal trends in acute myeloid leukemia and acute lymphoblastic leukemia incidence rates overall and for acute lymphoblastic leukemia immunophenotypes and for specific age groups were analyzed by Poisson regression adjusting for age, sex, and country. All statistical tests were two-sided. We identified 1595 girls and 1859 boys diagnosed with acute lymphoblastic leukemia between January 1, 1982, and December 31, 2001, and 260 girls and 224 boys diagnosed with de novo acute myeloid leukemia between January 1, 1985, and December 31, 2001. No statistically significant change was seen in the overall incidence rate for acute lymphoblastic leukemia during the 20-year study (annual change = 0.22%, 95% confidence interval [CI] = -0.36% to 0.80%). The incidence rate of B-precursor acute lymphoblastic leukemia remained unchanged (annual change = 0.30%, 95% CI = -0.57% to 1.18%) from January 1, 1986, through December 31, 2001. A somewhat lower incidence in the first years of the study period indicated an early increasing incidence of B-precursor acute lymphoblastic leukemia that corresponded to a simultaneous decreasing incidence of unclassified acute lymphoblastic leukemia. Incidences of T-cell acute lymphoblastic leukemia (annual change = 1.55%, 95% CI = -1.14% to 4.31%) and acute myeloid leukemia (annual change = 0.58%, 95% CI = -1.24% to 2.44%) were stable during the study period. Incidences of acute myeloid leukemia overall, acute lymphoblastic leukemia overall, and specific acute lymphoblastic leukemia immunophenotypes have been stable in the Nordic countries over the past two decades.


Long-term safety, tolerability and efficacy of flexible-dose fesoterodine in elderly patients with overactive bladder: open-label extension of the SOFIA trial.
To assess the long-term safety, tolerability, and efficacy of flexible-dose fesoterodine in elderly patients with OAB. Patients aged ≥65 years who completed a 12-week, randomized, double-blind, placebo-controlled trial were eligible for the 12-week, open-label (OL) extension phase. Patients who received double-blind placebo started on fesoterodine 4 mg and could increase to 8 mg after 4 or 8 weeks of OL treatment, while fesoterodine-treated patients continued on their double-blind dose; only one dose escalation or de-escalation was permitted. Discontinuations and adverse events (AEs) were monitored, and patients completed 3-day bladder diaries and patient-reported outcomes at the beginning and end of the 12-week OL phase. Six hundred fifty-four patients entered the 12-week OL extension (mean age 72 years; 52% women). AEs were reported by 30.7% and 48.1% of patients who had received double-blind fesoterodine and placebo, respectively; 1.9% and 9.4%, discontinued due to AEs, respectively. Patients who received double-blind fesoterodine maintained their efficacy response. After 12 weeks of OL treatment, efficacy outcomes in patients who received double-blind placebo were similar to those who had received double-blind fesoterodine. On average, the efficacy response was maintained for the duration of the study. Fesoterodine was well tolerated and improvements in OAB symptoms and quality of life measures were not diminished with longer-term treatment of patients aged ≥65 years.


Antibiotic consumption study in two hospitals in Asmara from 2014 to 2018 using WHO's defined daily dose (DDD) methodology.
This study compares the antibiotic consumption rates over a period of five years in two hospitals in Eritrea, Orotta National Referral and Teaching Hospital (ONRTH) and Hazhaz Zonal Referral Hospital (HZRH). Antibiotic consumption is an important parameter in the study of antibiotic use. However, no published data on consumption rates exist for these two hospitals, thus the aim of the study is to measure and compare a five year antibiotic consumption trends of the two hospitals' medical wards using Defined Daily Dose per 100 bed-days (DDD/100-BD). Antibiotics dispensed from January 2014 to December 2018 were considered. Non-parametric Pearson's correlation coefficient was used for comparison of consumption, while non-parametric Friedman's test measured annual rates. The total antibiotic consumption in the HZRH was almost double that of ONRTH. The analysis showed that antibiotic consumption in ONRTH was significantly decreased from 2014 to 2018 while there was no significant difference in consumption in HZRH. Benzyl penicillin was the most consumed antibiotic in HZRH and ONRTH throughout the study period at 87.8DDD/100-BD and 35.4 DDD/100-BD respectively. Ceftriaxone and ciprofloxacin were among the most commonly consumed antibiotics in both hospitals. Establishment of Antibiotic stewardship program would benefit both hospitals greatly, and further studies need to be done to establish the national antibiotic consumption baseline.


Mulberry extract supplements ameliorate the inflammation-related hematological parameters in carrageenan-induced arthritic rats.
Mulberry fruit (Morus Lhou Koidz.), a rich source of the major anthocyanin, cyanidin 3-glucoside (C3G), has traditionally been used for the treatment of inflammatory conditions including rheumatic arthritis. In this study, we evaluated the efficacy of orally administrated methanolic mulberry fruit extract (ME) in carrageenan-induced arthritic rats, based on previously observed in vitro antioxidant and anti-inflammatory activities. A significant attenuation of hind paw inflammation characterized by fluid accumulation, uric acid production, and rheumatoid factors induced by carrageenan was observed following the intake of both ME (50 mg/kg of body weight) and C3G (10 mg/kg of body weight). Moreover, alterations in hematological parameters such as serum triglyceride, high-density lipoprotein-cholesterol, and atherogenic index following carrageenan administration were partially reversed by the administration of ME. It is concluded that dietary mulberry fruit extracts elicited protection against carrageenan-induced inflammation.


[Magnetic resonance imaging of craniofacial pathology].
Effectiveness of nuclear magnetic resonance imaging (MRI) was compared with that of the CT scan in several cases involving different lesions: intracranial, base of skull, facial sinuses, parapharyngeal spaces. MRI provided excellent contrast in soft tissues with good detection of tumors and their limits, the condition of neighboring tissues and any local or regional tumor extension. Vessels were also visualized. It was not influenced by dental artefacts, and allowed three-dimensional sections to be obtained simply without manipulation of patients. In contrast, bone structures were analyzed less clearly than by the CT scan. Marked progress in MRI technical features and results obtained can be expected in the very near future.


Synthesis of Gold Nanoparticles Using Leaf Extract of Ziziphus zizyphus and their Antimicrobial Activity.
(1) Background: There is a growing need for the development of new methods for the synthesis of nanoparticles. The interest in such particles has raised concerns about the environmental safety of their production methods; (2) Objectives: The current methods of nanoparticle production are often expensive and employ chemicals that are potentially harmful to the environment, which calls for the development of "greener" protocols. Herein we describe the synthesis of gold nanoparticles (AuNPs) using plant extracts, which offers an alternative, efficient, inexpensive, and environmentally friendly method to produce well-defined geometries of nanoparticles; (3) Methods: The phytochemicals present in the aqueous leaf extract acted as an effective reducing agent. The generated AuNPs were characterized by Transmission electron microscopy (TEM), Scanning electron microscope (SEM), and Atomic Force microscopy (AFM), X-ray diffraction (XRD), UV-visible spectroscopy, energy dispersive X-ray (EDX), and thermogravimetric analyses (TGA); (4) Results and Conclusions: The prepared nanoparticles were found to be biocompatible and exhibited no antimicrobial or antifungal effect, deeming the particles safe for various applications in nanomedicine. TGA analysis revealed that biomolecules, which were present in the plant extract, capped the nanoparticles and acted as stabilizing agents.


Multicentric experience on the acute effect of nomifensine in hyperprolactinemic women.
The inhibitory effect of nomifensine ( Nom ; 200 mg orally) on prolactin (PRL) secretion was studied in 15 subjects with puerperal hyperprolactinemia and in 59 pathologic hyperprolactinemic women. The latter were grouped as follows: i) patients with surgically proven PRL secretory pituitary adenomas (proven tumors; 27 cases); ii) patients presenting radiological signs of sella indicative of a pituitary tumor (presumptive tumors; 10 cases); iii) subjects with non-drug induced hyperprolactinemia (hyperprolactinemia of uncertain etiology; 22 cases). A mean PRL fall of 30% or more of baseline hormone levels in samples collected within the 120-240 min post-treatment interval was adopted to define responsiveness to Nom . In 24 out of 27 subjects with proven tumors and in 9 out of 10 subjects with presumptive tumors Nom did not induce significant variations in PRL secretion. In only 11% of the patients with surgery-confirmed or highly suspected tumors a hormone decrease greater than 30% was observed. In addition, 13 subjects with hyperprolactinemia of uncertain etiology did not respond to Nom administration. In 5 of these, additional data suggesting the existence of an adenoma were collected. Finally, 3 out of 9 Nom -responder patients presented either a polycystic ovary syndrome or transitory hyperprolactinemia. The finding that hyperprolactinemic women, who did not show clinical or radiological signs of a tumor and patients with highly presumptive or proven pituitary tumors may present comparable responses to Nom , suggests that this pattern may be indicative of an early manifestation of a PRL-secreting adenoma which has yet to evolve. The follow-up of Nom -non-responder hyperprolactinemic subjects who did not show clinical signs of harboring a tumor, is therefore advisable.


Treatment of experimental Toxoplasma gondii infection by clarithromycin-based combination therapy with minocycline or pyrimethamine.
The efficacy of clarithromycin combined with either pyrimethamine or minocycline for treatment of experimental Toxoplasma gondii infection was investigated. Mice were infected intraperitoneally with 2 x 10(3) to 2 x 10(4) T. gondii strain RH or TS4 tachyzoites. Mortality was recorded for 35 days postinfection. Latency was evaluated by inoculation of brain homogenates from surviving mice into naive untreated mice. The combination of clarithromycin and pyrimethamine therapy caused a significantly greater reduction in mortality than did either drug alone. Similar synergy was observed between clarithromycin and minocycline. A 100% cure rate of active and latent infection was achieved in mice treated with the clarithromycin based combinations. Clarithromycin in combination with either pyrimethamine or minocycline produced efficacy comparable to combined therapy of pyrimethamine with sulfamethoxazole. The in vitro potency of clarithromycin, pyrimethamine, or minocycline against T. gondii on a mouse macrophage monolayer was not predictive of the in vivo efficacy in mice. Clarithromycin combined with minocycline or pyrimethamine could allow greater flexability for treatment of patients predisposed to the toxicity associated with standard pyrimethamine-sulfonamide or pyrimethamine-nonsulfonamide therapy. This therapy could be especially useful since clarithromycin-based therapy provides safe and effective treatment against Mycobacterium avium complex infections associated with AIDS patients.


An Efficient Approach in Analysis of DNA Base Calling Using Neural Fuzzy Model.
This paper presented the issues of true representation and a reliable measure for analyzing the DNA base calling is provided. The method implemented dealt with the data set quality in analyzing DNA sequencing, it is investigating solution of the problem of using Neurofuzzy techniques for predicting the confidence value for each base in DNA base calling regarding collecting the data for each base in DNA, and the simulation model of designing the ANFIS contains three subsystems and main system; obtain the three features from the subsystems and in the main system and use the three features to predict the confidence value for each base. This is achieving effective results with high performance in employment.


Milk basic protein (MBP) increases radial bone mineral density in healthy adult women.
We studied the effects of daily intake of milk basic protein (MBP) on radial bone mineral density (BMD) in healthy adult women. Thirty-three healthy women were randomly assigned to a 6-month trial with either placebo or MBP (40 mg per day). The radial BMD of each volunteer was measured at the beginning of and at six months after the trial. The mean BMD value at the 6th month in the MBP group increased significantly at both 1/6 and 1/10 portion from the distal end of the radius, whereas that in the control group did not. The BMD gain of each volunteer in the MBP group was significantly higher than that in the placebo group. Thus a daily MBP supplementation of 40 mg in healthy adult women can significantly increase radial BMD.


[The mechanisms of the development of tissue hypoxia and the criteria for its assessment in patients with hemorrhagic fever with renal syndrome].
Comparison of the parameters that characterize the activity of the sympathoadrenal system (urine adrenalin and noradrenalin) and the severity of hypoxia (lactic acid in blood and urine, pyruvic acid in blood and urine, lactate/pyruvate) in patients suffering from hemorrhagic fever with the renal syndrome (HFRS) showed them to be significantly and directly correlated. The time-course of changes in the study parameters mirrors the gravity of the pathological process. The authors hold that the sympathoadrenal system plays the leading role in the development of different types of tissue hypoxia in HFRS patients.


Treatment patterns, adherence, and persistence in ADHD: a Canadian perspective.
To understand attention-deficit/hyperactivity disorder (ADHD) treatment patterns and estimate adherence and persistence in Quebec, Canada. This cross-sectional, retrospective prescription claims analysis used a random sample of 15 838 patients with ADHD from a Quebec database (Régie de l'assurance maladie du Québec [RAMQ]) to assess treatment patterns, adherence (1-year medication possession ratio in new users), and persistence (proportion persistent at 3, 6, and 12 months after index prescription). The mean patient age was 14 years; 72.6% were male. During the 5-year study period (2004-2009), 416 646 ADHD prescriptions were filled. Short-acting (SA) medications declined from 72.8% to 26.4% of all claims, while stimulant and nonstimulant long-acting (LA) medications increased from 27.2% to 73.6%. Approximately half of the patients used both SA and LA medications (either concomitantly or subsequently), and the others used only SA (30%) or LA (19%) drugs. Among patients using both, switching from SA to LA was the most frequent (27.9%) treatment pattern. More patients on LA methylphenidates (6.4%) compared with LA amphetamines (1.9%; P < 0.01) required augmentation with an SA drug. Fewer patients on SA stimulants (39.4%) were ≥ 80% adherent compared with LA stimulants (63%; P < 0.001) and LA nonstimulants (60.2%; P < 0.001). More patients on LA stimulants (81.1%) were persistent at 12 months compared with LA nonstimulants (61.7%; P < 0.001) and SA stimulants (59.6%; P < 0.001). Similar trends were observed at all time points measured. Switching from SA to LA medications and treatment augmentation are common in ADHD management, with implications for patient care and health care resource use. This analysis found poor adherence in ADHD treatment, although adherence and persistence were improved with LA stimulant formulations.


Distributed optical synthetic aperture position-transformed method with high-frequency domain coverage.
Realizing an ultrahigh-equivalent aperture for space-based direct optical detection using a distributed optical synthetic aperture (DOSA) system with a very low filling ratio is challenging. This study proposes a position-transformation method for DOSA systems with high-frequency domain coverage called High-Frequency domain-Covering discrete Archimedean Spiral Arrays (HFCASA). The study shows that Golay3 HFCASA with a filling ratio of 0.0675% can greatly improve frequency domain coverage and fulfill the resolution requirements of a 200 m aperture telescope. HFCASA provides the theoretical basis for the future deep-space exploration of DOSA.


Validity and Reliability of the Korean Version of the Anesthesia Surrendering Instrument.
This study examined the reliability and validity of the Korean version of the anesthesia surrendering instrument (ASI), which was originally developed to measure anesthesia surrendering in Swedish adults. The study population consisted of 306 patients who received general anesthesia for abdominal, breast, knee, hip, lower back, or shoulder surgery in ten hospitals across five regions of Korea from June to September 2019. The validity of the content, construct, and criterion used, and the reliability of the ASI were assessed. The results showed that the instrument had appropriate content validity; the item-level content validity index ranged between 0.80 and 1.00, and the scale-level content validity index was 0.90. The construct validity test results confirmed four sub-categories with a total of 26 items, and the internal consistency reliability tests showed Cronbach's alpha values ranging between 0.71 and 0.88. The study findings confirmed the applicability of this instrument for measuring anesthesia surrendering in Korean adults. These results provide a foundation for future studies on anesthesia surrendering in Korean adult patients.


Survey Based Assessment of Burnout Rates Among US Plastic Surgery Residents.
The purpose of this study was to analyze the rates of burnout and contributory factors among US plastic surgery residents. The Maslach Burnout Inventory Human Services Survey was emailed to program coordinators of American College of Graduate Medical Education-accredited plastic surgery residencies. Scores are provided for 3 subscales: emotional exhaustion (EE), depersonalization (DP), and personal accomplishment. Normative scoring tables (low, average, high) were used for comparison. Residents were asked questions relating to their personal life (age, postgraduate year, marital status, and program characteristics). One hundred thirteen residents responded. The average age was 31.6 years (range, 25-43 years) and postgraduate year of 4.6 (range, 1-10). There were equal male and female respondents. Most were from integrated-only residencies (n = 59, 52.2%). On average, the majority reported working 50 to 80 hours per week (n = 93, 82.3%), spending the majority of time in tertiary referral centers (n = 107, 94.7%). Most received and took 3 weeks of vacation per year (n = 68, 60.7%). Furthermore, 65.5% met the definition of burnout by their scores from at least 1 subscale.The number of hours worked per week significantly correlated with increased scores in the EE and DP subscales. Residents who worked more than 80 hours per week had significantly higher scores in the EE and DP categories. Residents who had less than 2 weeks of vacation per year trended toward experiencing more EE (EE; 46.0, P = 0.077). The type of program (independent vs integrated), sex, having a significant other outside of the home, kids, and local family support did not significantly affect burnout scores for any subscales. Burnout exists among plastic surgery residents especially in the DP subscale. Working longer hours and less vacation correlates with increased rates of burnout among residents.


Efavirenz in plasma from HIV-infected patients does not directly block reverse transcriptase activity in cell-free assays but inhibits HIV replication in cellular assays.
The aim of this study was to characterize the potent nonimmunoglobulin (Ig) inhibitory activity defected in plasma from some HIV-infected, efavirenz (EFV)-treated patients. Concentration of EFV in plasma was measured by HPLC and correlation with reverse transcriptase (RT) inhibition or decrease in virus replication in cellular assays was searched. After plasma protein elimination by ethanol extraction, an inhibitory activity is measurable on RT in vitro that correlates with EFV concentration determined by HPLC. However, total plasma-containing EFV does not inhibit RT activity in cell-free assay, but it does efficiently inhibit virus replication in cell culture assays. Thus, despite being bound to plasma proteins (retention of EFV after extensive dialysis), EFV in plasma conserves its antiviral activity on infected cells. This observation precludes the use of crude sera and plasmas from EFV-treated patients for the study of antibody-mediated neutralizing activity.


Thy-1 is expressed in hepatic myofibroblasts and not oval cells in stem cell-mediated liver regeneration.
Thy-1, a marker of hematopoietic stem cells, has been reported to be expressed by oval cells proliferating during stem cell-mediated regeneration in rat liver, suggesting a relationship between the two cell populations. Consequently, Thy-1 has become an accepted cell surface marker to sort hepatic oval cells. In the present study we used the well-characterized 2-acetylaminfluorene/partial hepatectomy model to induce transit-amplification of hepatic oval cells in the regenerating liver and characterized Thy-1 expression using Northern hybridization, quantitative reverse transcriptase-polymerase chain reaction analysis, immunofluorescence confocal microscopy, and immunoelectronmicroscopy. We found that Thy-1 expression was induced during transit-amplification of the oval cell population, but Thy-1 mRNA was not present in the alpha-fetoprotein-expressing oval cells. Thy-1 protein was consistently present outside the basement membrane surrounding the oval cells. It overlapped frequently with smooth muscle actin staining. A similar cellular localization of the Thy-1 protein was found on human liver specimens with ductular reactions obtained from patients with fulminant liver failure. Furthermore, Thy-1 was expressed by myofibroblasts in experimental liver fibrosis models without oval cell proliferation. We conclude that Thy-1 is not a marker of oval cells but is present on a subpopulation of myofibroblasts/stellate cells.


Lactococcus piscium sp. nov. a new Lactococcus species from salmonid fish.
Chemical and molecular taxonomic studies were performed on a representative strain of some lactic acid bacteria of unknown taxonomic position isolated from salmonid fish. The results demonstrate that the fish bacterium represents a new species of the genus Lactococcus for which the name Lactococcus piscium sp. nov. is proposed. The type strain of Lactococcus piscium is NCFB 2778.


Influenza immunization coverage of children with sickle cell disease.
To assess receipt of annual flu immunization among children living with sickle cell disease (SCD). Receipt of flu immunization (2014-2019) by SCD status was assessed among all Michigan children <18 years of age using the statewide immunization registry. Logistic regression was used to estimate the odds of annual flu immunization by SCD status and age. Annual flu immunization coverage was higher among children with SCD (46.9%; n = 751) than without (23.2%; n = 2,012,846). The annual adjusted odds of flu immunization for those with SCD were 2.8 (95% CI: 2.5-3.1) times higher than for those without SCD; there were no significant differences by age among children with SCD. Among those without SCD, adolescents aged 13-17 were 2.2 (95% CI: 2.2-2.2) times less likely to receive annual flu immunization than children 6-35 months. Children with SCD had higher annual flu immunization rates than those without SCD, but >50% remain unimmunized.


The intra-articular residual rate of 131I-fibrinogen and microautoradiographs of the synovial tissue in rheumatoid arthritis.
In this study, 131I-labeled human plasma fibrinogen (200 muCi) was injected intravenously into 21 patients with rheumatoid arthritis and 10 control patients without rheumatic diseases. The residual rates of radioiodinated fibrinogen in the knee joints were calculated by measuring with a scintillation counter the microautoradiographs of the synovial tissue obtained by punch biopsy from the knee joints. The residual rates in the knee joints without as well as with objective symptoms of RA were higher than in control patients. Radio-iodinated fibrinogen was demonstrated on the synovial villous surface, on the area of inflammatory cellular infiltration and stromal necrosis, and on the perivascular region of the synovial tissue from the knee joints of patients with RA, not only with, but also without clinical objective symptoms and histopathologic findings of fibrinoid necrosis, vascular superficial fibrinoid coating and fibrinoid degeneration of vascular wall. It is suggested that fibrinogen plays a role even in the early synovial tissue lesions of knee joints affected by RA.


Stridor caused by a blue laryngeal mass in an infant: case report.
Stridor caused by.a blue laryngeal mass in an infant: case report. We describe an infant who had inspiratory stridor that began a few weeks after birth. Flexible upper airway endoscopy while the infant was awake showed a large blue mass at the posterior glottis, above the esophageal inlet. The lesion was only visible upon crying or coughing; it was undetectable when we examined the infant in the supine position during spontaneous breathing and did not respond to systemic treatment with propranolol. Based upon these typical features, we established a diagnosis of pressure- dependent postcricoid mass.


Hepatic dual-contrast CT imaging: slow triple kVp switching CT with CNN-based sinogram completion and material decomposition.
Purpose: Dual-contrast protocols are a promising clinical multienergy computed tomography (CT) application for focal liver lesion detection and characterization. One avenue to enable multienergy CT is the introduction of photon-counting detectors (PCD). Although clinical translation is highly desired because of the diagnostic benefits of PCDs, it will still be a decade or more before they are broadly available. In our work, we investigated an alternative solution that can be implemented on widely used conventional CT systems (single source and integrating detector) to perform multimaterial spectral decomposition for dual-contrast imaging. Approach: We propose to slowly alternate the x-ray tube voltage between 3 kVp levels so each kVp level covers a few degrees of gantry rotation. This leads to the challenge of sparsely sampled projection data in each energy level. Performing the material decomposition (MD) in the sinogram domain is not directly possible as the projection images of the three energy levels are not angularly aligned. In order to overcome this challenge, we developed a convolutional neural network (CNN) framework for sparse sinogram completion (SC) and MD. To evaluate the feasibility of the slow kVp switching scheme, simulation studies of an abdominal phantom, which included liver lesions, were conducted. Results: The line-integral SC network yielded sinograms with a pixel-wise RMSE < 0.05 of the line-integrals compared to the ground truth. This provided acceptable image quality up to a switching angle of 9 deg per kVp. The MD network we developed allowed us to differentiate iodine and gadolinium in the sinogram domain. The average relative quantification errors for iodine and gadolinium were below 10%. Conclusions: We developed a slow triple kVp switching data acquisition scheme and a CNN-based data processing pipeline. Results from a digital phantom validation illustrate the potential for future applications of dual-contrast agent protocols on practically available single-energy CT systems.


Construction of a novel microRNA-based signature for predicting the prognosis of glioma.
Background and purpose: Glioma is a frequent primary brain tumor. MicroRNAs (miRNA) have been shown to potentially play a crucial part in tumor development. Based on miRNAs and clinical factors, a model was constructed to predict the glioma prognosis. Methods: The miRNA expression profiles of glioma come from The Cancer Genome Atlas (TCGA, training group) and Chinese Glioma Genome Atlas (CGGA, validation group). Regression analyses of Cox and Lasso were applied to identity miRNAs associated with glioma prognosis in the TCGA database. The miRNAs were combined with clinical factors to construct individualized prognostic prediction models, whose performance was validated in the CGGA database. The role of miRNA in glioma development was investigated by in vitro experiments.Results: We identified five key miRNAs associated with glioma prognosis and constructed a prediction model. The area under ROC curve for predicting 3-year survival of glioma patients in the TCGA and CGGA groups was 0.844 and 0.770, respectively. The nomogram constructed using the miRNA risk scores and clinical factors showed high accuracy of prediction in the TCGA group (C-index of 0.820) and the CGGA group (C-index of 0.722). The miR-196b-5p altered the migration, proliferation, invasion, and apoptosis of glioma cells by regulating target genes, according to in vitro experiments.Conclusions: A miRNA-based individualized prognostic prediction model was constructed for glioma and miR-196b-5p was identified as a potential biomarker of glioma development.


Transwell-grown HepG2 cell monolayers as in vitro permeability model to study drug-drug or drug-food interactions.
HepG2 cell monolayers, formed during cell growth on collagen-coated Transwell® (Corning® Inc., Corning, NY, USA) inserts, can be used for the evaluation of interactions between food supplements and drugs that are substrates for P-glycoprotein (Pgp) and/or multidrug resistance-associated protein 2 (MRP-2). Samples obtained during such permeability studies were relatively free of intracellular proteins or cell debris compared to usually performed uptake experiments with HepG2 cells; therefore no special preparation protocol prior to the analysis was needed. In the presence of aged garlic extract the activities of hepatic efflux transporters (Pgp, MRP-2) changed, which was observed as significant permeability changes of tested human immunodeficiency virus (HIV) protease inhibitors. Darunavir efflux significantly increased, whereas that of saquinavir significantly decreased. Because of the observed in vitro interactions between aged garlic extract and HIV protease inhibitors (darunavir, saquinavir), any alterations of in vivo liver transport in the presence of garlic phytochemicals could also significantly influence darunavir/saquinavir hepatocyte intracellular concentrations and hence their bioavailabilities. Therefore this aspect needs further in vivo animal evaluation.


Electrooxidative Tandem Cyclization of Activated Alkynes with Sulfinic Acids To Access Sulfonated Indenones.
An electrooxidative direct arylsulfonlylation of ynones with sulfinic acids via a radical tandem cyclization strategy has been developed for the construction of sulfonated indenones under oxidant-free conditions. This method provides a simple and efficient approach to prepare various sulfonylindenones in good to excellent yields, demonstrating the tremendous prospect of utilizing electrocatalysis in oxidative coupling. Notably, this reaction could be easily scaled up with good efficiency.


Higher order and lower order variables in the visual perception of relative pulling force.
In 7 experiments, undergraduates judged the force exerted by a videotaped standing puller, a computer-generated (stick-figure) puller, or a computer-generated inverted pendulum. Single and stepwise multiple regression analyses determined the kinematic variables exploited by the participants. Results show that (a) judgments correlated highly with force and improved with feedback; (b) judgments correlated more highly with lower order kinematic variables than with force itself; (c) participants differed in the kinematic variables exploited; (d) participants changed over blocks of trials in the variables exploited; (e) some participants used compound kinematic variables; (f) the variables exploited depended on the type of feedback; and (g) judgments to upright pullers, inverted pullers, and simple pendula showed the same qualitative patterns. Implications for theories of direct perception, directed perception, and heuristics are considered.


Predictors of Clinical Outcomes in Sexually Abused Adolescents.
This cross-sectional, case control study examines the association between child sexual abuse and interpersonal and intrapersonal outcomes among 54 adolescents, examining specific clinical measures (depression, anxiety, dissociation, and posttraumatic stress disorder, attachment patterns, self-esteem, self-disclosure, and family environment characteristics). The research results point to a correlation between sexual abuse and higher levels of the clinical measures. In addition, a correlation was found between sexual abuse and level of avoidant attachment, self-esteem, and family environment characteristics. Stepwise hierarchical regressions were conducted to examine how adolescent attributes predicted depression, anxiety, and dissociation beyond the prediction based on sexual abuse. A combination of self-esteem, anxiety attachment, and family cohesiveness made sexual abuse insignificant when predicting levels of depression, anxiety, and dissociation. This study contributes to characterizing the emotional, personal, and family attributes of adolescents who experienced sexual abuse. It also raises questions about the clinical outcomes usually associated with sexual abuse.


The medical management of Graves' disease.
There are many different approaches to treat Graves' hyperthyroidism. Medical therapy is used short-term to prepare patients for radioiodine or surgery, or it is used long term with the hope of achieving a remission. b-adrenergic blocking agents are useful in all patients without a contraindication, especially selective long-acting agents such as atenalol. Thionamides are the mainstay of medical treatment. Methimazole is more potent, may be used as a single daily dose, and may have less toxicity than PTU. Severe hyperthyroidism or thyroid storm may be treated with methimazole and ipodate. Patients are prepared for surgery with methimazole and SSKI, or b-adrenergic blocking agents and ipodate.


Integrating Multiple Data Sources and Learning Models to Predict Infectious Diseases in China.
The outbreaks of infectious diseases do not only endanger people's lives and property, but can also result in negative social impact and economic loss. Therefore, establishing early warning technologies for infectious diseases is of great value. This paper was built on the historical morbidity and mortality incidence data of infectious diseases, including typhoid fever, Hemorrhagic Fever with Renal Syndrome (HFRS), mumps, scarlatina, malaria, dysentery, pertussis, conjunctivitis, pulmonary tuberculosis, diarrhea from 2012 to 2016 in China. We also integrated search engine query data and seasonal information into the prediction models. Multiple models for prediction, including linear model, time series analysis model, boosting tree model and deep learning model (recurrent neural network, RNN) were constructed in order to predict the morbidity incidence of 10 infectious diseases. The RNN model has better predictive capability for these diseases. The improvement of techniques for infectious disease prediction can facilitate constructive and positive change towards disease prevention.


Oxidative stress is a new avenue for treatment of neuropsychiatric disorders: hype of hope?
The biochemical integrity of the brain is critical in maintaining normal central nervous system (CNS) functions. One of the factors that plays an important role in causing biochemical impairment of the brain is known as oxidative stress. Oxidative stress is generally defined as the excessive formation of free radicals relative to antioxidant defenses. The brain is particularly susceptible to oxidative stress because of its high oxygen consumption and lipid-rich content. Therefore, oxidative stress damage is associated with abnormal CNS function. Psychiatric disorders are debilitating diseases. The underlying pathophysiology of psychiatric disorders is poorly defined and may involve the interplay of numerous clinical factors and mechanistic mechanisms. Considerable evidence suggests that oxidative stress plays a complex role in several neuropsychiatric disorders, including anxiety, bipolar disorder, depression, obsessivecompulsive disorder, panic disorder, and schizophrenia. To address these issues, we reviewed the literature and considered the role of oxidative stress as one of the first pathological changes in the course of neuropsychiatric disorders, which should receive more attention in future research.


Graphene-Based Materials In Vitro Toxicity and Their Structure-Activity Relationships: A Systematic Literature Review.
The unique properties of graphene-based materials (GBMs) placed them among the most exciting nanomaterials of the past decade. Scientists and industry are looking forward to working with not only efficient but also safe, sustainable GBMs. Designing a safer-by-design GBM implies to acquire the knowledge of which physicochemical characteristics (PCCs) can increase toxicity. In this systematic review, we extracted data from the literature to provide the available information about the structure-activity relationship of GBMs. 93 papers studying a total of 185 GBMs are included. Graphene oxides (GOs) and few-layer graphenes (FLGs) are the most studied GBMs. While reduced graphene oxides were often classified as poorly oxidant and weakly cytotoxic, graphene quantum dots were mostly moderately or highly cytotoxic. FLGs demonstrated relationships between median size and oxidative stress, between lateral size and both cytotoxicity and oxidative stress, and between thickness and cytotoxicity. We also underline relationships between median size, lateral size, and thickness of GOs and oxidative stress. However, it appears difficult to highlight clear structure-activity relationships for most PCCs and biological end points because despite a large amount of available data, the GBMs are often too poorly characterized in terms of PCCs descriptors and the biological end points investigation is not standardized enough. There is an urgent need for a better standardization of the experimental investigation of both PCCs and biological end points to allow research teams to play a part in the collaborative work toward the construction of a safer-by-design GBM through a better understanding of their key toxicity drivers.


Laser treatment of endobronchial extramedullary plasmacytoma.
A 68-year-old man presented with an endobronchial lesion and was subsequently found to have a plasmacytoma. After systemic involvement with multiple myeloma was ruled out, a diagnosis of extramedullary plasmacytoma was made. The diagnosis and treatment of extramedullary plasmacytoma is discussed with specific attention to the new role of laser therapy in this disease.


Addition of meperidine to bupivacaine for spinal anaesthesia for Caesarean section.
In a prospective, randomized, double-blind, placebo-controlled trial, we investigated the effect of adding meperidine 10 mg to intrathecal bupivacaine on the duration of early postoperative analgesia in 40 patients having elective Caesarean section under spinal anaesthesia. Patients received intrathecal injection of 0.5% hyperbaric bupivacaine 2.0 ml plus either normal saline 0.2 ml (saline group) or 5% meperidine 0.2 ml (meperidine group). After operation, all patients were given i.v. patient-controlled analgesia using morphine. The duration of effective analgesia, defined as the time from intrathecal injection to first patient-controlled analgesia demand, was greater in the meperidine group (mean 234 min, 95% confidence interval 200-269 min) compared with the saline group (mean 125 min, 95% confidence interval 111-138 min; P<0.001). The 24 h morphine requirement was similar in the two groups. The meperidine group had a greater incidence of intraoperative nausea or vomiting compared with the saline group (11 vs 3; P=0.02). Addition of meperidine 10 mg to intrathecal bupivacaine for Caesarean section is associated with prolonged postoperative analgesia but with greater intraoperative nausea and vomiting.


Assessment of thromboembolism after the Cox-Maze procedure for chronic atrial fibrillation secondary to mitral valve lesion.
To assess the occurrence of late thromboembolism after surgical repair of chronic atrial fibrillation (AF) simultaneously with repair of mitral valve using the Cox-Maze procedure. 69 patients underwent Cox 3 procedure, with no cryoablation simultaneously with mitral valvuloplasty or prosthesis. Mean age was 49.9+/-13.2 years. Mean follow-up was of 31.7+/-19 months. Types of lesion were as follows: 33 (48%) stenoses, 23 (33%) insufficiencies, and 13 (19%) double lesions. Procedures were: 64 (93%) valvuloplasties, 3 (4%) biological and 2 (3%) mechanical prosthesis placement. There were 9 (13%) patients with previous systemic embolism and 2 (3%) had left atrial thrombi. Early mortality was 7% and late 1%. 2 patients (3%) were reoperated for mitral placement. At last evaluation, 10 patients (15%), were in AF. The remaining 59 (85%) were either in sinus / atrial rythm (74%) or under pacing (12%). There were no occurrence of early or late, systemic or pulmonary embolism. Permanent anticoagulation was employed in 16 cases, 10 in regular rythm and 6 in AF. The remaining 47 (75%), 2 in AF and 45 in regular rythm, did not receive anticoagulants. These results are in accordance with others series, where the occurrence of embolism was rare after maze procedure. Permanent systemic anticoagulation seems to be unnecessary in those cases.


Illicit drug use and risky sexual behavior among African American and Puerto Rican urban adolescents: the longitudinal links.
The authors assessed whether (a) early illicit drug use predicted later risky sexual activity, (b) early risky sex predicted later illicit drug use, and (c) common factors affected both risky sexual behavior and illicit drug use. African American and Puerto Rican youth completed questionnaires in their classrooms at Time 1 (T1) and face-to-face interviews with the authors in their homes 5 years later at Time 2 (T2). Logistic regression analyses showed the association between T1 illicit drug use and T2 risky sexual activity and between T1 risky sexual behavior and T2 illicit drug use. With few exceptions, T1 illicit drug use was associated with all of the T2 risky sexual behaviors. After controlling for demographic factors, the authors found that multiple sex partners at T1 was not related to illicit drug use at T2. Condom use at T1 was related to illicit drug use at T2, whereas sexually transmitted diseases and adolescent pregnancy were not related to this drug use. The findings indicated that assessments of and treatments for substance use should focus on the risky sexual behaviors that seem to accompany illicit drug use.


A new direction for cleft palate research.
Successful outcomes in the treatment of complete unilateral cleft-lip and palate (CUCL/P) and complete bilateral cleft lip and palate (CBCLP) are not obtained universally, despite significant improvements in surgical techniques over the past three decades. In particular, deficient palatal growth may occur even when expert surgical treatment is rendered. The factors which contribute most significantly to unfavorable growth outcomes remain obscure.


Concise Review: Dental Pulp Stem Cells: A Novel Cell Therapy for Retinal and Central Nervous System Repair.
Dental pulp stem cells (DPSC) are neural crest-derived ecto-mesenchymal stem cells that can relatively easily and non-invasively be isolated from the dental pulp of extracted postnatal and adult teeth. Accumulating evidence suggests that DPSC have great promise as a cellular therapy for central nervous system (CNS) and retinal injury and disease. The mode of action by which DPSC confer therapeutic benefit may comprise multiple pathways, in particular, paracrine-mediated processes which involve a wide array of secreted trophic factors and is increasingly regarded as the principal predominant mechanism. In this concise review, we present the current evidence for the use of DPSC to repair CNS damage, including recent findings on retinal ganglion cell neuroprotection and regeneration in optic nerve injury and glaucoma. Stem Cells 2017;35:61-67.


Discounting and clinical decision making: physicians, patients, the general public, and the management of asymptomatic abdominal aortic aneurysms.
Clinical decisions often entail in intertemporal trade-off. Moreover, they often involve physicians of different specialities. In an experiment dealing with the management of small asymptomatic abdominal aortic aneurysms (a clinically relevant problem) we find that specialists in internal medicine exhibit higher implicit discount rates than vascular surgeons, general practitioners, and actual and prospective patients. Several personal characteristics expected to be directly related to pure time-preference and risk aversion (gender, smoking habits, age, place of employment) have the hypothesised effects. Additionally, financial incentives appear to affect the estimated implicit discount rates of physicians, but are unlikely to have caused the inter-group differences. Differences in discount rates could lead to variations in clinical practice, which may conflict with equality of treatment or equal access to health care.


Neuroendocrine manifestations of Erdheim-Chester disease.
Neuroendocrine manifestations are common in Erdheim-Chester disease (ECD) patients. ECD is a rare non-Langerhans form of histiocytosis with multisystemic infiltration. The involvement of the hypothalamo-pituitary axis is common and central diabetes insipidus (CDI) is one of the most common endocrine manifestations in ECD patients. CDI is the first manifestation of ECD in 25%-48% of the cases. Suprasellar region extension, due to the infiltration of ECD lesions, can cause neurologic manifestations by mass effects, such as headache, visual disturbance, and cranial nerve palsies. Recent studies have revealed that disorders affecting anterior pituitary hormones are common in ECD patients. Secondary adrenal insufficiency, secondary hypothyroidism, (adult) growth hormone deficiency, hypogonadotropic hypogonadism, hyperprolactinemia, and hypoprolactinemia can develop as the neuroendocrine manifestations of ECD. Since the symptoms of anterior pituitary hormone deficiencies tend to be nonspecific, the diagnosis of anterior pituitary hormone dysfunctions can be delayed. Some anterior pituitary dysfunctions such as adrenocorticotropic hormone and/or thyroid-stimulating hormone deficiencies can be life-threatening without adequate hormone supplementation therapies. An endocrinological evaluation of the function of the pituitary gland should be performed at the initial diagnosis of ECD. It is important to recognize that endocrine dysfunctions can develop later during the follow-up of ECD.


Detection of DNA sequence polymorphisms in carcinogen metabolism genes by polymerase chain reaction.
The glutathione transferase mu gene (GST1) and the debrisoquine hydroxylase gene (CYP2D6) are known to be polymorphic in the human population and have been associated with increased susceptibility to cancer. Smokers with low lymphocyte GST mu activity are at higher risk for lung cancer, while low debrisoquine hydroxylase activity has been correlated with lower risk for lung and bladder cancer. Phenotypic characterization of these polymorphisms by lymphocyte enzyme activity (GST) and urine metabolite ratios (debrisoquine) is cumbersome for population studies. Recent cloning and sequencing of the mutant alleles of these genes has allowed genotyping via the polymerase chain reaction (PCR). Advantages of PCR approaches are speed, technical simplicity, and minimal sample requirements. This article reviews the PCR-based methods for detection of genetic polymorphisms in human cancer susceptibility genes.


Hydroxysafflor yellow A, a natural compound from Carthamus tinctorius L with good effect of alleviating atherosclerosis.
Atherosclerosis is a chronic vascular inflammatory disease with complex pathogenesis. Its serious consequence is insufficient blood supply to heart and brain, which eventually leads to myocardial ischemia, infarction and stroke. Hydroxysafflor yellow A (HSYA), a single chalcone glycoside compound with a variety of pharmacological effects, which has shown a potential biological activity for prevention and treatment of atherosclerosis. The main purpose of this review is to comprehensively elucidate the mechanism of HSYA on atherosclerosis and its risk factors (hyperlipidemia, hypertension and diabetes mellitus). The literatures on HSYA in the treatment of atherosclerosis and its risk factors were searched in PubMed, Google Scholar, China National Knowledge Infrastructure, including in vitro (cell), in vivo (animal) and clinical (human) studies, and summarized reasonably. HSYA is a promising natural product for treating atherosclerosis. It can suppress foam cell formation, vascular endothelial cell dysfunction, vascular smooth muscle cell proliferation and migration, and platelet activation. The mechanisms are achieved by regulating the reverse cholesterol transport process, fatty acid synthesis, oxidative stress, PI3K/Akt/mTOR, NLRP3 inflammasome, TNFR1/NF-κB, NO-cGMP, Bax/Bcl-2, MAPKs, CDK/CyclinD and TLR4/Rac1/Akt signaling pathways. Besides, HSYA is devoted to lowering blood lipids, regulating ion channels, reducing vascular inflammation, and protecting pancreatic beta cells, which is conducive to reducing the harm of independent risk factors of atherosclerosis. HSYA exhibits the preventive and therapeutic effects on atherosclerosis and its risk factors in vivo and in vitro, which is relevant to multiple mechanisms. The clinical trials of HSYA need to be further investigated to provide a solid foundation for its clinical application.


Intrarater and interrater reliability of the flexicurve index, flexicurve angle, and manual inclinometer for the measurement of thoracic kyphosis.
Objective. This study aimed to describe the interrater and intrarater reliability of the flexicurve index, flexicurve angle, and manual inclinometer in swimmers. A secondary objective was to determine the level of agreement between the inclinometer angle and the flexicurve angle and to provide an equation to approximate one angle from the other. Methods. Thirty swimmers participated. Thoracic kyphosis was measured using the flexicurve and the manual inclinometer. Intraclass correlation coefficient, 95% confidence interval, and standard error of measurement were computed. Results. The flexicurve angle and index showed excellent intrarater (ICC = 0.94) and good interrater (ICC = 0.86) reliability. The inclinometer demonstrated excellent intrarater (ICC = 0.92) and interrater (ICC = 0.90) reliability. The flexicurve angle was systematically smaller and correlated poorly with the inclinometer angle (R (2) = 0.384). The following equations can be used for approximate conversions: flexicurve angle = (0.275 × inclinometer angle) + 8.478; inclinometer angle = (1.396 × flexicurve angle) + 8.694. Conclusion. The inclinometer and flexicurve are both reliable instruments for thoracic kyphosis measurement in swimmers. Although the flexicurve and inclinometer angles are not directly comparable, the approximate conversion factors provided will permit translation of flexicurve angle to inclinometer angle and vice versa.


Control of foot trajectory in human locomotion: role of ground contact forces in simulated reduced gravity.
We studied the changes of vertical contact forces, lower limb kinematics, and electromyographic activity (EMG) at different speeds and gravitational loads. To this end healthy subjects were asked to walk on a motorized treadmill while the percentage of body weight unloaded (body weight support, BWS) was modified in steps by means of a well-characterized unloading system. BWS was set at 0, 35, 50, 75, 95, or 100% of body weight. Walking speed was 0.7, 1.1, 2, 3, or 5 km/h. We found that changing BWS between 0 and 95% resulted in drastic changes of kinetic parameters but in limited changes of the kinematic coordination. In particular, the peak vertical contact forces decreased proportionally to BWS; at 95%-BWS they were 20-fold smaller than at 0% and were applied at the forefoot only. Also, there were considerable changes of the amplitude of EMG activity of all tested lower limb muscles and a complex re-organization of the pattern of activity of thigh muscles. By contrast, the corresponding variation of the parameters that describe shape and variability of the foot path was very limited, always <30% of the corresponding values at 0 BWS. Moreover, the planar co-variation of the elevation angles was obeyed at all speed and BWS values. Minimum variance of limb trajectory occurred at 3 km/h. At 100% BWS, subjects stepped in the air, their feet oscillating back and forth just above but never contacting the treadmill. In this case, step-to-step variability of foot path was much greater than at all other BWS levels but was restored to lower values when minimal surrogate contact forces were provided during the "stance" phase. The results did not depend on the specific instruction given to the subject. Therefore we conclude that minimal contact forces are sufficient for accurate foot trajectory control.


Mixed Valency in a 3D Semiconducting Iron-Fluoranilate Coordination Polymer.
A pair of coordination polymers of composition (NBu4)2[M2(fan)3] (fan = fluoranilate; M = Fe and Zn) were synthesized and structurally characterized. In each case the compound consists of a pair of interpenetrating three-dimensional, (10,3)-a networks in which metal centers are linked by chelating/bridging fluoranilate ligands. Tetrabutylammonium cations are located in the spaces between the two networks. Despite the structural similarity, significant differences exist between (NBu4)2[Fe2(fan)3] and (NBu4)2[Zn2(fan)3] with respect to the oxidation states of the metal centers and ligands. For (NBu4)2[Fe2(fan)3] the structure determination as well as Mössbauer spectroscopy indicate the oxidation state for the Fe is close to +3, which contrasts with the +2 state for the Zn analogue. The differences between the two compounds extends to the ligands, with the Zn network involving only fluoranilate dianions, whereas the average oxidation state for the fluoranilate in the Fe network lies somewhere between -2 and -3. Magnetic studies on the Fe compound indicate short-range ordering. Electrochemical and spectro-electrochemical investigations indicate that the fluoranilate ligand is redox-active in both complexes; a reduced form of (NBu4)2[Fe2(fan)3] was generated by chemical reduction. Conductivity measurements indicate that (NBu4)2[Fe2(fan)3] is a semiconductor, which is attributed to the mixed valency of the fluoranilate ligands.


Centromere sliding on a mammalian chromosome.
The centromere directs the segregation of chromosomes during mitosis and meiosis. It is a distinct genetic locus whose identity is established through epigenetic mechanisms that depend on the deposition of centromere-specific centromere protein A (CENP-A) nucleosomes. This important chromatin domain has so far escaped comprehensive molecular analysis due to its typical association with highly repetitive satellite DNA. In previous work, we discovered that the centromere of horse chromosome 11 is completely devoid of satellite DNA; this peculiar feature makes it a unique model to dissect the molecular architecture of mammalian centromeres. Here, we exploited this native satellite-free centromere to determine the precise localization of its functional domains in five individuals: We hybridized DNA purified from chromatin immunoprecipitated with an anti CENP-A antibody to a high resolution array (ChIP-on-chip) of the region containing the primary constriction of horse chromosome 11. Strikingly, each individual exhibited a different arrangement of CENP-A binding domains. We then analysed the organization of each domain using a single nucleotide polymorphism (SNP)-based approach and single molecule analysis on chromatin fibres. Examination of the ten instances of chromosome 11 in the five individuals revealed seven distinct 'positional alleles', each one extending for about 80-160 kb, were found across a region of about 500 kb. Our results demonstrate that CENP-A binding domains are autonomous relative to the underlying DNA sequence and are characterized by positional instability causing the sliding of centromere position. We propose that this dynamic behaviour may be common in mammalian centromeres and may determine the establishment of epigenetic alleles.


Selective inhibition of plasma membrane calcium ATPase 4 improves angiogenesis and vascular reperfusion.
Ischaemic cardiovascular disease is a major cause of morbidity and mortality worldwide. Despite promising results from pre-clinical animal models, VEGF-based strategies for therapeutic angiogenesis have yet to achieve successful reperfusion of ischaemic tissues in patients. Failure to restore efficient VEGF activity in the ischaemic organ remains a major problem in current pro-angiogenic therapeutic approaches. Plasma membrane calcium ATPase 4 (PMCA4) negatively regulates VEGF-activated angiogenesis via inhibition of the calcineurin/NFAT signalling pathway. PMCA4 activity is inhibited by the small molecule aurintricarboxylic acid (ATA). We hypothesize that inhibition of PMCA4 with ATA might enhance VEGF-induced angiogenesis. We show that inhibition of PMCA4 with ATA in endothelial cells triggers a marked increase in VEGF-activated calcineurin/NFAT signalling that translates into a strong increase in endothelial cell motility and blood vessel formation. ATA enhances VEGF-induced calcineurin signalling by disrupting the interaction between PMCA4 and calcineurin at the endothelial-cell membrane. ATA concentrations at the nanomolar range, that efficiently inhibit PMCA4, had no deleterious effect on endothelial-cell viability or zebrafish embryonic development. However, high ATA concentrations at the micromolar level impaired endothelial cell viability and tubular morphogenesis, and were associated with toxicity in zebrafish embryos. In mice undergoing experimentally-induced hindlimb ischaemia, ATA treatment significantly increased the reperfusion of post-ischaemic limbs. Our study provides evidence for the therapeutic potential of targeting PMCA4 to improve VEGF-based pro-angiogenic interventions. This goal will require the development of refined, highly selective versions of ATA, or the identification of novel PMCA4 inhibitors.


Survival of bacterial biofilms within neutrophil extracellular traps promotes nontypeable Haemophilus influenzae persistence in the chinchilla model for otitis media.
Nontypeable Haemophilus influenzae (NTHi) is a leading cause of acute and chronic otitis media, which are a major public health problem worldwide. The persistence of NTHi during chronic and recurrent otitis media infections involves multicellular biofilm communities formed within the middle-ear chamber. Bacterial biofilms resist immune clearance and antibiotic therapy due in part to encasement within a polymeric matrix. In this study, the contribution of biofilms to bacterial persistence in vivo and composition of the NTHi biofilm matrix during experimental otitis media were investigated. The presence of biofilms within the chinchilla middle-ear chamber was significantly correlated with increased bacterial load in middle-ear effusions and tissue. Examination of thin sections revealed polymorphonuclear cells within a DNA lattice containing elastase and histones, which is consistent with the definition of neutrophil extracellular traps. Viable multicellular biofilm communities with biofilm phenotypes were found within the DNA lattice throughout the biofilm. Further, NTHi was resistant to both phagocytic and extracellular neutrophil killing in vitro by means of lipooligosaccharide moieties that promote biofilm formation. These data support the conclusion that NTHi subverts neutrophil extracellular traps to persist in vivo. These data also indicate that a more inclusive definition for biofilms may be warranted.


Activation of proinflammatory signaling by 4-hydroxynonenal-Src adducts in aged kidneys.
In our previous study, reactive 4-hydroxy-2-nonenal (4-HNE) was shown to activate Src (a non-receptor tyrosine kinase) by forming an adduct on binding with a specific residue of Src, leading to the activation of proinflammatory signaling pathways in cultured cells. However, to date, the deleterious roles of 4-HNE in inflammatory signaling activation in kidneys during aging have not been explored. The purpose of the present study was to document the mechanisms by which 4-HNE induces inflammation in the kidney during aging. Initial experiments revealed that activated nuclear factor-κB (NF-κB) expression was caused by 4-HNE activation, which suppressed transcriptional activity in the aged kidney. Treatment of human umbilical vein endothelial cells with 4-HNE revealed that Src caused senescence via NF-κB activation. Furthermore, our immunohistochemistry data showed that 4-HNE-adducted Src significantly increased in aged kidney tissues. The data showed age-related upregulation of downstream signaling molecules such as mitogen activated protein kinases (MAPKs), activator protein-1 (AP-1), NF-κB, and COX-2 in a cell culture cell system.Taken together, the results of this study show that the formation of adducts between 4-HNE and Src activates inflammatory signaling pathways in the aged kidney, contributing to age-related nephropathy.


[An outbreak of gastroenteritis caused by poisonous Boletus mushroom in Sichuan, China, 2012].
To identify the source of infection and risk factors and to provide control measures regarding an outbreak of gastroenteritis involving 30 villagers. Who attended the same wedding party held on March 5(th), 2012, a survey was carried out. Case was defined as having onset of vomiting, nausea, stomachache or diarrhea among the attendees of a wedding party. We randomly selected and interviewed 140 from 470 attendees on their symptoms and food exposures at the wedding. We compared food-specific attack rates (AR) for gastroenteritis in a retrospective cohort study. The leftover foods were tested for Salmonella, Shigella, and Staphylococcus aureus. The leftover Boletus mushrooms were examined and species determined by the Kunming Institute of Botany, Chinese Academy of Sciences. Of the 140 attendees 61% (85) developed gastroenteritis. Case-attendees had vomiting (94%), nausea (89%), stomachache (53%), and diarrhea (51%). The AR among attendees who ate Boletus mushroom was 69% (81/118), compared to 18% (4/22) of those who did not (RR = 3.8, 95%CI: 1.5 - 9.2). When comparing the ARs between the attendees on consumption of other foods, data did not show statistically significant differences. Among the 7 species of Boletus identified from the leftover mushrooms, 3 (B. venenatus, B. sinicus and B. magnificus) were toxic. Store keepers bought dried or fresh mushrooms from local villagers who had picked up them from the mountains. Salmonella, Shigella, and Staphylococcus aureus tests on those leftover food showed negative results. Poisonous Boletus mushroom contributed to this outbreak. We recommended that education should be targeted on mushroom-pickers regarding how to recognize the poisonous mushrooms. Regulations and laws should also be developed to facilitate the necessary process.


Effect of diltiazem and its metabolites on the uptake of adenosine in blood: an in-vitro investigation.
Using whole blood from man and rabbits, the effect of diltiazem, its metabolites, and other calcium antagonists on the uptake of adenosine has been described. The uptake and metabolism of adenosine was extremely rapid with a half-life in plasma of less than 30 s. Adenosine is rapidly and extensively metabolized to hypoxanthine. Metabolites of diltiazem, deacetyl diltiazem and deacetyl O-desmethyl diltiazem were considerably more potent than the parent drug. Diltiazem was one-tenth as active as verapamil, but more active than nifedipine or amlodipine. Dipyridamole was the most potent uptake-inhibitor tested (IC50 less than 1 microM), whereas the angiotensin converting enzyme inhibitor enalapril was virtually devoid of any inhibitory activities (IC50 greater than 1000 microM). The results obtained from both man and rabbit were similar.


Structure of void space in polymer solutions.
The structure of void space in two- and three-dimensional (3D) polymer solutions is studied using Voronoi tessellation and percolation theory. The polymer molecules are modeled as freely jointed chains of N tangent hard disks (two dimensions) or spheres (three dimensions). Polymer chains are equilibrated via Monte Carlo simulations and the pore space in configurations of equilibrated chains is mapped using Voronoi tessellation. In d dimensions a Voronoi vertex is the center of the sphere tangent to the d+1 nearest monomers. An edge of the Voronoi diagram is the shortest route between two neighboring vertices. The edge is considered connected if a monomer can pass through and disconnected otherwise. The Voronoi construction is used to calculate the percolation threshold of the void space. The most interesting result is that the polymer area fraction at the percolation threshold is a nonmonotonic function of N in two dimensions but monotonically reaches a constant value in three dimensions. The crossover behavior of the percolation threshold is also observed in pseudo-3D. The pore size distribution decreases monotonically with increasing pore size. This is markedly different from that in configurations of hard disks (monomeric fluid) where the pore size distribution is peaked at finite size.


Evoked potential monitoring of the upper extremities during thoracic and lumbar spinal deformity surgery: a prospective study.
We prospectively investigated the usefulness of somatosensory evoked potential (SEP) monitoring to detect clinically significant peripheral nerve or brachial plexus compression in the upper extremities during spinal deformity surgery. All patients had bilateral median and ulnar nerve SEPs evaluated as a baseline, both intermittently throughout the surgical procedure and at termination of surgery. This information was correlated with pre- and postoperative upper extremity neurologic examinations. Twenty-five upper extremities in 21 patients had intraoperative SEP changes consisting of at least a 60% decline in amplitude or a 10% increase in latency. On many occasions, repositioning of the upper extremities improved the SEP responses to acceptable baselines. Overall, SEP monitoring of the upper extremities was 78% sensitive for detecting upper extremity sensory deficits, 100% sensitive for detecting combined sensory and motor deficits, and 98.5% specific for predicting normal postoperative upper extremity function. We recommend the simultaneous electrophysiologic monitoring of the upper and lower extremities during spinal surgery to allow identification of brachial plexus and/or peripheral nerve stretch/compression that may be amenable to intraoperative correction.