Hepatitis C: a multifaceted disease. Review of extrahepatic manifestations.
To review the available data on the association between hepatitis C virus (HCV) infection and conditions reportedly related to infection with the virus and to assess the clinical implications of these associations. Pertinent articles were identified using the Paperchase database, which simultaneously searches the MEDLINE (1966 to present), Health (1975 to present), AIDSLINE (1980 to present), and Cancerlit databases. All studies for a given association were reviewed, but special attention was paid to randomized controlled trials where applicable. According to the available data, HCV infection appears to be strongly associated with essential mixed cryoglobulinemia, membranoproliferative glomerulonephritis, and porphyria cutanea tarda. Evidence strongly suggests that HCV has a direct pathogenetic role in some patients with the first two conditions. The association with Mooren corneal ulcers and autoimmune thyroiditis is suggested, but more data are needed to confirm it. The data for the association between HCV infection and the Sjögren syndrome, lichen planus, and idiopathic pulmonary fibrosis remain weak. Although interferon therapy has been effective in patients with both essential mixed cryoglobulinemia and membranoproliferative glomerulonephritis, a high relapse rate has been noted in the latter condition. Patients with essential mixed cryoglobulinemia, membranoproliferative glomerulonephritis, and porphyria cutanea tarda should be tested for HCV infection. Conversely, signs and symptoms of these conditions should be sought in patients with chronic HCV infection. Interferon therapy is currently recommended only for patients with symptomatic essential mixed cryoglobulinemia.


Trends in breast conserving surgery among Asian Americans and Pacific Islanders, 1992-2000.
Breast-conserving surgery (BCS) has been the recommended treatment for early-stage breast cancer since 1990 yet many women still do not receive this procedure. To examine the relationship between birthplace and use of BCS in Asian-American and Pacific-Islander (AAPI) women, and to determine whether disparities between white and AAPI women persist over time. Retrospective cohort study. Women with newly diagnosed stage I or II breast cancer from 1992 to 2000 in the Surveillance, Epidemiology, and End Results program. Receipt of breast -conserving surgery for initial treatment of stage I or II breast cancer. Overall, AAPI women had lower rates of BCS than white women (47% vs 59%; P<.01). Foreign-born AAPI women had lower rates of BCS than U.S.-born AAPI and white women (43% vs 56% vs 59%; P<.01). After adjustment for age, marital status, tumor registry, year of diagnosis, stage at diagnosis, tumor size, histology, grade, and hormone receptor status, foreign-born AAPI women (adjusted OR [aOR], 0.49; 95% CI, 0.32 to 0.76) and U.S.-born AAPI women (aOR, 0.77; 95% CI, 0.62 to 0.95) had lower odds of receiving BCS than white women. Use of BCS increased over time for each racial/ethnic group; however, foreign-born AAPI women had persistently lower rates of BCS than non-Hispanic white women. AAPI women, especially those who are foreign born, are less likely to receive BCS than non-Hispanic white women. Of particular concern, differences in BCS use among foreign-born and U.S.-born AAPI women and non-Hispanic white women have persisted over time. These differences may reflect inequities in the treatment of early-stage breast cancer for AAPI women, particularly those born abroad.


SuperNoder: a tool to discover over-represented modular structures in networks.
Networks whose nodes have labels can seem complex. Fortunately, many have substructures that occur often ("motifs"). A societal example of a motif might be a household. Replacing such motifs by named supernodes reduces the complexity of the network and can bring out insightful features. Doing so repeatedly may give hints about higher level structures of the network. We call this recursive process Recursive Supernode Extraction. This paper describes algorithms and a tool to discover disjoint (i.e. non-overlapping) motifs in a network, replacing those motifs by new nodes, and then recursing. We show applications in food-web and protein-protein interaction (PPI) networks where our methods reduce the complexity of the network and yield insights. SuperNoder is a web-based and standalone tool which enables the simplification of big graphs based on the reduction of high frequency motifs. It applies various strategies for identifying disjoint motifs with the goal of enhancing the understandability of networks.


Comparison of CAPTIA syphilis G enzyme immunoassay with rapid plasma reagin test for detection of syphilis.
The CAPTIA Syphilis G enzyme-linked immunosorbent assay compared favorably with the rapid plasma reagin test when used to screen for syphilis in a low-risk population. The sensitivity and specificity of the CAPTIA Syphilis G test were 100 and 97.8%, respectively, for 646 routine specimens and 100 and 99.2%, respectively, for 265 specimens from obstetrics patients. Overall, for 911 specimens, the CAPTIA Syphilis G test showed a sensitivity of 100%, a specificity of 98.2%, and positive and negative predictive values of 78.9 and 100%, respectively. For the same population, the rapid plasma reagin test showed a sensitivity and a specificity of 96.4 and 97.5%, respectively, and positive and negative predictive values of 72 and 99.8%, respectively.


[Evolution of the pharmacological management of osteoarthritis: the biologics].
Proinflammatory cytokines such as IL-1 β et TNF α are implicated in osteoarthritis where they contribute to the local synovitis. Blocking IL-1 β is a promising tool in experimental animal's model of osteoarthritis (OA). So far in human clinical trials using IL-1 blockers, the results are inconclusive. The blockade of TNF α seems more appropriated for inflammatory forms of hand OA with some encouraging results. Intra-articular administration of biologics is hampered by their short resident time into the joint. Gene therapy is one of the possible way to prolong the local intra-articular delivery of biologics.


Research methodology: Part II, Essentials of factor analysis.
This article is part two of our four part series on basic statistical analytical methods. Using a case method presentation, the basic essentials of factor analysis is described.


Femur First navigation can reduce impingement severity compared to traditional free hand total hip arthroplasty.
Impingement is a major source of dislocation and aseptic loosening in total hip arthroplasty (THA). We compared impingement free range of motion (ROM) using a novel computer navigated femur first approach to conventional THA. In addition, impingement between genders was also explored. In a retrospective analysis of 121 THA patients, subject-specific post-operative ROM was simulated using post-operative 3D-CT data, and compared with the benchmark ROM, essential for activities of daily living. Three parameters were defined to express both implant-to-implant (ITI) and bone-to-bone (BTB) impingement - coverage percentage, third angle, and impingement severity. Although coverage percentage was similar between the navigated and conventional group for both ITI (p = 0.69) and BTB (p = 0.82) impingement, third angle was significantly reduced in the navigation group for both ITI (p = 0.02) and BTB (p = 0.05) impingement. Impingement severity for both ITI (p = 0.01) and BTB (p = 0.05) was significantly decreased in the navigation group compared to the conventional. Impingement severity in men was considerably higher compared to women for both ITI (p = 0.002) and BTB (p = 0.02). Navigation guided femur first THA is able to improve alignment of ROM axis, and consequently, to reduce impingement in THA. Men seem to be more prone to impingement than women.


Development and preliminary evaluation of VISLAN, a surgical planning and guidance system using intra-operative video imaging.
VISLAN is an integrated neurosurgical planning and guidance system. New segmentation and rendering techniques have been incorporated. A stereo video system is used intra-operatively and fulfils four roles. First, the video display is overlaid with graphical outlines showing the position of the planned craniotomy or the target (enhanced reality displays). Second, a skin surface patch is reconstructed from the stereo video images using patterned light (mean errors of surface point location are < 0.15 mm). Third, a freely mobile, hand-held localizer is tracked in real time (position errors are < 0.5 mm and with improved calibration < 0.2 mm), with its position superimposed on the pre-operative patient representation to assist surgical guidance. Fourth, markers fixed to the skull bone next to the cranial opening are used to detect intra-operative movement and to update registration. Initial results from phantom experiments show an overall system accuracy of better than 0.9 mm for intra-operative localization of features defined in pre-operative images. The prototype system has been tested during six neurosurgical operations with very good results.


In vitro activities of five antifungal agents against 199 clinical and environmental isolates of Aspergillus flavus, an opportunistic fungal pathogen.
Aspergillus flavus is the second leading cause of invasive and non-invasive aspergillosis, as well as the most common cause of fungal sinusitis, cutaneous infections, and endophthalmitis in tropical countries. Since resistance to antifungal agents has been observed in patients, susceptibility testing is helpful in defining the activity spectrum of antifungals and determining the appropriate drug for treatment. A collection of 199 clinical and environmental strains of Aspergillus flavus consisted of clinical (n=171) and environmental (n=28) were verified by DNA sequencing of the partial b-tubulin gene. MICs of amphotericin B, itraconazole, voriconazole, posaconazole, and MEC of caspofungin were determined in accordance with the Clinical and Laboratory Standards Institute M38-A2 document. Caspofungin, followed by posaconazole, exhibited the lowest minimum inhibitory concentrations (MIC). All isolates had caspofungin MEC90 (0.063μg/ml) lower than the epidemiologic cutoff values, and 3.5% of the isolates had amphotericin B MIC higher than the epidemiologic cutoff values. However, their clinical effectiveness in the treatment of A. flavus infection remains to be determined.


Transmission electron microscopy of plaque accumulations in denture stomatitis.
Denture pellicle in denture stomatitis has been studied with transmission electron microscopy after embedding the denture base in a water-miscible resin in seven patients with heavy plaque deposits on their dentures and in five patients with no apparent plaque accumulation. In the first group, the denture surface was covered by a well differentiated granular pellicle. A cell-free zone was interposed between the pellicle and the plaque, which consisted predominantly of rounded, rod-shaped, and filamentous microorganisms with a loose distribution, separated by an electron-lucent amorphous and gel-like matrix. C. albicans were scattered among the bacteria and often presented with degenerated cytoplasm. In the second group, a structurally heterogeneous pellicle was seen adjacent to the denture surface. A thin plaque that consisted mainly of dense accumulations of C. albicans, a narrow dense matrix, and few bacteria was found. Calculus accumulations on the dentures consisted of amicrobial calcifications in the deeper layers, whereas the superficial parts showed bacterial calcifications.


Knocking down HMGB1 using dendrimer-delivered siRNA unveils its key role in NMDA-induced autophagy in rat cortical neurons.
To explore the role of the High Mobility Group Box 1 (HMGB1) protein in NMDA-mediated excitotoxicity in rat cortical neurons. We knocked down HMGB1 using small-interfering RNA (siRNA) delivered into neurons by means of a dendrimer. We determined autophagy activation by measuring the ratio of light chain 3 protein isoforms (LC3B-I)/LC3B-II and by determining autophagolysosome labeling using the specific marker monodansyl cadaverine. Neuronal toxicity was induced by exposing the neurons to N-methyl-D-aspartate (NMDA) and it was determined by measuring Lactate dehydrogenase and MTT reduction. We found that NMDA receptor stimulation induced both neuronal death and autophagy in rat cortical neurons. In addition, NMDA also caused HMGB1 translocation from the neuronal nucleus to the cytoplasm where it formed a complex with Beclin1. HMGB1 was efficiently knocked down using a specific siRNA causing a blockade of NMDA-induced autophagy and potentiating NMDA-induced neuronal death. Our study demonstrates that HMGB1 plays a relevant role in neuronal autophagy regulation and suggest a protective role of autophagy during excitotoxicity. In addition, the dendrimer that we have used here is a good vector for siRNA delivery to neurons allowing lack-of-function studies.


Association between serum alkaline phosphatase levels in late pregnancy and the incidence of venous thromboembolism postpartum: a retrospective cohort study.
Two previous studies found alkaline phosphatase (ALP) levels were related with the development of venous thromboembolism (VTE) in hospitalised patients. VTE is a leading cause of death during pregnancy and postpartum. No prior study has investigated the associations of ALP levels and VTE postpartum, and the related mechanisms remain unclear. This study aimed to investigate the associations between ALP levels and VTE postpartum, and to reveal the potential mechanisms. In this retrospective cohort study, we included pregnant women who planned to deliver at the Department of Obstetrics and Gynecology in the three designated hospitals in a multicentre cohort of pregnant women in Wuhan, China, during two recruitment periods of January 1, 2018 to December 31, 2019, and May 14, 2020 to March 25, 2022. A total of 10,044 participants with serum ALP and whole blood hemoglobin measurements in late pregnancy (median, 37 (35, 39) weeks) were enrolled. The participants' incidences of VTE (deep venous thrombosis and/or pulmonary embolism) postpartum were confirmed from the medical records. Pregnant women with new-onset VTE postpartum (within 6 weeks after delivery) were confirmed as VTE cases. Approximately 0.8% (79/10,044) of the pregnant women were diagnosed with VTE postpartum. In the unadjusted model, pregnant women with the lowest quintile of serum ALP levels (≤116 U/L) in late pregnancy had higher risk of VTE postpartum compared with those with the highest quintile (≥199 U/L) (OR, 2.83 [1.32, 6.05]). After adjusting for covariates of demographic, life style, birth outcomes, and other liver enzymes, pregnant women with the lowest quintile of serum ALP levels (≤116 U/L) in late pregnancy had increased risk of VTE postpartum compared with those with the highest quintile (≥199 U/L) (OR, 2.48 [1.14, 5.40]). A one standard deviation decrease of ln-transformed ALP levels were associated with elevated risk of VTE postpartum (OR, 1.29 [1.02, 1.62]). Significant negative associations of ALP with VTE were found in the unadjusted and adjusted models. The negative associations between ALP and VTE remained consistent in sensitivity analyses among participants with non-GDM, single pregnancy, non-preeclampsia, non-postpartum hemorrhage, non-extremely/very preterm and cesarean delivery. Decreased serum ALP levels significantly (P < 0.05) related to decreased hemoglobin, which was significantly (P < 0.05) related to increased risk of VTE postpartum. Decreased hemoglobin significantly (P < 0.05) mediated 7.59% of ALP-associated VTE postpartum. This study suggested that low serum ALP levels in late pregnancy were associated with increased risk of VTE postpartum, and the ALP-associated VTE risk may be partially mediated by hemoglobin, suggesting that serum ALP in late pregnancy could be a promising biomarker for the prediction of VTE postpartum. The National Natural Science Foundation of China, and the Program for HUST Academic Frontier Youth Team.


Expression of pepsinogen II in gastric cancer. Its relationship to local invasion and lymph node metastases.
We have determined the prevalence of pepsinogen II (PG II) immunoreactive cells in a large series of early and advanced gastric cancers and relationships among PG II-positivity, tumor histologic type, extent of gastric wall invasion, and presence of lymph node metastases. Of the 316 cancers evaluated, 150 (47%) expressed PG II. The prevalence by histologic type was 55% in 146 glandular tumors, 43% in 83 diffuse tumors, 16% in 25 mucoid tumors, and 51% in 59 mixed-type cancers. Two parietal cell cancers and one undifferentiated cancer were PG II-negative. In glandular and diffuse cancers, but not mucoid and mixed tumors, both the extent of gastric wall invasion and incidence of lymph node metastases were associated positively with PG II expression by the primary tumor. In particular, PG II-reactive cells were found significantly more often in advanced than in early diffuse cancers (P less than 0.05) and significantly more often in submucosal early cancers than in intramucosal early cancers (P less than 0.01). The prevalence of PG II expression also was higher significantly in metastatic cancers than in nonmetastatic cancers. This was true for advanced gastric cancers as a whole (P less than 0.01), advanced glandular-type cancer alone (P less than 0.01), advanced glandular- and diffuse- type cancers together (P less than 0.001), and early diffuse-type cancer (P less than 0.05). Only four (3%) of 145 cancers evaluated for pepsinogen I (PG I) were positive, and each also was positive for PG II. The results suggest that the expression of PG II by glandular and diffuse types of gastric cancer may be a marker of increased malignancy.


Musical note onset detection based on a spectral sparsity measure.
If music is the language of the universe, musical note onsets may be the syllables for this language. Not only do note onsets define the temporal pattern of a musical piece, but their time-frequency characteristics also contain rich information about the identity of the musical instrument producing the notes. Note onset detection (NOD) is the basic component for many music information retrieval tasks and has attracted significant interest in audio signal processing research. In this paper, we propose an NOD method based on a novel feature coined as Normalized Identification of Note Onset based on Spectral Sparsity (NINOS2). The NINOS2 feature can be thought of as a spectral sparsity measure, aiming to exploit the difference in spectral sparsity between the different parts of a musical note. This spectral structure is revealed when focusing on low-magnitude spectral components that are traditionally filtered out when computing note onset features. We present an extensive set of NOD simulation results covering a wide range of instruments, playing styles, and mixing options. The proposed algorithm consistently outperforms the baseline Logarithmic Spectral Flux (LSF) feature for the most difficult group of instruments which are the sustained-strings instruments. It also shows better performance for challenging scenarios including polyphonic music and vibrato performances.


Risk of skin cancer in patients on chronic haemodialysis: a nationwide, population-based study in Taiwan.
Patients on chronic haemodialysis (HD) have a higher incidence of cancer. However, the risk of skin cancer in this population has rarely been investigated. To investigate the risk of nonmelanoma skin cancer (NMSC) and cutaneous melanoma in patients on chronic HD and to explore the associated risk factors. We performed retrospective cohort and nested case-control studies using records in the Taiwanese National Health Insurance Research Database between 1999 and 2013. The HD cohort included 79 668 incident patients on HD, for whom the standardized incidence ratios (SIRs) for incident NMSC and cutaneous melanoma were determined. In the nested case-control study, patients on HD with NMSC were matched to those without skin cancers. The impact of various factors on the development of NMSC was determined by conditional logistic regression analysis. Among the 79 668 patients on HD, 248 cases of NMSC and 22 cases of cutaneous melanoma occurred after a mean 4·95 years of follow-up. The SIRs for NMSC and cutaneous melanoma in patients on HD were 1·58 (95% confidence interval 1·39-1·79) and 1·44 (95% confidence interval 0·91-2·19), respectively. Of the patients on HD, a higher risk of NMSC was found in men (1·5-fold), South Taiwan residents (twofold) and patients with uraemic pruritus after long-term antihistamine treatment (1·53-fold). However, the incidence of NMSC was not increased in patients with uraemic pruritus receiving ultraviolet B phototherapy. Patients on chronic HD are at higher risk of NMSC. Uraemic pruritus further increases the risk of NMSC, which might be prevented by ultraviolet B phototherapy.


Down-regulation of TUFM impairs host cell interaction and virulence by Paracoccidioides brasiliensis.
The genus Paracoccidioides consist of dimorphic fungi geographically limited to the subtropical regions of Latin America, which are responsible for causing deep systemic mycosis in humans. However, the molecular mechanisms by which Paracoccidioides spp. causes the disease remain poorly understood. Paracoccidioides spp. harbor genes that encode proteins involved in host cell interaction and mitochondrial function, which together are required for pathogenicity and mediate virulence. Previously, we identified TufM (previously known as EF-Tu) in Paracoccidioides brasiliensis (PbTufM) and suggested that it may be involved in the pathogenicity of this fungus. In this study, we examined the effects of downregulating PbTUFM using a silenced strain with a 55% reduction in PbTUFM expression obtained by antisense-RNA (aRNA) technology. Silencing PbTUFM yielded phenotypic differences, such as altered translation elongation, respiratory defects, increased sensitivity of yeast cells to reactive oxygen stress, survival after macrophage phagocytosis, and reduced interaction with pneumocytes. These results were associated with reduced virulence in Galleria mellonella and murine infection models, emphasizing the importance of PbTufM in the full virulence of P. brasiliensis and its potential as a target for antifungal agents against paracoccidioidomycosis.


Flexible thermoelectric generator and energy management electronics powered by body heat.
Uninterrupted, efficient power supplies have posed a significant hurdle to the ubiquitous adoption of wearable devices, despite their potential for revolutionizing human‒machine interactions. This challenge is further compounded by the requirement of these devices to supply dependable energy for data-intensive sensing and transmission. Traditional thermoelectric solutions fail to deliver satisfactory performance under conditions of extremely low voltages. Here, we present a novel solution of a wearable thermoelectric generator integrated with an energy management system, which is capable of powering sensors and Bluetooth by harnessing body heat. Distinct from previous works, our innovation lies in its ability to consistently operate even with a minimal temperature difference (i.e., 4 K) between the human skin and the ambient environment, ensuring reliable data transmission within a time as short as 1.6 s. Furthermore, our system can recharge utilizing body heat under ultralow voltage conditions (30 mV). Our developed system provides a novel pathway for the continuous, reliable monitoring of self-contained wearable devices without depending on batteries.


Exercise and eating disorders: a 3-year inpatient hospital record analysis.
The purpose of this study was to describe the exercise behavior across the DSM-IV eating disorder diagnosis (anorexia nervosa (AN), bulimia nervosa (BN), and eating disorder not otherwise specified (EDNOS)) and determine if differences exist among exercise category (high level and low level), type of exercise (aerobic, strength, and total), Eating Attitudes Test (EAT), Eating Disorders Inventory (EDI-2), and the length of inpatient hospitalization. This study was a retrospective analysis of 199 inpatient hospital records of female patients (age M=20.6, S.D.=7.03) in the following diagnostic categories: AN (n=115, 58%), BN (n=38, 19%), and EDNOS (n=46, 23%). Patients were also grouped by a median split into low- and high-level exercise categories based on their total amount of weekly exercise. No significant relationship was found between diagnosis and exercise category (high and low) or diagnosis and exercise type (total, aerobic, and strength exercise). This is valuable because exercise specialist may be a worthwhile addition to treatment teams working with all eating disorder diagnostic groups. The high-level exercisers showed significantly greater scores on the EAT [F(2,1,110)=5.117, P<.05] and weight preoccupation [F(1,1010)=4.861, P<.05] than the low-level exercise groups. There were significant relationships between total exercise and EAT (r=.354, P<.01), drive for thinness (r=.262, P<.01), and body dissatisfaction (r=.312, P<.001). Total aerobic exercise was significantly related to EAT (r=.352, P<.001), drive for thinness (r=.272, P<.01), and body dissatisfaction (r=.268, P<.01). Finally, total strength exercise was related to body dissatisfaction (r=.249, P<.05). A significant difference was found among exercise group and length of hospitalization [F(1,155)=14.384, P<.000]. The high-level exercisers were in treatment for 3 weeks longer than their low-level exercisers. A forced stepwise multiple linear regression was calculated to predict the length of hospitalization. At Step 1, diagnosis and Body Mass Index (BMI) on admission explained 27% of the variance in length of inpatient hospitalization [F(4,154)=18.08, P<.004, r(2)=.273]. When two exercise variables were included, aerobic activity explained an additional 5% of variance, whereas strength activity explained an additional 0.3% of the variance. Three-fourths of the predictors explained significant components of the total 32% variance. The present study demonstrates that patients with greater total exercise and a greater total aerobic exercise show a significantly greater drive for thinness and require a longer length of hospitalization. This association was not present with total strength exercise levels. Effective clinical methods to modify total aerobic exercise levels need to be determined with inpatient populations.


Increased activity of serotonin uptake in platelets in medication overuse headache following regular intake of analgesics and triptans.
We investigated the effect of chronic administration of different pain medications on the activity of the serotonin transporter (SERT) in patients with medication overuse headache (MOH). We measured the kinetic of platelet 5-HT uptake (maximal velocity, Vmax and the Michaelis-Menten constant, Km in patients with overuse of triptans (tMOH, n = 15) or analgesics (aMOH, n = 14) before and after drug withdrawal, as well as in headache-free healthy subjects (n = 15) and patients with episodic migraine (EM, n = 16). Vmax was increased similarly in both, tMOH and aMOH compared to healthy subjects and patients with EM and normalized after withdrawal in parallel to the improvement of headache frequency. Average Km was similar in all groups at baseline and not affected by the withdrawal. The data demonstrate a transient increase of SERT activity in patients with analgesic and triptan induced MOH but do not allow to differentiate whether the increase of serotonin uptake is caused by regular intake of analgesics or triptans or is a consequence of frequent headache attacks.


Assessment of a liposomal CT/optical contrast agent for image-guided head and neck surgery.
This study evaluates a long-acting liposomal fluorescence / CT dual-modality contrast agent (CF800) in head and neck cancer to enhance intraoperative tumor demarcation with fluorescence imaging and cone-beam computed tomography (CBCT). CF800 was administered to 12 buccal cancer-bearing rabbits. Imaging was acquired at regular time points to quantify time-dependent contrast enhancement. Surgery was performed 5-7 days after, with intraoperative near-infrared fluorescence endoscopy and CBCT, followed by histological and ex-vivo fluorescence assessment. Tumor enhancement on CT was significant at 24, 96 and 120 hours. Volumetric analysis of tumor segmentation showed high correlation between CBCT and micro-CT. Fluorescence signal was apparent in both ex-vivo and in-vivo imaging. Histological correlation showed [100%] specificity for primary tumor. Sensitivity and specificity of CF800 in detecting nodal involvement require further investigation.CF800 is long acting and has dual function for CT and fluorescence contrast, making it an excellent candidate for image-guided surgery.


Radiosurgery for Medial Temporal Lobe Epilepsy Resulting from Mesial Temporal Sclerosis.
Medial temporal lobe epilepsy associated with mesial temporal sclerosis (MTS) is perhaps the most well-defined epilepsy syndrome that is responsive to structural interventions such as surgery. Several minimally invasive techniques have arisen that provide additional options for the treatment of MTS while potentially avoiding many of open surgery's associated risks. By evading these risks, they also open up treatment options to patients who otherwise are poor surgical candidates. Radiosurgery is one of the most intensively studied of these alternatives and has found a growing role in the treatment of medial temporal lobe epilepsy.


Increased feeding in response to bilateral injection of insulin antibodies in the VMH.
In order to investigate the role of insulin in the VMH in regulation of food intake in the rat, a specific antibody against rat insulin was injected in the VMH. The insulin antibody caused transient hyperphagia, when administered in the nighttime. This result is discussed in view of the glucostatic theory of the regulation of food intake.


Model of the extracellular domain of the human alpha7 nAChR based on the crystal structure of the mouse alpha1 nAChR extracellular domain.
Neuronal nicotinic acetylcholine receptors (nAChRs) are important therapeutic targets for various diseases, including Alzheimer's disease, Parkinson's disease, and schizophrenia, as well as for cessation of smoking. Based on the recently determined crystal structure of the extracellular domain (ECD) of the mouse nAChR alpha1 subunit complexed with alpha-bungarotoxin at 1.94A resolution, we have constructed three-dimensional models of the ECD of the monomer, homodimer, and homopentamer of the human alpha7 nAChR and investigated in detail the interface between the two alpha7 subunits. The docking of the agonist in the ligand-binding pocket of the human alpha7 dimer was also performed and found consistent with results from labeling and mutagenesis experiments. Since the nAChR ligand-binding site is a useful target for mutagenesis studies and the rational design of drugs against diseases, these models provide useful information for future work.


A polysomnographic and clinical report on sleep-related injury in 100 adult patients.
In 100 consecutive adults who came to a sleep disorders center complaining of repeated nocturnal injury, polysomnographic study identified five disorders: night terrors/sleepwalking (N = 54), REM sleep behavior disorder (N = 36), dissociative disorders (N = 7), nocturnal seizures (N = 2), and sleep apnea (N = 1). Ninety-five patients sustained ecchymoses, 30 had lacerations, and nine had fractures. DSM-III axis I disorders (past or current) were found in 48.1% of the group with night terrors/sleepwalking and in 30.6% of the group with REM sleep behavior disorder; these were mainly affective disorders. In these two groups, clonazepam controlled the symptoms of 51 of the 61 patients to whom it was given.


Immune risk phenotype is associated with nosocomial lung infections in elderly in-patients.
Nosocomial infections are extremely common in the elderly and may be related to ageing of the immune system. The Immune Risk Phenotype (IRP), which predicts shorter survival in elderly patients, has not been evaluated as a possible risk factor for nosocomial infection. Our aim was to assess the prevalence of nosocomial infections in elderly in-patients and to investigate potential relationships between nosocomial infections and the immunophenotype, including IRP parameters. We included 252 consecutive in-patients aged 70 years or over (mean age, 85 ± 6.2 years), between 2006 and 2008. Among them, 97 experienced nosocomial infections, yielding a prevalence rate of 38.5% (95% confidence interval, 32.5-44.5). The main infection sites were the respiratory tract (21%) and urinary tract (17.1%) When we compared immunological parameters including cell counts determined by flow cytometry in the groups with and without nosocomial infections, we found that the group with nosocomial infections had significantly lower values for the CD4/CD8 ratio and naive CD8 and CD4 T-cell counts and higher counts of memory CD8 T-cells with a significant increase in CD28-negative CD8-T cells. Neither cytomegalovirus status (positive in 193/246 patients) nor presence of the IRP was associated with nosocomial infections. However, nosocomial pneumonia was significantly more common among IRP-positive patients than IRP-negative patients (17/60 versus 28/180; p = 0.036). Immunological parameters that are easy to determine in everyday practice and known to be associated with immune system ageing and shorter survival in the elderly are also associated with an elevated risk of nosocomial pneumonia in the relatively short term.


Effect of sieved fractionation on the physical, flow and hydration properties of Boscia senegalensis Lam., Dichostachys glomerata Forssk. and Hibiscus sabdariffa L. powders.
This study aimed at evaluating the effect of successive grinding and sieving processes on the physicochemical properties of powders obtained from Boscia senegalensis seeds, Dichostachys glomerata fruits and Hibiscus sabdariffa calyxes. Plant powders were fractionated into four granulometric classes and their properties were compared to those of unsieved powders. Mean particle size exerted a significant influence (p < 0.05) on the plant powders properties. The smaller the particle size of the powder fraction, the higher the protein, lipid and ash contents and the lower the carbohydrate and fiber contents. The decrease in particle size increased particle sphericity and elongation and enhanced flowability of B. senegalensis and D. glomerata powders, whereas an inverse tendency seemed to be observed for H. sabdariffa powders. Water absorption capacity, water solubility index and dispersibility were improved for finer particles for all plants. Sieve fractionation is a novel approach for improving physicochemical properties of plant powders.


[Sickle cell disease and invasive osteoarticular Salmonella infections].
Non-typhi Salmonella are responsible for severe invasive infections in children with sickle cell disease, with osteoarticular locations that can affect short- and long-term outcomes. We describe the cases of 2 children with sickle cell disease who presented paucisymptomatic Salmonella osteoarticular infections on returning from North Africa. Progression was favorable in both cases after appropriate systemic antibiotic therapy, although one Salmonella was multidrug-resistant. Invasive salmonellosis remains rare in France, but, because of its severity, it should be suspected in any patient with sickle cell disease presenting fever, especially in the context of recent trips in Africa countries. Early clinical diagnosis is essential to start appropriate empirical treatment without waiting for bacteriological results.


Element partitioning in combustion- and gasification-based waste-to-energy units.
A critical comparison between combustion- and gasification-based waste-to-energy systems needs a deep knowledge of the mass flows of materials and elements inside and throughout the units. The study collected and processed data from several moving grate conventional incinerators and high-temperature shaft gasifiers with direct melting, which are in operation worldwide. A material and substance flow analysis was then developed to systematically assess the flows and stocks of materials and elements within each waste-to-energy unit, by connecting the sources, pathways, and intermediate and final sinks of each species. The patterns of key elements, such as carbon, chloride and heavy metals, in the different solid and gaseous output streams of the two compared processes have been then defined. The combination of partitioning coefficients with the mass balances on atomic species and results of mineralogical characterization from recent literatures was used to estimate a composition of bottom ashes and slags from the two types of waste-to-energy technologies. The results also allow to quantify some of the performance parameters of the units and, in particular, the potential reduction of the amount of solid residues to be sent to final disposal.


Allocation of reproductive effort to the male and female strategies in wind-pollinated plants.
Amaranthus and several other wind-pollinated species of plants are used to test some of the theoretical models of relative reproductive effort towards the male and female sexes. Consistent with these models, in self-compatible, monoecious Amaranthus, Chenopodium, Digitaria, Setaria, and Lepidium, female effort represented over 90% of the total reproductive effort. Also consistent with predictions, Lolium, a self-incompatible wind-pollinated species, was found to have about equal male and female effort. A method is described here that should prove useful in quantifying male and female effort in both wind and insect-pollinated species of plants.


Cholecystokinin-immunoreactive innervation of the ventromedial hypothalamus in the rat: possible substrate for autonomic regulation of feeding.
Cholecystokinin octapeptide (CCK) injected into the medial hypothalamus of the rat has been reported to suppress feeding. In this species, the superior lateral parabrachial subnucleus, which predominantly innervates the ventromedial nucleus of the hypothalamus, is composed primarily of CCK-immunoreactive neurons. Combined retrograde tracing using fluorescent dyes and immunofluorescence for CCK confirms that 80-90% of the neurons in the superior lateral parabrachial nucleus which innervate the ventromedial nucleus of the hypothalamus are CCK-positive. This pathway may underlie autonomic regulation of feeding behavior.


Resting Pd/Pa correlates with fractional flow reserve but not angiographic severity in calcified coronary arteries.
Study the effect of coronary artery calcium (CAC) on resting coronary physiological indices. Prior studies found no correlation between angiographic stenosis and fractional flow reserve (FFR) in heavily calcified arteries. Two hundred consecutive patients undergoing whole-cycle resting Pd/Pa and FFR evaluation of a single lesion of intermediate severity (40-80%) had CAC quantified based upon radiopacities at the site of the stenosis, where 0 = none or mild calcium, 1 = moderate calcium, and 2 = severe calcium. Mean age was 61 ± 11 years and 34% were female. The mean degree of stenosis, FFR, and resting Pd/Pa were 60 ± 12%, 0.83 ± 0.08, and 0.93 ± 0.05, respectively. Resting Pd/Pa correlated with degree of angiographic diameter stenosis (DS) as determined by quantitative coronary angiography (QCA) or visual estimation in arteries with calcium score of 0 or 1, but there was no correlation in severely calcified arteries. The diagnostic accuracy of DS ≥70% by QCA to predict hemodynamic significance was 68% with calcium scores of 0/1, but only 43% with calcium score = 2. Resting Pd/Pa was highly correlated with FFR irrespective of the degree of CAC (R2 = 0.68, p < .001) and the sensitivity of resting Pd/Pa ≤0.91 for predicting an FFR ≤0.80 was 0.67 in arteries with calcium scores of 0 or 1 and 0.69 in arteries with a calcium score of 2. There was no correlation between angiographic stenosis and either resting Pd/Pa or FFR in heavily calcified coronary artery lesions.


Minimally invasive surgical alternatives for left ventricle epicardial lead implantation in heart failure patients.
Biventricular pacing is a proven advantageous adjuvant therapy for patients with ventricular dyssynchrony associated with congestive heart failure. Endocardial left ventricular lead placement does have several limitations: anatomic variations of the coronary venous system and late lead dislodgement. Epicardial lead placement is often a rescue procedure but offers some advantages related to safety and a shorter implant time. Moreover, it allows visual selection of the best pacing site and multiplicity of pacing sites. Three minimally invasive surgical methods of left ventricular lead placement are outlined in this article, including specific indications and limitations. Biventricular pacing has been proposed as an adjuvant treatment for patients with heart failure and intraventricular conduction delay.


Arterial occlusion duration affects the cuff-induced hyperemic response in skeletal muscle BOLD perfusion imaging as shown in young healthy subjects.
Dynamic BOLD MRI with cuff compression, inducing ischemia and post-occlusive hyperemia in skeletal muscle, has been pointed out as a potential diagnostic tool to assess peripheral limb perfusion. The objective was to explore the robustness of this technique and its sensitivity to the occlusion duration. BOLD images were acquired at 3 T in 14 healthy volunteers. [Formula: see text]-imaging with 5- and 1.5-min occlusions were acquired and several semi-quantitative BOLD parameters were derived from ROI-based [Formula: see text]-time curves. Differences in parameters from the two different occlusion durations were evaluated in the gastrocnemius and soleus muscles using non-parametrical tests. Intra- and inter-scan repeatability were evaluated with coefficient of variation. Longer occlusion duration resulted in an increased hyperemic signal effect yielding significantly different values (p < 0.05) in gastrocnemius for all parameters describing the hyperemic response, and in soleus for two of these parameters. Specifically, 5-min occlusion yielded steeper hyperemic upslope in gastrocnemius (41.0%; p < 0.05) and soleus (59.7%; p = 0.03), shorter time to half peak in gastrocnemius (46.9%; p = 0.00008) and soleus (33.5%; p = 0.0003), and shorter time to peak in gastrocnemius (13.5%; p = 0.02). Coefficients of variation were lower than percentage differences that were found significant. Findings show that the occlusion duration indeed influences the hyperemic response and thus should play a part in future methodological developments.


The Long Head of the Biceps Has a Stabilizing Effect on the Glenohumeral Joint in Simulated Infraspinatus or Subscapularis but Not Supraspinatus Rotator Cuff Deficiency-A Biomechanical Study.
To investigate the stabilizing role of the long head of the biceps (LHB) for different simulated rotator cuff (RC) tears. Human cadaveric specimens (n = 8) were fixed in a robotic-based experimental setup with a static loading of the RC, deltoid, and the LHB. RC tears were simulated by unloading of the corresponding muscles. A throwing motion and an anterior load-and-shift test were simulated under different RC conditions by unloading the supraspinatus (SS), subscapularis (SSc), infraspinatus (IS), and combinations (SS + SSc, SS + IS, SS + SSc + IS). The LHB was tested in 3 conditions: unloaded, loaded, and tenotomy. Translation of the humeral head and anterior forces depending on loading of the RC and the LHB was captured. Loading of LHB produced no significant changes in anterior force or glenohumeral translation for the intact RC or a simulated SS tear. However, if SSc or IS were unloaded, LHB loading resulted in a significant increase of anterior force ranging from 3.9 N (P = .013, SSc unloaded) to 5.2 N (P = .001, simulated massive tear) and glenohumeral translation ranging from 2.4 mm (P = .0078, SSc unloaded) to 7.4 mm (P = .0078, simulated massive tear) compared to the unloaded LHB. Tenotomy of the LHB led to a significant increase in glenohumeral translation compared to the unloaded LHB in case of combined SS + SSc (2.6 mm, P = .0391) and simulated massive tears of all SS + SSc + IS (4.6 mm, P = .0078). Highest translation was observed in simulated massive tears between loaded LHB and tenotomy (8.1 mm, P = .0078). Once SSc or IS is simulated to be torn, the LHB has a stabilizing effect for the glenohumeral joint and counteracts humeral translation. With a fully loaded RC, LHB loading has no influence. With an intact RC, the condition of the LHB showed no biomechanical effect on the joint stability. Therefore, from a biomechanical point of view, the LHB could be removed from the joint when the RC is intact or reconstructable. However, since there was a positive effect even of the unloaded LHB in this study when SSc or IS is deficient, techniques with preservation of the supraglenoid LHB origin may be of benefit in such cases.


Review article: the management of long-term parenteral nutrition.
Home parenteral nutrition (HPN) is currently the management of choice for patients with chronic intestinal failure. To summarise the major issues in delivering long-term parenteral nutrition (>3 months) and assess outcome as per complications, mortality and quality of life. To assess the evidence for the therapeutic use of trophic factors such as teduglutide and to review evolving therapeutic options in the treatment of chronic intestinal failure. A literature search using PubMed and MEDLINE databases was performed. Safe delivery of HPN relies upon individualised formulations of parenteral nutrition administered via carefully maintained central venous catheters by trained patients or carers, supported by a skilled multidisciplinary team. Early diagnosis and treatment of complications including catheter-associated blood stream infection (reported incidence 0.14-0.83 episodes/patient-year on HPN) and central venous thrombosis (reported incidence 0.03 episodes/patient-year) is important to minimise mortality and morbidity. There is a significant variation in the reported incidence of both hepatobiliary complications (19-75%) and advanced liver disease (0-50%). Five-year survival rates in large centres are reported between 60% and 78% with survival primarily related to underlying diagnosis. Long-term survival remains higher on HPN than with intestinal transplantation. The role of intestinal lengthening procedures is yet to be validated in adults. Home parenteral nutrition delivered by skilled nutrition teams has low incidences of catheter-related complications. Most deaths relate to the underlying disease. Therapies such as teduglutide and small bowel transplantation appear promising, but home parenteral nutrition appears likely to remain the bedrock of management in the near term.


Use of Routine Emergency Department Care Practices with Deaf American Sign Language Users.
Deaf individuals who communicate using American Sign Language (ASL) seem to experience a range of disparities in health care, but there are few empirical data. To examine the provision of common care practices in the emergency department (ED) to this population. ED visits in 2018 at a U.S. academic medical center were assessed retrospectively in Deaf adults who primarily use ASL (n = 257) and hearing individuals who primarily use English, selected at random (n = 429). Logistic regression analyses adjusted for confounders compared the groups on the provision or nonprovision of four routine ED care practices (i.e., laboratories ordered, medications ordered, images ordered, placement of peripheral intravenous line [PIV]) and on ED disposition (admitted to hospital or not admitted). The ED encounters with Deaf ASL users were less likely to include laboratory tests being ordered: adjusted odds ratio 0.68 and 95% confidence interval 0.47-0.97. ED encounters with Deaf individuals were also less likely to include PIV placement, less likely to result in images being ordered in the ED care of ASL users of high acuity compared with English users of high acuity (but not low acuity), and less likely to result in hospital admission. Results suggest disparate provision of several types of routine ED care for adult Deaf ASL users. Limitations include the observational study design at a single site and reliance on the medical record, underscoring the need for further research and potential reasons for disparate ED care with Deaf individuals.


Phosphoinositides suppress gamma-secretase in both the detergent-soluble and -insoluble states.
gamma-Secretase is an aspartic protease that hydrolyzes type I membrane proteins within the hydrophobic environment of the lipid bilayer. Using the CHAPSO-solubilized gamma-secretase assay system, we previously found that gamma-secretase activity was sensitive to the concentrations of detergent and phosphatidylcholine. This strongly suggests that the composition of the lipid bilayer has a significant impact on the activity of gamma-secretase. Recently, level of secreted beta-amyloid protein was reported to be attenuated by increasing levels of phosphatidylinositol 4,5-diphosphate (PI(4,5)P2) in cultured cells. However, it is not clear whether PI(4,5)P2 has a direct effect on gamma-secretase activity. In this study, we found that phosphoinositides directly inhibited CHAPSO-solubilized gamma-secretase activity. Interestingly, neither phosphatidylinositol nor inositol triphosphate altered gamma-secretase activity. PI(4,5)P2 was also found to inhibit gamma-secretase activity in CHAPSO-insoluble membrane microdomains (rafts). Kinetic analysis of beta-amyloid protein production in the presence of PI(4,5)P2 suggested a competitive inhibition. Even though phosphoinositides are minor phospholipids of the membrane, the concentration of PI(4,5)P2 within the intact membrane has been reported to be in the range of 4-8 mm. The presence of PI(4,5)P2-rich rafts in the membrane has been reported in a range of cell types. Furthermore, gamma-secretase is enriched in rafts. Taking these data together, we propose that phosphoinositides potentially regulate gamma-secretase activity by suppressing its association with the substrate.


COPA A-to-I RNA editing hijacks endoplasmic reticulum stress to promote metastasis in colorectal cancer.
RNA editing is among the most common RNA level modifications for generating amino acid changes. We identified a COPA A-to-I RNA editing event in CRC metastasis. Our results showed that the COPA A-to-I RNA editing rate was significantly increased in metastatic CRC tissues and was closely associated with aggressive tumors in the T and N stages. The COPA I164V protein damaged the Golgi-ER reverse transport function, induced ER stress, promoted the translocation of the transcription factors ATF6, XBP1 and ATF4 into the nucleus, and activated the expression of MALAT1, MET, ZEB1, and lead to CRC cell invasion and metastasis. Moreover, the COPA A-to-I RNA editing rate was positively correlated with the immune infiltration score. Collectively, the COPA I164V protein hijacked ER stress to promote the metastasis of CRC, and the COPA A-to-I RNA editing rate may be a potential predictor for patient response to immune checkpoint inhibitor (ICIs) treatment.


Feasibility of an accelerated 2D-multi-contrast knee MRI protocol using deep-learning image reconstruction: a prospective intraindividual comparison with a standard MRI protocol.
The aim of this study was to evaluate the image quality and diagnostic performance of a deep-learning (DL)-accelerated two-dimensional (2D) turbo spin echo (TSE) MRI of the knee at 1.5 and 3 T in clinical routine in comparison to standard MRI. Sixty participants, who underwent knee MRI at 1.5 and 3 T between October/2020 and March/2021 with a protocol using standard 2D-TSE (TSES) and DL-accelerated 2D-TSE sequences (TSEDL), were enrolled in this prospective institutional review board-approved study. Three radiologists assessed the sequences regarding structural abnormalities and evaluated the images concerning overall image quality, artifacts, noise, sharpness, subjective signal-to-noise ratio, and diagnostic confidence using a Likert scale (1-5, 5 = best). Overall image quality for TSEDL was rated to be excellent (median 5, IQR 4-5), significantly higher compared to TSES (median 5, IQR 4 - 5, p < 0.05), showing significantly lower extents of noise and improved sharpness (p < 0.001). Inter- and intra-reader agreement was almost perfect (κ = 0.92-1.00) for the detection of internal derangement and substantial to almost perfect (κ = 0.58-0.98) for the assessment of cartilage defects. No difference was found concerning the detection of bone marrow edema and fractures. The diagnostic confidence of TSEDL was rated to be comparable to that of TSES (median 5, IQR 5-5, p > 0.05). Time of acquisition could be reduced to 6:11 min using TSEDL compared to 11:56 min for a protocol using TSES. TSEDL of the knee is clinically feasible, showing excellent image quality and equivalent diagnostic performance compared to TSES, reducing the acquisition time about 50%. • Deep-learning reconstructed TSE imaging is able to almost halve the acquisition time of a three-plane knee MRI with proton density and T1-weighted images, from 11:56 min to 6:11 min at 3 T. • Deep-learning reconstructed TSE imaging of the knee provided significant improvement of noise levels (p < 0.001), providing higher image quality (p < 0.05) compared to conventional TSE imaging. • Deep-learning reconstructed TSE imaging of the knee had similar diagnostic performance for internal derangement of the knee compared to standard TSE.


Endothelium-specific CYP2J2 overexpression improves cardiac dysfunction by promoting angiogenesis via Jagged1/Notch1 signaling.
Myocardial infarction (MI) contributes to the development of cardiac remodeling and heart failure. Insufficient post-MI myocardial angiogenesis has been identified as a non-negligible event which precipitates heart failure progression. Previous studies reported that cytochrome P450 epoxygenase and its metabolites exerted beneficial effects on cardiovascular diseases. However, the role of cytochrome P450 2J2 (CYP2J2) in post-MI heart failure is incompletely understood. First, western blot and real-time PCR analyses showed that CYP2J2 expression increased clearly in patients with acute MI and old MI, compared to control. Second, echocardiography and histological studies showed that transgenic (TG) rats had relatively preserved cardiac function, as well as attenuated remodeling, and reduced scar formation, compared to the wild-type (WT) littermates after MI eight weeks. Importantly, the cardioprotective effect induced by CYP2J2 overexpression was abrogated by VEGFR2 inhibitor-cediranib. More intriguingly, positron emission computed Tomography (PET) analyses showed that TG rats displayed better myocardial perfusion than WT rats. We found that these effects were linked to increasing circulating EETs and enhancing myocardial angiogenesis. Additionally, in vitro study demonstrated that 11, 12-epoxyeicosatrienoic acid (11, 12-EET) induced more robust tube formation and markedly increased VEGF-A and bFGF expression in hypoxia and normoxia. Finally, western blot analyses uncovered that CYP2J2 and 11, 12-EET promoted angiogenesis via the Jagged1/Notch1 signaling pathway. Our findings demonstrate that CYP2J2 improves cardiac function by increasing the concentration of circulating EETs, and boosting angiogenesis via the Jagged1/Notch1 signaling pathway in MI-induced heart failure.


Fronto-temporal dysfunction in appetitive regulation of bulimia nervosa with affective disorders: A regional homogeneity and remote connectivity pattern analysis.
The aim of this study was to assess brain functional alterations in BN patients with affective disorders and their association with maladaptive eating behaviors. A total of 42 BN patients with affective disorders (anxiety and depression) and 47 healthy controls (HCs) were enrolled in this study. The resting-state fMRI data were analyzed for functional changes as indicated by regional homogeneity based on Kendall's coefficient of concordance (KCC-ReHo) and seed-based functional connectivity (FC). A principal component analysis (PCA) model was used to identify the commonalities within the behavioral questionnaires from the BN group. Patients in the BN group showed decreased ReHo in the bilateral middle frontal gyrus (MFG) and right supramarginal gyrus (SMG). Additionally, the BN group showed increased FC between the left MFG and the right inferior temporal gyrus (ITG); decreased FC between the right MFG and the bilateral insula and the left middle temporal gyrus (MTG); and decreased FC between the right SMG and the left superior temporal gyrus (STG) and right inferior frontal gyrus (IFG). In the FC-behavior association analysis, the second principal component (PC2) was negatively correlated with FC between the left MFG and the right ITG. Based on a brain functional analysis (ReHo and FC), this study revealed significant aberrant changes in the frontal-temporal regions of BN patients with affective disorders. These regions, which serve as fronto-temporal circuitry, are associated with restraint and emotional eating behaviors. Our findings shed new light on the neural mechanisms underlying the condition.


Cortical recovery of swallowing function in wound botulism.
Botulism is a rare disease caused by intoxication leading to muscle weakness and rapidly progressive dysphagia. With adequate therapy signs of recovery can be observed within several days. In the last few years, brain imaging studies carried out in healthy subjects showed activation of the sensorimotor cortex and the insula during volitional swallowing. However, little is known about cortical changes and compensation mechanisms accompanying swallowing pathology. In this study, we applied whole-head magnetoencephalography (MEG) in order to study changes in cortical activation in a 27-year-old patient suffering from wound botulism during recovery from dysphagia. An age-matched group of healthy subjects served as control group. A self-paced swallowing paradigm was performed and data were analyzed using synthetic aperture magnetometry (SAM). The first MEG measurement, carried out when the patient still demonstrated severe dysphagia, revealed strongly decreased activation of the somatosensory cortex but a strong activation of the right insula and marked recruitment of the left posterior parietal cortex (PPC). In the second measurement performed five days later after clinical recovery from dysphagia we found a decreased activation in these two areas and a bilateral cortical activation of the primary and secondary sensorimotor cortex comparable to the results seen in a healthy control group. These findings indicate parallel development to normalization of swallowing related cortical activation and clinical recovery from dysphagia and highlight the importance of the insula and the PPC for the central coordination of swallowing. The results suggest that MEG examination of swallowing can reflect short-term changes in patients suffering from neurogenic dysphagia.


Psychological and neuroendocrinological characteristics associated with depressive symptoms in breast cancer patients at the initial cancer diagnosis.
Breast cancer patients can have biopsychosocial changes induced by distress related to the cancer diagnosis. This study investigated psychological characteristics and hypothalamic-pituitary-adrenal (HPA) axis function associated with depressive symptoms in breast cancer patients at the initial diagnosis. Seventy-eight breast cancer patients were enrolled, and 61 patients were included in the final analysis. Patients were evaluated concerning psychological adjustment to cancer diagnosis, self-concept and depressive symptoms and given a dexamethasone suppression test before the main surgical treatment. Self-concept scale scores and fighting spirit factor scores of the Korean version of the Mental Adjustment to Cancer (KMAC) scale showed inverse correlations. Anxious preoccupation (AP) factor scores of the KMAC scale positively correlated with depressive symptom scores. Depressive symptom scores were significantly correlated with postdexamethasone serum cortisol levels. In multiple regression analysis, postdexamethasone serum cortisol and the KMAC-AP factor score had significant partial effects in the final model. Hypothalamic-pituitary-adrenal axis dysfunction and anxious coping to cancer diagnosis may be associated with depressive symptoms in breast cancer patients before treatment. Based on this analysis, we recommend psychotherapeutic interventions to increase adaptive mental coping strategy and to ameliorate psychological distress. Screening for HPA axis dysfunction and provision of depression treatment may prevent breast cancer patients from developing depressive symptoms.


2D SnSe2 nanoflakes decorated with 1D ZnO nanowires for ppb-level NO2 detection at room temperature.
The detection of air pollutant nitrogen dioxide (NO2) is of great importance arising from its great harm to the ecological environment and human health. However, the detection range of most NO2 sensors is ppm-level, and it is still challenging to achieve lower concentration (ppb-level) NO2 detection. Herein, 2D tin diselenide nanoflakes decorated with 1D zinc oxide nanowires (SnSe2/ZnO) heterojunctions were first reported by facile hydrothermal and ultra-sonication methods. The response of the fabricated SnSe2/ZnO sensor enhances 3.41 times on average compared with that of pure SnSe2 sensor to 50-150 ppb NO2 with a high detection sensitivity (22.57 ppm-1) at room temperature. In addition, the SnSe2/ZnO sensor has complete recovery, negligible cross-sensitivity, and small relative standard deviation (6.98%) during the 1 month sensing test, which can meet the requirements for NO2 detection in environmental monitoring. The enhanced NO2 sensing performance can be attributed to the n-n heterojunction constructed between SnSe2 and ZnO. The as-prepared sensor based on SnSe2/ZnO hybrid significantly promotes the development of the low detection limit of the NO2 sensor at room temperature.


Evaluating and improving real-world evidence with Targeted Learning.
The Targeted Learning roadmap provides a systematic guide for generating and evaluating real-world evidence (RWE). From a regulatory perspective, RWE arises from diverse sources such as randomized controlled trials that make use of real-world data, observational studies, and other study designs. This paper illustrates a principled approach to assessing the validity and interpretability of RWE. We applied the roadmap to a published observational study of the dose-response association between ritodrine hydrochloride and pulmonary edema among women pregnant with twins in Japan. The goal was to identify barriers to causal effect estimation beyond unmeasured confounding reported by the study's authors, and to explore potential options for overcoming the barriers that robustify results. Following the roadmap raised issues that led us to formulate alternative causal questions that produced more reliable, interpretable RWE. The process revealed a lack of information in the available data to identify a causal dose-response curve. However, under explicit assumptions the effect of treatment with any amount of ritodrine versus none, albeit a less ambitious parameter, can be estimated from data. Before RWE can be used in support of clinical and regulatory decision-making, its quality and reliability must be systematically evaluated. The TL roadmap prescribes how to carry out a thorough, transparent, and realistic assessment of RWE. We recommend this approach be a routine part of any decision-making process.


False aneurysm of ascending aorta.
An unsuspected false aneurysm of the ascending aorta was discovered during a first pass, left-to-right shunt study.


β-Functionalization of Indolin-2-one-Derived Aliphatic Acids for the Divergent Synthesis of Spirooxindole γ-Butyrolactones.
β-Functionalization of indolin-2-one-derived aliphatic acids has been applied in formal [3 + 2] annualtions for catalyst-free and divergent synthesis of two series of structurally interesting 3,3'-spirooxindole γ-butyrolactones that may be attractive for potential drug discovery. These findings also pave the way for further diversity-oriented synthesis of spirooxindoles starting from indolin-2-one-derived aliphatic acids or their derivatives.


An ultrasonic device for continuous measurement of cervical dilation during labor.
This paper describes ultrasonic apparatus for continuous registration of cervical dilation during the first stage of labour. The techniques used ensure maximum safety for the patients and do not influence the normal birth process.


Association of long-term effects of low-level sulfamethoxazole with ovarian lipid and amino acid metabolism, sex hormone levels, and oocyte maturity in zebrafish.
Sulfamethoxazole (SMZ) is an important antibiotic used to prevent and treat infections in both clinical settings and animal husbandry. High levels of SMZ may exhibit endocrine toxicity. Environmental SMZ enters the human body via food and water; however, the toxicity of environmental doses of SMZ and its effects on reproductive health are unknown. In the present study, zebrafish were exposed to low concentrations of SMZ (1000 and 5000 ng/L) from 2 h post-fertilization to 120 d post-fertilization. Consequently, the proportion of mature oocytes in adult female zebrafish ovarian tissue increased by 98.2 %, indicating that SMZ promotes ovarian maturation. Metabolomics analysis revealed significant changes in ovarian lipid and amino acid levels after SMZ treatment. An enzyme-linked immunoassay used to detect sex hormones in the ovaries showed that SMZ exposure significantly increased the levels of estradiol, a follicle-stimulating hormone, and of luteinizing hormone. Furthermore, an association analysis showed that most of the differentially expressed metabolites in the ovary were strongly correlated with the levels of sex hormones secreted by the pituitary gland. Therefore, significantly increased transcript levels of gonadotropin-releasing hormone (GnRH) and follicle-stimulating hormone detected in brain tissue suggested that SMZ may exhibit ovarian toxicity via the hypothalamus. In vitro experiments were performed to demonstrate that SMZ targets neurons in the hypothalamus. Exposure to SMZ significantly increased the GnRH content in GnRH neurons. Finally, molecular docking simulations indicated the potential interaction of SMZ with G protein-coupled receptor 54; this molecular binding can activate, synthesize, and release GnRH in neurons. In conclusion, long-term environmental exposure to SMZ may induce ovarian toxicity by affecting the hypothalamus-pituitary-gonad axis.


Stimulated by retinoic acid gene 8 (STRA8) interacts with the germ cell specific bHLH factor SOHLH1 and represses c-KIT expression in vitro.
STRA8 (Stimulated by Retinoic Acid Gene 8) controls the crucial decision of germ cells to engage meiotic division up and down-regulating genes involved in the meiotic programme. It has been proven as an amplifier of genes involved in cell cycle control and chromosome events, however, how STRA8 functions as negative regulator are not well understood. In this study, we demonstrate that STRA8 can interact with itself and with other basic Helix-Loop-Helix (bHLH) transcription factors through its HLH domain and that this domain is important for its ability to negatively interfere with the Ebox-mediated transcriptional activity of bHLH transcription factors. Significantly, we show that STRA8 interacts with TCF3/E47, a class I bHLH transcription factors, and with SOHLH1, a gonadal-specific bHLH, in male germ cells obtained from prepuberal mouse testis. We demonstrated that STRA8, indirectly, is able to exert a negative control on the SOHLH1-dependent stimulation of c-KIT expression in late differentiating spermatogonia and preleptotene spermatocytes. Although part of this results were obtained only 'in vitro', they support the notion that STRA8 interacting with different transcription factors, besides its established role as 'amplifier' of meiotic programme, is able to finely modulate the balance between spermatogonia proliferation, differentiation and acquisition of meiotic competence.


Bilateral increases in ERK activation at the spinomedullary junction region by acute masseter muscle injury during temporomandibular joint inflammation in the rats.
We determined the role of persistent monoarthritis of temporomandibular joint region (TMJ) on bilateral masseter muscle (MM) nociception in male rats using orofacial nocifensive behaviors, phosphorylated extracellular signal-regulated kinase and Fos induction at the trigeminal subnucleus caudalis/upper cervical spinal cord (Vc/C2) region in response to formalin injection to the MM region. TMJ inflammation was induced by local injection of CFA into the left TMJ region. Orofacial nocifensive behaviors evoked by formalin injection ipsilateral or contralateral to the TMJ inflammation appeared to be increased at 1-14 days or at 1, 10 and 14 days after induction of TMJ inflammation, respectively, while increases in behavioral duration were seen mainly in the late phase rather than the early phase. The number of pERK positive cells was investigated in superficial laminae at the Vc/C2 region at 3, 10, 20, 60 and 80 min after MM stimulation with formalin at 14 days after TMJ inflammation. TMJ-inflamed rats displayed greater responses of pERK expression by the ipsilateral MM stimulation at 3-60 min, while contralateral MM stimulation increased pERK expression at 3, 10 and 20 min compared to non-CFA rats. Fos expression by MM stimulation was increased at 14 days after induction of TMJ inflammation regardless of the affected side. These findings showed that persistent TMJ inflammation for 10 and 14 days is sufficient to enhance MM nociception indicated by behaviors and neural responses in superficial laminae at the Vc/C2 region.


Hepatobiliary scintigraphy. An effective tool in the management of bile leak following laparoscopic cholecystectomy.
Bile leaks and bile duct injury has been the major postoperative complications described after laparoscopic cholecystectomy. In this study, we evaluated the role of hepatobiliary scintigraphy (HBS) in patients who underwent laparoscopic cholecystectomy, and there was a clinical suspicion of bile leak in postoperative period. Twenty-five patients (M/F=11:14, mean age 39+/-8 years; range 24-58 years) with suspected bile leak postlaparoscopic cholecystectomy underwent sequential HBS. Thirteen patients had normal hepatobiliary scintigraphic studies. Five patients had small bile leak in gall bladder fossa with primary route of bile flow into the gut. All these 18 patients improved on conservative management alone. Significant bile leak from the cystic stump region was demonstrated in four patients. All of them were subjected to endoscopic cholangiography (ERCP), which confirmed the site of leak. All patients had stenting and sphincterotomy. One patient showed bile leak and obstruction at the lower end of common bile duct, he improved spontaneously. Another patient showed poor hepatocytes function and no excretion of radiotracer and underwent ERCP followed by hepaticojejunostomy for common hepatic duct ligation. One patient had frank bile leak in the right paracolic gutter and had to undergo hepaticojejunostomy. HBS is a valuable noninvasive method of investigating possible bile leaks or other biliary disruptions in postlaparoscopic cholecystectomy patients. Negative study for significant bile leak can assure the surgeon to manage the patient conservatively. However, it cannot be relied on absolutely when determining the need for reoperation for a significant bile leak in early postoperative period.


Prothrombotic abnormalities in childhood ischaemic stroke.
Childhood ischaemic stroke, incorporating arterial ischaemic stroke and cerebral sinus venous thrombosis, is associated with significant morbidity and mortality in children. The majority of cases in children present with well-recognised risk factors. The appreciation of the role prothrombotic abnormalities have in disease states is developing rapidly. Prothrombotic abnormalities are abnormalities of the coagulation system, fibrinolytic system, endothelial cells or platelets that lead to a reduced threshold for pathological thrombus formation. Our understanding of the role of prothrombotic abnormalities in childhood ischaemic stroke is increasing and has a direct bearing on the development of effective management and prevention strategies. We provide a brief background of prothrombotic abnormalities and review the available literature on prothrombotic markers in childhood ischaemic stroke. Overall, prothrombotic abnormalities have been identified in 20-50% of children presenting with AIS and 33-99% of children with cerebral sinus venous thrombosis. There appear to be a number of associations emerging including an increased frequency of factor V Leiden mutation, elevated lipoprotein (a), protein C deficiency and antiphospholipid antibodies in children presenting with arterial ischaemic stroke. The pathogenic role of prothrombotic abnormalities as predisposing to initial and recurrent childhood ischaemic stroke is becoming increasingly evident. The impact on treatment, however, will only be clarified with carefully designed, multi-institutional prospective studies.


Proteomics for the authentication of fish species.
Assessment of seafood authenticity and origin, mainly in the case of processed products (fillets, sticks, baby food) represents the crucial point to prevent fraudulent deceptions thus guaranteeing market transparency and consumers health. The most dangerous practice that jeopardies fish safety is intentional or unintentional mislabeling, originating from the substitution of valuable fish species with inferior ones. Conventional analytical methods for fish authentication are becoming inadequate to comply with the strict regulations issued by the European Union and with the increase of mislabeling due to the introduction on the market of new fish species and market globalization. This evidence prompts the development of high-throughput approaches suitable to identify unambiguous biomarkers of authenticity and screen a large number of samples with minimal time consumption. Proteomics provides suitable and powerful tools to investigate main aspects of food quality and safety and has given an important contribution in the field of biomarkers discovery applied to food authentication. This report describes the most relevant methods developed to assess fish identity and offers a perspective on their potential in the evaluation of fish quality and safety thus depicting the key role of proteomics in the authentication of fish species and processed products. The assessment of fishery products authenticity is a main issue in the control quality process as deceptive practices could imply severe health risks. Proteomics based methods could significantly contribute to detect falsification and frauds, thus becoming a reliable operative first-line testing resource in food authentication.


The fatty acid profile of the skin surface lipid layer in papulopustular rosacea.
Patients with papulopustular rosacea (PPR) frequently complain of dry, sensitive skin. We have previously demonstrated that patients with PPR have reduced skin surface hydration levels in the presence of normal sebum casual levels, suggesting that it may be the quality and not the quantity of sebum that plays a role in PPR. To compare the sebaceous fatty acid composition of patients with PPR to that of controls with normal facial skin. The sebaceous fatty acid composition of 25 patients with PPR and 24 age- and sex-matched controls was analysed by gas chromatography - mass spectrometry. Results Myristic acid (C14:0) was present in greater concentrations in PPR sebum, while the long chain saturated fatty acids arachidic acid (C20:0), behenic acid (C22:0), tricosanoic acid (C23:0) and lignoceric acid (C24:0) as well as the monounsaturated fatty acid cis-11-eicosanoic acid (C20:1) were present in the sebum of patients with PPR in lesser concentrations as compared with controls. There is increasing evidence that sebaceous fatty acids play a role in the maintenance of skin barrier integrity. We have shown for the first time that patients with PPR have an abnormal sebaceous fatty acid composition, with reduced levels of long chain saturated fatty acids. These new findings may have therapeutic implications for the development of sebum-modifying nonantibiotic treatments for patients with PPR.


[Changes in threonine and Na+ counterflow absorption in rat small intestine under the effect of insulin and F-].
The in vivo experiments showed that insulin intensifies the threonine absorption and Na+ counterflow in the rat small intestine. Fluorine inhibits considerably the threonine absorption. The possible mechanism of the insulin and fluorine opposite effects on the threonine absorption in the small intestine is under discussion.


Suppression of pheromone biosynthesis and mating behavior by RNA interference of pheromone gland-specific fatty acyl reductase in Maruca vitrata.
In moths, various enzymes, such as fatty acid synthases, fatty acyl desaturases, and fatty acyl reductases (FARs), are involved in pheromone biosynthesis. In particular, pheromone gland-specific FAR (pgFAR) plays an important role in converting the functional group from carboxylic to alcohol during pheromone biosynthesis. A novel pgFAR of Maruca vitrata, Mvi-pgFAR, was identified through transcriptome sequencing of its pheromone gland. To investigate the involvement of Mvi-pgFAR in pheromone biosynthesis, Mvi-pgFAR was cloned from the pheromone gland and suppressed by RNA interference (RNAi). Mvi-pgFAR harbored several conserved motifs related to NAD(P)H-binding, N-glycosylation, and adenosine / guanosine triphosphate binding. Phylogenetic analysis revealed that Mvi-pgFAR with other lepidopteran pgFARs formed an independent clade. Mvi-pgFAR was specifically expressed only in the pheromone gland. Quantitative real-time polymerase chain reaction showed that the diurnal expression levels of Mvi-pgFAR in the pheromone gland were the highest at 2 h before the scotophase. After primarily confirming Mvi-pgFAR suppression by RNAi, (E,E)-10,12-hexadecadienal (E10E12-16:Ald), a major sex pheromone component, was quantified by gas chromatography. When Mvi-pgFAR was successfully suppressed, E10E12-16:Ald production was reduced by up to half of that of the control, and the mating rate was subsequently decreased. Our results demonstrate that Mvi-pgFAR downregulation can suppress mating behavior by changing the relative sex pheromone component ratio, suggesting that Mvi-pgFAR can be used as a novel control target.


Effects of electroconvulsive shock on food and water intake in the rat.
Forty-two male rats were habituated to laboratory conditions for four weeks under constant light conditions. Food and water intakes were recorded daily. Following the habituation period half of the animals were given electroconvulsive shock (ECS) and half Sham-ECS (SECS). ECS treatments produced significant decrements in both food and eater intakes which returned to baseline levels after three days.


Multifunctional micro/nanomotors as an emerging platform for smart healthcare applications.
Self-propelling micro- and nano-motors (MNMs) are emerging as a multifunctional platform for smart healthcare applications such as biosensing, bioimaging, and targeted drug delivery with high tissue penetration, stirring effect, and rapid drug transport. MNMs can be propelled and/or guided by chemical substances or external stimuli including ultrasound, magnetic field, and light. In addition, enzymatically powered MNMs and biohybrid micromotors have been developed using the biological components in the body. In this review, we describe emerging MNMs focusing on their smart propulsion systems, and diagnostic and therapeutic applications. Finally, we highlight several MNMs for in vivo applications and discuss the future perspectives of MNMs on their current limitations and possibilities toward further clinical applications.


Comparison of short-stem with conventional-stem prostheses in total hip arthroplasty: an 8-year follow-up study.
Coxarthrosis is a common disease of the adult hip joint. Elderly patients have mainly been treated with total hip arthroplasty (THA); however, younger patients are increasingly affected. Short-stem prostheses were developed for this special patient group. There have been few studies on the clinical outcomes of this type of prosthesis. This study compared the mid-term results of a short-stem prosthesis and a standard-stem prosthesis 8 years after implantation. According to our clinical registry, patients who received a short-stem prosthesis before 2011 were identified. Patients in the standard-stem prosthesis group were matched based on the sex, age, height, weight, and degree of arthrosis. At the follow-up time, the modified Harris Hip Score (mHHS), University of California Los Angeles (UCLA) activity score and visual analog scale (VAS) pain score were collected and compared with the preoperative values. Fifty-five patients could be matched and analyzed for both groups. No patients needed revision surgery. In both groups, there were significant improvements at the follow-up time. The pre- and postoperative mHHSs, UCLA scores, and VAS scores were 41.9 and 95 (p < 0.0001), 3.75 and 7.9 (p < 0.0001), and 7.6 and 0.9 (p < 0.0001), respectively, in the short-stem group and 44.8 and 96.25 (p < 0.0001), 3.6 and 7.7 (p < 0.0001), and 7.7 and 0.9 (p < 0.0001), respectively, in the control group, with no significant differences between the groups at the follow-up time. The short-stem prosthesis provides mid-term results comparable to those of a standard-stem prosthesis. In both groups, excellent patient-reported outcomes were achieved after an average of 8 years. IV.


Quantifying upper-limb motor impairment in people with multiple sclerosis: A physiological profiling approach.
. Upper-limb sensory and motor impairments are common in people with multiple sclerosis (MS), yet the current gold standard criteria for documenting functional impairment largely focuses on mobility, balance and postural stability. . We aimed to determine the validity of the upper-limb Physiological Profile Assessment (PPA) in people with MS by investigating whether the included domains of muscle strength, dexterity, arm stability, position sense, skin sensation and bimanual coordination 1) are sensitive in differentiating people with MS from healthy controls and 2) correlate with a validated measure of upper-limb function and a scale for quantifying disability in MS. . In a cross-sectional study, 40 participants with MS and 80 healthy controls completed all 13 of the upper-limb PPA tests within a single session. . People with MS were impaired across all physiological domains tested. Performance in 4 of the 13 tests was correlated with a validated measure of self-reported upper-limb function (Pearson's r or Spearman's rho -0.333-0.441), whereas 3 tests were associated with the degree of MS-specific disability (Spearman's rho -0.318; 0.456). . The upper-limb PPA offers a valid and clinically suitable assessment of upper-limb function in people with MS. Clinicians should prioritize assessments of motor speed, fine motor control and functional tasks in their assessment of upper-limb function in people with MS because these domains are the most commonly and significantly impaired.


Differences in the acceptability of non-abstinence goals by type of drug among American substance abuse clinicians.
To assess whether acceptability of non-abstinence outcome goals varied depending on the specific drug a client consumes (alcohol, cannabis, amphetamine, heroin, cocaine, MDMA/ecstasy, polydrug), severity of diagnosis (DSM-IV Abuse vs. Dependence), and finality of outcome goal (intermediate vs. final), we recruited 432 clinicians to complete a web-based questionnaire. More respondents rated non-abstinence acceptable as an intermediate goal for clients diagnosed with alcohol abuse (44%) or cannabis abuse (43%) than for clients diagnosed as abusing the other listed drugs (23 to 31%). Similarly, larger proportions of respondents rated non-abstinence as acceptable as a final goal for clients diagnosed with alcohol abuse (30%) or cannabis abuse (24%) than for clients diagnosed as abusing the other drugs (11 to 13%). Only 9 to 13% of respondents rated non-abstinence as an acceptable final goal for clients diagnosed with dependence, but 20% to 30% rated non-abstinence as acceptable as an intermediate goal for clients diagnosed as dependent.


Galanin binding sites in rat gastric and jejunal smooth muscle membrane preparations.
Receptors for galanin in membranes from the rat gastric and jejunal smooth muscle were studied using [125I] radioiodinated synthetic porcine galanin. Specific binding was time and temperature dependent. At 32 degrees C radioligand was degraded in the presence of smooth muscle membranes in a time-dependent manner. At optimal experimental conditions, the equilibrium binding analyses showed the presence of a single population of high affinity binding sites in both the rat stomach and jejunum (Kd value of 2.77 +/- 0.78 nM and 4.93 +/- 1.74 nM for stomach and jejunal smooth muscle membranes, respectively). The concentration of the high affinity binding sites was 58.19 +/- 11.04 and 32.36 +/- 5.68 fmol/mg protein, for gastric and jejunal preparations, respectively. Specific binding was completely inhibited by 10(-6) M of nonradioactive galanin; was 75% blocked by 1 microM of galanin(9-29); it was 10% blocked by 1 microM of galanin(15-29). Galanin(1-15) at a concentration of 1 microM was ineffective for inhibiting [125I]galanin binding. Deletion of four C-terminal amino acid residues from galanin(9-29) to give galanin(9-25) also resulted in almost complete loss of affinity. Radioiodinated galanin and N-terminally deleted fragments had receptor binding potency in the following order: galanin(1-29) greater than galanin(9-29) greater than galanin(15-29). We conclude that the C-terminal part of the galanin chain is important for the rat gastric and jejunal smooth muscle membrane receptor recognition and binding and that N-terminal amino acid sequences are probably not so important, since galanin(1-15) was not active but galanin(9-29) retained most of the receptor binding activity.


Effect of noise distractibility on the spans of apprehension of hyperactive boys.
Denton and McIntyre (1978), using a forced-choice letter-recognition procedure, demonstrated increasing reductions in the spans of apprehension of hyperactive as compared to normal boys when a signal letter was embedded within an increasing number of noise letters. In the present study, the effect of variations in the amount of physical signal-noise similarity and noise redundancy upon the spans of apprehension of hyperactive and normal boys was compared to determine whether noise letters act as more potent distractors for the hyperactive boys. Results indicated the spans of both groups were effected equivalently by variations in signal-noise similarity and noise redundancy. No evidence for a distractibility explanation was obtained.


Australian snake venoms and their in vitro effect on human platelets.
Thrombocytopenia is generally not associated with cases of envenomation by Australian snakes, however the clinical evidence is conflicting. The in vitro effect of these venoms upon platelets had hitherto not been studied. This study systematically examines the effect on human fresh and fixed platelets of twenty Australian snake venoms, nineteen elapid and an hydrophiid; for comparision four crotalid venoms from the Americas and S.E. Asia were also included. Electron micrographs were taken of platelets after exposure to some of the venoms. Results demonstrated that all venoms except the hydrophiid venom caused fresh platelets to irreversibly aggregate directly, and this was associated with degranulation as evidenced by electron microscopy (EM). Response to all venoms by fixed platelets was less marked and also suggests, that metabolically, active platelets are necessary for the venoms to exert their maximal effect. The hydrophiid venom's action on fresh platelets was unique, as a plasma co-factor was required before aggregation could be induced. Crotalid and hydrophiid venoms were more active against platelets than the elapid venoms. Nevertheless, platelet aggregation and degranulation in the presence of elapid venoms suggests that a platelet response in vitro may be a significant factor in the "defibrination syndrome" induced in humans by Australian snakes.


A Saccharomyces cerevisiae strain unable to store neutral lipids is tolerant to oxidative stress induced by α-synuclein.
Parkinson disease is a neurodegenerative pathology that has been linked to several genetic mutations of the SNCA gene encoding the pro-oxidant α-synuclein protein. The budding yeast Saccharomyces cerevisiae is a valuable model for studying the cellular and molecular mechanisms of α-synuclein toxicity. Indeed heterologous expression of α-synuclein is toxic to wild-type yeast and exhibits the main features of damage caused to mammalian neurons, including an increase in neutral lipid storage (triglycerides and steryl esters, embedded into lipid droplets). To address the significance of this accumulation, we forced α-synuclein production in a strain unable to synthesize triglycerides and steryl esters. Surprisingly, the inability to store neutral lipids rendered the cells more tolerant to α-synuclein. Our results indicate that the level of α-synuclein toxicity is correlated with fatty acid synthase activity and intracellular redox status.


Lignan and terpene constituents from the aerial parts of Saussurea pulchella.
Chromatographic separation of the MeOH extract from the aerial parts of Saussurea pulchella led to the isolation of seven terpenes (1-4, 11-13), and eight phenolics (5-10, 14-15). Their structures were determined by spectroscopic means to be (3S)-3-O-(3',4'-diangeloyl-beta-D-glucopyranosyloxy)-3,7-trimethylocta-1,6-diene (1), 7delta-methoxy- 4(14)- oppositen-1beta-ol (2) 4(15)- eudesmene-1beta, 6alpha-diol (3), 3alpha-hydroxy-5, 6-epoxy-7-megastigmen-9-one (4), (+)-syringaresinol (5), (7S, 8R, 8'R)-5,5'-dimethoxylariciresinol (6), 8alpha-hydroxypinoresinol (7), (7'R, 8'R)-2,2'- dimethoxy-4- (3-hydroxyl-propenyl)-4'-(1,2,3-trihydroxypropyl)-biphenyl ether (8), 4-allyl-2,6- dimethoxyphenyl glucoside (9), 2-methoxy-4-(2-propenyl)phenyl beta-D-glucoside (10), (-)-oplopan-4-one- 10alpha-O-beta-D-glucoside (11), linalyl-O-beta-D-glucoside (12), amarantholidoside IV (13), (+)-1-hydroxypinoresinol 1-O-beta-D-glucoside (14), and syringin (15). Compounds 1-3 and 8-13 were first isolated from the genus Saussurea. The isolated compounds were examined for cytotoxic activity against four human cancer cell lines in vitro using the sulforhodamin B bio assay method.


Chordoid glioma of the third ventricle.
Chordoid glioma is a rare tumour (World Health Organisation grade II) originating from the third ventricle with both glial and chordoid features. It was first described by Brat in 1998. Since there is no detailed information available on the outcome after surgery and adjuvant treatment, we reviewed the literature. A literature search through PUBMED revealed 50 cases of chordoid glioma. Most reports were found in pathology journals. Information on the postoperative course was sometimes very limited. We reviewed the available literature and studied in detail the presenting symptoms, mortality and postoperative complications in relation to the extent of resective surgery, as well as the importance of adjuvant treatment. Mortality in the immediate postoperative period is 32% and is higher after gross total resection as compared to subtotal resection. Non-fatal postoperative complications are hypothalamic disorders and mental alterations. Gross total resection is the treatment of choice since no recurrence has been reported after macroscopically complete resection, but this is often difficult because of the location and adherence to the hypothalamus. The role of postoperative radiotherapy is uncertain. There is some indication that radiosurgery with or without conventional irradiation is superior to conventional radiation alone. Planned subtotal resection followed by stereotactic radiosurgery can be a safe and effective alternative in a patient in whom gross total resection is considered to be too risky. There is no report on the use of chemotherapy in the treatment of chordoid gliomas. More information about the optimal treatment strategy is needed, and more reports are also needed.


Adrenal androgens rescue prostatic dihydrotestosterone production and growth of prostate cancer cells after castration.
Adrenal androgens dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEAS) are potential substrates for intracrine production of testosterone (T) and dihydrotestosterone (DHT), or directly to DHT, by prostate cancer (PCa) cells. Production of DHT from DHEAS and DHEA, and the role of steroid sulfatase (STS), were evaluated ex vivo using fresh human prostate tissue and in vitro using human PCa cell lines. STS was expressed in benign prostate tissue and PCa tissue. DHEAS at a physiological concentration was converted to DHT in prostate tissue and PCa cell lines, which was STS-dependent. DHEAS activation of androgen receptor (AR) and stimulation of PCa cell growth were STS-dependent. DHEA at a physiological concentration was not converted to DHT ex vivo and in vitro, but stimulated in vivo tumor growth of the human PCa cell line, VCaP, in castrated mice. The findings suggest that targeting metabolism of DHEAS and DHEA may enhance androgen deprivation therapy.


Factors associated with the prevalence of sarcopenia and frailty syndrome in elderly university workers.
Frailty and sarcopenia are highly prevalent, as a part of geriatric syndrome, among elderly individuals. However, little is known about how these syndromes can affect elderly individuals who continue to work. To estimate the prevalence of sarcopenia and frailty, and their individual and occupational factors among elderly individuals. This cross-sectional study included elderly individuals working in a public university in Brazil, who were classified according to their sarcopenia and frailty profiles. They answered a structured questionnaire comprising potential explanatory variables: individual sociodemographic factors, work related factors, and health behaviors. Additionally, they performed a physical performance test. Multinomial logistic regression was used to estimate odds ratios and respective 95% confidence intervals (95% CIs). All analyses were conducted using the Stata 13.0 software, considering a significance of 5%. Respectively, 55.8% and 6.3% of the elderly participants were classified in the Sarcopenia and Severe Sarcopenia groups. Frailty prevalence was 9.4%, with 62.5% classified as Pre-frail. Sarcopenia prevalence was significantly higher among men, and among those living with a partner, with a university degree, exhibiting poor lower limb function, and with multiple work demands. Frailty prevalence was significantly higher among women, and among those living without a partner, having a low educational level, with less work experience, working in an unhealthy/dangerous environment, and whose job was predominantly physical. This study identified different potential trigger factors for the development of sarcopenia and frailty. These findings confirm that individual and work factors could explain the incidence of sarcopenia and frailty syndrome.


Sequence/structural analysis of xylem proteome emphasizes pathogenesis-related proteins, chitinases and β-1, 3-glucanases as key players in grapevine defense against Xylella fastidiosa.
Background. Xylella fastidiosa, the causative agent of various plant diseases including Pierce's disease in the US, and Citrus Variegated Chlorosis in Brazil, remains a continual source of concern and economic losses, especially since almost all commercial varieties are sensitive to this Gammaproteobacteria. Differential expression of proteins in infected tissue is an established methodology to identify key elements involved in plant defense pathways. Methods. In the current work, we developed a methodology named CHURNER that emphasizes relevant protein functions from proteomic data, based on identification of proteins with similar structures that do not necessarily have sequence homology. Such clustering emphasizes protein functions which have multiple copies that are up/down-regulated, and highlights similar proteins which are differentially regulated. As a working example we present proteomic data enumerating differentially expressed proteins in xylem sap from grapevines that were infected with X. fastidiosa. Results. Analysis of this data by CHURNER highlighted pathogenesis related PR-1 proteins, reinforcing this as the foremost protein function in xylem sap involved in the grapevine defense response to X. fastidiosa. β-1, 3-glucanase, which has both anti-microbial and anti-fungal activities, is also up-regulated. Simultaneously, chitinases are found to be both up and down-regulated by CHURNER, and thus the net gain of this protein function loses its significance in the defense response. Discussion. We demonstrate how structural data can be incorporated in the pipeline of proteomic data analysis prior to making inferences on the importance of individual proteins to plant defense mechanisms. We expect CHURNER to be applicable to any proteomic data set.