Reversal of the in vitro susceptibility of enterococci to trimethoprim-sulfamethoxazole by folinic acid.
The in vitro susceptibilities of 21 clinical isolates of Streptococcus faecalis to trimethoprim (TMP) in combination with sulfamethoxazole (SMX) was evaluated in Mueller-Hinton broth (MHB) in the presence and absence of folinic acid as well as in urine. The mean MIC and MBC in MHB, expressed as the TMP concentration, was 0.13 and 0.32 micrograms of TMP-SMX per ml, respectively. In MHB supplemented with folinic acid, the mean MIC and MBC was 3.3 and 5.5 micrograms of TMP-SMX per ml, respectively. In urine the mean MIC of TMP-SMX for these isolates was 8.1 micrograms/ml (range, 1.6 to 50 micrograms/ml). All isolates were inhibited by less than 0.01 micrograms of TMP-SMX per ml when methotrexate was added to the urine.


Profiling, Bioinformatic, and Functional Data on the Developing Olfactory/GnRH System Reveal Cellular and Molecular Pathways Essential for This Process and Potentially Relevant for the Kallmann Syndrome.
During embryonic development, immature neurons in the olfactory epithelium (OE) extend axons through the nasal mesenchyme, to contact projection neurons in the olfactory bulb. Axon navigation is accompanied by migration of the GnRH+ neurons, which enter the anterior forebrain and home in the septo-hypothalamic area. This process can be interrupted at various points and lead to the onset of the Kallmann syndrome (KS), a disorder characterized by anosmia and central hypogonadotropic hypogonadism. Several genes has been identified in human and mice that cause KS or a KS-like phenotype. In mice a set of transcription factors appears to be required for olfactory connectivity and GnRH neuron migration; thus we explored the transcriptional network underlying this developmental process by profiling the OE and the adjacent mesenchyme at three embryonic ages. We also profiled the OE from embryos null for Dlx5, a homeogene that causes a KS-like phenotype when deleted. We identified 20 interesting genes belonging to the following categories: (1) transmembrane adhesion/receptor, (2) axon-glia interaction, (3) scaffold/adapter for signaling, (4) synaptic proteins. We tested some of them in zebrafish embryos: the depletion of five (of six) Dlx5 targets affected axonal extension and targeting, while three (of three) affected GnRH neuron position and neurite organization. Thus, we confirmed the importance of cell-cell and cell-matrix interactions and identified new molecules needed for olfactory connection and GnRH neuron migration. Using available and newly generated data, we predicted/prioritized putative KS-disease genes, by building conserved co-expression networks with all known disease genes in human and mouse. The results show the overall validity of approaches based on high-throughput data and predictive bioinformatics to identify genes potentially relevant for the molecular pathogenesis of KS. A number of candidate will be discussed, that should be tested in future mutation screens.


Aldosteronism and peripheral blood mononuclear cell activation: a neuroendocrine-immune interface.
Aldosteronism eventuates in a proinflammatory/fibrogenic vascular phenotype of the heart and systemic organs. It remains uncertain whether peripheral blood mononuclear cells (PBMCs) are activated before tissue invasion by monocytes/macrophages and lymphocytes, as is the case for responsible pathogenic mechanisms. Uninephrectomized rats treated for 4 weeks with dietary 1% NaCl and aldosterone (ALDOST, 0.75 microg/h) with or without spironolactone (Spi, 100 mg/kg per daily gavage) were compared with unoperated/untreated and uninephrectomized/salt-treated controls. Before intramural coronary vascular lesions appeared at week 4 of ALDOST, we found (1) a reduction of PBMC cytosolic free [Mg2+]i, together with intracellular Mg2+ and Ca2+ loading, whereas plasma and cardiac tissue Mg2+ were no different from controls; (2) increased H2O2 production by monocytes and lymphocytes together with upregulated PBMC gene expression of oxidative stress-inducible tyrosine phosphatase and Mn2+-superoxide dismutase and the presence of 3-nitrotyrosine in CD4+ and ED-1-positive inflammatory cells that had invaded intramural coronary arteries; (3) B-cell activation, including transcription of immunoglobulins, intracellular adhesion molecule-1, and CC and CXC chemokines and their receptors; (4) expansion of B lymphocyte subset and myosin heavy chain class II-expressing lymphocytes; and (5) autoreactivity with gene expression for antibodies to acetylcholine receptors and a downregulation of RT-6.2, which is in keeping with cell activation and associated with autoimmunity. Spi cotreatment attenuated the rise in intracellular Ca2+, the appearance of oxidative/nitrosative stress in PBMCs and invading inflammatory cells, and alterations in PBMC transcriptome. Thus, aldosteronism is associated with an activation of circulating immune cells induced by iterations in PBMC divalent cations and transduced by oxidative/nitrosative stress. ALDO receptor antagonism modulates this neuroendocrine-immune interface. The full text of this article is available online at http://www.circresaha.org.


Methodological advances in imaging intravital axonal transport.
Axonal transport is the active process whereby neurons transport cargoes such as organelles and proteins anterogradely from the cell body to the axon terminal and retrogradely in the opposite direction. Bi-directional transport in axons is absolutely essential for the functioning and survival of neurons and appears to be negatively impacted by both aging and diseases of the nervous system, such as Alzheimer's disease and amyotrophic lateral sclerosis. The movement of individual cargoes along axons has been studied in vitro in live neurons and tissue explants for a number of years; however, it is currently unclear as to whether these systems faithfully and consistently replicate the in vivo situation. A number of intravital techniques originally developed for studying diverse biological events have recently been adapted to monitor axonal transport in real-time in a range of live organisms and are providing novel insight into this dynamic process. Here, we highlight these methodological advances in intravital imaging of axonal transport, outlining key strengths and limitations while discussing findings, possible improvements, and outstanding questions.


Effectiveness of a problem-solving based intervention to prolong the working life of ageing workers.
An ageing workforce combined with increasing health problems in ageing workers implies the importance of evidence-based interventions to enhance sustainable employability. The aim of this study is to evaluate the effectiveness of the 'Staying healthy at work' problem-solving based intervention compared to business as usual. This study was designed as a quasi-experimental trial with a one-year follow-up. Measurements were performed at baseline, three and twelve months. The problem-solving based intervention provides a strategy for increasing the awareness of ageing workers of their role and responsibility in living sustainable, healthy working lives. The primary outcomes were work ability, vitality and productivity. Secondary outcomes were perceived fatigue, psychosocial work characteristics, work attitude, self-efficacy and work engagement. Analyses were performed on the 64 workers in the intervention and 61 workers from the business as usual group. No effects on productivity (OR = 0.83, 95% CI 0.23-3.00) and adverse effects on work ability (B = -1.33, 95% CI -2.45 to -0.20) and vitality (OR = 0.10, 95% CI 0.02-0.46) were found. Positive results were found for the work attitude secondary outcome (B = 5.29, 95% CI -9.59 to -0.99), the self-efficacy persistence subscale (B = 1.45, 95% CI 0.43-2.48) and the skill discretion subscale of the Job Content Questionnaire (B = 1.78, 95% CI 0.74-2.83). The results of the problem-solving intervention showed no positive effects on the three outcome measures compared to business as usual. However, effectiveness was shown on three of the secondary outcome measures, i.e. work attitude, self-efficacy and skill discretion. We presume that the lack of positive effects on primary outcomes is due to programme failure and not to theory failure. The trial is registered with the Dutch Trial Register under number NTR2270 .


Shared neurocognitive dysfunctions in young offspring at extreme risk for schizophrenia or bipolar disorder in eastern quebec multigenerational families.
Adult patients having schizophrenia (SZ) or bipolar disorder (BP) may have in common neurocognitive deficits. Former evidence suggests impairments in several neuropsychological functions in young offspring at genetic risk for SZ or BP. Moreover, a dose-response relation may exist between the degree of familial loading and cognitive impairments. This study examines the cognitive functioning of high-risk (HR) offspring of parents having schizophrenia (HRSZ) and high-risk offspring of parents having bipolar disorder (HRBP) descending from densely affected kindreds. The sample consisted of 45 young offspring (mean age of 17.3 years) born to a parent having SZ or BP descending from large multigenerational families of Eastern Québec that are densely affected by SZ or BP and followed up since 1989. The offspring were administered a lifetime best-estimate diagnostic procedure (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition [DSM-IV]) and an extensive standard neuropsychological battery. Raw scores were compared with age- and gender-matched controls. The offspring displayed differences in memory and executive functions when compared with controls. Moderate to large effect sizes (Cohen d) ranging from 0.65 to 1.25 (for IQ and memory) were observed. Several of the cognitive dysfunctions were present in both HRSZ and HRBP, even when considering DSM-IV clinical status. HRSZ and HRBP shared several aspects of their cognitive impairment. Our data suggest that the extremely high genetic and familial loading of these HRs may have contributed to a quantitatively increased magnitude of the cognitive impairments in both HR subgroups, especially in memory. These offspring at heightened risk present difficulties in processing information that warrant preventive research.


Gene expression in the mammary gland of the tammar wallaby during the lactation cycle reveals conserved mechanisms regulating mammalian lactation.
The tammar wallaby (Macropus eugenii), an Australian marsupial, has evolved a different lactation strategy compared with eutherian mammals, making it a valuable comparative model for lactation studies. The tammar mammary gland was investigated for changes in gene expression during key stages of the lactation cycle using microarrays. Differentially regulated genes were identified, annotated and subsequent gene ontologies, pathways and molecular networks analysed. Major milk-protein gene expression changes during lactation were in accord with changes in milk-protein secretion. However, other gene expression changes included changes in genes affecting mRNA stability, hormone and cytokine signalling and genes for transport and metabolism of amino acids and lipids. Some genes with large changes in expression have poorly known roles in lactation. For instance, SIM2 was upregulated at lactation initiation and may inhibit proliferation and involution of mammary epithelial cells, while FUT8 was upregulated in Phase 3 of lactation and may support the large increase in milk volume that occurs at this point in the lactation cycle. This pattern of regulation has not previously been reported and suggests that these genes may play a crucial regulatory role in marsupial milk production and are likely to play a related role in other mammals.


The Long and Winding Road: Thoracic Myelopathy Associated With Occipitocervical Dural Arteriovenous Fistula.
Spinal dural arteriovenous fistulas (DAVFs) have diverse presentations. Magnetic resonance imaging (MRI) reveals spinal cord swelling in only 45% to 74% of cases. We present an unusual case of a 57-year old man with a craniocervical junction DAVF in which the edema appeared in the thoracolumbar region, skipping the cervical spinal cord. A case report and literature review from a tertiary referral center are provided. In our patient, symptoms progressed over 3 months from low back and radicular pain to weakness, saddle anesthesia, and urinary retention. MRI showed T2 hyperintensity from T3-4 to the conus medullaris. The results from initial brain and spine angiograms were negative. Repeated angiography with the patient under anesthesia revealed a DAVF in the craniocervical junction composed of a cervical branch arising from the right vertebral artery and entering the nidus at the foramen magnum. A prominent intradural draining vein extended inferiorly along the posterior aspect of the cervical spinal cord. The patient was taken to the operating room, where the extradural vertebral artery was dissected and a suboccipital craniectomy was performed. After the dura was opened, the arterialized vein was visualized and clipped. Somatosensory evoked potentials and motor evoked potentials remained at baseline throughout the occlusion. The dura and fistula were removed en bloc, and the draining vein was confirmed to lose flow on indocyanine green. Postoperatively, the patient's symptoms completely resolved, and he experienced full strength in the lower extremities and perineal sensation. A review of 19 cases of DAVF at the craniocervical junction with cord edema shows that >90% involve the brainstem or cervical cord. Only 1 other patient had a similar "skip lesion," in which the cord edema first appeared in the thoracic cord. This rare presentation highlights the importance of diagnostic persistence when unexplained cord findings are seen on MRI. Repeated angiography and the inclusion of proximal vascular lesions may be considered in the evaluation of isolated thoracic edema.


Atherosclerosis and rheumatic heart disease.
The extent of aortic atherosclerosis in subjects with rheumatic heart diseases was similar to that in the standardized average atherosclerosis group of subjects. The extent of coronary atherosclerosis, particularly in men, was similar to that in the low atherosclerosis group. In the aorta, this finding was accounted for by the greater extent of complicated and raised lesions; in the coronary arteries, it was accounted for by the lesser extent of fibrous plaque. Coronary stenosis, fresh myocardial infarction, and large myocardial scar occurred much less frequently in rheumatic subjects than in the high atherosclerosis group. There was no difference in the frequency of stenosis between the rheumatic and low atherosclerosis groups.


Wound classification reporting in HPB surgery: can a single word change public perception of institutional performance?
The drive to improve outcomes and the inevitability of mandated public reporting necessitate uniform documentation and accurate databases. The reporting of wound classification in patients undergoing hepato-pancreatico-biliary (HPB) surgery and the impact of inconsistencies on quality metrics were investigated. The 2005-2011 National Surgical Quality Improvement Program (NSQIP) participant use file was interrogated to identify patients undergoing HPB resections. The effect of wound classification on post-operative surgical site infection (SSI) rates was determined through logistic regression. The impact of variations in wound classification reporting on perceived outcomes was modelled by simulating observed-to-expected (O/E) ratios for SSI. In total, 27,376 patients were identified with significant heterogeneity in wound classification. In spite of clear guidelines prompting at least 'clean-contaminated' designation for HPB resections, 8% of all cases were coded as 'clean'. Contaminated [adjusted odds ratio (AOR): 1.39, P = 0.001] and dirty (AOR: 1.42, P = 0.02] cases were associated with higher odds of SSI, whereas clean-contaminated were not (P = 0.99). O/E ratios were highly sensitive to modest changes in wound classification. Perceived performance is affected by heterogeneous reporting of wound classification. As institutions work to improve outcomes and prepare for public reporting, it is imperative that all adhere to consistent reporting practices to provide accurate and reproducible outcomes.


Comparative Study of Surgical Management of Fracture Neck of Femur with Cemented Versus Uncemented Bipolar Hemiarthroplasty.
There is evidence for use of cemented hemiarthroplasty resulting in greater anchoring and lesser peri prosthetic fracture. However, this procedure results in more haemodynamic instability and cardiopulmonary complications termed as 'cement reaction' or bone cement implantation syndrome. There has been a heightened interest among surgeons to compare cemented and uncemented hemiarthroplasty for fracture neck of femur. To compare cemented and uncemented hemiarthroplasty in terms of blood loss during the procedure, post-operative complications, mortality, functional recovery and long term clinical outcome. In a prospective study spanning 8 years from January 2006 to January 2014 in a tertiary care hospital, 52 cases of fracture of neck were selected. Twenty four patients underwent cemented and 28 patients underwent uncemented hemiarthroplasty. Mean follow up duration was 59.3 months. Harris Hip Score evaluation was done at each follow up. Radiological evaluation was done at each follow up for calcar length and periprosthetic fractures. Mean age of patients was 70 years. Harris Hip scores at 3, 6 and 12 months did not show statistically significant differences. Periprosthetic osteolysis or loosening was not seen in the present study. No complications noted in uncemented hemiarthroplasty. Four patients who had cemented hemiarthroplasty had infections. No mortality occurred during admission and within 12 months after surgery. No significant difference was noted between the cemented and uncemented hemiarthroplasty procedures on long term follow up in terms of functionality. No re-operations and no mortality reported. Cemented hemiarthroplasty had more blood loss and minimal post-operative complications.


Mathematical modeling of retinal birefringence scanning.
Retinal birefringence scanning (RBS) is a new technique that is used to detect the fixation of the eye remotely and noninvasively. The method is based on analysis of polarization changes induced by the retina. In this study, the principles of RBS were mathematically modeled to facilitate a better understanding of the origins of the signals obtained. Stokes vector analysis and Mueller matrix multiplication were augmented with Poincaré sphere representation. The cornea was modeled as a linear retarder. The foveal area was modeled as a radially symmetric birefringent medium. The model accurately predicted the frequency and phase of RBS signals obtained during central and paracentral fixation. The signal that indicates central fixation during RBS likely results from a combination of the radial birefringence of the Henle fibers and the overlying corneal birefringence.


Activation of the ventral and dorsal striatum during cue reactivity in Internet gaming disorder.
Studies conducted in drug addiction suggest a transition in processing of drug-related cues from the ventral to the dorsal component of the striatum. However, this process has not been studied in a behavioral addiction. Assessment of this process in a non-drug addiction can provide insight into the pathophysiology of both substance and behavioral addictions. Thirty-nine male Internet gaming disorder (IGD) subjects and 23 male matched healthy controls (HCs) participated in functional magnetic resonance imaging during performance of a cue-reactivity task involving alternating presentation of Internet gaming-related stimuli (game cues) and general Internet surfing-related stimuli (control cues). Cue-induced neural activations in the ventral and dorsal striatum (DS) were compared between IGD and HC participants. Associations between cue-reactivity within these regions and cue-induced craving and severity and duration of IGD were also explored. IGD participants exhibited higher cue-induced activations within both the ventral and DS when compared with HCs. Within the IGD group, activity within the left ventral striatum (VS) was correlated negatively with cue-induced craving; positive associations were found between activations within the DS (right putamen, pallidum and left caudate) and duration of IGD. Cue-induced activity within the left putamen was negatively associated with right VS volumes among IGD participants. Consistent with studies in substance addictions, our results suggest that a transition from ventral to dorsal striatal processing may occur among individuals with IGD, a condition without the impact of substance intake.


Spiro and dispiro-1,2,4-trioxolanes as antimalarial peroxides: charting a workable structure-activity relationship using simple prototypes.
This paper describes the discovery of synthetic 1,2,4-trioxolane antimalarials and how we established a workable structure-activity relationship in the context of physicochemical, biopharmaceutical, and toxicological profiling. An achiral dispiro-1,2,4-trioxolane (3) in which the trioxolane is flanked by a spiroadamantane and spirocyclohexane was rapidly identified as a lead compound. Nonperoxidic 1,3-dioxolane isosteres of 3 were inactive as were trioxolanes without the spiroadamantane. The trioxolanes were substantially less effective in a standard oral suspension formulation compared to a solubilizing formulation and were more active when administered subcutaneously than orally, both of which suggest substantial biopharmaceutical liabilities. Nonetheless, despite their limited oral bioavailability, the more lipophilic trioxolanes generally had better oral activity than their more polar counterparts. In pharmacokinetic experiments, four trioxolanes had high plasma clearance values, suggesting a potential metabolic instability. The toxicological profiles of two trioxolanes were comparable to that of artesunate.


Hypertriglyceridemic Pancreatitis: Is Insulin Monotherapy A Feasible Therapeutic Option?
Hypertriglyceridemic pancreatitis (HTGP) is an uncommon but well-established clinical entity. Although the initial clinical features are similar to pancreatitis due to other etiologies, the severity of the disease and the risk of complications are higher in these patients. Prompt diagnosis and appropriate treatment are crucial in patients with hypertriglyceridemia-induced pancreatitis to avoid life-threatening complications. The initial conservative treatment is applied followed by additional specific therapies tailored to decrease serum triglyceride levels. This includes plasmapheresis, insulin, heparin infusion, and hemofiltration. After the acute episode, lifestyle modifications along with hypolipidemic medications should be initiated to prevent further events. Currently, there is paucity of the medical literature directly comparing different treatment modalities. This article illustrates the use of insulin therapy for HTGP as a feasible therapeutic choice. Randomized controlled trials are warranted to outline a generalized and efficient treatment for this serious disorder.


Charting the course for the future of science in healthcare epidemiology: results of a survey of the membership of the Society of Healthcare Epidemiology of America.
To describe the results of a survey of members of the Society for Healthcare Epidemiology of America (SHEA) that (1) measured members' perceptions of gaps in the healthcare epidemiology knowledge base and members' priorities for SHEA research goals, (2) assessed whether members would be willing to participate in consortia to address identified gaps in knowledge, and (3) evaluated the need for training for the next generation of investigators in the field of healthcare epidemiology. Electronic and paper survey of members of SHEA, a professional society formed to advance the science of healthcare epidemiology through research and education. All society members were invited to participate. Of 1,289 SHEA members, 593 (46.0%) responded. Respondents identified the following issues as important for the Research Committee of SHEA: setting the scientific agenda for healthcare epidemiology, developing collaborative infrastructure to conduct research, and developing funding mechanisms for research. Respondents ranked multidrug-resistant gram-negative organisms, antimicrobial stewardship, methicillin-resistant Staphylococcus aureus, adherence to effective hand hygiene guidelines, and Clostridium difficile infections as the most important scientific issues facing the field. Respondents ranked inadequate project funding, lack of protected time for research, and inability to obtain a grant, contract, and/or outside funding as the most significant barriers to conducting research. More than 92% of respondents support creating a SHEA research consortium; more than 40% would participate even if no additional funding were available; nearly 90% identified developing research training as a key function for SHEA. These data provide a road map for the SHEA Research Committee for the next decade.


[Long-term results of endoscopic treatment of urethral strictures].
The aim of the study was assessment of efficacy of internal urethrotomies made in Research Institute of Urology and city urological hospital N 47. A total of 802 endoscopic operations were performed in 644 male patients aged from 16 to 89 years (mean age 58.6 years) with urethral stricture in 1994-2004. Internal optic urethrotomy was made in 733 cases with a cold knife, in 52--with electric knife and in 17 cases--with laser. Endoscopic urethral resection was conducted in 47 cases. The strictures (0.5-8 cm long, mean 1.4 cm) located most frequently in the bulbous urethra (n=426, 66.1%). Short-term results (12 months) of endoscopic treatment of urethral strictures showed that efficacy of the primary internal urethrotomy conducted according to the authors' technique reached 80.4%. Endoscopic reoperations (from 1 to 6) were performed in 98 (19.6%) patients. A complete rehabilitation (follow-up 9 years maximum) including stenting was achieved in 95.1% patients. In 32 (4.9%) patients endoscopic and rehabilitation measures failed to bring about satisfactory clinical outcomes. These patients were treated with open urethroplasty. Thus, internal optic urethrotomy is an effective therapeutic method. After primary urethrotomy recurrences of the strictures to be reoperated reach 19.6%. These can be successfully managed by endoscopic reoperations and rehabilitation measures.


[S-100 protein in amniotic fluid of the ancencephalic fetus].
S-100 protein, essentially of astrocytic origin, is present in the amniotic fluid of anencephalic fetuses. Its detection reflects tissue necrosis and could be complementary for prenatal diagnosis.


Impact of myocardial deformation on risk prediction in patients following acute myocardial infarction.
Strain analyses derived from cardiovascular magnetic resonance-feature tracking (CMR-FT) provide incremental prognostic benefit in patients sufferring from acute myocardial infarction (AMI). This study aims to evaluate and revalidate previously reported prognostic implications of comprehensive strain analyses in a large independent cohort of patients with ST-elevation myocardial infarction (STEMI). Overall, 566 STEMI patients enrolled in the CONDITIONING-LIPSIA trial including pre- and/or postconditioning treatment in addition to conventional percutaneous coronary intervention underwent CMR imaging in median 3 days after primary percutaneous coronary intervention. CMR-based left atrial (LA) reservoir (Es), conduit (Ee), and boosterpump (Ea) strain analyses, as well as left ventricular (LV) global longitudinal strain (GLS), circumferential strain (GCS), and radial strain (GRS) analyses were carried out. Previously identified cutoff values were revalidated for risk stratification. Major adverse cardiac events (MACE) comprising death, reinfarction, and new congestive heart failure were assessed within 12 months after the occurrence of the index event. Both atrial and ventricular strain values were significantly reduced in patients with MACE (p < 0.01 for all). Predetermined LA and LV strain cutoffs enabled accurate risk assessment. All LA and LV strain values were associated with MACE on univariable regression modeling (p < 0.001 for all), with LA Es emerging as an independent predictor of MACE on multivariable regression modeling (HR 0.92, p = 0.033). Furthermore, LA Es provided an incremental prognostic value above LVEF (a c-index increase from 0.7 to 0.74, p = 0.03). External validation of CMR-FT-derived LA and LV strain evaluations confirmed the prognostic value of cardiac deformation assessment in STEMI patients. In the present study, LA strain parameters especially enabled further risk stratification and prognostic assessment over and above clinically established risk parameters. ClinicalTrials.gov, identifier NCT02158468.


Determination of yolk contamination in liquid egg white using Raman spectroscopy.
Purified egg white is an important ingredient in a number of baked and confectionary foods because of its foaming properties. However, yolk contamination in amounts as low as 0.01% can impede the foaming ability of egg white. In this study, we used Raman spectroscopy to evaluate the hypothesis that yolk contamination in egg white could be detected based on its molecular optical properties. Yolk contaminated egg white samples (n = 115) with contamination levels ranging from 0% to 0.25% (on weight basis) were prepared. The samples were excited with a 785 nm laser and Raman spectra from 250 to 3,200 cm(-1) were recorded. The Raman spectra were baseline corrected using an optimized piecewise cubic interpolation on each spectrum and then normalized with a standard normal variate transformation. Samples were randomly divided into calibration (n = 77) and validation (n = 38) data sets. A partial least squares regression (PLSR) model was developed to predict yolk contamination levels, based on the Raman spectral fingerprint. Raman spectral peaks, in the spectral region of 1,080 and 1,666 cm(-1), had the largest influence on detecting yolk contamination in egg white. The PLSR model was able to correctly predict yolk contamination levels with an R(2) = 0.90 in the validation data set. These results demonstrate the capability of Raman spectroscopy for detection of yolk contamination at very low levels in egg white and present a strong case for development of an on-line system to be deployed in egg processing plants.


Early innate immune responses to Sin Nombre hantavirus occur independently of IFN regulatory factor 3, characterized pattern recognition receptors, and viral entry.
Sin Nombre virus (SNV) is a highly pathogenic New World virus and etiologic agent of hantavirus cardiopulmonary syndrome. We have previously shown that replication-defective virus particles are able to induce a strong IFN-stimulated gene (ISG) response in human primary cells. RNA viruses often stimulate the innate immune response by interactions between viral nucleic acids, acting as a pathogen-associated molecular pattern, and cellular pattern-recognition receptors (PRRs). Ligand binding to PRRs activates transcription factors which regulate the expression of antiviral genes, and in all systems examined thus far, IFN regulatory factor 3 (IRF3) has been described as an essential intermediate for induction of ISG expression. However, we now describe a model in which IRF3 is dispensable for the induction of ISG transcription in response to viral particles. IRF3-independent ISG transcription in human hepatoma cell lines is initiated early after exposure to SNV virus particles in an entry- and replication-independent fashion. Furthermore, using gene knockdown, we discovered that this activation is independent of the best-characterized RNA- and protein-sensing PRRs including the cytoplasmic caspase recruitment domain-containing RNA helicases and the TLRs. SNV particles engage a heretofore unrecognized PRR, likely located at the cell surface, and engage a novel IRF3-independent pathway that activates the innate immune response.


[The prognosis of the course of amebic liver abscess by the indices of the immune status].
The study of T- and B-lymphocyte content in 95 patients with amoeba-induced abscess in the liver has shown that the onset of complications are accompanied by secondary immune failure, which must be corrected with immunomodulators (T-activin, levamizole, gamma-globulin, antistaphylococcal plasma). A group of patients has been identified who despite pyo-resorptive fever are characterized by high resistance and good compensatory reactions. This group needs no special correction of the immune status. The prognostic formula suggested by the authors is based on clinical, laboratory and immunological indexes and promotes to the rational choice of immunocorrective therapy and to patients rehabilitation.


Lung carcinoma: survey of 2286 cases with emphasis on small cell type.
Lung carcinoma is the commonest major malignancy in men in the United States and its incidence is increasing rapidly in women. It is estimated that there will have been 117,000 new cases and 101,300 deaths in 1980. The 2286 patients with lung carcinoma admitted to the Hospital of the University of Mississippi from 1955 to 1980 were reviewed by decades of chronology and of life, with respect to age, cell type, sex and racial incidence. The greatest age incidence was in the sixth and seventh decades; cell types overall were epidermoid (45% of the patients), adenocarcinoma (12% of the patients), small (oat) cell (21% of the patients), and others (22% of the patients). There was a steady increase in the incidence of disease in females, adjusted for total hospital admissions, and a less certain increase among black patients. Twenty-eight per cent of 250 patients with small cell carcinoma so studied exhibited some feature of the paraneoplastic or paraendocrine syndromes. In 41 patients with small cell carcinoma treated with multiple drug chemotherapy, there was an overall response rate of 50% and an additional "stable disease" rate of 28%. Mean survival period in this group was 52 weeks, compared with 12 weeks in patients whose diseases went untreated. Clearly, definite progress is being made, not only in our knowledge of the biology of lung carcinoma, in general, but in the treatment of small cell carcinoma in particular.


Bistable Perception Is Biased by Search Items but Not by Search Priming.
During visual search, selecting a target facilitates search for similar targets in the future, known as search priming. During bistable perception, in turn, perceiving one interpretation facilitates perception of the same interpretation in the future, a form of sensory memory. Previously, we investigated the relation between these history effects by asking: can visual search influence perception of a subsequent ambiguous display and can perception of an ambiguous display influence subsequent visual search? We found no evidence for such influences, however. Here, we investigated one potential factor that might have prevented such influences from arising: lack of retinal overlap between the ambiguous stimulus and the search array items. In the present work, we therefore interleaved presentations of an ambiguous stimulus with search trials in which the target or distractor occupied the same retinal location as the ambiguous stimulus. Nevertheless, we again found no evidence for influences of visual search on bistable perception, thus demonstrating no close relation between search priming and sensory memory. We did, however, find that visual search items primed perception of a subsequent ambiguous stimulus at the same retinal location, regardless of whether they were a target or a distractor item: a form of perceptual priming. Interestingly, the strengths of search priming and this perceptual priming were correlated on a trial-to-trial basis, suggesting that a common underlying factor influences both.


Correlation of CD34+ cell yield in peripheral blood progenitor cell product with the pre-leukapheresis cell counts in peripheral blood.
Accurate timing of the leukapheresis procedures is of paramount importance to get the best possible CD34+ cell yield in the minimum number of leukapheresis procedures. To find if pre-harvest CD34+ cell concentration in peripheral blood correlates with CD34+ cells in the product. Sixty Leukapheresis procedures were performed for 25 patients (8 autologous and 17 allogeneic transplants) with hematological malignancies. Statistical analysis was performed to correlate the pre-harvest CD34+ cell count and the CD34+ cell yield. Volume processed during PBPC harvests was three times the blood volume. The best correlation was found between the leukapheresis product CD34+ cell count and the pre-harvest PB-CD34+ cell count (PCC=0.674) when compared with the other pre-harvest PB cell counts viz., WBC (PCC=0.229) and MNC (PCC=0.324). This correlation was better in the allogeneic harvest (PCC = 0.645) than the autologous harvest procedures (PCC = 0.348). Correlation analysis based on paired samples from the 60 leukapheresis procedures showed that when the pre-leukapheresis PB-CD34+ cell count was >20x10(3)/ul a yield of >1x10(6) CD34+ cells/Kg could be obtained in 95% of the cases and >2x10(6) CD34+ cells /Kg could be harvested in 68% of cases whereas when the pre-leukapheresis PB-CD34+ cell count was <5x10(3)/microl the yield was <1x10(6) CD34+ cells/Kg in 81% of the procedures. The yield of CD34+ cells in PBPC harvests depends on the pre-harvest CD34+ cell concentration and therefore it is more useful than the pre-harvest WBC or MNC counts for predicting the appropriate timing of the harvests and also to achieve the best possible yield of CD34+ cells.


Correlation between oral hygiene and Helicobacter pylori infection.
As introduced by different studies, dental plaque is known as a reservoir of Helicobacter Pylori (HP) and a potential source for gastric re-infection. Also, it has been demonstrated that individuals with gastric HP infection manifest a greater plaque index and a higher incidence rate for gingivitis. The goal of the present research was survey of severity and prevalence of periodontal diseases associated with gastric HP infection among patients having referred to the endoscopy wards of Imam Khomeini and Milad hospitals. In this research, 122 patients with gastric HP infection were investigated for determining 4 indices: plaque index (PI), gingival index (GI), clinical attachment loss (CAL) and pocket depth (PD), for all existing teeth, using RUT (rapid urease test). The results indicated that about 86.9% of patients had developed gingivitis of various degrees and 100% of them were afflicted with periodontitis of different degrees, and about 64.8% of patients showed a weak PI, and 61.5% had a low level of education. This low-level education seen in majority of the studied subjects, addresses a high degree of importance and influence of the oral hygiene in gastric HP infections. Hence, gastroentrologists are required to refer patients to dentists in line of preserving oral and dental health.


Effects of Spirulina platensis microalgae on antioxidant and anti-inflammatory factors in diabetic rats.
Lipid peroxidation and hyperglycemia are common signs for diabetes. Natural antioxidants such as Spirulina platensis microalgae (SPM) may prevent lipid peroxidation and hyperglycemia. This study aimed to evaluate the effects of SPM on antioxidant and anti-inflammatory in diabetic rats. Sixty-four rats were divided into eight groups (n=8) and orally treated with 0, 10, 20 and 30 mg/kg body weight of SPM extract. Experimental groups included diabetic rats fed with 0 (DC), 10, 20 and 30 mg/kg SPM. Healthy rats were treated with 0 mg/kg SPM (HC), 10 mg/kg SPM, 20 mg/kg SPM and 30 mg/kg SPM. At the end of the trial, blood samples were collected and the plasma concentrations of trace minerals (TMs), biochemical parameters, and antioxidant enzymes in liver were evaluated. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), TNF-α (tumor necrosis factor-alpha) and IL-6 (interleukin-6) were evaluated. Our findings showed that diabetes significantly lowered the plasma concentration of TMs and antioxidant enzymes in liver and also increased the levels of malondialdehyde, glucose, lipid profile, AST, ALT, TNF-α and IL-6 (DC vs HC). However, an oral supplement of SPM (20 and 30 mg/kg body weight) lowered levels of malondialdehyde level, glucose, lipid parameters, AST, ALT, TNF-α and IL-6. The same levels increased the plasma contents of zinc, iron, copper and selenium and activity of antioxidant enzymes (P<0.05). It can be concluded that diabetes decreases TM concentration and antioxidant enzymes and also increases lipid profile, glucose, AST, ALT, TNF-α and IL-6 concentrations. Inclusion of SPM supplementing (20 and 30 mg/kg body weight) increased some TMs and antioxidant enzymes. SPM may provide TMs for synthesis of antioxidant enzymes which subsequently reduce lipid profile, glucose concentration and anti-inflammatory responses.


Virulence regions and virulence factors of the ovine footrot pathogen, Dichelobacter nodosus.
Ovine footrot is a debilitating and highly infectious disease that is primarily caused by the Gram-negative, anaerobic bacterium Dichelobacter nodosus. The major antigens implicated in virulence are the type IV fimbriae and extracellular proteases. The fimbriae show sequence and structural similarity to other type IV fimbriae, this similarity extends to genes that are involved in fimbrial biogenesis. Several acidic and basic extracellular serine proteases are produced by both virulent and benign isolates of D. nodosus. Subtle functional differences in these proteases appear to be important in virulence. In addition, there are two chromosomal regions that have a genotypic association with virulence. The partially duplicated and rearranged vap regions appear to have arisen from the insertion of a plasmid into a tRNA gene via an integrase-mediated site-specific insertion event. The 27 kb vrl region has several genes often found on bacteriophages and has inserted into an ssrA gene that may have a regulatory role in the cell. The determination of the precise role that each of these genes and gene regions has in virulence awaits the development of methods for the genetic analysis and manipulation of D. nodosus.


Effects of sulphydryl reagents on the structure of dehistonized metaphase chromosomes.
Dehistonized metaphase chromosomes lose their apparent axial organization (the 'scaffold') and sediment more slowly following exposure to beta-mercaptoethanol (BME). We have subsequently treated BME chromosomes with reagents that oxidize protein sulphydryls to disulphides, and found that if calcium is also present during the oxidation an apparently similar axial structure is restored following dehistonization, as seen by microscopic examination. In general, however, we do not find that oxidation restores the higher sedimentation rate of dehistonized control chromosomes. Analysis of residual core protein in dehistonized chromosomes by sodium dodecyl sulphate/polyacrylamide gel electrophoresis fails to detect any differences in polypeptide composition related to the state of oxidation or to the presence or absence of visible axial organization. Combining our results with those of other workers, we conclude that the axial structure evident in dehistonized metaphase chromosomes is maintained, at least partially, by inter-protein cross-linking, although in vivo this may not be via simple disulphide bridges. Additional factors, which we have not yet characterized, but which possibly include heavy metal ions, appear to be involved in the axial organization existing in vivo.


Treatment of acyclovir-resistant herpes simplex virus with continuous infusion of high-dose acyclovir in hematopoietic cell transplant patients.
Infection because of herpes simplex virus (HSV) that is resistant to acyclovir (ACV) poses treatment challenges in hematopoietic cell transplant (HCT) patients. We present a series of patients with ACV-resistant HSV following HCT who were successfully treated with continuous infusion high-dose ACV after failing standard treatment regimens for ACV-resistant HSV.


High-affinity neoantigens correlate with better prognosis and trigger potent antihepatocellular carcinoma (HCC) activity by activating CD39+CD8+ T cells.
It remains controversial whether tumour mutational burden (TMB) or neoantigens are prognostic markers in hepatocellular carcinoma (HCC). This study aimed to define the function of TMB or neoantigens in antitumour immunotherapy. Neoantigens of patients (n=56) were analysed by pVAC tools with major histocompatibility complex-1 (MHC-I) algorithms based on whole exome sequencing and neoantigens with mutant type IC50 <50 nM were defined as high-affinity neoantigens (HANs). Patients were segregated into HAN-high/low groups by median of HAN value, and overall survival (OS) was analysed. Autologous organoid killing model was developed to clarify the antitumour activity of HANs. The value of HAN showed a better correlation with OS (p=0.0199) than TMB (p=0.7505) or neoantigens (p=0.2297) in patients with HCC and positively correlated with the frequency of CD39+CD8+ tumour infiltrating lymphocytes (TILs). Furthermore, HAN-specific CD8+ T cells were identified in CD39+CD8+ TILs, which showed better antitumour activity in HAN-high versus HAN-low group. In addition, more effective HAN peptides were identified in HAN-high versus HAN-low group. Besides, flow cytometry data showed that in fresh tumour, CD39+PD-1intCD8+ TILs displayed an effector phenotype and stronger antitumour activity in HAN-high versus HAN-low group. More importantly, patients in HAN-high versus HAN-low group showed a better prognosis after anti-PD-1 therapy. Our study first demonstrates that HAN value positively correlates with better OS in patients with HCC. HANs trigger antitumour activity by activating tumour-reactive CD39+CD8+ T cells, and patients in HAN-high group benefited more from anti-PD-1 therapy than HAN-low group. These findings may provide a novel strategy for personalised antitumour therapies for HCC.


Force production and spatial arm coordination profile in arm crawl swimming in a fixed position.
This study analyzed the relationship between mechanical force production and spatial arm position of the swimming movement for each side of the swimmer. Eight internationally recognized male swimmers performed fix positioned arm only swimming with a dynamometer synchronized with underwater cameras. The upper arm positions (α in side, β in frontal view) and the elbow angles (γ in 3D) were determined at the moment where the force production reached the peak (Fmax) and the maximal values of rate of force development (RFDmax). RFDmax and α values showed significant differences between the sides (P<0.05). To show the motion integration structure of the performance, Multiple Regression Analysis (MRA) was employed separately for both sides. For the criterion variable, the impulse of force (ImpF50%) was calculated. The defined parameters as the mechanical and spatial predictor system were used for the model. The results of the MRA showed that the predictor system yielded the model structure of the variables that explain the criterion variables for ImpF50% by the dominant (P=0.007) and by the nondominant side (P=0.001), respectively. The alternate contribution of the variables to the models can objectively express the performance difference between the two sides of the swimmer.


Optimized bzip2 compression for reducing diffraction effects in protein-based computing: a study of feasibility.
One of the current research directions in biological nanotechnology is the use of bacteriorhodopsin in the fabrication of protein-based photonic devices. Bacteriorhodopsin, with its unique light-activated photocycle, nanoscale size, cyclicity (> 107), and natural resistance to harsh environmental conditions, provides for protein-based memories that have a comparative advantage over magnetic and optical data storage devices. However, the construction of protein-based memories has been severely limited by fundamental issues that exist with such devices, such as unwanted diffraction effects. In this paper, we propose an algorithm for coping with diffraction effects, thus providing a solution to a long-standing problem.


The role of the adaptive immune system in regulation of gut microbiota.
The gut nourishes rich bacterial communities that affect profoundly the functions of the immune system. The relationship between gut microbiota and the immune system is one of reciprocity. The microbiota contributes to nutrient processing and the development, maturation, and function of the immune system. Conversely, the immune system, particularly the adaptive immune system, plays a key role in shaping the repertoire of gut microbiota. The fitness of host immune system is reflected in the gut microbiota, and deficiencies in either innate or adaptive immunity impact on diversity and structures of bacterial communities in the gut. Here, we discuss the mechanisms that underlie this reciprocity and emphasize how the adaptive immune system via immunoglobulins (i.e. IgA) contributes to diversification and balance of gut microbiota required for immune homeostasis.


Is non-pharmacological treatment an effective option for chronic low back pain?
Despite of pain being important warning signal for body ability to respond to internal or external threats, chronic pain is perceived as a discomfort by patients, leading to somatic, emotional and social negative changes. Lifestyle, wrong seating habits and some occupations may contribute to chronic back pain. Therapy for chronic back pain should include not only pharmacological or invasive interventions, but mostly change of lifestyle, physiotherapy and non-pharmacological methods. The main objective of the paper was to compare subjective perception of the effectiveness of various methods for treatment of low back pain. In total, 100 patients were asked to fill the questionnaire after completing the treatment, whether conventional or non-pharmacological. We have aimed to analyze not only the perception of the patients, but also indicators of the patient's lifestyle, their nutrition and physical activity. Oral drugs was the most effective option perceived by the patients, followed by non-pharmacological methods, such as massages, heat application and acupuncture. At the same time, all patients who changed their lifestyle, for example reduced smoking and alcohol and increased physical activity, achieved better results in non-pharmacological treatment and experienced higher pain alleviation compared to the patients treated by medications only. Non-pharmacological therapy of chronic non-malignant low back pain could be an effective option offered in combination with medicaments and change of lifestyle.


Evidence, ethics, and values: a framework for health promotion.
We propose a new approach to guide health promotion practice. Health promotion should draw on 2 related systems of reasoning: an evidential system and an ethical system. Further, there are concepts, values, and procedures inherent in both health promotion evidence and ethics, and these should be made explicit. We illustrate our approach with the exemplar of intervention in weight, and use a specific mass-media campaign to show the real-world dangers of intervening with insufficient attention to ethics and evidence. Both researchers and health promotion practitioners should work to build the capacities required for evidential and ethical deliberation in the health promotion profession.


Combined Effects of Gestational Phthalate Exposure and Zinc Deficiency on Steroid Metabolism and Growth.
Disruption of steroid hormone signaling has been implicated independently in the developmental abnormalities resulting from maternal phthalate plasticizer exposure and developmental zinc deficiency. This study investigated if secondary zinc deficiency may result from dietary exposure to a low level of di-2-ethylhexyl phthalate (DEHP) through gestation and if this could be associated with altered steroid metabolism. The interaction between marginal zinc nutrition and DEHP exposure to affect pregnancy outcome, zinc status, and steroid metabolism was also assessed. For this purpose, rats were fed a diet containing an adequate (25 mg/kg) or marginal (10 mg/kg) level of zinc without or with DEHP (300 mg/kg) from gestation day (GD) 0 until GD 19. Steroid profiles were measured in dam liver, plasma, adrenal glands, and in fetal liver by UPLC/MS-MS. In dams fed the adequate zinc diet, DEHP exposure decreased maternal weight gain and led to hepatic acute-phase response and zinc accumulation. The latter could compromise zinc availability to the fetus. DEHP and marginal zinc deficiency caused several adverse effects on the maternal and fetal steroid profiles. Interactions between DEHP exposure and marginal zinc deficient nutrition affected 17OH pregnenolone and corticosterone, while pregnenolone levels were specifically affected by DEHP exposure. Maternal marginal zinc deficiency specifically affected maternal progesterone and aldosterone, and presented evidence of increased androgen aromatization activity in maternal and fetal tissues. Results stress the potential major impact of mild DEHP exposure on maternal/fetal steroid metabolism that can be potentiated by nutritional and chronic disease states leading to zinc deficiency.


The Incidence of Primary Systemic Vasculitis in Jerusalem: A 20-year Hospital-based Retrospective Study.
The incidence of primary systemic vasculitides varies among different geographic regions and ethnic origins. The aim of this study was to examine the incidence rates of vasculitides in the Jerusalem Jewish population, and to examine possible trends in incidence rates over a 20-year period. The clinical databases of inpatients at the 2 medical centers in Jerusalem were searched for patients with vasculitis diagnosed between 1990-2009. Individual records were then reviewed by one of the authors. The significance of trends in incidence rates throughout the study period was evaluated by Pearson correlation coefficient. The average annual incidence rate of polyarteritis nodosa was 3.6/million adults (95% CI 1.6-4.7). Incidence rates did not change significantly during this period (r = 0.39, p = 0.088). The incidence of granulomatosis with polyangiitis (GPA) was 4.1 (2.2-5.9) for the whole period, during which it increased significantly (r = 0.53, p < 0.05). The incidence of microscopic polyangiitis (MPA) was lower: 2.3 (1.2-3.5)/million. It also increased significantly (r = 0.55, p < 0.05). The incidence of eosinophilic granulomatosis with polyangiitis was 1.2 (0.4-1.9), which remained stable throughout the study period. The incidence of Takayasu arteritis was 2.1/million (95% CI 1.2-2.9), and it also remained stable. Giant cell arteritis (GCA) incidence was 8.1 (5.7-10.6)/100,000 population aged 50 years or older. In sharp contrast with other vasculitides, its incidence decreased significantly throughout the study period (r = -0.61, p < 0.01). The incidence rates of vasculitides in the Jewish population of Jerusalem are in the lower range of global incidence rates. While GPA and MPA incidence are increasing, GCA incidence is decreasing.


A phycocyanin probe as a tool for monitoring cyanobacteria in freshwater bodies.
In many countries, the presence of cyanobacteria in freshwater bodies used for both drinking water and recreational purposes is under increasing public health attention. Water managers are considering how to implement monitoring that leads to a minimization of the risks incurred by the users of potentially contaminated sites. To address this question, this study involved assessing the performance of a submersible probe for measuring phycocyanin-specific fluorescence as a function of cyanobacterial biomass, with the aim of applying it as a tool for surveillance management. Its advantages and limits compared to more traditional analyses are discussed. The monitoring of cyanobacteria in the water bodies of western France was carried out using a minifluorimeter specific to the fluorescence of phycocyanin, a pigment specific to cyanobacteria. The results are compared with the analyses recommended by the World Health Organisation (chlorophyll a and cell counting). This study based on nearly 800 samples shows a significant correlation between the phycocyanin content and the cyanobacterial biomass, expressed as the number of cells per mL (R2 = 0.73). This submersible probe is simple and rapid to use, making it possible to take into account horizontal and vertical heterogeneities in the proliferation growth. In this way, we are able to detect at an early stage the conditions that could potentially lead to a risk, in order to start sampling. Due to its sensitivity, this tool proves suitable for monitoring aimed at reducing the risks incurred by the users of contaminated sites and launching preventative actions. The use of the phycocyanin probe provides an effective tool to complement traditional analyses of cyanobacterial presence. It is suggested that a surveillance protocol based on phycocyanin concentration can significantly improved the accuracy of the extent of cyanobacterial bloom development in the light of spatial and temporal variabilities associated with these occurrences.


Development of the Neuro-Immune-Vascular Plexus in the Ventricular Zone of the Prenatal Rat Neocortex.
Microglial cells make extensive contacts with neural precursor cells (NPCs) and affiliate with vasculature in the developing cerebral cortex. But how vasculature contributes to cortical histogenesis is not yet fully understood. To better understand functional roles of developing vasculature in the embryonic rat cerebral cortex, we investigated the temporal and spatial relationships between vessels, microglia, and NPCs in the ventricular zone. Our results show that endothelial cells in developing cortical vessels extend numerous fine processes that directly contact mitotic NPCs and microglia; that these processes protrude from vessel walls and are distinct from tip cell processes; and that microglia, NPCs, and vessels are highly interconnected near the ventricle. These findings demonstrate the complex environment in which NPCs are embedded in cortical proliferative zones and suggest that developing vasculature represents a source of signaling with the potential to broadly influence cortical development. In summary, cortical histogenesis arises from the interplay among NPCs, microglia, and developing vasculature. Thus, factors that impinge on any single component have the potential to change the trajectory of cortical development and increase susceptibility for altered neurodevelopmental outcomes.


Antigenic relationship between American and African isolates of Blastomyces dermatitidis as determined by immunofluorescence.
The antigenic relationship between American and African isolates of Blastomyces dermatitidis was investigated through the use of the fluorescent antibody technique. Preliminary results suggest that the American and African isolates studies are not antigenically identical. The American isolates share antigens with the African ones; however, it appears that they also possess distinct antigens. Additional studies are necessary to confirm these findings and to draw any conclusion whether the African isolates represent a serotype(s) of B. dermatitidis or a distinct species.


[An atypical case of Marcus Gunn's syndrome].
The authors examine a clinical case of the Marcus Gunn phenomenon, characterized by the lid retraction when the patient closes her mouth. The peculiarity of this clinical case would consist in a partial synkinesis involving the masseter and temporal muscles.


Family Support and Its Association with Glycemic Control in Adolescents with Type 1 Diabetes Mellitus in Riyadh, Saudi Arabia.
The prevalence of type 1 diabetes mellitus (T1DM) among children in Saudi Arabia is increasing with unfavorable outcomes. Therefore, in addition to pharmacotherapy, other measures should be studied regarding psychological aspects mainly among adolescents. The family, which acts as the primary caregiver at this age, may play a major role in disease management. Thus, this study is aimed at assessing the perception of adolescents about the behaviors of their families initially and at investigating the correlation between these behaviors and glycemic control. Up to our knowledge, there was no study in Saudi Arabia that addressed this issue previously. This cross-sectional observational study assessed adolescents aged 10-19 years diagnosed with T1DM on insulin and receiving follow-up care at the King Saud University Medical City in Riyadh, Saudi Arabia. Data were collected via telephone interview and the verified "Modified Diabetes Social Support Questionnaire-Family version". Glycemic control was then assessed using the most recent hemoglobin A1c (HbA1c) level recorded in their electronic files. Fifty-six adolescents participated in this study with an equal sex distribution (each n = 28). Almost all participants were Saudis, and the majority were living in Riyadh (n = 41). The mean age was 16.1 ± 2.41 years with a mean of 6.1 ± 4.14 years history of diabetes. The mean HbA1c level was 9.6 ± 2.12%. Participants perceived all behaviors as supportive with "support in critical situations" being the highest (77.3%) and the only factor significantly related to HbA1c (p = 0.017). Age was significantly related to all factors (p > 0.05). Family plays a major role in the management of diabetes. Their supportive behaviors are perceived by their family members diagnosed with T1DM, but there has been no optimal association with disease control. However, the involvement of the family can aid in decreasing possible complications of the disease by intervening in critical situations.


Comparison of Macintosh and Intubrite laryngoscopes for intubation performed by novice physicians in a difficult airway scenario.
In the difficult airway, the intubation skills are critically important. In selected cases, particularly in airway edema, laryngeal or tongue edema, endotracheal intubation can turn out very difficult, and repeated attempts may even worsen the airway edema, causing trauma and bleeding, and finally leading to complete airway obstruction and inability to ventilate the patient. The aim of the study was to compare the efficacy of endotracheal intubation performed by novice physicians using a standard Macintosh laryngoscope and an Intubrite videolaryngoscope. The study was designed as a prospective, randomized, crossover, simulation study and continues our research assessing the effectiveness of selected endotracheal intubation techniques in prehospital settings. All participants were experienced with the Macintosh direct laryngoscope but remained novice to videolaryngoscopy. Instructions on the correct use of the Macintosh and Intubrite laryngoscopes were given before the procedure, and all the 30 novice physicians were allowed to practice at least 10 times before the study on manikin with normal airways. We employed an airway manikin (Trucorp Airsim Bronchi; Trucorp Ltd., Belfast, Northern Ireland) to simulate difficult airway, with was obtained by inflating the tongue with 50mL of air. The participants were asked to perform tracheal intubation using an endotracheal tube with 7.5mm of internal diameter (Portex; Smiths Medical, Hythe, UK) through the vocal cords, applying either a conventional Macintosh laryngoscope with a size 3 blade (MAC; Mercury Medical, Clearwater, FL, USA) or the Intubrite videolaryngoscope, also with a Macintosh No. 3 blade (INT; Intubrite Llc, Vista, CA, USA). In both intubation techniques, a guide stylet (Rusch Inc., Duluth, GA, USA) was introduced into the endotracheal tube in order to obtain a C-shape curve to facilitate tracheal intubation. Each participating physician was randomly assigned to three attempts of tracheal intubation with each device. The effectiveness of the first intubation attempt using MAC and INT was 63.6% and 53.4%, respectively (p=0.023), and the total percentage of intubation was 100% for both methods. The median time to intubation was 29.5 (interquartile range [IQR], 27-35.5) s with MAC, and 229 (IQR, 25.5-37) s with INT. The total of 24 physicians out of all study participants would choose MAC as a device to intubate with in real terms, while only 6 physicians would choose INT. During the simulation study, the novice physicians were able to perform endotracheal intubation at the same time using both the Macintosh and Intubrite videolaryngoscope. However, the efficacy of the first intubation attempt was higher for MAC. Further studies are needed to confirm the results.


Structure, fluorescent properties and proposed function in phototaxis of the stigma apparatus in the ciliate chlamydodon mnemosyne
Chlamydodon mnemosyne, a brackish-water ciliate which feeds on cyanobacteria, is capable of sensing the direction of light. Cells are negatively phototactic in the well-fed state and tend to swim towards the light source when mildly starved. Severely starved cells normally fail to show phototactic responses. An autofluorescent substance, which is present in all life cycle stages, occurs in, or immediately beneath, the plasma membrane of this ciliate. It is located in the anterior left side of a cell, in the same region where mildly starved cells accumulate small orange globules that form a structure known as the stigma. The diameter of the whole area where the autofluorescent substance is located appears to be smaller than the stigma; typically, it consists of two rows of blue-green fluorescence, each row subdivided into 5-10 squares. Since the blue-green autofluorescence is excited by both blue (450-490 nm) and near-ultraviolet (340-380 nm) light, it possibly originates from flavin- and/or pterin-like molecules. We suggest that the autofluorescent substance located in or beneath the plasma membrane of Chlamydodon mnemosyne acts as a photoreceptor pigment in phototaxis and that photo-orientation of this ciliate is triggered by a combined mechanism involving the photoreceptor and either the stigma or a number of light-absorbing food vacuoles as a shading device.


Percutaneous ethanol injection may be a definitive treatment for symptomatic thyroid cystic nodules not treatable by surgery: five-year follow-up study.
We present a prospective study on the long-term efficacy of percutaneous ethanol injection (PEI) treatment for thyroid cystic nodules. Among patients referred for symptomatic thyroid cystic nodules who had relapsed after two aspirations or whose nodules could not be aspirated due to the thickness of the cystic fluid, PEI was given when surgery was either refused or contraindicated. Forty-three patients were treated; the mean basal volume of the cysts was 38.4 mL. The purpose of the study was to evaluate long-term efficacy of PEI treatment on: (1) amelioration of symptoms and signs of local compression and (2) nodule volume reduction. In three subjects (7%), PEI failed to induce a significant (>50%) nodule reduction, so that surgical treatment was performed. In 40 patients (93%), an impressive nodule shrinkage was observed, reaching a plateau after 24 months (volume reduction = 91.9%+/-11.4%). A new PEI session was needed in two patients in whom a recurrence was noted within the first 6 months. After 6 months, no significant (> or =1 mL volume) nodule regrowth was observed up to 60 months. Both symptoms and tracheal displacement rapidly (within 1 month) and significantly (p<0.01) improved. After PEI, mild pain was the only side effect observed. No suspicious cytology was observed in any residual nodule greater than 1 mL 6 and 24 months after the last PEI session. Our data suggest that PEI is a first-line safe, effective, probably definitive, treatment for cystic thyroid nodules for which surgery is either refused or contraindicated.


Short-term administration of Qipian®, a mixed bacterial lysate, inhibits airway inflammation in ovalbumin-induced mouse asthma by modulating cellular, humoral and neurogenic immune responses.
Qipian® is a commercialized agent composed of extracts of three genera of commensal bacteria, and its mechanism of action on asthma is unclear. This study aimed to examine the impact of Qipian® on airway inflammation and investigate the underlying mechanisms. Qipian® or dexamethasone (DEX) was administered before OVA challenge in an ovalbumin-induced asthma mouse model, and then asthmatic symptoms were observed and scored. Samples of lung tissues, blood, and bronchoalveolar lavage fluid (BALF) were collected, and eosinophils (Eos), immunoglobins (Igs), and type 1 T helper (Th1)/Th2 cell cytokines were measured. Mucus production in the lung was assessed by periodic acid-Schiff (PAS) staining. The effects of Qipian® on dendritic and T regulatory (Treg) cells were investigated using flow cytometry. The short-term administration of Qipian® significantly inhibited the cardinal features of allergic asthma, including an elevated asthmatic behaviour score, airway inflammation and immune response. Histological analysis of the lungs showed that Qipian® attenuated airway inflammatory cell infiltration and mucus hyperproduction. Qipian® restored Th1/Th2 imbalance by decreasing interleukin (IL)-4, IL-5, and IL-13 while increasing interferon (IFN)-γ and IL-10. Further investigation revealed that Qipian® treatment induced the upregulation of CD4+CD25+Foxp3+ Treg cells and CD103+ DCs and downregulation of tachykinins neurokinin A (NKA) and NKB in the lung. Our findings suggested that short-term treatment with Qipian® could alleviate inflammation in allergic asthma through restoring the Th1/Th2 balance by recruiting Treg cells to airways and inducing the proliferation of CD103+ DCs, which actually provides a new treatment option for asthma.


Cytochrome p450 genotyping by multiplexed real-time dna sequencing with pyrosequencing technology.
Individual differences in xenobiotic metabolism influence the therapeutic value of many drugs and are of major concern during the development of new drug candidates. A number of polymorphic cytochrome p450 enzymes account for a significant part of this variation. A better understanding of these genetic factors would be of value for drug development, as well as clinical practice. To fulfill the goal of a personalized medicine, methods for simple and accurate assessment of cytochrome p450 genes are required. We report on the development of multiplex assays for genotyping of the cytochrome p450 drug-metabolizing enzymes CYP2D6, CYP2C9, and CYP2C19 with Pyrosequencing technology. Eleven variable positions, representing 12 of the most frequent alleles, were scored: CYP2D6 alleles *2, *3, *4, *6, *7, *8, and *14, CYP2C19 alleles *2, *3, and *4, and CYP2C9 alleles *2 and *3. Four multiplex Pyrosequencing reactions per patient sample were performed to cover these positions, using either simplex or multiplex PCR for amplification of target DNA sequences. Unequivocal genotypes were obtained for all patient samples, and the results were validated by comparing with results obtained using PCR-RFLP. For positions addressed with both methods, the results were in complete agreement. Pyrosequencing technology offers a highly automated, rapid, and accurate method for identification of cytochrome p450 alleles, which is suitable for pharmacogenomic research, as well as for routine assessment of patient genotypes.


Benefits of a dual sagittal crystal transducer for ultrasound imaging during I-125 seed implantation for permanent prostate brachytherapy.
To investigate whether a longer sagittal view and less movement using a dual sagittal crystal probe (DSCP) for trans rectal ultra sound (TRUS) allow for more accurate online-planning in I-125 permanent implant brachytherapy of the prostate, compared to a single sagittal crystal probe (SSCP). Between March 2008 and March 2010, 50 patients with prostate cancer were consecutively included in the study. The first 25 of these patients had both their pre- and online-planning based on a single sagittal crystal probe (SSCP). The treatment-plans of the other 25 patients were based on a DSCP TRUS. Three weeks after implantation a post-planning was made based on CT. TRUS online and CT post-plan dose-volume histogram (DVH) parameters, D(90) and V(100), were compared for both groups. Also, the post-plan DVH parameters of SSCP were compared to DSCP. The possible factors that might influence the post-plan D(90) and V(100) were analysed using Analysis of Variance (ANOVA). SSCP and DSCP online mean D(90) and V(100) were significantly larger than post-plan mean D(90) and V(100) (P < 0.01). The post-plan mean D(90) and mean V(100) were both non-significantly larger for SSCP based post-plans compared to DSCP based post plans (P = 0.76 and P = 0.68). ANOVA showed significant impact of prostate volume on the post-plan D(90) and V(100). The advantages of the dual sagittal crystal probe did not lead to more accurate online planning by investigating DVH-parameters. The only factor found to have influence on the DVH-parameters was the prostate volume.


Escherichia coli O157:H7 biofilm formation on Romaine lettuce and spinach leaf surfaces reduces efficacy of irradiation and sodium hypochlorite washes.
Escherichia coli O157:H7 contamination of leafy green vegetables is an ongoing concern for consumers. Biofilm-associated pathogens are relatively resistant to chemical treatments, but little is known about their response to irradiation. Leaves of Romaine lettuce and baby spinach were dip inoculated with E. coli O157:H7 and stored at 4 degrees C for various times (0, 24, 48, 72 h) to allow biofilms to form. After each time, leaves were treated with either a 3-min wash with a sodium hypochlorite solution (0, 300, or 600 ppm) or increasing doses of irradiation (0, 0.25, 0.5, 0.75, or 1 kGy). Viable bacteria were recovered and enumerated. Chlorine washes were generally only moderately effective, and resulted in maximal reductions of 1.3 log CFU/g for baby spinach and 1.8 log CFU/g for Romaine. Increasing time in storage prior to chemical treatment had no effect on spinach, and had an inconsistent effect on 600 ppm applied to Romaine. Allowing time for formation of biofilm-like aggregations reduced the efficacy of irradiation. D(10) values (the dose required for a 1 log reduction) significantly increased with increasing storage time, up to 48 h postinoculation. From 0 h of storage, D(10) increased from 0.19 kGy to a maximum of 0.40 to 0.43 kGy for Romaine and 0.52 to 0.54 kGy for spinach. SEM showed developing biofilms on both types of leaves during storage. Bacterial colonization of the stomata was extensive on spinach, but not on Romaine. These results indicate that the protection of bacteria on the leaf surface by biofilm formation and stomatal colonization can reduce the antimicrobial efficacy of irradiation on leafy green vegetables.


Progress in hereditary tauopathies: a mutation in the Tau gene (G389R) causes a Pick disease-like syndrome.
We describe the clinical and pathologic phenotypes of the G389R mutation in exon 13 of the Tau gene. Progressive aphasia and memory disturbance are the initial signs and begin in the fourth or fifth decade of life, followed by apathy, indifference, hyperphagia, rigidity, pyramidal signs and dementia. Death occurs after two to five years. Magnetic resonance imaging and neuropathologic studies show frontal and temporal atrophy. Pick body-like and axonal filamentous inclusions found in the neocortex and subcortical white matter, respectively, are tau immunoreactive. Immunoblot analysis of sarkosyl-insoluble tau shows two major bands of 60 and 64 kDa that, upon dephosphorylation, resolve into four bands of three- and four-repeat isoforms. Isolated tau filaments are often straight and occasionally twisted. Recombinant mutant tau protein shows a reduced ability to promote microtubule assembly, suggesting that this may be the primary effect of the mutation. The present findings indicate that the G389R mutation in Tau can cause a dementia similar to that in Pick's disease.


Association of Interleukin-1 gene polymorphisms with central obesity and metabolic syndrome in a coronary heart disease population.
The objective of this study was to determine whether single nucleotide polymorphisms (SNPs) in the Interleukin-1 (IL-1) gene family are associated with central obesity and metabolic syndrome in a coronary heart disease population. The IL-1 alpha C-889T (rs1800587) and IL-1 beta +3954 (rs1143634) SNPs were studied in a Western Australian coronary heart disease (CHD) population (N = 556). Subjects who were TT homozygous at either SNP had larger waist circumference (IL-1 alpha: 1.8 cm greater, P = 0.04; IL-1 beta: 4 cm greater, P = 0.0004) compared with major allele homozygotes. Individuals with two copies of the IL-1 alpha:IL-1 beta T:T haplotype had greater waist circumference (4.7 cm greater, P = 0.0001) compared to other haplotypes. There was a significant interaction between the IL-1 beta SNP and BMI level on waist circumference (P = 0.01). When the cohort was stratified by median BMI, TT carriers for IL-1 beta with above median BMI had greater waist circumference (6.1 cm greater, P = 0.007) compared to baseline carriers, whilst no significant association was seen in the below median group. Similarly, when the cohort was stratified by median fibrinogen level (IL-1 alpha interaction P = 0.01; IL-1 beta interaction P = 0.04), TT carriers for both SNPs in the above median fibrinogen group had greater waist circumference (IL-1 alpha 2.7 cm greater, P = 0.007; IL-1 beta 3.3 cm greater, P = 0.003) compared with major allele homozygotes. This association was not seen in the below median group. Also, we found a trend of increased metabolic syndrome for IL-1 beta TT homozygotes (P = 0.07). In conclusion, our findings suggest that in a CHD population IL-1 gene polymorphisms may be involved in increased central obesity, and the genetic influences are more evident among patients who have a higher level of obesity or inflammatory markers.


Mitochondrial targeted catalase suppresses invasive breast cancer in mice.
Treatment of invasive breast cancer has an alarmingly high rate of failure because effective targets have not been identified. One potential target is mitochondrial generated reactive oxygen species (ROS) because ROS production has been associated with changes in substrate metabolism and lower concentration of anti-oxidant enzymes in tumor and stromal cells and increased metastatic potential. Transgenic mice expressing a human catalase gene (mCAT) were crossed with MMTV-PyMT transgenic mice that develop metastatic breast cancer. All mice (33 mCAT positive and 23 mCAT negative) were terminated at 110 days of age, when tumors were well advanced. Tumors were histologically assessed for invasiveness, proliferation and metastatic foci in the lungs. ROS levels and activation status of p38 MAPK were determined. PyMT mice expressing mCAT had a 12.5 per cent incidence of high histological grade primary tumor invasiveness compared to a 62.5 per cent incidence in PyMT mice without mCAT. The histological grade correlated with incidence of metastasis with 56 per cent of PyMT mice positive for mCAT showing evidence of pulmonary metastasis compared to 85.4 per cent of PyMT mice negative for mCAT with pulmonary metastasis (p ≤ 0.05). PyMT tumor cells expressing mCAT had lower ROS levels and were more resistant to hydrogen peroxide-induced oxidative stress than wild type tumor cells, suggesting that mCAT has the potential of quenching intracellular ROS and subsequent invasive behavior. The metastatic tumor burden in PyMT mice expressing mCAT was 0.1 mm2/cm2 of lung tissue compared with 1.3 mm2/cm2 of lung tissue in PyMT mice expressing the wild type allele (p ≤ 0.01), indicating that mCAT could play a role in mitigating metastatic tumor progression at a distant organ site. Expression of mCAT in the lungs increased resistance to hydrogen peroxide-induced oxidative stress that was associated with decreased activation of p38MAPK suggesting ROS signaling is dependent on p38MAPK for at least some of its downstream effects. Targeting catalase within mitochondria of tumor cells and tumor stromal cells suppresses ROS-driven tumor progression and metastasis. Therefore, increasing the antioxidant capacity of the mitochondrial compartment could be a rational therapeutic approach for invasive breast cancer.


The unidimensionality of the five Brain Injury Rehabilitation Trust Personality Questionnaires (BIRT-PQs) may be improved: preliminary evidence from classical psychometrics.
Objective: To assess the internal construct validity (ICV) of the five Brain Injury Rehabilitation Trust Personality Questionnaires (BIRT-PQ) with Classical Test Theory methods.Methods: Multicenter cross-sectional study involving 11 Italian rehabilitation centers. BIRT-PQs were administered to patients with severe Acquired Brain Injury and their respective caregivers. ICV was assessed by the mean of an internal consistency analysis (ICA) and a Confirmatory Factor Analysis (CFA).Results: Data from 154 patients and their respective caregivers were pooled, giving a total sample of 308 subjects. Despite good overall values (alphas ranging from 0.811 to 0.937), the ICA revealed that several items within each scale did not contribute as expected to the total score. This result was confirmed by the CFA, which showed the misfit of the data to a unidimensional model (RMSEA ranging from 0.077 to 0.097). However, after accounting for local dependency found within the data, fitness to a unidimensional model improved significantly (RMSEA ranging from 0.050 to 0.062).Conclusion: Despite some limitations, our analyses demonstrated the lack of ICV for the BIRT-PQ total scores. It is envisaged that a more comprehensive ICV analysis will be performed with Rasch analysis, aiming to improve both the measurement properties and the administrative burden of each BIRT-PQ.


Intracellular recordings from cells in the myenteric plexus of the rat duodenum.
Intracellular recordings were made in vitro from neurons in the myenteric plexus of freshly dissected preparations of the duodenum of the rat. Nearly one-quarter of neurons (18 out of 77) had long after-hyperpolarizations following their action potentials. Over 60% of neurons (20 out of 32) which were tested exhaustively by focal stimulation at seven points around the recording site were seen to receive fast excitatory synaptic inputs. These were of very short duration (10-30 ms) and were reversibly blocked by the nicotinic antagonist hexamethonium. Only four out of 18 after-hyperpolarization cells (22%) had visible fast synaptic inputs. Seven out of 32 neurons tested received slow excitatory synaptic inputs lasting up to 60 s that were associated with a decrease in conductance and an increase in excitability. No evidence for muscarinic synaptic potentials was seen; only four cells out of 30 with fast excitatory postsynaptic potentials had slow excitatory synaptic potentials visible after a single-shot stimulus; in none of these were the slow excitatory postsynaptic potentials blocked by atropine (up to 1 x 10(-5) M). No inhibitory postsynaptic potentials were recorded in any of the 77 neurons recorded in this study. The effects of five neurotransmitter candidates (acetylcholine, GABA noradrenaline, 5-hydroxytryptamine and substance P) applied by pressure microejection were studied. It is concluded that most of the neurophysiological features reported in the extensively studied guinea-pig small bowel myenteric plexus are present in the rat duodenum. However, the apparent lack of muscarinic synaptic potentials and inhibitory synaptic potentials suggests that there may be some differences between the two species. Our recordings also differ slightly from recently reported studies of rat myenteric neurons grown in cell culture.


Good Nursing Is Good Antibiotic Stewardship.
: Resistance to antibiotics has increased dramatically in the United States, with serious associated medical, social, and economic consequences. The most promising approach to this national crisis is a new understanding of the need for the careful and responsible use of antibiotics, both for the benefit of society and for the optimal care of each patient. This multidisciplinary approach, called antimicrobial stewardship, has typically involved specialists but not necessarily nurses, who perform numerous antibiotic-related activities daily and should be an integral part of antimicrobial stewardship programs. In this article, we use patient examples to review several stewardship activities and illustrate how nurses are essential to the appropriate use of antibiotics.


Recombinant ecto-5'-nucleotidase (CD73) has long lasting antinociceptive effects that are dependent on adenosine A1 receptor activation.
Ecto-5'-nucleotidase (NT5E, also known as CD73) hydrolyzes extracellular adenosine 5'-monophosphate (AMP) to adenosine in nociceptive circuits. Since adenosine has antinociceptive effects in rodents and humans, we hypothesized that NT5E, an enzyme that generates adenosine, might also have antinociceptive effects in vivo. To test this hypothesis, we purified a soluble version of mouse NT5E (mNT5E) using the baculovirus expression system. Recombinant mNT5E hydrolyzed AMP in biochemical assays and was inhibited by alpha,beta-methylene-adenosine 5'-diphosphate (alpha,beta-me-ADP; IC50 = 0.43 microM), a selective inhibitor of NT5E. mNT5E exhibited a dose-dependent thermal antinociceptive effect that lasted for two days when injected intrathecally in wild-type mice. In addition, mNT5E had thermal antihyperalgesic and mechanical antiallodynic effects that lasted for two days in the complete Freund's adjuvant (CFA) model of inflammatory pain and the spared nerve injury (SNI) model of neuropathic pain. In contrast, mNT5E had no antinociceptive effects when injected intrathecally into adenosine A1 receptor (A1R, Adora1) knockout mice. Our data indicate that the long lasting antinociceptive effects of mNT5E are due to hydrolysis of AMP followed by activation of A1R. Moreover, our data suggest recombinant NT5E could be used to treat chronic pain and to study many other physiological processes that are regulated by NT5E.


SOCS3 expression correlates with severity of inflammation in mouse hepatitis virus strain 3-induced acute liver failure and HBV-ACLF.
Recently, suppressor of cytokine signaling-3 (SOCS3) has been shown to be an inducible endogenous negative regulator of Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway which is relevant in inflammatory response, while its functions in acute liver failure and HBV-induced acute-on-chronic liver failure (HBV-ACLF) have not been fully elucidated. In this study, we explored the role of SOCS3 in the development of mouse hepatitis virus strain 3 (MHV-3)-induced acute liver failure and its expression in liver and peripheral blood mononuclear cells (PBMCs) of patients with HBV-ACLF. Inflammation-related gene expression was detected by real-time PCR, immunohistochemistry and Western blotting. The correlation between SOCS3 level and liver injury was studied. Our results showed that the SOCS3 expression was significantly elevated in both the liver tissue and PBMCs from patients with HBV-ACLF compared to mild chronic hepatitis B (CHB). Moreover, a time course study showed that SOCS3 level was increased remarkably in the liver of BALB/cJ mice at 72 h post-infection. Pro-inflammatory cytokines, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, were also increased significantly at 72 h post-infection. There was a close correlation between hepatic SOCS3 level and IL-6, and the severity of liver injury defined by alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, respectively. These data suggested that SOCS3 may play a pivotal role in the pathogenesis of MHV-3-induced acute liver failure and HBV-ACLF.


Na/K/Cl co-transport and its regulation.
NaCl and Na/K/Cl co-transport systems in many cell types show a number of similarities, among which are sensitivity to 'loop' diuretic inhibition and extremely high anion selectivity. Avian erythrocytes possess a NA+K+2Cl co-transporter that is stimulated by agents raising intracellular cAMP. The system is also inhibited following ATP-depletion of the cells, in agreement with results in other tissues; this nucleotide may exert a regulatory role on the operation of the co-transporter. A Na/K/Cl co-transport system is also present in flounder intestine, where it plays a central role in salt absorption at the luminal border of the tissue. In contrast to the avian erythrocyte this system is inhibited by raising intracellular cyclic nucleotide content, cGMP being more effective than cAMP. From these results it is concluded that second messenger regulation of Na/K/Cl co-transport processes is heterogeneous and may exhibit some tissue specificity.


Cytokines and male infertility.
Many male infertility cases have no apparent cause, being characterized as idiopathic. Both inflammation and obesity have long been associated with infertility. On one hand, inflammation, such as orchitis and male accessory gland infections (MAGIs), are regulated by inflammatory cytokines. The latter are also produced in the testis by Leydig and Sertoli cells, being associated with gap junctional communication at the blood-testis barrier. Furthermore, they regulate spermatogenesis through cell interaction, Toll-like receptors and production of reactive oxygen species. Additionally, they affect testosterone production, acting at many levels of the pituitary - gonadal axis. Any imbalance in their production may result in infertility. On the other hand, obesity has also been associated with infertility. Adipokines, cytokines produced by white adipose tissue, regulate the lipid and glucose metabolism and the inflammatory system. Recent data on leptin show that it regulates reproduction by adjusting hypothalamus - pituitary - gonadal axis at both the central and peripheral levels. In this regard, resistin, visfatin and the GH secretagogue peptic hormone ghrelin affect spermatogenesis, whereas data on adiponectin are rather scarce. In conclusion, inflammatory cytokines and adipokines seem to have a pivotal role in the regulation of spermatogenesis; any imbalance in this stable environment may lead to infertility. Nevertheless, further studies are needed to clarify their exact role.


Ineffective control of Epstein-Barr-virus-induced autoimmunity increases the risk for multiple sclerosis.
Multiple sclerosis (MS) is a demyelinating disease of the CNS. Epstein-Barr virus (EBV) contributes to the MS pathogenesis because high levels of EBV EBNA386-405-specific antibodies cross react with the CNS-derived GlialCAM370-389. However, it is unclear why only some individuals with such high autoreactive antibody titers develop MS. Here, we show that autoreactive cells are eliminated by distinct immune responses, which are determined by genetic variations of the host, as well as of the infecting EBV and human cytomegalovirus (HCMV). We demonstrate that potent cytotoxic NKG2C+ and NKG2D+ natural killer (NK) cells and distinct EBV-specific T cell responses kill autoreactive GlialCAM370-389-specific cells. Furthermore, immune evasion of these autoreactive cells was induced by EBV-variant-specific upregulation of the immunomodulatory HLA-E. These defined virus and host genetic pre-dispositions are associated with an up to 260-fold increased risk of MS. Our findings thus allow the early identification of patients at risk for MS and suggest additional therapeutic options against MS.


The existence and evolution of morphotypes in Anolis lizards: coexistence patterns, not adaptive radiations, distinguish mainland and island faunas.
The evolution of distinct ecologies and correlated morphologies ("ecomorphs," in combination) among similar species allows sympatric occupation of diverse microhabitats. Particular ecomorphs may evolve repeatedly, that is, convergently, as separate lineages arrive at similar solutions. Caribbean Anolis lizards (anoles) are a classic ecomorph system, particularly well-studied for the diverse morphotypes resulting from adaptive radiations. But few studies have analyzed the equally species-diverse mainland Anolis. Here, we use clustering analyses of nine traits for 336 species of Anolis to objectively identify morphological groups (morphotypes). We analyze the presence of recovered morphotypes on mainland and islands in general and relative to the composition of 76 mainland and 91 island anole assemblages. We test for evolutionary convergence of morphotypes within and between mainland and island environments by mapping our recovered morphotypes onto recent phylogenetic estimates and by analyzing four of our measured traits using program SURFACE. We find that particular morphotypes tend to be restricted to either mainland or island environments. Morphotype diversity and convergence are not concentrated within either island or mainland environments. Morphotype content of assemblages differs between mainland and island areas, with island assemblages displaying greater numbers of morphotypes than mainland assemblages. Taken with recent research, these results suggest a restructuring of one of the classic adaptive radiation stories and a reconsideration of research concerning island-mainland faunal differences. Island radiations of anoles are unexceptional relative to mainland radiations with regard to species count, rates of speciation and phenotypic evolution, morphotype diversity, and rates of convergence. But local island assemblage appear to be more diverse than mainland assemblages. The explanation for this assemblage disparity may reside in one of the classic hypothesized island-mainland environmental differences (i.e., greater numbers of predators/competitors/environmental complexity on the mainland). Similarity between mainland and island anole radiations may indicate exceptional evolution in the anole clade overall or ordinary evolution in an extraordinarily studied clade.


The platysma muscle in neck dissection.
Although the platysma muscle is usually preserved during neck dissection, removal of this muscle is generally considered inconsequential. The present case report shows that sacrifice of the cervical branch of the facial nerve innervating this muscle and removal of the platysma's upper portion impairs the caudal retraction and eversion of the ipsilateral half of the lower lip in grinning or laughing.


Time origin and structural analysis of the induced CRISPR/cas9 megabase-sized deletions and duplications involving the Cntn6 gene in mice.
In a previous study using one-step CRISPR/Cas9 genome editing in mouse zygotes, we created five founders carrying a 1,137 kb deletion and two founders carrying the same deletion, plus a 2,274 kb duplication involving the Cntn6 gene (encoding contactin-6). Using these mice, the present study had the following aims: (i) to establish stage of origin of these rearrangements; (ii) to determine the fate of the deleted DNA fragments; and (iii) to estimate the scale of unpredicted DNA changes accompanying the rearrangements. The present study demonstrated that all targeted deletions and duplications occurred at the one-cell stage and more often in one pronucleus only. FISH analysis revealed that there were no traces of the deleted DNA fragments either within chromosome 6 or on other chromosomes. These data were consistent with the Southern blot analysis showing that chromosomes with deletion often had close to expected sizes of removed DNA fragments. High-throughput DNA sequencing of two homozygotes for duplication demonstrated that there were no unexpected significant or scale DNA changes either at the gRNA and joint sites or other genome sites. Thus, our data suggested that CRISPR/Cas9 technology could generate megabase-sized deletions and duplications in mouse gametes at a reasonably specific level.


[Advances in anti-thrombotic therapy].
Improved understanding of the mechanisms of thrombogenesis has led to the discovery of new antithrombotic agents, anticoagulants, antiplatelets and fibrinolytics. Although most of them are still under development, low molecular weight heparins, glycoprotein IIb/IIIa receptor antagonists, inhibitors of the ADP receptor of platelets and new fibrinolytics have already proved their efficacy in the clinical setting. Compounds are being developed that have the potential to prevent and treat thrombosis by modulating vessel wall function.


Ellipsometry with polarisation-entangled photons.
Polarisation-entangled photon pairs from a two crystal, type-I spontaneous parametric down conversion source are used to make accurate measurements of the ellipsometric angles of a silicon dioxide film on silicon and of internal and external reflection from BK7 glass. Since our source produces an entangled state with some mixture, a novel technique based on quantum tomography was developed to estimate the components of the density matrix for the state before and after reflection from the samples. The ellipsometric angles are readily calculated from these components and experimental measurements made on the samples were found to be in good agreement with their expected values.


Evaluation After Sudden Death in the Young: A Global Approach.
Sudden cardiac death is defined as a death occurring usually within an hour of onset of symptoms, arising from an underlying cardiac disease. Sudden cardiac death is a complication of a number of cardiovascular diseases and is often unexpected. In individuals aged <35 years, unexplained sudden cardiac death is the most common presentation. A significant proportion of sudden cardiac death in the young (≤35 years) events may be precipitated by underlying inherited cardiac conditions, including both heritable cardiomyopathies and inherited arrhythmia syndromes (also known as cardiac channelopathies). Tragically, sudden death may be the first manifestation of the disease in a family and, therefore, clinical and genetic evaluation of surviving family members forms a key role in diagnosing the underlying inherited cardiac condition in the family. This is particularly relevant when considering that most inherited cardiac conditions are inherited in an autosomal dominant manner meaning that surviving family members have a 50% chance of inheriting the same disease substrate. This review will outline the underlying causes of sudden cardiac death in the young and outline our universal approach to familial evaluation following a young person's sudden death.