Mulberry leaf diet protects against progression of experimental autoimmune myocarditis to dilated cardiomyopathy via modulation of oxidative stress and MAPK-mediated apoptosis.
To examine the protective effects of dietary administration of Mulberry leaves (ML) on postmyocarditis dilated cardiomyopathy (DCM) focusing on oxidative and endoplasmic reticulum stresses and adverse myocardial remodeling. In this study, we used a rat model of cardiac myosin-induced experimental autoimmune myocarditis to test the effects of ML diet (MLD) (5%) on various markers of cardiac remodeling and function. After 4 weeks of immunization, the rats were fed with 5% MLD for 4 weeks. By the end of the study, echocardiography was performed to assess the myocardial dimensions. The heart tissue was used for histopathology and Western blotting analyses. Our study showed that the postmyocarditis rats exhibited increased oxidative stress when compared with the control rats. MLD supplementation suppressed this change, compared with vehicle treatment. In addition, postmyocarditis rats showed significant elevation of the endoplasmic reticulum stress markers, which were prevented by the MLD supplementation. Similarly the vehicle-treated rats suffered with the adverse myocardial remodeling in the form of fibrosis as evidenced by the Azan-Mallory staining and immunohistochemistry for collagen-III levels, compared with the control rats. However, MLD treatment not only markedly attenuated cardiac fibrosis, but also improved the left ventricular ejection fraction and fractional shortening. Interestingly, the myocardial levels of endothelin-1, activated members of mitogen-activated protein kinase (MAPK) pathway, and vascular endothelial growth factor (VEGF) were significantly attenuated by MLD, indicating that the antihypertrophic effects of MLD are partially mediated via endothelin-1, MAPK, and VEGF pathway. Collectively, these results suggest that supplementation of rats with 5% MLD has the ability to regulate cardiac remodeling and improves cardiac function and hence contributes to prevent the development of postmyocarditis dilated cardiomyopathy.


Preferential Recruitment of Neutrophils into the Cerebellum and Brainstem Contributes to the Atypical Experimental Autoimmune Encephalomyelitis Phenotype.
The JAK/STAT pathway is critical for development, regulation, and termination of immune responses, and dysregulation of the JAK/STAT pathway, that is, hyperactivation, has pathological implications in autoimmune and neuroinflammatory diseases. Suppressor of cytokine signaling 3 (SOCS3) regulates STAT3 activation in response to cytokines that play important roles in the pathogenesis of neuroinflammatory diseases, including IL-6 and IL-23. We previously demonstrated that myeloid lineage-specific deletion of SOCS3 resulted in a severe, nonresolving atypical form of experimental autoimmune encephalomyelitis (EAE), characterized by lesions, inflammatory infiltrates, elevated STAT activation, and elevated cytokine and chemokine expression in the cerebellum. Clinically, these mice exhibit ataxia and tremors. In this study, we provide a detailed analysis of this model, demonstrating that the atypical EAE observed in LysMCre-SOCS3(fl/fl) mice is characterized by extensive neutrophil infiltration into the cerebellum and brainstem, increased inducible NO synthase levels in the cerebellum and brainstem, and prominent axonal damage. Importantly, infiltrating SOCS3-deficient neutrophils produce high levels of CXCL2, CCL2, CXCL10, NO, TNF-α, and IL-1β. Kinetic studies demonstrate that neutrophil infiltration into the cerebellum and brainstem of LysMCre-SOCS3(fl/fl) mice closely correlates with atypical EAE clinical symptoms. Ab-mediated depletion of neutrophils converts the atypical phenotype to the classical EAE phenotype and, in some cases, a mixed atypical/classical phenotype. Blocking CXCR2 signaling ameliorates atypical EAE development by reducing neutrophil infiltration into the cerebellum/brainstem. Thus, neutrophils lacking SOCS3 display elevated STAT3 activation and expression of proinflammatory mediators and play a critical role in the development of atypical EAE.


Faster, sharper, more precise: Automated Cluster-FLIM in preclinical testing directly identifies the intracellular fate of theranostics in live cells and tissue.
Fluorescence microscopy is widely used for high content screening in 2D cell cultures and 3D models. In particular, 3D tissue models are gaining major relevance in modern drug development. Enabling direct multiparametric evaluation of complex samples, fluorescence lifetime imaging (FLIM) adds a further level to intensity imaging by the sensitivity of the fluorescence lifetime to the microenvironment. However, the use of FLIM is limited amongst others by the acquisition of sufficient photon numbers without phototoxic effects in live cells. Herein, we developed a new cluster-based analysis method to enhance insight, and significantly speed up analysis and measurement time for the accurate translation of fluorescence lifetime information into pharmacological pathways. Methods: We applied a fluorescently-labeled dendritic core-multishell nanocarrier and its cargo Bodipy as molecules of interest (MOI) to human cells and reconstructed human tissue. Following the sensitivity and specificity assessment of the fitting-free Cluster-FLIM analysis of data in silico and in vitro, we evaluated the dynamics of cellular molecule uptake and intracellular interactions. For 3D live tissue investigations, we applied multiphoton (mp) FLIM. Owing to Cluster-FLIM's statistics-based fitting-free analysis, we utilized this approach for automatization. Results: To discriminate the fluorescence lifetime signatures of 5 different fluorescence species in a single color channel, the Cluster-FLIM method requires only 170, respectively, 90 counts per pixel to obtain 95% sensitivity (hit rate) and 95% specificity (correct rejection rate). Cluster-FLIM revealed cellular interactions of MOIs, representing their spatiotemporal intracellular fate. In a setting of an automated workflow, the assessment of lysosomal trapping of the MOI revealed relevant differences between normal and tumor cells, as well as between 2D and 3D models. Conclusion: The automated Cluster-FLIM tool is fitting-free, providing images with enhanced information, contrast, and spatial resolution at short exposure times and low fluorophore concentrations. Thereby, Cluster-FLIM increases the applicability of FLIM in high content analysis of target molecules in drug development and beyond.


Distributed cognitive aid with scheduling and interactive task guidance.
A cognitive assistive technology system has been designed for use by people with memory and organizational impairments. This system will provide a distributed architecture for both scheduling assistance and task guidance, as well as intelligent, automatic replanning on the levels of both the schedule and individual tasks. A prototype of this architecture has been developed that focuses on interactive task guidance capabilities. Scheduling software has been developed but not fully integrated with the task guidance features. The system has been preliminarily tested through simulated trials, monitored use of the prototype in a clinical setting, and usability trials of the task-design interface with rehabilitation professionals. Participants were able to respond appropriately to cues provided by the system and complete prescribed tasks.


Role of aggregation conditions in structure, stability, and toxicity of intermediates in the Abeta fibril formation pathway.
beta-amyloid peptide (Abeta) is one of the main protein components of senile plaques associated with Alzheimer's disease (AD). Abeta readily aggregates to forms fibrils and other aggregated species that have been shown to be toxic in a number of studies. In particular, soluble oligomeric forms are closely related to neurotoxicity. However, the relationship between neurotoxicity and the size of Abeta aggregates or oligomers is still under investigation. In this article, we show that different Abeta incubation conditions in vitro can affect the rate of Abeta fibril formation, the conformation and stability of intermediates in the aggregation pathway, and toxicity of aggregated species formed. When gently agitated, Abeta aggregates faster than Abeta prepared under quiescent conditions, forming fibrils. The morphology of fibrils formed at the end of aggregation with or without agitation, as observed in electron micrographs, is somewhat different. Interestingly, intermediates or oligomers formed during Abeta aggregation differ greatly under agitated and quiescent conditions. Unfolding studies in guanidine hydrochloride indicate that fibrils formed under quiescent conditions are more stable to unfolding in detergent than aggregation associated oligomers or Abeta fibrils formed with agitation. In addition, Abeta fibrils formed under quiescent conditions were less toxic to differentiated SH-SY5Y cells than the Abeta aggregation associated oligomers or fibrils formed with agitation. These results highlight differences between Abeta aggregation intermediates formed under different conditions and provide insight into the structure and stability of toxic Abeta oligomers.


Force assessment of the stimulated arm flexors: quantification of contractile properties.
The primary objective was to develop equipment and evaluate protocols for non-invasive assessment of contractile properties of human arm flexors. The research design consisted of a non-randomized control trial, with repeated measures. Data from six males and two females were gathered in a clinical research laboratory. The elbow flexor torque following motor point or direct nerve stimulation was measured in response to single pulses or short trains of electrical pulses. Length--tension relationships were determined; comparative data were obtained at the identified optimal muscle lengths. Twitch waveforms and peak torques following either type of stimulation were reproducible (within 10%). Peak torques following a 4-pulse small interpulse interval stimulation were nearly identical for motor-point activation and direct nerve stimulation (15.2+/- 6.6Nm for motor point stimulation; 14.5 +/- 6.6Nm for nerve stimulation). Average perceived pain indexes associated with 4-pulse stimuli were slightly higher following nerve stimulation (782 for nerve versus 6.23 for motor-point, n=8). A reliable methodology (motor-point stimulation) has been identified to perform stimulated force assessment of human arm flexors.


Cardiogenic Shock in a Hemodialyzed Patient on Flecainide: Treatment with Intravenous Fat Emulsion, Extracorporeal Cardiac Life Support, and CytoSorb® Hemoadsorption.
A 67-year-old woman with a history of end-stage renal disease on hemodialysis received a therapeutic dose (150 mg daily) of flecainide for three weeks. She was admitted to the Emergency Department for malaise and dizziness, and the electrocardiogram revealed ventricular tachycardia treated by amiodarone. Hemodynamic condition remained stable, and the toxicity of flecainide was initially not suspected until she developed within 8 hours a cardiogenic shock requiring vasopressors. The patient then received sodium bicarbonate (300 mmol) and dobutamine but experienced cardiac arrest two hours later. The administration of intravenous fat emulsion (IFE) was associated with return of spontaneous circulation, but there was a relapse of cardiovascular shock at the end of IFE infusion. The patient was placed on extracorporeal cardiac life support (ECLS), continuous hemofiltration, and hemoadsorption using the CytoSorb® cartridge. Serial determinations of serum flecainide concentration were obtained during the course of hemoadsorption, with a terminal half-life of 3.7 h during the first four hours and a global plasma clearance of 40.3 ml/min over the first 22 hours. The weaning of ECLS was possible on day 7. Intravenous fat emulsion infusion was followed by a significant increase in serum flecainide concentration. In addition, while conventional techniques of extrarenal epuration usually appear as poorly effective for flecainide removal, a mean plasma clearance of 40.3 ml/min was observed using the hemoadsorption technique based on CytoSorb® cartridge. However, the impact on the clinical course was probably extremely modest in comparison with ECLS.


Changes in brain susceptibility in Wilson's disease patients: a quantitative susceptibility mapping study.
To assess changes in the susceptibility of the caudate nucleus (CN), putamen, and globus pallidus (GP) in patients with neurological and hepatic Wilson's disease (WD) by quantitative susceptibility mapping (QSM). The brain MRI images of 33 patients diagnosed with WD and 20 age-matched controls were analysed retrospectively. All participants underwent brain T1-weighted, T2-weighted, and QSM imaging using a 1.5 T magnetic resonance imaging (MRI) machine. QSM maps were evaluated with the STISuite toolbox. The quantitative susceptibility levels of the CN, putamen, and GP were analysed using region of interest analysis on QSM maps. Differences among neurological WD patients, hepatic patients, and controls were determined. Susceptibility levels were significantly higher for all examined structures (CN, putamen and GP) in patients with neurological WD compared with controls (all p<0.05) and hepatic WD patients (all p<0.05). No statistically significant differences were found in susceptibility levels between patients with hepatic WD and controls (all p>0.05). The QSM technique is a valuable tool for detecting changes in brain susceptibility in WD patients, indicating abnormal metal deposition. Notably, the current findings suggest that neurological WD patients exhibit more severe susceptibility changes compared with hepatic WD patients. Therefore, QSM can be utilised as a complementary method to detect brain injury in WD patients.


A probabilistic approach to compare the risk associated with heavy metals and bromine in honey from Dominican Republic, Mexico, Mozambique and Spain.
This study aims to analyse the risk to consumers given the presence of heavy metals and bromine in honey from different countries. A probabilistic approach was applied to assess carcinogenic risk. Concerning exposure, Al in Spain (3.3E-04 mg/kgBw/day), B in Dominican Republic and Mexico (2E-04 mg/kgBw/day in both cases) and Fe in Mexico and Mozambique had the highest values (5E-05 and 4.8E-05 mg/kgBw/day). In risk characterisation, the values were less than 1 for hazard index (HI), meaning that the consumption of honey represents a low level of concern for non-genotoxic effects. A combination of margin of exposure and probability of exceedance results that exposure to Pb pose no threat. The probability of suffering cancer for Br, Cd, Ni and Pb was lower than 1.0E-06 and, therefore, considered safe. However, the risk at the 95th percentile of Br in Dominican Republic was 1.18E-04 in adults and 2.45E-04 in children, exceeding 1.0E-04, and therefore, considered intolerable. Finally, the sensitivity analysis indicated that the most influential factor in the HI was the consumption in adults and the concentration of Ni in children, whereas for cancer risk, were the concentrations of Ni, Cd, Br and Pb, in both cases.


Proton Beam Therapy for Locally Advanced Head and Neck Tumors: An Analysis of Dosimetric and Clinical Outcomes.
Locally advanced tumors of the head and neck region often lie in close proximity to critical organs at risk (OARs). Providing effective treatment coverage to these malignancies while minimizing radiation dose to surrounding OARs is advantageous. Our aim is to compare dosimetric data of OARs from proton beam therapy (PBT) plans to volumetric modulated arc therapy (VMAT) treatment plans, and to evaluate clinical outcomes in patients treated with PBT. We identified patients with locally advanced head and neck tumors treated with PBT at our institution from 2016 to 2019. Study endpoints included mean and maximum doses for the OAR structures for each treatment plan, overall survival, time to local-regional or distant progression, and presence of acute and late toxicities. Mean and maximum doses to OAR structures were compared between treatment modalities using a paired Wilcoxon signed-rank test. P-values <0.05 were considered significant. A total of 42 patients were identified. Clinical target volume coverage was >95% for both PBT and VMAT plans. PBT plans showed a significant reduction to the mean doses to all OARs, and max doses to most OARs (P<0.05). The largest reduction mean dose was seen in the contralateral cochlea and parotid glands at 71% and 75%, respectively. Median follow-up was 27 months. Overall survival at 4 years was 44.75%. Freedom from local-regional progression was 73.28% at 2 years. The majority of patients developed Common Terminology Criteria for Adverse Events (CTCAE) grade I dermatitis, mucositis, or both. PBT resulted in meaningful dose reductions to OARs while maintaining comparable target coverage when compared with VMAT plans. Further refinements to proton therapy may have the potential to further minimize dose to critical structures.


Escherichia coli promoter -10 and -35 region homologies correlate with binding and isomerization kinetics.
The DNA promoter sequence at which gene transcription is initiated in Escherichia coli contains two distinct regions of conserved nucleotides. Coefficients of homology to the -10 region and the -35 region were computed for many different prokaryotic promoters. Linear equations were derived that relate the degree of homology for each promoter region to the two kinetic constants that describe the interaction of RNA polymerase with the promoter site on DNA: the strength KB of binding to form closed complex, and the rate kf of isomerization to form open complex. A graphical plot of -35 versus -10 promoter region homologies for many promoters suggest that certain classes of prokaryotic operons might utilize differential degrees of consensus homology in these two regions to achieve specific control over kf and KB, in addition to modulating overall promoter strength.


A case of multiple skeletal anomalies, ectodermal dysplasia, and severe growth and mental retardation.
A 17-year-old female patient presented extreme growth failure, severe microcephaly and developmental delay, and a unique pattern of congenital anomalies, predominantly of the skeleton and the skin. Prominent findings included hidrotic ectodermal dysplasia with virtually complete absence of body hair, ichthyosiform hyperkeratosis of the skin over the lower legs, dysplasia of toenails; small hands and feet with with short fifth fingers and toes complete cutaneous syndactyly between toes 4 and 5; in X-rays, fusion of several vertebral bodies, humero-radial ankylosis, fusion between talus and navicular bone, lunate and triquetral, and proximal fusion between metacarpals 4 and 5; and luxation of the right femoral head. The patient might represent a hitherto undescribed malformation syndrome of unknown etiology.


Hematopoietic disorders in Down syndrome.
Patients with Down syndrome have an increased risk of developing various hematological disorders. In this article, the clinical characteristics and differential diagnosis of the hematological disorders associated with Down syndrome are reviewed, and the underlying molecular mechanisms discussed.


Flexibility and critical hydrogen bonds in cytochrome c.
We show that protein flexibility can be characterized using graph theory, from a single protein conformation. Covalent and hydrogen bonds are modeled by distance and angular constraints, and a map is constructed of the regions in this network that are flexible or rigid, based on whether their dihedral bonds remain rotatable or are locked by other interactions in the network. This analysis takes only a second on a typical PC, and interatomic potentials; the most time-consuming aspect of molecular dynamics calculations, are not required. Our preliminary work has shown that this approach identifies the experimentally observed, biologically important flexible regions in HIV protease and lysine-arginine-ornithine binding protein. Here we analyze three evolutionarily distant cytochromes c, and find strong similarity between their flexible regions, despite having only 39% sequence identity. Furthermore, we show how the structural flexibility increases as the weaker hydrogen bonds are removed, as would happen under thermal denaturation of the protein. This approach identifies the critical hydrogen bonds that cross-link the tertiary structure.


Comorbid Vulvar Lichen Planus and Lichen Sclerosus.
The aims of the study are to assess the histopathologic characteristics of vulvar biopsies consistent with lichen planus (LP) in women with a previous or concurrent histopathologic diagnosis of vulvar lichen sclerosus (LS) and to describe the clinical features of comorbid LP and LS. Patients were included if a diagnosis of LP was confirmed after review of the hematoxylin and eosin slides and the histopathology reporting LS noted a band of abnormal collagen. Data were collected on anatomic site, clinical appearance, histopathology, microbiology, treatment, and follow-up. There were 31 cases with a mean age of 69.5 years. Thirty specimens showed erosive LP, of which 22 were from inner labium minus and 8 from vestibule. There were no significant differences between biopsy site in epithelial thickness, erosion, lymphocytic infiltrate, or basal layer pattern. One third of cases showed a regenerative pattern of LP. Of the 26 patients with clinical records available, erythema at the biopsy site was noted in all cases; in 23 the notes specified central erythema and peripheral pallor. Forty-six percent were prescribed topical corticosteroids before biopsy. All 26 were treated with topical corticosteroids, 23% were prescribed antimycotics, and 38% required other supplemental therapies. Comorbid vulvar LP and LS are not rare; clinicians suspecting one should evaluate for the other and consider separate biopsies of morphologically distinct areas. Clinicopathological correlation is an invaluable tool in assessing biopsies when both diagnoses are suspected, because the regenerative pattern of LP may otherwise be overlooked or misdiagnosed.


A data-smoothing approach to explore and test gene-environment interaction in case-parent trios.
Complex traits result from an interplay between genes and environment. A better understanding of their joint effects can help refine understanding of the epidemiology of the trait. Various tests have been proposed to assess the statistical interaction between genes and the environment (G×E) in case-parent trio data. However, these tests can lose power when the form of G×E departs from that for which the test was developed. To address this limitation, we propose a data-smoothing approach to estimate and test G×E between a single nucleotide polymorphism and a continuous environmental covariate. For estimating G×E, we fit a generalized additive model using penalized likelihood. The resulting point- and interval-estimates of G×E lead to a graphical display, which can serve as a visualization tool for exploring the form of interaction. For testing G×E, we propose a permutation approach, which accounts for the extra uncertainty introduced by the smoothing process. We investigate the statistical properties of the proposed methods through simulation. We also illustrate the use of the approach with an example data set. We conclude that the approach is useful for exploring novel interactions in data-rich settings.


Characterization and comparative 3D modeling of CmPI-II, a novel 'non-classical' Kazal-type inhibitor from the marine snail Cenchritis muricatus (Mollusca).
The complete amino acid sequence obtained by electrospray ionization tandem mass spectrometry of the proteinase inhibitor CmPI-II isolated from Cenchritis muricatus is described. CmPI-II is a 5480-Da protein with three disulfide bridges that inhibits human neutrophil elastase (HNE) (K(i) 2.6+/-0.2 nM), trypsin (K(i) 1.1+/-0.9 nM), and other serine proteinases such as subtilisin A (K(i) 30.8+/-1.2 nM) and pancreatic elastase (K(i) 145.0+/-4.4 nM); chymotrypsin, pancreatic and plasma kallikreins, thrombin and papain are not inhibited. CmPI-II shares homology with the Kazal-type domain and may define a new group of 'non-classical' Kazal inhibitors according to its Cys(I)-Cys(V) disulfide bridge position. The 3D model of CmPI-II exhibits similar secondary structure characteristics to Kazal-type inhibitors and concurs with circular dichroism experiments. A 3D model of the CmPI-II/HNE complex provides a structural framework for the interpretation of its experimentally determined K(i) value. The model shows both similar and different contacts at the primary binding sites in comparison with the structure of turkey ovomucoid third domain (OMTKY3)/HNE used as template. Additional contacts calculated at the protease-inhibitor interface could also contribute to the association energy of the complex. This inhibitor represents an exception in terms of specificity owing to its ability to strongly inhibit elastases and trypsin.


Patterns of computed tomography utilisation in injury management: latent classes approach using linked administrative data in Western Australia.
Whilst computed tomography (CT) imaging has been a vital component of injury management, its increasing use has raised concern regarding ionising radiation exposure. This study aims to identify latent classes (underlying patterns) of CT use over a 3-year period following the incidence of injury and factors predicting the observed patterns. A retrospective observational cohort study was conducted in 21,544 individuals aged 18 + years presenting to emergency departments (ED) of four tertiary public hospitals with new injury in Western Australia. Mixture modelling approach was used to identify latent classes of CT use over a 3-year period post injury. Amongst injured people with at least one CT scan, three latent classes of CT use were identified including a: temporarily high CT use (46.4%); consistently high CT use (2.6%); and low CT use class (51.1%). Being 65 + years or older, having 3 + comorbidities, history with 3 + hospitalisations and history of CT use before injury were associated with consistently high use of CT. Injury to the head, neck, thorax or abdomen, being admitted to hospital after the injury and arriving to ED by ambulance were predictors for the temporarily high use class. Living in areas of higher socio-economic disadvantage was a unique factor associated with the low CT use class. Instead of assuming a single pattern of CT use for all patients with injury, the advanced latent class modelling approach has provided more nuanced understanding of the underlying patterns of CT use that may be useful for developing targeted interventions.


Stable Expression of Basic Fibroblast Growth Factor in Chloroplasts of Tobacco.
Basic fibroblast growth factor (bFGF) is a multifunctional factor in acceleration of cell proliferation, differentiation and transference, and therefore widely used in clinical applications. In this study, expression vector pWX-Nt03 harboring a codon-optimized bFGF gene was constructed and introduced into the tobacco chloroplasts by particle bombardment. After four rounds of selection, bFGF was proved to integrate into the chloroplast genome of regenerated plants and two of four transgenic plants were confirmed to be homoplastomic by PCR and Southern hybridization. ELISA assay indicated that bFGF represented approximately 0.1% of total soluble protein in the leaves of transplastomic tobacco plants. This is the first report of bFGF expression via chloroplast transformation in model plant, providing an additional option for the production of chloroplast-produced therapeutic proteins.


Coherent amplification of radiation from two phase-locked Josephson junction arrays.
We analyze experimentally and theoretically mutual phase locking and electromagnetic interaction between two linear arrays with a large number of Josephson junctions. Arrays with different separation, either on the same chip or on two separate substrates are studied. We observe a large coherent gain, up to a factor of three, of emitted power from two simultaneously biased arrays, compared to the sum of powers from two individually biased arrays. The phenomenon is attributed to the phase locking of junctions in different arrays via a common electromagnetic field. Remarkably, the gain can exceed the factor of two expected for a simple constructive interference of two oscillators. The larger gain is explained by an additional consequence of mutual interaction between two large arrays. Mutual phase locking of large arrays does not only result in constructive interference outside the arrays, but also improved synchronization of junctions inside each array. Our conclusion is supported by numerical modelling.


OOC-3, a novel putative transmembrane protein required for establishment of cortical domains and spindle orientation in the P(1) blastomere of C. elegans embryos.
Asymmetric cell divisions require the establishment of an axis of polarity, which is subsequently communicated to downstream events. During the asymmetric cell division of the P(1) blastomere in C. elegans, establishment of polarity depends on the establishment of anterior and posterior cortical domains, defined by the localization of the PAR proteins, followed by the orientation of the mitotic spindle along the previously established axis of polarity. To identify genes required for these events, we have screened a collection of maternal-effect lethal mutations on chromosome II of C. elegans. We have identified a mutation in one gene, ooc-3, with mis-oriented division axes at the two-cell stage. Here we describe the phenotypic and molecular characterization of ooc-3. ooc-3 is required for the correct localization of PAR-2 and PAR-3 cortical domains after the first cell division. OOC-3 is a novel putative transmembrane protein, which localizes to a reticular membrane compartment, probably the endoplasmic reticulum, that spans the whole cytoplasm and is enriched on the nuclear envelope and cell-cell boundaries. Our results show that ooc-3 is required to form the cortical domains essential for polarity after cell division.


Return of autonomic nervous activity after delivery: role of aortocaval compression.
We have compared measures of heart rate variability (HRV) in 15 women in late pregnancy before and 3 months after delivery and in 20 non-pregnant controls, to study the effect of aortocaval compression on autonomic nervous activity. Normalized high-frequency power was used as an index of vagal activity and the low-/high-frequency power ratio as index of sympathovagal balance. We found that the decrease in vagal activity and increase in sympathovagal balance before delivery returned to normal 3 months after delivery. Percentage changes in vagal activity and sympathovagal balance 3 months after delivery in the left lateral decubitus position were least among three recumbent positions. The relief of aortocaval compression as a result of delivery of the fetus may be the main cause of return of autonomic nervous activity 3 months after delivery. Postpartum hormonal changes may also contribute to return of autonomic nervous activity after delivery.


[Urgent problems of prostatic cancer diagnosis in a small district clinic].
Diagnostic methods in prostatic pathology used in a surgical department of a small town of Pavlovo (Nizhny Novgorod Region) are analysed. Infrared spectroscopy was for the first time used in Pavlovo for diagnosis of cancer. Examination of 57 patients aged 38-89 years has detected prostatic cancer in 16 (28 +/- 5.9%) patients, chronic prostatitis in 6 (10.5 +/- 4%) patients, prostatic adenoma in 34 (59.6 +/- 6.4%) patients, prostatic abscess--in 1 (1.9 +/- 1.7%) patient. Infrared spectroscopy of the blood serum according to the proposed technique provides accurate (91.2 +/- 4.8%, p < 0.01) differential diagnosis of benign and malignant diseases of the prostate.


Attenuation of pressor response following intubation: Efficacy of nitro-glycerine lingual spray.
The role of nitro-glycerine (NTG) lingual spray for attenuation of the hemodynamic response associated with intubation is not much investigated. We conducted this study to evaluate the efficacy of NTG lingual pump or pen spray in attenuation of intubation induced hemodynamic responses and to elucidate the optimum dose. In a prospective randomized controlled trial, 90 adult patients of ASA I, II, 18-60 year posted for elective general surgery under general anesthesia with intubation were randomly allocated to three groups as Group C (control) - receiving no NTG spray, Group N1 - receiving 1 NTG spray and Group N2 - receiving 2 NTG spray one minute before intubation. Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate were recorded at baseline, just before intubation (i.e., 60 s just after induction and NTG spray), immediately after intubation, at 1, 2, 5 and 10 min after intubation. Incidence of hypertension was significantly higher in Group C (60%, n = 18) as compared to Group N1 and N2 (10%, n = 3 each), P < 0.01. Mean value of SBP, DBP and MAP showed a significant rise as compared to baseline, following intubation in control group (15.31% in SBP, 12.12% in DBP, 17.77% in MAP) that persisted till 5 min, while no significant rise was observed in Group N1 and N2. There was a trend toward fall in blood pressure in Group N2 (4.95% fall in SBP, 4.72% fall in MAP) 1-min following spray, which was clinically insignificant. Mean value of SBP, DBP and MAP was significantly higher in Group C than in Group N1, which was in turn greater than Group N2 (Group C > N1> N2), P < 0.05. However, incidence of tachycardia was comparable in three groups (70% in group C, 63.33% in Group N1 and 67.77% in Group N2, P > 0.05). We concluded that the NTG lingual spray in dose of 0.4 mg (1 spray) or 0.8 mg (2 sprays) was effective in attenuation of intubation induced hemodynamic response, in terms of preventing significant rise in SBP, DBP and MAP compared to control group.


Seroprevalence and risk factors of Toxoplasma gondii infection in rabbit of local Algerian population.
The objective of this investigation was to determine the seroprevalence and identify the risk factors of Toxoplasma gondii infection in the rabbit of the local Algerian population from five districts of Northern Algeria. Blood samples of 350 rabbits were collected and analyzed for the presence of anti-T. gondii immunoglobulin G antibodies using the indirect enzyme-linked immunosorbent assay. Additional data concerning the farms and management practices were obtained through a questionnaire used in surveys and interviews. The overall seroprevalence was 14.6% (51/350). The seroprevalence was significantly higher in outdoor rearing farms and was linked to the presence of animals from other species on the farm. A higher seroprevalence was found in older animals compared to younger ones. No difference in seroprevalence was noted with respect to the origin or gender of animals, type of cage, feed and water sources, presence of cats in the vicinity, hygiene status, or season. This study has shown that T. gondii prevalence in rabbits of the local population is relevant and may have important implications for public health in rural areas.


Pediatric patients hospitalized with myocarditis: a multi-institutional analysis.
The objective of this study was to identify the patient, institutional, and utilization characteristics associated with outcome in hospitalized pediatric patients with myocarditis. This was a nonconcurrent cohort study of all consecutive pediatric discharges from the 35 academic children's hospitals that are members of the Pediatric Health Information System (PHIS): patients from birth through age 21 years discharged from participating hospitals between January 1, 2005, and December 31, 2005. Patient-level, institution-level, and utilization variables were examined. A total of 427,615 patients were discharged, and 216 (0.05%) were diagnosed with myocarditis. Common etiologies were idiopathic (82%), related to other diseases (6%), and bacterial or viral (3%). Myocarditis patients required considerable support including intravenous immunoglobulin (IVIG; 49.1%), milrinone (45%), epinephrine (35%), mechanical ventilation (25%), extracorporeal membrane oxygenation (7%), and cardiac transplantation (5%). Even in patients with extreme illness scores, IVIG use did not impact survival (P = 0.67). Overall survival of myocarditis patients was 92%. Myocarditis patients who died presented with a higher severity of illness and required frequent use of extracorporeal membrane oxygenation and other ICU therapies. In conclusion, pediatric patients with myocarditis have considerable variability in their presentations and outcomes, use more resources, and die more often than children with other diagnoses. Attempts at using characteristics that uniformly predict illness severity or survival were not successful. Despite increased use in the sickest patients, IVIG conferred no survival advantage.


Convergent Validity of the Strength-Based Behavioral and Emotional Rating Scale with Youth in a Residential Setting.
Strength-based assessment has been identified as an appropriate approach to use in planning treatment and evaluating outcomes of youth in residential settings. In previous research, the Behavioral and Emotional Rating Scale-2, a standardized and norm-referenced strength-based measure, has demonstrated adequate reliability and validity with youth served in community and educational settings. The purpose of the present study was to examine the internal reliability and convergent validity of the BERS-2 by comparing the test to the Child Behavior Checklist and the Symptoms and Functioning Severity Scale. The results indicate that the scores from the BERS-2 are internally consistent and converge with other behavioral and emotional measures which, taken together, suggest that the BERS-2 could be acceptable for assessing the emotional and behavioral strengths of youth in residential settings. Study limitations and future research directions are identified.


Cystic lesions of the prostate.
As the use of ultrasound (US) for evaluating the prostate gland has grown, so has the variety of cystic prostatic lesions that can be identified with US. We review many of these cystic lesions seen in our department over the past several years. Lesions discussed include müllerian duct cyst, prostatic utricle cyst, ejaculatory duct cyst, cystic degeneration in benign prostatic hyperplasia, prostatic retention cyst, cavitary prostatitis, and prostatic abscess. The defect from transurethral resection of the prostate gland, which may have a sonographic appearance similar to that of a cystic prostatic mass, is also discussed. A diagnostic algorithm based on a combination of sonographic findings and the results of transperineal needle aspiration is presented.


Predicting stability of lyophilized products.
The usual purpose of freeze-drying is to enhance the stability and thus the marketability of a product. Increasing the length of a product's integrity, however, often requires that the formulator be able to predict the extent of that increased shelf life. Based on the Arrhenius principles, techniques are available that can allow such shelf life estimates with an acceptable degree of confidence. The presentation reviews examples of ongoing studies demonstrating predictive techniques as applied to freeze-dried products. The examples cover the most common situations which call for straight-forward and generally accepted principles of prediction; that is, measuring a specific potency loss at several elevated temperatures and then predicting the time for the same loss at normal storage. Other situations, however, as is the case with many in vitro diagnostic products used in clinical laboratories, require a modification of this technique. In those instances, monitoring of the proper "functioning" of samples of a product subjected to exaggerated temperature conditions with an eye to predicting shelf life is reviewed.


Maternal attitudes and behaviors regarding feeding practices in elementary school-aged Latino children: a pilot qualitative study on the impact of the cultural role of mothers in the US-Mexican border region of San Diego, California.
This study aimed to explore the attitudes and behaviors of Latino mothers around feeding their children. Using qualitative methods, we conducted four focus groups in Spanish with 41 Latino mothers of elementary school-age children in San Diego County, CA. Latino mothers' mean age was 41 years; 90% were foreign-born; and 74% had a high school education or less. We explored cultural viewpoints around feeding and cooking and feeding strategies used. Focus groups were analyzed based on a priori and emergent themes. The following themes around feeding emerged: feeding attitudes central to the maternal responsibility of having well-fed children and feeding behaviors that centered on cooking methods, supportive behaviors, and reinforcement strategies for "eating well." These findings increase our understanding of the Latino maternal role to feed children and can help to inform more culturally appropriate research to effectively address nutritional issues and obesity prevention in Latino children.


Pre- and postsynaptic effects of angiotensins in the femoral artery of spontaneously hypertensive and Wistar-Kyoto rats.
The effects of angiotensin I (AI) and angiotensin II (AII) on ring segments of femoral arteries from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) were studied. AI and AII elicited significantly greater direct contractile response in arteries from SHR than those from WKY. These peptides also potentiated the contractile response to transmural adrenergic nerve stimulation (TNS) in both preparations, but to a greater extent in those of WKY than SHR, without potentiating the contractile response to exogenous norepinephrine (NE). The potentiation of the TNS response and direct contraction caused by AI were markedly attenuated by captopril, an AI-converting enzyme inhibitor. Destruction of endothelium failed to alter the contractile response to AI in both WKY and SHR but augmented that to AII in WKY. Isoproterenol and salbutamol produced significant potentiation of TNS response only in arteries of SHR. Yohimbine and prostaglandin F2 alpha potentiated TNS response to a similar extent in arteries of WKY and SHR. These results suggest that AII locally generated from AI can act postsynaptically to cause contraction and presynaptically to promote adrenergic neurotransmission in the isolated rat femoral artery. The AI to AII conversion appears to take place mainly at sites other than endothelial cells. The postsynaptic effect of AII is greater in SHR than WKY, but its presynaptic effect is diminished in SHR unlike some other agents which facilitate adrenergic neurotransmission, and unlike that in mesenteric arteries of SHR.


Spinal cord injury II: Prognostic indicators, standards of care, and clinical trials.
This is the second of a 2-part review of spinal cord injury. The focus herein is to highlight recent findings regarding prognostic indicators used for spinal cord injury (SCI) in dogs, promote an awareness of the current recommendations of standard of care for traumatic spinal cord injury in veterinary medicine, and highlight the findings of clinical trials of therapies for spinal cord injury in dogs. This 2-part review provides information that will assist general and specialty veterinary practitioners in evidence-based veterinary medical practice in an area that has become particularly specialized.


Prospective payment for home care.
Prospective pay models propose to make one payment to cover an entire episode of care, rather than making one payment per visit. What elements must be considered in developing such a system? Is the new Congress likely to enact such a plan--and if so, what does that mean for the home care industry?


Spying on psychiatrists: surreptitious surveillance of the forensic psychiatric examination by the patient himself.
Lawyers have argued that surveillance of the forensic psychiatric examination is often necessary to protect clients' rights and assure more accurate reporting of the findings. This paper reports a new phenomenon which adds a disconcerting dimension to the current controversy over surveillance of such examinations, namely, surreptitious recording by patient/examinees of their own forensic examination. Their motivations range from psychotic delusions to perceptions that they are acting to protect their legal interests. Neither legal nor ethical code prohibitions in any way serve to bar such conduct. Moral arguments for and against secret recording by patient/examinees are explored, and its relationship to other techniques used to monitor professional practices in the health fields (such as pseudopatient studies) is discussed.


Schwann cell‑like cells derived from human amniotic mesenchymal stem cells promote sciatic nerve repair through an exosome‑induced SOX2/FN1 pathway in vitro.
The unsatisfactory sensory function reconstruction after flap transplantation to repair tissue defects and reconstruct organs results in decreased quality of life. Schwann cells (SCs) can promote sensory function reconstruction, but the underlying mechanism is not completely understood. The aim of the present study was to explore the in‑depth mechanism underlying SCs in sensory function reconstruction. Sciatic nerve transection and a repair animal model were performed to evaluate the effect of SC‑like cells (iSCs) and a neurotrophin 3 (NT‑3) chitosan conduit. SC RNA‑seq data indicated that the SOX2/fibronectin 1 (FN1) axis promoted proliferation and migration, which are the cytological bases of nerve regeneration. Subsequently, the effects of SOX2, FN1 and exosomes secreted by iSCs on SC proliferation and migration were assessed using scratch wound and EdU assays, respectively. The RNA‑seq of SCs indicated that SOX2 overexpression increased iSC viability and migration. Furthermore, SOX2 increased FN1 expression to promote nerve recovery by fibronectin fibrillogenesis. In addition, exosomes secreted by iSCs increased SC viability and migration. In conclusion, iSCs with an NT‑3 chitosan conduit promoted sciatic nerve recovery via the SOX2/FN1 axis and exosomes secreted by iSCs. Therefore, the present study identified potential effective therapeutic approaches for sciatic nerve repair.


Stem cells, mature adipocytes, and extracellular scaffold: what does each contribute to fat graft survival?
Soft tissue engineering offers new perspectives for improving fat graft survival, for which the appropriate association of cells and scaffold seems essential. This study aimed to analyze the survival of free-cell grafts compared with adipose-derived stem cells (ASCs) seeded on collagen scaffolds. Adipose tissue from a single volunteer was used for the following preparations: purified adipose tissue, isolated mature adipocytes (free-cell graft), cultured ASCs without scaffold (free-cell graft), collagen scaffold only, cultured ASCs in collagen scaffold without and with bioactive factors, and freshly-isolated ASCs in collagen scaffold. These were grafted on 18 nude mice for 2 months, after which specimens were evaluated grossly and histologically using hematoxylin-phloxine-safran (HPS), Oil-Red-O, and antivimentin labeling. Specimens and animals were weighed before implantation and after explantation, and weight values were statistically analyzed. Free-cell grafts (mature adipocytes and free ASCs) showed complete resorption in 50 and 60% of the animals (remaining weight fraction was 22.5 and 5.3%, respectively). The survival of purified adipose tissue was 81.8% (statistically greater compared with free-cell grafts; p < 0.05). In the ASCs-scaffold association, the remaining weight fractions (87.3-70.4%) were statistically greater than in free-cell grafts (5.3-22.5%; p < 0.05), but the difference between ASC-scaffolds and fat grafts was not statistically significant. These results were confirmed by clinical and histologic observations. Three-dimensional collagen scaffolds seem to improve survival of ASCs compared with free-cell grafts (adipocytes and free ASCs).


Oncolytic virus therapy using genetically engineered herpes simplex viruses.
An increasing number of oncolytic virus vectors has been developed lately for cancer therapy. Herpes simplex virus type 1 (HSV-1) vectors are particularly useful, because they can be genetically engineered to replicate and spread highly selectively in tumor cells and can also express multiple foreign transgenes. These vectors can manifest cytopathic effect in a wide variety of tumor types without damaging normal tissues, provide amplified gene delivery within the tumor, and induce specific antitumor immunity. Multiple recombinant HSV-1 vectors have been tested in patients with brain tumors and other cancers, which showed the feasibility of administering replication-competent HSV-1 vectors safely in human organs including the brain. Different approaches are currently undertaken to improve the efficacy of oncolytic HSV-1 therapy which include development of new generation vectors via further genetic engineering of existing safe vectors, combination with immune gene therapy, and combination with conventional therapies. Oncolytic virus therapy is a promising therapeutic modality that awaits establishing as an important treatment option for cancer patients in the near future.


[Methods of Prevention of Sudden Death in Chronic Heart Failure].
Chronic heart failure (CHF) is a natural finale of all cardiovascular diseases. Its prevalence in Russian Federation (as assessed using traditional Framingham criteria) is 4.5% what corresponds to 5 million patients. Prognosis of decompensation of cardiac action remains unfavorable even at the background of optimal drug therapy and use of nondrug methods of treatment. Main causes of death of patients with CHF are cardiac decompensation and sudden cardiac death (SCD). In this review, we present analysis of Russian and foreign studies which have investigated immediate causes of SCD as well as methods of its primary and secondary prevention.


Viral Pneumonia Screening on Chest X-Rays Using Confidence-Aware Anomaly Detection.
Clusters of viral pneumonia occurrences over a short period may be a harbinger of an outbreak or pandemic. Rapid and accurate detection of viral pneumonia using chest X-rays can be of significant value for large-scale screening and epidemic prevention, particularly when other more sophisticated imaging modalities are not readily accessible. However, the emergence of novel mutated viruses causes a substantial dataset shift, which can greatly limit the performance of classification-based approaches. In this paper, we formulate the task of differentiating viral pneumonia from non-viral pneumonia and healthy controls into a one-class classification-based anomaly detection problem. We therefore propose the confidence-aware anomaly detection (CAAD) model, which consists of a shared feature extractor, an anomaly detection module, and a confidence prediction module. If the anomaly score produced by the anomaly detection module is large enough, or the confidence score estimated by the confidence prediction module is small enough, the input will be accepted as an anomaly case (i.e., viral pneumonia). The major advantage of our approach over binary classification is that we avoid modeling individual viral pneumonia classes explicitly and treat all known viral pneumonia cases as anomalies to improve the one-class model. The proposed model outperforms binary classification models on the clinical X-VIRAL dataset that contains 5,977 viral pneumonia (no COVID-19) cases, 37,393 non-viral pneumonia or healthy cases. Moreover, when directly testing on the X-COVID dataset that contains 106 COVID-19 cases and 107 normal controls without any fine-tuning, our model achieves an AUC of 83.61% and sensitivity of 71.70%, which is comparable to the performance of radiologists reported in the literature.


Using the Uganda National Panel Survey to analyze the effect of staple food consumption on undernourishment in Ugandan children.
The United Nations' Millennium Development Goals Report, 2015, documents that, since 1990, the number of stunted children in sub-Saharan Africa has increased by 33% even though it has fallen in all other world regions. Recognizing this, in 2011 the Government of Uganda implemented a 5-year Nutrition Action Plan. One important tenet of the Plan is to lessen malnutrition in young children by discouraging over-consumption of nutritionally deficient, but plentiful, staple foods, which it defines as a type of food insecurity. We use a sample of 6101 observations on 3427 children age five or less compiled from three annual waves of the Uganda National Panel Survey to measure undernourishment. We also use the World Health Organization's Child Growth Standards to create a binary variable indicating stunting and another indicating wasting for each child in each year. We then use random effects to estimate binary logistic regressions that show that greater staple food concentrations affect the probability of stunting and wasting. The estimated coefficients are used to compute adjusted odds ratios (OR) that estimate the effect of greater staple food concentration on the likelihood of stunting and the likelihood of wasting. Controlling for other relevant covariates, these odds ratios show that a greater proportion of staple foods in a child's diet increases the likelihood of stunting (OR = 1.007, p = 0.005) as well as wasting (OR = 1.011, p = 0.034). Stunting is confirmed with subsamples of males only (OR = 1.006, p = 0.05) and females only (OR = 1.008, p = 0.027), suggesting that the finding is not gender specific. Another subsample of children aged 12 months or less, most of whom do not yet consume solid food, shows no statistically significant relationship, thus supporting the validity of the other findings. Diets containing larger proportions of staple foods are associated with greater likelihoods of both stunting and wasting in Ugandan children. Other causes of stunting and wasting identified in past research are also confirmed with the Uganda data. Finally, the analysis provides clues to other possible causes of undernourishment in young children.


Evidence for the existence of a constitutive nitric oxide synthase in vascular smooth muscle.
1. We have identified a neuronal nitric oxide synthase (NOS)-like constitutive form of NOS in vascular smooth muscle (VSM) using a functional contractility approach as well as immunohistochemical methods. 2. N(G)-Nitro-L-arginine methyl ester, N(G)-monomethyl-L- arginine and N(G)-nitro-L-arginine (L-NOARG), the competitive inhibitors of NOS, inhibited Mg(2+)-induced relaxation of de-endothelialized rat aorta precontracted with phenylephrine (PE). This Mg(2+) relaxation of VSM was not affected by inhibitors of inducible NOS. 3. Electrical field stimulation (EFS; 30-70 Hz) caused relaxation of rat aorta in the presence of tetrodotoxin (therefore not a neurogenic effect) and this EFS relaxation was effectively inhibited by L-NOARG, oxyhemoglobin and methylene blue. 4. Immunohistochemical studies of dog saphenous vein using antibodies raised against neuronal NOS indicated prominent staining along the plasmalemma in a punctate pattern similar to the distribution of antibodies against caveolin-1, a major constituent of the plasmalemmal caveolae. 5. We propose that a constitutive NOS of non-endothelial, non-neuronal origin is present in a special caveolae domain of VSM cell membranes and could be activated by an ionic mechanism yet to be characterized.


High-Mobility Group Box-1 Is Associated With Obesity, Inflammation, and Subclinical Cardiovascular Risk Among Young Adults: A Longitudinal Cohort Study.
We aimed to characterize circulating HMGB1 (high-mobility group box-1) levels, one of the better-characterized damage-associated molecular patterns, with respect to age, sex, and race in the general population, and investigate the longitudinal associations of HMGB1 with inflammatory markers, obesity, and preclinical markers of cardiovascular disease. Approach and Results: The analyses included 489 participants (50% Blacks, aged 24.6±3.3 years at the first visit) with up to 4 follow-up visits (1149 samples) over a maximum of 8.5 years. Systolic blood pressure, diastolic blood pressure, carotid-femoral pulse wave velocity, and carotid intima-media thickness together with plasma HMGB1, hs-CRP (high-sensitivity C-reactive protein), IFN-γ (interferon-γ), IL-6 (interleukin-6), IL-10 (interleukin-10), and TNF-α (tumor necrosis factor-α) were measured at each visit. At baseline, plasma HMGB1 concentrations were higher in Blacks compared with Whites (3.86 versus 3.20 ng/mL, P<0.001), and in females compared with males (3.75 versus 3.30 ng/mL, P=0.005). HMGB1 concentrations increased with age (P=0.007), and higher levels of obesity measures (P<0.001). Without adjustment for age, sex, race, and body mass index, HMGB1 concentrations were positively associated with hs-CRP, IL-6, TNF-α, systolic blood pressure, diastolic blood pressure, and carotid-femoral pulse wave velocity (P<0.05) but not IL-10, IFN-γ or carotid intima-media thickness. After covariate adjustments, the associations of HMGB1 with hs-CRP, and carotid-femoral pulse wave velocity remained statistically significant (P<0.05). This study demonstrates the age, sex, and race differences in circulating HMGB1. The increasing circulating concentrations of HMGB1 with age suggest a potential role of HMGB1 in the pathogenesis of chronic low-grade inflammation, obesity, and subclinical cardiovascular disease risk.


The use of granulocyte colony-stimulating factor for treatment of autoimmune neutropenia.
The advent of better diagnostic tools, molecular techniques, and cytokine therapies have come together at the end of the 20th century to provide an improved outlook for patients with autoimmune neutropenia. Severe chronic neutropenia is no longer idiopathic in most cases, and growth factor therapy can be safely offered to selected patient groups. Previously unsuccessful and even dangerous forms of treatment are no longer appropriate, and G-CSF treatment appears to be safe when administered long term. Fears about transformation of these disorders into acute myeloblastic leukemia probably relate to the underlying natural history of these disorders rather than to their treatment.


Utility of femorofemoral bypass. Comparison of results with indications for operation.
Sixty-eight patients underwent femorofemoral bypass (FFB) at the University of Louisville Affiliated Hospitals over a 9-year period from 1980 to 1989. There were patients with acute ischemia requiring emergency operation, those with chronic ischemia following failed aortic reconstruction, good-risk patients with chronic ischemia who had FFB as the procedure of choice, and poor-risk patients who were unsuitable for other procedures. Patients operated on for acute ischemia had a significant number of infectious complications, with five of eight graft failures in this group due to infection. Primary patency rates were similar in all groups, with a 5-year primary patency of 42 per cent. Overall operative mortality was 4.4 per cent. Satisfactory limb salvage rates (75%) suggest that FFB is an acceptable option for providing inflow in patients with acute ischemia or for patients with a failed previous vascular prosthesis. FFB provides adequate inflow in poor-risk patients not suitable for aortic reconstruction, but patency rates do not warrant its use as a procedure of choice in good-risk patients.


[Effect of cetyltrimethylammonium on the human blood cholinesterases activity].
The influence of cationic detergent cetyltrimethylammonium on the human blood cholinesterases activity (erythrocyte acetylcholinesterase and plasma butyrylcholinesterase) in reactions of hydrolysis of alpha-thionaphthylacetat and acetylthiocholine is studied. It is shown, that cetyltrimethylammonium is reversible effector for both cholinesterases. This compound competitively inhibited enzymatic hydrolysis of acetylthiocholine by both cholinesterases, and in the reactions of enzymatic hydrolysis alpha-thionaphthylacetat display as the synergistic activator--in experiments with butyrylcholinesterase, and as the reversible inhibitor--in experiments with acetylcholinesterase. Kinetic constants in reaction of acetylcholinesterase inhibition by cetyltrimethylammonium defined by means of different substrates--alpha-thionaphthylacetat and acetylthiocholin. They are close among themselves and amount (2.5 +/- 0.3) x 10(-5) and (2.8 +/- 0.3) x 10(-5) M, accordingly. Butyrylcholinesterase was more sensitive to influence of cetyltrimethylammonium. The kinetic constants defined for this enzyme by the effect of inhibition of acetylthiocholin hydrolysis or activation of alpha-thionaphthylatcetat hydrolysis, are also close among themselves and amount (3.9 +/- 0.4) x 10(-6) and (4.4 +/- 0.4) x 10(-6) M, accordingly.


The use of Fourier-transform infrared spectroscopy to characterize connective tissue components in skeletal muscle of Atlantic cod (Gadus morhua L.).
In the present study, Fourier-transform infrared spectroscopy (FTIR) is investigated as a method to measure connective tissue components that are important for the quality of Atlantic cod filets (Gadus morhua L.). The Atlantic cod used in this study originated from a feeding trial, which found that fish fed a high starch diet contained relative more collagen type I, while fish fed a low starch (LS) diet contained relative more glycosaminoglycans (GAGs) in the connective tissue. FTIR spectra of pure commercial collagen type I and GAGs were acquired to identify spectral markers and compare them with FTIR spectra and images from connective tissue. Using principal component analysis, high and LS diets were separated due to collagen type I in the spectral region 1800 to 800 cm-1 . The spatial distribution of collagen type I and GAGs were further investigated by FTIR imaging in combination with immunohistochemistry. Pixel-wise correlation images were calculated between preprocessed connective tissue images and preprocessed pure components spectra of collagen type I and GAGs, respectively. For collagen, the FTIR images reveal a collagen distribution that closely resembles the collagen distribution as imaged by immunohistochemistry. For GAGs, the concentration is very low. Still, the FTIR images detect the most GAGs rich regions.


Polysomnographic Endotyping to Select Patients with Obstructive Sleep Apnea for Oral Appliances.
Rationale: Oral appliance therapy is efficacious in many patients with obstructive sleep apnea (OSA), but prediction of treatment outcome is challenging. Small, detailed physiological studies have identified key OSA endotypic traits (pharyngeal collapsibility and loop gain) as determinants of greater oral appliance efficacy.Objectives: We used a clinically applicable method to estimate OSA traits from routine polysomnography and identify an endotype-based subgroup of patients expected to show superior efficacy.Methods: In 93 patients (baseline apnea-hypopnea index [AHI], ≥20 events/h), we examined whether polysomnography-estimated OSA traits (pharyngeal: collapsibility and muscle compensation; nonpharyngeal: loop gain, arousal threshold, and ventilatory response to arousal) were associated with oral appliance efficacy (percentage reduction in AHI from baseline) and could predict responses to treatment. Multivariable regression (with interactions) defined endotype-based subgroups of "predicted" responders and nonresponders (based on 50% reduction in AHI). Treatment efficacy was compared between the predicted subgroups (with cross-validation).Results: Greater oral appliance efficacy was associated with favorable nonpharyngeal traits (lower loop gain, higher arousal threshold, and lower response to arousal), moderate (nonmild, nonsevere) pharyngeal collapsibility, and weaker muscle compensation (overall R2 = 0.30; adjusted R2 = 0.19; P = 0.003). Predicted responders (n = 54), compared with predicted nonresponders (n = 39), exhibited a greater reduction in AHI from baseline (mean [95% confidence interval], 73% [66-79] vs. 51% [38-61]; P < 0.0001) and a lower treatment AHI (8 [6-11] vs. 16 [12-20] events/h; P = 0.002). Differences persisted after adjusting for clinical covariates (including baseline AHI, body mass index, and neck circumference).Conclusions: Quantifying OSA traits using clinical polysomnography can identify an endotype-based subgroup of patients that is highly responsive to oral appliance therapy. Prospective validation is warranted.


Bisdemethoxycurcumin, a curcumin derivative, ameliorates adjuvant-induced arthritis by suppressing inflammatory reactions and macrophage migration.
Rheumatoid arthritis (RA) is a highly prevalent and chronic inflammatory synovial joint disease manifested by hyperplasia and continuous inflammation. Curcumin (Cur) has been studied for alleviating RA. However, poor stability and oral bioavailability restrict its therapeutic value. Bisdemethoxycurcumin (BDMC), a curcumin (Cur) derivative, exerts better stability and oral bioavailability than Cur. However, the efficacy of BDMC on RA has not been fully clarified. The aim of the study was to investigate the therapeutic effects and underlying mechanisms of BDMC on RA. The in-vivo anti-arthritic activity of BDMC was determined via adjuvant-induced arthritis (AIA) rat model. Paw swelling, body weight, arthritic index, and histopathological assessments were performed. RAW264.7 cell was stimulated by lipopolysaccharides (LPS) in vitro. The cell viability were determined by CCK8 assay, while the migration ability was determined using cell wound healing and transwell assays. Furthermore, in-vivo and in-vitro levels of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) were assayed by ELISA, and that of IκBα, p-NF-κB, NF-κB, and COX-2 were assessed via Western blot or immunofluorescence. In AIA rat model, it suggested a higher anti-arthritic activity of BDMC than Cur, including amelioration of swelling in hind paws, reduced arthritic index, and alleviated histopathological injury in rats. Furthermore, BDMC also substantially decreased the levels of the aforementioned pro-inflammatory cytokines in both in-vivo and in-vitro, inhibited the IκBα degradation, down-regulated the COX-2 levels and p-NF-κB/NF-κB ratio in AIA rats and LPS-stimulated RAW264.7 cells. Additionally, BDMC showed an inhibitory effect on the migration of LPS-stimulated RAW264.7 cells. BDMC could effectively ameliorate RA by suppressing inflammatory reactions and inhibiting macrophage migration, more potentially than Cur.


Histopathological, morphological, and molecular characterization of Sarcocystis species in elk (Cervus elaphus) from Pennsylvania, USA.
Sarcocystis sarcocysts are common in many species of domestic and wild animals. Here, we report sarcocystosis in muscles from 91 free range elk (Cervus elaphus) from Pennsylvania, USA, tested by histopathology, transmission electron microscopy (TEM), and DNA sequencing. Sarcocysts were detected in hematoxylin and eosin (HE)-stained sections from 83 of 91 (91.2%) elk, including 83/91 (91.2%) tongues and 15/17 (88.2%) hearts. With respect to age, sarcocysts were found in 0/5 calves, 8/9 (88.8%) yearlings, and 75/77 (97.4%) adults. Sarcocysts were identified in 62/69 (89.4%) females and 21/22 (91.2%) males. Associated lesions were mild and consisted of inflammatory foci around degenerate sarcocysts. There were two morphologically distinct sarcocysts based on wall thickness, thin (< 0.5 μm) and thick-walled (> 4.0 μm). Thin-walled sarcocysts had a TEM "type 2" and villar protrusions (vps), identical to Sarcocystis wapiti previously described from elk in western USA. This species was present both in tongue and heart samples and was detected in all infected elk. Thick-walled sarcocysts consisted of three morphologic variants, referred to herein as subkinds A, B, C. Subkind A sarcocysts were rare; only four sarcocysts were found in three elk. Histologically, they had a 5-8-μm thick wall with tufted vp. By TEM, the sarcocyst wall was "type 12" and appeared similar to Sarcocystis sybillensis, previously described from elk in USA. Subkind B, Sarcocystis sp.1 sarcocysts were also rare, found in only 1 elk. These sarcocysts had 6.7-7.3-μm-thick wall with TEM "type 15b" vp. Subkind C Sarcocystis sp.2 sarcocysts were more common (22/91). Morphologically, the sarcocyst wall was 6.1-6.8 μm thick and contained "type 10b" vp. Comparisons of ribosomal DNA loci with published sequences indicated all sarcocysts were similar to what has previously been isolated from cervid hosts across the northern hemisphere. Phylogenetic analysis placed the thin-walled S. wapiti within a strongly supported clade with S. linearis and S. taeniata, while the thick-walled cysts were very closely related to S. truncata, S. elongata, S. silva, and S. tarandi. Further sequencing is needed to produce molecular diagnostics to distinguish among these species. North American elk are hosts to multiple Sarcocystis species with diverse morphology, deriving from two separate evolutionary lineages.


Metastatic small cell carcinoma masquerading as orbital myositis.
A case of discrete metastases to an extraocular muscle from a silent small cell carcinoma is described. Clinically, diagnostically, and pathologically this masqueraded as orbital myositis. It was not until a full thickness muscle biopsy was obtained that the diagnosis was realized. The need for deep biopsy is stressed. Discrete metastases to an extraocular muscle without other orbital soft tissue involvement is rarely reported. This is the first reported case from a small cell primary tumor. Metastatic orbital disease is discussed.


Phase-Selective Epitaxy of Trigonal and Orthorhombic Bismuth Thin Films on Si (111).
Over the past three decades, the growth of Bi thin films has been extensively explored due to their potential applications in various fields such as thermoelectrics, ferroelectrics, and recently for topological and neuromorphic applications, too. Despite significant research efforts in these areas, achieving reliable and controllable growth of high-quality Bi thin-film allotropes has remained a challenge. Previous studies have reported the growth of trigonal and orthorhombic phases on various substrates yielding low-quality epilayers characterized by surface morphology. In this study, we present a systematic growth investigation, enabling the high-quality growth of Bi epilayers on Bi-terminated Si (111) 1 × 1 surfaces using molecular beam epitaxy. Our work yields a phase map that demonstrates the realization of trigonal, orthorhombic, and pseudocubic thin-film allotropes of Bi. In-depth characterization through X-ray diffraction (XRD) techniques and scanning transmission electron microscopy (STEM) analysis provides a comprehensive understanding of phase segregation, phase stability, phase transformation, and phase-dependent thickness limitations in various Bi thin-film allotropes. Our study provides recipes for the realization of high-quality Bi thin films with desired phases, offering opportunities for the scalable refinement of Bi into quantum and neuromorphic devices and for revisiting technological proposals for this versatile material platform from the past 30 years.


Force-chain buckling in granular media: a structural mechanics perspective.
Parallels are drawn between the response of a discrete strut on a linear elastic foundation and force-chain buckling in a constrained granular medium. Both systems buckle initially into periodic shapes, with wavelengths that depend on relative resistances to lateral displacement, and curvature in the buckled shape. Under increasing end shortening, the classical structural model evolves to a localized form extending over a finite number of contributing links. By analogy, it is conjectured that the granular model of force-chain buckling might follow much the same evolutionary route into a shear band.


Molecular, physiological and clinical aspects of the iron storage protein ferritin.
Oxidative stress is a major factor in inflammatory, malignant and metabolic diseases in domestic and farm animals. Oxidative stress-mediated damage depends on the level of cellular and total body iron status because an excess iron (Fe(2+)) pool produces the most harmful free radicals (hydroxyls) through the Fenton reaction. Ferritin is a ubiquitous and conserved iron storage protein that plays a central role in iron metabolism and has the dual function of storing iron in bioavailable and non-toxic forms. Intracellular ferritin synthesis is controlled at translational and transcriptional levels in both an iron-dependent and an iron-independent manner. Ferritin is also found in extracellular fluids such as serum, synovial fluids and milk. Although serum ferritin is a sensitive indicator of body iron stores, the extracellular ferritins are elevated in inflammatory or malignant disease. Circulating ferritin interacts with ferritin-binding protein to form a complex, which is rapidly cleared from the body. This review describes recent research of physiological and clinical significance of ferritin and its application to future veterinary medicine.


Cloning of yeast gene for trichodermin resistance and ribosomal protein L3.
Yeast cells sensitive to the eukaryotic protein synthesis inhibitor trichodermin have been transformed with autonomously replicating recombinant plasmids carrying DNA fragments of the genome of a trichodermin-resistant yeast strain. After selection for trichodermin-resistant cells, several transformants yielded a plasmid containing a 13.5-kilobase (kb) DNA fragment that encodes the trichodermin resistance gene, tcm1, and the gene for ribosomal protein L3, the largest of the yeast ribosomal proteins. Cells carrying this plasmid are resistant to trichodermin and to the related drug verrucarin A as well as to the unrelated drug anisomycin. This pattern of resistance is similar to that exhibited by strains carrying a chromosomal copy of tcm1. Moreover, polyribosomes prepared from transformed cells are resistant to trichodermin when tested in an in vitro protein synthesis assay. Subcloning of the 13.5-kb DNA fragment revealed that the gene for tcm1 and the gene for protein L3 are contained within a 3.2-kb segment. These results suggest that the gene for trichodermin resistance in yeast specifies ribosomal protein L3.


Caring, objectivity and justice: an integrative view.
The argument of this article is framed by a debate between the principle of humanity and the principle of justice. Whereas the principle of humanity requires us to care about others and to want to help them meet their vital needs, and so to be partial towards those others, the principle of justice requires us to consider their needs without the intrusion of our subjective interests or emotions so that we can act with impartiality. I argue that a deep form of caring lies behind both approaches and so unites them. In the course of the argument, I reject Michael Slote's sentimentalist form of an ethics of care, and expound Thomas Nagel's moral theory, which seems to lie at the opposite end of a spectrum ranging from moral sentiments to impersonal objectivity. Nevertheless, Nagel's theory of normative realism provides unexpected support for the thesis that a deep and subjective form of caring lies at the base of even our most objective moral reasons.


Growth inhibition of Cyanobacteria by ultrasonic radiation: laboratory and enclosure studies.
The growth of Microcystis aeruginosa UTEX 2388 was repressed by ultrasonic radiation and resulted in an increased chlorophyll a content and cell size, suggesting the inhibition of cell division. However, growth was recovered immediately after the interruption of ultrasonication. In addition to the disruption of gas vesicles, other mechanisms of growth inhibition were also investigated. Although free radicals were produced by ultrasonication and hydrogen peroxide, the resulting lipid peroxidation in the cells was not comparable, indicating minimal damage by the free radicals. Ultrasonic radiation late in the day was found to be most effective in reducing the growth rate of M. aeruginosa, and this timing also corresponded to the phase of daily cell division. In an enclosure experiment, ultrasonic radiation reduced the pH, DO, total nitrogen, and total phosphorus, whereas it increased the water temperature, conductivity, and orthophosphate concentration. The algal cell density and chlorophyll a concentration drastically decreased after 3 d of ultrasonication, plus the cyanobacterial proportion was selectively reduced as compared to other algal species. Accordingly, ultrasonic radiation would appear to have considerable potential as an effective control method for cyanobacterial blooms.


Toward patient-specific, biologically optimized radiation therapy plans for the treatment of glioblastoma.
To demonstrate a method of generating patient-specific, biologically-guided radiotherapy dose plans and compare them to the standard-of-care protocol. We integrated a patient-specific biomathematical model of glioma proliferation, invasion and radiotherapy with a multiobjective evolutionary algorithm for intensity-modulated radiation therapy optimization to construct individualized, biologically-guided plans for 11 glioblastoma patients. Patient-individualized, spherically-symmetric simulations of the standard-of-care and optimized plans were compared in terms of several biological metrics. The integrated model generated spatially non-uniform doses that, when compared to the standard-of-care protocol, resulted in a 67% to 93% decrease in equivalent uniform dose to normal tissue, while the therapeutic ratio, the ratio of tumor equivalent uniform dose to that of normal tissue, increased between 50% to 265%. Applying a novel metric of treatment response (Days Gained) to the patient-individualized simulation results predicted that the optimized plans would have a significant impact on delaying tumor progression, with increases from 21% to 105% for 9 of 11 patients. Patient-individualized simulations using the combination of a biomathematical model with an optimization algorithm for radiation therapy generated biologically-guided doses that decreased normal tissue EUD and increased therapeutic ratio with the potential to improve survival outcomes for treatment of glioblastoma.


Surgically treated acute distal biceps tendon injuries: what results do they have in comparison with the contralateral healthy arm? A systematic review and meta-analysis.
Surgical repair of distal biceps tendon injury restores flexion and supination strength, resulting in good functional outcome. There are few studies that consider clinical results of the operated arm compared to the healthy contralateral arm, whereas there are many articles examining the results of different surgical techniques. We carried out a systematic review with meta-analysis of the studies that consider this comparison. The aim was to evaluate if there are significative differences in terms of functional results between the operated arm and the non-injured contralateral arm. In fact, we believe that this comparison is useful for assessing patient true satisfaction. In accordance with the PRISMA and QUORUM statements, a comprehensive search on PubMed, Scopus, Embase, Cochrane, Google Scholar and Web of Science databases was conducted to identify studies reporting comparative functional results of the operated arm with healthy contralateral arm from January 1985 until November 2022. Criteria for inclusion were acute complete injury of the distal biceps' tendon operated within 30 days; range of motion (ROM), isokinetic and isometric strength measurements; minimum patients follow-up of 24 months; studies written in English language. Then a DerSimonian and Laird meta-analysis was conducted to compare the functional outcomes of the operated arm to the non-injured arm. Of the 588 initial studies, 18 studies met the inclusion criteria; methodological quality was assessed using the Newcastle-Ottawa scale. A total of 272 surgically treated distal biceps ruptures were included in the study. The mean follow-up time was of 39.6 months (24 to 72 months).ROM flexion, pronation, and supination of the operated elbows were significantly decreased, with mean differences of -1.24° (p = .004), -7.95° (p = .003), and -9.27° (p = .004) respectively, compared to the non-injured healthy elbows. The difference of ROM extension was not-statistically significant (+ 0.21°; p = .66) The Isokinetic data showed a statistically significant reduction in the flexion strength (-4.56 Nm; p = .0004) and a statistical significative reduction in the supination strength (-1.18 Nm; p = .02) of the injured operated arm compared with the healthy one. The forest-plot table of the isometric data was not elaborated due to the small number of studies eligible for the meta-analysis. This study represents the first systematic review and meta-analysis to compare functional and clinical outcomes following operative treatment of distal biceps tendon ruptures with the contralateral healthy arm.Significant differences in ROM flexion, supination, and pronation and in isokinetic and isometric data were found between the operated and non-operated unaffected arm, demonstrating that, as expected, the unaffected arm performed better than the operated one. However, the functional differences between the data of the operated and healthy arm were slight and lead us to overall consider surgery as good functional result. III.


Sexual life in subjects with intellectual disability.
During the last decades, the expectancies towards sexual life of people with intellectual disability have been more and more recognized by researchers, clinicians, caregivers and parents. These expectancies, that largely depend on socio-cultural and personal factors, such as the level of disability, must be supported in order to help people with intellectual disability to reach the best quality of life as possible. Therefore, it is important to identify every patients and residents personal expectancies towards sexuality and which medical and educative support he/she needs according to his/her disability and co-morbidity. The aim of the present paper is to review the different research works conducted in this area.


Confronting mortality: faith and meaning across cultures.
Despite advances in technology and medicine, death itself remains an immutable certainty. Indeed, the acceptance and understanding of our mortality are among the enduring metaphysical challenges that have confronted human beings from the beginning of time. How have we sought to cope with the inevitability of our mortality? How do various cultural and social representations of mortality shape and influence the way in which we understand and approach death? To what extent do personal beliefs and convictions about the meaning of life or the notion of an afterlife affect how we perceive and experience the process of death and dying? Steve Paulson, executive producer and host of To the Best of Our Knowledge, moderated a discussion on death, dying, and what lies beyond that included psychologist Lani Leary, professor of philosophy and religion Jeffrey J. Kripal, and sociologist Allan Kellehear. The following is an edited transcript of the discussion that occurred February 5, 7:00-8:30 pm, at the New York Academy of Sciences in New York City.


Patterns of adaptive and neutral diversity identify the Xiaoxiangling mountains as a refuge for the giant panda.
Genetic variation plays a significant role in maintaining the evolutionary potential of a species. Comparing the patterns of adaptive and neutral diversity in extant populations is useful for understanding the local adaptations of a species. In this study, we determined the fine-scale genetic structure of 6 extant populations of the giant panda (Ailuropoda melanoleuca) using mtDNA and DNA fingerprints, and then overlaid adaptive variations in 6 functional Aime-MHC class II genes (DRA, DRB3, DQA1, DQA2, DQB1, and DQB2) on this framework. We found that: (1) analysis of the mtDNA and DNA fingerprint-based networks of the 6 populations identified the independent evolutionary histories of the 2 panda subspecies; (2) the basal (ancestral) branches of the fingerprint-based Sichuan-derived network all originated from the smallest Xiaoxiangling (XXL) population, suggesting the status of a glacial refuge in XXL; (3) the MHC variations among the tested populations showed that the XXL population exhibited extraordinary high levels of MHC diversity in allelic richness, which is consistent with the diversity characteristics of a glacial refuge; (4) the phylogenetic tree showed that the basal clades of giant panda DQB sequences were all occupied by XXL-specific sequences, providing evidence for the ancestor-resembling traits of XXL. Finally, we found that the giant panda had many more DQ alleles than DR alleles (33∶13), contrary to other mammals, and that the XXL refuge showed special characteristics in the DQB loci, with 7 DQB members of 9 XXL-unique alleles. Thus, this study identified XXL as a glacial refuge, specifically harboring the most number of primitive DQB alleles.


Promoter methylation of O(6)-methylguanine-DNA-methyltransferase in lung cancer is regulated by p53.
Methylation of the O(6)-methylguanine-DNA-methyltransferase (MGMT) promoter is associated with G:C to A:T transitions in the p53 gene in various human cancers, including lung cancer. In tumors with p53 mutation, MGMT promoter methylation is more common in advanced tumors than in early tumors. However, in tumors with wild-type p53, MGMT promoter methylation is independent of tumor stage. To elucidate whether p53 participates in MGMT promoter methylation, we engineered three cell models: A549 cells with RNA interference (RNAi)-mediated knockdown of p53, and p53 null H1299 cells transfected with either wild-type p53 (WT-p53) or mutant-p53 (L194R, and R249S-p53). Knockdown of endogenous p53 increased MGMT promoter methylation in A549 cells, and transient expression of WT-p53 in p53 null H1299 cells diminished MGMT promoter methylation, whereas the MGMT promoter methylation status were unchanged by expression of mutant-p53. Previous work showed that p53 modulates DNA-methyltransferase 1 (DNMT1) expression; we additionally examined chromatin remodeling proteins expression levels of histone deacetylase 1 (HDAC1). We found that p53 knockdown elevated expression of both DNMT1 and HDAC1 in A549 cells. Conversely, expressing WT-p53 in p53 null H1299 cells reduced DNMT1 and HDAC1 expression, but the reduction of both proteins was not observed in expressing mutant-p53 H1299 cells. CHIP analysis further showed that DNMT1 and HDAC1 binding to the MGMT promoter was increased by MGMT promoter methylation and decreased by MGMT promoter demethylation. In conclusion, MGMT promoter methylation modulated by p53 status could partially promote p53 mutation occurrence in advanced lung tumors.


Detection of copy number variations and their effects in Chinese bulls.
Copy number variations (CNVs) are a main source of genomic structural variations underlying animal evolution and production traits. Here, with one pure-blooded Angus bull as reference, we describe a genome-wide analysis of CNVs based on comparative genomic hybridization arrays in 29 Chinese domesticated bulls and examined their effects on gene expression and cattle growth traits. We identified 486 copy number variable regions (CNVRs), covering 2.45% of the bovine genome, in 24 taurine (Bos taurus), together with 161 ones in 2 yaks (Bos grunniens) and 163 ones in 3 buffaloes (Bubalus bubalis). Totally, we discovered 605 integrated CNVRs, with more "loss" events than both "gain" and "both" ones, and clearly clustered them into three cattle groups. Interestingly, we confirmed their uneven distributions across chromosomes, and the differences of mitochondrion DNA copy number (gain: taurine, loss: yak & buffalo). Furthermore, we confirmed approximately 41.8% (253/605) and 70.6% (427/605) CNVRs span cattle genes and quantitative trait loci (QTLs), respectively. Finally, we confirmed 6 CNVRs in 9 chosen ones by using quantitative PCR, and further demonstrated that CNVR22 had significantly negative effects on expression of PLA2G2D gene, and both CNVR22 and CNVR310 were associated with body measurements in Chinese cattle, suggesting their key effects on gene expression and cattle traits. The results advanced our understanding of CNV as an important genomic structural variation in taurine, yak and buffalo. This study provides a highly valuable resource for Chinese cattle's evolution and breeding researches.


High-dose intravenous corticosteroid therapy for Graves' ophthalmopathy.
In order to compare oral and high-dose iv corticosteroid therapy for Graves' disease, 25 patients with Graves' ophthalmopathy were treated with two weekly iv injections of 1 g of methylprednisolone diluted in 250-500 ml of physiological solution for 6 weeks, and were compared to a group of 26 patients treated with oral prednisone at a dose of 60-80 mg/day progressively reduced every 2 weeks for a total duration of 4-6 months. The efficacy of treatment was evaluated using the ophthalmopathy index score. Patients were followed at 3, 6, 12 months, and afterwards yearly. All patients showed a significant improvement in signs and symptoms of orbital inflammation and a slight improvement in proptosis and diplopia. Relevant side-effects were reported from patients receiving oral therapy, but no significant side-effects were observed in patients treated with high iv doses; a few cases presented with gastric pain (highly sensitive to aluminium oxide or ranitidine), while most of the patients referred to cutaneous rashes and a metal taste that disappeared some hours after the infusion. Improvements observed after treatment have been stable in both groups. In conclusion, in addition to a lower incidence of side-effects compared to the classic oral therapy, the high-dose iv steroid therapy provides efficient and stable improvement in Graves' ophthalmopathy.


[Transplantation surgery and immune regulation].
Although transplantation has revolutionized care for patients with end-stage organ failure due to the development of new immunosuppressive drugs, significant problems persist with treatments designed to prevent acute graft rejection. There is a real need for improved methods to maintain allograft function by preventing immune-mediated rejection. Accumulating evidence suggests that the inhibition of T cell costimulation may promote antigen-specific tolerance of transplants. In particular, blockade of the CD28 and CD40 costimulatory pathways has shown great promise in preventing transplant rejection in rodents and nonhuman primates. This paper discusses the human immune system, costimulatory pathways, and new therapeutic agents that regulate so-called costimulatory second signaling to maintain transplant function without general suppression of the immune system.


Functions of the mos oncogene family and associated gene products.
The mos oncogene present in Moloney murine sarcoma virus is one of the oldest known oncogenes, yet the identification of its biochemical function both in transformation and as a cellular proto-oncogene has been elusive. Only recently have low levels of c-mos transcripts been detected in a specific group of mouse tissues. The c-mos gene is implicated in tumorigenicity by its activation by the insertion of the intracisternal A particle genome in a mouse plasmacytoma. The murine c-mos gene is capable of oncogenic transformation when placed under the regulatory control of a long terminal repeat. The acquisition of the v-mos gene generated the transformation-competent Moloney murine sarcoma virus and several related strains. Myeloproliferative sarcoma virus is unique among the v-mos containing viruses in its ability to induce splenic foci and myeloproliferation in vivo in addition to the transformation of fibroblasts. The v-mos gene product, termed p37mos, is a cytoplasmic protein recently shown to possess serine kinase activity in immune complexes. Autophosphorylation of the mos gene product is not necessary for its biological activity as exemplified by the protein HT1-MSV which lacks phosphoserine residues. A transcriptional regulatory property has been attributed to the v-mos gene product during infection, which may play an essential role in subsequent transformation.


[Image guided and robotic treatment--the advance of cybernetics in clinical medicine].
The introduction of advanced technology in hospitals has changed the treatment practice towards more image guided and minimal invasive procedures. Modern computer and communication technology opens up for robot aided and pre-programmed intervention. Several robotic systems are in clinical use today both in microsurgery and in major cardiac and orthopedic operations. As this trend develops, professions which are new in this context such as physicists, mathematicians and cybernetic engineers will be increasingly important in the treatment of patients.


It does belong together: cross-modal correspondences influence cross-modal integration during perceptual learning.
Experiencing a stimulus in one sensory modality is often associated with an experience in another sensory modality. For instance, seeing a lemon might produce a sensation of sourness. This might indicate some kind of cross-modal correspondence between vision and gustation. The aim of the current study was to explore whether such cross-modal correspondences influence cross-modal integration during perceptual learning. To that end, we conducted two experiments. Using a speeded classification task, Experiment 1 established a cross-modal correspondence between visual lightness and the frequency of an auditory tone. Using a short-term priming procedure, Experiment 2 showed that manipulation of such cross-modal correspondences led to the creation of a crossmodal unit regardless of the nature of the correspondence (i.e., congruent, Experiment 2a or incongruent, Experiment 2b). However, a comparison of priming effects sizes suggested that cross-modal correspondences modulate cross-modal integration during learning, leading to new learned units that have different stability over time. We discuss the implications of our results for the relation between cross-modal correspondence and perceptual learning in the context of a Bayesian explanation of cross-modal correspondences.


Validity of a single item food security questionnaire in Arctic Canada.
Assess sensitivity and specificity of each of the 18 US Department of Agriculture (USDA) Household Food Security Scale Module (HFSSM) questionnaire items to determine whether a rapid assessment of child and adult food insecurity is feasible in an Inuit population. Food insecurity prevalence was assessed by the 18-item USDA HFSSM in a randomized sample of Inuit households participating in the Inuit Health Survey and the Nunavut Inuit Child Health Survey. Questions were evaluated for sensitivity, specificity, predictive value (+/2), and total percent accuracy for adult and child food insecurity (yes/no). Child food security items were evaluated for both surveys. For children, the question "In the last 12 months, were there times when it was not possible to feed the children a healthy meal because there was not enough money?" had the best performance in both samples with a sensitivity and specificity of 92.3% and 97.3%, respectively, for the Inuit Health Survey, and 88.5% and 95.4% for the Nunavut Inuit Child Health Survey. For adults, the question "In the last 12 months, were there times when the food for you and your family just did not last and there was no money to buy more?" demonstrated a sensitivity of 93.0% and a specificity of 93.4%. Rapid assessment of child and adult food insecurity is feasible and may be a useful tool for health care and social service providers. However, as prevalence and severity of food insecurity change over time, rapid assessment techniques should not replace periodic screening by using the full USDA HFSSM questionnaire.


A novel ligand on astrocytes interacts with natural cytotoxicity receptor NKp44 regulating immune response mediated by NK cells.
NK cells play important role in immunity against pathogens and cancer. NK cell functions are regulated by inhibitory and activating receptors binding corresponding ligands on the surface of target cells. NK cells were shown to be recruited to the CNS following several pathological conditions. NK cells could impact CNS physiology by killing glial cells and by secreting IFN-γ. Astrocytes are intimately involved in immunological and inflammatory events occurring in the CNS and reactive astrogliosis is a key feature in HIV-associated neurocognitive disorders. There is little data on NK-astrocyte interactions and ligands expressed on astrocytes that could impact NK cell function. Natural cytotoxicity receptors (NCRs) play a critical role in the cytolytic function of NK cells. Among the NCRs, NKp44 is unique in expression and signal transduction. NKp44 is expressed only upon activation of NK cells and it can mediate both activating and inhibitory signals to NK cells. Here, we have studied the expression and function of natural cytotoxicity receptor NKp44 upon NK-astrocytes interactions in the presence or absence of an HIV peptide (HIV-3S peptide) shown to induce NK cell killing of CD4+ T cells during HIV-infection. Using a fusion protein consisting of the extracellular domain of NKp44 fused to Fc portion of human IgG, we determined the expression of a novel ligand for NKp44 (NKp44L) on astrocytes. Incubation of astrocytes with HIV-3S peptide downregulated NKp44L expression on astrocytes implicating protection from NK mediated killing. Thus, our study showed that NKp44 have a protective effect on astrocytes from NK cell mediated killing during HIV infection and impact astrocyte role in HAND.