Interstitial fluid volume during cardiac surgery measured by means of a non-invasive conductivity technique.
Fluid accumulation in the interstitium is frequently found after cardiac surgery. In extreme this can lead to pulmonary and myocardial oedema. The origin of this accumulation is not exactly known and may be twofold. It is probably a combination of the noninfectious whole body inflammatory response and a change in Starling forces due to a decrease in colloid osmotic pressure (COP) which is caused by the primed extracorporeal circuit. To study the changes in interstitial fluid volume (ISFV) a non-invasive conductivity technique was used. The relationship between temperature and conductivity was first investigated in vitro. A linear relationship was found between conductivity and different saline solutions and temperature. From the in vitro experiments it can be concluded that temperature corrected conductivity does not depend on haematocrit. After the in vitro experiments eleven patients undergoing cardiac surgery were studied. During the first minutes of cardiopulmonary bypass (CPB) a steep significant decrease in COP to 61.4 +/- 6.9% (from 19.6 +/- 1.1 to 12.0 +/- 1.2 mmHg), and a rise in ISFV to 105.5 +/- 2.8% (from 12.3 +/- 1.4 mS to 14.0 +/- 1.3 mS) was noticed. After this decrease COP increased significantly, till the end of the operation, but did not reach the pre-operative level. An increase in ISFV was noticed till the rewarming point. After this point no significant change in ISFV was noticed. Furthermore, a significant correlation was found between the fluid balance and the ISFV increase at the start, at the end of CPB, and at the end of the operation.(ABSTRACT TRUNCATED AT 250 WORDS)


B-flow imaging of vascular structure for the diagnosis of liver tumor.
B-flow is a non-Doppler-based technology for visualizing blood flow and has a high spatial resolution. The aim of this study is to evaluate the blood flow information of liver tumors using B-flow in comparison with color Doppler sonography (CDS). Seventy-nine patients with 82 hepatic nodules were studied using B-flow and CDS. The study group included 45 HCC nodules, 23 liver metastasis nodules, four intrahepatic cholangiocarcinomas (ICC), and 13 hemangiomas. The visualized vascularity and morphological findings of the hepatic tumor vessel were evaluated. B-flow showed multiple vessels in 48 nodules (58.5 %) and a single vessel in 13 nodules (15.9 %). CDS showed multiple vessels in 44 nodules (53.7 %) and a single vessel in 23 nodules (28.0 %). Multivariate analysis showed basket pattern was significant for HCC (OR 49.263; p = 0.0002), and penetrating vessel was significant for liver metastasis or ICC (OR 14.545; p < 0.0001). B-flow detects hepatic tumor blood flow with sensitivity as high as that of CDS. Vascular structure information obtained using B-flow could be potentially used to diagnose liver tumors.


Early and late onset depression in young and middle aged adults: differential symptomatology, characteristics and risk factors?
Early onset depression (EOD) and late onset depression (LOD) may be different phenomena. In this study, differences between EOD and LOD in symptomatology, psychiatric characteristics and psychosocial/somatic factors were examined. Baseline data were from 1104 participants with a current major depressive disorder participating in the Netherlands Study of Depression and Anxiety (age range 18-65 years). DSM-IV diagnoses, depressive symptoms and age of onset were assessed with the Composite International Diagnostic Interview. Analyses were performed by using a continuous as well as a dichotomous (cut-off 40 years) age of onset indicator. Differences between EOD and LOD were observed: longer duration of symptoms (p<.001), a personal history of depressive episodes (p<.001), a serious suicide attempt (p<.001), childhood events (p<.001), a family history of depression (p=.03), and high neuroticism (p<.001) were more often present in EOD than in LOD. Also differences in symptomatology were observed: feelings of sadness (p<.001), diminished concentration (p=.02) and suicidal thoughts (p=.001) were significantly less prevalent at a higher age of onset, whereas decreased appetite/weight loss (p=.01) was more prominent at a higher age of onset. The age of first depression onset was asked retrospectively and might be biased by selective recall. However, participants can likely recall whether symptoms started earlier or later in life. Despite similarities, our observed differential findings in symptoms, psychiatric characteristics, and psychosocial factors between EOD and LOD further support that EOD is associated with more frequent occurrence of some clinical features of depression. These differential findings are important factors to keep in mind for diagnostics, treatment, and prevention.


Validation of the multi-metric D-index change in the assessment of keratoconus progression.
To validate the effectiveness of the multi-metric D-index by Pentacam in detecting keratoconus (KC) progression. This was a retrospective study of KC patients at the Rabin Medical Center, Petah Tikva, Israel, during 2016-2018 with at least two corneal tomography examinations six months apart. Agreement between clinical diagnosis of progression (1.5D increase in mean keratometric value, 1D increase in Kmax, a 5% decrease in central corneal thickness (CCT), worsening of visual acuity by more than one line, or deterioration of manifest corneal astigmatism > 1.5D) and the D-index was evaluated. Receiver operating characteristic (ROC) analysis was used to find the D-index's optimal cutoff value to show progression. We included KC eyes in the stable group (N = 7) and the progression group (N = 54). Patient demographics and tomographic parameters at baseline were similar between the groups. The D-index change was significantly higher in the progression group than in the stable group (median + 1 and 0.0, respectively, p = 0.024). Based on the ROC analysis, the optimal D-index cutoff change within at least six months was 0.32 (59.3% sensitivity and 100% specificity (area under the curve [AUC] = 0.771, Youden = 0.592). Subjects with a D-index change above this value had a 21.1-fold increase in odds for corneal ectasia progression requiring CXL (OR: 21.1, 95%CI 1.17-398.8, p = 0.038). The multi-metric D-index can serve as a clinically feasible parameter to detect KC progression and guide patients' referral for further interventions.


Clinical and Imaging Characteristics Associated with Color Vision Impairment in Lewy Body Disease.
Color vision impairment (CVI) has been reported in dementia with Lewy bodies (DLB) and prodromal Lewy body disease (pro-LBD). In order to better characterize the diagnostic value of CVI testing, we compared the prevalence of CVI in patients with with Lewy body disease compared to Alzheimer's disease (AD), and we examined clinical and imaging characteristics associated with CVI in patients with DLB and suspected pro-LBD. We retrospectively reviewed medical records, dopamine transporter (DaT-SPECT) imaging, and volumetric MRI from patients with AD, DLB, and suspected pro-LBD who underwent an online Farnsworth D-15 color vision test. 111 patients (62 DLB, 25 pro-LBD, and 24 AD) were included with a median age of 75 years. Newly diagnosed CVI was present in 67% of patients with DLB, 44% of patients with pro-LBD, and 18% of patients with AD. In patients with DLB, CVI was associated with lower Montreal Cognitive Assessment (MoCA) scores and lower sub-scores in visuospatial/executive function, naming, and language. In a multivariable logistic regression model, a diagnosis of DLB or pro-LBD compared to AD, and a lower composite MoCA score in visuospatial/executive function, naming, and language were associated with CVI controlling for age and gender. Among 17 DLB patients who underwent volumetric MRI, patients with CVI (n = 9) demonstrated lower normative volumetric percentiles in the right transverse superior temporal lobe. We provide further evidence that CVI can help differentiate DLB from AD, and we suggest that CVI may be an indicator of cognitive decline and disease progression in DLB.


Controlling the terminal layer atom of InTe for enhanced electrochemical oxygen evolution reaction and hydrogen evolution reaction performance.
Herein, we report the method of molecular-beam-epitaxial growth (MBE) for precisely regulating the terminal surface with different exposed atoms on indium telluride (InTe) and studied the electrocatalytic performances toward hydrogen evolution reaction (HER) and oxygen evolution reaction (OER). The improved performances result from the exposed In or Te atoms cluster, which affects the conductivity and active sites. This work provides insights into the comprehensive electrochemical attributes of layered indium chalcogenides and exhibits a new route for catalyst synthesis.


Decades of beauty: Achieving aesthetic goals throughout the lifespan.
Several elements, including age, influence judgments of beauty and attractiveness. Aging is affected by intrinsic factors (e.g., genetics, race/ethnicity, anatomical variations) and extrinsic factors (e.g., lifestyle, environment). To provide a general overview of minimally invasive injectable procedures for facial beautification and rejuvenation to meet the aesthetic goals of patients across their lifespan, organized by decade. This case study review describes aesthetic considerations of females in their third to sixth decade of life (i.e., 20-60 years of age or beyond). Each case study reports the treatments, specifically botulinum toxin type A and soft tissue fillers, used to address aesthetic concerns. Signs of aging, as well as aesthetic goals and motivations, vary by age groups, cultures, and races/ethnicities. However, there are overarching themes that are associated with each decade of life, such as changes in overall facial shape and specific facial regions, which can be used as a starting point for aesthetic treatment planning. Appropriate patient selection, thorough aesthetic evaluation, product knowledge, and injection technique, as well as good physician-patient communication, are essential for optimal treatment outcomes. Nonsurgical facial injectable treatments can successfully enhance and rejuvenate facial features across different age ranges. A comprehensive understanding of facial aging and the aesthetic considerations of patients by the decade contributes to optimal treatment planning and maintenance.


Sequential change of DNA synthesis in cultured aortic smooth muscle cells stimulated by hyperlipidemic serum.
Smooth muscle cells from monkey aorta quiescent in 5% calf serum have been shown to be stimulated to renewed proliferation by hyperlipidemic serum or LDL from such serum. This proliferative response evidently is not dependent on platelet-derived growth factor present in our system in large quantities. The least exposure time required for reaction between the mitogen and the cells in order to initiate maximal DNA synthesis by this mechanism was studied using autoradiography. Stationary primary cultures and subcultures from monkey aortic media required at least 4 and 8 hr of contact with hyperlipidemic serum or LDL so that a significant number of cells reentered the mitotic cycle. Compared to the primary culture system, subcultures needed a slightly longer time of contact with serum to initiate DNA synthesis. Since there was no significant difference in labeling index between the primary cultures stimulated by serum for 8 and 48 hr and the subcultures exposed between 6 and 48 hr, it is concluded that a relatively brief stimulation commits the majority of responsive cells to reenter the cycle and initiate DNA synthesis.


IRAG2 Interacts with IP3-Receptor Types 1, 2, and 3 and Regulates Intracellular Ca2+ in Murine Pancreatic Acinar Cells.
The inositol 1,4,5-triphosphate receptor-associated 2 (IRAG2) is also known as Jaw1 or lymphoid-restricted membrane protein (LRMP) and shares homology with the inositol 1,4,5-triphosphate receptor-associated cGMP kinase substrate 1 (IRAG1). IRAG1 interacts with inositol trisphosphate receptors (IP3 receptors /IP3R) via its coiled-coil domain and modulates Ca2+ release from intracellular stores. Due to the homology of IRAG1 and IRAG2, especially in its coiled-coil domain, it is possible that IRAG2 has similar interaction partners like IRAG1 and that IRAG2 also modulates intracellular Ca2+ signaling. In our study, we localized IRAG2 in pancreatic acinar cells of the exocrine pancreas, and we investigated the interaction of IRAG2 with IP3 receptors and its impact on intracellular Ca2+ signaling and exocrine pancreatic function, like amylase secretion. We detected the interaction of IRAG2 with different subtypes of IP3R and altered Ca2+ release in pancreatic acinar cells from mice lacking IRAG2. IRAG2 deficiency decreased basal levels of intracellular Ca2+, suggesting that IRAG2 leads to activation of IP3R under unstimulated basal conditions. Moreover, we observed that loss of IRAG2 impacts the secretion of amylase. Our data, therefore, suggest that IRAG2 modulates intracellular Ca2+ signaling, which regulates exocrine pancreatic function.


Dimethyloxaloylglycine-stimulated human bone marrow mesenchymal stem cell-derived exosomes enhance bone regeneration through angiogenesis by targeting the AKT/mTOR pathway.
Mesenchymal stem cell (MSC)-derived exosomes have been recognized as new candidate agents for treating critical-sized bone defects; they promote angiogenesis and may be an alternative to cell therapy. In this study, we evaluated whether exosomes derived from bone marrow-derived MSCs (BMSCs) preconditioned with a low dose of dimethyloxaloylglycine (DMOG), DMOG-MSC-Exos, exert superior proangiogenic activity in bone regeneration and the underlying mechanisms involved. To investigate the effects of these exosomes, scratch wound healing, cell proliferation, and tube formation assays were performed in human umbilical vein endothelial cells (HUVECs). To test the effects in vivo, a critical-sized calvarial defect rat model was established. Eight weeks after the procedure, histological/histomorphometrical analysis was performed to measure bone regeneration, and micro-computerized tomography was used to measure bone regeneration and neovascularization. DMOG-MSC-Exos activated the AKT/mTOR pathway to stimulate angiogenesis in HUVECs. This contributed to bone regeneration and angiogenesis in the critical-sized calvarial defect rat model in vivo. Low doses of DMOG trigger exosomes to exert enhanced proangiogenic activity in cell-free therapeutic applications.


Morphogenesis of termite mounds.
Several species of millimetric-sized termites across Africa, Asia, Australia, and South America collectively construct large, meter-sized, porous mound structures that serve to regulate mound temperature, humidity, and gas concentrations. These mounds display varied yet distinctive morphologies that range widely in size and shape. To explain this morphological diversity, we introduce a mathematical model that couples environmental physics to insect behavior: The advection and diffusion of heat and pheromones through a porous medium are modified by the mound geometry and, in turn, modify that geometry through a minimal characterization of termite behavior. Our model captures the range of naturally observed mound shapes in terms of a minimal set of dimensionless parameters and makes testable hypotheses for the response of mound morphology to external temperature oscillations and internal odors. Our approach also suggests mechanisms by which evolutionary changes in odor production rate and construction behavior coupled to simple physical laws can alter the characteristic mound morphology of termites.


Purified bovine plasma blocking factor decreases Bovine leukemia virus p24 expression while increasing protein synthesis and transcriptional activity of peripheral blood mononuclear cells in short-term culture.
Bovine leukemia virus (BLV) induces a persistent infection in the B-cells causing polyclonal expansion of B-cells in one-third of infected cattle and lymphosarcoma in less than 5% of infected cattle. While BLV is difficult to detect in vivo, it is readily produced by cultured lymphocytes and is diminished when supplemented by bovine plasma. This phenomenon is attributed to a poorly characterized plasma blocking factor (PBF). We assessed the effects of bovine plasma on cell viability and BLV p24 expression, and the effects of purified PBF on protein synthesis and gene expression of short-term cultures of bovine lymphocytes. The addition of 25% plasma or semi-purified PBF to cultures had no significant effect on cell viability but caused significant decreases in BLV p24 production and significantly increased de novo protein synthesis. Utilizing a human microarray, the RNA messages of 83 genes involved in cell division, cell metabolism, and gene regulation were up-regulated.


Apexification of a replanted tooth using mineral trioxide aggregate.
The most important factors determining periodontal healing after replantation of an avulsed tooth are the extra oral period and the media in which the tooth is preserved before replantation. This case report describes an adequate periodontal healing of an avulsed immature tooth replanted after 20 min of extra alveolar dry time. Vitality was not regained and after disinfection of the pulp space mineral trioxide aggregate was used as the root filling. Follow-up confirmed complete healing periradicularly.


Preparation and antigenic property of 3-dehydrolithocholylglycine 3-(O-carboxymethyl) oxime-bovine serum albumin conjugate.
The preparation and antigenic property of 3-dehydrolithocholyglycine-bovine serum albumin (BSA) conjugate in which the hapten is linked to the carrier protein through an (O-carboxymethyl) oxime bridge at the C-3 position on the steroid nucleus is described. Antibody raised against antigen in the rabbit possessed high titer and specificity to lithocholylglycine, exhibiting no significant cross-reaction with free lithocholic acid or lithocholyltaurine.


Valorization of lignin-derived compounds into poly(3-hydroxybutyrate-co-3-hydroxyvalerate) by engineered Halomonas sp. Y3.
Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) is a biopolyester with great potential, but its high production cost via the propionate-dependent pathway has hindered its development. Herein, we engineer Halomonas sp. Y3 to achieve efficient conversion of various LDCs into PHBV without propionate supplement. Initially, we successfully achieve PHBV production without propionate supplement by overexpressing threonine synthesis. The resulting biopolyester exhibits a 3 HV proportion of up to 7.89 mol%, comparable to commercial PHBV (8 mol%) available from Sigma Aldrich (403105). To further enhance PHBV production, we rationally design the reconstruction of aromatic compound catabolism. The engineered strain Y3_18 efficiently assimilates all LDCs containing syringyl (S), guaiacyl (G), and p-hydroxyphenyl-type (H) units. From 1 g/L of S-, G-, and H-type LDCs, Y3_18 produces PHBV at levels of 449 mg/L, 488 mg/L, and 716 mg/L, respectively, with yields of 44.9 % (g/g), 48.8 % (g/g), and 71.6 % (g/g). Moreover, to improve PHBV yield from lignin, we integrate laccase-secretion and PHBV production modules. This integration leads to the accumulation of 425.84 mg/L of PHBV with a yield of 21.29 % (g/g) and a 3 HV proportion of 6.38 mol%. By harnessing the capabilities of Halomonas sp. Y3, we demonstrate an efficient and sustainable approach for PHBV production from a variety of LDCs.


MicroRNA-377-3p released by mesenchymal stem cell exosomes ameliorates lipopolysaccharide-induced acute lung injury by targeting RPTOR to induce autophagy.
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the severe lung damage and respiratory failure without effective therapy. However, there was a lack of understanding of the mechanism by which exosomes regulate autophagy during ALI/ARDS. Here, we found lipopolysaccharide (LPS) significantly increased inflammatory factors, administration of exosomes released by human umbilical cord mesenchymal stem cells (hucMSCs) successfully improved lung morphometry. Further studies showed that miR-377-3p in the exosomes played a pivotal role in regulating autophagy, leading to protect LPS induced ALI. Compared to exosomes released by human fetal lung fibroblast cells (HFL-1), hucMSCs-exosomes overexpressing miR-377-3p more effectively suppressed the bronchoalveolar lavage (BALF) and inflammatory factors and induced autophagy, causing recoveration of ALI. Administration of miR-377-3p expressing hucMSCs-exosomes or its target regulatory-associated protein of mTOR (RPTOR) knockdown significantly reduced ALI. In summary, miR-377-3p released by hucMSCs-exosomes ameliorated Lipopolysaccharide-induced acute lung injury by targeting RPTOR to induce autophagy in vivo and in vitro.


Phase equilibria of the ternary system 1-palmitoyl-sn-glycero-3-phosphocholine/oleic acid/water studied by NMR.
Part of a phase diagram for the system 1-palmitoyl-sn-glycero-3-phosphocholine (PamGroPCho)/oleic acid/water has been constructed from mainly 31P-NMR data and a previous determination of the phase equilibria of the binary PamGroPCHo/water system. It was found that the appearance of the phase diagram is very similar to those found for several simple soap/fatty acid/water or soap/long-chain alcohol/water systems. The most striking features observed are: (1) the lamellar phase can swell towards very high water contents (2) vesicles are formed after sonication and (3) the cubic liquid crystalline phase disappears upon addition of very small amounts of oleic acid. The self-association of the amphiphiles and the shape of the aggregates are discussed in terms of existing first-order approximative theories.


Serum tumor markers in patients with metastatic germ cell tumors of the testis. A 10-year experience.
The serum values of alphafetoprotein, human chorionic gonadotropin, lactate dehydrogenase, and carcinoembryonic antigen in patients with metastatic testicular cancer were reviewed for the period 1972 to 1982. All values were obtained before chemotherapy was begun. Elevated values of alphafetoprotein were present in 47 percent of patients tested, of human chorionic gonadotropin in 60 percent, of lactate dehydrogenase in 64 percent, and of carcinoembryonic antigen in 11 percent. The frequency of elevated values of alphafetoprotein, human chorionic gonadotropin, and lactate dehydrogenase decreased during the study period. Inverse relations between elevated values of alphafetoprotein, human chorionic gonadotropin, and lactate dehydrogenase and both complete remission rate and survival rate were noted in some of the chemotherapy trials. Carcinoembryonic antigen was believed not to be useful as a marker in this disease. It is concluded that assays of alphafetoprotein, human chorionic gonadotropin, and lactate dehydrogenase are important both clinically and prognostically in patients with testicular cancer.


Theory of current-driven domain wall motion: spin transfer versus momentum transfer.
A self-contained theory of the domain wall dynamics in ferromagnets under finite electric current is presented. The current has two effects: one is momentum transfer, which is proportional to the charge current and wall resistivity (rho(w)); the other is spin transfer, proportional to spin current. For thick walls, as in metallic wires, the latter dominates and the threshold current for wall motion is determined by the hard-axis magnetic anisotropy, except for the case of very strong pinning. For thin walls, as in nanocontacts and magnetic semiconductors, the momentum-transfer effect dominates, and the threshold current is proportional to V(0)/rho(w), V0 being the pinning potential.


Interleukin-8 as a modulator of response to bevacizumab in preclinical models of head and neck squamous cell carcinoma.
Bevacizumab, a monoclonal antibody to VEGF-A, is under active clinical evaluation in head and neck squamous cell carcinoma (HNSCC) and appears to be a promising therapy in at least a subset of patients. However, there are no reliable predictive biomarkers to identify those patients most likely to benefit. In this study, we assessed the efficacy of bevacizumab in HNSCC xenograft models to characterize escape mechanisms underlying intrinsic resistance and identify potential biomarkers of drug response. We evaluated the angiogenic profile of HNSCC cells from sensitive and resistant cell lines using antibody array. We further examined the role of interleukin-8 (IL-8) in contributing to resistance both in vitro and in vivo, using a loss- and gain-of-function approach. Angiogenic profiling indicated that resistant cells expressed higher levels of proangiogenic factors including IL-8, interleukin-1α (IL-1α), vascular endothelial growth factor (VEGF), fibroblast growth factor-a (FGF-a), and tumor necrosis factor-α (TNF-α). IL-8 was the most differentially expressed protein. IL-8 signaling compensated for VEGF inhibition in endothelial cells. Downregulation of IL-8 resulted in sensitization of resistant tumors to bevacizumab by disrupting angiogenesis and enhancing endothelial cell apoptosis. Overexpression of IL-8 in sensitive tumors conferred resistance to bevacizumab. Serum analysis of HNSCC patients treated with a bevacizumab-containing regime revealed high baseline IL-8 levels in a subset of patients refractory to treatment but not in responders. These results implicate IL-8 in mediating intrinsic resistance to bevacizumab in HNSCC. Hence, co-targeting of VEGF and IL-8 may help overcome resistance and enhance therapeutic efficacy.


Facial electromyographic reactions and autonomic activity to auditory stimuli.
This study explored whether high- and low-intensity auditory stimuli evoke different facial electromyographic reactions and autonomic responses. Subjects were repeatedly exposed to 95-dB and 75-dB tones (1000 Hz, 40 ms rise and fall times) while their facial electromyograms from the corrugator and zygomatic muscle regions, heart rate, skin conductance responses, skin conductance half recovery time and ratings were measured. The 95-dB tone evoked a "negative" reaction with increased corrugator activity and an autonomic response pattern that carried aspects of a defense reaction, that is, slowly habituating skin conductance responses with retarded recovery rate and an initial tendency to heart rate acceleration. Furthermore, the 95-dB tone was rated as unpleasant. The 75-dB tone elicited an orienting response indicated by a distinct heart rate deceleration and fast habituating skin conductance responses with a relatively short recovery time. Thus, the present study demonstrated that the facial electromyographic technique is sensitive to simple environmental stimuli such as auditory stimuli and that the facial response is consistent with the autonomic response patterns and the experience of the stimuli.


Local orthogonality as a multipartite principle for quantum correlations.
In recent years, the use of information principles to understand quantum correlations has been very successful. Unfortunately, all principles considered so far have a bipartite formulation, but intrinsically multipartite principles, yet to be discovered, are necessary for reproducing quantum correlations. Here we introduce local orthogonality, an intrinsically multipartite principle stating that events involving different outcomes of the same local measurement must be exclusive or orthogonal. We prove that it is equivalent to no-signalling in the bipartite scenario but more restrictive for more than two parties. By exploiting this non-equivalence, it is then demonstrated that some bipartite supra-quantum correlations do violate the local orthogonality when distributed among several parties. Finally, we show how its multipartite character allows revealing the non-quantumness of correlations for which any bipartite principle fails. We believe that local orthogonality is a crucial ingredient for understanding no-signalling and quantum correlations.


Performance of common spatial pattern under a smaller set of EEG electrodes in brain-computer interface on chronic stroke patients: a multi-session dataset study.
Brain-computer interface (BCI) uses non-muscular channel of the nervous system for communication. Common Spatial Pattern (CSP) is a popular spatial filtering method used to reduce the effect of volume conduction on EEG signals. It is thought that CSP requires a large number of electrodes to be effective. Using a 20-session dataset of motor imagery BCI usage by 5 stroke patients, we demonstrated that after channel selection, CSP can still maintain a high accuracy with low number of electrodes using a newly proposed channel selection method called CSP-rank (higher than 90% with 8 electrodes). The results showed that using only the first session for channel selection, a high accuracy can be maintained in subsequent sessions. CSP-rank has been compared to the popular support vector machine recursive feature elimination (SVM-RFE). The results showed that the CSP-rank required less electrodes to maintain accuracy higher than 90% (a minimum of 8 compared to 12 of SVM-RFE) and it attained a higher maximum accuracy (91.7% compared with 90.7% of SVM-RFE). This could support clinicians to apply more BCI in routine rehabilitation.


Management of children with febrile seizures: a Greek nationwide survey.
The purpose of this study was to investigate knowledge, principles, and practices concerning the management of children with febrile seizures among pediatricians in Greece. A cross-sectional study was performed across Greece. Pediatricians completed an anonymous and voluntary 11-item questionnaire about their knowledge, attitudes, and practices with respect to the management of febrile seizures; the survey also collected demographic data. It was first administered in paper form in October 2017. This was followed by an online survey performed between June and August of 2018 and publicized by medical boards across Greece. Descriptive statistics and comparisons between groups were conducted with the significance level set at p ≤ 0.05. We recorded 457 responses. Pediatricians admitted to modifying their advice to the parents of children with febrile seizures by suggesting more "aggressive" fever management at low temperatures or systematically (63%), referral to a specialist after any episode of febrile seizures (63%), or hospitalization in a subsequent episode (67%), even though 72% admitted these practices were of no efficacy. Almost one in three pediatricians (28%) believed aggressive management of fever could delay the onset of febrile seizures; increasing age was associated with this perception. A minority (28%) would make parents aware of febrile seizures before a first episode regardless of family history; 38% would do so in the event of family history. Several pediatricians in Greece use outdated and ineffective practices for the management of febrile seizures, despite the availability of updated evidence-based guidelines. Further training of practitioners is needed to bridge this gap. •Aggressive management of fever at low temperatures with antipyretics, referral to a neurologist, and hospitalization are not supported by evidence or recent guidelines on childhood febrile seizures. •Febrile seizures are especially disturbing to uninformed parents, who may be inclined to pursue aggressive but ineffective treatments as a result. •Pediatricians in Greece use non-evidence-based practices for the management of febrile seizures, even when they are aware that these practices are not effective. •Older age increases the likelihood that a pediatrician will pursue guideline non-compliant practices in Greece. At the same time, physicians with over 20 years of experience are more likely to inform parents in advance about febrile seizures.


Demand risk transfer and government's cost efficiency: Focusing on Korean waste treatment PPP cases.
This study aimed to examine the government's cost efficiency considering the high-risk/high-return mechanism of PPP. Faced with increasing demand but with limited budget, the Korean government has relied on the Public-Private Partnership (PPP) to provide waste treatment services for the last couple of decades to expand fiscal space. However, most of waste treatment facilities projects have been promoted using the BTO (Build-Transfer-Operate) method with high rate of return due to the demand risk that is transferred to the private. We performed a conversion analysis of a BTO to a BTL (Build-Transfer-Lease) method, in which demand risk is borne by the government, for 18 PPP waste treatment cases with actual operation records. The result of comparing the life-cycle costs of government in employing each project method shows that the BTL can provide 5.26% of Value for Money (VfM) compared to the BTO as the government takes the demand risk and lowers the required rate of return of the private. This implies that transferring the demand risk to the private sector may not always be the best option for the government. From the government's perspective, instead of transferring the demand risk to the private and providing a high rate of return, the government can retain the demand risk and reduce the rate of return, and it can be fiscally more advantageous considering the cost structure of each PPP method. Through Korean PPP waste treatment cases, this study suggests that policy makers who implement PPP should consider the government's strategic risk sharing by understanding the predictability of demand and the nature of cost structure of each PPP method.


Fruticulosin: A novel type 2 ribosome-inactivating protein from Abrus fruticulosus seeds that exhibits toxic and antileishmanial activity.
Plant ribosome-inactivating proteins (RIPs) are a family of toxins that inhibit protein synthesis. In this study, we have isolated a novel type 2 ribosome-inactivating protein (RIP) present in seeds of the Abrus fruticulosus, named of fruticulosin. Fruticulosin, shows characteristics common to other type 2 RIPs, as specificity by galactosides (d-galactose, N-acetyl-d-galactosamine, and d-lactose), mass of approximately 60 kDa and presence of the of disulfide bonds. The N-terminal amino acid sequence (26 residues) of A-chain fruticulosin, determined by Edman degradation, revealed high similarity of the A-chain with those of other type 2 RIPs. The secondary structure of fruticulosin was analysed by circular dichroism, which showed that fruticulosin contains α-helices (22.3%), β-sheets (43.5%), and random coils and corners (34.2%). Furthermore, fruticulosin showed high toxicity in Artemia sp. (3.12 μg/mL), inhibited in vitro protein synthesis by a cell-free system and showed RNA N-glycosidase activity. Fruticulosin presented biological activities such as agglutination and antileishmanial activity on promastigote forms of Leishmania major.


Effects in postmenopausal women of estradiol and medroxyprogesterone alone and combined on resistance artery function and endothelial morphology and movement.
Endothelial dysfunction in resistance arteries after menopause is important for the development of high blood pressure and cardiovascular disease. Our objectives were to study the effects of different hormone replacement therapies on the function and morphology of isolated resistance arteries, and to look for their mechanistic basis. This was a randomized, placebo-controlled double-blind study in a University hospital, along with laboratory based studies. We isolated resistance arteries in sc biopsies from 55 postmenopausal women before and after 3-month therapy with estradiol (E2), medroxyprogesterone acetate (MPA), E2 plus MPA, or placebo. In addition, we studied isolated human endothelial cells. Artery flow-mediated dilatation was augmented after treatment with E2 or E2 plus MPA, whereas MPA or placebo had no effect. Pressure-induced myogenic tone was reduced by E2 plus MPA, whereas it was unchanged in the other groups. Scanning microscopy showed that E2 improved endothelial cell morphology and decreased signs of endothelial apoptosis, but the addition of MPA impaired these events. E2, MPA, or the combination all increased the expression and phosphorylation of the actin-binding protein, moesin and of the focal adhesion complex controller, focal adhesion kinase, and induced the rearrangement of cytoskeletal actin and vinculin fibers. All treatments promoted endothelial cell horizontal migration, with E2 inducing the strongest effect. This study suggests that hormone replacement therapy with estrogens or in combination with MPA may benefit the function of resistance arteries and may preserve the morphological integrity of endothelial cells by regulatory actions on the cytoskeleton.


[Induced androgenesis in fish: obtaining viable nucleocytoplasmic hybrids].
A self-review of long-standing studies of induced androgenesis in fish. The data are provided on the induction of diploid androgenesis in teleost fish via blocking the first cleavage division and the development of the method of dispermic androgenesis in sturgeon fish. Androgenetic nucleocytoplasmic hybrids were obtained using the method of dispermic androgenesis and eggs of previously produced true interspecific hybrids. Specific morphological features of androgenetic hybrids were described and dispermic androgenesis was realized using cryopreserved sperm. The mechanism of sex determination in sturgeon fish is discussed with reference to possible us of androgenesis for restoration of rare and disappearing species.


High-Risk Behaviors and Associated Factors among Iranian Adult Population: A National Survey.
There is no official and representative information on certain health-risk behaviors in Iran. This national survey was performed to determine the prevalence of five high-risk behaviors among the adult population and underlying factors. This cross-sectional study was performed in 23 provinces of Iran in 2019 involving 10,957 participants. The following five risky behaviors were evaluated: (a) using illicit drugs in the past month, (b) drinking alcohol in the past month, (c) having extramarital sex in the past year, (d) having suicidal thoughts in the past month, (e) and attempting suicide in the past year. The logistic regression model was used for analyses and associations were reported using odds ratio (OR) with its 95% confidence interval (CI). The prevalence of health-risk behaviors was as follows: illicit drug use 10.4%, drinking alcohol 16.8%, extramarital sex 9.9%, suicidal thoughts 8.8%, and suicide attempt 5.4%. Almost 27.6% of the participants were involved in at least one risky behavior. There was a strong association between illicit drugs use and male gender 2.51 (2.11-2.98) and using psychiatric medications 2.96 (2.46-3.55); between drinking alcohol and male gender 2.23 (1.93-2.58); between extramarital sex and divorced/widowed status 2.43 (1.72-3.44) and having an intimate friend of the opposite sex 3.75 (3.13-4.51); between suicidal thoughts and using psychiatric medications 2.23 (1.83-2.72); between suicide attempt and a history of running away from home 2.10 (1.64-2.68). More than one-fourth Iranian adult population is involved in at least one risky behavior. Engaging in any risky behavior may increase the possibility of engaging in other high-risk behaviors.


Subcellular location and topography of rat hepatic monoacylglycerol acyltransferase activity.
Monoacylglycerol acyltransferase activity from suckling rat liver was localized to the microsomal subcellular fraction by differential centrifugation and comparison with the partitioning of selected marker enzymes. Chymotrypsin, pronase, and proteinase K inactivated the monoacylglycerol acyltransferase activity in detergent-disrupted microsomes, but not in intact microsomes, falsely suggesting a lumenal location for the enzyme. The impermeant inhibitors mercury-dextran and 4,4'-diisothiocyano,-2,2'-disulfonic acid stilbene inhibited monoacylglycerol acyltransferase in intact microsomes. These data, as well as the lack of latency and the inability of the substrate palmitoyl-CoA to readily permeate hepatic microsomes from suckling rats, strongly suggest that the enzyme's active site faces the cytosolic surface of the endoplasmic reticulum.


PI3K/Akt: getting it right matters.
The Akt serine/threonine kinase (also called protein kinase B) has emerged as a critical signaling molecule within eukaryotic cells. Significant progress has been made in clarifying its regulation by upstream kinases and identifying downstream mechanisms that mediate its effects in cells and contribute to signaling specificity. Here, we provide an overview of present advances in the field regarding the function of Akt in physiological and pathological cell function within a more generalized framework of Akt signal transduction. An emphasis is placed on the involvement of Akt in human diseases ranging from cancer to metabolic dysfunction and mental disease.


Qualitative study on the use of emergency services by people with serious mental disorder in Spain.
The population with severe mental disorders (SMD) is a frequent user of emergency services. Situations of psychiatric decompensation can have devastating consequence and can cause problems in getting urgent medical care. The objective was to study the experiences and needs of these patients and their caregivers regarding the demand for emergency care in Spain. Qualitative methodology involving patients with SMD and their informal caregivers. Purposive sampling by key informants in urban and rural areas. Paired interviews were carried out until data saturation. A discourse analysis was conducted, obtaining a codification in categories by means of triangulation. Forty-two participants in twenty-one paired interviews (19 ± 7.2 min as mean duration). Three categories were identified. 1º Reasons for urgent care: poor self-care and lack of social support, as well as difficulties in accessibility and continuity of care in other healthcare settings. 2º Urgent care provision: trust in the healthcare professional and the information patients receive from the healthcare system is crucial, telephone assistance can be a very useful resource. 3º Satisfaction with the urgent care received: they request priority care without delays and in areas separated from the other patients, as well as the genuine interest of the professional who attends them. The request for urgent care in patients with SMD depends on different psychosocial determinants and not only on the severity of the symptoms. There is a demand for care that is differentiated from the other patients in the emergency department. The increase in social networks and alternative systems of care would avoid overuse of the emergency departments.


Molecular cloning and characterisation of cytosolic manganese superoxide dismutase (cytMn-SOD) from the giant freshwater prawn Macrobrachium rosenbergii.
A cytosolic manganese superoxide dismutase (cytMn-SOD) cDNA was cloned from the hepatopancreas of giant freshwater prawn Macrobrachium rosenbergii using reverse transcription polymerase chain reaction (RT-PCR) by degenerate primers. Both 3'- and 5'-regions were isolated by rapid amplification of cDNA end RACE method. Analysis of nucleotide sequence revealed that the cytMn-SOD cDNA clone consists of 1339 bp with an open reading frame of 858 bp encoding a protein of 286 amino acids. The calculated molecular mass of the mature proteins (286 amino acids) is 31 kDa with an estimated pI of 5.52. Two putative N-glycosylation sites, NXT and NXS were observed in the cytMn-SOD. Four conserved amino acids responsible for binding manganese were observed (H110, H158, D243 and H247). Sequence comparison showed that the cytMn-SOD deduced amino acid sequence of M. rosenbergii has an overall similarity of 77% and 54% to that of blue crab Callinectes sapidus and tiger shrimp Penaeus monodon, respectively. Quantitative real-time RT-PCR analysis showed that cytMn-SOD transcript in hepatopancreas of M. rosenbergii decreased 3h after Lactococcus garvieae injection, but no significant change in cytMn-SOD transcript was observed in the haemocytes 3-24 h after L. garvieae injection.


Comprehensive analysis of mitochondrial DNA based genetic diversity in Indian goats.
Thirty four distinct breeds and many non-descript populations represent the caprine diversity of India. Genetic characterization of breeds is an essential element in designing breeding strategies and preserving genetic diversity. Considering the popularity of mitochondrial DNA for phylogeographical studies, this study involved an extensive analysis of population structure and genetic diversity of 28 defined breeds and 5 lesser known populations representing all four major agro-climatic zones of India using mitochondrial DNA markers. Analysis of hypervariable region 1 of mtDNA control region in 443 goats together with 22 reference sequences, delineated 341 distinct haplotypes belonging to four maternal haplogroups; A, B, C and D, with haplogroup A representing 90% of the individuals. The haplotype and nucleotide diversity indices of Indian goats were 0.998 ± 0.001 and 0.028 ± 0.001, respectively indicating abundant genetic variability. Estimates of population demographic parameters from mismatch analysis suggested a relatively good fit to the model of either spatial or demographic expansion of Indian goats. AMOVA analysis and topology of MJ network suggested lack of phylogeographic structure in domestic goats, which can be attributed to unstructured animal breeding, dwindling pastures and nomadic pastoralism. Genetic differentiation between goats from different agro-ecological regions was in accordance with their geographical propinquity.


The effect of knee flexor and extensor fatigue on shock absorption during cutting movements after a jump landing.
Sporting situations include instances of continuous and/or integrated movements. However, the effect of fatigue on the performance of these movements remains unclear. To investigate the effect of knee flexor and extensor fatigue on the shock absorption strategy of the lower limb during cutting movements performed after jump landings. Twenty-four healthy participants performed cutting movements following jump landings from two heights - 30cm and 40cm - and under three levels of lower limb fatigue: pre-fatigue (100% peak knee extension torque), and post-fatigue 50% (post-50%) and 30% (post-30%) peak knee extension torque. Fatigue was induced by repeated isokinetic flexion/extension of the knee (60°/s). Compared to the pre-fatigue condition, power and work at the knee joint decreased under both post-50% and post-30% conditions (P<0.001), while the work performed by the ankle (P<0.001) increased significantly. An increase in height from 30cm to 40cm was associated with an increase in the range of motion of the ankle (P<0.001) and knee (P=0.022), peak vertical ground reaction force (P<0.001), rate of loading (P<0.001), knee stiffness (P=0.026) and peak power of the knee (P<0.001), as well as the work performed by the knee (P<0.001) and hip (P<0.001) joints. Under substantial muscle fatigue the proportion of shock absorption contributed by the knee for cutting movements performed after jump landings from a height of 40cm decreased; there was an adaptive increase in the contribution by the ankle.


Gene cloning and characterization of VcrM, a Na+-coupled multidrug efflux pump, from Vibrio cholerae non-O1.
We cloned a DNA fragment responsible for drug resistance from chromosome of Vibrio cholerae non-O1. Nucleotide sequence analysis of this fragment revealed the presence of a single open reading frame encoding a protein consisting of 445 amino acid residues. We designated the gene as vcrM. Hydropathy analysis of the deduced amino acid sequence of VcrM suggests the presence of 12 trans-membrane segments. A dendrogram showed that VcrM is a member of the DinF-subfamily within the MATE family of multidrug efflux pumps. Expression of the cloned vcrM gene in drug-hypersensitive Escherichia coli KAM32 cells made them resistant to acriflavine, 4', 6-diamidino-2-phenylindole, Hoechst 33342, rhodamine 6G, tetraphenylphosphonium chloride (TPPCl) and ethidium bromide. Efflux of acriflavine due to VcrM was dependent on Na+ or Li+. Moreover, Na+ efflux was observed with VcrM when TPPCl was added to Na+-loaded cells. Therefore, we conclude that VcrM is a Na+/drug antiporter-type multidrug efflux pump.


Expression of Secretin and its Receptor Along the Intestinal Tract in Type 2 Diabetes Patients and Healthy Controls.
The hormone secretin (SCT) is released from intestinal S cells and acts via the SCT receptor (SCTR). Circulating SCT levels increase after Roux-en-Y gastric bypass surgery and have been associated with massive weight loss and high remission rates of type 2 diabetes (T2D) linked to these operations. Exogenous SCT was recently shown to reduce ad libitum food intake in healthy volunteers. To understand SCT biology and its potential role in T2D pathophysiology, we examined the intestinal mucosal expression profile of SCT and SCTR and evaluated the density of S cells along the intestinal tract of individuals with T2D and healthy controls. Using immunohistochemistry and messenger RNA (mRNA) sequencing, we analyzed intestinal mucosa biopsies sampled along the small intestine at 30-cm intervals and from 7 well-defined anatomical sites along the large intestine (during 2 sessions of double-balloon enteroscopy) in 12 individuals with T2D and 12 healthy controls. Both groups exhibited a progressive and similar decrease in SCT and SCTR mRNA expression and S-cell density along the small intestine, with reductions of 14, 100, and 50 times, respectively, in the ileum compared to the duodenum (used as reference). Negligible amounts of SCTR and SCT mRNA, as well as low S-cell density, were found in the large intestine. No significant differences were observed between the groups. SCT and SCTR mRNA expression and S-cell density were abundant in the duodenum and decreased along the small intestine. Very low SCT and SCTR mRNA levels and S-cell numbers were observed in the large intestine, without aberrations in individuals with T2D compared to healthy controls.


Highly sulfated glycosaminoglycans augment the cross-linking of vitronectin by guinea pig liver transglutaminase. Functional studies of the cross-linked vitronectin multimers.
Vitronectin (VN) is an adhesive glycoprotein with roles in the complement, coagulation, and immune systems. Many of the functions of VN are mediated by a glycosaminoglycan binding site, near its carboxyl-terminal end. In this paper, we show that the highly sulfated glycosaminoglycans (GAGs), dextran sulfate, pentosan polysulfate, and fucoidan effectively augment [14C]putrescine incorporation into VN and cross-linking of VN into high molecular multimers by guinea pig liver transglutaminase (TG). Other GAGs including heparin, low molecular weight heparin, dermatan sulfate, keratan sulfate, and the nonsulfated dextrans were ineffective in accelerating these reactions. Dextran sulfate of average molecular mass 500 kDa was more effective than dextran sulfate of average molecular mass 5 kDa, supporting a template mechanism of action of the GAGs, in which VN molecules align on the GAG in a conformation suitable for cross-linking. The VN multimers catalyzed by TG retained functional activity in binding [3H]heparin, platelets, and plasminogen activator inhibitor type-1 (PAI-1). [3H]Heparin bound selectively to the 65-kDa monomeric band of VN and to the multimers derived from this band. PAI-1, however, bound equally to both the 75- and 65-kDa monomeric forms of VN, suggesting that the PAI-1 binding site on VN is distinct from the GAG binding site. The interaction of GAGs with the TG-catalyzed cross-linking of VN may facilitate studies of VN structure-function relationships.


An examination of the possibilities of preventive therapy in arteriolar retinopathies.
The identification of certain chronic vascular retinopathies has been marked by a search for their classification. Such proper classification has therapeutic implications. The similarities of these retinopathies are based on a shared pathogenic process, initiated by diminished arteriolar perfusion pressure, as the result of varied causes but leading to somewhat nonspecific capillary and reactive stages. On the basis of such a pathogenesis, various possible prophylactic and therapeutic measures and their organizational requirements are significant. These measures are directed to the correction of a blood perfusion pressure defect and to leaking capillaries and new vessels. Prophylactic and therapeutic exercises will be required for various chronic arteriolar capillaropathies, although the experience with one disease may be applicable to the others. Senile macular disciform degeneration provides the factors necessary for a therapeutic trial.


Immune dysfunction in the elderly and its reversal by antihistamines.
The decline in immunity seen in the elderly is a significant contributor to disease burden. This decline has largely been attributed to alterations in T cell immunity and contributes to an overall increased risk and severity of infection in the elderly. A key component of T cell immunity involves antigen presentation, an event where an antigen is processed and presented to specific immune cells for destruction. This event has been found to be crucial to immune function. Recent research has focused on a key antigen presenting cell (APC), the dendritic cell (DC), and changes within its function associated with aging. DCs are considered to be the most professional APCs, and are responsible for the initiation and outcome of effector T cells and their resultant immune response. DCs capture antigens and undergo a maturation process and polarize into either type 1 dendritic cells (DC1) or type 2 dendritic cells (DC2), based upon their ability to favor a T helper1 (Th1) or T helper 2 (Th2) T cell response, respectively. Evidence suggests that in normal healthy adults, a Th1 type response predominates, and in frail elders, a Th2 response predominates. It has been proposed that this change from a predominately Th1 type to a predominate Th2 type response is a possible mechanism for age-associated immune dysfunction. In addition, recent research has focused on how histamine, an inflammatory mediator, promotes a Th2 response. Histamine has also been shown to polarize human DCs into Th2 cell-promoting effector DCs or DC2s. This has been shown to occur via interaction with the H2 receptor. Therefore, we theorize that use of an H2 selective antihistamine will reverse this polarization back to a Th1 type response and therefore improve immune function of the frail elderly.


Sudden death in young adults: an autopsy-based series of a population undergoing active surveillance.
The purpose of this study was to define the incidence and characterization of cardiovascular cause of sudden death in the young. The epidemiology of sudden cardiac death (SCD) in young adults is based on small studies and uncontrolled observations. Identifying causes of sudden death in this population is important for guiding approaches to prevention. We performed a retrospective cohort study using demographic and autopsy data from the Department of Defense Cardiovascular Death Registry over a 10-year period comprising 15.2 million person-years of active surveillance. We reviewed all nontraumatic sudden deaths in persons 18 years of age and over. We identified 902 subjects in whom the adjudicated cause of death was of potential cardiac etiology, with a mean age of 38 ± 11 years. The mortality rate for SCD per 100,000 person-years for the study period was 6.7 for males and 1.4 for females (p < 0.0001). Sudden death was attributed to a cardiac condition in 715 (79.3%) and was unexplained in 187 (20.7%). The incidence of sudden unexplained death (SUD) was 1.2 per 100,000 person-years for persons <35 years of age, and 2.0 per 100,000 person-years for those ≥ 35 years of age (p < 0.001). The incidence of fatal atherosclerotic coronary artery disease was 0.7 per 100,000 person-years for those <35 years of age, and 13.7 per 100,000 person-years for those ≥ 35 years of age (p < 0.001). Prevention of sudden death in the young adult should focus on evaluation for causes known to be associated with SUD (e.g., primary arrhythmia) among persons <35 years of age, with an emphasis on atherosclerotic coronary disease in those ≥ 35 years of age.


Alteration of bleomycin cytotoxicity by glutathione depletion or elevation.
In part, some of the cytotoxicity of bleomycin may be lessened or enhanced by modulation of glutathione (GSH) concentrations. Enhancement of bleomycin cytotoxicity was observed when GSH levels were low and protection was observed when GSH levels were elevated. Since H2O2 is one of the reactive species produced by bleomycin catalyzed oxygen activation, we studied the effects of H2O2 exposure after GSH depletion. H2O2, like bleomycin, shows enhanced cytotoxicity in GSH depleted cells. It has been proposed that bleomycin cytotoxicity requires reducing equivalents from non-protein bound thiols (such as GSH) to activate the bleomycin-metal complex, which in turn reacts with oxygen to generate free radicals and peroxides. Our data suggest that either GSH is not required to cycle reducing equivalents to the oxidized bleomycin-metal complex, or the low levels of depleted GSH attained (less than 5% of control) were still sufficient to effect reduction. Further, our data shows that GSH in fact provides a means of protection and detoxification from the cytotoxic effects of bleomycin. Our data suggest that caution should be exercised clinically when one uses drugs that modulate GSH because there may be either enhancement of normal tissue toxicity or decreases in tumor targeted cytotoxicity resulting from bleomycin treatment.


Pathogenesis of an experimental coinfection of porcine parainfluenza virus 1 and influenza A virus in commercial nursery swine.
Porcine parainfluenza virus 1 (PPIV-1) is a recently characterized swine respirovirus. Previous experimental studies reported PPIV-1 replicates in the porcine respiratory tract causing minimal clinical disease or lesions. However, it is unknown if PPIV-1 co-infections with viral respiratory pathogens would cause respiratory disease consistent with natural infections reported in the field. The objective of this study was to evaluate if PPIV-1 increases the severity of influenza A virus respiratory disease in swine. Fifty conventional, five-week-old pigs were assigned to one of three challenge groups (n = 15) or a negative control group (n = 5). Pigs were challenged with a γ-cluster H1N2 influenza A virus in swine (IAV-S; A/Swine/North Carolina/00169/2006), PPIV-1 (USA/MN25890NS/2016), inoculum that contained equivalent titers of IAV-S and PPIV-1 (CO-IN), or negative control. Clinical scores representing respiratory disease and nasal swabs were collected daily and all pigs were necropsied five days post inoculation (DPI). The CO-IN group demonstrated a significantly lower percentage of pigs showing respiratory clinical signs relative to the IAV-S challenge group from 2 to 4 DPI. The IAV-S and CO-IN groups had significantly lower microscopic composite lesion scores in the upper respiratory tract compared to the PPIV-1 group although the IAV-S and CO-IN groups had significantly higher microscopic composite lung lesion scores. Collectively, PPIV-1 did not appear to influence severity of clinical disease, macroscopic lesions, or alter viral loads detected in nasal swabs or necropsy tissues when administered as a coinfection with IAV-S. Studies evaluating PPIV-1 coinfections with different strains of IAV-S, different respiratory pathogens or sequential exposure of PPIV-1 and IAV-S are warranted.


Lessons in speed from Formula One.
A COLLABORATION between Formula One team Williams and the University Hospital of Wales (UHW) has provided clinicians with a host of ideas about how to improve care.


Conformational dynamics and role of the acidic pocket in ASIC pH-dependent gating.
Acid-sensing ion channels (ASICs) are proton-activated Na+ channels expressed in the nervous system, where they are involved in learning, fear behaviors, neurodegeneration, and pain sensation. In this work, we study the role in pH sensing of two regions of the ectodomain enriched in acidic residues: the acidic pocket, which faces the outside of the protein and is the binding site of several animal toxins, and the palm, a central channel domain. Using voltage clamp fluorometry, we find that the acidic pocket undergoes conformational changes during both activation and desensitization. Concurrently, we find that, although proton sensing in the acidic pocket is not required for channel function, it does contribute to both activation and desensitization. Furthermore, protonation-mimicking mutations of acidic residues in the palm induce a dramatic acceleration of desensitization followed by the appearance of a sustained current. In summary, this work describes the roles of potential pH sensors in two extracellular domains, and it proposes a model of acidification-induced conformational changes occurring in the acidic pocket of ASIC1a.


Horse-related injuries in children.
To identify the frequency, spectrum and outcome of horse-related injuries in children. Retrospective case series of horse-related injuries in children admitted to the Children's Hospital at Westmead (CHW) from January 1988 to December 1999, the John Hunter Children's Hospital (JHCH) from January 1991 to December 1997 and deaths reported to the New South Wales Paediatric Trauma Death (NPTD) Registry from January 1988 to December 1999. Circumstances of injury; helmet use; adult supervision; type and number of injuries identified. 232 children were admitted with horse-related trauma, 97 to the CHW over 12 years and 135 to JHCH over seven years, with one death at each hospital. There were six deaths reported to the NPTD Registry over 12 years. The median age was 11 years (range, 1-17). Girls accounted for 65% of those injured and 75% of children were injured while riding. Falls caused the injury in 76.3% of cases. Head and upper-limb trauma accounted for 216 of the injuries (73%). Five out of six children with severe head injuries died. In the CHW group, helmet use was documented in only 24 riders (38%) and adult supervision in 22 (22.9%). Horse-related trauma accounts for a considerable number of deaths and injuries in children in NSW. The use of a Standards-approved helmet for riding or horse-related activities might have decreased the severity of head injuries.


Identification of potent, selective, CNS-targeted inverse agonists of the ghrelin receptor.
The optimization for selectivity and central receptor occupancy for a series of spirocyclic azetidine-piperidine inverse agonists of the ghrelin receptor is described. Decreased mAChR muscarinic M2 binding was achieved by use of a chiral indane in place of a substituted benzylic group. Compounds with desirable balance of human in vitro clearance and ex vivo central receptor occupancy were discovered by incorporation of heterocycles. Specifically, heteroaryl rings with nitrogen(s) vicinal to the indane linkage provided the most attractive overall properties.


A V region determinant (idiotope) expressed at high frequency in B lymphocytes is encoded by a large set of antibody structural genes.
Idiotope Ac38, a V region determinant of the lambda 1 chain-bearing, germ line encoded antibody B1-8, is expressed at high frequency (approximately 1/40) in lambda 1 chain-bearing B cells. Here, we describe the isolation of lambda-positive hybridomas from C57BL/6 mice which had been immunized with antibody Ac38, the antibody recognizing idiotope Ac38. In Northern blot analysis, mRNA isolated from 10 such hybridomas hybridizes with a cDNA probe from the VH gene expressed in the cell line B1-8. Amino acid sequence analysis of the VH regions of four of the hybridoma proteins reveals that they are all derived from related, though distinct, germ line VH genes. In one case the sequence data suggest that extensive somatic mutation has taken place. Only one of the four sequences derives from the same VH gene that is expressed in the cell line B1-8. Together with earlier evidence, the present data demonstrate that the Ac38 idiotope is a marker for at least five VH and three D region genes in the C57BL/6 germ line. This explains the high frequency at which this idiotope is expressed in the B cell population. In addition, our sequence determinations identify two VH genes in the C57BL/6 strain which are closely related (and possibly allelic) to two known BALB/c VH genes. One of these genes is the gene expressed in the BALB/c myeloma MOPC 104E.


A 2-in-1 adaptive phase 2/3 design for expedited oncology drug development.
We propose an adaptive design that allows us to expand an ongoing Phase 2 trial into a Phase 3 trial to expedite a drug development program with fewer patients. Rather than the usual practice of increasing sample size with a less positive interim outcome, here we propose maintaining sample size with such a result and wait for fully mature data. The final Phase 2 data may be negative, may warrant a larger Phase 3 trial, or, in the extreme, could provide a definitively positive outcome. If the interim outcome is more positive, the trial continues to an originally planned larger sample size for a definitive Phase 3 evaluation. All patients from the study are used for inference regardless of the interim expansion decision. We show that no penalty needs to be paid in order to control the overall Type I error of the study, under a mild assumption that is expected to generally hold in practice. The proposed design may be considered an alternative approach to sample size adjustment for ongoing trials. As such, the use of an intermediate endpoint for adaptive decision is a unique feature of the design. A hypothetical example is provided for illustration purpose.


A study of the physiological mechanisms contributing to neurotensin-induced hypothermia.
Although central administration of neurotensin is known to produce marked hypothermia in the rat, there are no studies which have investigated the effects of neurotensin on oxygen consumption and heat exchange, the physiological mechanisms which are the principal contributors to changes in body temperature. We report a significant correlation between dose and the duration and degree of post-injection heat loss following central administration of neurotensin. Oxygen consumption does not appear to be affected by neurotensin. We suggest that it is this dose-dependent, post-injection heat loss which is responsible for neurotensin-induced hypothermia. Furthermore, the hypothermia does not appear to reflect a change in set point.


Thin-layer chromatographic separation and in situ fluorimetric determination of ofloxacin in plasma and pleural fluid.
A thin-layer chromatographic assay for the determination of ofloxacin in human plasma and pleural fluid is described. After extraction of ofloxacin from samples with dichloromethane, chromatography was performed on thin-layer plates (silica gel) with a mobile phase consisting of ethanol and water; the tank atmosphere was equilibrated with concentrated ammonia. The precision of the assay could be considerably increased along with the measured fluorescence intensity of ofloxacin by spraying the plate with a citric acid solution and dipping it into paraffin or using a mixture of both components. Peaks were quantified by densitometric evaluation of the chromatograms. The method shows a very low limit of detection (1 ng/ml) as well as good precision and linearity in the range 0.001-2.0 micrograms/ml for both plasma and pleural fluid.


Pseudocopulation of an orchid by male ants: a test of two hypotheses accounting for the rarity of ant pollination.
The orchid Leporella fimbriata is pollinated by pseudocopulation with winged males of the ant Myrmecia urens. This recently studied interaction provides a unique opportunity to examine the two current hypotheses concerning the apparent rarity of ant pollination systems worldwide. The first hypothesis requires a series of specialized growth forms and floral characteristics regarded as adaptations to ant pollination. L. fimbriata does not possess them. The second considers the pollenicidal effects of secretions from the metapleural gland of ants. These glands are absent in M. urens males and it may be that the occurrence of ant pollination requires the absence of metapleural glands in the vector.


Schizophrenia, schizoaffective and bipolar disorder within an epidemiologically complete, homogeneous population in rural Ireland: small area variation in rate.
While a controversy has endured as to whether schizophrenia evidences the geographical variations in rate that characterise essentially all medical conditions, even less is known of such fundamental aspects of the epidemiology of schizoaffective and bipolar disorder. Within an ethnically and socioeconomically homogeneous region of rural Ireland, population 29,542, several methodological refinements were adopted to seek an epidemiologically complete population of 'all' cases of these disorders, with each potential case interviewed and diagnosed. Prevalence and morbid risk were calculated over the region as a whole and for each of the 39 constituent District Electoral Divisions [DEDs], by place at birth and by place at onset. Using multiple sources of information, 115 cases of schizophrenia, 33 of schizoaffective disorder and 77 of bipolar disorder were identified. Unremarkable overall prevalence and morbid risk values obscured marked variation between District Electoral Divisions for schizophrenia. No such variation was observed for bipolar disorder. These data indicate, using improved methodology, that what is often interpreted as an invariant overall rate of schizophrenia across countries and cultures may not apply to spatial microstructure; macroscopic rates can obscure small area variations when ethnic and socioeconomic diversity are minimised and effects of urbanicity are absent. Under these conditions, small area variations in bipolar disorder may be limited.


Biomechanical profile of cancer stem-like cells derived from MHCC97H cell lines.
Biomechanical properties and cytoskeletal organization of cancer cells are known to be closely related with their aggressive phenotype. In this study, based on atomic force microscopy (AFM), we aimed to evaluate the mechanical property of liver cancer stem-like cells (LCSCs) and compare it with human hepatoma cells (HHCs). LCSCs were enriched from human hepatoma cell line MHCC97H through a sphere culture system. AFM nanoindentation was investigated as a method for measuring the cell stiffness, and reflecting by Young׳s modulus. Microfilament bundles of F-actin were observed with immunofluorescence staining by confocal microscopy. We found that LCSCs show lower Young׳s modulus and higher migration ability compared to MHCC97H cells. Moreover, the decrease in Young׳s modulus is accompanied with a dramatic decline in F-actin content. These results demonstrated a close relationship between the cell Young׳s modulus and metastatic potential of HHCs, which suggest that Young׳s modulus detected by AFM can be used to evaluate metastatic potential of cancer cells.


The role of preoperative mesenteric arteriography in colon interposition.
In a series of mesenteric arteriograms, the marginal artery in the right colon was present in six of 20 studies (30 percent); in the left colon it was present in all of the 20 cases studied (100 percent). Such preoperative knowledge of the vascular pattern permits the surgeon to choose a suitable segment of bowel for successful colon interposition and assists him in shortening the operative time. When this information was applied in 19 consecutive left colon interpositions, only one major suture line dehiscence in the neck was encountered (5.3 percent).


Intestinal (mesenteric) vasculopathy. I. Acute superior mesenteric arteriopathy and venopathy.
Intestinal vasculopathy is not rare, comprising about 1 per 1000 hospital admissions. Primary mesenteric vasculopathy causes cardiovascular disease, whereas secondary mesenteric ischemia causes extrinsic vascular compression or vascular trauma. Acute superior mesenteric arteriopathy is caused by a mesenteric embolus, thrombus, or vasospasm (i.e., nonocclusive vasculopathy). Acute superior mesenteric venopathy is caused by a thrombus, which is often associated with a hypercoagulopathy. The clinical presentation of both diseases is often subtle and nonspecific at an early stage and becomes overt and specific only when advanced and severe, when ischemia progresses to necrosis. The mortality of acute superior mesenteric arteriopathy is still very high, whereas superior mesenteric venopathy is less rapidly progressive and has a lower, but still significant, mortality. Early diagnosis and aggressive therapy significantly reduces the mortality of these life-threatening diseases.


Study of benzphetamine-N-demethylase in streptozotocin-diabetic mice and rats: evidence for the induction of catalytically and immunologically specific forms of cytochrome P450.
Phenobarbital treatment and streptozotocin-diabetes both increase, in mouse and rat microsomes, a benzphetamine-N-demethylase activity which can be inhibited by a specific antibody raised against purified rat phenobarbital-induced cytochrome P-450. However, similar studies performed on cytochrome P-450 A and B fractions separated by DEAE-cellulose chromatography, clearly proved that streptozotocin-diabetes promotes in mice the synthesis of two new species of cytochrome P-450 and that the streptozotocin diabetes-induced forms are different in mouse and rat. No such modifications were observed in the mixed-function oxidase system of congenitally diabetic mice.


Stenosis map for volume visualization of constricted tubular structures: Application to coronary artery stenosis.
Although direct volume rendering (DVR) has become a commodity, effective rendering of interesting features is still a challenge. In one of active DVR application fields, the medicine, radiologists have used DVR for the diagnosis of lesions or diseases that should be visualized distinguishably from other surrounding anatomical structures. One of most frequent and important radiologic tasks is the detection of lesions, usually constrictions, in complex tubular structures. In this paper, we propose a 3D spatial field for the effective visualization of constricted tubular structures, called as a stenosis map which stores the degree of constriction at each voxel. Constrictions within tubular structures are quantified by using newly proposed measures (i.e. line similarity measure and constriction measure) based on the localized structure analysis, and classified with a proposed transfer function mapping the degree of constriction to color and opacity. We show the application results of our method to the visualization of coronary artery stenoses. We present performance evaluations using twenty eight clinical datasets, demonstrating high accuracy and efficacy of our proposed method. The ability of our method to saliently visualize the constrictions within tubular structures and interactively adjust the visual appearance of the constrictions proves to deliver a substantial aid in radiologic practice.


Towards the total synthesis of FD-838: modular enantioselective assembly of the core.
A rapid assembly of the tetracyclic core of FD-838, featuring a catalytic asymmetric Stetter reaction, is described.


Nerve cell degeneration and death in the trigeminal ganglion of the adult rat following peripheral nerve transection.
Trigeminal ganglia of normal rats and of adult rats subjected to unilateral transection of the infraorbital nerve were studied by light and electron microscopy. Counts of ganglion cells in ganglia on operated and unoperated sides were made following long postoperative survival times. The ultrastructural changes in ganglia of the operated side were studied from 3 to 70 days postoperatively. The quantitative observations show that a considerable loss of ganglion cells takes place on the operated side. The ultrastructural observations demonstrate the occurrence of ganglion cell degeneration, nerve fibre degeneration and phagocytosis by satellite and Schwann cells. The results are compatible with the view that degeneration of trigeminal afferents in the brain stem following lesions of peripheral trigeminal nerve branches is related to retrograde degeneration of trigeminal ganglion cells.


Handcrafted fuzzy rules for tissue classification.
This article proposes a handcrafted fuzzy rule-based system for segmentation and identification of different tissue types in magnetic resonance (MR) brain images. The proposed fuzzy system uses a combination of histogram and spatial neighborhood-based features. The intensity variation from one type of tissue to another is gradual at the boundaries due to the inherent nature of the MR signal (MR physics). A fuzzy rule-based approach is expected to better handle these variations and variability in features corresponding to different types of tissues. The proposed segmentation is tested to classify the pixels of the T2-weighted axial MR images of the brain into three primary tissue types: white matter, gray matter and cerebral-spinal fluid. The results are compared with those from manual segmentation by an expert, demonstrating good agreement between them.


Demonstration of enhanced iodine K-edge imaging using an energy-dispersive X-ray computed tomography system with a 25 mm/s-scan linear cadmium telluride detector and a single comparator.
An energy-dispersive (ED) X-ray computed tomography (CT) system is useful for carrying out monochromatic imaging. To perform enhanced iodine K-edge CT, we developed an oscillation linear cadmium telluride (CdTe) detector with a scan velocity of 25 mm/s and an energy resolution of 1.2 keV. CT is performed by repeated linear scans and rotations of an object. Penetrating X-ray photons from the object are detected by the CdTe detector, and event signals of X-ray photons are produced using charge-sensitive and shaping amplifiers. The lower photon energy is determined by a comparator device, and the maximum photon energy of 60 keV corresponds to the tube voltage. Rectangular-shaped comparator outputs are counted by a counter card. In the ED-CT, tube voltage and current were 60 kV and 0.30 mA, respectively, and X-ray intensity was 14.8 μGy/s at 1.0m from the source at a tube voltage of 60 kV. Demonstration of enhanced iodine K-edge X-ray CT for cancer diagnosis was carried out by selecting photons with energies ranging from 34 to 60 keV.


Estimation of alkane-water logP for neutral, acidic, and basic compounds using an alkylated polystyrene-divinylbenzene high-performance liquid chromatography column.
Reliable HPLC methods are available to estimate octanol-water partition coefficients, but there is no comparable method for alkane-water partition coefficients that is accurate and applicable across a broad span of logP(alk). This study describes a high-throughput method for determining HPLC-logP(alk), a chromatographic parameter closely related to logP(alk), using an alkylated polystyrene-divinylbenzene column and fast acetonitrile gradient. A structurally diverse set of neutral, acidic, and basic compounds was analyzed under ionization-suppressing pH conditions. In this chromatographic system, the relationship between gradient retention time and isocratic logk was essentially linear. Thus, gradient retention time could be used as the sole input needed to determine an apparent logP(alk)by HPLC. HPLC-logP(alk) showed linear correlation (R(2)>0.96, n=59) with reference logP(alk) values from shake-flask measurements over 8 orders of magnitude, ranging from -2.3 to +5.7. Linear solvation energy relationship (LSER) analysis revealed that the relative contributions of intermolecular forces effecting retention in the fast gradient system or its corresponding isocratic variant were highly similar to those governing partition in bulk alkane-water.


Limitations on Sphagnum growth and net primary production in the foothills of the Philip Smith Mountains, Alaska.
In the foothills of the Philip Smith Mountains, Brooks Range, Alaska, tussock tundra occurs on rolling hills and in valleys that were shaped by Pleistocene glaciations. During the 1986 and 1987 summer seasons, Sphagnum growth and production were determined in "water tracks" on tundra slopes that acted to channel water flow to the valley bottom stream and in "intertrack tundra" areas that were relatively homogeneous with respect to downslope drainage. Measurements were made under ambient environmental conditions and on mosses receiving supplemental irrigation in each area. Growth rate for Sphagnum spp. (cm shoot length increase/day) was low and relatively constant in intertrack tundra and highest but quite variable in water tracks. A strong negative correlation was found between Sphagnum spp. growth rate and solar irradiance in the shady environment below Salix canopies in the water tracks. Estimates of net annual dry weight (DW) production for Sphagnum spp. ranged from 0.10 g DW dm-2 yr-1 in intertrack tundra vegetation to 1.64 g DW dm-2 yr-1 in well-shaded water tracks. Experimental water additions had little effect on growth and production in intertrack tundra and well-developed water tracks, but significantly increased growth in a weakly-developed water track community. Low production over large areas of tundra slopes may occur due to presence of slow growing species resistant to dessication in intertrack tundra as opposed to rapidly growing less compact species within the limited extent of water tracks. We hypothesize that species capable of rapid growth occur also in weakly-developed water tracks, and that these are water-limited more often than plants occurring in well-developed water track situations. Where experienced, high light intensity may additionally limit growth due to photoinhibition.


The effect of lignin and sugars to the aerobic decomposition of solid wastes.
A series of experimental runs were conducted from 1995 to 1999 in Madison (WI, USA) with the goal to investigate the biodegradation process of seven (7) solid waste components and mixtures of them under near optimal aerobic conditions. It was shown that substrates with high initial lignin contents or high initial HWSM contents were observed to have relatively low and high degradation extents, respectively. Two linear equations were derived that correlate degradation extent (as indicated by the volatile solids reduction) to initial lignin and initial HWSM contents separately. The lignin equation was compared to a similar equation previously developed for anaerobic environments by Chandler et al. (Predicting methane fermentation biodegradability. In: Biotechnology and Bioengineering Symposium No. 10 (1980) New York: John Wiley & Sons). With comparison to the Chandler formula, lignin was found to be less inhibitory to the overall substrate decomposition in aerobic environments compared to anaerobic ones. Cellulose loss contributed to a higher than 50% to the overall dry mass loss for all substrates studied. In addition, the cellulose to lignin (C/L) ratio appeared to be a relatively accurate compost maturity indicator, since it reduced to a value less than 0.5 for most substrates that had reached their degradation extent.


Flanking host sequences can exert an inhibitory effect on the cleavage step of the in vitro mu DNA strand transfer reaction.
The effect of flanking host sequences on the cleavage step of the in vitro Mu DNA strand transfer reaction was investigated. Insertion of a mini-Mu molecule into certain sites in pUC19 results in insertions that demonstrate a decreased ability to form Type 1 complexes in subsequent rounds of transposition. Similarly, changes in the flanking host sequences directly adjacent to the Mu ends by in vitro mutagenesis can also result in Type 1-deficient mini-Mu molecules. Further examination of the inhibition revealed that Type 1 deficient mini-Mu molecules are capable of forming uncut synaptic complexes at normal levels but are compromised in their ability to serve as substrates for phosphodiester bond hydrolysis at the Mu ends. This cleavage defect can be overcome by addition of the Mu B protein and ATP to the reaction. Our data suggest that one of the roles of the B protein may be to provide a mechanism whereby Mu prophages with inhibitory flanking sequences can overcome this obstacle and avoid being trapped at unproductive locations.


On stent-graft models in thoracic aortic endovascular repair: a computational investigation of the hemodynamic factors.
In treating thoracic aortic diseases, endovascular repair involves the placement of a self-expanding stent-graft system across the diseased thoracic aorta. Computational fluid dynamic techniques are applied to model the blood flow by numerically solving the three-dimensional continuity equation and the time-dependent Navier-Stokes equations for an incompressible fluid. From our results, high blood pressure level and high systolic slope of the pressure waveform will significantly increase the drag force on a stent-graft whereas high blood viscosity causes only a mild increase. It indicates that hemodynamic factors might have an important impact on the drag force and thus play a significant role in the risk of stent-graft failure.


Responses of sea urchins (Strongylocentrotus intermedius) with different sexes to CO2-induced seawater acidification: Histology, physiology, and metabolomics.
Responses of different sexes of farmed Strongylocentrotus intermedius to chronic CO2-induced seawater acidification were investigated in 120-day lab-based experiments. Four experimental groups were set up as one control group and three seawater acidification groups. The results showed that 1) Specific growth rate and the numbers of mature gamete cells declined in a pH-dependent way in both sexes of adult S. intermedius. 2) There were differences in SDMs identified in females and males reared in acidified seawater reflecting sex-specific response variation in adult S. intermedius. 3) The number of altered metabolic pathways exhibited a linear increasing trend as seawater pH declined in both sexes of adult S. intermedius. Meanwhile seawater acidification might affect metabolic processes via changing the relative expression and activity of key enzymes controlling the corresponding metabolic pathways of adult S. intermedius.


Indications of plasma exchanges in combination with intravenous immunoglobulins or therapeutic monoclonal antibodies. How to combine them?
Plasma exchange (PEX) is a therapeutic procedure used to treat diseases caused by pathogenic antibodies or immune-complexes through the removal and the replacement of plasma. The frequency of complications and reactions associated with PEX are mild and of limited duration. In systemic autoimmune diseases and in a variety of other conditions, PEX might be use in association with intravenous immunoglobulin (IVIg) or therapeutic monoclonal antibodies for the management of acute or refractory patients to achieve a durable remission.


Identification of prognostic factors for pediatric myocarditis with a random forests algorithm-assisted approach.
Pediatric myocarditis is a rare disease with substantial mortality. Little is known regarding its prognostic factors. We hypothesize that certain comorbidities and procedural needs may increase risks of poor outcomes. This study aims to identify prognostic factors for pediatric myocarditis. The national Kids' Inpatient Database was used in the study. A random forests algorithm was implemented for mortality prediction based on comorbidities and procedures. Linear regression analysis was then performed to quantify their associations with mortality and length of stay. The prevalence of pediatric myocarditis among all pediatric hospitalizations doubled from 2003 to 2016. The mortality rate peaked in 2006 (6.7%) and declined steadily thereafter, with a rate of 3.2% in 2016. Brain injury (including encephalopathy, cerebral edema, and intracranial hemorrhage), acute kidney injury, dysrhythmias, coagulopathy, sepsis, and ECMO use were all independent prognostic factors associated with increased mortality and prolonged hospital stay. Prognostic factor identification may not be straightforward in rare diseases such as pediatric myocarditis due to small cohort size in each treating facility. Findings from this report provide insights into the prognostic factors for pediatric myocarditis, and may allow clinicians to be better prepared when informing patients and their families regarding disease outcomes. The rate of hospitalization due to pediatric myocarditis was increasing but the mortality rate was declining over the past decade. End organ damage, including the brain and the kidney, was associated with mortality and prolonged hospital stay in pediatric myocarditis. Tachyarrhythmias and cardiac function compromise requiring ECMO were also associated with mortality and prolonged hospital stay. A data science approach combining machine learning algorithms and conventional regression modeling using a large dataset may facilitate risk factor identification and outcome correlation in rare diseases, as illustrated in this study.


Doping control for methenolone using hair analysis by gas chromatography-tandem mass spectrometry.
A sensitive, specific and reproducible method for the quantitative determination of methenolone in human hair has been developed. The sample preparation involved a decontamination step of the hair with methylene chloride. The hair sample (about 100 mg) was solubilized in 1 ml 1 M NaOH, 15 min at 95 degrees C, in presence of 1 ng testosterone-d3 used as internal standard. The homogenate was neutralized and extracted using consecutively a solid-phase (Isolute C18 eluted with methanol) and a liquid-liquid (pentane) extraction. The residue was derivatized by adding 50 microl MSTFA-NH4I-2-mercaptoethanol (1000:2:5, v/v/v), then incubated for 20 ml at 60 degrees C. A 1.5-microl aliquot of the derivatized extract was injected into the column (HP5-MS capillary column, 5% phenyl-95% methylsiloxane, 30 m x 0.25 mm I.D., 0.25 microm film thickness) of a Hewlett-Packard (Palo Alto, CA, USA) gas chromatograph (6890 Series). Methenolone was detected by its parent ion at m/z 446 and daughter ions at m/z 208 and 195 through a Finnigan TSQ 700 MS-MS system. The assay was capable of detecting 1 pg/mg of methenolone when approximately 100 mg hair material was processed. Linearity was observed for methenolone concentrations ranging from 2 to 100 pg/mg with a correlation coefficients of 0.965-0.981. Intra-day and between-day precisions at 2, 10 and 25 pg/mg were 10.9-14.1% and 13.7-16.8%, respectively, with an extraction recovery of 97.6%. The analysis of a strand of hair obtained from two bodybuilders, revealed the presence of methenolone at the concentrations of 7.3 and 8.8 pg/mg.


Sibling Similarity in Metabolic Syndrome: The Portuguese Sibling Study on Growth, Fitness, Lifestyle and Health.
This study aims to estimate sibling resemblance in metabolic syndrome (MS) markers, and to investigate the associations of biological and behavioral characteristics with MS. The sample comprises 679 biological siblings (363 females; 316 males) aged 9-20 years. MS markers included waist circumference (WC), high-density lipoprotein cholesterol (HDL-C), triglycerides (TRI), fasting glucose (GLU) and systolic blood pressure (SBP). Body mass index (BMI), biological maturation, muscular, and cardiorespiratory fitness were also assessed. Behavioral characteristics, including dietary intake and physical activity, were self-reported by questionnaire. Multilevel models were used, and sibling resemblance was estimated using the intraclass correlation (ρ). In general, same-sex siblings showed higher resemblance in MS markers than opposite-sex siblings. However, variability in sibling resemblance in MS markers was evident with the inclusion of covariates. Biological characteristics including age, BMI and maturity offset influenced all MS markers except for TRI. Importantly, behavioral characteristics diversely influenced MS markers: fruit and vegetables only influenced SBP, whereas physical activity affected HDL-C. Additionally, muscular fitness impacted significantly on MS Z-score, WC, SBP and GLU, whilst cardiorespiratory fitness only affected WC. In conclusion, biological and behavioral characteristics influenced the expression of MS markers. These results confirmed the importance of considering individual characteristics when designing individualized programs for diminishing the adverse effects of specific MS markers.


Intraspecific competition in a reef coral: effects on growth and reproduction.
Growth rates and reproduction of a branching coral (Stylophora pistillata) were compared in the presence and in the absence of intraspecific competition. Field experiments demonstrated a significant decline in the growth rate of competing colonies compared to noncompeting control colonies; the growth rate slowed in all of the interacting individuals, irrespective of their place in the hierarchy of the intraspecific dominance or of their color morph. In case of immediate killing of the subordinate, the dominant colony grew at a normal rate. In addition to the marked decrease in the growth rate of interacting colonies, the typical symmetry shape of these colonies was changed to an abnormal growth form. The number of female gonads per polyp was significantly reduced in colonies competing intraspecifically, and the typical synchrony in reproduction among different branches of a given colony was changed and desynchronized. Again, these results did not correlate with the hierarchy of dominance. We conclude that intraspecific competition in reef corals involves great investment of energy. The ecological significance and the different pathways of this competition are discussed.


Paradigm shift for the treatment of hereditary haemophilia: Towards precision medicine.
Patients with haemophilia A (HA) or B (HB) experience spontaneous limb- or life-threatening bleedings which are prevented by regular prophylactic intravenous infusions of the deficient coagulation factor (FVIII or FIX). Prophylaxis with subcutaneous long-acting non-factor products that improve in vivo thrombin generation is now under intensive investigation (concizumab, fitusiran) or successfully employed (emicizumab) in haemophilia patients. Both haemophilia patients with/without inhibitors take advantage of non-factor products employed alone. In those who also need bypassing agents (or FVIII concentrates) for breakthrough bleeds, thromboembolic events and/or thrombotic microangiopathy may occur. By enhancing thrombin generation, prothrombotic mutations co-segregating with FVIII/FIX gene mutations may trigger thrombotic episodes in HA patients carrying acquired thrombogenic factors (e.g. venous catheters). A thorough knowledge of individual needs increasingly contributed to improve comprehensive care and personalize treatments in haemophilia. Integrating genomics, lifestyle and environmental data is expected to be key to: 1) identify which haemophilia patients are less likely to benefit from a given intervention; 2) define optimal dosing and scheduling of bypassing agents (or FVIII) to employ in combination with non-factor products; 3) establish tests to monitor in vivo thrombin generation; 4) improve communication and deliver results to individuals. As individual outcomes will be improved and the risk of adverse events minimized, non-factor products will come into wider use within the haemophilia community, and patients will hopefully have no more risks of breakthrough bleeds. The risks of a normal life for a "former haemophilia patient" is likely to change the treatment landscape and the structure of haemophilia Centers.


Congenital scalp defects associated with postaxial polydactyly.
A family is reported, several members of which had congenital scalp defects and postaxial polydactyly type A, with wide variability of expression. The hypothesis is formulated that this association is not fortuitous, but is a distinct malformation complex in which congenital scalp defects are associated with distinct malformation of the limbs.


Uptake of iodide into growing chicken oocytes.
Sodium 125iodide was injected intraperitoneally into laying hens and two modes of experimentation utilized to determine the nature of its distribution into plasma and yolk compartments.


An enzymatic hydrolysis approach for characterizing labile phosphorus forms in dairy manure under mild assay conditions.
Characterizing labile P forms in animal manure is a challenge due to their susceptibility to hydrolysis. In this study, we enzymatically characterized P forms in dairy manure (no bedding), collected from a representative dairy farm in New York, by separating into soluble and residual components under mild assay conditions using water and sodium acetate buffer (pH 5.0). About 75% of total manure P in the fresh manure was characterized, with the remainder (25%) regarded as recalcitrant or biochemically unidentified P. The hydrolyzable organic P in soluble and residual fractions was then characterized by using phosphatase enzymes to simple monoester P, polynucleotide P, phytate-like P, and non-hydrolyzable P. Of the total P in water extracts, 77% was inorganic P, 11% hydrolyzable organic P and 12% non-hydrolyzable P. In the residual resuspension, the distribution of characterized P was 25% spontaneous labile P, 32% simple monoester P, 7% polynucleotide P, 9% phytate-like P, and 26% non-hydrolyzable P. Ultrasonication increased the P(i) release from the manure residues, but the deviation in Pi concentrations due to the sampling variance was greater that the increase in P(i) due to sonication. Autoclaving sped up the release of both spontaneously labile P and enzymatically hydrolyzable P trapped in the manure residual matrix. Quantifying labile P forms by this approach may advance our ability to predict amount of manure P that will be hydrolyzed and eventually become bioavailable. The information obtained by our modified method would be complementary to that obtained by other methods (such as P-31 NMR and sequential fractionation) for a full spectrum of P species in animal manure.