Transitioning to civilian life: The importance of social group engagement and identity among Australian Defence Force veterans.
Veterans transitioning to civilian life after leaving the military face unique health concerns. Although there is a significant body of research exploring veterans' experiences of transition and predictors of well-being, there are limited studies examining how social group engagement influences veterans' transition. We explored how Australian Defence Force veterans' social group engagement and identity influenced their adjustment to civilian life and well-being. Forty Australian veterans (85% male; mean age = 37 years, range = 25-57 years) took part in in-depth, semi-structured interviews. Participants completed two mapping tasks (a social network map and life course map) that provided a visual component to the interviews. Interview transcripts were analysed thematically and interpreted by adopting a social identity approach. Joining the military involved a process of socialisation into military culture that for most participants led to the development of a military identity. An abrupt or difficult discharge from defence was often associated with a negative impact on social group engagement and well-being in civilian life. Veterans' social group memberships may act not only as positive psychological resources during transition but also as a potential source of conflict, especially when trying to re-engage with civilian groups with different norms or beliefs. Military values inscribed within a veteran's sense of self, including a strong sense of service, altruism and giving back to their community, may operate as positive resources and promote social group engagement. Engaging with supportive social groups can support transition to civilian life. Reintegration may be improved via effective linkage with programmes (e.g. volunteering, ex-service support organisations) that offer supportive social networks and draw upon veterans' desire to give back to community. Social mapping tasks that visualise veterans' social group structures may be useful for clinicians to explore the roles and conflicts associated with veterans' social group memberships during transition.


Effect of adenosine on oxygen uptake and electrolyte content of frog sartorius muscle.
Adenosine and ATP depressed resting O2 uptake in frog sartorius. This action was blocked by low levels of caffeine and by 8-phenyltheophylline. It was mimicked by a polymer of adenosine. Adenosine also decreased radioactive calcium uptake in muscles. Potassium and magnesium content were increased while sodium and calcium content were decreased by adenosine. Adenosine did not decrease oxygen uptake in muscles from frogs sacrificed in winter months. However, adenosine deaminase, which inactivates adenosine by removing the amino group, increased oxygen uptake, calcium content and lactate release of these muscles. Our results suggest that adenosine reduces resting metabolism, possibly through reducing passive leaks of electrolytes.


Simultaneous Quantification of Spatially Discordant Alternans in Voltage and Intracellular Calcium in Langendorff-Perfused Rabbit Hearts and Inconsistencies with Models of Cardiac Action Potentials and Ca Transients.
Rationale: Discordant alternans, a phenomenon in which the action potential duration (APDs) and/or intracellular calcium transient durations (CaDs) in different spatial regions of cardiac tissue are out of phase, present a dynamical instability for complex spatial dispersion that can be associated with long-QT syndrome (LQTS) and the initiation of reentrant arrhythmias. Because the use of numerical simulations to investigate arrhythmic effects, such as acquired LQTS by drugs is beginning to be studied by the FDA, it is crucial to validate mathematical models that may be used during this process. Objective: In this study, we characterized with high spatio-temporal resolution the development of discordant alternans patterns in transmembrane voltage (Vm) and intracellular calcium concentration ([Cai]+2) as a function of pacing period in rabbit hearts. Then we compared the dynamics to that of the latest state-of-the-art model for ventricular action potentials and calcium transients to better understand the underlying mechanisms of discordant alternans and compared the experimental data to the mathematical models representing Vm and [Cai]+2 dynamics. Methods and Results: We performed simultaneous dual optical mapping imaging of Vm and [Cai]+2 in Langendorff-perfused rabbit hearts with higher spatial resolutions compared with previous studies. The rabbit hearts developed discordant alternans through decreased pacing period protocols and we quantified the presence of multiple nodal points along the direction of wave propagation, both in APD and CaD, and compared these findings with results from theoretical models. In experiments, the nodal lines of CaD alternans have a steeper slope than those of APD alternans, but not as steep as predicted by numerical simulations in rabbit models. We further quantified several additional discrepancies between models and experiments. Conclusions: Alternans in CaD have nodal lines that are about an order of magnitude steeper compared to those of APD alternans. Current action potential models lack the necessary coupling between voltage and calcium compared to experiments and fail to reproduce some key dynamics such as, voltage amplitude alternans, smooth development of calcium alternans in time, conduction velocity and the steepness of the nodal lines of APD and CaD.


Guided migration of neural stem cells derived from human embryonic stem cells by an electric field.
Small direct current (DC) electric fields (EFs) guide neurite growth and migration of rodent neural stem cells (NSCs). However, this could be species dependent. Therefore, it is critical to investigate how human NSCs (hNSCs) respond to EF before any possible clinical attempt. Aiming to characterize the EF-stimulated and guided migration of hNSCs, we derived hNSCs from a well-established human embryonic stem cell line H9. Small applied DC EFs, as low as 16 mV/mm, induced significant directional migration toward the cathode. Reversal of the field polarity reversed migration of hNSCs. The galvanotactic/electrotactic response was both time and voltage dependent. The migration directedness and distance to the cathode increased with the increase of field strength. (Rho-kinase) inhibitor Y27632 is used to enhance viability of stem cells and has previously been reported to inhibit EF-guided directional migration in induced pluripotent stem cells and neurons. However, its presence did not significantly affect the directionality of hNSC migration in an EF. Cytokine receptor [C-X-C chemokine receptor type 4 (CXCR4)] is important for chemotaxis of NSCs in the brain. The blockage of CXCR4 did not affect the electrotaxis of hNSCs. We conclude that hNSCs respond to a small EF by directional migration. Applied EFs could potentially be further exploited to guide hNSCs to injured sites in the central nervous system to improve the outcome of various diseases.


Importin alpha3 interacts with HIV-1 integrase and contributes to HIV-1 nuclear import and replication.
HIV-1 employs the cellular nuclear import machinery to actively transport its preintegration complex (PIC) into the nucleus for integration of the viral DNA. Several viral karyophilic proteins and cellular import factors have been suggested to contribute to HIV-1 PIC nuclear import and replication. However, how HIV interacts with different cellular machineries to ensure efficient nuclear import of its preintegration complex in dividing and nondividing cells is still not fully understood. In this study, we have investigated different importin alpha (Impalpha) family members for their impacts on HIV-1 replication, and we demonstrate that short hairpin RNA (shRNA)-mediated Impalpha3 knockdown (KD) significantly impaired HIV infection in HeLa cells, CD4(+) C8166 T cells, and primary macrophages. Moreover, quantitative real-time PCR analysis revealed that Impalpha3-KD resulted in significantly reduced levels of viral 2-long-terminal repeat (2-LTR) circles but had no effect on HIV reverse transcription. All of these data indicate an important role for Impalpha3 in HIV nuclear import. In an attempt to understand how Impalpha3 participates in HIV nuclear import and replication, we first demonstrated that the HIV-1 karyophilic protein integrase (IN) was able to interact with Impalpha3 both in a 293T cell expression system and in HIV-infected CD4(+) C8166 T cells. Deletion analysis suggested that a region (amino acids [aa] 250 to 270) in the C-terminal domain of IN is involved in this viral-cellular protein interaction. Overall, this study demonstrates for the first time that Impalpha3 is an HIV integrase-interacting cofactor that is required for efficient HIV-1 nuclear import and replication in both dividing and nondividing cells.


[Ultrasonic examinations of thyroid newgrowths].
The results of complex ultrasonic, histological and cytological examination of 148 patients with newgrowths thyroid were analyzed. Grey-scale mode, colored and energy Doppler scanning, three-dimensional reconstruction of vessels were used. A new classification of nodular vascular pattern types based on 3-D reconstruction is proposed. The majority of malignant formations were characterized by perinodular hypervascularization and internodular hypovascularization (82.4%), adenomas--by peri- and intranodular hypervascularization (88.9%), colloid nodes--by perinodular hypervascularization (85.5%), the blood flow was absent in simple cysts (85.3%). It was established that complex of these methods increases informative value of ultrasonic examination in diagnosis of thyroid nodular diseases: in malignant neoplasms the sensitivity is 92.9%, specificity--86.1%, diagnostic accuracy--86.9%, in adenomas--93.4%, 79.2% and 82%, in colloid nodes--75.7%, 84.1% and 79.8%, respectively. In cystic masses diagnostic value of Doppler methods didn't change: sensitivity was 90.4%, specificity--63%, diagnostic accuracy--80.5%. The combined ultrasonic examination provides a differential approach to treatment of patients with thyroid nodular masses and decreases the number of unjustified surgical interventions.


Do obese persons comprehend their personal health risks?
To test whether overweight and obese individuals believe they are at greater risk of obesity-related diseases and premature mortality. Telephone survey of 1139 US adults analyzed using linear and ordered logistic regressions. Obese (overweight) adults forecast life expectancies 3.9 (2.4) years shorter than those of normal weight adults. Excess weight was associated with greater self-perceived risk of developing diabetes, cancer, heart disease, and stroke. All results were statistically significant. Overweight and obese adults recognize several personal health risks associated with obesity. Interventions focusing only on health risks of obesity may provide minimal new information and induce little new weight loss.


Proteomic definition of normal human luminal and myoepithelial breast cells purified from reduction mammoplasties.
Normal human luminal and myoepithelial breast cells separately purified from a set of 10 reduction mammoplasties by using a double antibody magnetic affinity cell sorting and Dynabead immunomagnetic technique were used in two-dimensional gel proteome studies. A total of 43,302 proteins were detected across the 20 samples, and a master image for each cell type comprising a total of 1,738 unique proteins was derived. Differential analysis identified 170 proteins that were elevated 2-fold or more between the two breast cell types, and 51 of these were annotated by tandem mass spectrometry. Muscle-specific enzyme isoforms and contractile intermediate filaments including tropomyosin and smooth muscle (SM22) alpha protein were detected in the myoepithelial cells, and a large number of cytokeratin subclasses and isoforms characteristic of luminal cells were detected in this cell type. A further 134 nondifferentially regulated proteins were also annotated from the two breast cell types, making this the most extensive study to date of the protein expression map of the normal human breast and the basis for future studies of purified breast cancer cells.


Efficacy of anakinra in bone: comparison to other biologics.
Three biologic therapies significantly slow radiographic progression in active rheumatoid arthritis. This paper compares the effects of anakinra, a recombinant human interleukin-1 receptor antagonist, with those of etanercept and infliximab, two drugs that target tumor necrosis factor-alpha. A Medline search identified controlled clinical trials that included radiographic progression as an endpoint. Anakinra 30 to 150 mg subcutaneously each day for 24 weeks was significantly more effective than placebo in slowing progression of erosion, joint-space narrowing, and total composite scores, as assessed by the Genant method, and erosive joint count, as assessed by the Larsen method. Erosion scores were slowed even further during a 24-week extension. Etanercept 25 mg subcutaneously twice weekly and infliximab 3 to 10 mg/kg intravenously every 4 or 8 weeks also slowed progressive joint damage, but these agents were studied under different study designs, patient populations, and radiographic assessments than those used in the anakinra study. Despite these differences, however, each biologic therapy appeared to slow progressive joint damage. In some studies, control of clinical symptoms did not correlate with slowing of radiographic progression. Agents that block interleukin-1 or tumor necrosis factor-alpha appear similarly effective in slowing radiographic progression in patients with active rheumatoid arthritis. Treatment strategies for this disease may need to consider clinical symptoms, progressive joint damage, and long-term safety effects separately.


Cyclical eosinophilia: a manifestation of periodic haemopoiesis?
A patient is described who has had a marked eosinophilia of unknown cause for 9 years in association with episodic facial swelling. Weekly blood counts for 8 months showed cyclical variations in eosinophils, neutrophils and monocytes (mean cycle length 35 d). Marrow culture studies showed fluctuation in the incidence of granulocyte-macrophage colonies (GM-CFC), and the proportion of eosinophil colonies was higher than the values reported for normals. The blood lymphocyte T4/T8 ratio was reversed, due to an increase of T8+ cells. It is suggested that this condition is a rare form of periodic haemopoiesis.


Activity and immunohistochemical localization of porphobilinogen deaminase in rat tissues.
Porphobilinogen deaminase (PBGD) is an enzyme involved in the synthesis of heme. Acute intermittent porphyria (AIP) is an inherited disease resulting from a reduced activity of PBGD. The symptoms seem to be due to a neurological dysfunction. Attacks of AIP are often provoked by conditions where the PBGD activity becomes insufficient as a result of an increased synthesis of heme in the liver. How this affects the nervous tissue is still unknown. It may well be that a reduced activity of PBGD in other tissues than the liver is of importance too. The aim of the present study was to examine the activity and the immunohistochemical localization of PBGD in the following tissues of wistar female rats: brain, heart, submandibular gland, liver, kidney, pancreas, ovary, stomach, duodenum, jejunum, ileum, colon and musculature. The PBGD activity varied considerably among the tissues. It was highest in the liver, 14 pkat/g, and lowest in the jejunum, 0.7 pkat/g. The immunohistochemical localization of PBGD was studied by antibodies raised against a 40 amino acid synthetic peptide that corresponds to a segment in the C-terminal part of PBGD. The study demonstrated that the PBGD immunoreactivity was not evenly distributed among the various cell types in a given tissue. Immunohistochemical reactions were pronounced in Kupffer cells in the liver, in smooth muscle cells of arteries and arterioles, in distal and collecting tubules in the kidney, in nerve axons in the brain and in ganglionic cells in the intestine. Especially, the immunohistochemical reaction in nerve cells is notable considering the nervous dysfunction in AIP.


Bacillus subtilis LmrA is a repressor of the lmrAB and yxaGH operons: identification of its binding site and functional analysis of lmrB and yxaGH.
The Bacillus subtilis lmrAB operon is involved in multidrug resistance. LmrA is a repressor of its own operon, while LmrB acts as a multidrug efflux transporter. LmrA was produced in Escherichia coli cells and was shown to bind to the lmr promoter region, in which an LmrA-binding site was identified. Genome-wide screening involving DNA microarray analysis allowed us to conclude that LmrA also repressed yxaGH, which was not likely to contribute to the multidrug resistance. LmrA bound to a putative yxaGH promoter region, in which two tandem LmrA-binding sites were identified. The LmrA regulon was thus determined to comprise lmrAB and yxaGH. All three LmrA-binding sites contained an 18-bp consensus sequence, TAGACCRKTCWMTATAWT, which could play an important role in LmrA binding.


Synthesis of 1,4-Thiazepines.
An efficient, general, and unprecedented methodology for the synthesis of 2-methylene-2,3-dihydro-1,4-thiazepines from N-propargylic β-enaminones is described. Initially, N-propargylic β-enaminones were thionated with Lawesson's reagent in good to high yields, and then the resulting N-propargylic β-enaminothiones were subjected to electrophilic cyclization. When treated with zinc chloride in refluxing chloroform, N-propargylic β-enaminothiones underwent electrophilic cyclization to yield 2-methylene-2,3-dihydro-1,4-thiazepines in good to high yields. A general trend was observed for all N-propargylic β-enaminothiones, and the cyclization proceeded with high efficiency and large functional group tolerance. This process is also applicable to the cyclization of internal alkyne-tethered N-propargylic β-enaminothiones. This operationally simple and facile method may represent a very rapid entry to a library of functionalized 1,4-thiazepines in the area of pharmaceuticals.


Repeatability of Scotopic Sensitivity and Dark Adaptation Using a Medmont Dark-Adapted Chromatic Perimeter in Age-related Macular Degeneration.
Functional studies of rods in age-related macular degeneration using the Medmont Dark-Adapted Chromatic Perimeter (DACP) have demonstrated impairments in scotopic sensitivities and dark adaptation (DA). We investigated the intersession repeatability of scotopic sensitivity and DA parameters including the rod intercept time recorded from the Medmont DACP. Scotopic thresholds (14 test points) and DA using a 30% photobleach (eight test points) were measured on two separate days from participants 50 years of age or older with a range of age-related macular degeneration severity at loci superior and inferior to the fovea. Repeatability coefficients were calculated for prebleach scotopic sensitivity, and for DA parameters including rod intercept time. Twelve participants (mean age, 79.7 ± 8.1 years) repeated Medmont DACP testing within 50 days. Repeatability coefficients for prebleach scotopic sensitivity to long wavelength (red, 625 nm) and short wavelength (cyan, 505 nm) were 5.9 dB and 7.2 dB, respectively. The DA curve-derived repeatability coefficients for cone threshold was 3.9 dB, final threshold 5.3 dB, with an R value of 0.075 decades/min, rod intercept time 7.6 minutes, and RITslope 0.54 min/degree. This study establishes repeatability coefficients for scotopic thresholds and multiple DA parameters obtained with the Medmont DACP in patients with age-related macular degeneration. These repeatability coefficients will serve as the basis for determining clinically meaningful change in rod function in future clinical trials. Measures of repeatability parameters of scotopic thresholds and DA are essential to the accurate interpretation of results in future studies and trials using these measures.


CSF otorhinorrhea in a child with inner ear dysplasia: diagnosis with T2-weighted and intrathecal contrast-enhanced MR cisternography.
During the follow-up of recurrent pneumonia in a 9-month-old girl, rhinorrhea with discharge of a positional and intermittent nature was discovered. Radiological assessment was requested to detect any skull base openings and cerebrospinal fluid (CSF) leakage. T2-weighted MR cisternography showed bilateral inner ear dysplasia, communication of the internal auditory canal with the vestibule, and effusion in the right middle ear. Intrathecal contrast-enhanced MR cisternography revealed a CSF fistula from the right internal auditory canal to the Eustachian tube. The patient was operated upon on the right side, and the presence of a CSF leak near the oval window was confirmed. No adverse effects were seen during the short-term and long-term follow-up. Diagnosing this case required special attention, careful examination, and relevant investigations to find the site of CSF leakage in this patient with bilateral inner ear dysplasia.


Pre-clinical experience with daptomycin.
Daptomycin is a broad-spectrum, bactericidal agent active against Gram-positive bacteria, acting largely and unusually through membrane depolarization. Activity is markedly affected in vitro by the availability of calcium ions, and its high molecular weight with associated poor diffusion means that conventional disc diffusion testing is not reliable (and as a consequence not available). In order to allow susceptibility categorization, it is recommended that the MIC be determined in the presence of a defined calcium concentration. The activity of daptomycin is concentration-dependent with a prolonged post-antibiotic effect. It has linear pharmacokinetics, with a half-life of 8-9 h, the primary route of excretion is renal, it exhibits serum protein binding of approximately 92% and there is no interaction with the P450 cytochrome. Daptomycin is inactivated by surfactant in the lung and, in consequence, is not recommended for the treatment of respiratory infections. Daptomycin is currently licensed for the treatment of complicated skin and soft tissue infections and for bacteraemia and right-sided endocarditis due to methicillin-susceptible and -resistant Staphylococcus aureus. To date, daptomycin-resistant bacteria have rarely been isolated from patients, although increases in vancomycin MIC may be linked to reduced susceptibility to daptomycin. Close monitoring of resistance is essential to maintain the clinical utility of the drug. Using once-daily dosing, daptomycin has been generally well tolerated; however, weekly monitoring of creatinine phosphokinase is recommended, as myopathy in skeletal muscles has been seen, albeit rarely. The rapid bactericidal action of daptomycin makes it a useful addition to the therapeutic armamentarium for the treatment of Gram-positive infections, providing a valuable alternative to vancomycin when it is inappropriate or resistance is a problem.


On the Links Among Face Processing, Language Processing, and Narrowing During Development.
From the beginning of life, face and language processing are crucial for establishing social communication. Studies on the development of systems for processing faces and language have yielded such similarities as perceptual narrowing across both domains. In this article, we review several functions of human communication, and then describe how the tools used to accomplish those functions are modified by perceptual narrowing. We conclude that narrowing is common to all forms of social communication. We argue that during evolution, social communication engaged different perceptual and cognitive systems-face, facial expression, gesture, vocalization, sound, and oral language-that emerged at different times. These systems are interactive and linked to some extent. In this framework, narrowing can be viewed as a way infants adapt to their native social group.


Low nonfasting triglycerides and reduced all-cause mortality: a mendelian randomization study.
Increased nonfasting plasma triglycerides marking increased amounts of cholesterol in remnant lipoproteins are important risk factors for cardiovascular disease, but whether lifelong reduced concentrations of triglycerides on a genetic basis ultimately lead to reduced all-cause mortality is unknown. We tested this hypothesis. Using individuals from the Copenhagen City Heart Study in a mendelian randomization design, we first tested whether low concentrations of nonfasting triglycerides were associated with reduced all-cause mortality in observational analyses (n = 13 957); second, whether genetic variants in the triglyceride-degrading enzyme lipoprotein lipase, resulting in reduced nonfasting triglycerides and remnant cholesterol, were associated with reduced all-cause mortality (n = 10 208). During a median 24 and 17 years of 100% complete follow-up, 9991 and 4005 individuals died in observational and genetic analyses, respectively. In observational analyses compared to individuals with nonfasting plasma triglycerides of 266-442 mg/dL (3.00-4.99 mmol/L), multivariably adjusted hazard ratios for all-cause mortality were 0.89 (95% CI 0.78-1.02) for 177-265 mg/dL (2.00-2.99 mmol/L), 0.74 (0.65-0.84) for 89-176 mg/dL (1.00-1.99 mmol/L), and 0.59 (0.51-0.68) for individuals with nonfasting triglycerides <89 mg/dL (<1.00 mmol/L). The odds ratio for a genetically derived 89-mg/dL (1-mmol/L) lower concentration in nonfasting triglycerides was 0.50 (0.30-0.82), with a corresponding observational hazard ratio of 0.87 (0.85-0.89). Also, the odds ratio for a genetically derived 50% lower concentration in nonfasting triglycerides was 0.43 (0.23-0.80), with a corresponding observational hazard ratio of 0.73 (0.70-0.77). Genetically reduced concentrations of nonfasting plasma triglycerides are associated with reduced all-cause mortality, likely through reduced amounts of cholesterol in remnant lipoproteins.


Prevention of fatal hemorrhagic shock in dog by pretreatment with chronic high-salt diet.
The ability of a chronic high-salt diet to prevent fatal hemorrhagic shock was examined in 36 mongrel dogs. Twenty-one dogs received a dietary supplement of 9 g sodium chloride/day for 6 wk, and 15 dogs received the same basic diet for 6 wk but without the sodium chloride supplement. Hemorrhagic shock was induced in all dogs by bleeding into an overhanging sealed reservoir. After 3 h of shock, salt-pretreated dogs had a lower systemic vascular resistance of 0.70 +/- 0.02 versus 1.44 +/- 0.04 mmHg X ml-1 X min X kg (P less than 0.01) and a higher cardiac output of 53 +/- 3 versus 26 +/- 3 ml X min-1 X kg-1 (P less than 0.01) than was observed in controls. At 2.5 h of shock, the salt-pretreated dogs also experienced an increase in gastrointestinal (P less than 0.01), hepatic arterial, (P less than 0.05), kidney (P less than 0.05), brain (P less than 0.01), and heart blood flows (P less than 0.001) compared with 0.5 h of shock, whereas the control dogs experienced no increased flow during this same period. We also observed that after 3 h of hypotension there was a significantly smaller increase in plasma renin activity in the salt-pretreated dogs. Administration of 0.1 U X kg-1 X min-1 of hog renin eliminated the differences in systemic vascular resistance, cardiac output, and survival in five salt-pretreated dogs.


Evidence of the existence of a factor that induces Fc receptors on bone marrow cells.
The existence of a molecule responsible for the induction of Fc receptor (FcR) on bone marrow cells (FcR inducer, FcRI) is demonstrated in conditioned media from the macrophage-like cell line WR19M.1 activated by bacterial lipopolysaccharides. The molecular weight obtained from molecular sieving chromatography in gel and density gradient sedimentation is found to be 18,500 daltons and 16,000 daltons, respectively, with an isoelectric pH of 7.4. The factor is found to be thermolabile and trypsin sensitive. The macrophage and granulocyte inducer (MGI), also known as colony-stimulating factor (CSF) or colony-stimulating activity (CSA), is identified from the same source and found to have a molecular weight and an isoelectric pH different from FcRI. The fractions that contained the MGI did not induce FcR on bone marrow cells, while the fractions rich in FcRI did not induce colony formation.


Proximal segment displacement in mandibular distraction osteogenesis.
Distraction osteogenesis has been advocated for treatment of the mandibular deformity in patients with hemifacial microsomia (HFM). During the active phase, the force of distraction pushes the distal segment of the mandible down, creating a distraction gap. Because of the abnormal temporomandibular joint anatomy in HFM patients, the proximal segment may not seat in the glenoid fossa and thus may be displaced with distraction. The purpose of this study was to determine the vector(s) of proximal segment movement during mandibular distraction using a semiburied device. Two investigators traced the immediate pre-and postdistraction panoramic radiographs of 12 HFM patients (mean age at operation = 8.4 years, mean distraction = 28 mm) who had mandibular distraction with a semiburied device. Radiographic analysis, based on a vertical maxillary reference line, measured change in condylar position with angular and linear measurements. Inter-rater reliability for the tracing and analysis was shown with a correlation coefficient between 0.89 and 0.99 for all measures. Based on the angular and linear measurements, 10 of the 12 patients had superior movement of the proximal segment with distraction. Sagittal movement of the proximal segment could not be judged adequately. This study was based on measurements made on panoramic radiographs. Direct measurements could not be made; thus, it was not possible to estimate proximal segment movement in millimeters or as a percentage of total movement. Further studies to document proximal segment movement using computed tomography scans may provide more quantitative data.


Latino early adolescents' psychological and physiological responses during the 2016 U.S. presidential election.
Research has documented increased psychological distress among adults during the 2016 U.S. presidential election; however, little is known about how major political events affect adolescents. Despite not actively participating in the election process (e.g., voting), adolescents generally, and Latino youth specifically, may experience a unique stress response during elections, particularly when perceived policy changes center on issues related to their own families' stability and well-being. We examined 42 Latino early adolescents (Mage = 12.50 years, SD = .88; 58% male; 94% immigrant background) living in Arizona and explored their psychological and physiological responses during the 2016 U.S. presidential election. Adolescents self-reported their mood and behaviors for 5 consecutive days across election week (November 6-10, 2016): 2 days before the election, election day, and 2 days after the election. They also completed a saliva sampling protocol at waking and bedtime each day, to capture diurnal cortisol concentrations. Multilevel growth models were utilized to examine intraindividual changes in positive affect, negative affect, and diurnal cortisol patterns across election week. Only 2 of the participants reported supporting the winning candidate. Changes in adolescents' stress hormone concentrations were evident; increases in evening cortisol levels and flatter diurnal cortisol slopes emerged across election week. Negative affect, positive affect, and morning cortisol concentrations did not change. This study provides preliminary evidence that macrolevel factors, such as the recent presidential election, may relate to adolescents' daily stress physiology. Further research is needed to better understand adolescents' responses to sociopolitical change. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


[Hematogenous (suspected-)septic inflammation of the synovial fossa in the adult horse: rare but deceptive (3 case reports)].
Septic inflammation of the synovial fossa in the horse is a severe disorder that can lead to permanent invalidity. The synovitis can occur as a result of a perforating trauma, or via the blood (haematogenous). The latter route is rare in the adult horse. Three cases of suspected haematogenous septic synovitis are described in adult horses (older than 1 year). In two horses, timely and adequate treatment resulted in recovery, but this was followed by fatal recurrence. In one of these horses a persistent primary infection was found as cause; the other horse was not available for autopsy. The third horse was euthanized without treatment because the primary process was difficult to treat. It can be concluded that, in horses with suspected haematogenous septic inflammation of the synovial fossa, attention should be paid to the primary process--it is not enough to treat the synovitis alone.


Effects of substrate stiffness on cell morphology, cytoskeletal structure, and adhesion.
The morphology and cytoskeletal structure of fibroblasts, endothelial cells, and neutrophils are documented for cells cultured on surfaces with stiffness ranging from 2 to 55,000 Pa that have been laminated with fibronectin or collagen as adhesive ligand. When grown in sparse culture with no cell-cell contacts, fibroblasts and endothelial cells show an abrupt change in spread area that occurs at a stiffness range around 3,000 Pa. No actin stress fibers are seen in fibroblasts on soft surfaces, and the appearance of stress fibers is abrupt and complete at a stiffness range coincident with that at which they spread. Upregulation of alpha5 integrin also occurs in the same stiffness range, but exogenous expression of alpha5 integrin is not sufficient to cause cell spreading on soft surfaces. Neutrophils, in contrast, show no dependence of either resting shape or ability to spread after activation when cultured on surfaces as soft as 2 Pa compared to glass. The shape and cytoskeletal differences evident in single cells on soft compared to hard substrates are eliminated when fibroblasts or endothelial cells make cell-cell contact. These results support the hypothesis that mechanical factors impact different cell types in fundamentally different ways, and can trigger specific changes similar to those stimulated by soluble ligands.


The challenges of research data management in cardiovascular science: a DGK and DZHK position paper-executive summary.
The sharing and documentation of cardiovascular research data are essential for efficient use and reuse of data, thereby aiding scientific transparency, accelerating the progress of cardiovascular research and healthcare, and contributing to the reproducibility of research results. However, challenges remain. This position paper, written on behalf of and approved by the German Cardiac Society and German Centre for Cardiovascular Research, summarizes our current understanding of the challenges in cardiovascular research data management (RDM). These challenges include lack of time, awareness, incentives, and funding for implementing effective RDM; lack of standardization in RDM processes; a need to better identify meaningful and actionable data among the increasing volume and complexity of data being acquired; and a lack of understanding of the legal aspects of data sharing. While several tools exist to increase the degree to which data are findable, accessible, interoperable, and reusable (FAIR), more work is needed to lower the threshold for effective RDM not just in cardiovascular research but in all biomedical research, with data sharing and reuse being factored in at every stage of the scientific process. A culture of open science with FAIR research data should be fostered through education and training of early-career and established research professionals. Ultimately, FAIR RDM requires permanent, long-term effort at all levels. If outcomes can be shown to be superior and to promote better (and better value) science, modern RDM will make a positive difference to cardiovascular science and practice. The full position paper is available in the supplementary materials.


Sociocognitive self-regulatory mechanisms governing transgressive behavior.
This longitudinal research examined a structural model of the self-regulatory mechanisms governing transgressive conduct. Perceived academic and self-regulatory efficacy concurrently and longitudinally deterred transgressiveness both directly and by fostering prosocialness and adherence to moral self-sanctions for harmful conduct. The impact of perceived social self-efficacy was mediated through prosocialness. Moral disengagement and prosocialness affected transgressiveness through the mediating influence of irascible affectivity and hostile rumination. Ruminative affectivity, in turn, both concurrently and longitudinally affected transgressiveness. Moral disengagement also contributed independently to variance in transgressiveness over time. This pattern of relations was obtained after controlling for prior transgressiveness. The structural model was replicated across gender and provided a better fit to the data than did several alternative models.


Chronic administration of the glucagon-like peptide-1 analog, liraglutide, delays the onset of diabetes and lowers triglycerides in UCD-T2DM rats.
The efficacy of liraglutide, a human glucagon-like peptide-1 (GLP-1) analog, to prevent or delay diabetes in UCD-T2DM rats, a model of polygenic obese type 2 diabetes, was investigated. At 2 months of age, male rats were divided into three groups: control, food-restricted, and liraglutide. Animals received liraglutide (0.2 mg/kg s.c.) or vehicle injections twice daily. Restricted rats were food restricted to equalize body weights to liraglutide-treated rats. Half of the animals were followed until diabetes onset, whereas the other half of the animals were killed at 6.5 months of age for tissue collection. Before diabetes onset energy intake, body weight, adiposity, and liver triglyceride content were higher in control animals compared with restricted and liraglutide-treated rats. Energy-restricted animals had lower food intake than liraglutide-treated animals to maintain the same body weights, suggesting that liraglutide increases energy expenditure. Liraglutide treatment delayed diabetes onset by 4.1 ± 0.8 months compared with control (P < 0.0001) and by 1.3 ± 0.8 months compared with restricted animals (P < 0.05). Up to 6 months of age, energy restriction and liraglutide treatment lowered fasting plasma glucose and A1C concentrations compared with control animals. In contrast, liraglutide-treated animals exhibited lower fasting plasma insulin, glucagon, and triglycerides compared with both control and restricted animals. Furthermore, energy-restricted and liraglutide-treated animals exhibited more normal islet morphology. Liraglutide treatment delays the development of diabetes in UCD-T2DM rats by reducing energy intake and body weight, and by improving insulin sensitivity, improving lipid profiles, and maintaining islet morphology.


Thoracic spondylolisthesis and spinal cord compression in diffuse idiopathic skeletal hyperostosis: a case report.
Diffuse idiopathic skeletal hyperostosis has long been regarded as a benign asymptomatic clinical entity with an innocuous clinical course. Neurological complications are rare in diffuse idiopathic skeletal hyperostosis. However, if they do occur, the consequences are often significant enough to warrant major neurosurgical intervention. Neurological complications occur when the pathological process of ossification in diffuse idiopathic skeletal hyperostosis extends to other vertebral ligaments, causing ossification of the posterior longitudinal ligaments and/or ossification of the ligamentum flavum. Thoracic spondylolisthesis with spinal cord compression in diffuse idiopathic skeletal hyperostosis has not previously been reported in the literature. A 78-year-old Japanese man presented with a 6-month history of gait disturbance. A magnetic resonance imaging scan of his cervical and thoracic spine revealed anterior spondylolisthesis and severe cord compression at T3 to T4 and T10 to T11, as well as high signal intensity in a T2-weighted image at T10/11. Computed tomography revealed diffuse idiopathic skeletal hyperostosis at T4 to T10. He underwent partial laminectomy of T10 and posterior fusion of T9 to T12. The postoperative magnetic resonance imaging revealed resolution of the spinal cord compression and an improvement in the high signal intensity on the T2-weighted image. We report the first case of thoracic spondylolisthesis and spinal cord compression in diffuse idiopathic skeletal hyperostosis. Neurosurgical intervention resulted in a significant improvement of our patient's neurological symptoms.


Evaluation of preoperative oral carbohydrate administration on insulin resistance in off-pump coronary artery bypass patients: A randomised trial.
In fasting cardiac surgery patients, preoperative carbohydrate (CHO) drink intake attenuated insulin resistance and improved cardiac metabolism, although its beneficial effects were not evident after cardiac surgery possibly due to cardiopulmonary bypass-related extreme systemic inflammation. We aimed to evaluate whether preoperative CHO intake affected insulin resistance and free-fatty acid (FFA) concentrations in off-pump coronary revascularisation. A randomised controlled trial. Primary care in a university hospital in Korea from January 2015 to July 2016. Sixty patients who underwent elective multi-vessel off-pump coronary revascularisation were randomised into two groups. Three patients were excluded from analysis and 57 patients completed study. The CHO group received oral CHO (400 ml) the prior evening and 2 to 3 h before surgery, and the control group was fasted from food and water according to standard protocol. Insulin resistance was assessed twice, after anaesthetic induction and after surgery via short insulin tolerance test. FFA, C-reactive protein and creatine kinase-myocardial band concentrations were determined serially for 48 h after surgery. Insulin sensitivity was greater (P = 0.002) and plasma FFA concentrations were lower (P = 0.001) after anaesthetic induction in the CHO group compared with the Control group, although there were no intergroup differences after surgery. The postoperative peak creatine kinase-myocardial band concentration was significantly lower in the CHO group compared with the Control group [8.8 (5.4 to 18.2) vs. 6.4 (3.5 to 9.7) ng ml, P = 0.031]. A preoperative CHO supplement significantly reduced insulin resistance and FFA concentrations compared with fasting at the beginning of the surgery, but these benefits were lost after off-pump coronary revascularisation. Despite their transient nature, these beneficial effects resulted in less myocardial injury, mandating further studies focused on the impact of preoperative CHO on myocardial ischaemia and cardiac function after coronary revascularisation. Clinicaltrials.gov identifier: NCT 02330263.


Site-Specific Conjugation of Monomethyl Auristatin E to Anti-CD30 Antibodies Improves Their Pharmacokinetics and Therapeutic Index in Rodent Models.
Antibody-drug conjugates (ADCs) have demonstrated clinical benefits that have led to the recent FDA approval of KADCYLA and ADCETRIS. Most ADCs that are currently in clinical use or development, including ADCETRIS, are produced by chemical conjugation of a toxin via either lysine or cysteine residues, inevitably leading to heterogeneous products with variable drug-to-antibody ratios (DARs). Here, we describe the in vitro and in vivo characterization of four novel ADCs that are based on the anti-CD30 antibody cAC10, which has the same polypeptide backbone as ADCETRIS, and compare the results with the latter. Bacterial transglutaminase (BTG) was exploited to site-specifically conjugate derivatives of monomethyl auristatin E (all comprising a cleavable linker) to the glutamine at positions 295 and 297 of cAC10, thereby yielding homogeneous ADCs with a DAR of 4. In vitro cell toxicity experiments using two different CD30-positive cell lines (Karpas 299 and Raji-CD30(+)) revealed comparable EC50 values for ADCETRIS (1.8 ± 0.4 and 3.6 ± 0.6 ng/mL, respectively) and the four cAC10-based ADCs (2.0 ± 0.4 to 4.9 ± 1.0 ng/mL). Quantitative time-dependent in vivo biodistribution studies (3-96 h p.i.) in normal and xenografted (Karpas 299 cells) SCID mice were performed with a selected (125)I-radioiodinated cAC10 ADC and compared with that of (125)I-ADCETRIS. The chemo-enzymatically conjugated, radioiodinated ADC showed higher tumor uptake (17.84 ± 2.2% ID/g 24 h p.i.) than (125)I-ADCETRIS (10.5 ± 1.8% ID/g 24 h p.i.). Moreover, (125)I-ADCETRIS exhibited higher nontargeted liver and spleen uptake. In line with these results, the maximum tolerated dose of the BTG-coupled ADC (>60 mg/kg) was significantly higher than that of ADCETRIS (18 mg/kg) in rats. These results suggest that homogeneous ADCs display improved pharmacokinetics and better therapeutic indexes compared to those of chemically modified ADCs with variable DARs.


Safety evaluation of FAD2 RNAi transgenic Brassica napus L. based on microbial diversity and metabonomic analysis.
Oleic acid desaturase (FAD2) is the key enzyme that produces polyunsaturated fatty acids in rapeseed (Brassica napus L), which is one of the main oil crops. RNA interference (RNAi) is an emerging technique that provides new opportunities for the generation of new traits in plants. To increase oleic acid content and reduce linoleic and linolenic acid content in rapeseed, we constructed an ihpRNA plant expression vector of the FAD2 gene and obtained transgenic plants for multiple generations by stable inheritance. In this study, third-generation transgenic plants (T3), seventh-generation transgenic plants (T7), and wild-type plants (WT) were used. The differences in microbial community diversity between transgenic plants and wild-type plants and the up- and downregulation of rhizosphere metabolite contents were investigated. In conclusion, the results showed that the soil microbial community structure was stable, the general microbial community structure was not changed by the transgenic rhizosphere exudates, and no significant harmful root exudate of transgenic rapeseed on the environment was found through the microbial community and metabolomics analysis. This work may provide an understanding of the impact of RNAi on plant metabolites and a safety evaluation method for transgenic plants and a reference for rapeseed breeding.


High throughput mutation screening by automated capillary electrophoresis.
Molecular diagnosis of complex inherited disorders, population screening of genetic diseases, studies of the genetic basis of variable drug response (pharmacogenetics) as well as discovery and investigation of new drug targets (pharmacogenomics) involve screening for mutations in multiple DNA samples. Furthermore, the development of a third generation of the human genome map, based on single nucleotide polymorphisms (SNPs), requires screening for allelic variants through all of the three billion basepairs in the human genome. Thus, the need for high throughput mutation screening methods is great and is rapidly increasing. Traditional methods for mutation screening often involve slab-gel electrophoresis analyses which are laborious and difficult to automate. However, recent developments in capillary electrophoresis systems for DNA fragment analysis have made fully automated mutation screening possible and have dramatically increased the possible sample throughput. This review describes the recent advances in capillary electrophoresis of DNA and summarize the various methods for mutation screening based on this technique.


Identification of Lead Compounds against Scm (fms10) in Enterococcus faecium Using Computer Aided Drug Designing.
(1) Background: Enterococcus faecium DO is an environmental microbe, which is a mesophilic, facultative, Gram-positive, and multiple habitat microorganism. Enterococcus faecium DO is responsible for many diseases in human. The fight against infectious diseases is confronted by the development of multiple drug resistance in E. faecium. The focus of this research work is to identify a novel compound against this pathogen by using bioinformatics tools and technology. (2) Methods: We screened the proteome (accession No. PRJNA55353) information from the genome database of the National Centre for Biotechnology Information (NCBI) and suggested a potential drug target. I-TASSER was used to predict the three-dimensional structure of the protein, and the structure was optimized and minimized by different tools. PubChem and ChEBI were used to retrieve the inhibitors. Pharmacophore modeling and virtual screening were performed to identify novel compounds. Binding interactions of compounds with target protein were checked using LigPlot. pkCSM, SwissADME, and ProTox-II were used for adsorption, distribution, metabolism, excretion, and toxicity (ADMET) properties. (3) Results: Novel selected compounds have improved absorption and have better ADMET properties. Based on our results, the chemically identified inhibitor ZINC48942 targeted the receptor that can inhibit the activity of infection in E. faecium. This research work will be beneficial for the scientific community and could aid in the design of a new drug against E. faecium infections. (4) Conclusions: It was observed that novel compounds are potential inhibitors with more efficacy and fewer side effects. This research work will help researchers in testing and identification of these chemicals useful against E. faecium.


Effect of Moderate-Intense Training and Detraining on Glucose Metabolism, Lipid Profile, and Liver Enzymes in Male Wistar Rats: A Preclinical Randomized Study.
Exercise training positively regulates glucose metabolism. This study investigated the impact of training and detraining on glucose metabolism, lipid profiles, and liver enzymes. Twenty-six rats completed an initial 4-week moderate-intense training (T0-T4). Then, the animals were randomly assigned to two groups at the end of week 4: AT4: detraining for 8 weeks; AT8: training for 8 weeks and 4-week detraining. Six animals were sacrificed at T0 and T4, four animals/group at T8, and three/group at T12. The study continued for 12 weeks, and all parameters were assessed at T0, T4, T8, and T12. IPGTT significantly improved after 4 weeks of training (p < 0.01) and was further reduced in AT8 at T8. In AT8, 8-week training significantly reduced total cholesterol at T4 and T12 vs. T0 (p < 0.05), LDL at T4, T8, and T12 vs. T0 (p < 0.01), ALP at T8, T12 vs. T0 (p < 0.01), and increased HDL at T8 and ALT at T8 and T12 vs. T0 (p < 0.05). Triglycerides and hexokinase activity increased significantly at T4 and T8 (p < 0.05) and then decreased at T12 in AT8. Pyruvate and glycogen increased at T12 in AT8 vs. AT4. Eight-week training improved LPL and ATGL expressions. Training positively modulated insulin, glucose metabolism, and lipid profiles, but detraining reduced the benefits associated with the initial training.


Dying "from" or "with" COVID-19 during the Pandemic: Medico-Legal Issues According to a Population Perspective.
There is still a lack of knowledge concerning the pathophysiology of death among COVID-19-deceased patients, and the question of whether a patient has died with or due to COVID-19 is still very much debated. In Italy, all deaths of patients who tested positive for SARS-CoV-2 are defined as COVID-19-related, without considering pre-existing diseases that may either contribute to or even cause death. Our study included nine subjects from two different nursing homes (Cases 1-4, Group A; Cases 5-9, Group B). The latter included patients who presumably died from CO poisoning due to a heating system malfunction. All subjects tested positive for COVID-19 both ante- and post-mortem and were examined using post-mortem computed tomography prior to autopsy. COVID-19 was determined to be a contributing cause in the deaths of four out of nine subjects (death due to COVID-19; i.e., pneumonia and sudden cardiac death). In the other five cases, for which CO poisoning was identified as the cause of death, the infection presumably had no role in exitus (death with COVID-19). In our attempt to classify our patients as dying with or due to COVID-19, we found the use of complete assessments (both histological analyses and computed tomography examination) fundamental.


The influence of a contoured seating base on pressure distribution and discomfort.
This research paper examines how contouring of a wheelchair seating base can help prevent pressure sores by distributing pressure over the buttocks. Contouring wheelchair cushioning is already done to some extent and has proved to be beneficial for pressure distribution. We researched the effect of contouring the seating base, and whether contouring the seating base affects effectiveness in pressure distribution and perceived discomfort. 13 healthy participants performed a within-subject experiment with three differently contoured seating bases. Perceived comfort and seating pressure were measured for each condition. Results indicate that a more contoured base is positive for both comfort and increased pressure distribution. Contoured seating bases can provide increased comfort and improved pressure distribution over flat seating bases. Future research should examine the effect of contouring on stability, as well as compare the effects of contoured seating bases and contoured cushions.Implications for rehabilitationWe evaluated the comfort and pressure characteristics of three differently contoured hard seating bases for a wheelchair. The outcomes of the research shows that providing increased contour to seatings could be beneficial to reduce pressure peaks in the buttocks.Contour in the seating is conventionally created by shaping the cushions, this research shows the possibility of using a hard base underneath a cushion to create the desired contour.


The significance of heart rate variability in patients with frequent premature ventricular complex originating from the ventricular outflow tract.
As an indicator of cardiac autonomic nervous activity, heart rate variability (HRV) is closely linked to premature ventricular complexes (PVCs). However, its role in patients with frequent PVCs originating from the ventricular outflow tract remains unclear. Here, we hypothesize that there may be alterations in HRV among patients with frequent PVCs originating from the ventricular outflow tract, which could play significant roles in the management of such patients. A retrospective study was conducted, including 106 patients with frequent outflow tract PVCs and 106 healthy participants as controls. HRV was assessed based on the 24-hour Holter recording. The originating foci of PVCs were identified during radiofrequency catheter ablation. Patients with frequent outflow tract PVCs exhibited decreased levels of high frequency (HF), standard deviation of all NN intervals, and standard deviation of the average NN intervals, but increased ratios of low frequency to HF (LF/HF ratio), even after propensity score-matched analysis. Further investigation revealed that patients with PVCs originating from right ventricular outflow tract (RVOT) had much higher LF/HF ratios. Multivariate logistic regression analysis demonstrated that the LF/HF ratio was independently associated with PVCs originating from RVOT. Receiver operating characteristics curve indicated that the LF/HF ratio effectively determined the origin of PVCs (the area under the curve = 0.75, p < .001). Patients with frequent outflow tract PVCs exhibited impaired HRV. Additionally, the LF/HF ratio played a significant role in determining the origin of outflow tract PVCs.


Single-cell immune landscape of human atherosclerotic plaques.
Atherosclerosis is driven by multifaceted contributions of the immune system within the circulation and at vascular focal sites. However, specific characteristics of dysregulated immune cells within atherosclerotic lesions that lead to clinical events such as ischemic stroke or myocardial infarction are poorly understood. Here, using single-cell proteomic and transcriptomic analyses, we uncovered distinct features of both T cells and macrophages in carotid artery plaques of patients with clinically symptomatic disease (recent stroke or transient ischemic attack) compared to asymptomatic disease (no recent stroke). Plaques from symptomatic patients were characterized by a distinct subset of CD4+ T cells and by T cells that were activated and differentiated. Moreover, some T cell subsets in these plaques presented markers of T cell exhaustion. Additionally, macrophages from these plaques contained alternatively activated phenotypes, including subsets associated with plaque vulnerability. In plaques from asymptomatic patients, T cells and macrophages were activated and displayed evidence of interleukin-1β signaling. The identification of specific features of innate and adaptive immune cells in plaques that are associated with cerebrovascular events may enable the design of more precisely tailored cardiovascular immunotherapies.


Count statistics of nonparalyzable photon-counting detectors with nonzero pulse length.
Photon-counting detectors are expected to be the next big step in the development of medical computed tomography (CT). Accurate modeling of the behavior of photon-counting detectors in both low and high count rate regimes is important for accurate image reconstruction and detector performance evaluations. The commonly used ideal nonparalyzable (delta pulse) model is built on crude assumptions that make it unsuitable for predicting the behavior of photon-counting detectors at high count rates. The aim of this work is to present an analytical count statistics model that better describes the behavior of photon-counting detectors with nonzero pulse length. An analytical statistical count distribution model for nonparalyzable detectors with nonzero pulse length is derived using tools from statistical analysis. To validate the model, a nonparalyzable photon-counting detector is simulated using Monte Carlo methods and compared against. Image performance metrics are computed using the Fisher information metric and a comparison between the proposed model, approximations of the proposed model, and those made by the ideal nonparalyzable model is presented and analyzed. It is shown that the presented model agrees well with the results from the Monte Carlo simulation and is stable for varying x-ray beam qualities. It is also shown that a simple Gaussian approximation of the distribution can be used to accurately model the behavior and performance of nonparalyzable detectors with nonzero pulse length. Furthermore, the comparison of performance metrics show that the proposed model predicts a very different behavior than the ideal nonparalyzable detector model, suggesting that the proposed model can fill an important gap in the understanding of pileup effects. An analytical model for the count statistics of a nonparalyzable photon-counting detector with nonzero pulse length is presented. The model agrees well with results obtained from Monte Carlo simulations and can be used to improve, speed up and simplify modeling of photon-counting detectors.


In vitro screening of per- and polyfluorinated substances (PFAS) for interference with seven thyroid hormone system targets across nine assays.
The US Environmental Protection Agency is evaluating the ecological and toxicological effects of per- and polyfluorinated chemicals. A number of perfluorinated chemicals have been shown to impact the thyroid axis in vivo suggesting that the thyroid hormone system is a target of these chemicals. The objective of this study was to evaluate the activity of 136 perfluorinated chemicals at seven key molecular initiating events (MIE) within the thyroid axis using nine in vitro assays. The potential MIE targets investigated are Human Iodothyronine Deiodinase 1 (hDIO1), Human Iodothyronine Deiodinase 2 (hDIO2), Human Iodothyronine Deiodinase 3 (hDIO3), Xenopus Iodothyronine Deiodinase (xDIO3); Human Iodotyrosine Deiodinase (hIYD), Xenopus Iodotyrosine Deiodinase (xIYD), Human Thyroid Peroxidase (hTPO); and the serum binding proteins Human Transthyretin (hTTR) and Human Thyroxine Binding Globulin (hTBG). Of the 136 PFAS chemicals tested, 85 had sufficient activity to produce a half-maximal effect concentration (EC50) in at least one of the nine assays. In general, most of these PFAS chemicals did not have strong potency towards the seven MIEs examined, apart from transthyretin binding, for which several PFAS had potency similar to the respective model inhibitor. These data sets identify potentially active PFAS chemicals to prioritize for further testing in orthogonal in vitro assays and at higher levels of biological organization to evaluate their capacity for altering the thyroid hormone system and causing potential adverse health and ecological effects.


Infection Status with Clinostomum complanatum Metacercariae in Fish from Water Systems of Nakdong-gang (River) in Korea.
The infection status of Clinostomum complanatum metacercariae (CcMc) was broadly surveyed in fishes from water systems of Nakdong-gang (River) in the Republic of Korea (Korea) for 5 years. All 4,468 fishes collected were individually examined by the artificial digestion methods. No CcMc were detected in fishes from Naeseongcheon in Yecheon-gun, Gigyecheon in Gyeongju-si, Gyeongsangbuk-do, and Hamancheon in Haman-gun, Gyeongsangnam-do. In fishes from Wicheon in Gunwi-gun, Gyeongsangbuk-do, CcMc were detected in 180 (15.4%) out of 1,168 fishes and their intensity was 5.8 per fish infected. The prevalences with CcMc in positive fish species from 3 other surveyed areas, i.e., Banbyeoncheon in Yeongyang-gun, Nakdong-gang in Sangju-si and Hoecheon in Goryeong-gun, in Gyeongsangbuk-do were 19.3%, 33.3%, and 19.0% and their intensities were 1.5, 17.6, and 2.6 per fish infected respectively. In fishes from Yangcheon in Sancheong-gun, Gyeongsangnam-do, CcMc were detected in 811 (45.6%) out of 1,779 fishes examined and their intensity was 9.8 per fish infected. The prevalence was most high in Squalidus spp. (97.7%) and followed by acheilognathinid fish (66.8%), Pungtungia herzi (52.0%), rasborinid fish (39.6%) and Hemibarbus spp. (25.9%) from Yangcheon. The intensity was also most high in Squalidus spp. (27.0). The endemicity with CcMc was very low in fishes from water systems of Nakdong-gang in the east coast of Korea. Conclusively, it is confirmed that various fish species act as the second intermediate hosts of C. complanatum, and the endemicities of CcMc are more or less different by the fish species and group from Yangcheon, in Sancheong-gun, Gyeongsangnam-do, Korea.


[Two Scabies Outbreaks at a Tertiary Care Hospital in Portugal].
Scabies outbreaks in healthcare institutions are an emerging problem. To determine the best management strategy is a topical matter. We analyzed two hospital scabies outbreaks and reviewed the management strategy of institutional scabies outbreaks. We performed an observational retrospective study of two independent scabies outbreaks that occurred in a Portuguese tertiary hospital in 2018. Following the identification of the index cases, scabies cases and exposed individuals, we calculated the attack rate in patients and professionals. We also evaluated the treatment and infection control measures, as well as the global cost of each outbreak. The hospital outbreaks of scabies occurred in two wards of Internal Medicine. Both had as index cases institutionalized patients with dermatosis at the time of admission. In the Ward 1, there have been identified 409 exposed individuals, 14 cases of scabies and the attack rate was 3.4%. In the Ward 2, there have been identified 254 exposed individuals, 17 cases and the attack rate was 6.7%. Topical treatment was prescribed to the cases and environmental measures were implemented. In our analysis, both outbreaks had as index cases institutionalized patients and had a significant impact, with hundreds of exposed individuals and considerable costs. The analysis of hospital scabies outbreaks is mostly retrospective and represents an opportunity to review its best management strategy. Implementation of guidelines on tackling scabies outbreaks in institutional settings is urgent.


Antimicrobial prophylactic practice in surgical patients.
To evaluate the prescribing patterns of surgeons for pre-operative antimicrobial prophylaxis. A retrospective study based on data obtained from case records of surgical patients admitted into the Department of Surgery. Department of Surgery, Royal Commission Medical Center, Madinat Yambu Al-Sinayah. The study population comprised of 888 surgical patients who received antibiotic therapy either for prophylaxis or treatment during the period 1st November 1992 and 28th February 1995. A total of 888 surgical patients received antibiotics during the study period, 191 (21.5%) for prophylaxis while 697 (78.5%) were given antibiotics for therapy before and after surgery. Ceftriaxone was the most commonly used antibiotic for prophylaxis, followed by augmentin and cefotaxime, and these were frequently given in multiple doses, extending beyond 24 hours. There was unwarranted and over use of prophylactic agents in at least 70% of the patients, with increased costs to the Hospital. Effective prophylaxis can be accomplished with a single dose of a cephalosporin, such as ceftriaxone, cefuroxime or cefazolin, for the common surgical procedures. It is recommended that better compliance with principles of surgical antimicrobial prophylaxis be implemented Prophylactic antibiotic audit measures should be carried out by the control committee. The development of guidelines and standing orders for antimicrobial prophylaxis should help to improve compliance.


Taking up the cyanine challenge with quantum tools.
Cyanine derivatives, named from the Greek word kyanos meaning dark-blue, were discovered more than 150 years ago and remain one of the most widely used classes of organic dyes with contemporary applications in photography (panchromatic emulsions), information storage (CD-R and DVD-R media) and biochemistry (DNA and protein labeling) fields. Cyanine chromogens consist of a charged π-conjugated segment containing an odd number of sp(2) carbon atoms with the chain capped at the extremities by two electronegative centers, typically nitrogen or oxygen atoms. Cyanines are characterized by a vanishing bond length alternation indicating nearly equal carbon-carbon bond lengths, as well as a very intense and sharp absorption band presenting a shoulder. This hallmark band undergoes a strong red shift when the chain is extended. This so-called vinyl shift is extremely large (ca. 100 nm for each pair of carbon atoms added in the π-conjugated path), making cyanines ideal building blocks for the design of devices with near-infrared applications. Numerous cyanines also exhibit emission bands with large quantum yields. These exceptional optical properties explain why both canonical cyanines and the corresponding fluoroborates (e.g., boron-dipyrromethene, BODIPY) remain the focus of an ever-growing body of experimental work. In turn, this popularity has stimulated quantum mechanical investigations aiming, on the one hand, at probing the specific electronic nature of cyanine dyes and, on the other hand, at helping to design new dyes. However, the adiabatic approximation to time-dependent density functional theory, the most widespread ab initio model for electronically excited states, fails to accurately reproduce the absorption spectra of cyanine derivatives: it yields a systematic and large underestimation of the experimental wavelengths irrespective of the details of the computational protocol. In contrast, highly correlated wave function approaches provide accurate transition energies for model systems but are hardly applicable to real-life cyanines and BODIPY. This indicates that setting up a computationally tractable theoretical protocol that provides both robust and accurate optical spectra for cyanine-based dyes is a major challenge that has only been taken up lately. In this Account, we compile the most recent advances in the field by considering both compact streptocyanines and large fluoroborates. For the former, we summarize the key results obtained with a large panel of theoretical approaches, allowing us not only to understand the origin of the cyanine challenge but also to pinpoint the schemes presenting the most promising accuracy/effort ratio. For the latter, we show via selected examples how theoretical models can be used to reproduce simultaneously experimental band shapes and transition energies, thus paving the way to an efficient in silico design of new compounds.


Intracranial displacement of the eye after blunt trauma.
A 67-year-old man fell from an agricultural vehicle and struck his right eye on a protruding element. Eight hours later, he was brought to the emergency unit of an ophthalmology hospital where examiners could not find the right eye and believed it to have been completely destroyed. However, CT disclosed that the eye, apparently still intact, had been displaced into the anterior cranial fossa through a fracture in the orbital roof. This is the first documentation of such a phenomenon.


A randomized trial comparing conventional and endovascular repair of abdominal aortic aneurysms.
Although the initial results of endovascular repair of abdominal aortic aneurysms were promising, current evidence from controlled studies does not convincingly show a reduction in 30-day mortality relative to that achieved with open repair. We conducted a multicenter, randomized trial comparing open repair with endovascular repair in 345 patients who had received a diagnosis of abdominal aortic aneurysm of at least 5 cm in diameter and who were considered suitable candidates for both techniques. The outcome events analyzed were operative (30-day) mortality and two composite end points of operative mortality and severe complications and operative mortality and moderate or severe complications. The operative mortality rate was 4.6 percent in the open-repair group (8 of 174 patients; 95 percent confidence interval, 2.0 to 8.9 percent) and 1.2 percent in the endovascular-repair group (2 of 171 patients; 95 percent confidence interval, 0.1 to 4.2 percent), resulting in a risk ratio of 3.9 (95 percent confidence interval, 0.9 to 32.9). The combined rate of operative mortality and severe complications was 9.8 percent in the open-repair group (17 of 174 patients; 95 percent confidence interval, 5.8 to 15.2 percent) and 4.7 percent in the endovascular-repair group (8 of 171 patients; 95 percent confidence interval, 2.0 to 9.0 percent), resulting in a risk ratio of 2.1 (95 percent confidence interval, 0.9 to 5.4). On the basis of the overall results of this trial, endovascular repair is preferable to open repair in patients who have an abdominal aortic aneurysm that is at least 5 cm in diameter. Long-term follow-up is needed to determine whether this advantage is sustained.


Spin propensities of octahedral complexes from density functional theory.
The fundamental balance between high- and low-spin states of transition metal systems depends on both the metal ion and the ligands surrounding it, as often visualized by the spectrochemical series. Most density functionals do not reproduce this balance, and real spin state propensities depend on orbital pairing and vibrational entropies absent in the spectrochemical series. Thus, we systematically computed the tendency toward high or low spin of "text-book" octahedral metal complexes versus ligand and metal type, using eight density functionals. Dispersion effects were generally <5 kJ/mol, favoring low-spin states. Zero-point energies favored high-spin states up to 33 kJ/mol for strong ligands, but down to a few kilojoules per mole for weak ligands. Vibrational entropy also favored high-spin states up to 40 kJ/mol, most for strong ligands. Jahn-Teller distortion in Co(II) low-spin states, particularly stable d(6) low-spin states, and entropy corrections were consistent with experiment. Entropy and zero-point energy corrections were markedly lower for Co(II) and Mn(III), viz., the differential ligand field stabilization energy, and can only be ignored for weak ligands. The data enable simple assessment of spin state propensities versus ligand and metal type and reveal, e.g., that CN(-) is consistently weaker than CO for M(II) but stronger than CO for M(III) and SCN(-) and NCS(-) change order in M(II) versus M(III) complexes. Contrary to expectation based on the spectrochemical series, Cl(-) and Br(-) are very close in spin state propensity because the pairing penalty for low spin is smaller in Br(-). Thus, for the M(II) complexes, we find a consensus order of Br(-) ∼ Cl(-) < H2O < SCN(-) < NCS(-) ∼ NH3 < CN(-) < CO, whereas for the M(III) complexes, an approximate order is Br(-) ∼ Cl(-) < H2O ∼ NCS(-) ∼ SCN(-)< NH3 < CO < CN(-).


Update of liver fibrosis and steatosis with transient elastography (Fibroscan).
Assessment of liver fibrosis and steatosis is now almost indispensable in most of the chronic liver diseases in order to determine prognosis and need for treatment, and to monitor disease progression and response to treatment. Liver biopsy is limited by its invasiveness and patient acceptability. Transient elastography (TE; Fibroscan) is a non-invasive tool with satisfactory accuracy and reproducibility to estimate liver fibrosis. To review the existing evidence concerning the clinical applications of TE in major liver diseases, including chronic hepatitis B and -C, non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease, primary biliary cirrhosis and primary sclerosing cholangitis. As alanine aminotransferase (ALT) is one of the major confounding factors of liver stiffness in chronic hepatitis B, an ALT-based algorithm has been developed and higher liver stiffness measurements (LSM) cut-off values for different stages of liver fibrosis should be used in patients with elevated ALT levels up to five times the upper limit of normal. Furthermore, falsely-high LSM results up to the cirrhotic range may occur during ALT flare. TE is also useful predicting patient prognosis in the development of hepatocellular carcinoma (HCC), portal hypertension, postoperative complications in HCC patients and survival. Unfortunately, failed acquisition of TE is common in obese patients. Furthermore, obese patients may have higher LSM results, even in the same stage of liver fibrosis. To better evaluate NAFLD a new XL probe, with a larger probe with lower ultrasound frequency and deeper penetration, increases the success rate of TE in obese patients. The median LSM value with the XL probe was found to be lower than that by the conventional M probe, hence cut-off values were approximately 1.2 to 1.3 kilopascals lower than those of the M probe, suggesting its adoption. Studies reveal that a novel ultrasonic controlled attenuation parameter is potentially useful to detect and quantify hepatic steatosis non-invasively. TE is a non-invasive, accurate and reproducible test of liver fibrosis and possibly hepatic steatosis and has been validated in a wide spectrum of liver diseases. TE is also useful to predict patient outcomes.


[The "Well-being paradox" in quality-of-life research].
In quality-of-life research an empirical phenomenon has been observed independently in medicine and in the social sciences which is so contrary to what intuition tells us that it has been called paradoxical. In medicine it is called the "satisfaction paradox" and in the social sciences the "well-being paradox". What is meant in both cases is that objectively negative factors in one's life have relatively little effect on subjective quality of life. In the present paper examples are given of relevant research findings from both fields. An attempt is then made to explain the phenomenon, with the topic being examined not only from a methodological but also from a personality, cognition and social psychology perspective. Finally, the implications for research and clinical work are discussed.


Is endometrial receptivity affected in women with endometriosis? Results from a matched pair case-control study of assisted reproductive technology treatments.
Is endometriosis detrimental to embryo implantation? A retrospective matched case-control study of women with a surgical or ultrasound diagnosis of endometriosis at Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico di Milano between 2015 and 2021. Women with endometriosis who underwent a 'freeze-all' cycle during an IVF treatment were eligible to be included. They were matched to patients without the disease, who also underwent cryopreserved blastocyst transfer cycles, in a 1:1 ratio by age (±1 year), and number (=) and quality (±1 top versus low) of cryopreserved blastocysts. All women underwent single frozen embryo transfer, and assisted reproductive technology outcomes suggested by the Core Outcome Measure for Infertility Trials initiative were evaluated. The main outcome was the cumulative live birth rate per cycle. One hundred and one women with endometriosis and 101 matched unaffected women were included. Cumulative live birth rate per cycle did not vary between women with and without endometriosis (50% versus 58%, respectively; P = 0.32). On the basis of the Kaplan-Meier analysis, the predicted success rates over four embryos transferred were also similar (74% versus 82%, respectively; P = 0.67). In women with moderate or severe endometriosis, these retrospective results seem to indicate no or a limited effect of the disease on endometrial receptivity.


Large-scale vortex lattice emerging from collectively moving microtubules.
Spontaneous collective motion, as in some flocks of bird and schools of fish, is an example of an emergent phenomenon. Such phenomena are at present of great interest and physicists have put forward a number of theoretical results that so far lack experimental verification. In animal behaviour studies, large-scale data collection is now technologically possible, but data are still scarce and arise from observations rather than controlled experiments. Multicellular biological systems, such as bacterial colonies or tissues, allow more control, but may have many hidden variables and interactions, hindering proper tests of theoretical ideas. However, in systems on the subcellular scale such tests may be possible, particularly in in vitro experiments with only few purified components. Motility assays, in which protein filaments are driven by molecular motors grafted to a substrate in the presence of ATP, can show collective motion for high densities of motors and attached filaments. This was demonstrated recently for the actomyosin system, but a complete understanding of the mechanisms at work is still lacking. Here we report experiments in which microtubules are propelled by surface-bound dyneins. In this system it is possible to study the local interaction: we find that colliding microtubules align with each other with high probability. At high densities, this alignment results in self-organization of the microtubules, which are on average 15 µm long, into vortices with diameters of around 400 µm. Inside the vortices, the microtubules circulate both clockwise and anticlockwise. On longer timescales, the vortices form a lattice structure. The emergence of these structures, as verified by a mathematical model, is the result of the smooth, reptation-like motion of single microtubules in combination with local interactions (the nematic alignment due to collisions)--there is no need for long-range interactions. Apart from its potential relevance to cortical arrays in plant cells and other biological situations, our study provides evidence for the existence of previously unsuspected universality classes of collective motion phenomena.


Nephrotoxicity of Kalach 360 SL: biochemical and histopathological findings.
Kalach 360 SL (KL) is a commercial herbicide which contains 360 g/l of glyphosate used in both agricultural and urban areas throughout the world including Tunisia. We aimed to evaluate the effects of KL on rats' renal system. Female Wistar rats were divided into three groups: group 1 (n = 6) received a standard diet and served as control, groups 2 and 3 (n = 12 each) received 0.07 ml (D1: 126 mg/kg), and 0.175 ml (D2: 315 mg/kg) of KL, respectively, for 60 d. The chronic exposure to KL induced a significant increase in plasma creatinine, urea, and uric acid levels. Creatinine clearance decreased in KL-treated groups, compared with controls. Several urine parameters, such as urine-specific gravity and urine osmolality, significantly decreased, while dieresis and urinary Na/K + ratio increased in KL-treated groups. These findings suggested a distal tubular damage caused by tubular necrosis. Moreover, the chronic exposure to KL induced an increase in lipid peroxidation (LPO) and a decrease in antioxidant status, enzymatic activities (superoxide dismutase and catalase) and non-enzymatic levels (vitamin C), which led to an oxidative stress. Histopathological studies showed a peritubular inflammatory reaction, nephrose, fragmented glomeruli, necrotic epithelial cells, and tubular dilatation. These results could have significant health implications for animal and human populations. Further data are necessary to investigate the potential consequences of chronic dose exposure during life.


[The disinfection of fish in the family Cyprinidae of Opisthorchis felineus Riv. metacercariae by the combined use of acetic acid and table salt].
The studies were aimed at optimizing the procedure for disinfection of carps from the larvae of a pathogen of opisthorchiasis. The effects of different concentrations of acetic acid solutions on the viability of encysted O. felineus metacercariae isolated from ide (Leuciscus idus L.) tissue, as well as on that of larvae located in the fish muscles were examined by consequently using the solutions of acetic acid and salt. Acetic acid solutions (3 and 6%) are minimally effective in suppressing the viability of encysted O. felineus metacercariae isolated from fish tissues, 6% acetic solution being approximately 6 times higher. Acetic acid pretreatment of fish led to the higher salt penetration rate into the muscles of fish when it was salted thereafter and accelerated the death of O. felineus metacercariae. To correct the way of salting the fish invaded by Opisthorchis metacercariae, 4-hour fish presoaking in 6% acetic acid solution is most promising, which promotes the acceleration of the death of metacercariae and exerts no noticeable effect on the marketable state and taste of fish.


Expression of CD44 variants in osteosarcoma.
The standard form of CD44 (CD44H) is a transmembranous glycoprotein, widely distributed on a variety of human lymphoid cells, epithelial cells and tumours. CD44 has many variant forms, which are generated by alternative splicing. In recent years, CD44 has been reported to be related to the degree of tumour differentiation, tumour cell invasion, and metastasis. We investigated 44 tumour specimens in 39 patients with osteosarcoma immunochemically to analyse the expression of CD44 standard (CD44H) and variant exon-encoded gene products (CD44v3, v4, v5, v6, v7, v9, and v10). Furthermore, the relationship between CD44 expression and the clinical outcome of patients with osteosarcoma was analysed. Membrane accentuation and exclusive cytoplasmic reactivity were analysed as separate staining patterns. Tumour cells and some multinucleated giant cells were markedly stained. CD44H, v3, v4, v5, v6, v7, v9, and v10 were expressed in 85%, 49%, 54%, 59%, 46%, 5%, 28%, and 10% of the specimens respectively. The cumulative 5-year metastasis-free survival was 58% in CD44v6-negative cases and 24% in CD44v6-positive cases (P=0.046). However, the cumulative 5-year metastasis-free survival was not significantly different between cases positive and negative for other variants of CD44. Multivariate analysis (Cox proportional-hazard model) with CD44v6 expression (positive or negative), chemotherapy (intensive or non-intensive), tumour site (proximal or distal), and age (at least 30 years or less than 30 years) showed that expression of CD44v6 and chemotherapy were important prognostic factors in patients with osteosarcoma. Overexpression of CD44 isoforms containing variant v6 is correlated with poor prognosis in patients with osteosarcoma.


Characterization and outcomes of renal leukocyte chemotactic factor 2-associated amyloidosis.
Amyloidosis derived from leukocyte chemotactic factor 2 (ALECT2) is a recently described disease. Here, we report the characteristics and outcome of 72 patients with renal ALECT2, which included 19 who had another kidney disease on biopsy. Ninety-two percent of patients were Hispanics and over half were elderly. Three had other organ, but not cardiac, amyloidosis involvement. All patients without concurrent disease, except three, presented with chronic renal insufficiency. Proteinuria was variable and absent in a third, whereas nephrotic syndrome and hematuria were rare. After a median follow-up of 26 months, one-third developed end-stage renal disease (ESRD). The median renal survival was 62 months. Independent predictors of renal survival were serum creatinine at diagnosis, with a value of 2.0 mg/dl being the best cutoff for predicting ESRD, percentage global glomerulosclerosis, and presence of diabetes. Only four patients died and four had received chemotherapy for an erroneous diagnosis of immunoglobulin light chain-derived amyloidosis. Five patients underwent kidney transplantation; none had graft loss but one had disease recurrence. Patient survival is superior to renal immunoglobulin light chain-derived amyloidosis and reactive amyloidosis largely due to the absence of cardiac involvement. Thus, renal ALECT2 mainly affects elderly Hispanics who typically present with chronic renal insufficiency and bland urine sediment, with or without proteinuria.


Advanced hyphenated chromatographic-mass spectrometry in mycotoxin determination: current status and prospects.
Mass spectrometric techniques are essential for advanced research in food safety and environmental monitoring. These fields are important for securing the health of humans and animals, and for ensuring environmental security. Mycotoxins, toxic secondary metabolites of filamentous fungi, are major contaminants of agricultural products, food and feed, biological samples, and the environment as a whole. Mycotoxins can cause cancers, nephritic and hepatic diseases, various hemorrhagic syndromes, and immune and neurological disorders. Mycotoxin-contaminated food and feed can provoke trade conflicts, resulting in massive economic losses. Risk assessment of mycotoxin contamination for humans and animals generally depends on clear identification and reliable quantitation in diversified matrices. Pioneering work on mycotoxin quantitation using mass spectrometry (MS) was performed in the early 1970s. Now, unambiguous confirmation and quantitation of mycotoxins can be readily achieved with a variety hyphenated techniques that combine chromatographic separation with MS, including liquid chromatography (LC) or gas chromatography (GC). With the advent of atmospheric pressure ionization, LC-MS has become a routine technique. Recently, the co-occurrence of multiple mycotoxins in the same sample has drawn an increasing amount of attention. Thus, modern analyses must be able to detect and quantitate multiple mycotoxins in a single run. Improvements in tandem MS techniques have been made to achieve this purpose. This review describes the advanced research that has been done regarding mycotoxin determination using hyphenated chromatographic-MS techniques, but is not a full-circle survey of all the literature published on this topic. The present work provides an overview of the various hyphenated chromatographic-MS-based strategies that have been applied to mycotoxin analysis, with a focus on recent developments. The use of chromatographic-MS to measure levels of mycotoxins, including aflatoxins, ochratoxins, patulin, trichothecenes, zearalenone, and fumonisins, is discussed in detail. Both free and masked mycotoxins are included in this review due to different methods of sample preparation. Techniques are described in terms of sample preparation, internal standards, LC/ultra performance LC (UPLC) optimization, and applications and survey. Several future hyphenated MS techniques are discussed as well, including multidimensional chromatography-MS, capillary electrophoresis-MS, and surface plasmon resonance array-MS.


Maji: a new tool to prevent overhydration of children receiving intravenous fluid therapy in low-resource settings.
We designed and evaluated the accuracy and usability of a device to regulate the volume of fluid dispensed during intravenous drip therapy. The mechanical system was developed in response to a pressing need articulated by clinicians in pediatric wards throughout sub-Saharan Africa, who require a tool to prevent overhydration in children receiving intravenous fluid in settings that lack burettes or electronic infusion pumps. The device is compatible with most intravenous bags and limits the volume dispensed to a preset amount that can be adjusted in 50 mL increments. Laboratory accuracy over a range of clinically-relevant flow rates, initial bag volumes, and target volumes was within 12.0 mL of the target volume. The ease of use is "excellent," with a mean system usability score of 84.4 out of 100. Use of the device limits the volume of fluid dispensed during intravenous therapy and could potentially reduce the morbidity and mortality associated with overhydration in children receiving intravenous therapy.


Genogroup I and II noroviruses detected in stool samples by real-time reverse transcription-PCR using highly degenerate universal primers.
Genogroup I noroviruses from five genetic clusters and genogroup II noroviruses from eight genetic clusters were detected in stool extracts using degenerate primers and single-tube, real-time reverse transcription-PCR (RT-PCR) with SYBR Green detection. Two degenerate primer sets, designated MON 431-433 and MON 432-434, were designed from consensus sequences from the major clusters of norovirus based on the RNA-dependent RNA polymerase region of the norovirus genome. Viruses were extracted from stool samples within 20 min using a viral RNA extraction kit. Real-time RT-PCR for noroviruses generated semiquantitative results by means of the cycle threshold data and dilution endpoint standard curves. Presumptive product verification was achieved by evaluation of first-derivative melt graphs. Multiple clusters of noroviruses were identified simultaneously in a multiplex fashion by virtue of slight differences in melting temperature. The detection of 13 different genetic clusters suggests that the MON primers may serve as universal primers for most, if not all, of the noroviruses in a multiplex assay. Our technique provides a framework for broad application of real-time RT-PCR in clinical, environmental, and food testing laboratories for a wide range of noroviruses.


Community effects of the opening of the Niagara casino.
The impacts on the community of the opening of a casino in Niagara Falls are studied. The study uses a pre/post design for the community data, with pre/post data from Ontario as a whole as a comparison. The study site is the city of Niagara Falls, Ontario, where a casino opened in early December, 1996. Using random-digit dialing, telephone interviews were conducted with adult residents of Niagara Falls in 1996 and 1997, and with adult residents of Ontario in 1995 and 1997. Aside from demographic variables, measures included general attitudes to gambling, expectations about (1996) and experiences with (1997) the casino's opening, extent of participation in 11 types of gambling and 18 items on problems with gambling: five key items from a standard gambling problems score (SOGS), five life-area problems items, and items on pressures from others concerning the respondent's gambling and on gambling problems among family and friends. Attitudes to gambling remained stable in Niagara Falls, while there was some evidence of decline in approval in Ontario as a whole. While strong majorities of 1996 respondents had expected many positive and negative effects on The Community of the Casino's opening, Significantly fewer respondents in 1997 reported actually experiencing most of these effects. While a small increase in employment was found, it fell far below projections, a result probably reflecting displacement effects. The rate and level of casino gambling increased in Ontario, but increased even more in Niagara Falls, with little displacement of other gambling. Reported gambling problems increased significantly in Niagara Falls for two of 10 gambling problem items and for the short SOGS score, while rates were generally stable or declining in the province. Pressure from others about gambling rose significantly in Niagara Falls (in contrast to the province), and reported rates of family members or friends with gambling problems also rose substantially. There was an increasing trend in Niagara Falls for all 18 problem indicators. The casino's opening brought more gambling by local residents, and an increase in reported gambling problems; yet support for the casino, already strong, if anything grew. At least in the short term, problems from the increased availability of gambling manifested themselves not in the public arena but rather in the arena of private life.


Predicting treatment effects using biomarker data in a meta-analysis of clinical trials.
A biomarker (S) measured after randomization in a clinical trial can often provide information about the true endpoint (T) and hence the effect of treatment (Z). It can usually be measured earlier and more easily than T and as such may be useful to shorten the trial length. A potential use of S is to completely replace T as a surrogate endpoint to evaluate whether the treatment is effective. Another potential use of S is to serve as an auxiliary variable to help provide information and improve the inference on the treatment effect prediction when T is not completely observed. The objective of this report is to focus on its role as an auxiliary variable and to identify situations when S can be useful to increase efficiency in predicting the treatment effect in a new trial in a multiple-trial setting. Both S and T are continuous. We find that higher efficiency gain is associated with higher trial-level correlation but not individual-level correlation when only S, but not T is measured in a new trial; but, the amount of information recovery from S is usually negligible. However, when T is partially observed in the new trial and the individual-level correlation is relatively high, there is substantial efficiency gain by using S. For design purposes, our results suggest that it is often important to collect markers that have high adjusted individual-level correlation with T and at least a small amount of data on T. The results are illustrated using simulations and an example from a glaucoma clinical trial.


Vasopressin-dependent and -independent control of the release of adrenocorticotropin.
We tested the possibility that vasopressin mediates the responses of adrenocorticotropin (ACTH) to electrical stimulation of various areas of the hypothalamus. Thirty-three cats were anesthetized with chloralose-urethane, immobilized with gallamine, and respired artificially. Plasma ACTH was measured by RIA. Intraventricular administration of antiserum to vasopressin blocked the release of ACTH induced by electrical stimulation of the paraventricular nucleus (PVN), suggesting a role for the vasopressinergic projection from PVN to the external zone of the median eminence. In contrast, the release of ACTH induced by stimulation of areas ventral to PVN was unaffected by the antiserum. Thus, there is at least one corticotropin releasing factor released from nuclei other than PVN that is distinct from vasopressin.


Rac and Arp2/3-Nucleated Actin Networks Antagonize Rho During Mitotic and Meiotic Cleavages.
In motile cells, the activities of the different Rho family GTPases are spatially segregated within the cell, and during cytokinesis there is evidence that this may also be the case. But while Rho's role as the central organizer for contractile ring assembly is well established, the role of Rac and the branched actin networks it promotes is less well understood. To characterize the contributions of these proteins during cytokinesis, we manipulated Rac and Arp2/3 activity during mitosis and meiosis in sea urchin embryos and sea star oocytes. While neither Rac nor Arp2/3 were essential for early embryonic divisions, loss of either Rac or Arp2/3 activity resulted in polar body defects. Expression of activated Rac resulted in cytokinesis failure as early as the first division, and in oocytes, activated Rac suppressed both the Rho wave that traverses the oocyte prior to polar body extrusion as well as polar body formation itself. However, the inhibitory effect of Rac on cytokinesis, polar body formation and the Rho wave could be suppressed by effector-binding mutations or direct inhibition of Arp2/3. Together, these results suggest that Rac- and Arp2/3 mediated actin networks may directly antagonize Rho signaling, thus providing a potential mechanism to explain why Arp2/3-nucleated branched actin networks must be suppressed at the cell equator for successful cytokinesis.