The relation of the Krebs cycle to viral synthesis. II. The effect of sodium fluoroacetate on the propagation of influenza virus in mice.
A further study has been made of the relationship of reactions of the Krebs cycle to the propagation of influenza virus. By the administration of sublethal doses of sodium fluoroacetate which were found to increase the concentration of citrate in the mouse lung, it was possible to demonstrate a blocking of the citric acid cycle in that organ. Further, the intraperitoneal administration of these concentrations of fluoroacetate was found to inhibit markedly the propagation of influenza, Type A, virus in the lungs of mice. The inhibition was observed when the fluoroacetate was administered 15 minutes, 6 hours, or 12 hours after the mice were inoculated with virus. This effect was also demonstrable when the concentration of the viral inoculum was varied over a range of virus titers from 10(3.5) to 10(6.5). Sodium fluoroacetate was found to have no effect in vitro on the infectivity or hemagglutinating property of the virus. The significance of these findings with regard to chemotherapy and to the mechanism of viral synthesis is described.


Secular Trends in the Clinical Characteristics of Type 2 Diabetic Patients With Severe Hypoglycemia Between 2008 and 2013.
We investigated the trends in the clinical characteristics and prescriptions of type 2 diabetic patients with severe hypoglycemia because the prescription rate of antidiabetic agents has significantly changed recently. A total of 193 patients with type 2 diabetes with severe hypoglycemia induced by antidiabetic agents between 2008 and 2013 were divided into three groups based on the period of visit: 2008 - 2009, 2010 - 2011 and 2012 - 2013. While the proportion of patients with severe hypoglycemia using insulin (from 55% to 74%), biguanides (from 6% to 20%), glinides, and dipeptidyl peptidase-4 inhibitors significantly increased, those using sulfonylureas (from 45% to 20%) significantly decreased. Errors of drug use significantly increased as a trigger of hypoglycemia in recent years. The number of antidiabetic agents (from 1.9 ± 0.6 to 2.3 ± 0.7), non-diabetic agents (from 2.3 ± 2.4 to 4.3 ± 3.3), and total drugs prescribed were significantly higher in recent years among patients receiving insulin therapy. Polypharmacy especially in patients receiving insulin therapy and errors of drug use have increased in type 2 diabetic patients with severe hypoglycemia in recent years. Intensive education in the usage rule of drugs is considered to be important in order to prevent severe hypoglycemia.


Bevacizumab for advanced cervical cancer: patient-reported outcomes of a randomised, phase 3 trial (NRG Oncology-Gynecologic Oncology Group protocol 240).
GOG 240 was a practice-changing randomised phase 3 trial that concluded that chemotherapy plus bevacizumab for advanced cervical cancer significantly improves overall and progression-free survival, and the proportion of patients achieving an overall objective response, compared with chemotherapy alone. In this study, we aimed to analyse patient-reported outcomes in GOG 240. Eligible adult participants (aged ≥18 years) had primary stage IVB or recurrent or persistent carcinoma of the cervix with measurable disease and GOG performance status of 0-1. Participants were randomly assigned by web-based permuted block randomisation (block size 4) in a 1:1:1:1 ratio to the four treatment groups: cisplatin (50 mg/m(2) intravenously on day 1 or 2 of the treatment cycle) and paclitaxel (135 mg/m(2) intravenously over 24 h or 175 mg/m(2) intravenously over 3 h on day 1), with or without bevacizumab (15 mg/kg intravenously on day 1 or 2), or paclitaxel (175 mg/m(2) over 3 h on day 1) and topotecan (0·75 mg/m(2) for 30 min on days 1-3) with or without bevacizumab (15 mg/kg intravenously on day 1). Treatment assignment was concealed at randomisation (everyone was masked to treatment assignment, achieved by the use of a computer encrypted numbering system at the National Cancer Institute) and became open-label when each patient was registered to the trial. Treatment cycles were repeated every 21 days until disease progression or unacceptable toxicity, whichever occurred first. The coprimary endpoints of the trial were overall survival and safety; the primary quality-of-life endpoint was the score on the Functional Assessment of Cancer Therapy-Cervix Trial Outcome Index (FACT-Cx TOI). For our analysis of patient-reported outcomes, participants were assessed before treatment cycles 1, 2, and 5, and at 6 and 9 months after the start of cycle 1, with the FACT-Cx TOI, items from the FACT-GOG-Neurotoxicity subscale, and a worst pain item from the Brief Pain Inventory. All patients who completed baseline quality-of-life assessments and at least one further follow-up assessment were evaluable for quality-of-life outcomes. This study is registered with ClinicalTrials.gov, number NCT00803062. Between April 6, 2009, and Jan 3, 2012, a total of 452 patients were enrolled in the trial, of whom 390 completed baseline quality-of-life assessment and at least one further assessment and were therefore evaluable for quality-of-life outcomes. In these patients, patient-reported outcome completion declined from 426 (94%) of 452 (at baseline) to 193 (63%) of 307 (9 months post-cycle 1), but completion rates did not differ significantly between treatment regimens (p=0·78). The baseline FACT-Cx TOI scores did not differ significantly between patients who received bevacizumab versus those who did not (p=0·27). Compared with patients who received chemotherapy alone, patients who received chemotherapy plus bevacizumab reported FACT-Cx TOI scores that were an average of 1·2 points lower (98·75% CI -4·1 to 1·7; p=0·30). Improvements in overall survival and progression-free survival attributed to the incorporation of bevacizumab into the treatment of advanced cervical cancer were not accompanied by any significant deterioration in health-related quality of life. Patients responding to anti-angiogenesis therapy who maintain an acceptable quality of life could be suitable at progression for treatment with other novel therapies that might confer additional benefit. National Institutes of Health.


Transgenic mouse lines subdivide medial vestibular nucleus neurons into discrete, neurochemically distinct populations.
The identification of neuron types within circuits is fundamental to understanding their relevance to behavior. In the vestibular nuclei, several classes of neurons have been defined in vivo on the basis of their activity during behavior, but it is unclear how those types correspond to neurons identified in slice preparations. By targeting recordings to neurons labeled in transgenic mouse lines, this study reveals that the continuous distribution of intrinsic parameters observed in medial vestibular nucleus (MVN) neurons can be neatly subdivided into two populations of neurons, one of which is GABAergic and the other of which is exclusively glycinergic or glutamatergic. In slice recordings, GABAergic neurons labeled in the EGFP (enhanced green fluorescent protein)-expressing inhibitory neuron (GIN) line displayed lower maximum firing rates (<250 Hz) than glycinergic and glutamatergic neurons labeled in the yellow fluorescent protein-16 (YFP-16) line (up to 500 Hz). In contrast to cortical and hippocampal interneurons, GABAergic MVN neurons exhibited wider action potentials than glutamatergic (and glycinergic) neurons. Responses to current injection differed between the neurons labeled in the two lines, with GIN neurons modulating their firing rates over a smaller input range, adapting less during steady depolarization, and exhibiting less rebound firing than YFP-16 neurons. These results provide a scheme for robust classification of unidentified MVN neurons by their physiological properties. Finally, dye labeling in slices shows that both GABAergic and glycinergic neurons project to the contralateral vestibular nuclei, indicating that commissural inhibition is accomplished through at least two processing streams with differential input and output properties.


It's time to fear! Interval timing in odor fear conditioning in rats.
Time perception is crucial to goal attainment in humans and other animals, and interval timing also guides fundamental animal behaviors. Accumulating evidence has made it clear that in associative learning, temporal relations between events are encoded, and a few studies suggest this temporal learning occurs very rapidly. Most of these studies, however, have used methodologies that do not permit investigating the emergence of this temporal learning. In the present study we monitored respiration, ultrasonic vocalization (USV) and freezing behavior in rats in order to perform fine-grain analysis of fear responses during odor fear conditioning. In this paradigm an initially neutral odor (the conditioned stimulus, CS) predicted the arrival of an aversive unconditioned stimulus (US, footshock) at a fixed 20-s time interval. We first investigated the development of a temporal pattern of responding related to CS-US interval duration. The data showed that during acquisition with odor-shock pairings, a temporal response pattern of respiration rate was observed. Changing the CS-US interval duration from 20-s to 30-s resulted in a shift of the temporal response pattern appropriate to the new duration thus demonstrating that the pattern reflected the learning of the CS-US interval. A temporal pattern was also observed during a retention test 24 h later for both respiration and freezing measures, suggesting that the animals had stored the interval duration in long-term memory. We then investigated the role of intra-amygdalar dopaminergic transmission in interval timing. For this purpose, the D1 dopaminergic receptors antagonist SCH23390 was infused in the basolateral amygdala before conditioning. This resulted in an alteration of timing behavior, as reflected in differential temporal patterns between groups observed in a 24 h retention test off drug. The present data suggest that D1 receptor dopaminergic transmission within the amygdala is involved in temporal processing.


Learning oncogenetic networks by reducing to mixed integer linear programming.
Cancer can be a result of accumulation of different types of genetic mutations such as copy number aberrations. The data from tumors are cross-sectional and do not contain the temporal order of the genetic events. Finding the order in which the genetic events have occurred and progression pathways are of vital importance in understanding the disease. In order to model cancer progression, we propose Progression Networks, a special case of Bayesian networks, that are tailored to model disease progression. Progression networks have similarities with Conjunctive Bayesian Networks (CBNs) [1],a variation of Bayesian networks also proposed for modeling disease progression. We also describe a learning algorithm for learning Bayesian networks in general and progression networks in particular. We reduce the hard problem of learning the Bayesian and progression networks to Mixed Integer Linear Programming (MILP). MILP is a Non-deterministic Polynomial-time complete (NP-complete) problem for which very good heuristics exists. We tested our algorithm on synthetic and real cytogenetic data from renal cell carcinoma. We also compared our learned progression networks with the networks proposed in earlier publications. The software is available on the website https://bitbucket.org/farahani/diprog.


Possible mechanism of phorbol diester-induced maturation of human promyelocytic leukemia cells.
The phorbol diesters are the most potent inducers of differentiation of the promyelocytic leukemia cell line, HL-60. Soluble phorbol diester receptors from HL-60 cells were obtained from the cytosolic fraction and from the particulate fraction by either divalent ion chelation or detergent extraction. The partially purified soluble phorbol diester receptors required exogenous Ca2+ and phospholipid for maximal binding and displayed a dissociation constant (KD) of 8.1 nM for [3H]phorbol 12,13-dibutyrate. Phorbol diester analogues inhibited [3H]phorbol 12,13-dibutyrate binding in a stereospecific manner consistent with their biologic potency. The soluble phorbol diester receptors prepared by all three methods copurified in a constant ratio with the Ca2+/phospholipid-dependent protein kinase C through ammonium sulfate precipitation, DEAE ion exchange, and gel filtration chromatography. Partially purified protein kinase C was directly activated by the phorbol diesters even in the absence of exogenous Ca2+. The ability of a series of phorbol analogues to activate the kinase correlated with their known activity as inducers of cell differentiation. In addition, phorbol diester stimulation altered the phosphate acceptor substrate profile of protein kinase C, at least in part, by alteration of the Michaelis constant (Km). These data suggest that protein kinase C is the phorbol diester receptor and that phorbol diester-induced macrophage maturation of HL-60 cells may be mediated by activation of intracellular protein kinase C.


Nonfamilial VACTERL-H Syndrome in a Dizygotic Twin: Prenatal Ultrasound and Postnatal 3D CT Findings.
Background: VACTERL association is a widely known congenital malformation that includes vertebral, anal, cardiac, tracheoesophageal, renal, and limb anomalies. Patients with VACTERL and hydrocephalus appear to form a distinct group, both genetically and phenotypically, and their condition has been called VACTERL-H syndrome. Most cases of VACTERL-H have been reported postnatally, as VACTER-H syndrome is difficult to diagnose prenatally. Case Presentation: Here, we report a case of VACTERL-H syndrome in a dichorionic and diamniotic twin diagnosed prenatally by ultrasonography and confirmed postnatally by three-dimensional computed tomography (3D CT). A 34-year-old multiparous female was referred to our institution at 31 + 3 weeks gestation for suspected fetal ventriculomegaly. Detailed examinations using two-dimensional and Doppler ultrasounds revealed hydrocephalus, bilateral dysplastic upper arms, radial aplasia, unilateral pulmonary agenesis, dextrocardia with right atrial enlargement, a unilateral hypoplastic ectopic kidney, a single umbilical artery, a tracheoesophageal fistula with a small stomach, polyhydramnios, and anal atresia. Findings from the postnatal 3D CT aligned with the prenatal diagnosis, showing upper-limb agenesis, dextrocardia with pulmonary hypoplasia, tracheoesophageal fistula, imperforate anus, and colon dilatation. The affected 1390-g male twin had an unaffected 1890-g female twin sister and a healthy 6-year-old brother. Conclusions: Upon encountering fetuses with multiple anomalies, including ventriculomegaly, a small stomach with polyhydramnios, an abnormally positioned heart, and upper-limb abnormalities, clinicians should perform systematic ultrasonographic examinations to detect associated anomalies and be aware of VACTERL-H syndrome.


Room decontamination with UV radiation.
To determine the effectiveness of a UV-C-emitting device to eliminate clinically important nosocomial pathogens in a contaminated hospital room. This study was carried out in a standard but empty hospital room (phase 1) and in a room previously occupied by a patient with methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococcus (VRE) infection (phase 2) in an acute care tertiary hospital in North Carolina from January 21 through September 21, 2009. During phase 1, 8 x 8 cm Formica sheets contaminated with approximately 10(4)-10(5) organisms of MRSA, VRE, multidrug-resistant (MDR) Acinetobacter baumannii, or Clostridium difficile spores were placed in a hospital room, both in direct line of sight of the UV-C device and behind objects. After timed exposure, the presence of the microbes was assessed. During phase 2, specific sites in rooms that had housed patients with MRSA or VRE infection were sampled before and after UV-C irradiation. After timed exposure, the presence of MRSA and VRE and total colony counts were assessed. In our test room, the effectiveness of UV-C radiation in reducing the counts of vegetative bacteria on surfaces was more than 99.9% within 15 minutes, and the reduction in C. difficile spores was 99.8% within 50 minutes. In rooms occupied by patients with MRSA, UV-C irradiation of approximately 15 minutes duration resulted in a decrease in total CFUs per plate (mean, 384 CFUs vs 19 CFUs; P < .001), in the number of samples positive for MRSA (81 [20.3%] of 400 plates vs 2 [0.5%] of 400 plates; P < .001), and in MRSA counts per MRSA-positive plate (mean, 37 CFUs vs 2 CFUs; P < .001). This UV-C device was effective in eliminating vegetative bacteria on contaminated surfaces both in the line of sight and behind objects within approximately 15 minutes and in eliminating C. difficile spores within 50 minutes.


Localization of reactive oxygen species and change of antioxidant capacities in mesophyll and bundle sheath chloroplasts of maize under salinity.
In maize, the structure of bundle sheath cell (BSC) chloroplasts is less subject to salinity stress than that of mesophyll cell (MC) chloroplasts. To elucidate the difference in sensitivity to salinity, antioxidant capacities and localization of reactive oxygen species were investigated in both chloroplasts. Transmission electron microscopic observation showed that O2 (-) localization was found in both chloroplasts under salinity, but the accumulation was much greater in MC chloroplasts. H2 O2 localization was observed only in MC chloroplasts of salt-treated plants. In isolated chloroplasts, the activities of superoxide dismutase (SOD, EC 184.108.40.206), ascorbate peroxidase (APX, EC 184.108.40.206) and dehydroascorbate reductase (DHAR, EC 184.108.40.206) were increased by salinity. While the enhancement of SOD activity was similar in both chloroplasts, the increase of APX and DHAR activities were more pronounced in BSC chloroplasts than in MC chloroplasts. Monodehydroascorbate reductase (MDHAR, EC 220.127.116.11) and glutathione reductase (GR, EC 188.8.131.52) were undetectable in BSC chloroplasts, while they increased in MC chloroplasts under salinity. Although ascorbate content increased by salinity only in BSC chloroplasts, glutathione content increased significantly in both chloroplasts, and was higher in MC chloroplasts than in BSC chloroplasts. The content of thiobarbituric acid-reactive substances, which is an indicator of lipid peroxidation, was significantly increased by salinity in both chloroplasts. These results suggested O2 (-) -scavenging capacity was comparable between both chloroplasts, whereas H2 O2 -scavenging capacity was lower in MC chloroplasts than in BSC chloroplasts. Moreover, the increased lipid peroxidation under salinity was associated with the structural alteration in MC chloroplasts, while it had less impact on the structure of BSC chloroplasts.


Inhibin B and luteinizing hormone levels in girls aged 6-11 years from NHANES III, 1988-1994.
To evaluate inhibin B and luteinizing hormone (LH) levels in a large, representative cross-sectional sample of US girls and characterize the relationships of these laboratory values with age, clinical signs of puberty and other correlates. Cross-sectional analysis of LH and inhibin B in banked serum from 720 girls aged 6-11 years who participated in the Third National Health and Nutrition Examination Survey (NHANES III). Levels of inhibin B and LH, race, ethnicity and anthropometric measurements were compared for all girls. Visual assessment of pubertal stage was performed on girls aged 8 years and older. A two-part model was used to establish normative data and Tobit regression models were used to evaluate associations with participant characteristics. Receiver operating characteristic (ROC) analysis was performed to identify optimum cut points predictive of puberty onset. Mean hormone levels progressively increased with age. LH levels progressively increased with pubertal stage. Inhibin B levels increased gradually from breast stage I to II, then more sharply to peak at stage III, followed by a plateau at stages IV and V. ROC curves indicated that both hormones were consistent with pubertal onset as indicated by breast stage II. This study characterizes inhibin B and LH values in a large, representative cross-sectional sample of US girls. Inhibin B can be a useful tool in combination with other clinical and biochemical parameters to evaluate gonadal function as a reflection of pubertal progression in girls.


The historical origins of interstitial cystitis.
We identify early descriptions of interstitial cystitis and trace its evolution as a clinical entity during the 19th century. Primary and secondary source documents relating to interstitial cystitis, bladder inflammation and bladder stones were reviewed. What is believed to be the earliest published record of interstitial cystitis appeared in an 1836 textbook by the Philadelphia surgeon Joseph Parrish, who documented a syndrome of chronic frequency, urgency, dysuria and pelvic pain he called "tic doloureux of the bladder." Tic doloureux was a contemporaneous diagnosis used to describe painful, idiopathic disorders of nerves. Parrish attributed this term to his mentor, Dr. Phillip Syng Physick, who applied it to patients with severe lower urinary tract symptoms with no discernible etiology, with the most common etiology during the 19th century being bladder stones. A review of archival material from the Philadelphia College of Physicians indicates that by 1808 Physick had developed a concept of bladder inflammation, a "bladder ulcer," that produced lower urinary tract symptoms in the absence of bladder stone. By 1808 Philip Syng Physick had described an inflammatory condition of the bladder producing the same lower urinary tract symptoms as a bladder stone. By 1836 he had expanded this concept to include a chronic frequency, urgency and pain syndrome occurring in the absence of demonstrable etiology. We propose that these are the earliest known descriptions of bladder inflammation and interstitial cystitis.


Septation deficiency and phosphilipid perturbation in Escherichia coli genetically constitutive for the beta oxidation pathway.
Mutants of Escherichia coli defective in the regulation of the fatty acids beta oxidation pathway show an ultrastructural deficiency in septum formation at high growth rate. Several independent pairs of parent and mutant strains have been analyzed biochemically. Each parent strain displays a well-defined pattern of cellular phospholipids, which varies with the growth conditions. High ratios of phosphatidylglycerol to cardiolipin characterize fast-growth conditions. None of the mutant strains, although they grow in mass nearly as rapidly as their respective parents, can reach these high ratios. The beta oxidation pathway regulatory mutation leads to an increased turnover of the glycerol moieties of these phospholipids in the inner as well as in the outer cell membrane.


Enantiomeric cannabidiol derivatives: synthesis and binding to cannabinoid receptors.
(-)-Cannabidiol (CBD) is a major, non psychotropic constituent of cannabis. It has been shown to cause numerous physiological effects of therapeutic importance. We have reported that CBD derivatives in both enantiomeric series are of pharmaceutical interest. Here we describe the syntheses of the major CBD metabolites, (-)-7-hydroxy-CBD and (-)-CBD-7-oic acid and their dimethylheptyl (DMH) homologs, as well as of the corresponding compounds in the enantiomeric (+)-CBD series. The starting materials were the respective CBD enantiomers and their DMH homologs. The binding of these compounds to the CB(1) and CB(2) cannabinoid receptors are compared. Surprisingly, contrary to the compounds in the (-) series, which do not bind to the receptors, most of the derivatives in the (+) series bind to the CB(1) receptor in the low nanomole range. Some of these compounds also bind weakly to the CB(2) receptor.


Effects of Framingham 10-Year Cardiovascular Risk Score and Viral Load on Brain Integrity in Persons With HIV.
Combination antiretroviral therapy (cART) has allowed for viral load (VL) suppression and increased life expectancy for persons with HIV (PWH). Altered brain integrity, measured by neuropsychological (NP) performance and neuroimaging, is still prevalent among virally suppressed PWH. Age-related conditions such as cardiovascular disease may also affect brain integrity. This study investigated the effects of cardiovascular risk, VL, and HIV serostatus on cerebral blood flow (CBF), brain volumetrics, and cognitive function in PWH and persons without HIV (PWoH). Ten-year cardiovascular risk, using the Framingham Heart Study criteria, was calculated in PWH (n = 164) on cART with undetectable (≤20 copies/mL; n = 134) or detectable (>20 copies/mL; n = 30) VL and PWoH (n = 66). The effects of cardiovascular risk on brain integrity (CBF, volume, and cognition) were compared for PWH (undetectable and detectable VL) and PWoH. PWH had smaller brain volumes and worse NP scores than PWoH. PWH with detectable and undetectable VL had similar brain integrity measures. Higher cardiovascular risk was associated with smaller volumes and lower CBF in multiple brain regions for PWH and PWoH. Significant interactions between HIV serostatus and cardiovascular risk on brain volumes were observed in frontal, orbitofrontal, and motor regions. Cardiovascular risk was not associated with cognition for PWH or PWoH. Neuroimaging, but not cognitive measures, was associated with elevated cardiovascular risk. HIV serostatus was associated with diminished brain volumes and worse cognition while CBF remained unchanged, reflecting potential protective effects of cART. Neuroimaging measures of structure (volume) and function (CBF) may identify contributions of comorbidities, but future longitudinal studies are needed.


Structural requirements for arthritogenicity of peptidoglycans from Staphylococcus aureus and Lactobacillus plant arum and analogous synthetic compounds.
The comparative studies on the arthritogenicity of chemically well defined peptidoglycans (PG)2 from the cell walls of Staphylococcus aureus (FDA 209P) and Lactobacillus plantarum (ATCC 8014) showed that 1) a polymer of disaccharide-peptide with or without the presence of N-acetylglucosaminyl-ribitol-teichoic acid produced severe arthritis; 2) oligosaccharide-peptides with or without the special structure (N-acetylglucosaminyl-ribitol-teichoic acid in S. aureus, a polymer of rhamnose and glucose in L. plantarum) produced severe disease; 3) disaccharide-heptapeptide-disaccharide with or without the presence of either glucose-ribitol-teichoic acid or a polymer of rhamnose and glucose appeared to be arthritogenic but much less effective for disease production; 4) N-acetylmuramyl-heptapeptide-N-acetylmuramic acid and disaccharide-hexapeptide were non-arthritogenic; 5) none of the synthetic N-acetylmuramyl-peptides, including tetrapeptide, produced the disease. Thus it is concluded that arthritis-inducing activity is related to the peptidoglycan moiety but not to the special structure, and the most important moiety responsible for disease production may be located in a chain length of two or more disaccharide units on PG subunits. However, it is discussed that non-arthritogenicity of peptidoglycans, including synthetic compounds, may be due to a lack of adjuvanticity in rats rather than a lack of antigenic determinant(s) responsible for production of arthritis.


Visual flow scene effects on the somatogravic illusion in non-pilots.
The somatogravic illusion (SGI) is easily broken when the pilot looks out the aircraft window during daylight flight, but it has proven difficult to break or even reduce the SGI in non-pilots in simulators using synthetic visual scenes. Could visual-flow scenes that accommodate compensatory head movement reduce the SGI in naive subjects? We investigated the effects of visual cues on the SGI induced by a human centrifuge. The subject was equipped with a head-tracked, head-mounted display (HMD) and was seated in a fixed gondola facing the center of rotation. The angular velocity of the centrifuge increased from near zero until a 0.57-G centripetal acceleration was attained, resulting in a tilt of the gravitoinertial force vector, corresponding to a pitch-up of 30 degrees. The subject indicated perceived horizontal continuously by means of a manual adjustable-plate system. We performed two experiments with within-subjects designs. In Experiment 1, the subjects (N = 13) viewed a darkened HMD and a presentation of simple visual flow beneath a horizon. In Experiment 2, the subjects (N = 12) viewed a darkened HMD, a scene including symbology superimposed on simple visual flow and horizon, and this scene without visual flow (static). In Experiment 1, visual flow reduced the SGI from 12.4 +/- 1.4 degrees (mean +/- SE) to 8.7 +/- 1.5 degrees. In Experiment 2, the SGI was smaller in the visual flow condition (9.3 +/- 1.8 degrees) than with the static scene (13.3 +/- 1.7 degrees) and without HMD presentation (14.5 +/- 2.3 degrees), respectively. It is possible to reduce the SGI in non-pilots by means of a synthetic horizon and simple visual flow conveyed by a head-tracked HMD. This may reflect the power of a more intuitive display for reducing the SGI.


Sall4 is essential for mouse primordial germ cell specification by suppressing somatic cell program genes.
The Spalt-like 4 (Sall4) zinc finger protein is a critical transcription factor for pluripotency in embryonic stem cells (ESCs). It is also involved in the formation of a variety of organs, in mice, and humans. We report the essential roles of Sall4 in mouse primordial germ cell (PGC) specification. PGC specification is accompanied by the activation of the stem cell program and repression of the somatic cell program in progenitor cells. Conditional inactivation of Sall4 during PGC specification led to a reduction in the number of PGCs in embryonic gonads. Sall4(del/del) PGCs failed to translocate from the mesoderm to the endoderm and underwent apoptosis. In Sall4(del/del) PGC progenitors, somatic cell program genes (Hoxa1 and Hoxb1) were derepressed, while activation of the stem cell program was not impaired. We demonstrated that in differentiated ESCs, Sall4 bound to these somatic cell program gene loci, which are reportedly occupied by Prdm1 in embryonic carcinoma cells. Given that Sall4 and Prdm1 are known to associate with the histone deacetylase repressor complex, our findings suggest that Sall4 suppresses the somatic cell program possibly by recruiting the repressor complex in conjunction with Prdm1; therefore, it is essential for PGC specification.


Insights into the Genetic Relationships and Breeding Patterns of the African Tea Germplasm Based on nSSR Markers and cpDNA Sequences.
Africa is one of the key centers of global tea production. Understanding the genetic diversity and relationships of cultivars of African tea is important for future targeted breeding efforts for new crop cultivars, specialty tea processing, and to guide germplasm conservation efforts. Despite the economic importance of tea in Africa, no research work has been done so far on its genetic diversity at a continental scale. Twenty-three nSSRs and three plastid DNA regions were used to investigate the genetic diversity, relationships, and breeding patterns of tea accessions collected from eight countries of Africa. A total of 280 African tea accessions generated 297 alleles with a mean of 12.91 alleles per locus and a genetic diversity (H S) estimate of 0.652. A STRUCTURE analysis suggested two main genetic groups of African tea accessions which corresponded well with the two tea types Camellia sinensis var. sinensis and C. sinensis var. assamica, respectively, as well as an admixed "mosaic" group whose individuals were defined as hybrids of F2 and BC generation with a high proportion of C. sinensis var. assamica being maternal parents. Accessions known to be C. sinensis var. assamica further separated into two groups representing the two major tea breeding centers corresponding to southern Africa (Tea Research Foundation of Central Africa, TRFCA), and East Africa (Tea Research Foundation of Kenya, TRFK). Tea accessions were shared among countries. African tea has relatively lower genetic diversity. C. sinensis var. assamica is the main tea type under cultivation and contributes more in tea breeding improvements in Africa. International germplasm exchange and movement among countries within Africa was confirmed. The clustering into two main breeding centers, TRFCA, and TRFK, suggested that some traits of C. sinensis var. assamica and their associated genes possibly underwent selection during geographic differentiation or local breeding preferences. This study represents the first step toward effective utilization of differently inherited molecular markers for exploring the breeding status of African tea. The findings here will be important for planning the exploration, utilization, and conservation of tea germplasm for future breeding efforts in Africa.


Understanding if the reward is worth the influenza risk: The true cost of showing pigs.
Influenza A virus transmission between pigs and humans has been reported periodically worldwide, and spillover events across the animal-human species barrier could lead to the next influenza pandemic. Swine exhibitions serve as a unique interface conducive to zoonotic disease transmission due to extensive commingling of pigs and humans for prolonged periods of time. The majority of zoonotic influenza A virus transmission in the United States has been linked to swine exhibitions, leading some to suggest additional controls for influenza A virus at the swine-human interface. Determining the value of the exhibition swine industry and gauging the financial impacts influenza A virus outbreaks could have on society, helps to inform adoption decisions of mitigation recommendations. This study estimates the total value of the exhibition swine industry in the United States and calculates the predicted costs of the most extreme mitigation strategy, cancelling swine exhibitions to reduce zoonotic influenza A virus transmission. Mixed methods, including a survey, were used to collect data and inform the study model. We estimated that the direct economic impact of the exhibition swine sector in 2018 was $1.2 billion. If pig shows were to be cancelled for one year, the estimated direct economic impact would be $357.1 million. A permanent, > 3-year ban on swine exhibitions would result in a $665 million economic impact, which is a 45% reduction from baseline. The direct economic impact of cancelling the swine show circuit could not be determined, as youth exhibitors may pursue alternative activities that cannot be precisely accounted for. However, the estimated loss to the swine industry justifies seeking enhanced mitigation to prevent disease transmission. Moreover, economic losses secondary to exhibition cancellations may explain hesitancy to participate in active influenza A virus surveillance efforts.


Cocaine acutely inhibits DNA synthesis in developing rat brain regions: evidence for direct actions.
Perinatal exposure to cocaine has been shown to cause morphological and neurobehavioral abnormalities. In the current study, neonatal rats were given an acute injection of cocaine (30 mg/kg s.c.) at 1, 3, 5, 8, 11 or 15 days of age, and [3H]thymidine incorporation into DNA examined over the ensuing 30 min period. Three brain regions were used that differ in their timetables of cell maturation: cerebellum, cerebral cortex and midbrain + brainstem. Cocaine inhibited DNA synthesis in all brain regions, with diminishing impact as the animals matured; by 15 days of age, the effect of cocaine was no longer significant. Inhibition of macromolecule synthesis was selective for DNA, as [3H]leucine incorporation into protein was much less affected by cocaine. Although inhibition of [3H]thymidine incorporation by a single injection of cocaine was short-lived, repeated administration could have cumulative effects: chronic treatment on days 2, 3 and 4 did not desensitize the adverse effect of a subsequent dose administered on day 5. Additionally, with chronic cocaine, the cerebellum displayed a pronounced rebound elevation of DNA synthesis 24 h after the last dose, a characteristic finding in delayed cell maturation. Inhibition of DNA synthesis by cocaine in developing brain was not secondary to ischemia, nor to local anesthesia, as alpha-adrenergic blockade with phenoxybenzamine afforded no protection, and lidocaine could not substitute for cocaine. In contrast, a small amount (15 micrograms) of cocaine injected directly into the central nervous system readily caused inhibition of DNA synthesis; the same dose given systemically had no effect. These data suggest that cocaine damages the developing brain, in part, through direct interference with DNA synthesis.


The Rivermead Behavioural Memory Test can predict social functioning among schizophrenic patients treated with clozapine.
OBJECTIVE The aim of this study was to find out whether clinical symptoms, such as positive and negative symptoms, or cognitive problems, such as impairment in memory, are predictive of social outcome among patients with schizophrenia and treated with clozapine in the long-term. METHODS Twelve subjects with a DSM-III-R diagnosis of schizophrenia treated with clozapine were recruited from an inpatient rehabilitation psychiatry unit. Subjects were assessed at baseline, and 6, 12 and 24 months, using symptoms measures, the Social Behaviour Scale (SBS) and the Rivermead Behavioural Memory Test (RBMT), which tests episodic memory. Three multivariate stepwise regression models were created with SBS at 6, 12 and 24 months score as dependent variable, and the other measures at baseline as independent variables. RESULTS The only significant contribution on social functioning in each model was made by the RBMT, which was therefore the only significant predictor of social functioning in all models. CONCLUSIONS The authors discuss the importance of episodic memory in the prediction of social functioning.


Synthesis of Er- and Yb-doped gadolinium oxide polymorphs and influence of their structures on upconversion properties.
Nanocrystalline Gd(2)O(3) products doped with Er(3+) and Yb(3+) cations were synthesized by combustion method. We showed that the temperature of combustion can be tuned by using different types of organic fuels within reaction mixture. The combustion process is performed at lower temperature in the presence of urea as an organic fuel leading to pure cubic Gd(2)O(3):Er,Yb phase, on the other hand higher combustion temperature, yielding pure monoclinic Gd(2)O(3):Er,Yb polymorph is achieved in the mixture of urea and b-alanine. Effective doping of Er(3+) and Yb(3+) cations within Gd(2)O(3) were confirmed by XRD analysis. Both polymorphs show upconversion in green and red areas and possess strong dependence of fluorescence intensity ratios (I(525)/I(549) or I(525)/I(560) for monoclinic and cubic polymorphs, respectively) on temperature. This indicates that both phases can be applied for the temperature sensor devices based on upconversion intensity ratio changes.


Efficiently learning multilayer perceptrons.
A learning algorithm for multilayer perceptrons is presented which is based on finding the principal components of a correlation matrix computed from the example inputs and their target outputs. For large networks our procedure needs far fewer examples to achieve good generalization than traditional on-line algorithms.


HIV risk practices sought by men who have sex with other men, and who use internet websites to identify potential sexual partners.
Men who have sex with men (MSM) account for the largest number of persons diagnosed with AIDS in the USA, with higher than average rates of drug use and unprotected sex being cited as the principal reasons underlying their high rates of HIV infection. Recent evidence has suggested that the use of websites specifically designed to promote unsafe sexual practices may be particularly common among MSM, thereby fostering their risky behaviours. In light of these findings, the present study is based on a content analysis of 1316 ads/profiles posted on one of the most popular MSM websites that specifically fosters unprotected sex. Ads/profiles were selected randomly based on the American ZIP code of residence. Data were collected between September 2006 and January 2007. Rates of advertised for high-risk sexual behaviours were very high, particularly for oral sex involving ejaculation into the mouth (88.0% for receptive oral sex, 77.4% for insertive oral sex), anal sex involving ejaculation into the anus (79.7% for insertive anal sex, 69.4% for receptive anal sex), multiple partner sex (77.9%) and felching (16.5%). A multivariate analysis of the correlates of sexual risk preferences identified seven factors that were related to a propensity towards enhanced sexual risk: younger age (beta = 0.12, P = 0.0001), not being African American (beta = 0.05, P = 0.0341), self-identification as a sexual 'bottom' (beta = 0.20, P = 0.0001), not caring about one's potential sex partners' HIV serostatus (beta = 0.15, P = 0.0001), preferring to have sex while under the influence of drugs (beta = 0.08, P = 0.0022), a greater involvement in and commitment to the use of the website to locate potential unprotected sex partners (beta = 0.16, P = 0.0001) and not being HIV-negative (beta = 0.08, P = 0.0081). The HIV intervention-related implications of these findings are discussed.


What do evaluation instruments tell us about the quality of complementary medicine information on the internet?
Developers of health information websites aimed at consumers need methods to assess whether their website is of "high quality." Due to the nature of complementary medicine, website information is diverse and may be of poor quality. Various methods have been used to assess the quality of websites, the two main approaches being (1) to compare the content against some gold standard, and (2) to rate various aspects of the site using an assessment tool. We aimed to review available evaluation instruments to assess their performance when used by a researcher to evaluate websites containing information on complementary medicine and breast cancer. In particular, we wanted to see if instruments used the same criteria, agreed on the ranking of websites, were easy to use by a researcher, and if use of a single tool was sufficient to assess website quality. Bibliographic databases, search engines, and citation searches were used to identify evaluation instruments. Instruments were included that enabled users with no subject knowledge to make an objective assessment of a website containing health information. The elements of each instrument were compared to nine main criteria defined by a previous study. Google was used to search for complementary medicine and breast cancer sites. The first six results and a purposive six from different origins (charities, sponsored, commercial) were chosen. Each website was assessed using each tool, and the percentage of criteria successfully met was recorded. The ranking of the websites by each tool was compared. The use of the instruments by others was estimated by citation analysis and Google searching. A total of 39 instruments were identified, 12 of which met the inclusion criteria; the instruments contained between 4 and 43 questions. When applied to 12 websites, there was agreement of the rank order of the sites with 10 of the instruments. Instruments varied in the range of criteria they assessed and in their ease of use. Comparing the content of websites against a gold standard is time consuming and only feasible for very specific advice. Evaluation instruments offer gateway providers a method to assess websites. The checklist approach has face validity when results are compared to the actual content of "good" and "bad" websites. Although instruments differed in the range of items assessed, there was fair agreement between most available instruments. Some were easier to use than others, but these were not necessarily the instruments most widely used to date. Combining some of the better features of instruments to provide fewer, easy-to-use methods would be beneficial to gateway providers.


Clinical Outcomes and Complications Following Surgical Management of Traumatic Posterior Sternoclavicular Joint Dislocations: A Systematic Review.
Traumatic posterior sternoclavicular joint dislocations are rare orthopaedic emergencies. Treatment typically consists of closed reduction, with surgical management reserved for unstable cases. Because of the low prevalence of this condition, limited clinical evidence exists for a superior surgical stabilization technique. A systematic review of the literature following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was performed. MEDLINE and Embase databases were searched using a comprehensive search strategy. A descriptive and critical analysis of the results was performed. Forty relevant studies (108 cases) were identified. Favorable subjective and objective outcomes were reported for all 5 categories of stabilization described. The overall complication rate was 16%, including 4 cases of recurrent instability. Ligament reconstruction using tendon graft had the lowest recurrent instability and complication rates, and open reduction and internal fixation techniques required a second operation for implant removal in 80% of cases. A comprehensive review of the surgical management of traumatic posterior sternoclavicular joint dislocations is presented. Results suggest favorable outcomes for all of the methods of stabilization, with a modest complication rate. The trends observed have helped to guide the development of clinical care recommendations that aid in treatment decision-making for these injuries. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.


Polyelectrolytes as Building Blocks for Next-Generation Membranes with Advanced Functionalities.
The global society is in a transition, where dealing with climate change and water scarcity are important challenges. More efficient separations of chemical species are essential to reduce energy consumption and to provide more reliable access to clean water. Here, membranes with advanced functionalities that go beyond standard separation properties can play a key role. This includes relevant functionalities, such as stimuli-responsiveness, fouling control, stability, specific selectivity, sustainability, and antimicrobial activity. Polyelectrolytes and their complexes are an especially promising system to provide advanced membrane functionalities. Here, we have reviewed recent work where advanced membrane properties stem directly from the material properties provided by polyelectrolytes. This work highlights the versatility of polyelectrolyte-based membrane modifications, where polyelectrolytes are not only applied as single layers, including brushes, but also as more complex polyelectrolyte multilayers on both porous membrane supports and dense membranes. Moreover, free-standing membranes can also be produced completely from aqueous polyelectrolyte solutions allowing much more sustainable approaches to membrane fabrication. The Review demonstrates the promise that polyelectrolytes and their complexes hold for next-generation membranes with advanced properties, while it also provides a clear outlook on the future of this promising field.


Expert consensus of the French Society of Geriatrics and Gerontology and the French Society of Cardiology on the management of atrial fibrillation in elderly people.
Atrial fibrillation (AF) is a common and serious condition in the elderly. AF affects between 600,000 and one million patients in France, two-thirds of whom are aged above 75 years. AF is a predictive factor for mortality in the elderly and a major risk factor for stroke. Co-morbidities are frequent and worsen the prognosis. The management of AF in the elderly should involve a comprehensive geriatric assessment (CGA), which analyses both medical and psychosocial elements, enabling evaluation of the patient's functional status and social situation and the identification of co-morbidities. The CGA enables the detection of "frailty" using screening tools assessing cognitive function, risk of falls, nutritional status, mood disorders, autonomy and social environment. The objectives of AF treatment in the elderly are to prevent AF complications, particularly stroke, and improve quality of life. Specific precautions for treatment must be taken because of the co-morbidities and age-related changes in pharmacokinetics or pharmacodynamics. Preventing AF complications relies mainly on anticoagulant therapy. Anticoagulants are recommended in patients with AF aged 75 years or above after assessing the bleeding risk using the HEMORR2HAGES or HAS-BLED scores. Novel oral anticoagulants (NOACs) are promising treatments, especially due to a lower risk of intracerebral haemorrhage. However, their prescriptions should take into account renal function (creatinine clearance assessed with Cockcroft formula) and cognitive function (for adherence to treatment). Studies including frail patients in "real life" are necessary to evaluate tolerance of NOACs. Management of AF also involves the treatment of underlying cardiomyopathy and heart rate control rather than a rhythm-control strategy as first-line therapy for elderly patients, especially if they are paucisymptomatic. Antiarrhythmic drugs should be used carefully in elderly patients because of the frequency of metabolic abnormalities and higher risk of drug interactions and bradycardia.


Fostering Health Literacy Responsiveness in a Remote Primary Health Care Setting: A Pilot Study.
Primary healthcare organisations have an important role in addressing health literacy as this is a barrier to accessing and utilising health care. Until recently, no organisational development tool operationalising health literacy in an Australian context existed. This research evaluated the efficacy of the Organisational Health Literacy Responsiveness (Org-HLR) tool and associated assessment process in a primary healthcare organisation in the Pilbara region of Western Australia. This study utilised a sequential explanatory mixed methods research design incorporating the collection and analysis of data in two phases: (1) Pre- and post-survey data and; (2) seven semi-structured interviews. Survey results showed that participants' confidence in core health literacy concepts improved from baseline following the intervention. Analysis of the interview data revealed participants' initial understanding of health literacy was limited, and this impeded organisational responsiveness to health literacy needs. Participants reported the workshop and tool content were relevant to their organisation; they valued involving members from all parts of the organisation and having an external facilitator to ensure the impartiality of the process. External barriers to improving their internal organisational health literacy responsiveness were identified, with participants acknowledging the management style and culture of open communication within the organisation as enablers of change. Participants identified actionable changes to improve their organisational health literacy responsiveness using the process of organisational assessment and change.


Experimental evidence for mediation of competition by habitat succession.
Habitat succession is thought to influence the importance of competition in assemblages. Competitive interactions are considered of critical importance in structuring ant assemblages, but field experiments show varied effects. I tested how succession in managed boreal forests affects the outcome of competition from dominant red wood ants, Formica aquilonia, through a removal experiment in replicated stands of three different ages (0-4, 30-40, and 80-100 years old). F. aquilonia abundance was reduced by 87%, and procedural controls showed no nontarget effects. The succession gradient revealed the full range of possible responses from ant species: decreases in 1-4-year-old stands, increases in 30-40-year-old stands, and no effects in 80-100-year-old stands, where diversity was lowest. Habitat succession thus regulates competitive interactions in this system. I propose a model for this system, where competitive effects depend on time since disturbance. In this case, soon after disturbance the dominant species facilitates increases in the abundance of other species. At intermediate times, competition reduces the abundance of some species. Finally, in long-undisturbed habitats, competitors may fail to evolve, particularly in high-stress environments. Interactions between competition and habitat succession may explain why structuring effects of ecologically dominant species appear inconsistent.


Classical decay of Coulomb charges.
In this paper we postulate and solve the following problem: Prove in the framework of Newtonian mechanics that three Coulomb charges (-1,Q,Q) for Q>4 will leave any initial volume in a finite time and estimate this time. We also discuss possible generalizations of the problem and its relation to stability of ions and molecules.


Clove oil reverses learning and memory deficits in scopolamine-treated mice.
The present study was performed to examine the effect of Eugenia caryophyllata (Myrtaceae) on learning and memory, and also evaluate whether it can modulate oxidative stress in mice. Passive avoidance step-down task and elevated plus-maze were used to assess learning and memory in scopolamine-treated mice. Oxidative stress parameters were also assessed in brain samples by estimating the malondialdehyde (MDA) and reduced glutathione (GSH) levels at the end of the study. Scopolamine (0.3 mg/kg, i. p.) produced impairment of acquisition memory as evidenced by a decrease in step-down latency and an increase in transfer latency on day 1, and also impairment of retention of memory on day 2. Pretreatment with clove oil (0.05 mL/kg and 0.1 mL/kg) for 3 weeks significantly reversed the increase in acquisition latency and all the doses (0.025, 0.05, 0.1 mL/kg, i. p.) reversed the increase in retention latency induced by scopolamine (0.3 mg/kg, i. p.) in elevated plus-maze. However, 0.05 mL/kg clove oil attenuated memory deficits in the passive avoidance step-down task. Brain samples showed a significant decrease in MDA levels in the group treated with clove oil (0.05 and 0.025 mL/kg). GSH levels were also increased in clove oil-treated mice though the results were not significant. Thus, it can be concluded that clove oil can reverse the short-term and long-term memory deficits induced by scopolamine (0.3 mg/kg, i. p.) and this effect can, to some extent, be attributed to decreased oxidative stress.


Clinical assessment of spasticity in individuals with spinal cord injury.
To evaluate the effect of neuromuscular electrical stimulation on spasticity in patients with spinal cord injury. The study included eleven subjects with spinal cord injuries (C4 to T5). The modified Ashworth scale and pendulum test, which is accomplished through the Pendular Test Device - PTD (equipment which has a quartz crystal transducer accelerometer and optic fiber flexible electrogoniometer measuring the tensions and angular displacements). Patients underwent neuromuscular electrical stimulation (NMES) to the quadriceps muscle from fibular nerve, and the tests were administered before and after therapy. The data show a decrease in spasticity after NMES, with features such as increased variation between maximum and minimum peaks, i.e. increased amplitude of the curves. Furthermore, data from the subjective scale, and modified Ashworth scale after neuromuscular electrical stimulation also showed a reduction in the values of spasticity. The data suggest that NMES is effective in reducing spasticity immediately after completion. Level of Evidence II, Therapeutic Studies-Investigating the Results of Treatment .


Steroidogenic factor-1 enhances basal and forskolin-stimulated transcription of the human glycoprotein hormone alpha-subunit gene in GH3 cells.
Steroidogenic factor-1 (SF-1) is a key regulator of endocrine development, and mediates expression of gonadotrophin-specific genes in the pituitary. Basal and hormone stimulated transcription of the human glycoprotein hormone alpha-subunit gene (alphaGSU) in gonadotrophs involves SF-1 and its cognate binding site, the gonadotroph-specific element (GSE). In this study, we demonstrate that SF-1 significantly enhances basal and forskolin-stimulated transcription of the human alphaGSU promoter in GH(3) cells. Mutation of the GSE abolished the SF-1-mediated transactivation of basal alphaGSU promoter activity, and significantly attenuated the forskolin effect by 50%. Mutation of the Ser203 residue in SF-1 to Ala blocked basal transactivation of alphaGSU promoter activity, and halved the forskolin effect. These data collectively reveal a direct role for SF-1 and the GSE in mediating basal and forskolin-stimulated transcription of the human alphaGSU promoter in GH(3) cells. The phosphorylation site at Ser203 appears to be required for these effects.


Patient-reported prostate cancer treatment regret following primary partial gland cryoablation.
Prostate cancer treatment-related regret (TRR) incorporates the myriad effects of diagnosis and treatment with associated behavioral, emotional, and interpersonal changes within the context of patient values and expectations. We aimed to investigate TRR following primary partial gland cryoablation (PPGCA). Men with prostate cancer undergoing PPGCA since 3/2017 enrolled in a prospective outcome registry. Between June and August 2022, a validated prostate cancer related TRR decision scale was distributed. TRR score ≥40 was considered significant TRR. Men were considered potent if they reported ability to have penetration at least half the time sexual intercourse was initiated. Associations between significant TRR and baseline characteristics and longitudinal outcomes were assessed using logistic regressions. Of 245 men who met inclusion criteria, 163 (67%) completed the survey with median time since cryoablation 2.3 years (IQR: 1.3, 3.6). Overall, the mean composite TRR score was 12.4/100. Significant TRR was expressed by 14% of men. Among those who were potent/had erectile function at baseline, loss of potency and erectile function were associated with higher probability of significant TRR, respectively. No associations were identified between TRR and recurrence of clinically significant prostate cancer or salvage treatment. The overwhelming majority of men do not express TRR following PPGCA. The loss of potency or development of erectile dysfunction predisposes to TRR. It is imperative to elucidate short-, intermediate- and long-term functional and oncological outcomes in order to define factors associated with TRR to improve counseling and reduce patient regret.


Transfer of antibiotics and their metabolites in human milk: Implications for infant health and microbiota.
Antibiotics are an essential tool for perinatal care. While antibiotics can play a life-saving role for both parents and infants, they also cause collateral damage to the beneficial bacteria that make up the host gut microbiota. This is especially true for infants, whose developing gut microbiota is uniquely sensitive to antibiotic perturbation. Emerging evidence suggests that disruption of these bacterial populations during this crucial developmental window can have long-term effects on infant health and development. Although most current studies have focused on microbial disruptions caused by direct antibiotic administration to infants or prenatal exposure to antibiotics administered to the mother, little is known about whether antibiotics in human milk may pose similar risks to the infant. This review surveys current data on antibiotic transfer during lactation and highlights new methodologies to assess drug transfer in human milk. Finally, we provide recommendations for future work to ensure antibiotic use in lactating parents is safe and effective for both parents and infants.


A novel and lightweight system to secure wireless medical sensor networks.
Wireless medical sensor networks (MSNs) are a key enabling technology in e-healthcare that allows the data of a patient's vital body parameters to be collected by the wearable or implantable biosensors. However, the security and privacy protection of the collected data is a major unsolved issue, with challenges coming from the stringent resource constraints of MSN devices, and the high demand for both security/privacy and practicality. In this paper, we propose a lightweight and secure system for MSNs. The system employs hash-chain based key updating mechanism and proxy-protected signature technique to achieve efficient secure transmission and fine-grained data access control. Furthermore, we extend the system to provide backward secrecy and privacy preservation. Our system only requires symmetric-key encryption/decryption and hash operations and is thus suitable for the low-power sensor nodes. This paper also reports the experimental results of the proposed system in a network of resource-limited motes and laptop PCs, which show its efficiency in practice. To the best of our knowledge, this is the first secure data transmission and access control system for MSNs until now.


Rooting the eukaryote tree by using a derived gene fusion.
Single-gene trees have failed to locate the root of the eukaryote tree because of systematic biases in sequence evolution. Structural genetic data should yield more reliable insights into deep phylogenetic relationships. We searched major protist groups for the presence or absence of a gene fusion in order to locate the root of the eukaryote tree. In striking contrast to previous molecular studies, we show that all eukaryote groups ancestrally with two cilia (bikonts) are evolutionarily derived. The root lies between bikonts and opisthokonts (animals, Fungi, Choanozoa). Amoebozoa either diverged even earlier or are sister of bikonts or (less likely) opisthokonts.


Reliability of tibiofemoral contact area and centroid location in upright, open MRI.
Imaging cannot be performed during natural weightbearing in biomechanical studies using conventional closed-bore MRI, which has necessitated simulating weightbearing load on the joint. Upright, open MRI (UO-MRI) allows for joint imaging during natural weightbearing and may have the potential to better characterize the biomechanical effect of tibiofemoral pathology involving soft tissues. However open MRI scanners have lower field strengths than closed-bore scanners, which limits the image quality that can be obtained. Thus, there is a need to establish the reliability of measurements in upright weightbearing postures obtained using UO-MRI. Knees of five participants with prior anterior cruciate ligament (ACL) rupture were scanned standing in a 0.5 T upright open MRI scanner using a 3D DESS sequence. Manual segmentation of cartilage regions in contact was performed and centroids of these contact areas were automatically determined for the medial and lateral tibiofemoral compartments. Inter-rater, test-retest, and intra-rater reliability were determined and quantified using intra-class correlation (ICC3,1), standard error of measurement (SEM), and smallest detectable change with 95% confidence (SDC95). Accuracy was assessed by using a high-resolution 7 T MRI as a reference. Contact area and centroid location reliability (inter-rater, test-retest, and intra-rater) for sagittal scans in the medial compartment had ICC3,1 values from 0.95-0.99 and 0.98-0.99 respectively. In the lateral compartment, contact area and centroid location reliability ICC3,1 values ranged from 0.83-0.91 and 0.95-1.00 respectively. The smallest detectable change in contact area was 1.28% in the medial compartment and 0.95% in the lateral compartment. Contact area and centroid location reliability for coronal scans in the medial compartment had ICC3,1 values from 0.90-0.98 and 0.98-1.00 respectively, and in the lateral compartment ICC3,1 ranged from 0.76-0.94 and 0.93-1.00 respectively. The smallest detectable change in contact area was 0.65% in the medial compartment and 1.41% in the lateral compartment. Contact area was accurate to within a mean absolute error of 11.0 mm2. Knee contact area and contact centroid location can be assessed in upright weightbearing MRI with good to excellent reliability. The lower field strength used in upright, weightbearing MRI does not compromise the reliability of tibiofemoral contact area and centroid location measures.


Campylobacter jejuni 81-176 forms distinct microcolonies on in vitro-infected human small intestinal tissue prior to biofilm formation.
Human small and large intestinal tissue was used to study the interaction of Campylobacter jejuni with its target tissue. The strain used for the study was 81-176 (+pVir). Tissue was processed for scanning and transmission electron microscopy, and by immunohistochemistry for light microscopy. Organisms adhered to the apical surface of ileal tissues at all time points in large numbers, in areas where mucus was present and in distinct groups. Microcolony formation was evident at 1-2 h, with bacteria adhering to mucus on the tissue surface and to each other by flagellar interaction. At later time points (3-4 h), biofilm formation on ileal tissue was evident. Flagellar mutants did not form microcolonies or biofilms in tissue. Few organisms were observed in colonic tissue, with organisms present but not as abundant as in the ileal tissue. This study shows that C. jejuni 81-176 can form microcolonies and biofilms on human intestinal tissue and that this may be an essential step in its ability to cause diarrhoea in man.


[Effects of fertilization on soil CO2 flux in Castanea mollissima stand].
In June 2011-June 2012, a fertilization experiment was conducted in a typical Castanea mollissima stand in Lin' an of Zhejiang Province, East China to study the effects of inorganic and organic fertilization on the soil CO2 flux and the relationships between the soil CO2 flux and environmental factors. Four treatments were installed, i. e., no fertilization (CK), inorganic fertilization (IF), organic fertilization (OF), half organic plus half inorganic fertilization (OIF). The soil CO2 emission rate was determined by the method of static closed chamber/GC technique, and the soil temperature, soil moisture content, and soil water-soluble organic carbon (WSOC) concentration were determined by routine methods. The soil CO2 emission exhibited a strong seasonal pattern, with the highest rate in July or August and the lowest rate in February. The annual accumulative soil CO2 emission in CK was 27.7 t CO2 x hm(-2) x a(-1), and that in treatments IF, OF, and OIF was 29.5%, 47.0%, and 50.7% higher than the CK, respectively. The soil WSOC concentration in treatment IF (105.1 mg kg(-1)) was significantly higher than that in CK (76.6 mg x kg(-1)), but was obviously lower than that in treatments OF (133.0 mg x kg(-1)) and OIF (121.2 mg x kg(-1)). The temperature sensitivity of respiration (Q10) in treatments CK, IF, OF, and OIF was 1.47, 1.75, 1.49, and 1.57, respectively. The soil CO2 emission rate had significant positive correlations with the soil temperature at the depth of 5 cm and the soil WSOC concentration, but no significant correlation with soil moisture content. The increase of the soil WSOC concentration caused by fertilization was probably one of the reasons for the increase of soil CO2 emission from the C. mollissima stand.


[Biopsychosocial determinants of the labor inclusion process of the person with a stoma].
This study focused the social determinants of people with an ostomy that facilitate and / or hamper their work inclusion. The objectives were to identify and analyze the difficulties and facilities for people with an ostomy for work inclusion. Descriptive exploratory, qualitative research, carried out with 20 stomized through semi-structured interviews, using the Thematic Content Analysis. The results revealed that the main difficulties of ostomy to step into the working environment were the loss of sphincter control, social isolation and lack of opportunities suitable to your health condition new jobs. The main facilitators were the creation of adapted toilets and flexible schedules. We conclude that the biopsychosocial changes caused by the presence of the stoma may hinder inclusion in the work of ostomy patients, however, with social support can be created flexible terms that help them in their return to work activities.


Severe dioxin-like compound (DLC) contamination in e-waste recycling areas: An under-recognized threat to local health.
Electrical and electronic waste (e-waste) burning and recycling activities have become one of the main emission sources of dioxin-like compounds (DLCs). Workers involved in e-waste recycling operations and residents living near e-waste recycling sites (EWRS) are exposed to high levels of DLCs. Epidemiological and experimental in vivo studies have reported a range of interconnected responses in multiple systems with DLC exposure. However, due to the compositional complexity of DLCs and difficulties in assessing mixture effects of the complex mixture of e-waste-related contaminants, there are few studies concerning human health outcomes related to DLC exposure at informal EWRS. In this paper, we have reviewed the environmental levels and body burdens of DLCs at EWRS and compared them with the levels reported to be associated with observable adverse effects to assess the health risks of DLC exposure at EWRS. In general, DLC concentrations at EWRS of many countries have been decreasing in recent years due to stricter regulations on e-waste recycling activities, but the contamination status is still severe. Comparison with available data from industrial sites and well-known highly DLC contaminated areas shows that high levels of DLCs derived from crude e-waste recycling processes lead to elevated body burdens. The DLC levels in human blood and breast milk at EWRS are higher than those reported in some epidemiological studies that are related to various health impacts. The estimated total daily intakes of DLCs for people in EWRS far exceed the WHO recommended total daily intake limit. It can be inferred that people living in EWRS with high DLC contamination have higher health risks. Therefore, more well-designed epidemiological studies are urgently needed to focus on the health effects of DLC pollution in EWRS. Continuous monitoring of the temporal trends of DLC levels in EWRS after actions is of highest importance.


Understanding the molecular mechanism of sigma-1 receptors: towards a hypothesis that sigma-1 receptors are intracellular amplifiers for signal transduction.
Although sigma receptors were discovered in 1982, the biochemical and physiological roles of sigma receptors have just begun to unveil. Sigma receptors are non-opioid, non-phencyclidine receptors that contain two subtypes: sigma-1 and sigma-2 receptors. The sigma-1 receptor has been cloned and its sequence does not resemble that of any mammalian protein. Sigma-2 receptors have not been cloned. The focus of this review will be on sigma-1 receptors. Sigma-1 receptors contain 223 amino acids and reside primarily at the endoplasmic reticulum. Sigma-1 receptors exist mainly in the central nervous system, but also in the periphery. Sigma-1 receptor ligands include cocaine, (+)-benzomorphans like (+)-pentazocine and (+)N-allyl-normetazocine (or (+)-SKF-10047), and endogenous neurosteroids like progesterone and pregnenolone sulfate. Many pharmacological and physiological actions have been attributed to sigma-1 receptors. These include the regulation of IP3 receptors and calcium signaling at the endoplasmic reticulum, mobilization of cytoskeletal adaptor proteins, modulation of nerve growth factor-induced neurite sprouting, modulation of neurotransmitter release and neuronal firing, modulation of potassium channels as a regulatory subunit, alteration of psychostimulant-induced gene expression, and blockade of spreading depression. Behaviorally, sigma-1 receptors are involved in learning and memory, psychostimulant-induced sensitization, cocaine-induced conditioned place preference, and pain perception. Notably, in almost all the aforementioned biochemical and behavioral tests, sigma-1 agonists, while having no effects by themselves, caused the amplification of signal transductions incurred upon the stimulation of the glutamatergic, dopaminergic, IP3-related metabotropic, or nerve growth factor-related systems. Thus, it is hypothesized that sigma-1 receptors, at least in part, are intracellular amplifiers creating a supersensitized state for signal transduction in the biological system.


A qualitative dominant mixed methods exploration of novel educational material for patients considering total knee arthroplasty.
To optimize non-operative management and decision making surrounding TKR we created educational whiteboard videos for patients with knee OA. The purpose of this study was to pilot our educational videos with end-users (patients) to determine patients' experiences and perspectives regarding the content and clarity of videos and to better understand their potential impact on patient's health behaviour. This was a mixed methods evaluation, using a qualitative descriptive approach, of patients attending their first consultation with an arthroplasty surgeon for TKR. We conducted in-depth semi-structured interviews with patients. Three members of the research team coded data independently, implementing a thematic analysis. Thirteen participants were included. Participants indicated that the videos enhanced their confidence and clarity surrounding their decision to undergo TKR. The videos also addressed several knowledge gaps in their understanding of OA management. Barriers to uptake of the education were identified including limited access to PTs and the challenge of weight loss. Conclusions: The current educational intervention was valued by patients with knee OA. Implementation of these videos may have important implications for patients, providers, and our health care system.IMPLICATIONS FOR REHABILITATIONPatients with knee OA referred by primary care physicians to arthroplasty surgeons have knowledge gaps that may influence their self-management and decision making surrounding their condition.Educational materials can address these gaps and support patients in their understanding and management of their condition, which may have important downstream implications.Barriers to accessing non-operative care including physiotherapy must be pre-emptively addressed to ensure that enhanced knowledge is met with improved access for patients.


Comparative in vitro responses of fetal, pregnant and non-pregnant rabbits' adrenal glands to steroidogenic agents.
The in vitro secretion of aldosterone and corticosterone by the adrenal glands of fetal (day 30), pregnant and non-pregnant rabbits was examined under basal and stimulated conditions. In general, non-pregnant animals basally secreted less aldosterone than either pregnant or fetal rabbits, whereas basal corticosterone secretion by pregnant animals exceeded that of either fetal or non-pregnant animals. At similar doses of adrenocorticotropin (ACTH), fetal and pregnant adrenal glands produced comparatively more aldosterone than non-pregnant animals, while corticosterone secretion was accelerated to a greater degree in fetal rabbits than in the other groups. Angiotensin II had its greatest effect on the aldosterone secretory rates of fetal and non-pregnant animals without affecting corticosterone secretion in any group. Elevated potassium (K+) enhanced the secretory rates of aldosterone and corticosterone in fetal animals, while increasing only aldosterone secretion in non-pregnant rabbits. Serotonin accelerated aldosterone secretion in all animals, whereas it increased corticosterone secretion only in non-pregnant animals. These results suggest that (1) in fetal rabbits, the secretory rates of both aldosterone and corticosterone are regulated primarily by ACTH and to a much lesser extent by angiotensin II and K+, (2) the corticosterone secretory rates of pregnant and non-pregnant rabbits are controlled mainly by ACTH, and (3) aldosterone secretion by non-pregnant animals is regulated primarily by angiotensin II and secondarily by ACTH and K+, while in pregnant animals ACTH may be the primary regulator of aldosterone secretion as it is in the fetus.


Fibroblast growth factor 15/19 (FGF15/19) protects from diet-induced hepatic steatosis: development of an FGF19-based chimeric molecule to promote fatty liver regeneration.
Fibroblast growth factor 15/19 (FGF15/19), an enterokine that regulates synthesis of hepatic bile acids (BA), has been proposed to influence fat metabolism. Without FGF15/19, mouse liver regeneration after partial hepatectomy (PH) is severely impaired. We studied the role of FGF15/19 in response to a high fat diet (HFD) and its regulation by saturated fatty acids. We developed a fusion molecule encompassing FGF19 and apolipoprotein A-I, termed Fibapo, and evaluated its pharmacological properties in fatty liver regeneration. Fgf15-/- mice were fed a HFD. Liver fat and the expression of fat metabolism and endoplasmic reticulum (ER) stress-related genes were measured. Influence of palmitic acid (PA) on FGF15/19 expression was determined in mice and in human liver cell lines. In vivo half-life and biological activity of Fibapo and FGF19 were compared. Hepatoprotective and proregenerative activities of Fibapo were evaluated in obese db/db mice undergoing PH. Hepatosteatosis and ER stress were exacerbated in HFD-fed Fgf15-/- mice. Hepatic expression of Pparγ2 was elevated in Fgf15-/- mice, being reversed by FGF19 treatment. PA induced FGF15/19 expression in mouse ileum and human liver cells, and FGF19 protected from PA-mediated ER stress and cytotoxicity. Fibapo reduced liver BA and lipid accumulation, inhibited ER stress and showed enhanced half-life. Fibapo provided increased db/db mice survival and improved regeneration upon PH. FGF15/19 is essential for hepatic metabolic adaptation to dietary fat being a physiological regulator of Pparγ2 expression. Perioperative administration of Fibapo improves fatty liver regeneration.


Dynamic ankle-foot orthoses as a part of treatment in children with spastic diplegia--parents' perceptions.
Dynamic ankle-foot orthoses (DAFOs) are often recommended for children with spastic diplegia in order to facilitate better function. The aim of the present study was to explore how the parents of children with diplegic cerebral palsy experience the use of DAFOs. A qualitative interview study with a broad research question: 'How do you perceive that DAFOs influence your child?' The parents of 15 children, aged 4-18 years, who all had spastic diplegia and wore DAFOs were interviewed. Content analysis resulted in the following categories: 'Physical effects'; 'New functions and activities'; 'The orthosis as a part of the treatment'; 'Opportunity for independence and play'; and 'Problems with DAFOs'. According to the parents, DAFOs appeared to contribute to the (mechanical) changes in posture affecting the muscular system. They meant that when wearing DAFOs the foot and ankle are more stable. This in turn enables postural control and alignment, contributing to functional activities under more favourable physiological conditions. The psychosocial effects were regarded by parents as being just as important as the physical effects. In clinical practice, DAFOs may (according to parents) be regarded as a suitable complement to other treatments in children with diplegic cerebral palsy.


Continuously updating one's predictions underlies successful interception.
This paper reviews our understanding of the interception of moving objects. Interception is a demanding task that requires both spatial and temporal precision. The required precision must be achieved on the basis of imprecise and sometimes biased sensory information. We argue that people make precise interceptive movements by continuously adjusting their movements. Initial estimates of how the movement should progress can be quite inaccurate. As the movement evolves, the estimate of how the rest of the movement should progress gradually becomes more reliable as prediction is replaced by sensory information about the progress of the movement. The improvement is particularly important when things do not progress as anticipated. Constantly adjusting one's estimate of how the movement should progress combines the opportunity to move in a way that one anticipates will best meet the task demands with correcting for any errors in such anticipation. The fact that the ongoing movement might have to be adjusted can be considered when determining how to move, and any systematic anticipation errors can be corrected on the basis of the outcome of earlier actions.


Acid-sensing ion channel 3: An analgesic target.
Acid-sensing ion channel 3 (ASIC3) belongs to the epithelial sodium channel/degenerin (ENaC/DEG) superfamily. There are 7 different ASIC subunits encoded by 5 different genes. Most ASIC subunits form trimeric ion channels that upon activation by extracellular protons mediate a transient inward current inducing cellular excitability. ASIC subunits exhibit differential tissue expression and biophysical properties, and the ability of subunits to form homo- and heteromeric trimers further increases the complexity of currents measured and their pharmacological properties. ASIC3 is of particular interest, not only because it exhibits high expression in sensory neurones, but also because upon activation it does not fully inactivate: a transient current is followed by a sustained current that persists during a period of extracellular acidity, i.e. ASIC3 can encode prolonged acidosis as a nociceptive signal. Furthermore, certain mediators sensitize ASIC3 enabling smaller proton concentrations to activate it and other mediators can directly activate the channel at neutral pH. Moreover, there is a plethora of evidence using transgenic mouse models and pharmacology, which supports ASIC3 as being a potential target for development of analgesics. This review will focus on current understanding of ASIC3 function to provide an overview of how ASIC3 contributes to physiology and pathophysiology, examining the mechanisms by which it can be modulated, and highlighting gaps in current understanding and future research directions.


Central neuropeptide Y signaling ameliorates N(omega)-nitro-L-arginine methyl ester hypertension in the rat through a Y1 receptor mechanism.
Neuropeptide Y is a potent inhibitory neurotransmitter expressed in the central neurons that control blood pressure. NO also serves as an inhibitory neurotransmitter, and its deficit causes sympathetic overactivity, which then contributes to hypertension. This study tested the hypothesis that neuropeptide Y functions as a central neurotransmitter to lower blood pressure, therefore its increased signaling ameliorates hypertension induced by NO deficiency. Conscious neuropeptide Y transgenic male rats, overexpressing the peptide under its natural promoter, and nontransgenic littermates (controls) were used in this study. Neuropeptide Y, Y1 receptor antagonist BIBP3226, or vehicle (saline) were administered continuously for 14 days into the cerebral lateral ventricle in unrestrained animals using osmotic pumps. Blood pressure was measured by radiotelemetry. Compared with control animals, transgenic overexpression of neuropeptide Y significantly ameliorated (by 9.7+/-1.5 mm Hg) NO deficiency hypertension (induced by administration of N(omega)-nitro-L-arginine methyl ester in the drinking water). This hypotensive effect of neuropeptide Y upregulation was associated with reduced proteinuria and cardiac hypertrophy and fibrosis. Central administration of neuropeptide Y in nontransgenic rats also reduced (by 10.2+/-1.6 mm Hg) the NO deficiency hypertension, whereas a neuropeptide Y1 receptor antagonist centrally administered in the transgenic subjects during NO deficiency hypertension completely attenuated the depressor effect of neuropeptide Y upregulation. Thus, acting at the level of the central nervous system distinctively via a Y1 receptor-mediated mechanism, endogenous neuropeptide Y exerted a potent antihypertensive function, and its enhanced signaling ameliorated NO deficiency hypertension.


Use of bacteriophage phi chi 174 replicative from progeny DNA as templates for transcription.
The synthesis of phiX174-specific RNA has been studied in infected cells in which the thymine of the viral (+) strand of the parental RF(*), of the complementary (-) strand of the parental RF, or of both strands of the progeny RF molecules has been replaced with 5-bromouracil (5 BU). By irradiation of such cells with UV light at a wavelength of 313 nm it was possible to affect, specifically, the 5 BU-labeled strands. When the progeny RF molecules contain thymine, irradiation has no effect upon the synthesis of viral-specific RNA, regardless of 5 BU substitution in either strand of parental RF. If, however, progeny RF is labeled with 5 BU, irradiation produces a major decrease of viral RNA synthesis. It is concluded that many progeny RF molecules can serve as templates for transcription at late times of infection. Irradiation, prior to RF replication, of cells in which, particularly, the complementary strand of RF contains 5 BU, appears to decrease the ability of the parental RF to replicate.


Ca channels induced in Xenopus oocytes by rat brain mRNA.
RNA was isolated from brains of 16-d-old rats and poly(A) samples were injected into stage V and VI oocytes. After allowing 2-5 d for expression, most oocytes were exposed to medium in which the K had been replaced by Cs for 24 hr prior to recording. Ba currents were usually measured in Cl-free Ba-methanesulfonate saline. IBa in noninjected oocytes was often undetectable, but ranged up to 50 nA (22 +/- 4 nA, n = 21). In contrast, injected oocytes showed a peak IBa of 339 +/- 42 nA (n = 33). The threshold for activation of IBa was -40 mV, with peak currents at +10 to +20 mV. After a peak, currents decayed to a nearly steady level along a single-exponential time course (tau = 650 +/- 50 msec at +20 mV). The maintained current was 67 +/- 6% (n = 9) of the early peak amplitude. A prepulse duration of 5 sec was needed to examine the inactivation of barium currents in injected oocytes. The inward IBa could be observed in BaCl2 solutions at potentials positive to ECl and also in Na-free salines, indicating that neither Cl- nor Na+ was carrying the inward current. Although IBa displayed voltage-independent blockade by Cd (50% inhibition at 6 microM), the peptide Ca channel antagonist, omega-CgTX (1 microM), and the organic Ca channel-blocking agents (verapamil, compound W-7, and nifedipine) were uniformly ineffective. No effects were observed with the dihydropyridine antagonist nifedipine (even at 10 microM, or when cells were held at -40 mV) or agonist Bay K-8644. However, IBa was enhanced via activation of protein kinase C with 4-beta-phorbol dibutyrate (PBT2). In contrast, use of forskolin to activate protein kinase A did not alter IBa.(ABSTRACT TRUNCATED AT 250 WORDS)


Role of changes in insulin and glucagon in glucose homeostasis in exercise.
This experiment was performed to determine if plasma glucose homeostasis is maintained in normal human volunteers during light exercise (40% maximal oxygen consumption [VO2 max]) when changes in insulin and glucagon are prevented. Hormonal control was achieved by the infusion of somatostatin, insulin, and glucagon. Glucose kinetics and oxidation rates were determined with stable isotopic tracers of glucose, and by indirect calorimetry. Two different rates of replacement of insulin and glucagon were used; in one group, insulin was clamped at 19.8 +/- 2.6 microU/ml (high-insulin group), and in the other group insulin was clamped at 9.2 +/- 1.3 microU/ml (low-insulin group). Glucagon was maintained at 261 +/- 16.2 and 124 +/- 6.4 pg/ml, respectively, in the high-insulin and low-insulin groups. Without hormonal control, plasma glucose homeostasis was maintained during exercise because the increase in glucose uptake was balanced by a corresponding increase in glucose production. When changes in insulin and glucagon were prevented, plasma glucose concentration fell, particularly in the high-insulin group. Glucose uptake increased to a greater extent than when hormones were not controlled, and glucose production did not increase sufficiently to compensate. The increase in glucose uptake in the hormonal control groups was associated with an increased rate of glucose oxidation. When euglycemia was maintained by glucose infusion in the hormonal control subjects, the modest increase in glucose production that otherwise occurred was prevented. It is concluded that during light exercise there must be a reduction in insulin concentration and/or an increase in glucagon concentration if plasma glucose homeostasis is to be maintained. If such changes do not occur, hypoglycemia, and hence exhaustion, may occur.


Automatic Model Generation Framework for Computational Simulation of Cochlear Implantation.
Recent developments in computational modeling of cochlear implantation are promising to study in silico the performance of the implant before surgery. However, creating a complete computational model of the patient's anatomy while including an external device geometry remains challenging. To address such a challenge, we propose an automatic framework for the generation of patient-specific meshes for finite element modeling of the implanted cochlea. First, a statistical shape model is constructed from high-resolution anatomical μCT images. Then, by fitting the statistical model to a patient's CT image, an accurate model of the patient-specific cochlea anatomy is obtained. An algorithm based on the parallel transport frame is employed to perform the virtual insertion of the cochlear implant. Our automatic framework also incorporates the surrounding bone and nerve fibers and assigns constitutive parameters to all components of the finite element model. This model can then be used to study in silico the effects of the electrical stimulation of the cochlear implant. Results are shown on a total of 25 models of patients. In all cases, a final mesh suitable for finite element simulations was obtained, in an average time of 94 s. The framework has proven to be fast and robust, and is promising for a detailed prognosis of the cochlear implantation surgery.


Physician anaesthesia providers in Switzerland today and tomorrow: results of the National Anaesthesia Workforce Study (NAWOS).
The Swiss healthcare system is highly ranked, given its unrestricted access to specialised care and short waiting lists for surgery. However, the need for anaesthetic and surgical care is escalating owing to the increasing size and ageing of the Swiss population. In addition, to address the persistent and recurrent SARS-CoV-2 pandemic crisis, the speciality of anaesthesia is under tremendous pressure to maintain an effective workforce in order to address population needs. The current number, characteristics and future evolution of the physician anaesthesia workforce in Switzerland are currently unknown. The purpose of this study was to assess the size and professional and sociodemographic characteristics of the current anaesthesia workforce in Switzerland and to forecast its development up to 2034. We performed a cross-sectional study using a 150-item questionnaire prepared by the National Anaesthesia Workforce Study Group (NAWOS). We included all physicians (trainees and certified) practising anaesthesia in Switzerland. We collected demographic and professional information, such as the current position, hospital characteristics, workload, number of shifts and future life plans. We built a computer-based Markov model with Monte Carlo simulations to project both supply and demand for physician anaesthesia provider positions. Of the 2661 distributed questionnaires, 1985 (74.2%) were completed and returned. We found that the average age of anaesthesiologists practising in Switzerland was 45.2 years, with 44.3% of them being women and 76.9% holding a Swiss specialist title. Only 59.6% of respondents worked full time. The forecasting model showed a steady increase in the number of anaesthesiologists retiring by 2034, with 27% of full-time equivalent jobs being lost in the next 8 years. Even if existing full-time equivalent training positions are all filled, a gradual deficit of anaesthesiologists is to be expected after 2022, and the deficit should culminate in 2034 with a deficit ratio of 0.87. Due to the upcoming high retirement rate of anaesthesiologists, Switzerland is likely to face a shortage of anaesthesiologists in the near future. To compensate for the shortage, the country will likely increase its reliance on medical staff trained abroad. Southern and eastern cantons of Switzerland are particularly at risk, given that they already heavily rely on foreign anaesthesia workforce. This reliance should be considered a national priority because anaesthesiologists are heavily involved in both the treatment of patients with respiratory complications of SARS-CoV2 infection and the care of surgical patients, the number of which is expected to rise steadily in upcoming years.


[Radiation modification of the ATPase properties of submitochondrial particles].
The appreciable changes in hydrophobic properties of ATPase of rat liver submitochondrial particles were discovered 3 days after whole-body X-irradiation with a dose of 7 Gy. The sensitivity of ATPase activity to stimulating anions decreased. The radiation damages to ATPase were detected and the ratio of concentrations of magnesium and ATP exceeded a unity.


Towards a low-cost mobile subcutaneous vein detection solution using near-infrared spectroscopy.
Excessive venipunctures are both time- and resource-consuming events, which cause anxiety, pain, and distress in patients, or can lead to severe harmful injuries. We propose a low-cost mobile health solution for subcutaneous vein detection using near-infrared spectroscopy, along with an assessment of the current state of the art in this field. The first objective of this study was to get a deeper overview of the research topic, through the initial team discussions and a detailed literature review (using both academic and grey literature). The second objective, that is, identifying the commercial systems employing near-infrared spectroscopy, was conducted using the PubMed database. The goal of the third objective was to identify and evaluate (using the IEEE Xplore database) the research efforts in the field of low-cost near-infrared imaging in general, as a basis for the conceptual model of the upcoming prototype. Although the reviewed commercial devices have demonstrated usefulness and value for peripheral veins visualization, other evaluated clinical outcomes are less conclusive. Previous studies regarding low-cost near-infrared systems demonstrated the general feasibility of developing cost-effective vein detection systems; however, their limitations are restricting their applicability to clinical practice. Finally, based on the current findings, we outline the future research direction.


Angiogenic factor-enriched platelet-rich plasma enhances in vivo bone formation around alloplastic graft material.
Although most researchers agree that platelet-rich plasma (PRP) is a good source of autogenous growth factors, its effect on bone regeneration is still controversial. The purpose of this study was to evaluate whether increasing angiogenic factors in the human PRP to enhance new bone formation through rapid angiogenesis. In vitro, the human platelets were activated with application of shear stress, 20 µg/ml collagen, 2 mM CaCl(2) and 10U thrombin/1 × 10(9) platelets. Level of vascular endothelial growth factor (VEGF) and platelet microparticle (PMP) in the activated platelets were checked. In the animal study, human angiogenic factors-enriched PRP was tested in 28 athymic rat's cranial critical bone defects with β-TCP. Angiogenesis and osteogenesis were evaluated by laser Doppler perfusion imaging, histology, dual energy X-ray densinometry, and micro-computed tomography. In vitro, this human angiogenic factors-enriched PRP resulted in better cellular proliferation and osteogenic differentiation. In vivo, increasing angiogenic potential of the PRP showed significantly higher blood perfusion around the defect and enhanced new bone formation around acellular bone graft material. Angiogenic factor-enriched PRP leads to faster and more extensive new bone formation in the critical size bone defect. The results implicate that rapid angiogenesis in the initial healing period by PRP could be supposed as a way to overcome short term effect of the rapid angiogenesis.


Vitamin K3 (menadione)-induced oncosis associated with keratin 8 phosphorylation and histone H3 arylation.
The vitamin K analog menadione (K3), capable of both redox cycling and arylating nucleophilic substrates by Michael addition, has been extensively studied as a model stress-inducing quinone in both cell culture and animal model systems. Exposure of keratin 8 (k-8) expressing human breast cancer cells (MCF7, T47D, SKBr3) to K3 (50-100 microM) induced rapid, sustained, and site-specific k-8 serine phosphorylation (pSer73) dependent on signaling by a single mitogen activated protein kinase (MAPK) pathway, MEK1/2. Normal nuclear morphology and k-8 immunofluorescence coupled with the lack of DNA laddering or other features of apoptosis indicated that K3-induced cytotoxicity, evident within 4 h of treatment and delayed but not prevented by MEK1/2 inhibition, was due to a form of stress-activated cell death known as oncosis. Independent of MAPK signaling was the progressive appearance of K3-induced cellular fluorescence, principally nuclear in origin and suggested by in vitro fluorimetry to have been caused by K3 thiol arylation. Imaging by UV transillumination of protein gels containing nuclear extracts from K3-treated cells revealed a prominent 17-kDa band shown to be histone H3 by immunoblotting and mass spectrometry (MS). K3 arylation of histones in vitro followed by electrospray ionization-tandem MS analyses identified the unique Cys110 residue within H3, exposed only in the open chromatin of transcriptionally active genes, as a K3 arylation target. These findings delineate new pathways associated with K3-induced stress and suggest a potentially novel role for H3 Cys110 as a nuclear stress sensor.