Shared decision making, a buzz-word in the Netherlands, the pace quickens towards nationwide implementation….
Currently, shared decision making (SDM) is on the agenda among target patient representative groups, policy makers and professional bodies. Although the International Conference for Shared Decision Making (ISDM) 2011 generated a positive boost, hesitation was also felt among Dutch clinicians, who are challenged by many new tasks. No hesitation is seen among the majority of patients, opting mostly for the SDM model. We haven't reached these patients' needs fully yet, given disappointing research data on patients' experiences and professional behaviour. There is plenty of room for improvement in daily practice, for which many best practices are being designed and increasingly implemented, such as national campaigns to empower patients, central governance of patient decision aids that are developed along clinical practice guidelines, postgraduate training, collaborative learning and system changes, and merging goal setting and SDM in complex care. This is explicitly supported by the Dutch government, the Ministry of Health, patient groups, professional bodies and health insurers. The culture shift in the minds and hearts of patients and clinicians has started but is still ongoing. Enthusiasm for this way of working could be undermined if SDM is defined and implemented in a simplistic, dogmatic manner leading to irresponsible transferring of the professionals' uncertainty, responsibility, and decisional stress to patients.


Effects of combined endurance and strength training on left ventricular morphology in male and female rowers.
The effects of 10 weeks of combined endurance and strength training on left ventricular (LV) morphology, muscular strength, maximal oxygen consumption (VO2max) and rowing performance were assessed. Twenty-five subjects (eight males, mean age 23.0 +/- 6.1 years, and 17 females, 22.7 +/- 5.0 years) were tested at baseline and after five and 10 weeks of training. Combined training was associated with significant improvements in VO2max, rowing performance and muscular strength after 10 weeks of training. A significant increase in LV diastolic dimension was found in males after 10 weeks of training; however, no significant alteration was found for any other measured echocardiographic variable. Therefore, with the exception of LV diastolic dimension in males, 10 weeks of combined endurance and strength training appears to be an insufficient stimulus to elicit significant alterations in LV morphology despite changes in VO2max, muscular strength or rowing performance.


Student outcomes associated with service-learning in a culturally relevant high school program.
The Hawaiian Studies Program (HSP) integrates the learning of Hawaiian culture with more traditional secondary curriculum in science, social studies, and English. Students also participate in weekly community service-learning sessions. Fifty-five HSP students and 29 peers (who were not involved in the program), completed a survey measuring: students' connection to, pride in, and responsibility for their community; civic attitudes; and career knowledge and preparedness. HSP teachers, community members, and students were also interviewed about program outcomes. Compared to other peers, HSP students tended to report feeling more connected to their community and school and to agree that they had career-related skills. Participants believed that service- learning contributed to these outcomes by making connections between school and community life and by exposing students to a variety of careers.


Substances derived from 4-ethyl octanoic acid account for primer pheromone activity for the "male effect" in goats.
A major constituent of the characteristic "goaty odor" 4-ethyl octanoic acid (4EOA) was previously shown to have no primer pheromone activity. This was also confirmed by our own bioassay system utilizing the recording technique of neural activity of the hypothalamic gonadotropin-releasing hormone pulse generator in goats. However, when the synthetic 4EOA solution was kept at room temperature for several months, primer pheromone activity appeared in the same solution. Headspace gas chromatography/mass spectrometry analysis revealed that there were several newly formed substances in addition to 4EOA samples with primer pheromone activity. These results suggest that 4EOA derived substance(s) but not 4EOA itself is(are) primer pheromone in goats.


Radiation tolerance in the tardigrade Milnesium tardigradum.
Tardigrades are known to survive high doses of ionizing radiation. However, there have been no reports about radiation effects in tardigrades under culture conditions. In this study, we investigated tolerance of the tardigrade, Milnesium tardigradum, against gamma-rays and heavy ions by determining short-term or long-term survival, and reproductive ability after irradiation. Hydrated and anhydrobiotic animals were exposed to gamma-rays (1000 - 7000 Gy) or heavy ions (1000 - 8000 Gy) to evaluate short-term survival at 2, 24 and 48 h post-irradiation. Long-term survival and reproduction were observed up to 31 days after irradiation with gamma-rays (1000 - 4000 Gy). At 48 h after irradiation, median lethal doses were 5000 Gy (gamma-rays) and 6200 Gy (heavy ions) in hydrated animals, and 4400 Gy (gamma-rays) and 5200 Gy (heavy ions) in anhydrobiotic ones. Gamma-irradiation shortened average life span in a dose-dependent manner both in hydrated and anhydrobiotic groups. No irradiated animals laid eggs with one exception in which a hydrated animal irradiated with 2000 Gy of gamma-rays laid 3 eggs, and those eggs failed to hatch, whereas eggs produced by non-irradiated animals hatched successfully. M. tardigradum survives high doses of ionizing radiation in both hydrated and anhydrobiotic states, but irradiation with >1000 Gy makes them sterile.


Clivus and apicopetroclivus meningiomas--report of 24 cases.
The authors describe the clinical and radiological features, surgical procedures, and outcome of 18 cases of clivus meningiomas and six of apicopetroclivus meningiomas. There were 17 females and seven males, ranging in age from 26 to 69 years, with a mean age of 47 years. All except one showed cranial nerve deficits. Computed tomography accurately demonstrated tumor size and location. Cerebral angiography showed characteristic displacement of the basilar artery and its tributaries, with blood supply to the tumor largely via the meningohypophyseal trunk. Magnetic resonance imaging was excellent in delineating the relationship of the tumor to the brainstem and major vasculature. The surgical approaches used were transpetrosal-transtentorial (n = 9), combined transpetrosal-transtentorial-transzygomatic preauricular transpetrosal (n = 9), suboccipital-subtemporal (n = 2), suboccipital (n = 1), frontotemporal (first stage operation) followed by suboccipital (second stage operation) (n = 1), suboccipital-transpetrosal (n = 1), and orbitozygomatic-infratemporal preauricular transpetrosal (n = 1). Seventeen tumors were totally removed and seven subtotally. The operative mortality was 8% (two patients). Twenty patients developed new cranial nerve deficits within 1 month of surgery. The average follow-up period was 5 years, and the outcome was good or excellent in 12 cases. Transpetrosal approaches proved relatively safe and effective for radical tumor removal and, in two cases, permitted preservation of useful hearing.(ABSTRACT TRUNCATED AT 250 WORDS)


Eosinophilia in mouse regulated by multiple factors following repeated stimulations with ascaris eggs into the peritoneal cavity.
Repeated injections of viable eggs of Ascaris suum into the peritoneal cavity of BALB/c mice induced marked peritoneal eosinophilia (9.3 X 10(6) cells/mouse, 52.8%) without infection. Extracted antigen (Asc) and eggs that had been killed also were able to induce marked eosinophilia; however, their levels were significantly lower (p less than 0.001). This experimental system was able to demonstrate how various multiple factors cumulatively affected the degree of peritoneal eosinophilia. These factors included: mechanical stimulation, caused by the repeated peritoneal lavages (4.4 X 10(5) cells/mouse), against a background level of peritoneal eosinophils of 4.5 X 10(4) cells/mouse; T-cell-independent stimulation, observed when the viable eggs were injected repeatedly into athymic nude mice (nu/nu; 1.6 X 10(6) cells/mouse), while on the other hand, neither eggs that had been killed nor Asc displayed any T-cell-independent augmentation of eosinophilia; and, T-cell-dependent augmentation of peritoneal eosinophilia, observed in heterozygous athymic mice (nu/+), in thymocyte-reconstituted nu/nu, and in normal BALB/c mice. Egg culture supernatant could not act on bone marrow cells to support eosinophil colony formation. In conclusion, only viable eggs were considered prime inducers, consisting of T-independent and T-dependent parts exerting cumulative effects.


Camellia sinensis L. Extract and Its Potential Beneficial Effects in Antioxidant, Anti-Inflammatory, Anti-Hepatotoxic, and Anti-Tyrosinase Activities.
The aims of this study were to investigate the potential benefits of antioxidant, anti-inflammatory, anti-hepatotoxic, and anti-tyrosinase activities of a methanolic extract of fresh tea leaves (FTE) (Camellia sinensis L.). The antioxidant capacity was investigated using three different methods at different temperatures. The anti-inflammatory activity was studied in vitro by the inhibition of 5-lipoxygenase assay. The anti-hepatotoxic effect was investigated in CCl₄-induced liver injury in rats. The anti-tyrosinase activities of the FTE and its principal phenolic compounds were investigated in l-3,4-dihydroxyphenylalanine (l-DOPA) oxidation by a mushroom tyrosinase. A molecular docking study was conducted to determine how the FTE's principal catechins interact with the tyrosinase. The FTE exhibited the best shelf life at low temperatures and demonstrated concentration-dependent antioxidant, anti-inflammatory, anti-hepatotoxic, and anti-tyrosinase effects compared to positive references. Treatment of rats with the FTE at 2000 mg/kg/day for 28 consecutive days reversed CCl₄-induced oxidative damage in hepatic tissues by lowering the levels of alanine aminotransferase by 69% and malondialdehyde by 90%. Our findings suggest that the FTE has the capacity to scavenge free radicals and can protect against oxidative stress induced by CCl₄ intoxication. The docking results were consistent with our in vitro data, indicating the anti-tyrosinase potency of the principal catechins.


Development and validation of spectroscopic methods for monitoring density changes in pressurized gaseous and supercritical fluid systems.
The further development of new processes utilizing liquid or supercritical CO2 as a solvent will benefit from the rational design of new CO2-philes. Understanding solvation structures and mechanisms of these molecules is an important part of this process. In such studies, determining the change in density as a function of the measured thermodynamic conditions (pressure and temperature) provides an excellent means of directly monitoring the solution conditions in the detection volume for a given technique. By integrating spectroscopic peaks, changes in area can be used to determine changes in analyte concentration in the detection volume, and thus, it should be possible to monitor the system density in situ. In the present study, we examine the utility of Raman and NMR spectroscopy as a means of following changes in solution density conditions and validate this approach in pure fluids and gases (N2 and CO2) and supercritical fluid mixtures (acetaldehyde vapor in N2). In addition, we present the design of a simple, inexpensive cell for conducting Raman and NMR measurements under moderate pressure conditions.


IPL-M1 interaction shapes pre-reflective social differentiation in the human action system: new insights from TBS and TMS combined.
The conscious experience of being the author of our own actions is thought to be grounded in pre-reflective and low-level sensorimotor representations of the self as different from the other. It has been suggested that the inferior parietal lobe (IPL) is generally involved in self-other differentiation processes and in providing an explicit sense of action authorship. However, direct evidence for its causal and functional role in distinguishing self-related and other-related sensorimotor representations is lacking. The current study employed theta-burst stimulation (TBS) to condition left IPL's activity before a social version of the rubber hand illusion led participants to illusorily attribute observed finger movements to their own body. We recorded motor evoked potentials to single-pulse transcranial magnetic stimulation over the primary motor cortex (M1) as proxies of action authorship during action observation. The results showed that in a control condition (intermediate TBS over the left IPL) others' actions facilitated whereas self-attributed movements inhibited the motor system. Critically, continuous TBS disrupted this mismatch between self and other representations. This outcome provides direct evidence for the IPL's role in providing fundamental authorship signals for social differentiation in the human action system.


Casual Associations and Shape Between Prepuberty Body Mass Index and Early Onset of Puberty: A Mendelian Randomization and Dose-Response Relationship Analysis.
There is an ongoing controversial issue regarding whether onset of puberty is related to childhood BMI. This study aims at investigating the causal association and its shape between prepuberty BMI and early puberty onset. Breast development and testicular volume were assessed annually from a population-based prospective cohort of 997 children for consecutive years by professional endocrinologists. Seventeen puberty- and BMI-related SNPs were selected to calculate the polygenic risk score. The two-stage least square method was used to assess and confirm causal effects. A dose-response association between prepuberty BMI and early puberty onset was conducted by using restricted cubic spline Cox regression. After adjusting for covariates, prepuberty BMI was positively associated with early thelarche among girls (coefficients = 0.18, 95% CI: 0.01, 0.29). A non-linear model suggested an inverted U-shaped relationship between prepuberty BMI and risk for early thelarche (χ2 = 276.3, p < 0.001). The risk for early thelarche increased rapidly from prepuberty BMI at 15.70 kg/m2 (P25) to 20.75 kg/m2 (P85) and gradually decreased afterward. Compared with the P25 of prepuberty BMI, the HRs (95% CI) for early thelarche were 5.08 (1.15, 8.55), 4.48 (1.02, 7.74), 10.15 (3.93, 17.50), and 8.43 (1.91, 13.71) for percentiles P25-P50, P50-P75, P75-P85, and ≥P85 of BMI categories, respectively. In boys, compared with the P25 of prepuberty BMI, boys with BMI between P25 and P50 showed an increased risk of early puberty (HR: 3.94, 95% CI: 1.44, 6.80). Prepuberty BMI may serve the purpose of identifying the girls at higher risk of early thelarche, which could assist in the adaptation of prevention and intervention strategies targeting childhood obesity. The findings emphasize a non-linear correlation between prepuberty BMI and early puberty onset.


The role of informed consent in patient complaints: Reducing hidden health system costs and improving patient engagement through shared decision making.
Patient complaints about physicians are strongly associated with malpractice risk. Physicians at high risk for lawsuits tend to have poor communication skills and are more commonly the subject of patient complaints about communication issues. If a malpractice action does not arise, patient complaints nonetheless represent significant prelitigation transaction costs for the healthcare system that have not been previously quantified. Informed consent complaints represent a unique constellation of clinical communication skills clearly tied to malpractice risk. The goal of this study was to measure institutional resource consumption allocated to informed consent (IC) complaints, which are both costly and preventable. We compared IC complaints to other complaints about medical care in a single medical center in the United States, estimating the absolute and relative burden of IC deficiencies within this healthcare system. Resource consumption for the resolution of IC complaints far exceeded their proportional representation of complaints, representing half of all complaints, while disproportionately absorbing two-thirds of staff time devoted to complaint resolution. Complaint resolution represents an unrecognized remediable cost and an underappreciated opportunity for reducing waste in healthcare. We suggest that healthcare systems can reduce costs and elevate their patient-centered care practices by improving patient-provider communication during medical decision making via engagement strategies such as shared decision making.


Cyclophilin A in Ruptured Intracranial Aneurysm: A Prognostic Biomarker.
Cyclophilin A (CyPA), an oxidative stress-induced factor, was found to play an important role in the aneurysm formation. Our working hypothesis was that the plasma level of CyPA in ruptured intracranial aneurysm could predict the neurological outcome. From 2011 to 2013, a total of 36 patients with ruptured saccular intracranial aneurysm were recruited in our study. Before coil embolization, we draw blood samples at the orifice of a culprit aneurysm and in the remote peripheral vein for measurements of the CyPA levels. We utilized the modified Rankin scale 30 days after aneurysm rupture as the outcome measure. Generalized linear models were used to estimate the adjusted odds ratios of the poor neurological outcome given the presence of high plasma level of CyPA. The aneurysmal and venous CyPA levels were significantly associated with the initial clinical severity (P = 0.004 and 0.03, respectively) and 30-day outcome (P = 0.01 and 0.02, respectively). The aneurysmal CyPA levels modestly correlated with age and high Fisher grade (ρ = 0.39 and 0.41; P = 0.02 and 0.01, respectively). The aneurysmal CyPA levels strongly correlated with the venous counterpart (ρ = 0.89; P < 0.001). Patients with high levels of aneurysmal CyPA were 15.66 times (95% CI, 1.48-166.24; P = 0.02) more likely to have worse neurological outcome than those with the low levels after adjustment of the age, gender, and the documented confounding factors. High plasma level of CyPA is a significant prognostic biomarker for poor neurological outcome in patients with ruptured intracranial aneurysm.


Analysis of the human SOX10 mutation Q377X in mice and its implications for genotype-phenotype correlation in SOX10-related human disease.
Human SOX10 mutations lead to various diseases including Waardenburg syndrome, Hirschsprung disease, peripheral demyelinating neuropathy, central leukodystrophy, Kallmann syndrome and various combinations thereof. It has been postulated that PCWH as a combination of Waardenburg and Hirschsprung disease, peripheral neuropathy and central leukodystrophy is caused by heterozygous SOX10 mutations that result in the presence of a dominantly acting mutant SOX10 protein in the patient. One such protein with postulated dominant action is SOX10 Q377X. In this study, we generated a mouse model, in which the corresponding mutation was introduced into the Sox10 locus in such a way that Sox10 Q377X is constitutively expressed. Heterozygous mice carrying this mutation exhibited pigmentation and enteric nervous system defects similar to mice in which one Sox10 allele was deleted. However, despite presence of the mutant protein in Schwann cells and oligodendrocytes throughout development and in the adult, we found no phenotypic evidence for neurological defects in peripheral or central nervous systems. In the nervous system, the mutant Sox10 protein did not act in a dominant fashion but rather behaved like a hypomorph with very limited residual function. Our results question a strict genotype-phenotype correlation for SOX10 mutations and argue for the influence of additional factors including genetic background.


Mapping and targeting of C1ql1-expressing cells in the mouse.
The C1Q complement protein C1QL1 is highly conserved in mammals where it is expressed in various tissues including the brain. This secreted protein interacts with Brain-specific Angiogenesis Inhibitor 3, BAI3/ADGRB3, and controls synapse formation and maintenance. C1ql1 is expressed in the inferior olivary neurons that send projections to cerebellar Purkinje cells, but its expression in the rest of the brain is less documented. To map C1ql1 expression and enable the specific targeting of C1ql1-expressing cells, we generated a knockin mouse model expressing the Cre recombinase under the control of C1ql1 regulatory sequences. We characterized the capacity for Cre-driven recombination in the brain and mapped Cre expression in various neuron types using reporter mouse lines. Using an intersectional strategy with viral particle injections, we show that this mouse line can be used to target specific afferents of Purkinje cells. As C1ql1 is also expressed in other regions of the brain, as well as in other tissues such as adrenal glands and colon, our mouse model is a useful tool to target C1ql1-expressing cells in a broad variety of tissues.


Stentian structural plasticity in the developing visual system.
In a small fraction of Xenopus tadpoles, a single retinal ganglion cell (RGC) axon misprojects to the ipsilateral optic tectum. Presenting flashes of light to the ipsilateral eye causes that ipsilateral axon to fire, whereas stimulating the contralateral eye excites all other RGC inputs to the tectum. We performed time-lapse imaging of individual ipsilaterally projecting axons while stimulating either the ipsilateral or contralateral eye. Stimulating either eye alone reduced axon elaboration by increasing branch loss. New branch additions in the ipsi axon were exclusively increased by contralateral eye stimulation, which was enhanced by expressing tetanus neurotoxin (TeNT) in the ipsilateral axon, to prevent Hebbian stabilization. Together, our results reveal the existence of a non-cell-autonomous "Stentian" signal, engaged by activation of neighboring RGCs, that promotes exploratory axon branching in response to noncorrelated firing.


Enhancing Reviews and Surveillance to Eliminate Maternal Mortality.
Multisectoral investments over the past decade have accelerated the growth of Maternal Mortality Review Committee (MMRC) programs across the United States. The U.S. Centers for Disease Control and Prevention (CDC) launched the Enhancing Reviews and Surveillance to Eliminate Maternal Mortality (ERASE MM) Initiative in 2019. Under ERASE MM, CDC directly funds 24 U.S. jurisdictions supporting MMRCs in 25 states. With increased investment in programs nationally, the CDC has designed a performance management framework to identify areas for improvement or sustained achievement and standardize measurement of key process benchmarks across programs. This article presents a report on the baseline measures collected through this performance management approach and suggests key partnerships required to continue to accelerate progress toward the elimination of preventable maternal mortality in the United States.


Contributions of prestrains, hyperelasticity, and muscle fiber activation on mitral valve systolic performance.
The present study addresses the contributions of prestrains and muscle fiber activation to the global response of the mitral valve during systole. A finite element model of a porcine mitral valve is created using anatomical measurements and 3D echocardiographic recordings. The passive behavior of the leaflets is modeled using a transversely isotropic hyperelastic constitutive model, and we assume orthotropic muscle activations in the anterior leaflet. A simple approach to incorporate prestrains in the mitral valve apparatus is used by expanding the mitral annulus before applying the ventricular pressure to the mitral leaflets. Several finite element analyses are run with or without muscle activation and with or without prestrains. The analysis results are compared at peak systole with the echocardiograpic recordings. The case where prestrains and activation are accounted for simultaneously is the most efficient to approach the physiological flat shape of the closed valve observed in the echocardiograpic measurements. These results suggest that the active components present in the mitral leaflets and the presence of prestrains contribute to the physiological deformations of the mitral valve at peak systole and that material models based on in vitro mechanical testing are not sufficient for numerical studies of the mitral apparatus. Copyright © 2016 John Wiley & Sons, Ltd.


Tibial dyschondroplasia is closely related to suppression of expression of hypoxia-inducible factors 1α, 2α, and 3α in chickens.
Tibial dyschondroplasia (TD) cases has not been reported in Tibetan chickens (TBCs), but it is commonly seen in commercial broilers characterized by lameness. The underlying mechanism remains unclear. Hypoxia-inducible factors (HIFs) are important regulators of cellular adaptation to hypoxic conditions. In this study, we investigated the role of HIF-1α, -2α, and -3α in hypoxia and thiram-induced TD and their effect on tibial growth plate development in Arbor Acres chickens (AACs) and TBCs. RNA and protein expression levels of HIF-1α, -2α, and -3α were determined by using quantitative reverse transcriptase polymerase chain reaction and western blotting analyses, respectively. Interestingly, the results showed that HIF-1α, -2α, and -3α expressions in the tibial growth plate of TBCs were upregulated by hypoxia and the change was more significant in TBCs than in AACs. However, these factors were downregulated in thiram-induced TD. To further clarify the effect of thiram on tibial growth plate in commercial broilers, AACs were observed to exhibit more pronounced changes in their growth plate that that in TBCs. Taken together, these results demonstrate that HIF-1α, -2α, and -3α may be important in tibial growth plate development and in the prevention of TD. The present study contributes novel insights on a therapeutic target for poultry TD.


"Killer" character does not influence the transmission of mitochondrial genes in Saccharomyces cerevisiae.
Three cytoplasmic genetic elements have been shown to be separate from mitochondrial deoxyribonucleic acid (DNA), [rho], in Saccharomyces cerevisiae: the killer character [k], omicron-DNA, and psi [psi]. Griffiths has suggested genetic interactions between [VENR] and [TETR] mutants possibly located on omicron-DNA and mitochondrial genetic markers, but possible interactions between the best characterized of the three, the killer character, and mitochondrial DNA have not been investigated. To test this we isolated cycloheximide-induced nonkiller segregants (NKS) of killer cells with suitable genetic markers and mated them in [k] x [k], [k] x [k], and (NKS) x (NKS) combinations. No differences in quantitative mitochondrial marker transmission between these groups were found in crosses illustrating the mitochondrial phenomena of bias, polarity, and suppressiveness. Our studies show that no intercellular interactions between [k] and (NKS) cells influence mitochondrial transmission genetics. Intracellular interactions between the smaller double-stranded ribonucleic acid of [k] and mitochondrial DNA also were not detected.


Dento-craniofacial phenotypes and underlying molecular mechanisms in hypohidrotic ectodermal dysplasia (HED): a review.
The hypohidrotic ectodermal dysplasias (HED) belong to a large and heterogeneous nosological group of polymalfomative syndromes characterized by dystrophy or agenesis of ectodermal derivatives. Molecular etiologies of HED consist of mutations of the genes involved in the Ectodysplasin (EDA)-NF-kappaB pathway. Besides the classic ectodermal signs, craniofacial and bone manifestations are associated with the phenotypic spectrum of HED. The dental phenotype of HED consists of various degrees of oligodontia with other dental abnormalities, and these are important in the early diagnosis and identification of persons with HED. Phenotypic dental markers of heterozygous females for EDA gene mutation-moderate oligodontia, conical incisors, and delayed dental eruption-are important for individuals giving reliable genetic counseling. Some dental ageneses observed in HED are also encountered in non-syndromic oligodontia. These clinical similarities may reflect possible interactions between homeobox genes implicated in early steps of odontogenesis and the Ectodysplasin (EDA)-NF-kappaB pathway. Craniofacial dysmorphologies and bone structural anomalies are also associated with the phenotypic spectrum of persons with HED patients. The corresponding molecular mechanisms involve altered interactions between the EDA-NF-kappaB pathway and signaling molecules essential in skeletogenic neural crest cell differentiation, migration, and osteoclastic differentiation. Regarding oral treatment of persons with HED, implant-supported prostheses are used with a relatively high implant survival rate. Recently, groundbreaking experimental approaches with recombinant EDA or transgenesis of EDA-A1 were developed from the perspective of systemic treatment and appear very promising. All these clinical observations and molecular data allow for the specification of the craniofacial phenotypic spectrum in HED and provide a better understanding of the mechanisms involved in the pathogenesis of this syndrome.


[Asystolic seizures].
Epileptic seizures may alter autonomic functions. This is especially the case with complex focal seizures (of temporal lobe origin) and grand mal. Most frequently, such seizures cause ictal tachycardia, sometimes tachypnea, probably caused by the propagation of epileptic discharges to autonomic cerebral structures. Ictal bradycardia and asystole are rare phenomena. However, they may be life threatening. Their differentiation from primary cardiac arrest is possible by the use of ictal EEG and ECG registration. Postictal serum prolactin measurement does not differentiate syncope from seizure. However, a postictal increase of creatine kinase is only measured after epileptic seizures and not after syncope. Treatment of such epileptic seizures includes an optimization of anticonvulsant drug therapy and the implantation of a cardiac demand stimulator. There is growing evidence that ictal asystole is a cofactor in sudden unexplained death in epileptic patients.


Synthesis, structure, and 15N NMR studies of paramagnetic lanthanide complexes obtained by reduction of dinitrogen.
The recently discovered LnZ3/M and LnZ2Z'/M methods of reduction (Ln = lanthanide; M = alkali metal; Z, Z' = monoanionic ligands that allow these combinations to generate "LnZ2" reactivity) have been applied to provide the first crystallographically characterized dinitrogen complexes of cerium, [C5Me5)2(THF)Ce]2(mu-eta2.eta2-N2) and [(C5Me4H)2(THF)Ce]2(mu-eta2.eta2-N2), so that the utility of 15N NMR spectroscopy with paramagnetic lanthanides could be determined. [(C5Me5)2(THF)Pr]2(mu-eta2.eta2-N2) and [(C5Me4H)2(THF)Pr]2(mu-eta2.eta2-N2) were also synthesized, crystallographically characterized, and studied by 15N NMR methods. The data were compared to those of [(C5Me5)2Sm]2(mu-eta2.eta2-N2). [(C5Me5)2(THF)Ce]2(mu-eta2.eta2-N2) and [(C5Me5)2(THF)Pr]2(mu-eta2.eta2-N2) are unlike their (C5Me4H)1- analogs in that the solvating THF molecules are cis rather than trans. Structural information on precursors, (C5Me4H)3Ce, (C5Me4H)3Pr, and the oxidation product [(C5Me5)2Ce]2(mu-O) is also presented.


Social cognition and revictimization risk.
The ability to accurately detect violations in social contracts likely helps people to avoid or to withdraw from relationships in which they are at risk of being cheated or harmed. Betrayal trauma theory argues that detecting violations of social contracts may be counter-productive to survival under certain conditions, such as when a victim is dependent on a perpetrator. When dependent on a perpetrator (as in the case of child abuse perpetrated by a caregiver), the victim may be better able to preserve the necessary attachment with the caregiver by remaining unaware of the abuse. Thus, the victim may develop a compromised capacity to detect violations of social contracts in the caregiving relationship. Over time, the victim may develop more generalized problems detecting violations in social exchange rules; in turn, generalized problems in detecting violations of social contracts may increase risk for later victimization. Participants in the current study were asked to detect violations in three types of conditional (if-then) rules: abstract, social contract (rules involving a social exchange), and precautionary (rules involving safety). Young adults who reported experiences of revictimization made more errors on social contract and precautionary problems than a no revictimization group; group performance did not differ for abstract problems, suggesting these findings are not explained by general deficits in conditional reasoning. Pathological dissociation significantly predicted errors on social contract and precautionary problems.


Fluorescent antibody studies in chlamydial infections.
Irradiated McCoy cells infected with genital strains of Chlamydia trachomatis were grown in wells on slides coated with polytetrafluoroethylene. The inclusions produced in this system formed the antigen in an indirect immunofluorescence test, which detected group-specific chlamydial antibodies in sera from patients attending veneral disease clinics. Chlamydial antibodies were found more frequently and in higher titer in sera from women attending veneral disease clinics then in sera from a less promiscuous population attending a Family Planning Association clinic. Paired sera from 13 patients with nongonococcal urethritis from whom chylamydiae had been isolated were tested against the homologous isolates; seroconversion was demonstrated in only one instance, and antibody was present in the first serum specimens of all the other patients. Chlamydia-specific immunoglobulin M was found in four of eight patients with psittacosis and in a proportion of sera from patients attending veneral disease and Family Planning Association clinics. The antigen for this immunofluorescence test can easily be prepared in laboratories with cell culture facilities for the isolation of C. trachomatis, and the test should be useful for laboratories which cannot undertake the micro-immunofluorescence test.


Isolation, purification and assay of the macerating enzyme produced by Penicillium oxalicum Curie and Thom.
Penicillium oxalicum produced two isozymes of polygalacturonase (PG) and a pectate lyase (PL). The enzymes were separated and purified following ammonium sulphate precipitation, ion exchange chromatography, ultrogel column chromatography and isoelectric focusing. The first isozyme of polygalacturonase (PGI) was rather unstable hence its properties could not be much assayed. PGII macerated and killed yam tissue in 4 hours but PL was unable to do so. Enzyme assay for the end-products of degradation of sodium polypectate and yam tissue showed that PGI was an exo-enzyme while PGII and PL were endo-enzymes. Endo-polygalacturonase (PGII) appears to play the major role (as the macerating enzyme) in the pathogenesis of yam tissue infected by P. oxalicum.


Development and validation of a virtual human vignette to compare nurses' assessment and intervention choices for pain in critically ill children.
As virtual experiences are increasingly used in health care training and research, it is important that adequate processes are applied for developing valid scenarios. We describe the development and validation of virtual human (VH) vignettes, computer-generated scenarios with animated patients and clinical information, for a mixed-methods study regarding nurses' assessment and intervention choices for critically ill children's pain. We followed the case development and review process for high-fidelity simulation case scenarios, including the use of validated written vignettes and content experts. Forty nurses described their pain assessment and intervention choices for the newly derived VH vignettes and completed a pain questionnaire. Nurses' reports of VH vignette consistency with their professional experience and recognition of VH facial expressions were evaluated to establish face validity. Their pain ratings for the VH and written (questionnaire) vignettes were evaluated for convergent validity. Qualitative content analysis, descriptive statistics, correlations, and paired t tests were used. Most nurses (68.4%) supported vignette consistency with their professional experience. Facial expression recognition was 98.4%. Smiling children's pain was rated significantly lower than grimacing children in both VH and written vignettes. Pain was rated significantly lower for grimacing children in the VH vignettes than the written vignettes. Virtual human vignette pain ratings were strongly correlated with their written counterparts. This process was effective for developing VH vignettes that demonstrated good face validity with participants and convergent validity with written vignettes. Virtual human vignettes may be useful in studying the influence of facial actions on nurses' choices for children's pain assessment and treatment.


Inhibition of fatty acid desaturation impairs cuticle differentiation in Drosophila melanogaster.
Previously, we showed that inhibition of the activity of fatty acid desaturases (Desat) perturbs signalling of the developmental timing hormone ecdysone in the fruit fly Drosophila melanogaster. To understand the impact of this effect on cuticle differentiation, a process regulated by ecdysone, we analysed the cuticle of D. melanogaster larvae fed with the Desat inhibitor CA10556. In these larvae, the expression of most of the key cuticle genes is normal or slightly elevated at day one of CA10556 feeding. As an exception, expression of twdlM coding for a yet uncharacterised cuticle protein is completely suppressed. The cuticle of these larvae appears to be normal at the morphological level. However, these animals are sensitive to desiccation, a trait that according to our data, among others, may be associated with reduced TwdlM amounts. At day two of CA10556 feeding, expression of most of the cuticle genes tested including twdlM is suppressed. Expression of cpr47Eb coding for a chitin-binding protein is, by contrast, highly elevated suggesting that Cpr47Eb participates at a specific compensation program. Overall, the cuticle of these larvae is thinner than the cuticle of control larvae. Taken together, lipid desaturation is necessary for a coordinated deployment of a normal cuticle differentiation program.


Invited review: Milk phospholipid vesicles, their colloidal properties, and potential as delivery vehicles for bioactive molecules.
The milk fat globule membrane (MFGM) is a unique colloidal assembly of phospholipids and proteins, with numerous potential applications as functional ingredient. The phospholipid components of the MFGM are gaining interest as they are a useful matrix for use as a constituent of delivery systems such as liposomes. Liposomes formulated with milk phospholipids are becoming an alternative to other sources of phospholipids such as soybean or egg yolk. However, incorporation of phospholipids fractionated from the milk fat globule membrane in dairy products requires an in-depth understanding of the functional properties of phospholipids. In particular, it is critical to understand which factors play a role in their stability and bioefficacy as delivery systems. Moreover, chemical and physical modifications of phospholipid liposomes occurring during digestion and the fate of the encapsulated compounds are very important to understand. This review discusses recent findings on the structure and functionality of MFGM, the bioactivity of the phospholipids fraction, their utilization as delivery systems, and their stability through gastrointestinal transit.


High-dose alcohol induces reactive oxygen species-mediated apoptosis via PKC-β/p66Shc in mouse primary cardiomyocytes.
Cardiac dysfunction caused by excessive alcohol consumption is a specific disease, alcoholic cardiomyopathy (ACM). High-dose alcohol has been found to induce oxidation stress and apoptosis in cardiomyocytes, but the signaling link between alcohol-induced oxidation stress and apoptosis in cardiomyocytes remains to be elucidated. To address the issue, we exposed primary cardiomyocytes from neonatal mouse hearts to high doses of alcohol (50mM, 100mM, and 200 mM). We found that alcohol induced dose-dependent phosphorylation of p66shc, and reactive oxygen species (ROS) production increased in parallel with phosphorylation levels of p66shc. Exposure to alcohol also led to loss of mitochondrial membrane potential and cytochrome c release. Depletion of p66Shc and inhibition of protein kinase C-β (PKC-β) successfully reversed all the effects and suppressed alcohol-induced apoptosis in cardiomyocytes. Collectively, our study provides a molecular basis for signaling transduction of alcohol-induced oxidation stress and apoptosis of cardiomyocytes, which may facilitate the prevention and treatment of ACM.


Heart rate variability from short electrocardiographic recordings predicts mortality from all causes in middle-aged and elderly men. The Zutphen Study.
Low heart rate variability is associated with high risk of sudden death in myocardial infarction patients. This has been attributed to unfavorable autonomic cardiac control. In the present study, the predictive value of heart rate variability for sudden death, mortality from coronary heart disease, and from all causes was investigated in the general population, using brief electrocardiographic recordings. From 1960 to 1985, 878 middle-aged Dutch men, aged 40-60 years, were followed and repeatedly examined as part of the Zutphen Study. In 1985 the remaining cohort was extended to 885 elderly men, aged 65-85 years, and followed until 1990. Heart rate variability (standard deviation of duration of normal RR intervals) was determined from the resting 12-lead electrocardiogram. The 5-year age-adjusted relative rate of total mortality of men with heart rate variability of < 20 milliseconds (msec) compared with men with heart rate variability of 20-39 msec was 2.1 (95 percent confidence interval 1.4-3.0) in middle-aged men and 1.4 (95% confidence interval 0.9-2.2) in elderly men. Death from noncoronary causes, especially cancer, contributed significantly to this elevated risk. The association of low heart rate variability with sudden death or coronary heart disease mortality was less consistent. In conclusion, in middle-aged men and probably in elderly men, low heart rate variability is predictive of mortality from all causes. This suggests that low heart rate variability is an indicator of compromised health in the general population.


Control of erythropoiesis by erythropoietin and stem cell factor: a novel role for Bruton's tyrosine kinase.
Erythropoietin (Epo) and stem cell factor (SCF) are essential factors in the control of survival, expansion and differentiation of erythroid progenitors. Upon activation, their receptors, the EpoR and c-Kit, initiate multiple signalling pathways that control many cellular processes. To control erythropoiesis, the strength, duration and specificity of signalling must be tightly controlled. Negative feed-back regulation is extensively studied, but positive feed-forward control is relatively little studied. The cytoplasmic tyrosine kinase Bruton's tyrosine kinase (Btk) was found to be phosphorylated by Jak2 in response to Epo and appeared to be required for fast and efficient phosphorylation of Epo-induced targets including the EpoR itself and downstream targets such as PLCgamma and Stat5. Erythroid progenitors deficient in Btk fail to undergo renewal divisions and differentiate instead at low, physiologic concentrations of Epo and SCF. In addition, Btk is phosphorylated by SCF, which causes association of Btk with TRAIL-receptor1. In absence of Btk, erythroid progenitors are hypersensitive to TRAIL. Thus, Btk modulates signalling in erythroid progenitors to enhance expansion of erythroid progenitors. The complexity of signalling by the EpoR/c-Kit signalosome and its control by Btk is discussed with respect to normal and aberrant erythropoiesis.


An exploration into diffusion tensor imaging in the bovine ocular lens.
We describe our development of the diffusion tensor imaging modality for the bovine ocular lens. Diffusion gradients were added to a spin-echo pulse sequence and the relevant parameters of the sequence were refined to achieve good diffusion weighting in the lens tissue, which demonstrated heterogeneous regions of diffusive signal attenuation. Decay curves for b-value (loosely summarizes the strength of diffusion weighting) and TE (determines the amount of magnetic resonance imaging-obtained signal) were used to estimate apparent diffusion coefficients (ADC) and T2 in different lens regions. The ADCs varied by over an order of magnitude and revealed diffusive anisotropy in the lens. Up to 30 diffusion gradient directions, and 8 signal acquisition averages, were applied to lenses in culture in order to improve maps of diffusion tensor eigenvalues, equivalent to ADC, across the lens. From these maps, fractional anisotropy maps were calculated and compared to known spatial distributions of anisotropic molecular fluxes in the lens. This comparison suggested new hypotheses and experiments to quantitatively assess models of circulation in the avascular lens.


Oncoplastic Breast Reduction: A Systematic Review of Postoperative Complications.
Breast-conserving therapy with oncoplastic reduction is a useful strategy for partial mastectomy defect reconstruction. The most recently published systematic review of oncoplastic breast reduction outcomes from 2015 showed wound dehiscence in 4.3%, hematoma in 0.9%, infection in 2.8%, and nipple necrosis in 0.9% of patients. We performed a systematic review of oncoplastic breast reduction literature, comparing outcomes and complication rates reported over the past 8 years. Studies describing the use of oncoplastic breast reduction and discussion of postoperative complications were included. The primary outcome assessed was the postoperative complication rate; secondary outcomes analyzed were rates of margin expansion, completion mastectomy, and delays in adjuvant therapy due to complications. Nine articles met inclusion criteria, resulting in 1715 oncoplastic breast reduction patients. The mean rate of hematoma was 3%, nipple necrosis was 2%, dehiscence was 4%, infection was 3%, and seroma was 2%. The need for re-excision of margins occurred in 8% of patients, and completion mastectomy in 2%. Finally, delay in adjuvant treatment due to a postoperative complication occurred in 4% of patients. Oncoplastic breast reduction is an excellent option for many patients undergoing breast-conserving therapy; however, postoperative complications can delay adjuvant radiation therapy. Results of this systematic literature review over the past 8 years showed a slight increase in complication rate compared to the most recent systematic review from 2015. With increased popularity and surgeon familiarity, oncoplastic breast reduction remains a viable option for reconstruction of partial mastectomy defects despite a slight increase in complication rate.


Perineal repair of pelvic fracture urethral distraction defects: experience in 120 patients during the last 10 years.
We report the long-term success of a 1-stage perineal anastomotic repair in patients with pelvic fracture urethral distraction defects. A retrospective analysis of 120 patients undergoing perineal bulboprostatic anastomotic repair of pelvic fracture urethral distraction defect in a single stage using our progressive approach between May 1991 and May 2001 was performed. Patients with posterior urethral stricture due to other etiologies, or those who underwent substitution urethroplasty or abdominoperineal repair were excluded from this review. Preoperative evaluation of the urethral defect included simultaneous retrograde urethrogram and voiding cystourethrogram. Postoperative retrograde urethrogram was performed at 3 weeks, 3 months, 12 to 18 months and as indicated thereafter. Mean patient age was 32 (range 6 to 82) years. The estimated preoperative radiographic length of the distraction defect was 3.1 cm (range 0.5 to 10). Mean followup was 64 (range 9 to 128) months, mean hospital stay was 1.8 days and duration of urethral stenting was 3.4 weeks. Perineal anastomotic repair was successful in 103 of 109 (95%) adults, in 8 of 11 (73%) prepubescent boys and in 25 of 29 (86%) undergoing secondary repairs. All treatment failures were at the anastomosis and occurred within the first postoperative year. Successful management of failed repairs was accomplished endoscopically in 3 of 7 and by repeat perineal anastomotic repair in 2 of 2, resulting in a final success rate of 97% in adults, 91% in prepubescent boys and 97% in secondary repairs. The overall success of our progressive 1-stage perineal anastomotic repair of pelvic fracture urethral distraction defect continues to be excellent with the majority of failures occurring in prepubescent boys and secondary repairs.


Screening of GABA(A)-receptor gene mutations in primary dystonia.
Several lines of evidence suggest that GABA-ergic neurotransmission plays a role in the pathogenesis of primary dystonia in humans. In this study, we tested the hypothesis that mutations in the GABRA1, GABRB3, and GABRG2 genes encoding the alpha1, beta3, and gamma subunits of the GABA(A) receptor are involved in familial primary dystonia. All exons and exon-intron boundaries of the above genes were amplified by PCR from genomic DNA in 28 patients who had primary dystonia and a positive family history but had no mutation in any other genes known to be involved in primary dystonia. The PCR products were analyzed by single strand conformation polymorphism followed by sequencing of variant conformers compared with normal controls (n = 54). We found no mutations in these genes. We did, however, find a new polymorphism, 559 + 80G>A in intron 5 of GABRA1, and we also confirmed several that were previously reported, including 315C>T in exon 3 and 588C>T in exon 5 of GABRG2, but there were no significant differences between controls and patients in the allele and genotype frequencies of these polymorphisms. In conclusion, mutations of GABRA1, GABRB3, and GABRG2 appear not to play a major role in the development of familial primary dystonia.


Operational efficiency of an immunization clinic attached to rural health training centre in delhi, India: a time and motion study.
Background. Obtaining baseline data about current patterns of work is important for assessing the effects of interventions designed to improve care delivery. Time and motion studies allow for the most accurate measurement of structured components. Therefore, the present study was conducted to study the operational efficiency of an immunization clinic in Delhi, India. Methods. An observational cross-sectional study was conducted at the immunization clinic of Rural Health Training Centre in Delhi, India, from January 2014 to March 2014. The study composed two stage evaluations, a passive observation and a time and motion study. Systemic random sampling method was used to select 863 mothers/caregivers attending the immunization clinic. Results. At the immunization clinic, the study participants spent 64.1% of their total time in waiting. For new cases, the mean time taken for initial registration and receiving postvaccination advice was found to be significantly longer than old cases. Delivering health care services took more time during Mondays and also during the first hour of the day. Conclusion. Results of this study will guide public health decision-makers at all government levels in planning and implementation of immunization programs in developing countries.


Can delta-V be adjusted with structural and occupant restraint performance to improve prediction of chest acceleration?
The purpose of this study is to investigate whether delta-V can be modified with a measure of vehicle structure performance and occupant restraint performance to better predict occupant peak chest acceleration during a frontal crash. A total of 619 full-scale frontal crash tests, with impact speeds ranging from 14 to 42 mph, were analyzed. Multiple linear regression was used to correlate combinations of crash severity, vehicle structure performance, and occupant restraint performance descriptors to the maximum measured crash test dummy chest acceleration. Using an adjusted R(2) selection method, the best combination of metrics were selected and then compared to a baseline model that used only delta-V to predict occupant chest kinematics. The combination of delta-V, ridedown efficiency, and the kinetic energy factor was found to provide the best prediction of the occupant chest acceleration. This combination accounted for approximately 4 times the variation in the maximum chest acceleration when compared to a model based solely on vehicle delta-V.


[Two cases of adult tethered cord syndrome with surgical treatment].
We report two cases of adult tethered cord syndrome alleviated by untethering surgery. Case 1 was a 35 year-old female who complained of incontinence while exercising. Radiograph revealed spinal disraphism below the L5 level. In addition, magnetic resonance imaging (MRI) showed low placed conus medullaris at the levels of S2 and sacral intradural lipoma. Further urodynamic studies demonstrated normal sphincteric function and autonomous bladder. Diagnosis resulted in the decision to perform an untethering operation. The patient had increased bladder compliance after surgery for untethering and has continued to be continent 16 months post-operatively. Case 2 was a 27-year old female who complained of apprehension to void and straining during urination. Radiograph demonstrated spinal disraphism below the S2 level and MRI revealed low placed conus medullaris at the level of S5 and sacral intradural lipoma. Urodynamic examination verified normal sphincteric function and autonomous bladder. After complete diagnosis, an untethering operation was performed. Post-operatively, bladder compliance and urinary sensation normalized. Furthermore, the patient spontaneously delivered a baby 3 years after having the untethering operation.


Formulation of magnetically perturbed time-dependent density functional theory.
A formulation of time-dependent density functional theory (TDDFT) in the presence of a static imaginary perturbation is derived. A perturbational approach is applied leading to corrections to various orders in the quantities of interest, namely, the excitation energies and transition densities. The perturbed TDDFT equations are relatively straightforward to derive but the resulting expressions are rather cumbersome. Simplifications of these equations are suggested. Both the simplified and full expressions are used to obtain equations for first- and second-order corrections to the excitation energy, the first-order correction to the transition density, and the corrections for both quantities to first-order in two different perturbations. This formulation, called magnetically perturbed TDDFT, details how conventional TDDFT calculations can be corrected to allow for the inclusion of a static magnetic field and/or spin-orbit coupling.


Ethnopharmacological approaches in mood and anxiety disorders. The relevance of the oxidative stress status.
Neurodegenerative diseases and psychiatric disorders are one of the most important pathologies that lead to increased morbidity in populations. Both mood and anxiety disorders include mental disorders not caused by detectable organic abnormalities of the brain. At the molecular level, affective spectrum symptomatology is due to neurotransmitter dysregulation including receptor or transporter impairments and also due to faulty intracellular signaling that generally leads to impaired neurotransmission. Also, recent studies have shown the relationship between oxidative stress and the development of affective disorders. Since classical medication can cause major side effects and alternative approaches tend to be more and more trusted, it seems that plant extracts-based complementary therapies may offer superior yielding and safety compared to traditional medication.


Physiological girdling of pine trees via phloem chilling: proof of concept.
Quantifying below-ground carbon (C) allocation is particularly difficult as methods usually disturb the root-mycorrhizal-soil continuum. We reduced C allocation below ground of loblolly pine trees by: (1) physically girdling trees and (2) physiologically girdling pine trees by chilling the phloem. Chilling reduced cambium temperatures by approximately 18 degrees C. Both methods rapidly reduced soil CO2 efflux, and after approximately 10 days decreased net photosynthesis (P(n)), the latter indicating feedback inhibition. Chilling decreased soil-soluble C, indicating that decreased soil CO2 efflux may have been mediated by a decrease in root C exudation that was rapidly respired by microbes. These effects were only observed in late summer/early autumn when above-ground growth was minimal, and not in the spring when above-ground growth was rapid. All of the effects were rapidly reversed when chilling was ceased. In fertilized plots, both chilling and physical girdling methods reduced soil CO2 efflux by approximately 8%. Physical girdling reduced soil CO2 efflux by 26% in non-fertilized plots. This work demonstrates that phloem chilling provides a non-destructive alternative to reducing the movement of recent photosynthate below the point of chilling to estimate C allocation below ground on large trees.


Synthesis and structure of amido- and imido(pentafluorophenyl)borane zirconocene and hafnocene complexes: N-H and B-H activation.
Treatment of Me(2)S·B(C(6)F(5))(n) H(3-n) (n=1 or 2) with ammonia yields the corresponding adducts. H(3)N·B(C(6)F(5))H(2) dimerises in the solid state through N-H···H-B dihydrogen interactions. The adducts can be deprotonated to give lithium amidoboranes Li[NH(2)B(C(6)F(5))(n)H(3-n)]. Reaction of the n=2 reagent with [Cp(2)ZrCl(2)] leads to disubstitution, but [Cp(2)Zr{NH(2)B(C(6)F(5))(2)H}(2)] is in equilibrium with the product of β-hydride elimination [Cp(2)Zr(H){NH(2)B(C(6)F(5))(2)H}], which proves to be the major isolated solid. The analogous reaction with [Cp(2)HfCl(2)] gives a mixture of [Cp(2)Hf{NH(2)B(C(6)F(5))(2)H}(2)] and the N-H activation product [Cp(2)Hf{NHB(C(6)F(5 )(2)H}]. [Cp(2)Zr{NH(2)B(C(6)F(5))(2)H}(2)]·PhMe and [Cp(2)Hf{NH(2)B(C(6)F(5))(2)H}(2)]·4(thf) exhibit β-B-agostic chelate bonding of one of the two amidoborane ligands in the solid state. The agostic hydride is invariably coordinated to the outside of the metallocene wedge. Exceptionally, [Cp(2)Hf{NH(2)B(C(6)F(5))(2)H}(2)]⋅PhMe has a structure in which the two amidoborane ligands adopt an intermediate coordination mode, in which neither is definitively agostic. [Cp(2)Hf{NHB(C(6)F(5))(2)H}] has a formally dianionic imidoborane ligand chelating through an agostic interaction, but the bond-length distribution suggests a contribution from a zwitterionic amidoborane resonance structure. Treatment of the zwitterions [Cp(2)MMe(μ-Me)B(C(6)F(5))(3)] (M=Zr, Hf) with Li[NH(2)B(C(6)F(5))(n)H(3-n)] (n=2) results in [Cp(2) MMe{NH(2)B(C(6)F(5))(2)H}] complexes, for which the spectroscopic data, particularly (1)J(B,H), again suggest β-B-agostic interactions. The reactions proceed similarly for the structurally encumbered [Cp''(2)ZrMe(μ-Me)B(C(6)F(5))(3)] precursor (Cp''=1,3-C(5)H(3)(SiMe(3))(2) , n=1 or 2) to give [Cp''(2)ZrMe{NH(2)B(C(6)F(5))(n)H(3-n)}], both of which have been structurally characterised and show chelating, agostic amidoborane coordination. In contrast, the analogous hafnium chemistry leads to the recovery of [Cp''(2)HfMe(2)] and the formation of Li[HB(C(6)F(5))(3)] through hydride abstraction.


Recruitment and Retention for Community-Based eHealth Interventions with Populations of Low Socioeconomic Position: Strategies and Challenges.
Given persistent communication inequalities, it is important to develop interventions to improve Internet and health literacy among underserved populations. These goals drove the Click to Connect (C2C) project, a community-based eHealth intervention that provided novice computer users of low socioeconomic position (SEP) with broadband Internet access, training classes, a Web portal, and technical support. In this paper, we describe the strategies used to recruit and retain this population, the budgetary implications of such strategies, and the challenges and successes we encountered. Results suggest that personal contact between study staff and participants and provision of in-depth technical support were central to successful recruitment and retention. Such investments are essential to realize the promise of eHealth with underserved populations.


Scoring single-nucleotide polymorphisms at the single-molecule level by counting individual DNA cleavage events on surfaces.
Single-nucleotide polymorphisms (SNPs) are the most frequent type of human genetic variation. Recent work has shown that it is possible to directly analyze SNPs in unamplified human genomic DNA samples using the surface-invasive cleavage reaction followed by rolling circle amplification (RCA) of the cleavage products. The ability of RCA to produce single-stranded DNA tens of thousands of nucleotides in length from a single cleaved DNA molecule on the surface suggested the possibility of detecting individual cleavage events on the surface. The feasibility of this approach to SNP scoring is shown here. Individual cleavage events on the surface are detected using fluorescence microscopy to visualize the single-stranded DNA product of the RCA reaction labeled with the fluorescent dye SYBR Green I. The surface density of fluorescent features observed is dependent upon the concentration of target DNA. Future reductions of the sample volume and optimization of the reaction conditions offer the potential of being able to perform such analyses on as little as a single copy of genomic DNA target.


[Comparative double-blind study of cefroxadine and cephalexin in the treatment of complicated urinary tract infection].
To evaluate the efficacy, safety, and utility of cefroxadine (CXD) for the treatment of complicated urinary tract infections, a double blind study comparing CXD with cephalexin (CEX) was carried out. Patient received either 1,500 mg/day of CXD 3 times a day, or 2,000 mg/day of CEX 4 times a day for 5 days by oral route, and the following results were obtained. Of the 305 patients, clinical efficacies were evaluated in 220 cases (CXD 105 cases, CEX 115 cases) except that excluded or dropped out. Side effect was evaluated in 301 cases (CXD 150 cases, CEX 151 cases). There was no statistically significant difference in the back ground characteristics between the 2 groups. Overall clinical assessment by the committee according to the "Criteria for Evaluation of Clinical Efficacy of Antimicrobial Agents on Urinary Tract Infection" patients evaluated as better than "good" were 64 of 105 (61.0%) for CXD and 75 of 115 (65.2%) for CEX. The difference between the 2 groups was not statistically significant. In effect on pyuria, patients evaluated as better than "decreased" were 58 of 105 (55.2%) for CXD and 69 of 115 (60.0%) for CEX. The difference between the 2 groups was not statistically significant. In effect of bacteriuria, patients evaluated as better than "decreased" were 57 of 105 (54.3%) for CXD and 69 of 115 (60.0%) for CEX. The difference between the 2 groups was not statistically significant. Analyses were stratified according to classification by the type of infection, diagnosis, degree of pyuria before treatment, and bacterial count before treatment. There were no statistically significant differences between the 2 treatment groups as to any item. In evaluation by attending physician, patients evaluated as better than "good" were 81 of 140 (57.9%) for CXD, and 85 of 141 (60.3%) for CEX. Statistically significant difference was not observed between the 2 groups. In drug usefulness by attending physician, patients evaluated as better than "usefulness" were 106 of 140 (75.7%) for CXD, and 109 of 141 (77.3%) for CEX. The difference between the 2 groups was not statistically significant. In evaluation of the infections with sensitive species to both CXD and CEX by the committee according to "Criteria for Evaluation of Clinical Efficacy of Antimicrobial Agents on Urinary Tract Infections, overall clinical efficacies were evaluated in 102 (CXD 48 cases, CEX 54 cases) which were infected with sensitive species. There was no statistically significant difference in the back ground characteristics between the 2 treatment groups.(ABSTRACT TRUNCATED AT 400 WORDS)


Reducing the Primary Cesarean Birth Rate: A Quality Improvement Project.
Research continues to support vaginal birth as the safest mode of childbirth, but despite this, cesarean birth has become the most common surgical procedure performed on women. The rate has increased 500% since the 1970s without a corresponding improvement in maternal or neonatal outcomes. A Colorado community hospital recognized that its primary cesarean birth rate was higher than national and state benchmark levels. To reduce this rate, the hospital collaborated with its largest maternity care provider group to implement a select number of physiologic birth practices and measure improvement in outcomes. Using a pre- and postprocess measure study design, the quality improvement project team identified and implemented 3 physiologic birth parameters over a 12-month period that have been shown to promote vaginal birth. These included reducing elective induction of labor in women less than 41 weeks' gestation; standardizing triage to admit women at greater than or equal to 4 cm dilation; and increasing the use of intermittent auscultation as opposed to continuous fetal monitoring for fetal surveillance. The team also calculated each obstetrician-gynecologist's primary cesarean birth rate monthly and delivered these rates to the providers. Outcomes showed that the provider group decreased its primary cesarean birth rate from 28.9% to 12.2% in the 12-month postprocess measure period. The 57.8% decrease is statistically significant (odds ratio [OR], 0.345; z = 6.52, P < .001; 95% confidence interval [CI], 0.249-0.479). While this quality improvement project cannot be translated to other settings, promotion of physiologic birth practices, along with audit and feedback, had a statistically significant impact on the primary cesarean birth rate for this provider group and, consequently, on the community hospital where they attend births.


Minireview: regulation of epithelial Na+ channel trafficking.
The epithelial Na(+) channel (ENaC) is a pathway for Na(+) transport across epithelia, including the kidney collecting duct, lung, and distal colon. ENaC is critical for Na(+) homeostasis and blood pressure control; defects in ENaC function and regulation are responsible for inherited forms of hypertension and hypotension and may contribute to the pathogenesis of cystic fibrosis and other lung diseases. An emerging theme is that epithelial Na(+) transport is regulated in large part through trafficking mechanisms that control ENaC expression at the cell surface. ENaC trafficking is regulated at multiple steps. Delivery of channels to the cell surface is regulated by aldosterone (and corticosteroids) and vasopressin, which increase ENaC synthesis and exocytosis, respectively. Conversely, endocytosis and degradation is controlled by a sequence located in the C terminus of alpha, beta, and gammaENaC (PPPXYXXL). This sequence functions as an endocytosis motif and as a binding site for Nedd4-2, an E3 ubiquitin protein ligase that targets ENaC for degradation. Mutations that delete or disrupt this motif cause accumulation of channels at the cell surface, resulting in Liddle's syndrome, an inherited form of hypertension. Nedd4-2 is a central convergence point for ENaC regulation by aldosterone and vasopressin; both induce phosphorylation of a common set of three Nedd4-2 residues, which blocks Nedd4-2 binding to ENaC. Thus, aldosterone and vasopressin regulate epithelial Na(+) transport in part by altering ENaC trafficking to and from the cell surface.


Clinical evaluation of a new digitizing device for improved film mammography.
The study was designed to evaluate a new digitizing device, the iView (Maxxvision, LLC, Gainesville, FL), which aims to replace the magnifying glass in mammography with real-time film digitization, display, and processing. A receiver operating characteristic (ROC) experiment was performed with 5 certified mammographers and 114 mammograms that were read with and without the iView. A satisfaction survey was also conducted on the system's features and usefulness. Data analysis suggested that (1) Cancer sensitivity could improve with the use of the iView system. ROC area differences showed improvements from 2% to 24% although these were not always statistically significant. At a false positive rate of 0.2, the true positive rate increased up to 60% depending on the set of cases and the observer's experience. (2) Specificity could also be improved. At a true positive rate of 0.9, the false positive rate decreased by as much as 55%. (3) Most observers felt more confident in their decisions when using the iView, although the prototype's ergonomic problems did not allow full utilization of its capabilities. Our pilot clinical study showed that the iView has the potential to improve mammogram interpretation. In addition, the system could broaden the applicability of electronic information and provide wider access to digital technology through a relatively simple and cost-effective approach. Observers recommended several improvements in the ergonomics and default display of the system that are currently implemented by the company. A larger clinical study of the improved system is necessary to clearly demonstrate its clinical value for mammography.


A Rare Presentation of Tuberculosis in Transplanted Kidney on Fluorodeoxyglucose Positron Emission Tomography with Computed Tomography Scan.
Tuberculosis (TB) is currently the world's leading cause of infectious mortality. Infective complications are common after renal transplantation. TB is one of the leading infections following renal transplantation; however, TB affecting the transplanted kidney is a rare presentation. Reactivation of the Mycobacterium tuberculosis is the most common mode of infection. The use of immunosuppressive agents such as cyclosporin, azathioprine, and steroids advance the onset of TB to an earlier date which most often presents as a fever or pyrexia of unknown origin (PUO). The use of 18F-fluorodeoxyglucose positron emission tomography with computed tomography (18F-FDG-PET/CT) scan images of the whole body and provides the metabolic map of the infection as well as also helps in its radiological localization and characterization and selecting the most appropriate site of the biopsy. Currently, the combined FDG-PET/CT scan modality is the investigation of the choice of physicians for the diagnosis of PUO. Not only the diagnosis but 18F-FDG-PET/CT is also very valuable in assessing early disease response to therapy, and plays an important role in cases where conventional microbiological methods are unavailable for monitoring response to the therapy in cases of pulmonary, extrapulmonary, or multidrug resistant TB.


Acute changes in the pacing threshold after lead implantation. Comparison between retractable and sweet-tip active-fixation leads.
Although the pacing threshold of steroid-eluting active-fixation leads remains stable over the long term, it changes rapidly after screw-in. We compared the pacing threshold in the acute phase between retractable and Sweet-Tip active-fixation leads. We studied 132 patients who were implanted with active-fixation leads for new pacemaker implantation or additional leads required due to disconnected/leaking leads. Pacing threshold was measured at 4 time points: before screw-in, immediately, and 5 and 10 minutes after screw-in. If the pacing threshold was > 1.5 volts (V) at 5 minutes, we changed the pacing site so that it became ≤ 1.5 V. A total of 169 retractable leads (Medtronic: 107 leads, St. Jude Medical: 62 leads) and 33 Sweet-Tip leads (Boston: 33 leads) were implanted. Eighty-nine leads were implanted in the atrium and 113 leads in the ventricle. Seventy patients were implanted with both atrial and ventricular leads. The pacing threshold of Sweet-Tip leads increased immediately after screw-in, while that of retractable leads decreased (Sweet-Tip: 0.20 ± 0.57 V, Retractable: -0.15 ± 0.53 V, P < 0.05). The pacing threshold of both types of leads decreased similarly from immediately to 5 minutes after screw-in (Sweet Tip: -0.29 ± 0.43 V, Retractable: -0.25 ± 0.36 V, P = NS). Few changes in the threshold were detected between 5 and 10 minutes. Because the pacing threshold of Sweet-Tip active-fixation leads increased immediately after screw-in and that of both type leads decreased from immediately to 5 minutes, we should measure the pacing threshold from 5 minutes after screw-in.


Fibroblast growth factor-10 prevents H2O2-induced cell cycle arrest by regulation of G1 cyclins and cyclin dependent kinases.
We studied the effects of fibroblast growth factor (FGF-10) on H2O2-induced alveolar epithelial cell (AEC) G1 arrest and the role of G1 cyclins. FGF-10 prevented H2O2-induced AEC G1 arrest. FGF-10 induced 2-4-fold increase in cyclin E, cyclin A and CDKs (2,4) alone and in AEC treated with H2O2. H2O2 downregulated cyclin D1; FGF-10 blocked these effects. FGF-10 prevented H2O2-induced upregulation of CDK inhibitor, p21. SiRNAp21 blocked H2O2-induced downregulation of cyclins, CDKs and AEC G1 arrest. Accordingly, we provide first evidence that FGF-10 regulates G1 cyclins and CDKs, and prevents H2O2-induced AEC G1 arrest.


The Effects of Quercetin Supplementation on Eccentric Exercise-Induced Muscle Damage.
The aim of the present investigation was to test the hypothesis that quercetin (Q) may prevent the strength loss and neuromuscular impairment associated with eccentric exercise-induced muscle damage (EEIMD). Twelve young men (26.1 ± 3.1 years) ingested either Q (1000 mg/day) or placebo (PLA) for 14 days using a randomized, double-blind, crossover study design. Participants completed a comprehensive neuromuscular (NM) evaluation before, during and after an eccentric protocol able to induce a severe muscle damage (10 sets of 10 maximal lengthening contractions). The NM evaluation comprised maximal voluntary isometric contraction (MVIC) and force⁻velocity relationship assessments with simultaneous recording of electromyographic signals (EMG) from the elbow flexor muscles. Soreness, resting arm angle, arm circumference, plasma creatine kinase (CK) and lactate dehydrogenase (LDH) were also assessed. Q supplementation significantly increased the isometric strength recorded during MVIC compared to baseline (+4.7%, p < 0.05). Moreover, the torque and muscle fiber conduction velocity (MFCV) decay recorded during the eccentric exercise was significant lower in Q compared to PLA. Immediately after the EEIMD, isometric strength, the force⁻velocity relationship and MFCV were significantly lower when participants were given PLA rather than Q. Fourteen days of Q supplementation seems able to attenuate the severity of muscle weakness caused by eccentric-induced myofibrillar disruption and sarcolemmal action potential propagation impairment.


MicroRNA PC-3p-2869 Regulates Antler Growth and Inhibits Proliferation and Migration of Human Osteosarcoma and Chondrosarcoma Cells by Targeting CDK8, EEF1A1, and NTN1.
MicroRNAs (miRNAs) play a crucial role in maintaining the balance between the rapid growth and suppression of tumorigenesis during antler regeneration. This study investigated the role of a novel miRNA, PC-3p-2869 (miR-PC-2869), in antler growth and its therapeutic potential in human osteosarcoma and chondrosarcoma. Stem-loop RT-qPCR showed that miR-PC-2869 was expressed extensively in diverse layers of antler tissues. Overexpression of miR-PC-2869 suppressed the proliferation and migration of antler cartilage cells. Similarly, heterologous expression of miR-PC-2869 reduced the proliferation, colony formation, and migration of osteosarcoma cell line MG63 and U2OS and chondrosarcoma cell line SW1353. Moreover, 18 functional target genes of miR-PC-2869 in humans were identified based on the screening of the reporter library. Among them, 15 target genes, including CDK8, EEF1A1, and NTN1, possess conserved miR-PC-2869-binding sites between humans and red deer (Cervus elaphus). In line with this, miR-PC-2869 overexpression decreased the expression levels of CDK8, EEF1A1, and NTN1 in MG63, SW1353, and antler cartilage cells. As expected, the knockdown of CDK8, EEF1A1, or NTN1 inhibited the proliferation and migration of MG63, SW1353, and antler cartilage cells, demonstrating similar suppressive effects as miR-PC-2869 overexpression. Furthermore, we observed that CDK8, EEF1A1, and NTN1 mediated the regulation of c-myc and cyclin D1 by miR-PC-2869 in MG63, SW1353, and antler cartilage cells. Overall, our work uncovered the cellular functions and underlying molecular mechanism of antler-derived miR-PC-2869, highlighting its potential as a therapeutic candidate for bone cancer.


The burden of paediatric intensive care: a South American perspective.
Paediatric intensive care is a relatively new medical specialty that has shown a marked growing up around the world over the last three decades. The limits and the development of this new specialty are not uniform from country to country. Original articles relating to paediatric intensive care and some South American data bases of health care were evaluated and relevant results were selected. Using these data, we describe the main characteristics of paediatric intensive care in South America and discuss some associated factors (e.g. economic aspects, health systems, ethical aspects) that could interfere with the quality and extent of care. A strong relationship between the financial stability of each region and the complexity and quality of paediatric intensive care was seen. A better coverage and more sophisticated paediatric intensive care units (PICUs) are concentrated in the more developed countries (Brazil, Chile and Argentina). Compared to the northern hemisphere, children admitted to the South American PICUs have higher mortality and higher rates of intervention (mechanical ventilation and indwelling catheters). Medical paternalism has a strong influence in the decision-making process offered to terminally ill patients. This phenomenon increases the length of stay, reduces the number of available beds and increases costs. In conclusion, during the last 20 years PICUs have developed and increased their coverage in South America. However, the most sophisticated and well equipped PICUs are preferentially located in the more developed areas whereas those areas with higher infant mortality rates have few PICU beds. Improvements in the economical stability, regional health organisation as well as the rationale for PICU localisation are some of the important goals to be reached in the near future.


Anti-gamma-aminobutyric acid receptor type A encephalitis: a review.
To systematically review the clinical features, diagnosis, and management of anti-gamma-aminobutyric acid receptor Type A (GABAA) autoimmune encephalitis with a focus on recent data. In a review of published reports, we identified 50 cases of anti-GABAA receptor encephalitis with clinical features reported. The median age at presentation was 47 years old (range, 2.5 months-88 years old), 64% were adults, 36% were children and it occurred in both males and females. Eight-two percent (41/50) presented with seizures, 72% (36/50) with encephalopathy, and 58% (29/50) with both. Of those presenting with seizures, 42% developed status epilepticus during their disease course. Ninety-six percent (48/50) had MRI results reported, with 83% of these cases having abnormal findings, most commonly multifocal/diffuse cortical and subcortical T2/FLAIR hyperintense lesions without associated gadolinium enhancement. Almost one-third, 28% (14/50), had an associated malignancy detected by the time of diagnosis, 64% (9/14) of which was thymoma. Of 44 patients with outcomes reported, 80% had partial or complete recovery, whereas 20% had poor outcomes including 11% (5/44) who died. Of the 42 patients with type of treatment(s) and outcomes reported, 54% (23/42) received only first-line immunotherapy and 31% (13/42) received first-line and second-line immunotherapy. Receiving a combination of first-line and second-line immunotherapy may be associated with higher likelihood of complete recovery. When follow-up MRIs were reported, all showed improvement, and sometimes complete resolution, of T2/FLAIR hyperintensities. Anti-GABAA receptor encephalitis can present across the age spectrum and should be considered in patients who present with rapidly progressive encephalopathy and/or seizures. Brain MRI often shows a distinctive pattern of multifocal cortical and subcortical T2/FLAIR hyperintense lesions, generally not typical of other known central nervous system autoantibody associated encephalitis syndromes. High clinical suspicion and early diagnosis are important given the potential for clinical improvement with immunotherapy.


Thermodynamics of electron flow in the bacterial deca-heme cytochrome MtrF.
Electron-transporting multi-heme cytochromes are essential to the metabolism of microbes that inhabit soils and carry out important biogeochemical processes. Recently the first crystal structure of a prototype bacterial deca-heme cytochrome (MtrF) has been resolved and its electrochemistry characterized. However, the molecular details of electron transport along heme chains in the cytochrome are difficult to access via experiment due to the nearly identical chemical nature of the heme cofactors. Here we employ large-scale molecular dynamics simulations to compute the redox potentials of the 10 hemes of MtrF in aqueous solution. We find that as a whole they fall within a range of ~0.3 V, in agreement with experiment. Individual redox potentials give rise to a free energy profile for electron transport that is approximately symmetric with respect to the center of the protein. Our calculations indicate that there is no significant potential bias along the orthogonal octa- and tetra-heme chains, suggesting that under aqueous conditions MtrF is a nearly reversible two-dimensional conductor.


Dentritic CuPtPd Catalyst for Enhanced Electrochemical Oxidation of Methanol.
The CuPtPd catalyst is designed and synthesized successfully via directly reducing metal ions. The composition, morphology, and structure of the as-prepared CuPtPd nanohybrids are characterized by scanning electron microscopy and transmission electron microscopy, energy-dispersive spectrometry, selected-area electron diffraction, X-ray diffraction, and inductively coupled plasma atomic emission spectrometry. By comparison of the electrocatalytic properties of the ternary CuPtPd catalyst with bimetallic catalysts, we find that ternary nanocomposites perform better electrocatalytic and antipoisoning activity toward oxidation of methanol. The catalytic mass activity of the CuPtPd nanoparticles is 5.51-fold of commercial Pd black and 12.1-fold of Pt black.


H2O2 augments cytosolic calcium in nucleus tractus solitarii neurons via multiple voltage-gated calcium channels.
Reactive oxygen species (ROS) play a profound role in cardiorespiratory function under normal physiological conditions and disease states. ROS can influence neuronal activity by altering various ion channels and transporters. Within the nucleus tractus solitarii (nTS), a vital brainstem area for cardiorespiratory control, hydrogen peroxide (H2O2) induces sustained hyperexcitability following an initial depression of neuronal activity. The mechanism(s) associated with the delayed hyperexcitability are unknown. Here we evaluate the effect(s) of H2O2 on cytosolic Ca2+ (via fura-2 imaging) and voltage-dependent calcium currents in dissociated rat nTS neurons. H2O2 perfusion (200 µM; 1 min) induced a delayed, slow, and moderate increase (~27%) in intracellular Ca2+ concentration ([Ca2+]i). The H2O2-mediated increase in [Ca2+]i prevailed during thapsigargin, excluding the endoplasmic reticulum as a Ca2+ source. The effect, however, was abolished by removal of extracellular Ca2+ or the addition of cadmium to the bath solution, suggesting voltage-gated Ca2+ channels (VGCCs) as targets for H2O2 modulation. Recording of the total voltage-dependent Ca2+ current confirmed H2O2 enhanced Ca2+ entry. Blocking VGCC L, N, and P/Q subtypes decreased the number of cells and their calcium currents that respond to H2O2 The number of responder cells to H2O2 also decreased in the presence of dithiothreitol, suggesting the actions of H2O2 were dependent on sulfhydryl oxidation. In summary, here, we have shown that H2O2 increases [Ca2+]i and its Ca2+ currents, which is dependent on multiple VGCCs likely by oxidation of sulfhydryl groups. These processes presumably contribute to the previously observed delayed hyperexcitability of nTS neurons in in vitro brainstem slices.


Biopsychosocial Predictors of Depression and Anxiety Symptoms among First-Generation Black African Immigrants.
Few studies examine factors associated with mental health distress among immigrants from African countries. Using cross-sectional data from first-generation Black African immigrants across the United States (N = 180), this study examined biopsychosocial factors that influence depression and anxiety symptoms among African immigrants in the United States. Ordinary least squares regression was conducted to analyze the data. Approximately 22 percent of the sample reported depression and anxiety symptoms in the moderate to severe range. Results indicated that being male, substance use, discrimination, and loneliness were significantly associated with worse depression and anxiety symptoms. In addition, worries about safety and financial strain were associated with increased mental health distress. Loneliness also moderated the association between discrimination and depression and anxiety symptoms. Findings imply that relational interventions in direct practice settings may play a critical role in helping African immigrants ameliorate depression and anxiety symptoms. This study supports the use of the biopsychosocial approach in assessment and intervention of mental health symptoms as well as a systems approach when understanding the experiences of African immigrants.


Osmotic and electroosmotic fluid transport across the retinal pigment epithelium: A mathematical model.
The retinal pigment epithelium (RPE) is the outermost cell layer of the retina. It has several important physiological functions, among which is removal of excess fluid from the sub-retinal space by pumping it isotonically towards the choroid. Failure of this pumping leads to fluid accumulation, which is closely associated with several pathological conditions, such as age-related macular degeneration, macular oedema and retinal detachment. In the present work we study mechanisms responsible for fluid transport across the RPE with the aim of understanding how fluid accumulation can be prevented. We focus on two possible mechanisms, osmosis and electroosmosis, and develop a spatially resolved mathematical model that couples fluid and ion transport across the epithelium, accounting for the presence of Na+,K+ and Cl- ions. Our model predicts spatial variability of ion concentrations and the electrical potential along the cleft gap between two adjacent cells, which osmotically drives the flow across the lateral membranes. This flow is directed from the sub-retinal space to the choroid and has a magnitude close to measured values. Electroosmosis is subdominant by three orders of magnitude to osmosis and has an opposite direction, suggesting that local osmosis is the main driving mechanism for water transport across the RPE.


A Utstein-style analysis of prognostic factors related to survival in out-of-hospital cardiac arrests in Akita-City, Japan.
To analyze the epidemiology of out-of-hospital cardiac arrests and to elucidate modifiable factors affecting survival, we conducted a prospective cohort study in a middle-sized urban city served by a single emergency medical service (EMS) system in which emergency medical technicians use an automated external defibrillator. Data were collected from out-of-hospital cardiac arrests occurring between 1 January, 1994 and 31 December, 1998 by applying the Utstein style. The main outcome measure was survival at 1 year after hospital discharge. The overall incidence of out-of-hospital cardiac arrest was 71.7/100 000 inhabitants/year. Resuscitations were attempted in 762 of 1118 patients with confirmed cardiac arrest. Of the 762 patients, 37 (4.86%) survived. The cause of cardiac arrest was presumed to be cardiac in 340 (44.6%). Of the 340 cardiac arrests, 180 (52.9%) were witnessed by bystanders. Ventricular fibrillation (VF) was recorded as an initial rhythm in 56 (31.1%) of the 180 patients, and cardiopulmonary resuscitation (CPR) was performed by bystanders in 89 (49.4%). The survival rate was 39.2% (22/56) when cardiac arrest was bystander-witnessed and of cardiac origin with VF as an initial rhythm. VF as an initial rhythm, age of the patients and intervals of call-to-first CPR attempt and collapse-to-arrival at patient's side were major factors relating to survival in the witnessed cardiac arrests of cardiac origin. The age, and gender of the patients, place of collapse and intervals of collapse-to-first CPR and collapse-to-arrival at patient's side were representative factors affecting the incidence of VF as an initial rhythm. The survival rate in Akita-City from bystander-witnessed cardiac arrests of cardiac origin with VF as an initial rhythm was comparable to those in other regions with advanced EMS systems. However, the incidence of VF as an initial rhythm is extremely low. Reduction of intervals of call (collapse)-to-first CPR attempt and collapse-to-arrival at patient's side or authorization of use of automated external defibrillator in basic life support may increase the incidence of VF as an initial rhythm and improve the survival from witnessed cardiac arrests with cardiac origin.


Lymphocyte positions in the dome epithelium of the rabbit appendix.
The apico-basal distribution of lymphocytes within the epithelium covering the domes of lymphatic tissue in the wall of the rabbit appendix was investigated in single and serial sections stained either for general histology, for cytoplasmic basophilia and acidophilia, or for nonspecific esterase activity. From the base to the summit of a dome, four zones numbered proximo-distally 1-4 were distinguished. Epithelial cells migrate from base to summit, as indicated by mitotic figures in zone 1, the gradual change from cytoplasmic basophilia to acidophilia in zones 2 to 4, and visible extrusion of cells from zone 4 at the summit. Zone 1 was free of lymphocytes. Most of the lymphocytes in zone 2 were intercellular and randomly arranged, but a few in this zone were within tapered epithelial cells modified by a process extending basally to the basement membrane. Small numbers of these tapered epithelial cells also occurred in zone 3. The large clusters of ten to 12 lymphocytes that characterized zone 3 were intercellular and impinged the apical regions of epithelial cells. Serial sections at the level of the distal cluster of zone 3 showed lymphocytes located also more basally, and some of these lymphocytes appeared to be passing through the basement membrane back into the lymphoid tissue of the dome. Epithelium of zone 4 over the distal surface of a dome was largely free of lymphocytes. Apparently most infiltrating lymphocytes form intercellular clusters and then return to the subepithelial lymphatic tissue.


CORRELATION OF MANOMETRIC, OESOPHAGOSCOPIC, AND RADIOLOGICAL FINDINGS IN THE COLUMNAR-LINED GULLET (BARRETT SYNDROME).
An intensive study has been made of the columnar-lined gullet (Barrett syndrome) and in the patient described it was shown to have the motor characteristics of the body of the oesophagus. At the distal end there was the normal receptive relaxation with swallowing. There was no discontinuity between the squamous and the columnar-lined portions.


Detection of Chlamydia pneumoniae in liver transplant patients with chronic allograft rejection.
Chlamydia pneumoniae is one of the possible pathogenetic factors of atherosclerotic processes. Foam cell arteriopathy is a generally accepted pathologic feature of chronic liver allograft rejection and has several similarities to the early lesions of atherosclerosis. The aim of the authors' study was to show any existing correlation between the occurrence of Chlamydia pneumoniae and the presence of foam cell arteriopathy in transplanted livers with chronic rejection. Ten liver samples from patients with chronic liver rejection including foam cell arteriopathy and 10 liver samples from healthy individuals were analyzed for the presence of Chlamydia pneumoniae by specific immunohistochemistry and polymerase chain reaction (PCR). Liver samples from two transplant patients with chronic liver rejection without any evidence of foam cell arteriopathy and nine patients with acute liver allograft rejection were also investigated by PCR. In all 10 rejected liver samples, Chlamydia pneumoniae was detected by PCR, whereas only one of the healthy control samples and one of the samples with acute rejection were found to be positive. Immunohistochemistry showed similar results. The positive signals of Chlamydia pneumoniae were localized mainly in the hepatocytes, sinusoidal and perisinusoidal cells, and the cells of portal tracts, whereas most of the altered hepatic arteries showed no or very weak positivity. The results strongly suggest an association between the occurrence of Chlamydia pneumoniae and the presence of foam cell arteriopathy in transplanted livers.


Efficacy of carbosilane dendrimers with an antiretroviral combination against HIV-1 in the presence of semen-derived enhancer of viral infection.
Amyloid fibrils, which are present in semen, were considered to be a cause of topical vaginal gel ineffectiveness in vivo after microbicides failed as HIV-1 prophylaxis. Therefore, it was necessary to determine whether a dendrimer was suitable for further evaluation in an in vitro model of semen-enhanced viral infection (SEVI). We demonstrated that SEVI in TZM.bl cell cultures increased the infectivity of R5-HIV-1NL(AD8), pTHRO.c and pCH058.c isolates, causing higher IC50 values for two polyanionic carbosilane dendrimers, G2-STE16 and G3-S16. However, both dendrimers maintained protection rates of 90% at non-toxic concentrations. When dendrimers were combined with Tenofovir/Maraviroc (TDF/MVC), the anti-HIV-1 effect remained at a minimum IC50 increase between 1- and 7-fold in the presence of amyloid fibrils. In peripheral blood mononuclear cells (PBMC), IC50 values were slightly influenced by the presence of semen. In brief, dendrimers combined with antiretrovirals showed a synergistic effect. This result plays a crucial role in new microbicide formulations, as it overcomes the negative effects of amyloid fibrils.


[Salbutamol intoxication].
A 20-year-old asthmatic woman who ingested 300 mg of salbutamol (Albuterol) and 30 g of paracetamol is presented. She had sinus tachycardia up to 160/min, hypotension (80/50 mmHg), tremor, hypokalemia (2.1 mEq/l) and hyperglycemia (12.1 mEq/l). Treatment was by gastric lavage, fluids, potassium and N-acetylcysteine. Symptoms resolved in 24 hours.


Measurements of temperature distribution of flames by moire deflectometry.
Mapping of temperature of a premixed hydrogen-oxygen flame by moire deflectometry is demonstrated. The technique is based on deflection mapping of rays from a collimated light beam due to gradients of the refractive index across the flame. For an axially symmetric flame the radial distribution of the refractive index was derived by Abel transformation. The temperature profile of the flame was calculated for a known gas composition assuming ideal gas behavior.


Gender may be related to the side of the motor syndrome and cognition in idiopathic Parkinson's disease.
and Sex and cognitive profile may be related to the laterality of motor symptoms in idiopathic Parkinson's disease. Parkinson's disease (PD) is well recognised as an inherently asymmetric disease with unilateral onset of motor symptoms. The laterality of motor symptoms may be linked to sex, clinical and demographic variables, and neuropsychological disorders. However, the available data are inconsistent. This study aimed to explore the potential association between the laterality of motor symptoms and clinical and demographic variables and deficits in specific cognitive domains. We retrospectively recruited 97 participants with idiopathic PD without dementia; 60 presented motor symptoms on the left side and 37 on the right side. Both groups were comparable in terms of age, age at disease onset, disease duration, and severity of the neurological deficits according to the Unified Parkinson's Disease Rating Scale and the Hoehn and Yahr scale. Participants with left-side motor symptoms scored lower on the Schwab and England Activities of Daily Living scale. Our sample included more men than women (67% vs. 33%). Both sexes were not equally represented in the 2 groups: there were significantly more men than women in the group of patients with left-side motor symptoms (77% vs. 23%), whereas the percentages of men and women in the group of patients with right-side motor symptoms were similar (51% vs. 49%). Both groups performed similarly in all neuropsychological tasks, but women, independently of laterality, performed better than men in the naming task. We found a clear prevalence of men in the group of patients with left-side motor symptoms; this group also scored lower on the Schwab and England Scale. Female sex was predictive of better performance in the naming task. Sex should always be considered in disorders that cause asymmetric involvement of the brain, such as PD.