ROS-related mitochondrial dysfunction in skeletal muscle of an ALS mouse model during the disease progression.
In amyotrophic lateral sclerosis (ALS), mitochondrial dysfunction and oxidative stress form a vicious cycle that promotes neurodegeneration and muscle wasting. To quantify the disease-stage-dependent changes of mitochondrial function and their relationship to the generation of reactive oxygen species (ROS), we generated double transgenic mice (G93A/cpYFP) that carry human ALS mutation SOD1G93A and mt-cpYFP transgenes, in which mt-cpYFP detects dynamic changes of ROS-related mitoflash events at individual mitochondria level. Compared with wild type mice, mitoflash activity in the SOD1G93A (G93A) mouse muscle showed an increased flashing frequency prior to the onset of ALS symptom (at the age of 2 months), whereas the onset of ALS symptoms (at the age of 4 months) is associated with drastic changes in the kinetics property of mitoflash signal with prolonged full duration at half maximum (FDHM). Elevated levels of cytosolic ROS in skeletal muscle derived from the SOD1G93A mice were confirmed with fluorescent probes, MitoSOX™ Red and ROS Brite™570. Immunoblotting analysis of subcellular mitochondrial fractionation of G93A muscle revealed an increased expression level of cyclophilin D (CypD), a regulatory component of the mitochondrial permeability transition pore (mPTP), at the age of 4 months but not at the age of 2 months. Transient overexpressing of SOD1G93A in skeletal muscle of wild type mice directly promoted mitochondrial ROS production with an enhanced mitoflash activity in the absence of motor neuron axonal withdrawal. Remarkably, the SOD1G93A-induced mitoflash activity was attenuated by the application of cyclosporine A (CsA), an inhibitor of CypD. Similar to the observation with the SOD1G93A transgenic mice, an increased expression level of CypD was also detected in skeletal muscle following transient overexpression of SOD1G93A. Overall, this study reveals a disease-stage-dependent change in mitochondrial function that is associated with CypD-dependent mPTP opening; and the ALS mutation SOD1G93A directly contributes to mitochondrial dysfunction in the absence of motor neuron axonal withdrawal.


LRRK2 at Striatal Synapses: Cell-Type Specificity and Mechanistic Insights.
Mutations in leucine-rich repeat kinase 2 (LRRK2) cause Parkinson's disease with a similar clinical presentation and progression to idiopathic Parkinson's disease, and common variation is linked to disease risk. Recapitulation of the genotype in rodent models causes abnormal dopamine release and increases the susceptibility of dopaminergic neurons to insults, making LRRK2 a valuable model for understanding the pathobiology of Parkinson's disease. It is also a promising druggable target with targeted therapies currently in development. LRRK2 mRNA and protein expression in the brain is highly variable across regions and cellular identities. A growing body of work has demonstrated that pathogenic LRRK2 mutations disrupt striatal synapses before the onset of overt neurodegeneration. Several substrates and interactors of LRRK2 have been identified to potentially mediate these pre-neurodegenerative changes in a cell-type-specific manner. This review discusses the effects of pathogenic LRRK2 mutations in striatal neurons, including cell-type-specific and pathway-specific alterations. It also highlights several LRRK2 effectors that could mediate the alterations to striatal function, including Rabs and protein kinase A. The lessons learned from improving our understanding of the pathogenic effects of LRRK2 mutations in striatal neurons will be applicable to both dissecting the cell-type specificity of LRRK2 function in the transcriptionally diverse subtypes of dopaminergic neurons and also increasing our understanding of basal ganglia development and biology. Finally, it will inform the development of therapeutics for Parkinson's disease.


Do small swarms have an advantage when house hunting? The effect of swarm size on nest-site selection by Apis mellifera.
Reproductive swarms of honeybees are faced with the problem of finding a good site to establish a new colony. We examined the potential effects of swarm size on the quality of nest-site choice through a combination of modelling and field experiments. We used an individual-based model to examine the effects of swarm size on decision accuracy under the assumption that the number of bees actively involved in the decision-making process (scouts) is an increasing function of swarm size. We found that the ability of a swarm to choose the best of two nest sites decreases as swarm size increases when there is some time-lag between discovering the sites, consistent with Janson & Beekman (Janson & Beekman 2007 Proceedings of European Conference on Complex Systems, pp. 204-211.). However, when simulated swarms were faced with a realistic problem of choosing between many nest sites discoverable at all times, larger swarms were more accurate in their decisions than smaller swarms owing to their ability to discover nest sites more rapidly. Our experimental fieldwork showed that large swarms invest a larger number of scouts into the decision-making process than smaller swarms. Preliminary analysis of waggle dances from experimental swarms also suggested that large swarms could indeed discover and advertise nest sites at a faster rate than small swarms.


[Primary care research in Hungary. Results and experiences in comparison with Europe].
This paper presents the history, the achievements and the current status in the research performed by family physicians in Hungary and makes suggestions for the future. The comparative analysis of research domains, results infrastructural differences and perspectives between Hungary and other European countries is also performed. A wide range of primary care bibliography is also offered for readers who are interested in this topic.


Effect of treatment variation on outcomes in patients with Clostridium difficile.
New guidelines for the treatment of Clostridium difficile-associated diarrhea were published by the Infectious Disease Society of America (IDSA) in 2010, however, there has been no literature evaluating the effectiveness of these guidelines. The purpose of this study was to examine the clinical outcomes of Clostridium difficile infection including death, C difficile infection recurrence, toxic megacolon, and surgery between patients who received guideline-concordant therapy vs guideline-discordant therapy. Retrospective case-control study of hospitalized adults with C difficile infection presenting to a 420-bed tertiary care referral county teaching hospital. Patients were identified by International Classification of Diseases-9th Revision codes, and included if they were ≥18 years of age and treated for C difficile infection during their hospital visit. Complication rates (death, infection recurrence, toxic megacolon, and surgery) of patients with C difficile infection were measured to determine if following the IDSA guidelines improves outcomes. Only 51.7% of the patients' prescribers followed the 2010 IDSA guidelines. Patients whose prescribers followed the IDSA guidelines experienced fewer complications than patients whose prescribers strayed from the guidelines (17.2% vs 56.3%, P <.0001). This difference was mainly due to a reduction in mortality (5.4% vs 21.8%, P = .0012) and infection recurrence (14% vs 35.6%, P = .0007). Patients who presented with severe and complicated disease received guideline-based therapy significantly less often than patients with mild disease (19.7%, 35.3%, and 81.2%, respectively, P <.0001). There was a significant reduction in C difficile infection recurrence and mortality when prescribers followed the IDSA/Society for Healthcare Epidemiology of America guidelines for treatment of C difficile infection.


Pharmacogenetic interactions of rifapentine plus isoniazid with efavirenz or nevirapine.
The effect of rifapentine plus isoniazid on efavirenz pharmacokinetics was characterized in AIDS Clinical Trials Group protocol A5279 (NCT01404312). The present analyses characterize pharmacogenetic interactions between these drugs, and with nevirapine. A subset of HIV-positive individuals receiving efavirenz- or nevirapine-containing antiretroviral therapy in A5279 underwent pharmacokinetic evaluations at baseline, and again weeks 2 and 4 after initiating daily rifapentine plus isoniazid. Associations with polymorphisms relevant to efavirenz, nevirapine, isoniazid, and rifapentine pharmacokinetics were assessed. Of 128 participants, 101 were evaluable for associations with rifapentine and its active 25-desacetyl metabolite, 87 with efavirenz, and 38 with nevirapine. In multivariable analyses, NAT2 slow acetylators had greater week 4 plasma concentrations of rifapentine (P = 2.6 × 10) and 25-desacetyl rifapentine (P = 7.0 × 10) among all participants, and in efavirenz and nevirapine subgroups. NAT2 slow acetylators also had greater plasma efavirenz and nevirapine concentration increases from baseline to week 4, and greater decreases from baseline in clearance. CYP2B6 poor metabolizers had greater efavirenz concentrations at all weeks and greater nevirapine concentrations at baseline. None of 47 additional polymorphisms in 11 genes were significantly associated with pharmacokinetics. Among HIV-positive individuals receiving efavirenz or nevirapine, and who then initiated rifapentine plus isoniazid in A5279, NAT2 slow acetylators had greater rifapentine and 25-desacetyl rifapentine concentrations, and greater increases from baseline in plasma efavirenz and nevirapine concentrations. These associations are likely mediated by greater isoniazid exposure in NAT2 slow acetylators.


Pretreatment with detergents modulates the effects of epinephrine on uveal flow and intraocular pressure.
Prior administration of detergents modulates the effects of epinephrine (epi) in isolated, arterially perfused rabbit eyes. Pretreatment with Tween 80, Triton X-100, digitonin and sodium dodecyl sulphate (SDS) caused a dose-dependent reduction of epi induced vasoconstriction of uveal vessels. There also was a dose-dependent reduction of the epi induced fall in intraocular pressure (IOP) after pretreatment with Tween 80 and Triton X-100; digitonin and SDS enhanced the effects of epi on IOP but these effects were not dose-dependent. Significant effects of all four detergents on the efficacy of epi were irreversible. Digitonin probably increased the affinity of epi for the adrenergic receptor as shown by the decrease of the ED50-value; the three other detergents did not significantly affect the affinity. The sequence of administration of epi and detergents is of minor importance for the effects of Tween 80 and Triton X-100 but differs significantly for the effects of digitonin and SDS.


The release of platelet-activating factor from human endothelial cells in culture.
The release of platelet-activating factor (PAF) from stimulated human endothelial cells (HEC) cultured from normal term, umbilical cord veins is described. HEC in primary cultures released PAF after challenge with A23187, rabbit anti-human factor VIII (RaHu/FVIII), angiotensin II, and vasopressin. HEC subcultures maintained the ability to release PAF in the presence of A23187 and RaHu/FVIII, whereas the release of PAF in response to angiotensin II and vasopressin was not constant and was reduced. Control cultured, smooth muscle cells derived from umbilical cord veins, previously depleted of endothelial cells, did not release PAF under the above-mentioned stimulation. Plastic-adherent or cultured monocytes released PAF with A23187, but not with RaHu/FVIII, angiotensin II, and vasopressin. The release of PAF from HEC in primary cultures required the presence of extracellular cations and the activation of membrane phospholipase A2. PAF release induced by A23187, RaHu/FVIII, angiotensin II, and vasopressin was unaffected by indomethacin, an inhibitor of cyclooxygenase, which, however, favored the release of PAF from HEC stimulated with thrombin, a stimulus that did not affect HEC in the absence of indomethacin. PGI2 inhibited PAF release from stimulated HEC. The relevance of an acetylation process in the biosynthesis of PAF and HEC was supported by the following evidence: 1) the increase in PAF yield in the presence of sodium acetate and, particularly, of acetyl-CoA; 2) the incorporation of [14C]acetate into PAF molecules; 3) the loss of radioactivity and of biologic activity after treatment with phospholipase A2. These results indicate that HEC in culture are able to release PAF and that metabolic pathways similar to those described for leukocytes are involved.


Stimulation of the caudate nucleus induces contraversive saccadic eye movements as well as head turning in the cat.
The effects of stimulation of the caudate nucleus were investigated in alert cats, with special reference to the induction of eye and head movements. Stimulation of caudal portions of the caudate nucleus on one side with trains of current pulses induced gaze shifts towards the contralateral side. When the head of the animal was restrained, the majority of evoked eye movements were single conjugate saccades. The amplitude and direction of the evoked saccade varied depending on the initial eye position. The amplitude of the horizontal component tended to be larger for saccades initiated from more ipsilateral positions, and became gradually smaller as the initial eye position shifted to the contralateral side. If the eye was far into the contralateral positions, no saccades were induced. Furthermore, the saccades tended to have a downward component when the eye was initially focused upward, and an upward component when the eye was focused downward. When the head was made free to move, the same stimulation induced a sequence of contraversive staircase gaze shifts composed of coordinated eye and head movements. The eye movements in the orbit resembled nystagmus, consisting of contraversive saccades followed by reverse compensatory movements. The head turning, though smooth and continuous, was also suggested to consist of a series of movements coupled with saccadic eye movements. This study indicates a potential role of the caudate nucleus in the control of orienting reflexes.


Multiplexed 129Xe HyperCEST MRI Detection of Genetically Reconstituted Bacterial Protein Nanoparticles in Human Cancer Cells.
Gas vesicle nanoparticles (GVs) are gas-containing protein assemblies expressed in bacteria and archaea. Recently, GVs have gained considerable attention for biotechnological applications as genetically encodable contrast agents for MRI and ultrasonography. However, at present, the practical use of GVs is hampered by a lack of robust methodology for their induction into mammalian cells. Here, we demonstrate the genetic reconstitution of protein nanoparticles with characteristic bicone structures similar to natural GVs in a human breast cancer cell line KPL-4 and genetic control of their size and shape through expression of reduced sets of humanized gas vesicle genes cloned into Tol2 transposon vectors, referencing the natural gas vesicle gene clusters of the cyanobacteria planktothrix rubescens/agardhii. We then report the utility of these nanoparticles as multiplexed, sensitive, and genetically encoded contrast agents for hyperpolarized xenon chemical exchange saturation transfer (HyperCEST) MRI.


Investigating the key membrane protein changes during in vitro erythropoiesis of protein 4.2 (-) cells (mutations Chartres 1 and 2).
Protein 4.2 deficiency caused by mutations in the EPB42 gene results in hereditary spherocytosis with characteristic alterations of CD47, CD44 and RhAG. We decided to investigate at which stage of erythropoiesis these hallmarks of protein 4.2 deficiency arise in a novel protein 4.2 patient and whether they cause disruption to the band 3 macrocomplex. We used immunoprecipitations and detergent extractability to assess the strength of protein associations within the band 3 macrocomplex and with the cytoskeleton in erythrocytes. Patient erythroblasts were cultured from peripheral blood mononuclear cells to study the effects of protein 4.2 deficiency during erythropoiesis. We report a patient with two novel mutations in EPB42 resulting in complete protein 4.2 deficiency. Immunoprecipitations revealed a weakened ankyrin-1-band 3 interaction in erythrocytes resulting in increased band 3 detergent extractability. CD44 abundance and its association with the cytoskeleton were increased. Erythroblast differentiation revealed that protein 4.2 and band 3 appear simultaneously and associate early in differentiation. Protein 4.2 deficiency results in lower CD47, higher CD44 expression and increased RhAG glycosylation starting from the basophilic stage. The normal downregulation of CD44 expression was not seen during protein 4.2(-) erythroblast differentiation. Knockdown of CD47 did not increase CD44 expression, arguing against a direct reciprocal relationship. We have established that the characteristic changes caused by protein 4.2 deficiency occur early during erythropoiesis. We postulate that weakening of the ankyrin-1-band 3 association during protein 4.2 deficiency is compensated, in part, by increased CD44-cytoskeleton binding.


Pregnant women at increased risk of adverse perinatal outcomes: A combination of less healthy behaviors and adverse psychosocial and socio-economic circumstances.
Smoking during pregnancy is associated with a multitude of health behaviors and with the psychosocial and socio-economic circumstances of pregnant women. Limited research has so far been conducted on the clustering of these characteristics and on their effect on pregnancy outcomes. This study aimed to identify different groups of pregnant women based on their behavioral, psychosocial and socio-economic characteristics and their pregnancy outcomes. In total, 2455 women who were 12 weeks pregnant completed a questionnaire on smoking behavior, health behaviors and psychosocial and socio-economic characteristics. Neonatal and maternal outcomes were extracted from the Dutch perinatal registration. Subgroups were identified with latent class analysis and adverse pregnancy outcomes were compared between subgroups with logistic regression. Women were classified into four latent classes. Two classes represented the healthy higher-educated pregnant women who did not smoke: one group of multigravida women and one of primigravida women, also characterized by less pregnancy-specific knowledge and more pregnancy-related stress. The remaining women were grouped into two less healthy groups. One group frequently quit smoking, reported less healthy eating, less physical activity and comparable stress levels as the healthy higher-educated groups. The last group contained the most smokers, had the highest scores on psychosocial and pregnancy-related stress and the most adverse socio-economic circumstances. This group had an increased risk of adverse maternal outcomes, in particular developing diabetes during pregnancy. A comprehensive and integrated approach is needed to improve outcomes in pregnancies with a combination of adverse health, psychosocial, and socio-economic conditions.


Polymerization of Physisorbed Molecular Monolayers via Overhanging Alkynyl Chains: Characterization of Polymerization Kinetics and Monolayer Durability.
Monolayers self-assembled by triphenyleneethynylene (TPE) compounds bearing two terminal alkynyl chains were polymerized by Glaser-Hay (G-H) alkyne coupling at the acetonitrile-HOPG interface. The alkynyl chains extend into the solution due to the monolayer's dense-packed morphology. Reacting substructures that have no morphology-determining roles is a potential strategy for preserving monolayer morphology throughout polymerization. Monolayer G-H reaction kinetics and polymerized monolayer durability were characterized by using mass spectrometry and fluorescence. Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) and time-of-flight (TOF) MS were used to identify TPE-oligomers in the monolayer and to track the monolayer populations of TPE-monomer, -dimer, and -trimer as a function of G-H reaction duration. Comparison of the observed kinetics to a Monte Carlo simulation provided evidence of step-growth polymerization. The durability of polymerized monolayers depended strongly on the length of the alkynyl chains linked by G-H reaction. Polymerized T6y monolayers (O(CH2)3C≡CH alkynyl chains) desorbed minimally during 16-h immersion in 90 °C o-dichlorobenzene (oDCB), whereas polymerized T8y (O(CH2)5C≡CH alkynyl chains) and polymerized T11y (O(CH2)8C≡CH alkynyl chains), desorbed 33 and 60%, respectively, of their TPE units after 4 h in 90 °C oDCB. All the polymerized monolayers are much more durable than unpolymerized monolayers, which desorb quantitatively from HOPG when rinsed with 25 μL of oDCB. Polymerized T6y monolayer is a highly durable anchor that may be adapted to build multilayer structures "permanently" attached to the HOPG surface. The alkynyl chain length dependence may be useful for tuning polymerized TPE monolayer durability for specific applications.


Transgene expression in zebrafish: A comparison of retroviral-vector and DNA-injection approaches.
To assess alternative methods for introducing expressing transgenes into the germ line of zebrafish, transgenic fish that express a nuclear-targeted, enhanced, green fluorescent protein (eGFP) gene were produced using both pseudotyped retroviral vector infection and DNA microinjection of embryos. Germ-line transgenic founders were identified and the embryonic progeny of these founders were evaluated for the extent and pattern of eGFP expression. To compare the two modes of transgenesis, both vectors used the Xenopus translational elongation factor 1-alpha enhancer/promoter regulatory cassette. Several transgenic founder fish which transferred eGFP expression to their progeny were identified. The gene expression patterns are described and compared for the two modes of gene transfer. Transient expression of eGFP was detected 1 day after introducing the transgenes via either DNA microinjection or retroviral vector infection. In both cases of gene transfer, transgenic females produced eGFP-positive progeny even before the zygotic genome was turned on. Therefore, GFP was being provided by the oocyte before fertilization. A transgenic female revealed eGFP expression in her ovarian follicles. The qualitative patterns of gene expression in the transgenic progeny embryos after zygotic induction of gene expression were similar and independent of the mode of transgenesis. The appearance of newly synthesized GFP is detectable within 5-7 h after fertilization. The variability of the extent of eGFP expression from transgenic founder to transgenic founder was wider for the DNA-injection transgenics than for the retroviral vector-produced transgenics. The ability to provide expressing germ-line transgenic progeny via retroviral vector infection provides both an alternative mode of transgenesis for zebrafish work and a possible means of easily assessing the insertional mutagenesis frequency of retroviral vector infection of zebrafish embryos. However, because of the transfer of GFP from oocyte to embryo, the stability of GFP may create problems of analysis in embryos which develop as quickly as those of zebrafish.


Severe and progressive neurotransmitter release aberrations in familial hemiplegic migraine type 1 Cacna1a S218L knock-in mice.
Familial hemiplegic migraine type 1 (FHM1) is caused by mutations in the CACNA1A gene, encoding neuronal presynaptic Ca(V)2.1 (P/Q-type) Ca(2+) channels. These channels mediate neurotransmitter release at many central synapses and at the neuromuscular junction (NMJ). Mutation S218L causes a severe neurological phenotype of FHM and, additionally, ataxia and susceptibility to seizures, delayed brain edema, and fatal coma after minor head trauma. Recently, we generated a Cacna1a S218L knock-in mutant mouse, displaying these features and reduced survival. A first electrophysiological study showed high susceptibility for cortical spreading depression, enhanced neuronal soma Ca(2+) influx, and at diaphragm NMJs, a considerable increase of neurotransmitter release. We here assessed the function of S218L knock-in NMJs at several muscle types in great detail. Pharmacological analyses using specific Ca(V) subtype-blocking toxins excluded compensatory contribution of non-Ca(V)2.1 channels. Endplate potentials were considerably broadened at many NMJs. High rate (40 Hz)-evoked acetylcholine release was slightly reduced; however, it was not associated with block of neurotransmission causing weakness, as assessed with grip strength measurements and in vitro muscle contraction experiments. The synaptopathy clearly progressed with age, including development of an increased acetylcholine release at low-rate nerve stimulation at physiological extracellular Ca(2+) concentration and further endplate potential broadening. Our results suggest enhanced Ca(2+) influx into motor nerve terminals through S218L-mutated presynaptic Ca(V)2.1 channels, likely because of the earlier reported negative shift of activation potential and reduced inactivation. Similar severe aberrations at central synapses of S218L mutant mice and humans may underlie or contribute to the drastic neurological phenotype.


The Rotterdam Study: 2014 objectives and design update.
The Rotterdam Study is a prospective cohort study ongoing since 1990 in the city of Rotterdam in The Netherlands. The study targets cardiovascular, endocrine, hepatic, neurological, ophthalmic, psychiatric, dermatological, oncological, and respiratory diseases. As of 2008, 14,926 subjects aged 45 years or over comprise the Rotterdam Study cohort. The findings of the Rotterdam Study have been presented in over a 1,000 research articles and reports (see www.erasmus-epidemiology.nl/rotterdamstudy ). This article gives the rationale of the study and its design. It also presents a summary of the major findings and an update of the objectives and methods.


Prevention and therapy of experimental Escherichia coli infection with monoclonal antibody.
Mouse hybridoma antibody of immunoglobulin class M prepared with live group B meningococci was evaluated for its ability to protect against and treat Escherichia coli infections in a newborn-rat model. In these studies, antibody was administered intraperitoneally and bacteria were administered subcutaneously to avoid introducing the antibody and bacteria to the same site. The activity of this hybridoma antibody was specific; the antibody provided protection against the K-1 strain, but not against the K-92 strain. In addition, the amount of the antibody required for protection was dependent upon the size of bacterial challenge. With an increase of the bacterial inocula from the 100% lethal dose to 10 times the 100% lethal dose there was a threefold increase in the amount of the antibody required for 50% protection. Similarly, therapeutic efficacy of the antibody was also dependent upon the magnitude of bacteremia before therapy. The antibody successfully cleared the bacteremia only when the pretherapy bacterial counts in blood were less than 10(4) CFU/ml. These findings suggest that the monoclonal immunoglobulin M antibody against the capsular polysaccharide of the group B meningococcus may be useful in the prevention and treatment of K-1 E. coli infections.


Comparison of surgical outcomes of intra-articular calcaneal fractures by age.
Internal fixation is an accepted treatment for displaced fractures of the calcaneus. Operative intervention in older patients, however, is traditionally discouraged in the literature. The purpose of this study was to compare the outcomes of internal fixation of intra-articular fractures of the calcaneus on the basis of patient age. One hundred and seventy-five patients (191 fractures) who underwent internal fixation between 1992 and 2007 for a displaced, intra-articular calcaneal fracture were identified. The American Society of Anesthesiologists score, the fracture pattern, and the mechanism of injury were recorded. Each patient was contacted to complete a follow-up survey from which clinical outcome scores were calculated. One hundred and forty-six patients with 158 fractures were available for follow-up and were divided into two groups for comparison. Group I consisted of 108 fractures in patients who were less than fifty years old. Group II was composed of fractures in fifty patients who were fifty years of age or older. The mean duration of follow-up was 8.98 years. The average patient age was thirty-six years for Group I and fifty-eight years for Group II. The average adjusted American Orthopaedic Foot & Ankle Society score was 64 for Group I and 75 for Group II. The mean calcaneal fracture scoring system score was 66 for Group I, and 76 for Group II. Similarly, the average Foot Function Index was 24 and 15 for Groups I and II, respectively. Each clinical outcome measure suggests significantly better outcomes for Group II as compared with Group I (all p < 0.05). Overall, the complication rates were similar between groups. Conversion to subtalar fusion was 15% for Group I and 8% for Group II. In this series, outcomes of older patients are at least equivalent to those of younger patients undergoing internal fixation for an intra-articular calcaneal fracture. Operative intervention appears to be a reasonable option for displaced calcaneal fractures in older patients. Physiologic age should be considered when evaluating older patients, and individualized treatment plans remain critical because patients with low physical demands or who have medical complications may be better candidates for nonoperative treatment. Prospective studies are needed in this area.


Structural comparison of three types of staphylococcal cassette chromosome mec integrated in the chromosome in methicillin-resistant Staphylococcus aureus.
The beta-lactam resistance gene mecA of Staphylococcus aureus is carried by a novel mobile genetic element, designated staphylococcal cassette chromosome mec (SCCmec), identified in the chromosome of a Japanese methicillin-resistant S. aureus (MRSA) strain. We now report identification of two additional types of mecA-carrying genetic elements found in the MRSA strains isolated in other countries of the world. There were substantial differences in the size and nucleotide sequences between the elements and the SCCmec. However, new elements shared the chromosomal integration site with the SCCmec. Structural analysis of the new elements revealed that they possessed all of the salient features of the SCCmec: conserved terminal inverted repeats and direct repeats at the integration junction points, conserved genetic organization around the mecA gene, and the presence of cassette chromosome recombinase (ccr) genes responsible for the movements of SCCmec. The elements, therefore, were considered to comprise the SCCmec family of staphylococcal mobile genetic elements together with the previously identified SCCmec. Among 38 epidemic MRSA strains isolated in 20 countries, 34 were shown to possess one of the three typical SCCmec elements on the chromosome. Our findings indicated that there are at least three distinct MRSA clones in the world with different types of SCCmec in their chromosome.


Hydroxymethylbilane synthase gene mutations and polymorphisms in Brazilian families with acute intermittent porphyria.
Acute intermittent porphyria (AIP), an autosomal dominant disorder, is caused by a deficiency of hydroxymethylbilane synthase (HMBS). In the present study, we sought to establish a correlation between HMBS activity with the presence of mutations and polymorphisms. Enzyme activity was measured in red blood cells of four Brazilian unrelated AIP families (n = 124) and in blood donors (n = 80). The HMBS mutations in AIP family members were studied by PCR-SSCP followed by direct sequencing. Six intragenic SNPs (1345 G>A, 1500 T>C, 2377 C>A, 2478 A>G, 3581 A>G, and 7064 C>A) were determined by PCR-RFLP. Abnormal SSCP patterns in exons 7, 9, 12, and 15 were observed. DNA sequencing analysis revealed one nonsense mutation, R149X, two missense mutations, G111R and L338P, and one deletion, CT 730-731. All mutation carriers had lower enzyme activity. All polymorphisms, except 2377 C>A and 7064 C>A, showed no significant differences compared with previous reports. Mutation screening allowed the detection of the missense mutation, L338P, and the 730_731delCT deletion, two as yet unreported mutations in Brazilian AIP patients. Our findings also showed a high frequency of 2478 A>G and 3581 A>G polymorphism combinations suggesting that these polymorphisms contributed to enzymatic activity reduction in our study population.


Retrospective study of functional outcomes and disability after non-ischaemic vascular causes of spinal cord dysfunction.
Objective: Describe demographic characteristics, functional outcomes and disability following rehabilitation for non-ischemic vascular spinal cord dysfunction (SCDys).Design: Retrospective, open cohort, case series.Setting: Tertiary rehabilitation unit, Victoria, Australia.Participants: Patients with non-ischemic vascular SCDys admitted over a 21-year-period (01/01/1995-31/12/2015) were identified using International Classification of Diseases codes.Outcome Measures: Demographic characteristics, etiology, neurologic classification, length of stay (LOS), and complications. On admission and discharge, the following were collected: functional independence measure (FIM) motor subscale, details on bowel, bladder, mobility, living arrangement, and support services.Results: 36 patients (female 58%; mean age 69 ± 16 years) were identified. The main causes of non-ischemic vascular SCDys were epidural hematoma (39%), dural arteriovenous fistula (17%), and arteriovenous malformation (11%). 22 cases (61%) were iatrogenic. Most (86%) had incomplete paraplegia. Urinary tract infection was the most common complication (64%). Median LOS in rehabilitation was 68 days. Significant improvement in FIM motor scores was observed from admission (median 25, interquartile range [IQR] 20-38) to discharge (median 69, IQR 38-77) (P < 0.001). On discharge, 4 patients (11%) walked >100 m unaided, 6 (17%) walked >100 m with assistive device, 10 (28%) walked >10 m with assistive device, 15 (41%) were wheelchair dependent and 1 (3%) patient remained non-mobile. 20 patients (56%) were discharged home, 8 (22%) to nursing home, and 8 (22%) transferred to another hospital.Conclusion: Most patients returned home with significantly improved functional outcomes compared to rehabilitation admission, but with the majority having ongoing major disabilities based on FIM motor scores.


Physiology in Medicine: Understanding dynamic alveolar physiology to minimize ventilator-induced lung injury.
Acute respiratory distress syndrome (ARDS) remains a serious clinical problem with the main treatment being supportive in the form of mechanical ventilation. However, mechanical ventilation can be a double-edged sword: if set improperly, it can exacerbate the tissue damage caused by ARDS; this is known as ventilator-induced lung injury (VILI). To minimize VILI, we must understand the pathophysiologic mechanisms of tissue damage at the alveolar level. In this Physiology in Medicine paper, the dynamic physiology of alveolar inflation and deflation during mechanical ventilation will be reviewed. In addition, the pathophysiologic mechanisms of VILI will be reviewed, and this knowledge will be used to suggest an optimal mechanical breath profile (MBP: all airway pressures, volumes, flows, rates, and the duration that they are applied at both inspiration and expiration) necessary to minimize VILI. Our review suggests that the current protective ventilation strategy, known as the "open lung strategy," would be the optimal lung-protective approach. However, the viscoelastic behavior of dynamic alveolar inflation and deflation has not yet been incorporated into protective mechanical ventilation strategies. Using our knowledge of dynamic alveolar mechanics (i.e., the dynamic change in alveolar and alveolar duct size and shape during tidal ventilation) to modify the MBP so as to minimize VILI will reduce the morbidity and mortality associated with ARDS.


A Three-Dimensional Model of Women's Empowerment: Implications in the Field of Microfinance and Future Directions.
Women's empowerment is an important goal in achieving sustainable development worldwide. Offering access to microfinance services to women is one way to increase women's empowerment. However, empirical evidence provides mixed results with respect to its effectiveness. We reviewed previous research on the impact of microfinance services on different aspects of women's empowerment. We propose a Three-Dimensional Model of Women's Empowerment to integrate previous findings and to gain a deeper understanding of women's empowerment in the field of microfinance services. This model proposes that women's empowerment can take place on three distinct dimensions: (1) the micro-level, referring to an individuals' personal beliefs as well as actions, where personal empowerment can be observed (2) the meso-level, referring to beliefs as well as actions in relation to relevant others, where relational empowerment can be observed and (3) the macro-level, referring to outcomes in the broader, societal context where societal empowerment can be observed. Importantly, we propose that time and culture are important factors that influence women's empowerment. We suggest that the time lag between an intervention and its evaluation may influence when empowerment effects on the different dimensions occur and that the type of intervention influences the sequence in which the three dimensions can be observed. We suggest that cultures may differ with respect to which components of empowerment are considered indicators of empowerment and how women's position in society may influence the development of women's empowerment. We propose that a Three-Dimensional Model of Women's Empowerment should guide future programs in designing, implementing, and evaluating their interventions. As such our analysis offers two main practical implications. First, based on the model we suggest that future research should differentiate between the three dimensions of women's empowerment to increase our understanding of women's empowerment and to facilitate comparisons of results across studies and cultures. Second, we suggest that program designers should specify how an intervention should stimulate which dimension(s) of women's empowerment. We hope that this model inspires longitudinal and cross-cultural research to examine the development of women's empowerment on the personal, relational, and societal dimension.


MHC class II-associated invariant chain-induced enlarged endosomal structures: a morphological study.
The major histocompatibility complex class II-associated invariant chain is believed to direct newly synthesized class II to endocytic compartments. Invariant chain synthesized at high levels in transiently transfected cells induces formation of large vesicular structures. We have examined the effect of stable expression of invariant chain in human fibroblasts by light and electron microscopy. Invariant chain expression dramatically modified endocytic compartments and induced the formation of greatly enlarged structures. These modifications were not lethal. Ultrastructurally, at least three morphologically distinct enlarged compartments could be discerned in the cells. These three compartments may represent early and late endosomes and lysosomes. Internalization of anti-invariant chain antibodies shows that invariant chain may reach the large endosomes via rapid internalization from the plasma membrane. Internalized protein remained in the enlarged vesicles for 4-6 h, indicating an invariant chain-induced delay in the pathway to lysosomes. Although the large invariant chain-induced vesicles have not yet been seen in professional antigen-presenting cells, the invariant chain-induced effects may play a role in regulating the endocytic pathway, creating a special environment for MHC class II to bind antigen.


Inflammatory bowel disease in children: a pediatrician's perspective.
Crohn's disease (CD) and ulcerative colitis (UC) are common and heterogeneous chronic inflammatory bowel disorders of childhood that account for up to 25% of all patients with inflammatory bowel disease (IBD). In CD, the familial pattern of disease concordance would suggest that genetics contribute to disease etiology. Children are more likely to have proximal small bowel disease complicated by stricture formation, fistulization and the need for surgical intervention. The predisposition for small bowel disease has been associated with mutations of the nucleotide oligomerization domain 2 (NOD2)/Caspase activation and recruitment domain 15 (CARD15) gene on chromosome 16 in 1/3 of patients with CD. Homozygous patients also show an early age at disease onset and a relatively high relative risk for isolated stricturing distal ileal disease. The potential clinical role for NOD2 testing in either the diagnosis or the therapeutic management of patients with CD has yet to be determined. The precise age of onset of CD and UC can be difficult in children. Subclinical phases of disease can be identified through a decrease in weight and height velocity, and a delay in pubertal development. However, a confident distinction between CD and UC also remains a taxonomic dilemma in 25% of pediatric patients with IBD, despite recent technological advances in diagnostic techniques, including gadolinium enhanced magnetic resonance imaging (MRI) and capsule endoscopy, and serological testing. The early introduction of immunomodulators, including azathioprine and 6-mercaptopurine have proven efficacy in maintaining long-term remission without concurrent corticosteroids. The pharmacogenomic of 6-MP metabolism has been shown to be useful in predicting susceptibility to antimetabolite induced toxicity, and possibly allowing physician's to individualize drug therapy to improve clinical response. Novel treatment strategies, including infliximab are being developed in Pediatrics with the aim at improving overall treatment efficacy and potentially avoid surgery.


Autocorrelation functions from optical scattering for one-dimensionally rough surfaces.
The relationship between the height autocorrelation function of a one-dimensionally rough surface and the Fourier transform of the intensity distribution of the light scattered by that surface is tested experimentally. The theory is derived by using the Fraunhofer approximation, without recourse to the inconsistent Kirchhoff boundary conditions. In spite of the limitations imposed by the approximations used, the results obtained from optical data agree well with those obtained from stylus data, even for an autocorrelation length as small as the optical wavelength. However, this method should be limited to surfaces with rms roughness smaller than approximately 0.14 times the wavelength of light.


Does rituximab have a place in treating classic hodgkin lymphoma?
Monoclonal antibodies targeting surface proteins on the malignant Hodgkin and Reed-Sternberg (HRS) cells are currently under intensive investigation with promising early results. Of particular interest is the CD20 antigen, because it is expressed not only on a small fraction of HRS cells but also on the benign reactive B cells in the microenvironment. The rationale of using rituximab in classic Hodgkin lymphoma (cHL) comprises several points: 1) HRS cells infrequently express CD20; 2) elimination of CD20-positive reactive B cells supporting HRS cells would deprive the malignant cells of survival signals; 3) elimination of reactive B cells may also potentially increase host immune response against HRS cells; 4) HRS stem cells express CD20. Although this rationale has not generally been confirmed in patients, promising results in managing cHL have occurred in early-phase clinical trials of rituximab, including trials of rituximab as a single agent in refractory or recurrent cHL, rituximab plus gemcitabine in refractory or recurrent cHL, and rituximab plus ABVD in newly diagnosed cHL. Based on the results of these trials, several prospective clinical trials using rituximab in the management of advanced-stage cHL and early-stage cHL are ongoing. These trials further clarify the role of rituximab in cHL. Enrollment of patients with this "classic" disease in clinical trials is encouraged.


Contraceptive usage, knowledge and correlates of usage among female emergency department patients.
For female emergency department (ED) patients, we sought to assess the prevalence of contraceptive usage as well as the extent of contraceptive knowledge and to determine if demographic and sexual health history factors, comprehension of contraceptive methods and moral/religious opinions on contraception were associated with current usage of birth control pills (BCPs), prior usage of emergency contraception (EC) and frequency of condom usage. English-speaking female ED patients aged between 18 and 55 years at a northeastern United States urban ED were surveyed on their usage, comprehension and opinions regarding BCPs, EC and condoms. Of the 539 respondents (64.6% were aged </=35 years), most were White (63.1%), single (42.5%), Catholic (48.4%) and privately insured (55.3%). Among the 223 women at pregnancy risk [not currently pregnant, not using any form of nonsurgical birth control (except condoms) and with no prior tubal ligation or hysterectomy], about 25% were using BCPs, fewer than 10% had used EC and almost 40% never used condoms. Most women displayed good knowledge about BCPs and condoms but poor understanding about EC. In multivariate logistic regression analyses, current BCP usage among women at risk of pregnancy was associated with younger age [odds ratio (OR)=0.54; 95% confidence interval (CI)=0.37-0.79], private insurance (OR=2.52; 95% CI=1.30-4.86) and recent intercourse (OR=1.61; 95% CI=1.19-2.18). Among women at risk of pregnancy, those who had an abortion (OR=2.56; 95% CI=1.17-5.61) and those who displayed greater EC knowledge (OR=3.23; 95% CI=1.50-6.95) had greater odds of having used EC. Among all women, more frequent condom usage was associated with being younger (OR=0.57; 95% CI=0.46-0.70), having never been married (OR=0.44; 95% CI=0.28-0.68) and not having intercourse recently (OR=0.79; 95% CI=0.64-0.98). A high percentage of female ED patients (41.4%) were at risk of pregnancy. Demographic and sexual history factors can help identify women who might benefit from receiving referrals or education on contraceptive measures.


[Electricity generation from sweet potato fuel ethanol wastewater using microbial fuel cell technology].
Air cathode microbial fuel cell (MFC) were investigated for electricity production from sweet potato fuel ethanol wastewater containing 5000 mg/L of chemical oxygen demand (COD). Maximum power density of 334.1 mW/m2, coulombic efficiency (CE) of 10.1% and COD removal efficiency of 92.2% were approached. The effect of phosphate buffer solution (PBS) and COD concentration on the performance of MFC was further examined. The addition of PBS from 50 mmol/L to 200 mmol/L increased the maximum power density and CE by 33.4% and 26.0%, respectively. However, the COD removal efficiency was not relative to PBS concentration in the wastewater. When the COD increased from 625 mg/L to 10 000 mg/L, the maximum value of COD removal efficiency and the maximum power density were gained at the wastewater strength of 5 000 mg/L. But the CE ranged from 28.9% to 10.3% with a decreasing trend. These results demonstrate that sweet potato fuel ethanol wastewater can be used for electricity generation in MFC while at the same time achieving wastewater treatment. The increasing of PBS concentration can improve the power generation of MFC. The maximum power density of MFC increases with the rise of COD concentration, but the electricity generation will decrease for the acidification of high wastewater concentration.


Independent component analysis of SNPs reflects polygenic risk scores for schizophrenia.
Schizophrenia is a psychiatric disorder with high heritability. Recent genome-wide association studies have provided a list of risk loci reliably derived from unprecedentedly large samples. However, further delineation of the diagnosis-associated susceptibility variants is needed to better characterize the genetic architecture given the disease's complex nature. In this sense, a data-driven approach might hold promise for identifying functionally related clusters of genetic variants that might not be captured by hypothesis-based models. In the current study, independent component analysis (ICA) was applied to the Psychiatric Genomics Consortium's schizophrenia-related single nucleotide polymorphisms (SNPs) in 104 schizophrenia patients and 142 healthy controls of European Ancestry. We found that, for 13 out of 16 extracted independent components, the associated loadings correlated highly (r>0.5) with the polygenic risk scores for SZ of the corresponding SNPs. These correlations were likely not inflated by the linkage disequilibrium structure (permutation p<0.001). In brief, we demonstrate an example of ICA analysis on SNP data yielding functionally meaningful clusters, which motivates further application of data-driven approaches as a complimentary tool for hypothesis-based methods to enrich our knowledge on the genetic basis of complex disorders.


Recurrence, Reactivation, or Inflammatory Rebound of SARS-CoV-2 Infection With Acute Vestibular Symptoms: A Case Report and Revision of Literature.
A case of recurrent coronavirus disease 2019 (COVID-19) with neurovestibular symptoms was reported. In March 2020, a physician working in an Italian pediatric hospital had flu-like symptoms with anosmia and dysgeusia, and following a reverse transcription PCR (RT/PCR) test with a nasopharyngeal swab tested positive for SARS-CoV-2. After home quarantine, 21 days from the beginning of the symptoms, the patient tested negative in two subsequent swabs and was declared healed and readmitted to work. Serological testing showed a low level of immunoglobulin G (IgG) antibody title and absence of immunoglobulin M (IgM). However, 2 weeks later, before resuming work, the patient complained of acute vestibular syndrome, and the RT/PCR test with mucosal swab turned positive. On the basis of the literature examined and reviewed for recurrence cases and vestibular symptoms during COVID-19, to our knowledge this case is the first case of recurrence with vestibular impairment as a neurological symptom, and we defined it as probably a viral reactivation. The PCR retest positivity cannot differentiate re-infectivity, relapse, and dead-viral RNA detection. Serological antibody testing and viral genome sequencing could be always performed in recurrence cases.


Evaluation of an ELISA and four on-farm tests to estimate colostrum quality for dairy cows.
The objectives of this study were to evaluate different analytical methods to determine colostrum quality in dairy cattle, including one laboratory-based method (ELISA) and 4 on-farm tests. We hypothesized that the colostral immunoglobulin G (IgG) concentration using different analytical methods, i.e., ELISA (mg/mL), digital Brix refractometer (% Brix), colostrometer (specific gravity and mg/mL), an outflow funnel (seconds), and a lateral flow assay (mg/mL) were highly correlated with the reference method, radial immunodiffusion (RID; mg/mL) and would generate comparable results. Colostrum samples were collected from 209 Holstein Friesian cows on 2 commercial dairy farms in Germany. Colostrum weight and colostrum temperature were measured. Test characteristics, such as optimum thresholds, sensitivity (Se), specificity (Sp), and area under the curve (AUC) were determined using a receiver operating characteristic (ROC) curve analyses for each test. Out of 209 colostrum samples assessed by RID, 186 (89%) samples had high quality (≥50 mg IgG/mL), while 23 colostrum samples (11%) showed poor quality with IgG concentrations less than 50 mg/mL. The mean IgG concentration (±SD) was 101.3 ± 45.9 mg/mL and the range was 6.0 to 244.3 mg IgG/mL. The Pearson correlation coefficient between RID and ELISA was r = 0.78. In comparison to RID, Pearson correlation coefficients for the on-farm tests were: r = 0.79 (digital Brix refractometry), r = 0.58 (colostrometer: specific gravity), r = 0.61 (colostrometer: temperature corrected), r = 0.26 (outflow funnel) and r = 0.43 (lateral flow assay), respectively. The optimal threshold to identify high-quality colostrum using ELISA was at 50.8 mg/mL with sensitivity 91.3%, specificity 92.3%, and AUC of 0.94. For the on-farm tests sensitivity ranged from 95.7% (Brix refractometry) to 60.9% (lateral flow assay). Specificity ranged from 88.6% (lateral flow assay) to 75.9% (colostrometer after temperature correction). The AUC ranged from 0.93 (Brix refractometry) to 0.73 (outflow funnel). Based on the AUC, ELISA (0.94) and Brix refractometry (0.93) can be considered highly accurate. In conclusion, the ELISA is accurate to assess colostrum quality. Regarding the on-farm tests only the digital Brix refractometer and the colostrometer were adequate to determine colostrum quality.


PDF receptor expression reveals direct interactions between circadian oscillators in Drosophila.
Daily rhythms of behavior are controlled by a circuit of circadian pacemaking neurons. In Drosophila, 150 pacemakers participate in this network, and recent observations suggest that the network is divisible into M and E oscillators, which normally interact and synchronize. Sixteen oscillator neurons (the small and large lateral neurons [LNvs]) express a neuropeptide called pigment-dispersing factor (PDF) whose signaling is often equated with M oscillator output. Given the significance of PDF signaling to numerous aspects of behavioral and molecular rhythms, determining precisely where and how signaling via the PDF receptor (PDFR) occurs is now a central question in the field. Here we show that GAL4-mediated rescue of pdfr phenotypes using a UAS-PDFR transgene is insufficient to provide complete behavioral rescue. In contrast, we describe a approximately 70-kB PDF receptor (pdfr) transgene that does rescue the entire pdfr circadian behavioral phenotype. The transgene is widely but heterogeneously expressed among pacemakers, and also among a limited number of non-pacemakers. Our results support an important hypothesis: the small LNv cells directly target a subset of the other crucial pacemaker neurons cells. Furthermore, expression of the transgene confirms an autocrine feedback signaling by PDF back to PDF-expressing cells. Finally, the results present an unexpected PDF receptor site: the large LNv cells appear to target a population of non-neuronal cells that resides at the base of the eye.


[Nutrition in AIDS].
The infection by HIV continues to be the most aggressive pandemic of our century, with a high economical, social, and health care cost. In the last years the development of new, highly effective therapies has made it possible to change the prognosis, the quality of life, and the survival of many patients. However, the associated malnutrition continues to appear, with dramatic consequences. It affects between 50 and 90% of the seropositive patients. Its origin is multi-factorial and its early detection allows positive therapeutic responses to be obtained, with nutritional repletion, if the correct treatment is given. The future of the nutritional therapeutic approach in patients with HIV infection passes through a combined therapy that includes: nutritional education, drugs, and nutritional support.


Peri-implantitis in a specialist clinic of periodontology. Clinical features and risk indicators.
Implant therapy has become a widely recognized treatment alternative for replacing missing teeth. Several long term follow-up studies have shown that the survival rate is high. However, complications may appear and risk indcators associated with early and late failures have been identified. The purpose of the present retrospective clinical study was to describe some clinical features of patients with clinical signs of peri-implantitis and to identify risk indicators of peri-implantitis in a population at a specialist clinic of Periodontology. In total,the material consisted of 377 implants in 111 patients with the diagnosis peri-implantitis. The mean age at the examination was found to be 56.3 years (range 22-83) for females and 64.1 years (range 27-85) for males. The mean number of remaining teeth was found to be 10.5 (S.D. 8.89) and the mean number of implants was 5.85 (S.D. 3.42). For a majority of the subjects, more than 50% of the remaining teeth had a marginal bone loss of more than 1/3 of the root length. Forty-sex percent of the patients visited regularly dental hygienists for supportive treatment. The percentage of implants with peri-implantitis was significantly increased for smokers compared to non-smokers (p = 0.04). In the group of non-smokers, 64% of the implants had the diagnosis peri-implantitis, while the corresponding relative frequency for smokers was 78%. A majority of the individuals had a Plaque index and Bleeding on probing index >50%. The median of the follow-up time after implant placement was 7.4 years and the observation period was not significantly correlated to the degree of bone loss around the implants. Among the subjects with a mean bone loss >6 mm at implants with peri-implantitis, more than 70% had a mean marginal bone loss > 1/3 of the root length of the remaining teeth. A positive and significant correlation was found between the degree of marginal bone loss in remaining teeth and the degree of bone loss around implants with peri-implantitis. In conclusion, the results of the present study indicate that smoking as well as previous history of periodontitis are associated with peri-implantitis and may represent risk factors for this disease.


Preventive Healthcare Screening Completion Among Midlife and Older Adults With Intellectual and Developmental Disabilities.
Individuals with intellectual and developmental disabilities (IDD) face several barriers to healthcare, making them less likely to receive numerous routine preventive health screenings. Preventive healthcare is a critical aspect to maintaining health and wellness, particularly for people with complex health needs. This study examines individual- and state-level factors associated with mammogram and colonoscopy screenings in mid- and later-life foradults with IDD receiving state services. Multilevel logistic regression models analyzed data from the 2012-2013 and 2018-2019 waves of the National Core Indicators In-Person Survey (NCI-IPS). Results indicated that factors such as age, living situation, transportation access, and community involvement were associated with completion of both preventive screenings. Medicaid expansion was associated with a significantly greater likelihood of completing a colonoscopy screening only among younger persons in the sample (i.e., in their 50s). These findings may have implications for completion of preventive health screenings for adults with IDD.


Large splittings of the 4f shell of Ce3+ in garnets.
Ab initio embedded cluster calculations on Ce(3+)-doped Y3Al5O12, Lu3Al5O12, Gd3Al5O12, Y3Ga5O12, Lu3Ga5O12, and Gd3Ga5O12, which do not make use of any adjustable parameter, support recent assignments of the seventh 4f level of Ce(3+) in garnets [Przybylińska et al., Appl. Phys. Lett., 2013, 102, 241112] and that the splitting of the 4f shell of Ce(3+) in these materials is slightly smaller than 4000 cm(-1) and much larger than the 2000-2500 cm(-1) commonly assumed in analyses of 5d → 4f emission bands. Why this wrong assumption has been working well so far is explained by the fact that the intensity of the emission to the seventh level of the 4f(1) configuration is found to be only one hundredth of the integrated intensity of the emissions to the other six levels, which group themselves into two sets of three individual levels separated by 2000-2500 cm(-1). The effective field splitting and the spin-orbit coupling splitting are found to be of the same size. From a strong field coupling point of view, the first six levels result from the interactions between (2)T(2u) and (2)T(1u) cubic levels and the higher, isolated seventh level comes directly from the cubic (2)A(2u). From a weak field coupling point of view, the first three levels result from the splitting of (2)F(5/2), the second three levels from the splitting of (2)F(7/2) and the seventh level from a strong, cubic field driven interaction between (2)F(7/2) and (2)F(5/2) components [Herrmann et al., J. Appl. Phys., 1966, 37, 1312].


The AOSpine North America Geriatric Odontoid Fracture Mortality Study: a retrospective review of mortality outcomes for operative versus nonoperative treatment of 322 patients with long-term follow-up.
Retrospective, multicenter cohort study. Assess for differences in short- and long-term mortality between operative and nonoperative treatment for elderly patients with type II odontoid fractures. There is controversy regarding whether operative or nonoperative management is the best treatment for elderly patients with type II odontoid fractures. This is a retrospective study of consecutive patients aged 65 years or older with type II odontoid fracture from 3 level I trauma centers from 2003-2009. Demographics, comorbidities, and treatment were abstracted from medical records. Mortality outcomes were obtained from medical records and a public database. Hazard ratios (HRs) and 95% confidence intervals (CI) were calculated. A total of 322 patients were included (mean age, 81.8 yr; range, 65.0-101.5 yr). Compared with patients treated nonoperatively (n = 157), patients treated operatively (n = 165) were slightly younger (80.4 vs. 83.2 yr, P = 0.0014), had a longer hospital (15.0 vs. 7.4 d, P < 0.001) and intensive care unit (1.5 vs. 1.1 d, P = 0.008) stay, and were more likely to receive a feeding tube (18% vs. 5%, P = 0.0003). Operative and nonoperative treatment groups had similar sex distribution (P = 0.94) and Charlson comorbidity index (P = 0.11). Within 30 days of presentation, 14% of patients died, and at maximal follow-up (average = 2.05 yr; range = 0 d-7.02 yr), 44% had died. On multivariate analysis, nonoperative treatment was associated with higher 30-day mortality (HR = 3.00, 95% CI = 1.51-5.94, P = 0.0017), after adjusting for age (HR = 1.10, 95% CI = 1.05-1.14; P < 0.0001), male sex (P = 0.69), and Charlson comorbidity index (P = 0.16). At maximal follow-up, there was a trend toward higher mortality associated with nonoperative treatment (HR = 1.35, 95% CI = 0.97-1.89, P = 0.079), after adjusting for age (HR = 1.07, 95% CI = 1.05-1.10; P < 0.0001), male sex (HR = 1.55, 95% CI = 1.10-2.16; P = 0.012), and Charlson comorbidity index (HR = 1.28, 95% CI = 1.16-1.40; P < 0.0001). Surgical treatment of type II odontoid fracture in this elderly population did not negatively impact survival, even after adjusting for age, sex, and comorbidities. The data suggest a significant 30-day survival advantage and a trend toward improved longer-term survival for operatively treated over nonoperatively treated patients. 4.


Subconscious manipulation of pain expectation can modulate cortical nociceptive processing.
To determine whether manipulation of the expectation of pain inhibition can enhance the efficacy of conditioned pain modulation in healthy participants A conditioned pain modulation paradigm was used to investigate the effect of psychological manipulation of expectation on pain inhibition. In 19 healthy men, the lower limb nociceptive flexion reflex was elicited in isolation (test stimulus) and during application of 2 forms of conditioning stimuli. Following application of the first conditioning stimulus (CS1), the participants were informed that the subsequent conditioning stimulus (CS2) would elicit a greater amount of inhibition of test pain compared with the first. Lower limb flexion reflex size, perceived pain ratings of the test stimulus, and ratings of expected pain modulation were obtained for both test and conditioning protocols. The inhibition of perceived pain was significantly greater with CS2 compared with CS1; however, there was no significant difference in inhibition of nociceptive flexion reflex size or the participant's reported expectation of pain modulation between the 2 conditioning stimuli. As perceived pain inhibition was enhanced but flexion reflex size unchanged following the intervention, we suggest that the intervention gave rise to an inhibition of ascending nociceptive information at a supraspinal level resulting in reduced pain perception without influencing spinal level processing of nociceptive input. The finding that conditioned pain modulation can be enhanced is of relevance to clinical pain populations who commonly show impaired inhibition.


Protective effect of aqueous suspension of dried latex of Calotropis procera against oxidative stress and renal damage in diabetic rats.
Calotropis species have been used in the traditional medicinal system for the treatment of diseases of the liver and abdomen. In view of the antioxidant and anti-hyperglycemic properties of an aqueous suspension obtained from the dried latex of Calotropis procera, the present study was carried out to evaluate its efficacy in affording protection against alloxan induced changes in rat kidney. A single intraperitoneal injection of alloxan (150 mg/kg) in rats produced hyperglycemia within 3 days and altered kidney functions over a period of 90 days. Daily oral administration of the aqueous suspension (100 and 400 mg/kg) in diabetic rats produced anti-hyperglycemic effect that was comparable to that of glibenclamide (10 mg/kg). Unlike glibenclamide, the aqueous suspension did not increase the serum insulin levels in diabetic rats. However, it produced a marked reduction in the levels of urinary glucose and protein and normalized the renal tissue levels of thiobarbituric acid-reactive substances (TBARS) and glutathione (GSH) in diabetic rats and the effect was comparable to that of glibenclamide. The protection afforded by the aqueous suspension was also evident from the histological analysis of the renal tissue. Our study shows that by exhibiting antioxidant and anti-hyperglycemic property the aqueous suspension of dried latex of C. procera affords protection against the complications associated with diabetes.


Reflecting on death amidst COVID-19 and individual creativity: Cross-lagged panel data analysis using four-wave longitudinal data.
The current COVID-19 pandemic has claimed millions of lives all across the globe, making death more salient to many who may not have been readily cognizant of their mortality. While employees in certain occupations routinely deal with the idea of death or mortality (e.g., hospital workers, firefighters, and police officers), it is uncommon for the average employee to be within an environment that makes them aware of death. However, death awareness has been found to be negatively related to many important outcomes for the organization, including creativity. In the present study, using four-wave longitudinal data collected weekly-during late-June to late-July, 2020, we examine how employees react during the initial peak of COVID-19 pandemic in the United States in terms of death anxiety and death reflection (two different reactions to death awareness) and whether or not death anxiety and death reflection are related to creativity. Conducting cross-lagged panel modeling on four-wave longitudinal data obtained from 605 full-time employees, we find that positive outcomes can come from such trying times as death reflection is positively related to creativity. We offer timely, valuable implications for theory and practice. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Occupational therapy education: the relationship of purpose, objectives, and teaching models.
A clearly stated purpose of basic professional education in occupational therapy provides a base for educational programs to develop learning objectives and identify effective teaching models and behaviors. The primary purpose of professional education should be the development of problem-solving skills, self-awareness, and creative productive thinking, with "hands-on" skills relegated to a secondary purpose. Specific learning objectives and the teaching models that have been developed to meet these objectives are presented. The authors further suggest that there must be a relationship between what occurs in the classroom (implementation of teaching models) and the purpose of professional education. A survey of current occupational therapy faculty members was conducted to identify a) their preparedness in the use of teaching models and b) other factors affecting their classroom behavior (years of experience, educational level, area of concentration). Survey results portray a relatively young faculty in both rank and experience. Other data indicate that although 85% of the respondents had taken at least one education course, only slightly more than half were familiar with teaching models. Most respondents felt that course work in educational methods and models aids in the development of more effective teaching strategies.


Lost in the loop - a qualitative study on patient experiences of care in standardized cancer patient pathways.
The Norwegian health authorities introduced standardized cancer patient pathways (CPPs) in 2015, aiming to reduce practice variations across hospitals and regions, and improve the continuity, coordination and overall quality of the health care service provided to cancer patients. There has been few studies investigating this change, and that have looked into the organisational and economic benefits of standardized pathways, however the element of care and the patient perspective has been especially neglected. This study explored the care element in cancer patient pathways through an in-depth study of patient experiences. The patients were enrolled approximately three years after the introduction of standardized CPPs in Norway. Through a qualitative design with in-depth interviews, a total of 21 interviews were conducted with seven patients between 2018 and 2020. The first interview took place after the diagnosis was established and before treatment, the second interview during treatment, and the final interview approximately one year after the completion of active treatment. The empirical catchment area was eastern Norway. Data were analysed using a theoretical thematic analysis. This study sheds light on the complex challenges patients' faces, while navigating CPPs, including the need for better transition support, improved coordination and continuity in care, and a more holistic approach that encompasses emotional well-being and family support. Three overarching themes were identified: [1] Navigating CPPs: patient care and transition challenges, [2] Fragmented cancer care: challenges in coordination and continuity [3] Unmet needs and overlooked opportunities in CPPs. Patients experience that cancer patient pathways offer good medical treatment, but that the care element deserves more attention. Current CPPs are trapped in a logic of choice, preventing room for the element of care to receive the attention it requires for the patient to truly experience holistic person-centred care and continuous, well-coordinated services. Based in our study we argue there is a need to look into the missed opportunities for using the CPPs as points of departure for more holistic collaborative models for cancer care.


No association of the genetic polymorphisms of endothelial nitric oxide synthase, dimethylarginine dimethylaminohydrolase, and vascular endothelial growth factor with preeclampsia in Korean populations.
The purpose of this study was to investigate whether there is any association between preeclampsia and eNOS, DDAH, and VEGF gene polymorphisms, and also to search for a possible association between haplotypes in eNOS, DDHA, and VEGF genes and the risk for preeclampsia. DNA was extracted from whole blood of 223 preeclampsia patients and 237 healthy pregnant women. The genotypes were analyzed by a single base primer extension assay using a SNaPShot assay kit. Results were analyzed with the Student's t-test, Chi-square test, and Logistic regression analysis. Haplotype analyses were performed using Haploview 3.2 version. There were no significant differences in genotype or allele frequencies of eNOS, DDAH, and VEGF gene polymorphisms between preeclampsia patients and controls. No increase in the risk of preeclampsia for those genes was observed under any model of inheritance and there were no statistically significant associations between any haplotypes and preeclampsia risk. Polymorphisms in eNOS, DDAH, and VEGF gene do not seem to be risk factors for preeclampsia.


Biportal complete video-assisted thoracoscopic lobectomy and systematic lymphadenectomy.
The video-assisted thoracoscopic approach (VATS) for lobectomy of non-small-cell lung cancer (NSCLC) has not been standardized. Although three to four incisions are usually made, with the right surgical technique, the operation can be successfully carried out via only two incisions. This video demonstrates a case undergoing biportal complete VATS (biportal cVATS) right upper lobectomy and systematic lymphadenectomy. Here we describe our technique of biportal approach by using a combination of conventional and endoscopic instruments. As our experience gained, we consider the knacks of biportal cVATS lobectomy imply two radical changes of perspectives from the traditional triportal technique. One fundamental step is how to achieve satisfactory exposure in the case of single utility incision for multiple instruments to insert. Another technical tip that should be taken into account is how to introduce staplers conveniently without the third posterior port. Optimization of the whole procedures is critical for accomplishing anatomic hilar vascular, bronchial, and lymphatic dissection via two ports. In conclusion, biportal cVATS lobectomy for lung cancer is a safe and reliable procedure that can achieves good postoperative results without oncological compromise.


Fine needle aspiration of gastrointestinal stromal tumors.
Gastrointestinal stromal tumors (GISTs) are uncommon mesenchymal tumors of the gastrointestinal tract. Fine needle aspiration (FNA) is one option for diagnosing GISTs before surgery. This study was designed to evaluate the clinical utility of FNA in the diagnosis of GISTs. FNAs from 19 GISTs originating in the stomach, small bowel and colon obtained from 1988 to 1998 were studied. Immunocytochemistry was performed on 12 cases. The GISTs were classified as benign, borderline and malignant, according to location, size, mitotic activity and clinical outcome. Benign (three) and borderline (five) GISTs were all spindle cell type; malignant GISTs included five spindle cell type and six epithelioid type. Most smears contained abundant cellular material. Benign and borderline GISTs of spindle cell type tended to have cells arranged in tightly cohesive clusters, while malignant GISTs were more likely to exhibit loosely cohesive groups with many single cells, occasional nuclear pleomorphism, hyperchromasia and irregular nuclear contours. Epithelioid-type GISTs mimicked adenocarcinoma. Mitoses were seldom observed in either type. CD117 (KIT protein product) was demonstrated by immunocytochemistry in 9 cases, CD34 in 11, desmin in 3, S-100 protein in 2 and smooth muscle actin in 6 cases. FNA can be used to diagnose GISTs as spindle cell and epithelioid types, but cytomorphology alone cannot be used to assess malignant potential. Immunocytochemical staining for CD117 is helpful in confirming the diagnosis. Care must be taken to differentiate epithelioid-type GISTs from adenocarcinoma.


Cost-effectiveness of HIV drug resistance testing to inform switching to second line antiretroviral therapy in low income settings.
To guide future need for cheap resistance tests for use in low income settings, we assessed cost-effectiveness of drug resistance testing as part of monitoring of people on first line ART - with switching from first to second line ART being conditional on NNRTI drug resistance mutations being identified. An individual level simulation model of HIV transmission, progression and the effect of ART which accounts for adherence and resistance development was used to compare outcomes of various potential monitoring strategies in a typical low income setting in sub-Saharan Africa. Underlying monitoring strategies considered were based on clinical disease, CD4 count or viral load. Within each we considered a strategy in which no further measures are performed, one with a viral load measure to confirm failure, and one with both a viral load measure and a resistance test. Predicted outcomes were assessed over 2015-2025 in terms of viral suppression, first line failure, switching to second line regimen, death, HIV incidence, disability-adjusted-life-years averted and costs. Potential future low costs of resistance tests ($30) were used. The most effective strategy, in terms of DALYs averted, was one using viral load monitoring without confirmation. The incremental cost-effectiveness ratio for this strategy was $2113 (the same as that for viral load monitoring with confirmation). ART monitoring strategies which involved resistance testing did not emerge as being more effective or cost effective than strategies not using it. The slightly reduced ART costs resulting from use of resistance testing, due to less use of second line regimens, was of similar magnitude to the costs of resistance tests. Use of resistance testing at the time of first line failure as part of the decision whether to switch to second line therapy was not cost-effective, even though the test was assumed to be very inexpensive.


The impact of Campath 1H induction in adult liver allotransplantation.
We report our experience with Campath 1H in adult liver allotransplantation. Between December 2001 and February 2004, 77 patients underwent liver transplantation using Campath 1H induction and low-dose maintenance tacrolimus immunosuppression. The control group consisted of 50 patients with similar baseline characteristics and the same eligibility criteria, transplanted under our standard Tacrolimus/steroids regimen. Hepatitis C patients were excluded from the study. Patient and graft survival were similar for both groups. The incidence of rejection was significantly lower in the Campath vs the control group (51% vs 65% at 12 months, P = .009). Tacrolimus trough levels and conversion from Tacrolimus or the addition of other immunosuppressive drugs due to nephrotoxicity were also significantly lower in the Campath 1H group. Campath 1H induction with low-dose Tacrolimus maintenance immunosuppression is an effective regimen in reducing acute rejection in adult liver transplantation, while maintaining lower tacrolimus levels and less nephrotoxicity than our conventional immunosuppressive regimen.


Mutagenesis of pairwise combinations of histone amino-terminal tails reveals functional redundancy in budding yeast.
A large body of literature provides compelling evidence for the role of evolutionarily conserved core histone residues in various biological processes. However, site-directed mutagenesis of individual residues that are known to be sites of posttranslational modifications often does not result in clear phenotypic defects. In some cases, the combination of multiple mutations can give rise to stronger phenotypes, implying functional redundancy between distinct residues on histones. Here, we examined the "histone redundancy hypothesis" by characterizing double deletion of all pairwise combinations of amino-terminal tails (N-tails) from the four core histones encoded in budding yeast. First, we found that multiple lysine residues on the N-tails of both H2A and H4 are redundantly involved in cell viability. Second, simultaneous deletion of N-tails from H2A and H3 leads to a severe growth defect, which is correlated with perturbed gross chromatin structure in the mutant cells. Finally, by combining point mutations on H3 with deletion of the H2A N-tail, we revealed a redundant role for lysine 4 on H3 and the H2A N-tail in hydroxyurea-mediated response. Altogether, these data suggest that the N-tails of core histones share previously unrecognized, potentially redundant functions that, in some cases are different from those of the widely accepted H2A/H2B and H3/H4 dimer pairs.


Hormonal regulation of gluconeogenesis in cultured proximal tubular cells: role of cytosolic calcium.
Gluconeogenic competence of primary cultures of canine renal proximal tubular cells has been examined. Cells grown in 5 mM glucose media or in glucose-free media exhibited pyruvate-stimulated glucose production, as opposed to cells grown in 20 mM glucose media. By 72 h after the last media change, confluent cells grown in 5 mM glucose medium turn from a predominantly glycolytic to an oxidative type of metabolism. By this time, glucose production exhibited pH, 3-mercaptopicolinate, and insulin sensitivity. Parathyroid hormone, angiotensin II, and phenylephrine stimulated glucose production in a nonadditive fashion. Single-cell cystolic Ca2+ measurements using microspectrofluorometric techniques revealed that all three hormones elicited Ca2+ transients in proximal tubular cells. Ionomycin stimulated glucose production by proximal tubular cells, suggesting that Ca2+ transients could represent a sufficient stimulus for glucose production. When hormone-induced Ca2+ transients were curtailed by a pretreatment with the membrane-permeant Ca2+ chelator, Maptam, hormonal stimulation of glucose production was abolished, suggesting that Ca2+ transients represent not only a sufficient, but a necessary event in the stimulation of glucose production by these hormones.


Fatigue reduces the complexity of knee extensor torque fluctuations during maximal and submaximal intermittent isometric contractions in man.
Neuromuscular fatigue increases the amplitude of fluctuations in torque output during isometric contractions, but the effect of fatigue on the temporal structure, or complexity, of these fluctuations is not known. We hypothesised that fatigue would result in a loss of temporal complexity and a change in fractal scaling of the torque signal during isometric knee extensor exercise. Eleven healthy participants performed a maximal test (5 min of intermittent maximal voluntary contractions, MVCs), and a submaximal test (contractions at a target of 40% MVC performed until task failure), each with a 60% duty factor (6 s contraction, 4 s rest). Torque and surface EMG signals were sampled continuously. Complexity and fractal scaling of torque were quantified by calculating approximate entropy (ApEn), sample entropy (SampEn) and the detrended fluctuation analysis (DFA) scaling exponent α. Fresh submaximal contractions were more complex than maximal contractions (mean ± SEM, submaximal vs. maximal: ApEn 0.65 ± 0.09 vs. 0.15 ± 0.02; SampEn 0.62 ± 0.09 vs. 0.14 ± 0.02; DFA α 1.35 ± 0.04 vs. 1.55 ± 0.03; all P < 0.005). Fatigue reduced the complexity of submaximal contractions (ApEn to 0.24 ± 0.05; SampEn to 0.22 ± 0.04; DFA α to 1.55 ± 0.03; all P < 0.005) and maximal contractions (ApEn to 0.10 ± 0.02; SampEn to 0.10 ± 0.02; DFA α to 1.63 ± 0.02; all P < 0.01). This loss of complexity and shift towards Brownian-like noise suggests that as well as reducing the capacity to produce torque, fatigue reduces the neuromuscular system's adaptability to external perturbations.


Analytical partial wave expansion of vector Bessel beam and its application to optical binding.
Explicit partial wave coefficients are derived for nondiffractive vector Bessel beam of arbitrary order and polarization. Calculations based on the analytical partial wave expansion yield results that agree well with recent numerical calculations and experiments on optical binding. We have also investigated how one can tailor the interparticle interaction by overlaying different coatings. It is found that the Ag and low dielectric coating can increase the number of equilibrium positions, whereas the antireflection coating reduces it.


[Use of honey in conservative treatment of senile cataracts].
Instillations of 25, 33, or 50 percent aqueous solutions of flower honey in combs were administered to patients with developing senile cortical cataracts. 1-2 three-month courses of honey instillations into the conjunctival sac were carried out annually. The rest time the patients were administered three-month courses of vitamin drops or vicein. A total of 108 patients (202 eyes) were followed up for 2 to 15 years (7 years on an average). Visual acuity of at least 0.1 was preserved in 95.5 percent of eyes, in 55.9 percent of these it did not get worse over the course of follow-up, whereas it was preserved in but 35.3 percent of the controls.


Microfossils in Wisconsinan Loess and Till from Western Illinois and Eastern Iowa.
Wisconsinan loess from Illinois and Iowa contains a varied assemblage of microfossils including radiolaria, foraminifera, sponge spicules, and opal phytoliths. The foraminifera and radiolaria are derived from Cretaceous rocks occurring on the northern Great Plains. The sponge spicules are from fresh-water sponges living during the epoch of loess deposition. The phytoliths were produced by vegetation growing during deposition. These microfossils are valuable in determining loess and till provenance and in paleoecological reconstruction.


Importance of early objective auditory testing in the presentation of sudden sensorineural hearing loss in children.
Functional hearing loss can be due to an auditory manifestation of functional neurological disorder, previously known as conversion disorder. This is a case series of 3 pediatric patients with a diagnosis of idiopathic SSNHL who ultimately were found to have functional neurological disorder. Average age was 12.7 years at presentation (range 10-14 years). All three patients underwent invasive interventions prior to their initial clinic visit. All patients demonstrated profound SNHL on behavioural audiogram, but normal otoacoustic emissions (OAE) and auditory brainstem response testing. With counselling, both patients demonstrated significant hearing improvement. Early use of OAE's in the workup of SSNHL can avoid unnecessary and potentially harmful therapies and expedite access to counselling services which may help lead to symptom resolution.


The Full Mediating Role of Loneliness on the Relationship Between Social Support and Depression Among Rural Family Caregivers of Persons With Severe Mental Illness.
Objective: Depression is a common and overwhelming psychiatric disorder among family caregivers of persons with severe mental illness (SMI). The interrelationships among social support, loneliness, and depression, especially among this relatively vulnerable group, are poorly understood. The aim of the present study was to test the hypothesis that the social support contributes to the alleviation of depression, through its effect on reducing loneliness. Methods: A survey of 256 rural family caregivers of persons with SMI was conducted between December 2017 and May 2018 in Chengdu City, Sichuan Province, China. Social support, loneliness and depression were measured. A series of multiple linear regression models and bootstrapping procedure were performed to examine the mediating effects of loneliness on the association between social support as well as its components and depression. Results: The proportion of family caregivers of persons with SMI who reported significant depressive symptoms was 53.5%. Loneliness fully mediated the negative association between social support and depression. As to three components of social support, subjective support and objective support only had indirect associations with depression mediated by loneliness, while support utilization had both direct and indirect relationships with depression. Conclusion: The current study highlighted that social support and its three components may acted as protective factors by decreasing the feelings of loneliness, which created a beneficial effect on depression among family caregivers of persons with SMI.


Solid cancer incidence and low-dose-rate radiation exposures in the Techa River cohort: 1956 2002.
This is the first analysis of solid cancer incidence in the Techa River cohort, a general population of men and women of all ages who received chronic low-dose rate exposures from environmental radiation releases associated with the Soviet nuclear weapons programme. This cohort provides one of the few opportunities to evaluate long-term human health risks from low-dose radiation exposures. Cancer incidence rates in this cohort were analysed using excess relative risk (ERR) models. The analyses make use of individualized dose estimates that take into account residence history, age and other factors. Cases are identified on the basis of continuing, active follow-up of mortality and cancer incidence. Based on 1836 solid cancer cases with 446 588 person years accrued over 47 years of follow-up, solid cancer incidence rates were found to increase with dose and about 3% of the cases were attributable to radiation exposure. The ERR was 1.0/Gy (P = 0.004 95% CI (0.3; 1.9) in a linear dose-response model. There was no significant non-linearity in the dose response and no indication of effect modification by gender, ethnicity, attained age or age at first exposure. The Techa River cohort provides strong evidence that low-dose, low-dose rate exposures lead to significant increases in solid cancer risks that appear to be linear in dose. The results do not suggest that risks associated with low-dose rate exposures are less than those seen following acute exposures such as were received by atomic bomb survivors.


A review of diagnostic tests for diagnosing failure of transfer of passive immunity in dairy calves in New Zealand.
The aim of this review is to critically assess the test characteristics and practicality of published data on direct and indirect tests for diagnosing failure of transfer of passive immunity (FPT) in dairy calves in New Zealand, to provide recommendations for veterinary practitioners, and to examine the recommended sample size for assessing herd-level prevalence of FPT and the confidence in the results obtained. The definition of FPT is based on measurement of concentrations of IgG in serum of neonatal calves after colostrum intake. The gold standard method for measurement of concentrations of IgG is radial immunodiffusion. However its cost, requirements for laboratory equipment, and the time taken to obtain results have meant that alternative tests have been developed. The turbidimetric immunoassay and ELISA also directly measure concentrations of IgG. Indirect tests include measurement of concentrations of total proteins (TP) in the laboratory or using a refractometer, γ-glutamyl transferase (GGT) activity, and the zinc sulfate turbidity (ZST) test. Of the indirect tests, measurement of concentrations of TP in the laboratory or using a refractometer combine high specificity and sensitivity with a consistent association with concentrations of IgG in calves between 1-7 days of age. Using a refractometer is less accurate than direct measurement in a laboratory, but is still a suitable test if low cost and speed are important. Although GGT activity is strongly associated with concentrations of IgG in serum, the relationship varies with time after birth. Therefore the target thresholds change with time, increasing error compared to the measurement of concentrations of TP in serum. Similarly, factors other than total concentrations of IgG have a significant effect on the association with ZST test, complicating interpretation. Thus, when direct measurement of concentrations of IgG is not feasible, the recommendation is that concentrations of TP in serum should be used as the diagnostic test for diagnosis of FPT, providing calves are not dehydrated. Using a sample size of 12 calves is suitable for estimating whether the herd-level prevalence of FPT is <20% or >20%, if there are no calves or >5 calves diagnosed with FPT, respectively, but is limited in diagnostic confidence when 1-4 calves test positive. Diagnostic interpretation can be significantly improved if tests of FPT are used alongside information on the likely risk of FPT on the tested farm.


Management of chronic viral hepatitis in patients with thalassemia: recommendations from an international panel.
Chelation therapy with new drugs prevents cardiac damage and improves the survival of thalassemia patients. Liver diseases have emerged as a critical clinical issue. Chronic liver diseases play an important role in the prognosis of thalassemia patients because of the high frequency of viral infections and important role of the liver in regulating iron metabolism. Accurate assessment of liver iron overload is required to tailor iron chelation therapy. The diagnosis of hepatitis B virus- or hepatitis C virus-related chronic hepatitis is required to detect patients who have a high risk of developing liver complications and who may benefit by antiviral therapy. Moreover, clinical management of chronic liver disease in thalassemia patients is a team management issue requiring a multidisciplinary approach. The purposes of this paper are to summarize the knowledge on the epidemiology and the risks of transmission of viral infections, to analyze invasive and noninvasive methods for the diagnosis of chronic liver disease, to report the knowledge on clinical course of chronic viral hepatitis, and to suggest the management of antiviral therapy in thalassemia patients with chronic hepatitis B or C virus or cirrhosis.


PDGF stimulates the massive expansion of glial progenitors in the neonatal forebrain.
Platelet-derived growth factor (PDGF) plays a major role in regulating migration, proliferation, and differentiation of glial progenitors during normal brain development and in the abnormal proliferation and dispersion that drives the formation of malignant gliomas. To further explore the relationship between PDGF's effects on normal glial progenitors and its role in the formation of gliomas, we infected progenitor cells in the subventricular zone (SVZ) of the lateral ventricle of neonatal rat pups with a retrovirus that expresses PDGF and green fluorescent protein (GFP). At 3 days post-injection (dpi), a proliferation of PDGFRalpha+ progenitors was seen in the SVZ and white matter around the injection site and by 10 dpi the animals had large diffusely infiltrating tumors that resembled glioblastomas. The tumors contained a massive proliferation of both infected and uninfected PDGFRalpha+ progenitors, suggesting that PDGF was driving tumor formation via both autocrine and paracrine signaling. Rats co-injected with two retroviruses (one that expresses PDGF-IRES-DSRED and one that expresses only GFP) formed tumors that contained a mixture of DSRED+ cells (PDGF producers) and GFP+ cells (recruited progenitors). Time-lapse microscopy of slice cultures confirmed that both DSRED+ and GFP+ cells were highly migratory and proliferative. Furthermore, adding exogenous PDGF to slice cultures generated from nontumor-bearing brains (injected with control GFP retrovirus only) stimulated the migration and proliferation of GFP+ progenitors. These findings reveal the inherent growth factor responsiveness and tumorigenic potential of PDGFRalpha+ progenitors and highlight the importance of paracrine signaling in stimulating glioma growth and infiltration.


Primary meningeal rhabdomyosarcoma in a child with hypomelanosis of Ito.
Intracranial rhabdomyosarcomas are rare neoplasms, and those thought to be primary meningeal tumors are even more rare. Hypomelanosis of Ito is a neurocutaneous disorder believed to involve a defect in cells of neural crest origin. We report the case of a 15-month-old boy with hypomelanosis of Ito who developed a primary meningeal rhabdomyosarcoma. The patient initially presented with hydrocephalus and 2 months later developed neurologic signs localizing to the spinal cord. Radiologic studies revealed widespread leptomeningeal enhancement with compression of the spinal cord at C5-C7. A brain biopsy revealed a tumor diffusely involving the meninges. Microscopically, the tumor was composed of rhabdomyoblasts, many of which showed prominent cross-striations on routine hematoxylin-eosin staining. To the best of our knowledge, this is the first reported case of meningeal rhabdomyosarcoma in a patient with hypomelanosis of Ito and the fourth reported case of a primary meningeal rhabdomyosarcoma reported in the world literature.


[Modification of the effect of high temperature on biochemical processes by perturbed geomagnetic field].
The biochemical data on the influence of perturbed geomagnetic field on the hormonal-mediator regulation systems are presented. The possibility of biological effects modification under combined action of perturbed geomagnetic field and high temperature of environment is discussed.