Method validation and simultaneous quantification of eight organochlorines/organophosphates in apple by gas chromatography.
The increasing and extensive use of pesticides worldwide has resulted in a significant loss of non-target populations particularly humans by direct or indirect exposures. Also, various methods have been used for the estimation of pesticide residues in fruits and vegetables from recent past which are either tedious, time consuming or expensive. Therefore, the present study was performed to determine the pesticide residues from apple by simple and novel validated gas chromatography. A novel, accurate, ecofriendly and cost-effective gas chromatography method was developed for simultaneous quantification of eight pesticides, namely chlorpyrifos-methyl (1), chlorpyrifos (2), quinolphos (3), profenofos (4), myclobutnil (5), ethion (6), fenpropathrin (7) and cypermethrin (8). The developed method was validated as per the SANTE guidelines. All calibration curves showed a good linear relationship (r > 0.99) within the test range. Precision was evaluated by intra- and inter-day tests with relative standard deviations (RSDs) < 2.0%, recovery in between 70% and 120% with RSDs < 2.00%. The results demonstrate that the concentration of pesticides 1 to 8 were found below the detectable limit. Method validation parameters like linearity, precision, accuracy, specificity, robustness, detection and quantification limits were found within the acceptable range. The proposed method makes it possible to determine simultaneously pesticides 1-8 in one run which can be extended for residue-based standardization of pesticides from apple and other fruits and vegetables. © 2019 Society of Chemical Industry.


Journalists' networks: Homophily and peering over the shoulder of other journalists.
Social media plays an important role in how journalists gather and report news. To understand journalists' professional environment, we examine the networks of journalists on Twitter who cover politics for U.S. newspapers in conjunction with a sample of journalists who completed a survey. By combining both their network data and survey responses, we examine the distribution of journalists' ideology (n = 264) and journalistic values (n = 247); and using the network data, we examine the directional relationships between journalists working at large and small papers (n = 4,661). We find that journalists tend to form connections with those who share similar journalistic values. However, we find little evidence that journalists build professional relationships based on similarity in political ideology. Lastly, journalists at larger media outlets are more likely to be central in journalists' Twitter networks, providing evidence that journalists look to other journalists at larger outlets for direction in news coverage. Our evidence provides unique insights into how social media illuminates journalists' professional environment and how that environment may shape news coverage.


Mapping of B-cell epitopes of the human hepatitis B virus X protein.
The immune response to the X protein of human hepatitis B virus (HBV) was studied by epitope mapping by using a set of MS2-HBx fusion proteins and synthetic peptides. Antibodies in sera of patients with acute and chronic HBV infection showed a multispecific immune response. Each serum contained antibodies to a different set of epitopes, which taken together cover most of the HBx sequence. Some of the epitopes were detectable only by immunoblotting with fusion proteins; others were detectable only by an enzyme-linked immunosorbent assay (ELISA) with synthetic peptides. The carboxy-terminal half of the HBx protein was preferentially recognized by antibodies from patients with chronic hepatitis and contained a short immunodominant antigenic region with at least two major nonoverlapping epitopes. Anti-HBx antibody titers as revealed by peptide ELISAs were highest and most frequent in patients with chronic hepatitis and usually low in acutely infected patients and asymptomatic carriers. The data demonstrate a remarkable qualitative and quantitative heterogeneity of the humoral HBx immune response which can be monitored by HBx-specific peptide ELISAs. Such tests may become useful diagnostic tools.


Evaluation of mammographic viewbox luminance, illuminance, and color.
Twenty-three viewboxes were evaluated in six mammography facilities. Luminance and illuminance measurements were made with a recently calibrated photometer. Color temperatures were measured with a Minolta color meter. The average luminance for the 23 viewboxes was 2920 nit (lumen/Sr/m2), the lowest value was 1610 nit, and the highest value was 3630 nit. The average illuminance was 40 lux (lumen/m2), with 6 lux as the lowest value, and 97 lux as the highest. The average color temperature was 8400 K with the lowest value of 4900 K, and the highest of 10,900 K.


A fast BK-type KCa current acts as a postsynaptic modulator of temporal selectivity for communication signals.
Temporal patterns of spiking often convey behaviorally relevant information. Various synaptic mechanisms and intrinsic membrane properties can influence neuronal selectivity to temporal patterns of input. However, little is known about how synaptic mechanisms and intrinsic properties together determine the temporal selectivity of neuronal output. We tackled this question by recording from midbrain electrosensory neurons in mormyrid fish, in which the processing of temporal intervals between communication signals can be studied in a reduced in vitro preparation. Mormyrids communicate by varying interpulse intervals (IPIs) between electric pulses. Within the midbrain posterior exterolateral nucleus (ELp), the temporal patterns of afferent spike trains are filtered to establish single-neuron IPI tuning. We performed whole-cell recording from ELp neurons in a whole-brain preparation and examined the relationship between intrinsic excitability and IPI tuning. We found that spike frequency adaptation of ELp neurons was highly variable. Postsynaptic potentials (PSPs) of strongly adapting (phasic) neurons were more sharply tuned to IPIs than weakly adapting (tonic) neurons. Further, the synaptic filtering of IPIs by tonic neurons was more faithfully converted into variation in spiking output, particularly at short IPIs. Pharmacological manipulation under current- and voltage-clamp revealed that tonic firing is mediated by a fast, large-conductance Ca(2+)-activated K(+) (KCa) current (BK) that speeds up action potential repolarization. These results suggest that BK currents can shape the temporal filtering of sensory inputs by modifying both synaptic responses and PSP-to-spike conversion. Slow SK-type KCa currents have previously been implicated in temporal processing. Thus, both fast and slow KCa currents can fine-tune temporal selectivity.


Enzyme-linked immunosorbent assay as a helpful diagnostic tool for pemphigus erythematosus with equivocal histologic and immunofluorescent findings.
Enzyme-linked immunosorbent assay is a sensitive and specific method for the detection of circulating autoantibodies in pemphigus vulgaris and foliaceus. Herein, pemphigus erythematosus with equivocal immunofluorescence and non-diagnostic histology, but confirmed by enzyme-linked immunosorbent assay, is described. As a non-invasive, sensitive, and specific assay with additional utility for monitoring disease activity, this case adds to growing evidence supporting ELISA as the diagnostic method of choice for common and less common variants of pemphigus.


[Neurochemical mechanisms of the involvement of sensorimotor cortex neurons in food and orienting-exploratory behavior].
Reactions of individual neurons to electrical stimulation of motivational areas of the lateral hypothalamus were studied in the somatosensory cortex of alert rabbits during micro. iontophoretic application of acetylcholine, norepinephrine or cycloheximide. The former two drugs altered equally the neuron reactions both on weak (inducing an orienting response) and strong stimulation (causing feeding behaviour). The latter drug also affected the neuron reactions. The feeding and orienting responses seem to be actualized through a specific peptide synthesis in the somatosensory cortex's neurons altering their sensitivity to neurotransmitters.


Pharmacokinetics and protein adduct formation of the pharmacologically active acyl glucuronide metabolite of mycophenolic acid in pediatric renal transplant recipients.
The acyl glucuronide metabolite (AcMPAG) of mycophenolic acid (MPA) has been found to possess both immunosuppressive and pro-inflammatory activity in vitro. In this study its pharmacokinetics were determined in pediatric renal transplant recipients receiving cyclosporine, steroids, and mycophenolate mofetil. Twelve-hour concentration-time profiles for AcMPAG, MPA, and the phenolic glucuronide (MPAG) were determined by high-performance liquid chromatography (HPLC) in the initial (1-3 wk; n = 16) and stable (3-12 mo; n = 22) phases after transplantation. In addition, the formation of covalent adducts between AcMPAG and plasma albumin (AcMPAG-Alb) was investigated using Western Blot analysis. AcMPAG-AUC(12h) showed significant (p < 0.05) correlations with MPA-AUC(12h) (r = 0.78) and MPAG-AUC(12h) (r = 0.78). In molar equivalents the median AcMPAG-AUC(12h) was 10.3% (range, 4.6%-45.5%) of MPA-AUC(12h). Values (median [range]) of AcMPAG-AUC(12h) (10.1 [3.30-30.1] mg.h/L), AcMPAG-C(0) (0.48 [0.08-1.43] mg/L), and AcMPAG-C(max) (1.95 [0.88-5.35] mg/L) were significantly (p < 0.05) higher in the stable phase than in the initial phase: 3.54 [2.07-20.0] mg.h/L for AUC(12h); 0.25 [<0.04-0.97] mg/L for C(0), and 1.12 [0.32-2.44] mg/L for C(max). The increases in the AcMPAG pharmacokinetic variables were paralleled by significant increases in the corresponding MPA variables. In addition, a strong negative correlation (r = -0.69; p < 0.05) was found between AcMPAG concentrations and the creatinine clearance. AcMPAG-Alb adducts were detected in all patient samples. They showed considerable interindividual variation and increased significantly with time from the initial phase to the stable phase. AcMPAG-Alb correlated significantly (p < 0.05) with AcMPAG-AUC(12h) (r = 0.70) and plasma albumin (r = 0.40). AcMPAG plasma concentrations are dependent on renal function, MPA disposition, and glucuronidation. The pharmacokinetics of AcMPAG is characterized by broad interindividual variation. In some patients AcMPAG may significantly contribute to the immunosuppression during mycophenolate mofetil therapy. AcMPAG-Alb adduct formation may serve as a marker for extended AcMPAG exposure. The association of AcMPAG with adverse effects must be further investigated.


Methylmethacrylate induces pulmonary hypertension and increases lung vascular permeability in sheep.
Methylmethacrylate (MMA) is a bone cement used to attach prosthetic joints to raw bone surfaces. Occasional reports of pulmonary complications following total hip replacement suggest that MMA may induce pulmonary microvascular abnormalities. We studied the hemodynamic and pulmonary edemagenic effects of 2 mg/kg and 12 mg/kg MMA in 23 sheep. After the 12 mg/kg dose there was a marked fall in mean systemic blood pressure (SBP) within 30 s from 92 +/- 7 to 59 +/- 3 mmHg (p less than 0.05). The SBP returned to normal and then decreased, again becoming significantly lower than baseline at 120 min. Mean pulmonary artery pressure (PAP) increased from 16.8 +/- 1.2 to 27.0 +/- 1.5 mmHg at 0.5 min (p less than 0.01 then slowly returned to normal over 1 h. Despite the transient changes in pulmonary hemodynamics, baseline lymph flow (QL) doubled at 30 min and tripled at 120 min to 3.0 +/- 0.4 and 4.4 +/- 0.6, respectively (p less than 0.01). Lymph/plasma ratio for albumin was 0.83 +/- 0.03 at baseline and was unchanged throughout the study. Lung tissue water/blood free dry weight ratio was 5.4 +/- 0.4 compared to 3.6 +/- 0.3 for normal sheep (p less than 0.05). After the low dose there was no change in SBP or PAP, and QL only doubled (1.0 +/- 0.3 to 2.3 +/- 0.7). The L/P albumin was unchanged. We found no evidence of polymorphonuclear leukocyte (PMN) trapping in the pulmonary parenchyma by lung biopsy or by counts of PMNs in pulmonary artery and aortic blood.(ABSTRACT TRUNCATED AT 250 WORDS)


An Investigation on the Correlation between the Mechanical Properties of Human Skull Bone, Its Geometry, Microarchitectural Properties, and Water Content.
With increasingly detailed imaging and mechanical analysis, modalities need arises to update methodology and assessment criteria for skull bone analysis to understand how bone microarchitecture and the presence of attached tissues may affect the response to mechanical load. The main aim was to analyze the effect of macroscopic and microstructural features, as well as periosteal attachment, on the mechanical properties of human skull bone. Fifty-six skull specimens from ethanol-phenoxyethanol-embalmed cadavers were prepared from two human cadavers. Assuming symmetry of the skull, all samples from one-half each were stripped of periosteum and dura mater, while the soft tissues were kept intact on the remaining samples on the contralateral side. The specimens were analyzed using microcomputed tomography to assess trabecular connectivity density, total surface area, and volume ratio. The specimens were loaded under three-point bend tests until fracture with optical co-registration. The bone fragments were then lyophilized to measure their water content. With increasingly detailed imaging and mechanical analysis modalities, there is a need to update methodology and assessment criteria for skull bone analysis to understand how the bone microarchitecture and the presence of attached tissues may affect the response to mechanical load. The mechanical properties were negatively correlated to bone thickness and water content. Conversely, most microarchitectural features did not influence either mechanical parameter. The correlation between mechanical response data and morphologic properties remains similar between the results of embalmed tissues presented here and fresh osseous tissue from literature data. The findings presented here add to the existing methodology to assess human skull for research purposes. The interaction between most microarchitectural features in ethanol-phenoxyethanol-embalmed embalmed skull samples and bending stress appear to be minute.


The effect of visual biofeedback on balance in elderly population: a systematic review.
Balance is commonly affected by multiple factors, especially among the elderly population. Visual biofeedback (VBF) is an intervention tool that can be used in balance rehabilitation. This study aimed to systematically review randomized controlled trials that examine whether VBF training is effective in improving balance in an elderly population. Three databases were searched: CIAHL, EMBASE, and MEDLINE. The searches were limited to the period from 2010 to 2016. Healthy adults, aged ≥65 years, with no specific disorders were included. Interventions were any VBF intervention with the aim of improving balance and were compared to no intervention, traditional exercises, placebo, or standard care. The outcome measures were balance as measured by any validated outcome measure. The Physiotherapy Evidence Database quality assessment tool and The Cochrane Collaboration tool for assessing risk of bias were used by two independent authors (HA and FM) in order to appraise the included studies. The database search resulted in 879 articles, of which five papers were included. VBF was compared to no intervention, a placebo, and traditional exercise. The total number of participants in all the five included studies was 181, with a mean age of 74.3 years (standard deviation 6.7). Two studies were rated as high-quality studies, and three were rated as fair quality. Engaging elderly people living in the community in VBF training was found to be effective and could improve their balance ability. However, the variation between studies in methodology, intervention protocol, and outcomes utilized made it difficult to inform a definitive statement regarding the potential application of VBF for balance training with the elderly. Furthermore, high-quality randomized control trials are required. The systematic review level of evidence is moderate, and the strength of recommendation is that VBF is likely to be beneficial.


Morphological evidence for penetration of anti-O antibody through the capsule of Klebsiella pneumoniae.
The role of the capsule in the reaction with anti-O or anti-K serum was examined morphologically by the techniques of freeze-substitution and immunoelectron microscopy in two strains of Klebsiella pneumoniae differing in virulence for mice. Strain Chedid (O1:K2), an encapsulated virulent strain, has a thicker capsule (150 nm) than the encapsulated avirulent strain 277 (O1:K2) (60 nm). Two morphologically recognizable domains in the capsule created by the arrangement of the capsular filaments were clearly seen in strain Chedid but were less evident in strain 277. Anti-O antibody could penetrate through the capsular layer of both strains. The capsule has no function as a barrier for the penetration of the antibody. Anti-K antibody reacted only on the surface of the capsule and induced swelling of the capsule.


Increasing trend of HIV seropositivity among commercial sex workers attending the Voluntary and Confidential Counseling and Testing Centre in Manipur, India.
A total of 1903 commercial sex workers (CSWs) attending the Voluntary and Confidential Counseling and Testing Centre at the Department of Microbiology, Regional Institute of Medical Sciences, Manipur, were screened for HIV infection over a period of five years from March 1998 to February 2003. All cases were in the age group 13-55 years. Most cases were in the age group 20-30 years (50.86%). Out of 1903 CSWs, 304 were found to be HIV-seropositive, confirmed by three tests (ELISA/RAPID/SIMPLE) of different biological antigen principles according to India's National AIDS Control Organisation guidelines. The annual rising trend in incidence of HIV seropositivity among CSWs from March 1998 (10.93%) to February 2003 (29.68%) was observed in the test site attenders, in contrast to the declining trend among injecting drug users in the state from March 1998 (76%) to February 2003 (59.82%). In all, 622 sexually transmitted infection (STI) cases were diagnosed, of which 242 (38.90%) had syphilis, which was the commonest STI, and 172 (27.65%) had ulcerative lesions. Increasing HIV seropositivity among CSWs observed in this study reflects the changing pattern of HIV transmission in Manipur.


Cell resolved, multiparticle model of plastic tissue deformations and morphogenesis.
We propose a three-dimensional mechanical model of embryonic tissue dynamics. Mechanically coupled adherent cells are represented as particles interconnected with elastic beams which can exert non-central forces and torques. Tissue plasticity is modeled by a stochastic process consisting of a connectivity change (addition or removal of a single link) followed by a complete relaxation to mechanical equilibrium. In particular, we assume that (i) two non-connected, but adjacent particles can form a new link; and (ii) the lifetime of links is reduced by tensile forces. We demonstrate that the proposed model yields a realistic macroscopic elasto-plastic behavior and we establish how microscopic model parameters determine material properties at the macroscopic scale. Based on these results, microscopic parameter values can be inferred from tissue thickness, macroscopic elastic modulus and the magnitude and dynamics of intercellular adhesion forces. In addition to their mechanical role, model particles can also act as simulation agents and actively modulate their connectivity according to specific rules. As an example, anisotropic link insertion and removal probabilities can give rise to local cell intercalation and large scale convergent extension movements. The proposed stochastic simulation of cell activities yields fluctuating tissue movements which exhibit the same autocorrelation properties as empirical data from avian embryos.


Conbercept and Ranibizumab Pretreatments in Vitrectomy with Silicone Oil Infusion for Severe Diabetic Retinopathy.
We compared the efficacies of intravitreal ranibizumab (IVR) and intravitreal conbercept (IVC) as the adjuvant pretreatments for vitrectomy with silicone oil infusion for tractional retinal detachment (TRD) secondary to proliferative diabetic retinopathy. This retrospective study comprised 74 patients (79 eyes) who underwent vitrectomy with silicone oil tamponade for diabetic TRD. They received IVC (37 eyes) or IVR (42 eyes) at standard doses 3-5 days preoperatively and were followed up for ∼6 months. Anatomic success rate, intra- and postoperative complications, and visual outcomes were compared between both groups. Initial (IVC vs. IVR: 97% vs. 98%) and final anatomic success rates (100% in each group) and mean visual acuity changes were not significantly different (P = 0.46). Intraoperative complications [iatrogenic retinal breaks (P = 0.58) and intraoperative bleeding (P = 0.66)], postoperative complications [fibrin formation (P = 0.51), postoperative preretinal bleeding (P = 0.88), progressing or persistent neovascular glaucoma (P = 0.63), progressive fibrovascular proliferation (P = 0.93), and recurrent retinal detachment (P = 0.93)], and surgical variables [surgical time (P = 0.53)] were similar between both groups. Conbercept and ranibizumab are equally effective surgical adjuvants for vitrectomy with silicone oil infusion in patients with diabetic TRD.


Quadrupole Order in the Frustrated Pyrochlore Tb_{2+x}Ti_{2-x}O_{7+y}.
A hidden order that emerges in the frustrated pyrochlore Tb_{2+x}Ti_{2-x}O_{7+y} with T_{c}=0.53 K is studied using specific heat, magnetization, and neutron scattering experiments on a high-quality single crystal. Semiquantitative analyses based on a pseudospin-1/2 Hamiltonian for ionic non-Kramers magnetic doublets demonstrate that it is an ordered state of electric quadrupole moments. The elusive spin liquid state of the nominal Tb_{2}Ti_{2}O_{7} is most likely a U(1) quantum spin-liquid state.


NATURAL HERITABILITIES: CAN THEY BE RELIABLY ESTIMATED IN THE LABORATORY?
The validity of the assumption, that laboratory estimates of heritabilities will tend to overestimate natural heritabilities, due to a reduction in environmental variability and thus the phenotypic variance of traits, is examined. One hundred sixty-five field estimates of narrow sense heritabilities derived from the literature are compared with 189 estimates from laboratory studies on wild, outbred animal populations derived from the data set of Mousseau and Roff. The results indicate that 84% of field heritabilities are significantly different from zero and that for morphological, behavioral, and life-history traits there are no significant differences between laboratory and field estimates of heritability. Unexpectedly, mean heritabilities for morphological and life-history traits are actually higher in the field than in the lab. Twenty-two cases were found for which both laboratory and natural heritabilities had been estimated on the same traits. For this subset of the data, laboratory heritabilities tended to be higher than field estimates, but the difference was not significant. Also, the correlation between lab and field estimates was high (r = 0.6, P < 0.001), and the regression slope did not differ significantly from one. The major implications of this study are that laboratory estimates of heritability should generally provide reasonable estimations of both the magnitude and the significance of heritabilities in nature.


Effects of the interaction range on structural phases of flexible polymers.
We systematically investigate how the range of interaction between non-bonded monomers influences the formation of structural phases of elastic, flexible polymers. Massively parallel replica-exchange simulations of a generic, coarse-grained model, performed partly on graphics processing units and in multiple-gaussian modified ensembles, pave the way for the construction of the structural phase diagram, parametrized by interaction range and temperature. Conformational transitions between gas-like, liquid, and diverse solid (pseudo) phases are identified by microcanonical statistical inflection-point analysis. We find evidence for finite-size effects that cause the crossover of "collapse" and "freezing" transitions for very short interaction ranges.


Effects of hypertonic (7%) saline on brain injury in experimental Escherichia coli meningitis.
We sought to know whether hypertonic (7%) saline (HTS) attenuates brain injury by improving cerebral perfusion pressure (CPP) and down-modulating acute inflammatory responses in experimental bacterial meningitis in the newborn piglet. Twenty-five newborn piglets were assorted into three groups: 6 in the control group (C), 10 in the meningitis group (M), and 9 in the meningitis with HTS infusion group (H). Meningitis was induced by intracisternal injection of 10(8) colony forming units of Escherichia coli in 100 microL of saline. 10 mL/kg of HTS was given intravenously as a bolus 6 hr after induction of meningitis, thereafter the infusion rate was adjusted to maintain the serum sodium level between 150 and 160 mEq/L. HTS significantly attenuated meningitis-induced brain cell membrane disintegration and dysfunction, as indicated by increased lipid peroxidation products and decreased Na+, K+-ATPase activity in the cerebral cortex in M. HTS significantly attenuated acute inflammatory markers such as increased intracranial pressure, elevated lactate level and pleocytosis in the cerebrospinal fluid observed in M. Reduced CPP observed in M was also significantly improved with HTS infusion. These findings implicate some attenuation of the meningitis-induced alterations in cerebral cortical cell membrane structure and function with HTS, possibly by improving CPP and attenuating acute inflammatory responses.


Animal transmission of enteric non-A, non-B hepatitis infection to Macaca mulatta by faeco-oral route.
M. mulatta monkeys were inoculated faeco-orally by enteric non-A, non-B virus to study the development of clinical, biochemical, histopathological and serological changes in the blood and liver. Pooled stool samples positive for putative non-A, non-B viral antigen by micro-ELISA and aggregated viral particles by immune electron microscopy, were administered in two M. mulatta monkeys. Biochemical, histopathological and serological changes were seen in the blood and liver and excretion of 27 nm virus like particles around 27 days of inoculation in the experimental monkey but not in the control animal.


Qualitative age interactions in breast cancer studies: a mini-review.
A qualitative age interaction is defined as the reversal of relative risks or rates according to age at onset, and is often evident in studies that examine the etiology, prognosis and treatment of breast cancer. For example, incidence rates (or risks) are higher for aggressive when compared with indolent breast cancers prior to age 40-50 years, after which rates are higher for indolent tumors. Nulliparity and obesity decrease breast cancer risk in younger women, but increase risk in older women. Curves depicting the annual hazard of breast cancer death are shaped differently for the early- and late-onset tumors. Clinical trials for mammography screening, fenretinide chemoprevention and neo-adjuvant chemotherapy show opposite effects in younger and older women. Finally, high-risk/early onset breast cancers are more common among African-American women than Caucasian women, and this may partly account for the racial survival disparities. Taken together, these examples imply that aging may modify breast cancer risk, prognosis and treatment. These qualitative age interactions (or effect modifications) are important because they suggest that high-risk/early-onset and low-risk/late-onset breast cancers are different diseases, derived from different carcinogenic pathways. When age interactions are suspected, breast cancer studies should be stratified by early versus late age of onset or analyzed age specifically.


Specialist training of Slovene family physicians.
Family medicine in Europe started to develop in the 1960s with the introduction of obligatory specialist training. Slovenia is a country with a long tradition of family medicine specialist training, but up until 2002 this was neither elaborated on nor conducted by peers in general practice/family medicine. When the country's socialist system started to transform due to political reforms, Slovenia began to modify its system in order to meet the criteria of the European Union. One of the changes was the introduction of a new healthcare system with an influential Medical Chamber responsible for postgraduate training in all specialities. A new model for vocational training in family medicine was established in 2002, following the recommendations of the European Union of General Practitioners (UEMO). According to the new programme, which lasts 4 years, trainees spend half of their training in a hospital setting and half in general practice, where they are supervised by a trainer in practice. This article describes the legal process of introducing new forms of specialist training in Slovenia, and its content. A comparison with UEMO countries shows that the new model is comparable to other countries.


Use of an intraoral scanner and CAD-CAM for simultaneous restoration with a personalized titanium post-core and a zirconia crown.
Customized posts-and-cores have been widely used for improved fitness within a prepared post space. However, in comparison to direct restoration, they necessitate an increased number of appointments for patients. A 24-year-old man presented with a maxillary left canine that had fractured due to trauma 10 months previously. For this case, a digital process was used for simultaneous restoration with a personalized titanium post-and-core and a zirconia crown achieved with an intraoral scanner (IOS) and computer-aided design/computer-aided manufacturing (CAD-CAM). This workflow allowed the restoration to be completed in 2 visits, facilitating more effective and predictable treatment, with reduced time and cost for the patient.


Social relationships, knowledge and adjustment to multiple sclerosis.
A number of factors thought to influence psychological adjustment to multiple sclerosis were studied. Patients' knowledge about their disorder was assessed, but neither their knowledge, level of disability, nor demographic characteristics were related to adjustment. Better adjustment was however associated with having more contact with able-bodied people.


Identification of 5,8-oxyretinoic acid isolated from small intestine of vitamin A-deficient rats dosed with retinoic acid.
A retinoid was isolated by a multistep procedure from the small intestines of vitamin A-deficient rats given a single dose of retinoic acid. The compound, designated 8II, was pure, as demonstrated by four high-pressure liquid chromatographic procedures. It was positively identified as 5,8-oxyretinoic acid by ultraviolet spectrophotometry, mass spectrometry, and spectral and chromatographic comparison to known compounds. It is probable that 5,8-oxyretinoic acid was produced from 5,6-epoxyretinoic acid under the acidic conditions used in the isolation. It is highly probable, therefore, that the natural product is 5,6-epoxyretinoic acid.


Noise improves modulation detection by cochlear implant listeners at moderate carrier levels.
Envelope detection and processing are very important for cochlear implant (CI) listeners, who must rely on obtaining significant amounts of acoustic information from the time-varying envelopes of stimuli. In previous work, Chatterjee and Robert [JARO 2(2), 159-171 (2001)] reported on a stochastic-resonance-type effect in modulation detection by CI listeners: optimum levels of noise in the envelope enhanced modulation detection under certain conditions, particularly when the carrier level was low. The results of that study suggested that a low carrier level was sufficient to evoke the observed stochastic resonance effect, but did not clarify whether a low carrier level was necessary to evoke the effect. Modulation thresholds in CI listeners generally decrease with increasing carrier level. The experiments in this study were designed to investigate whether the observed noise-induced enhancement is related to the low carrier level per se, or to the poor modulation sensitivity that accompanies it. This was done by keeping the carrier amplitude fixed at a moderate level and increasing modulation frequency so that modulation sensitivity could be reduced without lowering carrier level. The results suggest that modulation sensitivity, not carrier level, is the primary factor determining the effect of the noise.


Soil Microbial Community Response Differently to the Frequency and Strength of Freeze-Thaw Events in a Larix gmelinii Forest in the Daxing'an Mountains, China.
Sustained climate warming increases the frequency and strength of soil freeze-thaw (FT) events, which strongly affect the properties of soil microbial communities. To explore the responses and mechanisms of the frequency and strength of freeze-thaw events on soil microbial communities, a lab-scale FT test was conducted on forest soil in permafrost region from the Daxing'an Mountains, China. The number of FT cycles (FTN) had a greater effect on microbial communities than FT temperature fluctuation (FTF). The FTN and FTF explained 20.9 and 10.8% of the variation in microbial community structure, respectively, and 22.9 and 11.6% of the variation in enzyme activities, respectively. The total and subgroup microbial biomass, the ratio of fungi to bacteria (F/B), and C- and N-hydrolyzing enzyme activities all decreased with an increase in FTN. Among microbial groups, arbuscular mycorrhizal fungi (AMF) were the most sensitive to FT events. Based on the changes of F/B and AMF, the reduction in soil carbon sequestration caused by frequent FT events can be explained from a perspective of microorganisms. Based on redundancy analysis and Mental Test, soil moisture, total organic carbon, and total nitrogen were the major factors affecting microorganisms in FT events. In the forest ecosystem, soil water and fertilizer were important factors to resist the damage of FT to microorganism, and sufficient water and fertilizer can lighten the damage of FT events to microorganisms. As a result of this study, the understanding of the responses of soil microorganisms to the variation in FT patterns caused by climate changes has increased, which will lead to better predictions of the effects of likely climate change on soil microorganisms.


The association of topical flurbiprofen with the incidence of postoperative glaucoma after phacoemulsification in dogs.
To investigate the relationship between topical administration of flurbiprofen plus corticosteroids versus corticosteroids alone following phacoemulsification and the development of postoperative glaucoma in dogs. Thirty-eight/eighty-three (45.8%) eyes were prescribed topical flurbiprofen plus corticosteroids immediately postop while 45/83 (54.2%) eyes received topical corticosteroids alone. Logistic regression models were performed to analyze the relationship between topical flurbiprofen and development of glaucoma and to predict potential risk factors for postoperative glaucoma occurrence. Eighty-three eyes (65 dogs) were included. The mean age at surgery was 8.2 years, with even gender distribution. Increasing age at the time of surgery significantly increased the probability of postoperative glaucoma occurrence (odds ratio [OR] = 1.344, 95% confidence interval [CI] 1.093-1.652; p = 0.005). Glaucoma occurred in 17/83 (20.5%) eyes; of these, 15/38 (39.5%) and 2/45 (4.4%) eyes were prescribed topical flurbiprofen plus corticosteroids and topical corticosteroids alone, respectively. Immediate postoperative use of topical flurbiprofen was significantly associated with an increased probability of postoperative glaucoma occurrence (OR = 19.183 [95% CI 3.367-109.286], p = 0.001). Immediate postoperative use of topical flurbiprofen was a potential predisposing risk factor for the development of glaucoma following phacoemulsification. Restriction of postoperative use of topical flurbiprofen might decrease the possibility of postoperative glaucoma development in dogs.


Geometry of escort distributions.
Given an original distribution, its statistical and probabilistic attributes may be scanned using the associated escort distribution introduced by Beck and Schlögl and employed in the formulation of nonextensive statistical mechanics. Here, the geometric structure of the one-parameter family of the escort distributions is studied based on the Kullback-Leibler divergence and the relevant Fisher metric. It is shown that the Fisher metric is given in terms of the generalized bit variance, which measures fluctuations of the crowding index of a multifractal. The Cramér-Rao inequality leads to a fundamental limit for the precision of the statistical estimate of the order of the escort distribution. We also show quantitatively that it is inappropriate to use the original distribution instead of the escort distribution for calculating the expectation values of physical quantities in nonextensive statistical mechanics.


Characterization of alpha-adrenoceptors in the preprostatic urethra of sexually immature male lambs.
Strips of preprostatic urethra from immature male lambs (3-4 months old) were used to study alpha-adrenoceptor-mediated contractions in vitro. The rank order of potency of the agonists was noradrenaline = phenylephrine greater than adrenaline. B-HT 920 was ineffective and clonidine behaved as a weak partial agonist. The rank order of efficacy was found to be noradrenaline greater than phenylephrine greater than adrenaline. Prazosin (10(-9)-10(-6) M) and rauwolscine (10(-6)-10(-4) M) antagonized noradrenaline-induced contractions. The pA2 values were 7.89 and 5.38 for prazosin and rauwolscine, respectively. Phenoxybenzamine reduced the maximal response to noradrenaline and shifted the concentration-response curve to the right. The dissociation constant (KA) of noradrenaline was calculated to be 4.05 +/- 0.21 x 10(-6) M and the occupancy-response plot for noradrenaline showed a linear relationship. It is concluded that alpha-adrenergic contraction of the preprostatic urethra from immature lambs are mediated by alpha 1-adrenoceptors. It is also suggested that the lack of a receptor reserve may affect the degree of urethral constriction and could be related to hormonal status.


The efficacy of Interceed(TC7)* for prevention of reformation of postoperative adhesions on ovaries, fallopian tubes, and fimbriae in microsurgical operations for fertility: a multicenter study. Nordic Adhesion Prevention Study Group.
To evaluate the efficacy of Interceed as an adjuvant in the prevention of postoperative adhesion reformation to the ovary, fallopian tube, and fimbria when used together with microsurgical techniques. Prospective, randomized, multicenter, controlled clinical study. Normal human volunteers in an academic research environment. Sixty-six women suffering from infertility due at least in part to bilateral tubal disease with bilateral adhesions attached to ovaries, fallopian tubes, and fimbriae. Adhesiolysis bilaterly through laparotomy with microsurgical techniques, application of Interceed on one of the sides randomly assigned not known by the surgeon before application, follow-up laparoscopy 4 to 10 weeks postoperatively, with each patient serving as her own control. Adhesion severity scores at all sites and number of adhesion free organs after laparotomy and follow-up laparoscopy. When the initial scores registered at the operation for fertility were compared with those registered at the second-look laparoscopy, the results indicated that gentle microsurgical techniques resulted in a significant reduction of postoperative adhesions. Adnexa, which were covered with Interceed, had significantly lower adhesion scores than the control adnexa, representing an improvement of 39% compared with microsurgery alone (control) in reducing adhesion reformation scores. When combined with microsurgical techniques, Interceed reduced adhesion reformation scores by 70%. The number of ovaries, fallopian tubes, and fimbriae without adhesions at the time of second-look laparoscopy was significantly increased by approximately twofold when organs were covered with Interceed. In a prospective, randomized, multicenter, controlled clinical study using a protocol in which other adjuvants have been shown not to be efficacious, Interceed was shown to reduce significantly the incidence and severity of adhesion reformation to the ovary, fallopian tube, and fimbria after infertility surgery.


Sorbicillinoids From the Fungus Ustilaginoidea virens and Their Phytotoxic, Cytotoxic, and Antimicrobial Activities.
Ustilaginoidea virens, the causal fungus of rice false smut, was found in previous studies to produce two types of metabolites, ustiloxins and ustilaginoidins. However, genome sequencing of U. virens revealed a plethora of secondary-metabolites-biosynthetic core genes that were capable to biosynthesize unreported metabolites. A large-scale fermentation of U. virens was thus performed, and the fungal extract was chemically re-investigated. After removing the known metabolites, we found a fraction containing unknown phytotoxic substances. Fractionation of this part has led to the isolation of six new sorbicillinoids, namely ustisorbicillinols A~F (1~6), and two new sorbicillinoid-related pyrones, named ustilopyrones A (7) and B (8), together with nine known cogeners (9~17). The structures of the new compounds were elucidated by analysis of their NMR, HRMS, and CD spectra, while ECD, 13C NMR and optical rotation calculations were additionally used for configurational assignments. Plausible biosynthetic pathways for the new compounds were proposed. Phytotoxicity assays revealed that the major sorbicillinoids (12~14, and 16) showed strong inhibition against the radicle and germ elongation of rice and lettuce seeds, with compound 12 displaying the strongest inhibition. The isolated compounds were also evaluated for their cytotoxic, antibacterial, and antifungal activities. Compounds 10, and 12~14 showed moderate cytotoxicities against the tested cell lines with IC50s of 8.83~74.7 μM. Compounds 2, and 10~13 were active against the tested bacteria (MICs 4~128 μg/mL), while compounds 11~13 displayed moderate antifungal activities.


Role of neo-adjuvant hormonal therapy in the treatment of breast cancer: a review of clinical trials.
The clinical benefits of endocrine therapy for patients with hormonosensitive breast cancer are well established. For many years, 5 years of tamoxifen was the gold standard of adjuvant treatment. The recent development of new endocrine agents provides physicians with a more effective therapeutic approach. Nevertheless, the success of neoadjuvant endocrine therapy is much more recent and less reported in the literature. This article reviews the studies published about neoadjuvant endocrine treatment (tamoxifen and aromatase inhibitors). According to the literature, neoadjuvant endocrine therapy seems to be effective. In contrast to neoadjuvant chemotherapy, neoadjuvant endocrine therapy is well tolerated, with very few patients having to discontinue the treatment because of side effects. It does not constitute a standard treatment but could have potential for elderly women with operable, hormonosensitive, well differentiated and slowly progressing (SBR I) tumor or for patients with lobular MSBR 1 carcinoma (low chemosensitivity). The newer generation of aromatase inhibitors (letrozole, anastrozole, exemestane) appears to be more active (in terms of overall response rates and conservative surgery rate) than tamoxifen. Patients with an estrogen receptor Allred score of 6 and over are more likely to respond and gain a clinical benefit. The optimal duration of neoadjuvant therapy has not yet been investigated in detail. These preliminary results should be confirmed by further studies.


GENETIC CONSEQUENCES OF OUTCROSSING IN THE CLEISTOGAMOUS ANNUAL, IMPATIENS CAPENSIS. II. OUTCROSSING RATES AND GENOTYPIC CORRELATIONS.
The genetic consequences of a plant's mating system depend on both the degree of outcrossing and the genetic relationship between mates. We examined the electrophoretic genotypes of seeds derived from cleistogamous (CL) and chasmogamous (CH) flowers in six populations of the facultatively cleistogamous annual, Impatiens capensis. Multilocus estimates of the outcrossing rates for the strongly protandrous CH flowers ranged from 0.29 to 0.71 and were higher than estimates based on single-locus data. Such results suggest that the CH flowers experience variable levels of both geitonogamous self-fertilization and biparental inbreeding. A new and generally applicable technique based on the relative level of inbreeding within progeny groups provided direct estimates of the correlation between the genotypic values of outcrossed mates. These correlations varied widely among populations and contributed up to half of the inbreeding observed among the CH progeny. Such biparental inbreeding biases estimates of the outcrossing rate based on the mixed-mating model downward and influences mating-system evolution by decreasing the "cost of meiosis."


Probing planetary biodiversity with DNA barcodes: The Noctuoidea of North America.
This study reports the assembly of a DNA barcode reference library for species in the lepidopteran superfamily Noctuoidea from Canada and the USA. Based on the analysis of 69,378 specimens, the library provides coverage for 97.3% of the noctuoid fauna (3565 of 3664 species). In addition to verifying the strong performance of DNA barcodes in the discrimination of these species, the results indicate close congruence between the number of species analyzed (3565) and the number of sequence clusters (3816) recognized by the Barcode Index Number (BIN) system. Distributional patterns across 12 North American ecoregions are examined for the 3251 species that have GPS data while BIN analysis is used to quantify overlap between the noctuoid faunas of North America and other zoogeographic regions. This analysis reveals that 90% of North American noctuoids are endemic and that just 7.5% and 1.8% of BINs are shared with the Neotropics and with the Palearctic, respectively. One third (29) of the latter species are recent introductions and, as expected, they possess low intraspecific divergences.


Functional sites in the laminin alpha chains.
Laminins, heterotrimers composed of alpha, beta, and gamma chains, are multifunctional glycoproteins present in basement membranes. Laminins, the most important component of basement membranes during basement membrane assembly in early development, are involved in various biological activities such as cell adhesion, migration, growth, differentiation, tumor metastasis, and angiogenesis. Fully 15 laminin isoforms have been identified and are tissue- and/or developmental stage-specifically expressed. Integrins, dystroglycan, syndecans, and the other several cell surface molecules are cellular receptors for laminins. The globular domains located in the N- and C-terminus of the laminin alpha chains are critical for interactions with the cellular receptors. There are highly conserved functional sites and chain-specific functional sites among the laminin alpha chains. Additionally, laminins are processed by specific endogenous proteases and the processing regulates laminin functions. Binding of the functional sequences in laminins to the cellular receptors triggers intracellular signaling, followed by inducing various cell activities including cell spreading and migration. Laminins possess multifunctional sequences and are key molecules that determine cell fate.


Chiropractic Day 2023: A Report and Qualitative Analysis of How Thought Leaders Celebrate the Present and Envision the Future of Chiropractic.
This study aimed to (1) collect and analyze statements about how to celebrate chiropractic in the present and roles that chiropractors may fulfill in the future, (2) identify if there was congruence among the themes between present and future statements, and (3) offer a model about the chiropractic profession that captures its complex relationships that encompass its interactions within microsystem, mesosystem, exosystem, and macrosystem levels. For this qualitative analysis, we used pattern and grounded theory approaches. A purposive sample of thought leaders in the chiropractic profession were invited to answer the following 2 open-ended questions: (1) envision the chiropractor of the future, and (2) recommendations on how to celebrate chiropractic. Information was collected during April 2023 using Survey Monkey. The information was entered into a spreadsheet and analyzed for topic clusters, which resulted in matching concepts with social-ecological themes. The themes between the responses to the 2 questions were analyzed for congruence. We used the Standards for Reporting Qualitative Research to report our findings. Of the 54 experts invited, 32 (59%) participated. Authors represented 7 countries and have a median of 32 years of chiropractic experience, with a range of 5 to 51 years. Nineteen major topics in the future statements and 23 major topics in statements about celebrating chiropractic were combined in a model. The topics were presented using the 4 levels of the social-ecological framework. Individual (microsystem): chiropractors are competent, well-educated experts in spine and musculoskeletal care who apply evidence-based practices, which is a combination of the best available evidence, clinical expertise, and patient values. Interpersonal relationships (mesosystem): chiropractors serve the best interests of their patients, provide person-centered care, embrace diversity, equity, and inclusion, consider specific health needs and the health of the whole person. Community (exosystem): chiropractors provide care within integrated health care environments and in private practices, serve the best interests of the public through participation in their communities, participate through multidisciplinary collaboration with and within the health care system, and work together as a profession with a strong professional identity. Societal (macrosystem): chiropractors contribute to the greater good of society and participate on a global level in policy, leadership, and research. There was concordance between both the future envisioning statements and the present celebration recommendations, which suggest logical validity based on the congruence of these concepts. A sample of independent views, including the perceptions from a broad range of chiropractic thought leaders from various backgrounds, philosophies, diversity characteristics, and world regions, were assembled to create a comprehensive model of the chiropractic profession. The resulting model shows an array of intrinsic values and provides the roles that chiropractors may provide to serve patients and the public. This study offers insights into the roles that future chiropractors may fulfill and how these are congruent with present-day values. These core concepts and this novel model may have utility during dialogs about identity, applications regarding chiropractic in policy, practice, education, and research, and building positive relationships and collaborations.


Disentangling the evolutionary history of peri-Mediterranean cyprinids using host-specific gill monogeneans.
The diversification of Mediterranean fish appears to be far more complex than could be explained by a single dispersion model. Cyprinids represent one of the most species-rich groups of freshwater fishes living in this region. The current distribution of several highly divergent cyprinid taxa is most likely the result of multiple dispersion events. Cyprinid fish serve as hosts for the highly diversified and host-specific monogenean parasites of the genus Dactylogyrus. On the assumption that the distribution of Dactylogyrus spp. reflects the biogeography and evolutionary history of their hosts, we used these parasites as an additional tool to shed new light on the evolutionary history of peri-Mediterranean cyprinids of the subfamily Barbinae. The degree of congruence between host and parasite phylogenies was investigated using 29 Dactylogyrus spp. and 34 Barbinae hosts belonging to the genera Aulopyge, Barbus and Luciobarbus. We showed that the morphological adaptation of Dactylogyrus (i.e. of the ventral bar, representing the most variable morphological character of the attachment organ) is linked with parasite phylogeny. By applying distance-based and event-based cophylogenetic approaches, we revealed a significant global coevolutionary signal. A total of 62% of individual host-parasite links contributed significantly to the coevolutionary structure evidenced between hosts of Barbus spp. and Iberian Luciobarbus spp., and their host-specific Dactylogyrus spp. The host switching of parasites was revealed as the most important coevolutionary event in the Dactylogyrus-Barbinae system in the peri-Mediterranean region. Cophylogenetic analyses and the mapping of the morphological character of the parasite attachment organ onto the phylogeny of Dactylogyrus indicate that endemic southern European Dactylogyrus spp. parasitizing cyprinids of Barbinae have multiple origins. We suggest that continental bridges connecting southern Europe and North Africa played a crucial role in the dispersion of cyprinids, affecting the distribution of their host-specific gill parasites.


Right-to-left frequency gradient during atrial fibrillation initiated by right atrial ectopies and its augmentation by adenosine triphosphate: Implications of right atrial fibrillation.
A left-to-right dominant frequency (DF) gradient commonly exists in paroxysmal atrial fibrillation (AF). AF initiated by right atrial (RA) ectopy (AF-RAE) is rare. This study aimed to investigate characteristics of AF-RAE using pharmacological maneuvers and spectral analysis. Seventy-nine consecutive patients referred for catheter ablation of paroxysmal AF were enrolled. Infusions of isoproterenol and adenosine triphosphate (ATP) were used to induce AF. Patients with AF-RAE and patients with AF initiated only by pulmonary vein (PV) ectopies were classified into the RA-ectopy group (n = 7[9%]) and PV-ectopy group (n = 32[41%]), respectively. ATP was also injected during ongoing AF to unmask the driver of AF. High RA, coronary sinus, and PV-left atrial junction electrograms and electrocardiogram lead V1 underwent spectral analyses. Patients in the RA-ectopy group were younger (51 ± 13 years vs 63 ± 7 years; P = .01) and more commonly had a family history of AF (71% vs 9%; P < .001) than patients in the PV-ectopy group. There was a baseline right-to-left DF gradient in the RA-ectopy group (PV-left atrial junction: 6.0 ± 0.4 Hz; coronary sinus: 5.7 ± 0.6 Hz; RA: 7.3 ± 0.8 Hz; P < .05) in contrast to a left-to-right DF gradient in the PV-ectopy group (5.9 ± 0.8, 5.3 ± 0.7, 5.2 ± 0.8 Hz; P < .01). ATP injection predominantly increased the DF of the high RA in the RA-ectopy group and augmented a right-to-left DF gradient (7.9 ± 1.8, 7.6 ± 1.0, 10.7 ± 0.7 Hz; P < .001), whereas it augmented a left-to-right DF gradient in the PV-ectopy group (7.9 ± 1.0, 6.4 ± 0.5, 6.6 ± 1.2 Hz; P < .05). A rare type of paroxysmal AF initiated by RA ectopy may be maintained by a reentrant driver localized in the RA (so-called RA fibrillation).


Isozyme pattern of thymidine kinase during liver regeneration.
Liver regeneration after partial hepatectomy is characterized by an active phase of cell proliferation that is associated with a marked increase in thymidine kinase activity. Using non-denaturing gel electrophoresis and different substrate specificity, two isozymes could be detected. One was identified as the adult isozyme while the other was the fetal one. Both forms were present during liver regeneration. When the regenerative process was completed, the total enzymatic activity dropped to normal values and the fetal isozyme was displaced by the adult type.


The triple pyrophosphate Cs3CaFe(P2O7)2.
The complex phosphate tricaesium calcium iron bis(diphosphate), Cs(3)CaFe(P(2)O(7))(2), has been prepared by the flux method. Isolated [FeO(5)] and [CaO(6)] polyhedra are linked by two types of P(2)O(7) groups into a three-dimensional framework. The latter is penetrated by hexagonal channels along the a axis where three Cs atoms are located. Calculations of caesium Voronoi-Dirichlet polyhedra give coordination schemes for the three Cs atoms as [8 + 3], [9 + 1] and [9 + 4]. The structure includes features of both two- and three-dimensional frameworks of caesium double pyrophosphates.


Melanomas of the mucosa in the oral cavity and the upper respiratory passages.
Thirty-eight patients with malignant melanoma of the mucosa in the nasal and oral cavity have been treated at the Radium Centres in Arhus, Copenhagen and Odense in the years from 1956 to 1978. Twenty cases were localized to the nasal cavity and the nasal sinuses, and 18 cases to the oral cavity and oropharynx. Twenty-nine patients had local tumors, eight had local lymph node metastases, and one patient had lung metastases. The primary treatment has been surgery, which was radical in 50% of the cases, whereas 14 patients received irradiation and combined treatment. Complete response was seen locally in five of six irradiated nasal tumors and in three of eight oral tumors. Only two patients with nasal and one patient with oral tumors had recurrence later. Active treatment for recurrence has had the result that 10 patients have survived for 2 additional years, and 1 patient for almost 5 additional years. Eight patients lived for more than 5 years; crude survival is 26%.


Formation of Large Hypericin Aggregates in Giant Unilamellar Vesicles-Experiments and Modeling.
The incorporation of hypericin (Hyp) from aqueous solutions into giant unilamellar vesicle (GUV) membranes has been studied experimentally and by means of kinetic Monte Carlo modeling. The time evolution of Hyp fluorescence originating from Hyp monomers dissolved in the GUV membrane has been recorded by confocal microscopy and while trapping individual GUVs in optical tweezers. It was shown that after reaching a maximum, the fluorescence intensity gradually decreased toward longer times. Formation of oversized Hyp clusters has been observed on the GUV surface at prolonged time. A simplified kinetic Monte Carlo model is presented to follow the aggregation/dissociation processes of Hyp molecules in the membrane. The simulation results reproduced the basic experimental observations: the scaling of the characteristic fluorescence decay time with the vesicle diameter and the buildup of large Hyp clusters in the GUV membrane.


Genetic and structural analyses of cytochrome P450 hydroxylases in sex hormone biosynthesis: Sequential origin and subsequent coevolution.
Biosynthesis of steroid hormones in vertebrates involves three cytochrome P450 hydroxylases, CYP11A1, CYP17A1 and CYP19A1, which catalyze sequential steps in steroidogenesis. These enzymes are conserved in the vertebrates, but their origin and existence in other chordate subphyla (Tunicata and Cephalochordata) have not been clearly established. In this study, selected protein sequences of CYP11A1, CYP17A1 and CYP19A1 were compiled and analyzed using multiple sequence alignment and phylogenetic analysis. Our analyses show that cephalochordates have sequences orthologous to vertebrate CYP11A1, CYP17A1 or CYP19A1, and that echinoderms and hemichordates possess CYP11-like but not CYP19 genes. While the cephalochordate sequences have low identity with the vertebrate sequences, reflecting evolutionary distance, the data show apparent origin of CYP11 prior to the evolution of CYP19 and possibly CYP17, thus indicating a sequential origin of these functionally related steroidogenic CYPs. Co-occurrence of the three CYPs in early chordates suggests that the three genes may have coevolved thereafter, and that functional conservation should be reflected in functionally important residues in the proteins. CYP19A1 has the largest number of conserved residues while CYP11A1 sequences are less conserved. Structural analyses of human CYP11A1, CYP17A1 and CYP19A1 show that critical substrate binding site residues are highly conserved in each enzyme family. The results emphasize that the steroidogenic pathways producing glucocorticoids and reproductive steroids are several hundred million years old and that the catalytic structural elements of the enzymes have been conserved over the same period of time. Analysis of these elements may help to identify when precursor functions linked to these enzymes first arose.


Catheter-directed laser coagulation of atrial myocardium in dogs.
The feasibility of transcatheter laser coagulation of atrial myocardium was tested in a canine model by using a combined electrode-laser catheter. In 17 anaesthetized beagles a total of 264 lesions, 12-19 per dog, and 3-5 in each area were produced in: (1) the lateral walls, (2) the posterior right atrial walls, (3) the inter-atrial septum, and (4) the atrial appendage. The power source was a continuous wave Nd:YAG laser. Irradiance was 1 kW.cm-2, at a wave length of 1064 nm, the irradiated spot diameter was 2.0-2.5 mm, and the pulse duration 5-60 s. Local intra-cardiac atrial potentials recorded from the targeted areas during laser irradiation dwindled after onset of the laser pulse, and their amplitude was reduced persistently by pulses of 15 s or longer. Histopathologically, the acute lesions showed intramural haemorrhage and coagulation necrosis, but there was no tissue vaporization or crater formation. Chronic lesions showed clear-cut oval-shaped areas of transmural fibrosis. Diameters of lesions, dependent on the amount of laser energy applied, measured from 4.6 +/- 0.5 mm (450 J) to 7.8 +/- 1.4 mm (1800 J). Follow-up lasted 6-25 months (average 10.5). All the animals survived the procedure without complications. Transcatheter laser coagulation of atrial myocardium is safe and can be performed in a controllable manner by using the catheter system presented.


Consensus for Linear Multiagent Systems With Time-Varying Delays: A Frequency Domain Perspective.
This paper investigates the consensus problem for multiagent systems with time-varying delays. The bounded delays can be arbitrarily fast time-varying. The communication topology is assumed to be undirected and fixed. With general linear dynamics under average state feedback protocols, the consensus problem is then transformed into the robust control problem. Further, sufficient frequency domain criteria are established in terms of small gain theorem by analyzing the delay dependent gains for both continuous-time and discrete-time systems. The controller synthesis problems can be solved by applying the frequency domain design methods. Numerical examples are demonstrated to verify the effectiveness of the proposed approaches.


Sequenced questioning to elicit the patient's perspective on illness: effects on information disclosure, patient satisfaction, and time expenditure.
During the medical interview, clinicians frequently overlook the patient's perspective on illness (PPI), ie, the patient's explanations and concerns about the presenting symptoms and expectations for the encounter. Without special efforts, the PPI surfaces spontaneously in only about one fourth of medical interviews. We determined whether asking the patient a series of sequenced questions would elicit the PPI and what effect such questioning would have on patient and physician satisfaction and on the length of the clinical encounter. Fifty-five interviews in a family practice clinic setting were studied by videotape and post-interview debriefings. On a random basis, 29 patients were asked sequenced questions at the end of the history, while 26 experienced usual medical interviews. Measures of patient and physician satisfaction were compared by descriptive statistics and the Mann-Whitney test for ordinal data. In response to sequenced questioning, 44% of patients revealed specific, significant concerns that had not been otherwise disclosed. Among patients without prior contact with their provider, satisfaction with the encounter was significantly higher when the sequenced questions were used than when they were not; perception of time spent in discussion with the physician was also higher. Paradoxically, resident physicians expressed lower confidence that they had helped the patient when the sequenced questions were used to elicit the PPI. Use of sequenced questions to elicit the PPI results in significant sharing of new information and increased patient satisfaction and requires only a modest investment of time.


International telepharmacy education: another venue to improve cancer care in the developing world.
In developed countries, pharmacists play a crucial role in designing and implementing cancer treatments as part of a multidisciplinary oncology team. However, developing countries have a shortage of pharmacists, and their role is generally limited to dispensing and selling drugs. The aim of this study was to investigate the feasibility of providing clinical pharmacy educational activities via international teleconferencing to improve cancer care in developing countries. Meticulous preparation and intense promotion of the workshop were done in Egypt before the telepharmacy conferences began. Multiple connectivity tests were performed to resolve technical problems. Nine telepharmacy conferences were delivered during 3-h sessions that were held on three consecutive days. Talks were subsequently made available via Web streaming. Attendees were requested to complete a survey to measure their satisfaction with the sessions. The teleconference was attended by a total of 345 persons, and it was subsequently reviewed online via 456 log-in sessions from 10 countries. Technical issues (e.g., poor auditory quality) were resolved on the first day of the event. The rate of attendees' responses on the survey was 30.1%, and satisfaction with the event was generally good. Telecommunication is a relatively inexpensive approach that may improve pharmacy practices, especially those used to treat patients with cancer in developing countries. Special attention to patient-based telepharmacy education, including the use of cost-effective technology, should be considered.


A major susceptibility locus on chromosome 22q12 plays a critical role in the control of kala-azar.
Kala-azar (KA) is a life-threatening protozoal disease caused by Leishmania parasites (L. donovani, L. chagasi, and L. infantum). The disease, which is also called "visceral leishmaniasis," is prevalent in Africa, South America, Asia, and the Mediterranean basin. Epidemics occur periodically, killing a large number of infected individuals. Factors determining whether a patient remains asymptomatic or develops KA are still largely unknown. In a previous study that was performed during an outbreak of KA in a village on the Ethiopian-Sudanese border, we showed that KA was more frequent in certain families and ethnic groups, thereby suggesting that host genetic factors play an important role in the development of the disease. Here, we report the results of a genomewide linkage study performed on 63 Sudanese families selected from the most affected ethnic group and including 169 children with KA. Significant linkage (LOD score 3.50 [P=3x10-5] in all patients; LOD score 3.90 [P=10-5] in patients who were affected early in the outbreak) was obtained with markers on chromosome 22q12. These results are the first evidence of a major genetic effect on the development of human KA. They may lead to identification of genes critical in the pathogenesis of this disease and to new therapeutic interventions against this parasite, which is developing resistance to available drugs.


Computed tomography-guided wire localization of pulmonary lesions before thoracoscopic resection: results in 101 cases.
The authors determine the success rate, safety, and potential complications of computed tomography-guided preoperative hookwire localization of small peripheral pulmonary nodules. One hundred one consecutive wire localizations with addition of methylene blue injection were performed in 94 patients immediately before thoracoscopic resection of small lung lesions. Sixty-two patients had a known primary malignancy, whereas 32 had an asymptomatic nodule. Eighty-eight patients underwent single lesion localization, five underwent double localization, and one underwent triple wire placement. Five patients had previously undergone percutaneous biopsy that was nondiagnostic. The nodule was within the first wedge biopsy of lung tissue in 95 of 97 specimens (98%). A second wedge and an open lobectomy were required in one patient each. Three additional biopsies were intraoperatively deferred after the histologic diagnosis was established after removal of another nodule. The procedure was terminated before wire placement in one patient who was unable to successfully hold his breath. The wire dislodged with the tip in the pleural space rather than in the lung parenchyma in 22 cases; however, methylene blue tattoo allowed localization in 13 of these (59%). In the other nine cases, extra portals, digital palpation, or expanded wedge resection was required. Complications included pneumothorax in 48 cases, moderate pleuritic pain in five cases, seven small intercostal hematomas, and a 7-mm wire fragment retained in one patient's lung along the suture line. No patient required a preoperative drain for treatment of pneumothorax. Wire dislodgement occurred in 6 of 52 (12%) cases without an initial pneumothorax and in 16 of 48 (33%) cases if a pneumothorax occurred. Wires dislodged less frequently if placed either directly into or through the nodule in 11 of 64 (17%) cases than if placed adjacent to the nodule in 11 of 36 (31%) cases. Average wire tip depth from the visceral pleura was significantly less when the wire dislodged (11 mm) than when the wire remained in place (25 mm). Wire localization of small peripheral pulmonary nodules is a safe and effective procedure to assist thoracoscopic sublobectomy resection.


Stepwise combination of simple noninvasive fibrosis scoring systems increases diagnostic accuracy in nonalcoholic fatty liver disease.
Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease ranging from simple fatty liver to steatohepatitis, fibrosis, and cirrhosis. We aimed to analyze the diagnostic performance and clinical utility of simple noninvasive tests alone or in combination for the detection of advanced fibrosis in patients with NAFLD. Data from 323 patients with biopsy-proven NAFLD/NASH who presented to the Clinic for Gastroenterology and Hepatology, University Hospital of Cologne between July 1998 and November 2009, were analyzed retrospectively. Sensitivity, specificity, positive predictive values, and negative predictive values were determined along with the area under receiver operating characteristic curves (AUROC) using published formulas for NAFLD, FIB-4, and BARD fibrosis scores. The area under receiver operating characteristic curves were as follows: NAFLD fibrosis score 0.96 [95% confidence interval (CI), 0.92-0.99], FIB-4 0.95 (95% CI, 0.91-1.00), BARD 0.82 (95% CI, 0.71-0.92) with negative predictive values for advanced fibrosis of 96%, 98%, and 96%, respectively. When applying the NAFLD, FIB-4, or BARD scoring systems 25%, 15%, or 26% of cases with advanced fibrosis would have been missed. Combining FIB-4 and BARD in a stepwise fashion, patients would have been correctly classified without biopsy in 67% of cases without missing a single case of advanced fibrosis. The FIB-4 and NAFLD fibrosis scores perform better than the BARD scoring system. Liver biopsy can securely be replaced only with a stepwise combination of simple noninvasive tests, otherwise the assessment of risk due to advanced fibrosis may be misleading in a clinically meaningful proportion of patients.


[Alzheimer drugs for mild cognitive impairment].
Improved diagnostic procedures allow to detect more patients with early stages of Alzheimer's disease (AD) within the increasing old population especially in the setting of specialised Memory Clinics. As no disease modifying or secondary preventive pharmacological treatments are presently available for AD this article discusses whether the established pharmacological treatment strategies for Alzheimer's dementia (DAT) could be beneficial as well for patients with amnestic mild cognitive impairment (MCI) that can be regarded a transitional stage between normal aging and DAT in many patients. The author does not recommend to treat MCI patients with Cholinesterase Inhibitors (ChE-I) or memantine first of all due to the general problems of a low specificity of the MCI concept and the missing data concerning the treatment of MCI patients with memantine. Moreover, ChE-I therapy in MCI showed weak beneficial effects on cognition and the delay of DAT onset whereas it is costly and has a high risk of side effects. Additionally, the pooled galantamin-data suggest an increased mortality compared to placebo. Finally, cortical cholinergic deficits and the corresponding cognitive deficits are commonly not present in MCI.


Chemoenzymatic flow cascade for the synthesis of protected mandelonitrile derivatives.
A chemoenzymatic two-step cascade process, with both steps having incompatible reaction conditions, was successfully performed in continuous flow. The chemoenzymatic aqueous formation of cyanohydrins was integrated with a subsequent organic phase protection step in a single flow process utilising a membrane-based phase separation module. The wider applicability of our setup was demonstrated with the synthesis of nine protected cyanohydrin derivatives, all obtained in good yields and high to excellent enantioselectivity.


Effect of prostaglandin F3 alpha on gastric mucosal injury by ethanol in rats: comparison with prostaglandin F2 alpha.
In humans eicosapentaenoic acid can be converted to 3-series prostaglandins (PGF3 alpha, PGI3, and PGE3). Whether 3-series prostaglandins can protect the gastric mucosa from injury as effectively as their 2-series analogs is unknown. Therefore, we compared the protective effects of PGF3 alpha and PGF2 alpha against gross and microscopic gastric mucosal injury in rats. Animals received a subcutaneous injection of either PGF3 alpha or PGF2 alpha in doses ranging from 0 (vehicle) to 16.8 mumol/kg and 30 min later they received intragastric administration of 1 ml of absolute ethanol. Whether mucosal injury was assessed 60 min or 5 min after ethanol, PGF3 alpha was significantly less protective against ethanol-induced damage than PGF2 alpha. These findings indicate that the presence of a third double bond in the prostaglandin F molecule between carbons 17 and 18 markedly reduces the protective effects of this prostaglandin on the gastric mucosa.


Sub-apoptotic dosages of pro-oxidant vitamin cocktails sensitize human melanoma cells to NK cell lysis.
Alpha-tocopheryl succinate (αTOS), vitamin K3 (VK3) and vitamin C (ascorbic acid, AA) were previously shown to synergistically promote different death pathways in carcinoma cells, depending on their concentrations and combinations. Similar effects were observed herein in melanoma cells, although αTOS behaved as an antagonist. Interestingly, suboptimal cell death-inducing concentrations (1.5 μM αTOS/20 μM AA/0.2 μM VK3) effectively up-regulated activating Natural Killer (NK) cell ligands, including MICA (the stress-signaling ligand of the NKG2D receptor), and/or the ligands of at least one of the natural cytotoxicity receptors (NKp30, NKp44 and NKp46) in 5/6 melanoma cell lines. Only an isolated MICA down-regulation was seen. HLA class I, HLA class II, ULBP1, ULBP2, ULBP3, Nectin-2, and PVR displayed little, if any, change in expression. Ligand up-regulation resulted in improved lysis by polyclonal NK cells armed with the corresponding activating receptors. These results provide the first evidence for concerted induction of cell death by cell-autonomous and extrinsic (immune) mechanisms. Alarming the immune system much below the cell damage threshold may have evolved as a sensitive readout of neoplastic transformation and oxidative stress. Cocktails of vitamin analogues at slightly supra-physiological dosages may find application as mild complements of melanoma treatment, and in chemoprevention.


Ladder distyrylbenzenes with silicon and chalcogen bridges: synthesis, structures, and properties.
[reaction: see text] A cascade-type anionic double cyclization of (o-silylphenyl)(o-halophenyl)acetylenes via lithiation followed by treatment with elemental chalcogen produces silicon and chalcogen-bridged stilbenes. Based on this reaction, a series of silicon and sulfur- or silicon and selenium-bridged ladder distyrylbenzenes have been synthesized. Their chemical modification by oxidation, crystal structures, and photophysical properties are described.


Instructions emphasizing speed improves hemiparetic arm kinematics during reaching in stroke.
Stroke severely compromises the capacity for skilled motor control including the ability to reach with the stroke-affected upper-extremity. Research incorporating intensive motor therapies has broadly demonstrated the ability to improve hemiparetic reaching post-stroke, yet the role of specific task parameters has received less attention. These task parameters, such as speed-of-performance, may be important to the structure and delivery of motor rehabilitation. The objective of the study was to determine the influence of task pacing demands on hemiparetic reaching strategies in survivors of stroke. Kinematic motion analysis was used to examine upper-extremity reaching patterns in 11 survivors of stroke. Participants were instructed to reach between two targets at a self-selected pace and as fast as possible. Outcome measures included maximal movement speed, accuracy, movement smoothness, and reaching strategies (anterior trunk flexion, elbow extension, and shoulder flexion). Participants reached significantly faster and smoother during the task that emphasized speed while maintaining target accuracy. Participants used significantly less anterior trunk displacement during the fast condition, yet no change in shoulder flexion. Task parameters that emphasize speed positively influence reaching strategies with the more-affected upper-extremity. Survivors of stroke were able to respond to changes in pacing demands while significantly reducing reliance on compensatory trunk movement. This outcome highlights the need to further understand the impact of task parameters during intensive motor therapies.


Involvement of dopamine D1 and D2 receptors in the rat nucleus accumbens in immunostimulation.
Analysis of the nature of changes in the immune response in operated Wistar rats showed that electrolytic lesioning of the nucleus accumbens, the site of the greatest density of dopamine D1 and D2 receptors, led to suppression of the immune response in animals immunized with sheep erythrocytes. Administration of SKF 38393 (20 mg/kg) and quinpirol (1 mg/kg), selective agonists of dopamine D1 and D2 receptors respectively, to sham-operated rats induced significant increases in immune responses. However, no immunostimulation was seen on administration of the selective dopamine D2 agonist quinpirol to animals with lesions to the nucleus accumbens as compared with controls. At the same time, treatment of animals with nucleus accumbens lesions using the dopamine D1 receptor agonist SKF 38393 had no effect on the immune response as compared with that in sham-operated animals given the D1 receptor agonist. These data provide evidence that dopamine D2 receptors in the nucleus accumbens have a role in the mechanisms of immunostimulation, though D2 receptors in other brain structures may also make some contribution to this process; D1 receptors in the nucleus accumbens make no significant contribution to controlling the immune response.


Postinfectious Bronchiolitis Obliterans Misdiagnosed as Bronchial Asthma in a Pediatric Patient.
Bronchiolitis obliterans is a chronic obstructive respiratory disease involving stenosis or occlusion of the bronchioles and smaller airways. The prognosis of bronchiolitis obliterans is poor, and the patient might require home oxygen therapy and/or lung transplantation. Bronchiolitis obliterans has various etiologies; in children, the most common causes are infections by respiratory pathogens like adenoviruses. In such cases, the condition is termed as postinfectious bronchiolitis obliterans. A 7-year-old girl was diagnosed with bronchial asthma at the age of 1 year and was on a regimen of a leukotriene receptor antagonist and an inhaled corticosteroid. At 1 year of age, she was admitted to our hospital with a respiratory syncytial virus infection, and despite continued treatment with the above drugs, she required frequent readmissions. At the age of 7 years, she was diagnosed with postinfectious bronchiolitis obliterans based on the following findings: mosaic perfusion on high-resolution chest computed tomography and ventilation-perfusion mismatch on ventilation-perfusion scintigraphy. A lung biopsy was not performed due to its invasiveness. It has been suggested that appropriate treatment during the early stage improves the prognosis of bronchiolitis obliterans. This disease might be misdiagnosed as bronchial asthma because of the clinical similarities. In patients who do not respond to the treatment for bronchial asthma, pediatricians should consider other diseases with similar signs and symptoms, such as bronchiolitis obliterans, in the differential diagnosis.


Early insights into the genome sequence of Uromyces fabae.
Uromyces fabae is a major pathogen of broad bean, Vicia faba. U. fabae has served as a model among rust fungi to elucidate the development of infection structures, expression and secretion of cell wall degrading enzymes and gene expression. Using U. fabae, enormous progress was made regarding nutrient uptake and metabolism and in the search for secreted proteins and effectors. Here, we present results from a genome survey of U. fabae. Paired end Illumina sequencing provided 53 Gb of data. An assembly gave 59,735 scaffolds with a total length of 216 Mb. K-mer analysis estimated the genome size to be 329 Mb. Of a representative set of 23,153 predicted proteins we could annotate 10,209, and predict 599 secreted proteins. Clustering of the protein set indicates families of highly likely effectors. We also found new homologs of RTP1p, a prototype rust effector. The U. fabae genome will be an important resource for comparative analyses with U. appendiculatus and P. pachyrhizi and provide information regarding the phylogenetic relationship of the genus Uromyces with respect to other rust fungi already sequenced, namely Puccinia graminis f. sp. tritici, P. striiformis f. sp. tritici, Melampsora lini, and Melampsora larici-populina.


Experiences of operational managers regarding record keeping by new professional nurses in public hospitals in the North West province, South Africa.
Documentation can be written or computerised and is used to communicate healthcare and treatment among healthcare professionals. Documentation is the tool that records and measures the healthcare provided to patients, and it must be accurate, complete and timely. This study aims to explore and describe the experiences of the operational managers regarding record keeping by new nurses in selected public hospitals in South Africa. The study was conducted in selected public hospitals in the North West province. This study used a qualitative, explorative and descriptive approach with a purposive sampling method. A total of 35 operational managers participated in the process of data collection. The following themes emerged from this study: gaps in record keeping, the impact of inaccurate documentation and the need for improvement in record keeping. The study has shown the need to bring technological innovation to strengthen the effective improvement of digitalisation in nursing record keeping in the facilities furthermore, nurses should be supported through programmes on intentional and mindful record keeping curbing the incidences of inaccuracy and incompleteness. This study's findings confirmed that new nurses were not consistent with accurate documentation of patient records, and this needs further strengthening in public hospitals to have an impact on the health and safety of the patient.


Prevalence of Brucella sp. antibodies in feral swine in Florida.
Serum samples collected from feral swine (Sus scrofa) throughout Florida (USA) from 1974 to 1989 were tested for antibodies to Brucella sp. by the card test, the standard tube test, the rivanol test or the complement fixation test. Seropositive swine were detected at six of 18 sites with a composite prevalence of 23.4% (238 of 1,015 samples; range = 5.5% to 33.3%) for sites with seropositive swine. At one site for which age and sex data were available there was no significant difference (P = 0.50) in seroprevalence between males and females. Antibody prevalence in adult (> or = 8 mo) and juvenile swine (< 8 mo), however, was significantly different (P < 0.05). Based on these data, Brucella sp. infections are limited only to certain populations of feral swine. To avoid the spread of Brucella sp. organisms, however, relocation of feral swine is not recommended.


Eye movement correlates of younger and older adults' strategies for complex addition.
This study examined performance measures and eye movements associated with complex arithmetic strategies in young and older adults. Participants added pairs of three-digit numbers using two different strategies, under choice and no-choice conditions. Older adults made more errors but were not significantly slower than young adults, and response times and errors showed no interaction between age and the number of carries. Older adults chose strategies less adaptively than young adults. Eye movements were consistent with use of required strategies on no-choice trials and reported strategies on choice trials. Eye movement data also suggested that young adults more successfully distinguished between strategies. Implications of these findings for understanding aging effects in complex arithmetic are discussed.


Seasonal differences in the day-of-the-week pattern of suicide in Queensland, Australia.
Various temporal patterns of suicide events, according to time of day, day of week, month and season, have been identified. However, whether different dimensions of time interact has not been investigated. Using suicide data from Queensland, Australia, this study aims to verify if there is an interaction effect between seasonal and day-of-the-week distribution. Computerized suicide data from the Queensland Suicide Register for those aged 15+ years were analyzed according to date of death, age, sex and geographic location for the period 1996-2007. To examine seasonal differences in day-of-the-week pattern of suicide, Poisson regressions were used. A total of 6,555 suicides were recorded over the whole study period. Regardless of the season, male residents of Brisbane had a significantly marked day-of-the-week pattern of suicide, with higher rates between Mondays and Thursdays. When seasonal differences were considered, male residents in Brisbane showed a Monday peak in summer and a wave-shape pattern with a peak on Thursday and a nadir on Saturdays in winter. Whilst males have distinctive peaks in terms of days of the week for summer and winter, females do not show similar patterns.


Genome-wide characterization of SOS1 gene family in potato (Solanum tuberosum) and expression analyses under salt and hormone stress.
Salt Overly Sensitive 1 (SOS1) is one of the members of the Salt Overly Sensitive (SOS) signaling pathway and plays critical salt tolerance determinant in plants, while the characterization of the SOS1 family in potato (Solanum tuberosum) is lacking. In this study, 37 StSOS1s were identified and found to be unevenly distributed across 10 chromosomes, with most of them located on the plasma membrane. Promoter analysis revealed that the majority of these StSOS1 genes contain abundant cis-elements involved in various abiotic stress responses. Tissue specific expression showed that 21 of the 37 StSOS1s were widely expressed in various tissues or organs of the potato. Molecular interaction network analysis suggests that 25 StSOS1s may interact with other proteins involved in potassium ion transmembrane transport, response to salt stress, and cellular processes. In addition, collinearity analysis showed that 17, 8, 1 and 5 of orthologous StSOS1 genes were paired with those in tomato, pepper, tobacco, and Arabidopsis, respectively. Furthermore, RT-qPCR results revealed that the expression of StSOS1s were significant modulated by various abiotic stresses, in particular salt and abscisic acid stress. Furthermore, subcellular localization in Nicotiana benthamiana suggested that StSOS1-13 was located on the plasma membrane. These results extend the comprehensive overview of the StSOS1 gene family and set the stage for further analysis of the function of genes in SOS and hormone signaling pathways.


Pencil and paper tests--sensitivity to psychotropic drugs.
The literature on pencil and paper tests and the effects of psychotropic drugs is reviewed. Performance at digit symbol substitution, symbol copying, letter cancellation, arithmetic, logic and cognitive processing with a relatively constant level of triazolam was compared with placebo. Analysis of variance, covariance analysis and principal component analysis were applied to the data. Pencil and paper tests which measure various skills are useful for detecting drug effects. Letter cancellation, arithmetic and DSST appear to be most sensitive, although logic and symbol copying may be useful.


Mediastinal parathyroid carcinoma.
To describe a patient with a mediastinal parathyroid carcinoma and hypercalcemia as well as to compare the features of parathyroid carcinoma with those of hypercalcemia due to other causes of primary hyperparathyroidism. We present a case report and discuss the diagnosis and management of this rare tumor. In a 44-year-old man, severe hypercalcemia and normal findings on neck exploration led to referral and ultimate detection of an anterior mediastinal mass. Surgical resection and pathologic examination of the mass revealed a cystic parathyroid carcinoma. Subsequently, normalization of serum calcium and parathyroid hormone levels ensued. Parathyroid carcinoma as an alternative to the diagnosis of primary hyperparathyroidism should be considered in patients with dramatically increased serum calcium and parathyroid hormone levels at the time of initial examination. The mainstay of therapy for parathyroid carcinoma is complete surgical resection. Accurate preoperative localization of parathyroid carcinoma is helpful, especially in instances of reoperation or hypercalcemic crisis.


Alterations in characteristics of canine articular chondrocytes in non-passaged long-term monolayer culture: Matter of differentiation, dedifferentiation and redifferentiation.
This study investigated the effects of culture time on phenotype stability of canine articular chondrocytes (CACs) in non-passaged long-term monolayer culture. Third passage (P3) CACs isolated from four cartilage samples were seeded at three different initial seeding densities (0.2 × 104, 1.0 × 104 and 5.0 × 104 cells/cm2) and maintained in monolayer condition up to 8 weeks without undergoing subculture after confluence. The characteristic changes of chondrocytes during the culture period were evaluated based on the cell morphology, cell proliferation, glycosaminoglycans (GAGs) content, DNA quantification, mRNA expression and ultrastructure of chondrocytes. Chondrocytes maintained under post-confluence condition exhibited a capability to grow and proliferate up to 4 weeks. Alcian blue staining and Dimethylmethylene blue (DMMB) assay revealed that the extracellular matrix (ECM) synthesis was increased in a time-dependent manner from 2 to 8 weeks. The chondrocyte mRNA expression profile was dramatically affected by prolonged culture time, with a significant downregulation of collagen type I, whereas the expression of collagen type II, aggrecan, Sox9 and matrix metalloproteinase 13 (MMP-13) were significantly upregulated. In addition, transmission electron microscopy (TEM) result indicated dilation of rough endoplasmic reticulum (RER) in these long-term monolayer cultured chondrocytes. These findings demonstrate that the chondrocytes phenotype could be partially redifferentiated through the spontaneous redifferentiation process in long-term cultures using standard culture medium without the addition of chondrogenic supplements or tissue-culture scaffolds.


Junior League Football: risks versus benefits.
Major concerns about physical injury, emotional stress, poor adult leadership, and interference with junior high school football programs contribute to the Junior League Football controversy. In the final analysis, benefits of participation in these football programs are shown to far outweigh the risks.


Transcriptomic and metabolomic analysis of liver cirrhosis.
Liver cirrhosis is one of the leading causes of decreased life expectancy worldwide. However, the molecular mechanisms underlying liver cirrhosis remain unclear. In this study, we performed a comprehensive analysis using transcriptome and metabolome sequencing to explore the genes, pathways, and interactions associated with liver cirrhosis. We performed transcriptome and metabolome sequencing of blood samples from patients with cirrhosis and healthy controls (1:1 matched for sex and age). We validated the differentially expressed microRNA (miRNA) and mRNAs using real-time quantitative polymerase chain reaction. For transcriptome analysis, we screened for differentially expressed miRNAs and mRNAs, analyzed mRNAs to identify possible core genes and pathways, and performed co-analysis of miRNA and mRNA sequencing results. In terms of the metabolome, we screened five pathways that were substantially enriched in the differential metabolites. Next, we identified the metabolites with the most pronounced differences among these five metabolic pathways. We performed receiver operating characteristic (ROC) curve analysis of these five metabolites to determine their diagnostic efficacy for cirrhosis. Finally, we explored possible links between the transcriptome and metabolome. Based on sequencing and bioinformatics, we identified miRNAs and genes that were differentially expressed in the blood of patients with liver cirrhosis. By exploring pathways and disease-specific networks, we identified unique biological mechanisms. In terms of metabolomes, we identified novel biomarkers and explored their diagnostic efficacy. We identified possible common pathways in the transcriptome and metabolome that could serve as candidates for further studies.


Assessing the reliability of dose coefficients for exposure to radioiodine by members of the public, accounting for dosimetric and risk model uncertainties.
Assessments of risk to a specific population group resulting from internal exposure to a particular radionuclide can be used to assess the reliability of the appropriate International Commission on Radiological Protection (ICRP) dose coefficients used as a radiation protection device for the specified exposure pathway. An estimate of the uncertainty on the associated risk is important for informing judgments on reliability; a derived uncertainty factor, UF, is an estimate of the 95% probable geometric difference between the best risk estimate and the nominal risk and is a useful tool for making this assessment. This paper describes the application of parameter uncertainty analysis to quantify uncertainties resulting from internal exposures to radioiodine by members of the public, specifically 1, 10 and 20-year old females from the population of England and Wales. Best estimates of thyroid cancer incidence risk (lifetime attributable risk) are calculated for ingestion or inhalation of 129I and 131I, accounting for uncertainties in biokinetic model and cancer risk model parameter values. These estimates are compared with the equivalent ICRP derived nominal age-, sex- and population-averaged estimates of excess thyroid cancer incidence to obtain UFs. Derived UF values for ingestion or inhalation of 131I for 1 year, 10-year and 20-year olds are around 28, 12 and 6, respectively, when compared with ICRP Publication 103 nominal values, and 9, 7 and 14, respectively, when compared with ICRP Publication 60 values. Broadly similar results were obtained for 129I. The uncertainties on risk estimates are largely determined by uncertainties on risk model parameters rather than uncertainties on biokinetic model parameters. An examination of the sensitivity of the results to the risk models and populations used in the calculations show variations in the central estimates of risk of a factor of around 2-3. It is assumed that the direct proportionality of excess thyroid cancer risk and dose observed at low to moderate acute doses and incorporated in the risk models also applies to very small doses received at very low dose rates; the uncertainty in this assumption is considerable, but largely unquantifiable. The UF values illustrate the need for an informed approach to the use of ICRP dose and risk coefficients.


[Vaccination in adults].
While immunization programs for children are well accepted in Switzerland, vaccinations of adults are still a problem. This paper deals with indications for vaccinations in adults. While the whole adults population should be immunized (boostered) against diphtheria, poliomyelitis and tetanus, other vaccinations (CEE, hepatitis A, hepatitis B, influenza, measles, mumps, rubella, rabies, varicella) should be administered according to risks at the workplace. Guidelines for vaccination programs in occupational medicine are presented and discussed.