A comprehensive lipid binding and activity validation of a cancer-specific peptide-peptoid hybrid PPS1.
We recently identified a peptide-peptoid hybrid, PPS1, which recognizes lipids that have an overall negative charge, such as phosphatidylserine (PS), phosphatidylglycerol (PG), phosphatidic acid (PA), and phosphatidylinositol (PI), but that does not bind to neutral lipids, such as phosphatidylcholine (PC), phosphatidylethanolamine (PE), and sphingomyelin (SM). The simple dimeric version of PPS1, PPS1D1, displayed strong cytotoxicity to cancer cells over normal cells in vitro and tumor burden in vivo. In this study, we comprehensively characterized the direct binding and activity of PPS1 on PS, PG, and PA using liposome-based assays and lung cancer cell lines that express these negatively charged lipids. First, the fluorescence polarization (FP) binding studies of fluoresceinated-PPS1 (PPS1-FITC) to PS-, PG-, and PA-containing PC-liposomes showed that the binding of PPS1 to PC-liposomes increased as concentrations of these lipids increased. In terms of activity, PPS1D1 induced the release of calcein from large, unilamellar PC-liposomes containing 15-30% PS, PG, and PA. PPS1D1 had no activity when the liposomes were composed of 100% PC. This effect was higher at 30% lipids than 15%, and the EC50 for PG and PA were higher than that of PS, indicating that PPS1D1 is more specific towards PS. PPS1D1 binds to and induces significant cytotoxicity in lung cancer cell lines H1693, HCC95, and H1395, which express negatively charged lipids, but had no effect on normal HBEC30KT cells, which has mostly PC in the outer layer. In addition, a series of previously developed PPS1D1 derivatives, which retain or lose activity, were tested with these liposome-based assays, and the data were equivalent to previous observations. This study provides comprehensive binding and activity validations of a unique peptide-peptoid hybrid, PPS1, on negatively charged lipids PS, PA, and PG that are elevated on cancer cell surfaces relative to normal human cell surfaces.


Creatinine clearance and signs of end-organ damage in primary hypertension.
A reduction in renal function is associated with high cardiovascular morbidity and mortality in hypertension. The aim of the present study was to investigate the relationship between creatinine clearance and subclinical organ damage in 957 never previously treated, middle-aged patients with primary hypertension. Renal function was estimated by means of the serum creatinine level using the Cockcroft-Gault formula; left ventricular hypertrophy (LVH) was determined according to electrocardiographic criteria; and retinal vascular changes were evaluated by direct ophthalmoscopy. Creatinine clearance was, on the average, 83+/-21.2 ml/min, and the prevalence of LVH and retinopathy was 13 and 49%, respectively. Creatinine clearance was inversely related to the duration of disease (r=-0.132, P<0.0001), systolic blood pressure (r=-0.110, P=0.001), serum glucose (r=-0.090, P=0.007), total cholesterol (r=-0.196, P<0.0001), and LDL-cholesterol (r=-0.196, P<0.0001). Patients in the lower quintile of creatinine clearance showed a higher prevalence of electrocardiogram (ECG) determined LVH (P=0.04), as well as retinal changes (P=0.02). The risk of having LVH or retinal vascular changes increases significantly with each s.d. decrease in creatinine clearance, regardless of traditional cardiovascular risk factors. Moreover, patients with ECG-determined LVH and retinal changes showed lower creatinine clearance as compared to those with lesser degrees of target organ involvement (P<0.01). In conclusion, a mild reduction in creatinine clearance is associated with preclinical end-organ damage in patients with normal creatinine and primary hypertension. These data may help explain the high cardiovascular mortality observed in patients with renal dysfunction. Routine evaluation of creatinine clearance could be useful for identifying patients at higher cardiovascular risk.


Inhibition of the NF-κB pathway by R65 ribozyme gene via adeno-associated virus serotype 9 ameliorated oxidized LDL induced human umbilical vein endothelial cell injury.
NF-κB signaling plays a central role in the regulation of inflammatory responses in atherosclerosis. R65 ribozyme gene suppresses activation of NF-κB pathway, therefore we studied whether R65 gene therapy can ameliorate oxidized low-density lipoprotein (ox-LDL) induced human umbilical vein endothelial cells (HUVECs) injury. Recombinant adeno-associated virus serotype 9 (rAVV9) vector was used to transfect the R65 ribozyme gene (rAVV9-R65) into HUVECs then following ox-LDL stimulation, expression of NF-κB p65 and p50 subunits, inflammatory mediators and cell apoptosis were examined. First, rAVV9-enhanced green fluorescent protein (eGFP)-R65 at 1×10(7) v.g./cell multiplicity of infection reached a long-lasting and significant increase in R65 gene expression. Second, ox-LDL treatment led to time- and dose-dependent activation of NF-κB pathway, and enhanced inflammatory response and cell death evidenced by increased expression of nuclear NF-κB p65 and p50 subunits, greater production of tumor necrosis factor α, interleukin-6 and von willebrand factor and 20.57% increased apoptotic HUVECs. Third, over-expression of R65 gene was 2-fold increased in HUVECs attenuated ox-LDL induced unclear accumulation and expression of p65 subunit and ameliorated inflammation and cell death (all P < 0.05). rAAV9-mediated R65 ribozyme gene transfection in cultured HUVECs effectively inhibits ox-LDL induced activation of NF-κB and production of inflammatory cytokines and prevents cell apoptosis.


Frequency judgements of abstract designs by patients with diencephalic, temporal lobe or frontal lobe lesions.
Patients with diencephalic, temporal lobe or frontal lobe lesions were compared with healthy controls on a frequency judgement task. The three patient groups were disproportionately impaired at estimating how often a series of abstract designs had been presented relative to controls. Diencephalic and temporal lobe patients did not differ from each other. It is argued that the results may reflect a 'core' memory deficit in the temporal lobe patients. The impairment in the frontal patients may reflect their difficulty in making an organised search in memory for multiple traces of an item, while the deficit shown by the diencephalic patients (particularly those with Korsakoff syndrome) may be due to the combined effects of a generally poor memory and superimposed frontal pathology.


Decreased urine production in the near-term fetal lamb after maternal ethanol infusion.
Intravenous infusion of 1 gm ethanol/kg maternal body weight over 1 hour to three conscious catheterized near-term pregnant ewes decreased fetal urine production for 3 hours (overall decrease of 54% from control). This effect in the near-term fetus is opposite to the ethanol-induced diuresis that occurs in adults.


Circling elicited from the anteromedial cortex and medial pons: refractory periods and summation.
Contraversive circling is evoked by stimulating the anteromedial cortex (AMC) of rats, and ipsiversive circling is evoked by stimulating the medial pons (PONS). During AMC circling, lateral and vertical head movements and vibrissae movements were exhibited. During PONS circling, although lateral head movements were exhibited, vertical head movements and vibrissae movements were not exhibited. Refractory periods were estimated by delivering trains of paired pulses and measuring the frequency thresholds for circling at various intrapair intervals. Refractory periods at AMC circling sites were much longer (range 1.4-3.3 ms) than at PONS circling sites (range 0.5-1.0 ms). To determine the degree of summation between the AMC and contralateral PONS, the two sites were stimulated concurrently. Summation of 95-100% was observed for AMC and PONS circling. No collision was observed at short intrapair intervals of paired pulses. Thus, the AMC and PONS are not connected axonally but are related, perhaps serially, for the production of circling.


Thursdays with Marion: the therapist's tale.
We who work with people with chronic and/or terminal illnesses are often confounded about what we ought to do and what we can do for those who suffer. This paper presents a case study of my work with Marion who began therapy after her presymptomatic testing for HD to address her depression and anxiety. The approach we took is a narrative one. The impact of illness on existing family stories is described followed by an examination of the premises of a narrative model. The case description demonstrates the collaborative nature of the therapy. Some thoughts on the role of the therapist in this model are offered.


Ultrasonographic Evaluation of the Femoral Cartilage, Achilles Tendon, and Plantar Fascia in Young Women Wearing High-Heeled Shoes.
Specific attention on the musculoskeletal impact of wearing high-heeled shoes (HHS) has mainly focused on knee osteoarthritis and the literature is limited to biomechanical changes. The distal femoral cartilage has not been morphologically studied. Additionally, although heel elevation is coupled with a shear stress at the heel and overloaded calf muscles, Achilles tendon (AT) and plantar fascia (PF) thicknesses have not been assessed either. To investigate whether the distal femoral cartilage, AT, and PF were different in women wearing HHS and flat-heeled shoes (FHS) and specifically, different in terms of AT/PF and distal femoral cartilage thicknesses. Cross-sectional observational study. Tertiary care center. There were 34 women (mean age; 31.1 ± 6.4, body mass index [BMI]; 21.6 ± 2.4 kg/m2 ) in the HHS group and 54 women (mean age; 29.5 ± 7.2 years, BMI 22.5 ± 2.9 kg/m2 ) in the FHS group (P = .271, P = .102, respectively). Women wearing shoes with a heel height of >5 cm were enrolled in the HHS group, and those wearing shoes with a heel height of <1.4 cm were included in the FHS group. Distal femoral cartilage from the lateral condyle, intercondylar area and medial condyle (MFC), AT and PF thicknesses, and any abnormalities were evaluated bilaterally by ultrasound. Within-group comparisons yielded thicker right MFC (P = .022) and left AT (P = .028) only in the HHS group. Between-group comparisons yielded thicker left AT in the HHS group (P = .040). PF thicknesses were similar both within and between group comparisons (all P > .05). Right AT thickness was positively correlated with right (r = .469, P = .005) and left (r = .402, P = .018) PF thicknesses only within the HHS group. Only calcaneal irregularity/spur was found to be common in the HHS group (P = .038). We found thickening of the right MFC and left AT in those wearing HHS, whereas PF thickness was not significantly different between those wearing HHS and those wearing FHS. III.


Assessment of nutritional interventions for modification of age-associated cognitive decline using a canine model of human aging.
The present review focuses on the utility of a canine model in evaluating nutritional interventions for age-related cognitive dysfunction. Aged dogs demonstrate progressive cognitive decline with concurrent amyloid-beta pathology that parallels the pathology observed in aging humans. Dogs, therefore, provide a natural model of human pathological aging. We have and are in the process of evaluating several nutritional-based interventions aimed at preventing cognitive decline and brain aging. In a three-year longitudinal study, we examined the effects of a diet enriched with antioxidants and mitochondrial cofactors on several measures of cognition and brain aging. Compared to controls, aged dogs on the enriched diet demonstrated both short- and long-term cognitive benefits, as well decreased deposition of amyloid-beta protein. The diet also reduced behavioral signs associated with canine Cognitive Dysfunction Syndrome when assessed in veterinary clinical trials. We also have preliminary evidence suggesting a beneficial effect of a proprietary blend of docosahexaenoic acid and phospholipids on both cognitive and physiological measures. Collectively, our data indicate (1) that the dog, either in the laboratory or in the clinic, provides an important tool for assessing nutritional interventions and (2) that combination interventions aimed at several mechanisms of pathological aging may prove more effective than single nutritive components in human trials.


RNA-protein complexes responsible for replication and transcription of the double-stranded RNA bacteriophage phi 6.
RNA-protein complexes active for transcription and replication of the double-stranded RNA bacteriophage phi 6 have been partially purified from lysates of infected Pseudomonas phaseolicola. Transcribing particles (filled procapsids) contain the three viral dsRNAs and all four procapsid proteins P1, P2, P4, and P7. Particles with replicase activity contain the same four proteins as well as single plus RNA strands duplexed with various extents of minus strands initiated in vivo. The in vitro replication reaction is insensitive to RNaseA. Sarkosyl destroys transcription complexes but does not reduce the activity of replication complexes, although the latter lose 80% of their P4 and the single-strand RNA template becomes sensitive to RNase. The detection of complexes that replicate small only, or both small and medium, RNA suggests that the RNAs are packaged sequentially in the order small, medium, large.


A novel nucleophilic approach to 1-alkyladenosines. A two-step synthesis of [1-15N]adenosine from inosine.
A novel ANRORC mechanism in the reaction of 1-(2,4-dinitrobenzenesulfonyl)inosines with amines has allowed the preparation of 1-alkyladenosines and [1-15N]adenosines in a straightforward way from inosines.


Corneal astigmatic change after photorefractive keratectomy and photoastigmatic refractive keratectomy.
To evaluate and compare the efficacy, safety, predictability, and surgically induced astigmatism (SIA) of photorefractive keratectomy (PRK) and photoastigmatic refractive keratectomy (PARK). Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan. In this retrospective study, 70 eyes were treated for myopia and 70 eyes were treated for myopic astigmatism. Refraction, corneal topography, slitlamp findings, and visual acuity in the 2 groups at 1, 3, and 6 months were evaluated and compared. Vector analysis was performed to determine the SIA in both groups. The mean preoperative spherical equivalent at the glasses plane in the PRK and PARK groups was -6.06 diopters (D) and -7.18 D, respectively. At 6 months, the mean reduction in astigmatism in the PARK group was 61.0%. Predictability was within +/-1.0 D in 85.2% of eyes in the PRK group and 62.5% in the PARK group. An uncorrected visual acuity of 20/40 or better was achieved in 91.8% and 83.9% of eyes, respectively. The mean SIA was 0.64 D in the PRK group, with a general with-the-rule axis shift. The results of vector analysis were more favorable when calculated from refractive values than from Sim-K corneal topography values. The mean astigmatism correction index and index of success calculated from refractive data were 0.75 and 0.38 in the PARK group. The mean magnitude and angle of error were 0.22 +/- 0.52 D and -2.13 +/- 24.41 degrees, respectively. Photorefractive keratectomy and PARK were effective and safe procedures for the correction of myopia and myopic astigmatism. However, SIA occurred with spherical myopic treatments. This small SIA may be a confounding factor in low astigmatic treatments.


The vitamin K-dependent bone protein is accumulated within cultured osteosarcoma cells in the presence of the vitamin K antagonist warfarin.
Osteosarcoma cells grown in normal culture medium secrete bone gamma-carboxyglutamic acid protein (BGP, osteocalcin) which is identical with BGP purified from the bone matrix. Two tests indicate that the secreted medium protein contains the full complement of three gamma-carboxyglutamate residues present on BGP purified from the bone matrix. First, the secreted protein from ROS 17/2 and bone matrix BGP have identical isoelectric points (pI = 4.0). Second, they have identical hydroxyapatite binding behavior. If warfarin is added to the culture medium, the secreted protein has a higher isoelectric point (pI = 4.6) and a lower affinity for hydroxyapatite characteristic of thermally decarboxylated or non-gamma-carboxylated BGP. The observed shift in isoelectric point of secreted BGP after warfarin treatment from pH 4.0 to 4.6 is also reflected in the presence of pI = 4.1 and pI = 4.6 species intracellularly. These isoelectric species correspond to fully carboxylated BGP and noncarboxylated BGP, which are in the process of secretion. Addition of 10 micrograms/ml of warfarin causes a specific 47% reduction in secretion rate of BGP, while at the same time, the intracellular BGP concentration increases 3-fold. These phenomena appear related to the interruption by warfarin of the normal sequence of processing of precursor BGP proteins, as a new, immunoreactive species with a higher isoelectric pH not present in control cells appears to be responsible for the increased intracellular antigen within warfarin-treated cells. Our results show that vitamin K-dependent processing is important for normal secretion of BGP from the cell.


Hit-to-lead optimization of a pyrazinylpiperazine series against Leishmania infantum and Leishmania braziliensis.
An early hit-to-lead optimization of a novel pyrazinylpiperazine series against L. infantum and L. braziliensis has been performed after an extensive SAR focusing on the benzoyl fragment of hit (4). Deletion of the meta-Cl of (4) led to the obtention of the para-hydroxyl derivative (12), on which the design of most monosubstituted derivatives of the SAR was based. Further optimization of the series, involving disubstituted benzoyl fragments and the hydroxyl substituent of (12), allowed the obtention of a total of 15 compounds with increased antileishmanial potency (IC50 < 10 μM), nine of which displayed activity in the low micromolar range (IC50 < 5 μM). This optimization ultimately identified the ortho, meta-dihydroxyl derivative (46) as an early lead for this series (IC50 (L. infantum) = 2.8 μM, IC50 (L. braziliensis) = 0.2 μM). Additional assessment of some selected compounds against other trypanosomatid parasites revealed that this series is selective towards Leishmania parasites, and in silico ADMET predictions revealed satisfactory profiles for these compounds, allowing further lead optimization of the pyrazinylpiperazine class against Leishmania.


Molecular characterization of Aeromonas species isolated from farmed eels (Anguilla japonica).
Seventy Aeromonas strains were identified by phylogenetic analysis using housekeeping genes (gyrB and rpoD) in order to investigate etiological agents for aeromoniasis in farmed eels (Anguilla japonica). The phylogenetic analysis showed that Aeromonas aquariorum (n=22, 31.4%) was the predominant species among the investigated eel strains, followed by Aeromonas caviae (n=16, 22.9%), A. veronii (n=13, 18.6%), A. hydrophila (n=12, 17.1%), A. jandaei (n=4, 5.7%), A. media (n=2, 2.9%), and A. trota (n=1, 1.4%). The potential virulence of the present strains was estimated by performing PCR assays using the following seven virulence genes: cytotoxic enterotoxin (act), two cytotonic enterotoxins (alt and ast), glycerophospholipid:cholesterol acyltransferase (gcaT), DNase (exu), lipase (lip), and flagellin (fla). The detection rates of act, alt, ast, gcaT, exu, lip, and fla among all 70 strains were 91.4%, 55.7%, 27.1%, 97.1%, 95.7%, 100%, and 98.6%, respectively. In genotyping of enterotoxin genes, act(+)/alt(+)/ast(+), act(+)/alt(+)/ast(-), and act(+)/alt(-)/ast(-) genotypes were prevalent in A. hydrophila (8/12 strains), A. aquariorum (13/22 strains), and A. caviae (14/16 strains), respectively, suggesting a high heterogeneity among Aeromonas species. In this study, A. aquariorum, which has been an unrecorded species in Korea, can be an etiological agent for aeromoniasis of eel.


Rapid smoking of menthol and nonmenthol cigarettes by black and white smokers.
White subjects took significantly more puffs of cigarette smoke before stopping than did black subjects in a modified, controlled-dose rapid smoking procedure. Paradoxically, however, no racial differences were detected for changes in carbon monoxide levels, or changes in cardiovascular variables (systolic and diastolic blood pressure, and heart rate). Due to the cooling and topical anesthetic properties of menthol, it was hypothesized that menthol and regular cigarette smokers would take more puffs from menthol cigarettes than from regular cigarettes before stopping in the controlled-dose rapid smoking procedure. However, no difference was observed for the number of puffs taken from regular as opposed to menthol cigarettes (cigarette type condition) and no differences were found for Cigarette Preference (regular smokers vs. menthol smokers).


Waterborne copper exposure up-regulated lipid deposition through the methylation of GRP78 and PGC1α of grass carp Ctenopharyngodon idella.
Early molecular events after the exposure of heavy metals, such as aberrant DNA methylation, suggest that DNA methylation was important in regulating physiological processes for animals and accordingly could be used as environmental biomarkers. In the present study, we found that copper (Cu) exposure increased lipid content and induced the DNA hypermethylation at the whole genome level. Especially, Cu induced hypermethylation of glucose-regulated protein 78 (grp78) and peroxisome proliferator-activated receptor gamma coactivator-1α (pgc1α). CCAAT/enhancer binding protein α (C/EBPα) could bind to the methylated sequence of grp78, whereas C/EBPβ could not bind to the methylated sequence of grp78. These synergistically influenced grp78 expression and increased lipogenesis. In contrast, DNA methylation of PGC1α blocked the specific protein 1 (SP1) binding and interfered mitochondrial function. Moreover, Cu increased reactive oxygen species (ROS) production, activated endoplasmic reticulum (ER) stress and damaged mitochondrial function, and accordingly increased lipid deposition. Notably, we found a new toxicological mechanism for Cu-induced lipid deposition at DNA methylation level. The measurement of DNA methylation facilitated the use of these epigenetic biomarkers for the evaluation of environmental risk.


Impalpable breast lesion localisation, a logistical challenge: results of the UK iBRA-NET national practice questionnaire.
Breast conserving surgery of impalpable breast lesions requires safe and effective localisation techniques. Wire localisation has traditionally been used, but has limitations. Newer techniques are now being introduced to mitigate this. The iBRA-NET group aims to robustly evaluate these new techniques in well-designed prospective studies. We report the first phase of this evaluation, a survey to establish current practice and service provision of breast localisation techniques in the UK. A national practice questionnaire was designed using 'SurveyMonkey®' and was circulated to UK breast surgeons via the Association of Breast Surgery and the Mammary Fold. The questionnaire was live from 6th October 2018 to 6th April 2019. Only one response per unit was requested to reflect the unit's practice. Complete responses were received from 98 breast units across the UK. Wires were the mostly commonly used localisation technique (n = 82) with fewer units using Magseed® (n = 9), Radioguided Occult Lesion Localisation (n = 5) and Radioiodine Seed Localisation (n = 2). There was significant variation in practice and logistics involved. Frequent delays and theatre overruns were reported in 39 and 16 units, respectively. The median satisfaction score of the current technique was 7 out of 10. The main perceived limitation of existing localisation methods was logistics affecting theatre scheduling and the main barrier to introducing a new technique was cost. Wires are currently the most commonly used localisation technique but are associated with significant logistical issues. Newer techniques may offer a better solution but will need robust evaluation before they are adopted to ensure safety and efficacy.


Light participates in the auxin-dependent regulation of plant growth.
Light is the energy source for plant photosynthesis and influences plant growth and development. Through multiple photoreceptors, plant interprets light signals through various downstream phytohormones such as auxin. Recently, Chen et al. (2020) uncover a new layer of regulation in IPyA pathway of auxin biosynthesis by light. Here we highlight recent studies about how light controls plant growth through regulating auxin biosynthesis and signaling.


Time course of ethylcholine aziridinium ion (AF64A)-induced cholinotoxicity in vivo.
The time course of the cholinotoxicity of ethylcholine aziridinium ion (AF64A) has been investigated. Rats were injected with AF64A (3 nmols/3 microliters/side, bilateral, i.c.v.) or with vehicle. One day to one year after treatment, the hippocampus, cortex and striatum were analyzed for the activity of choline acetyltransferase (ChAT) and acetylcholinesterase (AchE) and high-affinity transport of choline (HAChT). In addition, the release of K+-stimulated acetylcholine (ACh) from superfused slices of hippocampus was determined. The first parameter affected was high affinity transport of choline. One day after treatment with AF64A, the high affinity transport of choline in the hippocampus was reduced by 23%. This reduction was maximal one week after treatment (-67%) and persisted for at least 6 months. The high affinity transport of choline in the striatum and cortex was not altered by treatment with AF64A. The activity of ChAT and AChE in the hippocampus was reduced by 2 days after treatment with AF64A. These deficits persisted for at least 6 months (AChE) to 1 year (ChAT). The activity of ChAT and AChE in the cortex and striatum was minimally affected up to 1 year after treatment with AF64A, at which time significant reductions were noted. The release of ACh was affected 3 days after treatment with AF64A, and remained attenuated 6 months later. These data indicate that the cholinergic deficit caused by in vivo treatment with AF64A was first apparent at the level of high affinity uptake of choline in the hippocampus HAChT. Subsequently, the activity of ChAT and AChE and release of ACh in the hippocampus were affected.(ABSTRACT TRUNCATED AT 250 WORDS)


Identification and characterization of a novel circovirus species in domestic laying ducks designated as duck circovirus 3 (DuCV3) from Hunan province, China.
Duck circovirus (DuCV) is an immunosuppressive virus and can induce immunosuppression increasing rates of infection caused by other pathogens, which has resulted in gross economic losses in poultry industries. The genome sizes of DuCVs varied from 1987 to 1996 nucleotides (nt). Up to date two DuCV genotypes/lineages, DuCV1 and DuCV2, have been defined, with genome identities of around 83% between each other. In this study, a novel duck circovirus having a genome size of 1755 nt was identified from laying ducks with a disease of egg production declining or abrogation from Hunan province, China. Two major open reading frames (ORFs) were identified, with ORF1 (882 nt) and ORF2 (738 nt) encoding replicase (Rep) and capsid protein (Cap), respectively. Its genome showed the highest identities of 62.3-63.7% and 66.3%- 67.8% to the known genomes of DuCVs and goose circoviruses (GoCVs) available in GenBank, respectively, while it showed less than 50% identities to the genomes of other circoviruses. The amino acid sequence of capsid of this virus showed the highest identities of 45.4%- 47.3% and 42.9%- 44.5% to capsids of the known DuCVs and GoCVs, respectively, while it showed less than 27% identity to the capsid proteins of other circoviruses available in GenBank. Further phylogenetic analyses based on genomes, amino acid sequences of Rep and Cap proteins demonstrated that the present duck circovirus was clustered in a separate clade, distinct from other DuCVs and GoCVs, corroborating it is a distinct novel circovirus species in ducks, tentatively designated as duck cirovirus 3 (DuCV3). The clinical significance and pathogenesis of this virus needs further investigation.


[What about the weekend effect? Impact of the day of admission on in-hospital mortality, length of stay and cost of hospitalization].
There is no agreement on the existence of the weekend effect in healthcare or, if it exists, on its possible causes. The objective of the study was to evaluate the differences in healthcare outcomes between patients admitted on weekdays or weekends in a high-complexity hospital. Observational and retrospective study of patients admitted between 2016 and 2019 in a public hospital with more than 1300 beds. Hospitalization episodes were classified according to whether admission took place between Friday at 3:00 p.m. and the following Monday at 8:00 a.m. (weekend admission) or not (admission on weekdays). Mortality, length of stay and associated costs were compared, applying their respective risk-adjustment models. Of the total 169,495 hospitalization episodes analyzed, 48,201 (28.44%) corresponded to the weekend, presenting an older age (54.9 years vs. 53.9; P<.001), a higher crude mortality rate (5.22% vs. 4.59%; P<0.001), and a longer average length of stay (7.42 days vs. 6.74; P<.001), than those admitted on weekdays. The median crude cost of stay was lower (€731.25 vs. €850.88; P<0.001). No significant differences were found when applying the adjustment models, with a risk-adjusted mortality ratio of 1.03 (0.99-1.08) vs. 0.98 (0.95-1.01), risk-adjusted length of stay of 1.002 (0.98-1.005) vs. 0.999 (0.997-1.002) and risk-adjusted cost of stay of 0.928 (0.865-0.994) vs. 0.901 (0.843-0.962). The results of the study reveal that the assistance provided during the weekends does not imply worse health outcomes or increased costs. Comparing the impact between hospitals will require a future homogenization of temporal criteria and risk adjustment models.


[Incidence of methicillin-resistant Staphylococcus aureus in community-onset paediatric skin infections: a retrospective study 2000-2005].
A dramatic increase in the incidence of methicillin-resistant Staphylococcus aureus (MRSA) in community-onset skin infections has been reported over the last 10 years in the USA. The emergence of MRSA has been recently described in France. The aims of this study were to assess the incidence of MRSA in community-onset skin infections and to analyse the characteristics of MRSA skin infections in a French paediatric population. This is a retrospective study covering the period January 2000 to December 2005. Patients aged under 15 years with S. aureus isolated from skin and a clinical diagnosis of skin infection were included. One hundred and thirty-four children were included with a median age of 3.4 years. There were no significant differences in MRSA prevalence between the different years of the study. The overall prevalence of MRSA was 8.2% (n=11/134). None of the isolated strains presented an antimicrobial susceptibility profile suggestive of the ST80-type community-acquired MRSA described in France. Three MRSA strains were isolated from serious superantigen-mediated skin infections. The antimicrobial susceptibility and genetic profile (tst-positive agr2 MSRA) for one strain of S. aureus militated strongly in favour of an MRSA ST5 clone skin infection. In this study we found no evidence of epidemic spread of MRSA in community-onset childhood skin infections between 2000-2005. Nevertheless, we report three cases of serious MRSA-induced superantigen-associated skin infection. This argues in favour of the presence of virulent community MRSA clones in France.


Intraventricular conduction delay after bupropion overdose.
Bupropion overdose mainly is characterized by tachycardia, agitation, and seizures. The few reports of QRS complex widening after bupropion overdose that have been published in peer-reviewed literature are notable for failure to have confirmed elevated plasma bupropion concentrations or failure to have excluded other causes of QRS widening. We describe two patients in whom bupropion overdose was confirmed with elevated plasma bupropion concentrations and in whom other cardiotoxic ingestions were excluded with comprehensive analytical toxicology testing. Our findings are in keeping with ex vivo studies in which bupropion antagonizes cardiac voltage-gated sodium channels. Bupropion overdose should be considered in the differential diagnosis of unexpected QRS widening.


Amber Light Emitting Samarium Incorporated Barium Cerate Perovskite with 100% Color Purity for Pharmaceutical Industry.
Numerous structural and conductive properties of barium cerate (BC) make this material a promising candidate for energy storage applications. In this work, we demonstrated that BC can be proficiently functionalized by incorporating trivalent samarium ions to give rise to optical properties. Single-phased BaCeO3:Sm3+ (BCS) phosphors were synthesized by gel combustion technique followed by calcination. The crystal structure, optical properties, and prospective applications in LEDs were investigated systematically. By linking the information acquired from the diffuse reflectance spectra with that of the PL spectra, we better understood the electronic level structure and energy transfer mechanism. Fine yellow-orange luminescence with 100% color purity (CP) and lower Correlated Color Temperature (CCT) has been achieved via energization at 348 nm wavelength. The x = 0.02 Sm3+ has been identified as the optimized content for the luminescence with a quantum efficiency of 34.2%. Obtained yellow-orange coordinates (0.564, 0.435) are proximate to commercialized L3 rank amber LED (Nichia corporation). The present results signify that UV light can suitably energize the BCS phosphor to get monochromatic amber light which can be used to guard medications during manufacture and storage.


Comparison of Consensus on Life-sustaining Treatment of the Elderly in Care Facilities and Family Member Dyad.
The purpose of this study is to compare the agreement in opinion between the elderly in care facilities and their family members regarding the life-sustaining treatment at the deathbed and to find out if the intentions of the elderly are being properly reflected in their deathbed treatment. Data were collected from 85 elderly individuals at five care facilities in Chunkcheongnam-do and 85 family members. The data were collected with a self-administered questionnaire from July 22, 2013 to August 15, 2014. A total of 170 cases were analyzed using SPSS version 21. First, the family members' preference for life-sustaining treatment was higher than the patients' preference. The preference between the elderly and their family members regarding life-sustaining treatment was statistically significant with regards to oral nutrition, pain control through oral and anal administration, pain control through intravenous administration, transfusion, and admission to an intensive care unit. Second, looking at the agreement between elderly and guardians regarding life-sustaining treatment, there was significant concordance about general testing, oral nutrition, intravenous hydration, intravenous nutrition, antibiotic treatment for severe infection with low resiliency, admission to an intensive care unit, blood pressure increase medication use, cardiopulmonary resuscitation, and tracheotomy. It is essential for the medical staff to confirm agreement between the elderly and their family members regarding life-sustaining treatment, and if such a prior agreement is not feasible, the patient's intention should be considered more actionable than their family members.


NMR study of whole rat bile: the biliary excretion of cefoperazone and benzyl chloride by an isolated perfused rat liver.
1H NMR spectroscopy at 400 MHz has been applied to the analysis of whole bile samples produced by the isolated perfused rat liver. Using relatively simple NMR experiments biliary excretory products of cefoperazone and benzyl chloride were identified as cefoperazone itself and a benzyl-glutathione conjugate, respectively. Our use of 13C isotopic labelling demonstrates how 1H/13C heteronuclear NMR techniques can be used to produce uncrowded and informative spectra from whole bile. From the use of a HMQC-COSY experiment the structure of a benzyl-glutathione conjugate contained in whole bile was confirmed.


The impact of development and malaria control activities on its vectors in the Kinabatangan area of Sabah, East Malaysia.
A study was carried out from July 2001 until January 2003 in the Kinabatangan area of Sabah, part of Borneo island, where malaria used to be mesoendemic. Vector surveys determined that Plasmodium falciparum was the predominant species and Anopheles balabacensis the primary vector. Malaria cases have dropped drastically over the years but P. falciparum is still predominant. In the present study, Anopheles donaldi was the predominant species and was positive for sporozoites. Although An. balabacensis was present, none were infective. An. donaldi bite more outdoors than indoors and have a peak biting time from 18:00 to 19:00 h when most people are still out of their homes. An integrated malaria control programme along with area development has helped in the control of malaria and its vector.


Aphidicolin potentiates apoptosis induced by arabinosyl nucleosides in human myeloid leukemia cell lines.
We investigated the effect of aphidicolin, an inhibitor of DNA polymerase alpha and delta, on the induction of apoptosis by arabinosyl nucleosides in a human promyelocytic leukemia cell line, HL-60. Pretreatment of HL-60 cells with aphidicolin (2 microM) significantly increased the number of morphologically apoptotic cells induced by 1-beta-D arabinofuranosylcytosine (ara-C) during 4 hr of incubation. This is consistent with the appearance of DNA fragmentation as determined quantitatively by diphenylamine or by agarose gel electrophoresis. The inhibition of cell growth on day 3 after drug exposure was correlated with the degree of apoptosis: Such synergistic interaction between aphidicolin and ara-C has also been observed in other human myeloid leukemia cell lines, U937 and KG-1. In addition, the induction of apoptosis by 9-beta-D arabinofuranosyladenine or 9-beta-D arabinofuranosylguanine is augmented by aphidicolin.


Continuous rt-PA infusion as a salvage strategy to maintain patency of the infarct artery; safety of high cumulative dose and subsequent emergency coronary artery angioplasty and bypass surgery.
Acute re-occlusion of an infarct artery reperfusion attained by thrombolytic therapy may be treated by emergency coronary angioplasty or bypass surgery. Repeated infusion of a thrombolytic agent is an additional treatment strategy. Three patients with reinfarctions that occurred very early after successful reperfusion were treated with continuous infusion of recombinant tissue-type plasminogen activator (rt-PA). These patients received a rt-PA dose of 300-360 mg while they awaited emergency mechanical revascularization procedures. Two patients had coronary angioplasty immediately after receiving repeated infusions of rt-PA and one underwent coronary bypass surgery while receiving a third rt-PA infusion. There were no bleeding complications in the 2 patients who underwent coronary angioplasty, and no excessive bleeding in the patient who received coronary bypass surgery. Thus, repeated continuous rt-PA infusions can be used to maintain the patency of recurrently occluding infarct arteries until definitive mechanical revascularization can be performed.


Effectiveness of very low doses of subcutaneous recombinant human erythropoietin in facilitating autologous blood donation before orthopedic surgery.
Clinical and pharmacokinetic data suggest that very low doses of subcutaneous recombinant human erythropoietin (rHuEPO) may be effective in a preoperative autologous blood deposit program. Fifty-two patients, scheduled for orthopedic surgery, were enrolled in a double-blind and placebo-controlled study. Patients were randomly assigned to the placebo group or to receive 30, 60, or 100 IU per kg of rHuEPO subcutaneously twice a week for 2 weeks before surgery. The dose of rHuEPO that was effective in facilitating the collection of 4 units of blood in the 2 weeks before surgery and that prevented a sharp decrease in hematocrit was determined. Only in patients receiving 100 IU per kg of rHuEPO did the outcome measurements differ significantly from those in the placebo group. With a higher (p < 0.01) cumulative increase in red cell volume during the study period (297 +/- 127 vs. 121 +/- 44 mL), 64 percent of those receiving 100 IU per kg of rHuEPO were able to donate 4 units of blood for autologous use, as compared with 23 percent of the placebo group (p < 0.05). Allogeneic transfusion was avoided, and the preoperative hematocrit and reticulocyte count were significantly higher in the patients receiving 100 IU per kg of rHuEPO (p < 0.05 and p < 0.01, respectively). Subcutaneously administered rHuEPO at a dose of 100 IU per kg twice a week for 2 weeks is effective in facilitating the collection of blood for autologous use and may improve the cost-benefit ratio of blood conservation interventions. Doses < or = 60 IU per kg are ineffective in facilitating such collections in this surgical setting.


Polyaniline@g-C3N4 derived N-rich porous carbon for selective degradation of phenolic pollutants via peroxymonosulfate activation: An electron transfer mechanism.
N-doped carbons have attracted extensive attention as catalysts for peroxymonosulfate (PMS) activation towards environmental remediation. However, synthesis of N-rich carbocatalysts is challenging and PMS activation mechanism is still unclear. Herein, novel N-rich porous carbocatalysts (C-PxCN-T) were synthesized by carbonization of polyaniline nanorods coated g-C3N4. C-P50CN-900 (polyaniline content 50%) calcined at 900 °C had high surface area (358 m2/g), product yield (27.1%) and N content (12.27 at%). It showed superior performance in activating PMS to degrade and mineralize various phenolic pollutants in a wide pH range (2-11) and with the co-existence of water constituents. A positive correlation was observed between phenol oxidation rates and contents of CO, C-C/CC and graphitic N, which served as active sites to facilitate adsorption of pollutants and PMS on C-P50CN-900 and subsequent electron-transfer from pollutants to PMS. Overall, this study provides new insights into rational design of N-doped carbocatalysts and elucidation of electron transfer pathway in PMS activation.


Redesigning incident reporting systems in the post-Mid-Staffordshire era.
Incident reporting systems are vital to safe health care. Existing systems should be made simpler and more accessible, proper feedback given to those who complete reports and lessons learned from investigations shared more widely. A major shift in culture is required so health-care professionals feel safe completing incident reports.


Palladium-Catalyzed Intramolecular Diarylation of 1,3-Diketone in Total Synthesis of (±)-Spiroaxillarone A.
A sterically congested all-carbon quaternary center was installed for the first time via a Pd-catalyzed cascade diarylation with aryl bromides and acyclic 1,3-diketones. This method was used as a key step in the total synthesis of (±)-spiroaxillarone A. Computational experimental results indicated that the selective diarylation is accelerated by the higher free-energy barriers of the endothermic transmetalation and reductive elimination in the first arylation step.


Serious Pseudomonas infections associated with endoscopic retrograde cholangiopancreatography.
After observing a single case of Pseudomonas aeruginosa bacteremia following endoscopic retrograde cholangiopancreatography (ERCP), six other P. aeruginosa infections that were temporally related to ERCP were retrospectively found over one year (August 1985 through July 1986) at LDS Hospital. In all seven patients, infection developed within five days after an ERCP. Five patients had bacteremia and two had cholangitis. All five of the Pseudomonas isolates available for testing were serotype 010. Cultures from the ERCP endoscope and several other endoscopes also yielded P. aeruginosa serotype 10, as did environmental cultures from equipment used to clean endoscopes. Among 167 ERCPs performed during the outbreak period, no other patient acquired P. aeruginosa infection. Each of the patients in the outbreak received the first scheduled ERCP of the day. The mean duration between the cleaning of the ERCP endoscope and its subsequent use was significantly longer in cases than in matched controls, a factor that may have permitted contaminating organisms to achieve high inocula in the inadequately cleaned endoscope. Epidemic control measures included improved disinfection of endoscopes, ongoing surveillance, and appropriate antimicrobial prophylaxis. This experience suggests that exogenous infection with Pseudomonas is associated with ERCP, that protracted and insidious outbreaks may occur, and that the occurrence of even a single case of Pseudomonas infection after ERCP should stimulate an epidemiologic investigation.


Expression and function of bone morphogenetic proteins in the development of the embryonic endocardial cushions.
Bone morphogenetic proteins (BMPs) are considered to be significant factors in the morphogenesis of the endocardial cushions of the developing embryonic heart. Previous studies have suggested that they are involved in the epithelial-mesenchymal transformation and migration of the cells forming the cushions, or in triggering an apoptotic cascade in a sub-population of cushion cells. We investigated the expression and function of BMP2 and BMP4 proteins in the developing heart of the chick and mouse embryos. In the chick, by immunocytochemistry, we find expression of BMP2 protein in the endocardial cushions of the outflow tract (OT) and atrio-ventricular (AV) regions at embryonic days (ED) 5-6, as well as in adjacent myocardial layers. Immunoblotting indicated that such expression persisted through ED 4-7, but peaked at ED4-5 in the OT and 5-6 in the AV cushions. This temporal sequence correlated with the peaks of apoptotic cell death found previously in the OT and AV cushions of the chick embryo. At equivalent stages in mouse, no such expression of BMP2 was found in the cushions, although expression was detected in adjacent myocardial layers. In the case of BMP4, in both chick and mouse, expression was found only in the myocardia and not in the cushions. Furthermore, BMP-specific receptors were found in the cushions, but not the myocardia, in both the AV and OT regions of the chick embryo. These results provide circumstantial evidence to support the contention that BMPs, originating from the myocardium, could be significant in the induction of apoptosis in chick embryo cushion cells, and confirms that there is species-specific variation in the expression pattern of BMP proteins, as had been predicted from previous studies of mRNA expression. Culture media conditioned by the growth of tissues from various regions of the developing heart were tested for their ability to induce apoptosis in cushion cells in culture. It was found that medium derived from the myocardia induced significant levels of cell death in the cushion cells, and that BMP4 could be detected in such media; however, retroviral over-expression of constitutively active (CA) and dominant-negative (DN) isoforms of BMP-specific receptors 1A and 1B (BMPR-1A and BMPR-1B) in cultured cells of the AV cushions did not alter levels of apoptosis or cell proliferation. Similar over-expression in cultured endocardial cells resulted in a significant change in cell shape, from endothelial to fibroblastic, with BMPR-1A CA and BMPR-1B DN, suggesting an influence of these receptors on cell transformation and/or cell migration. Taken together, these results provide support for the contention that BMP2 and BMP4 are important factors in the phenotypic transformational events involved in the morphogenesis of the chick embryo endocardial cushions, and could be involved in the induction of apoptosis in the cushion cells.


Inhibition of bovine leukaemia virus replication by the antisense RNA in cell line CC81.
A model system has been developed for quantitative evaluation of bovine leukaemia virus (BLV) replication in a permanent cell line CC81. Transfection of the BLV DNA into these cells evoked typical signs of retroviral infection: formation of syncytia, manifestation of reverse transcriptase activity and appearance of characteristic budding retroviral particles. To inhibit BLV replication, a recombinant plasmid pAGR with an antisense RNA gene targeted at the R-U5 region (147th-342th nt) of the viral genome has been engineered. Cotransfection of CC81 cells with infectious BLV DNA and pAGR led to effective inhibition of BLV replication by the antisense RNA, evidenced by a drop in the number of syncytia and reverse transcriptase activity. Maximal inhibition of BLV replication (95-97%) was observed at a weight ratio of input viral and plasmid DNAs equal to 1:10.


Real-world impact of ongoing regular exercise in overweight and obese US adults with diabetes on health care utilization and expenses.
To assess the effect of regular exercise on health care utilization patterns and expenses in a real-world national sample of overweight and obese US adults with diabetes. Medical Expenditure Panel Survey data (2010-2015) identified adults with diabetes and a body mass index (kg/m2) ≥25. Two groups were created: exercise (moderate or vigorous physical activity >30min at least five times weekly) and non-exercise groups. average total health care expenses (per-person per-annum) and the likelihood of hospitalization. Among 5140 overweight and obese adults with diabetes, 49.1% reported exercising at least five times weekly. The exercise group showed lower medical care and prescription drug utilization than the non-exercise group (p<0.001). Total unadjusted health expenses in the exercise group were $5651 lower than the non-exercise group (p<0.001). After controlling for socioeconomic and health-related variables, regular exercise reduced total health care expenses by 22.1% (p<0.001) and the likelihood of hospitalization by 28% (p=0.001). Reduced hospitalization and health care expenses were associated with regular exercise (≥30min at least five times weekly) in overweight and obese adults with diabetes.


Conjunctival goblet cells density and preservative-free tafluprost therapy for glaucoma: an in vivo confocal microscopy and impression cytology study.
To evaluate the density of conjunctival goblet cells (GCs) in glaucomatous patients treated with preservative-free (PF) tafluprost, using laser scanning confocal microscopy (LSCM) and impression cytology (IC). Thirty glaucomatous patients (30 eyes) naive for therapy and thirty healthy subjects (30 eyes) were enrolled. Conjunctiva was examined by means of Heidelberg Retina Tomography/Rostock cornea module. Afterwards, the specimens for IC were obtained. Patients were randomized to PF-tafluprost (Group 1) or preserved latanoprost (Group 2) and controls to the vehicle of latanoprost (Group 3) or physiological buffered saline solution (Group 4). Both LSCM and IC were performed at baseline, and after the 1st and 6th months of therapy, GC density (GCD) (cells/mm(2) ) was the main outcome measurement. Baseline. Mean GCD was 240.69 ± 25.43 and 232.65 ± 23.52, for LSCM, and 162.10 ± 23.44 and 164.71 ± 21.03 for IC in Group 1 and 2, respectively. GC density values were not significantly different in Group 3 and 4 (p > 0.05%). Month one. Mean GCD increased to 284.16 ± 43.88 and 230.62 ± 48.32 in Group 1 (p < 0.001) and to 297.86 ± 26.87 and 221.78 ± 43.02 in Group 2 (p < 0.05), measured with LSCM and IC, respectively. In Group 3, GCD decreased to 205.88 ± 25.04 and 139.54 ± 17.37 measured with LSCM and IC, respectively (p < 0.05). Month six. Mean GCD did not change in Group 1 (p > 0.05) whereas it decreased in Group 2 (p < 0.05), compared to month 1. In Group 3, GCD further decreased to 166.32 ± 22.31 and 120.76 ± 11.66, measured with LSCM and IC, respectively (p < 0.05); in Group 4, mean GCD did not change during the study period (p > 0.05). Treatment with PF tafluprost was associated with an increase in conjunctival GCD in glaucomatous eyes naïve for therapy. Further studies are mandatory to verify this finding because its validation may have important consequences in the medical management of glaucoma.


Synthesis of Sustainable Polyesters via Organocatalytic Ring-Opening Polymerization of O-carboxyanhydrides: Advances and Perspectives.
Sustainable polyesters can be furnished via ring-opening polymerization (ROP) of O-carboxyanhydrides (OCAs). Various catalysts, especially metal-based catalysts, are devised to achieve controlled ROP of OCAs. In the following mini review, the recent progress on the organocatalytic ROP of OCAs, including the usage of thiourea-based bifunctional single-molecule organocatalysts for eliminating epimerization in OCAs polymerization is summarized. Moreover, the future development of the organocatalytic ROP of OCAs for the synthesis of sustainable polyesters will be discussed.


Real-time PCR of CD146 mRNA in peripheral blood enables the relative quantification of circulating endothelial cells and is an indicator of angiogenesis.
Angiogenesis is a fundamental process in tumour growth and metastatic dissemination. Possible surrogate markers for tumour angiogenesis are the amounts of circulating endothelial cells (CEC) in peripheral blood and the plasma concentration of vascular endothelial growth factor (VEGF). We tested the suitability of real-time PCR for CD146, an endothelial cell-specific antigen, to quantify CEC numbers in comparison to a flow cytometry quantification. Real-time PCR of CD146 mRNA showed high sensitivity and linearity for the quantification of cultivated primary endothelial cells added in different amounts to blood samples. Circulating endothelial cell numbers were quantified in peripheral blood samples of breast cancer patients and healthy controls by four-colour flow cytometry analysis and CD146 real-time PCR, and VEGF plasma concentrations were measured by ELISA. The amounts of CEC detected with both methods correlated significantly and CEC numbers were significantly increased in newly diagnosed breast cancer patients compared to healthy controls. Vascular endothelial growth factor concentrations correlated significantly with CEC numbers, but there was no significant difference in VEGF levels between breast cancer patients and healthy controls indicating that VEGF plasma levels cannot be used as surrogate marker for tumour angiogenesis. Taken together, the quantification of CEC by CD146 real-time PCR showed equivalent results to the flow cytometry analysis. Thus, CD146 real-time PCR may be an easy and reliable approach to quantify CEC in peripheral blood samples and could facilitate the integration of CEC measurements in clinical studies exploring the efficacy of antiangiogenic therapies.


The effect of Camphor-Crataegus berry extract combination on blood pressure and mental functions in chronic hypotension--a randomized placebo controlled double blind design.
A number of studies have provided evidence for reduced cognitive performance due to chronically low blood pressure. The present studies explored whether these deficits can be reduced by pharmacological blood pressure elevation. Effects of the Camphor-Crataegus berry extract combination (Korodin(®)) were investigated in two studies with 40 and 48 hypotensive women based on a randomized, placebo controlled double blind design. The participants were presented with different tasks assessing performance in attention and cognition. Blood pressure was measured repeatedly during the experiment. The administration of the drug led to positive and differential effects on blood pressure and cognitive performance as compared to placebo. These effects were already visible within the time range of 2-5 min. A positive correlation between blood pressure increase and performance enhancement could be demonstrated for two of the four tasks. The results show that the application of Korodin(®) results in beneficial effects on resting blood pressure and cognitive performance. The positive association between the increase in blood pressure and cognitive enhancement suggests that blood pressure plays a causal role in the cognitive deficits in hypotension and underlines that they can be reduced through antihypotensive treatment.


Similar hematologic and nutritional outcomes after proximal gastrectomy with double-tract reconstruction in comparison to total gastrectomy for early upper gastric cancer.
Proximal gastrectomy offers theoretical benefits over total gastrectomy in terms of hematologic and nutritional outcomes. However, little evidence confirming these benefits has been reported. The aim of this study was to assess the hematologic and nutritional outcomes of proximal gastrectomy with double-tract reconstruction in comparison to those of total gastrectomy. We retrospectively analyzed data from 80 patients with stage I gastric cancer who underwent proximal gastrectomy with double-tract reconstruction (n = 38) or total gastrectomy (n = 42) from September 2014 to December 2015. We compared hematologic (including hemoglobin, ferritin, vitamin B12, etc.) and nutritional outcomes [including body mass index (BMI), serum total protein, albumin, total cholesterol, and total lymphocyte count] between the two groups. We found no significant differences in changes in hemoglobin (P = 0.250) or cumulative incidence of iron deficiency anemia (P = 0.971) during a median follow-up period of 24 months (range 18-30 months) after surgery. Cumulative incidence of vitamin B12 deficiency also did not differ significantly between the proximal and total gastrectomy groups (P = 0.087). BMI changes from baseline were not significantly different between the two groups (P = 0.591). Likewise, there were no statistically significant differences in nutritional outcomes. Proximal gastrectomy with double-tract reconstruction exhibited similar outcomes in terms of hematologic and nutritional features in comparison to total gastrectomy.


Computed tomography in the diagnosis of brain stem gliomas.
Twenty patients with brain stem gliomas were diagnosed by CT. The diagnosis was established on the basis of characteristic appearance, density pattern and mass effect. Differentiation from brain stem metastasis or angioma is frequently possible based on CT findings.


Rheumatoid arthritis of the temporomandibular joint: radiologic evaluation based on standard reference films.
A radiologic scoring system that uses tomography and panoramic radiography to evaluate severity of rheumatoid arthritis in the temporomandibular joint of adults is presented. The scoring system is based on six verbally described grades illustrated by standard reference films. The interobserver agreement was significantly higher for the grading with reference films than for that without reference films. Intraobserver performance was similar for grading with and without reference films. The grading system with reference films is recommended in epidemiologic studies of rheumatoid arthritis localized to the temporomandibular joint or other studies in which multiple observers are involved.


Management of postoperative nausea and vomiting in women scheduled for breast cancer surgery.
Breast cancer surgery performed under general anesthesia is associated with a high incidence of postoperative nausea and vomiting (PONV). A number of approaches are available for the management of PONV after breast cancer surgery. First, the risk factors related to patient characteristics, surgical procedure, anesthetic technique, and postoperative care can be reduced. More specifically, the use of propofol-based anesthesia can reduce the incidence of PONV. Secondly, a wide range of prophylactic antiemetics, including butyrophenones (droperidol), benzamides (metoclopramide), glucocorticoids (dexamethasone), clonidine, a small dose of propofol, and serotonin receptor (SR) antagonists (ondansetron, granisetron, tropisetron, dolasetron, ramosetron, and palonosetron), are available for preventing PONV. Thirdly, antiemetic therapy combined with granisetron and droperidol or dexamethasone, and a multimodal management strategy which includes a package consisting of dexamethasone, total intravenous anesthesia with propofol, and ondansetron are highly effective in preventing PONV. Unfortunately, the use of glucocorticoids and SR antagonists for preventing PONV is not permitted in Japan according to national health insurance guidelines. Fourth, electro-acupoint stimulation at the P6 point (Nei-Guwan) as a non-pharmacologic therapy is as effective as ondansetron for preventing PONV. Knowledge of the risk factors for PONV, antiemetics, and a non-pharmacologic approach are needed for the management of PONV in women undergoing breast cancer surgery.


Recent progress in development of monoclonal antibodies against human cytomegalovirus.
Human cytomegalovirus (HCMV) is a ubiquitous pathogen that can cause permanent childhood disabilities following in utero infection and life threatening diseases in immune-compromised individuals such as those post transplantation. Without an effective vaccine, small molecule antiviral drugs are routinely used in high-risk transplant recipients, but the effectiveness of which is limited by side effects and drug resistance. The potentials of antibody-based passive immune therapies alone or in combination with the small molecule antivirals to treat or prevent HCMV infection have been actively studied. In this review, we focus on the recent publications on identification and characterization of monoclonal antibodies that have the potential to be developed as anti-HCMV therapies. We review the progress in clinical evaluation of antibody-based therapies to prevent HCMV-associated diseases.


Early adversity and the development of explore-exploit tradeoffs.
Childhood adversity can have wide-ranging and long-lasting effects on later life. But what are the mechanisms that are responsible for these effects? This article brings together the cognitive science literature on explore-exploit tradeoffs, the empirical literature on early adversity, and the literature in evolutionary biology on 'life history' to explain how early experience influences later life. We propose one potential mechanism: early experiences influence 'hyperparameters' that determine the balance between exploration and exploitation. Adversity might accelerate a shift from exploration to exploitation, with broad and enduring effects on the adult brain and mind. These effects may be produced by life-history adaptations that use early experience to tailor development and learning to the likely future states of an organism and its environment.


Charting differentially methylated regions in cancer with Rocker-meth.
Differentially DNA methylated regions (DMRs) inform on the role of epigenetic changes in cancer. We present Rocker-meth, a new computational method exploiting a heterogeneous hidden Markov model to detect DMRs across multiple experimental platforms. Through an extensive comparative study, we first demonstrate Rocker-meth excellent performance on synthetic data. Its application to more than 6,000 methylation profiles across 14 tumor types provides a comprehensive catalog of tumor type-specific and shared DMRs, and agnostically identifies cancer-related partially methylated domains (PMD). In depth integrative analysis including orthogonal omics shows the enhanced ability of Rocker-meth in recapitulating known associations, further uncovering the pan-cancer relationship between DNA hypermethylation and transcription factor deregulation depending on the baseline chromatin state. Finally, we demonstrate the utility of the catalog for the study of colorectal cancer single-cell DNA-methylation data.


Nuchal translucency measurement: are qualitative and quantitative quality control processes related?
Two types of quality assurance processes for nuchal translucency (NT) measurement have been described: qualitative through review of images and quantitative comparison of operator's specific NT distribution to reference distributions. The aim of this study was to assess the results of these two approaches. Prospective evaluation of sonologists affiliated to the French Ultrasound College who first underwent qualitative evaluation based on the College Français d'Echographie Foetale (CFEF) score. During one year, those same sonologists measured the NT for Down syndrome screening purposes. The operator's specific NT distributions were compared to their CFEF score, their number of unsatisfactory images and their number of NT measurements per year. The study involved 1726 sonologists who performed 174 722 first-trimester examinations. Mean (SD) quantitative score was 23.4/32 (+/-7.4). The median [inter-quantile range] number of examinations per sonologist was 69 [37; 123]. The median [range] NT multiples of the mean (MoM) value was 0.81 [0.46; 1.22]. NT (MoM) absolute deviation from 1 MoM was significantly correlated with mean score obtained (R(2) = -0.17, p < 0.0001), number of unacceptable images (R(2) = 0.14, p < 0.0001) and number of ultrasound scans performed per year (R(2) = -0.19, p < 0.0001). Our results suggest that both processes are clearly related.


Carbon reduction strategies for regionally produced and consumed wine: From farm to fork.
I) BACKGROUND: Carbon footprint studies of locally produced and consumed wine are missing. II) PURPOSE(S): The objective of the present study was to identify management strategies and carbon reduction potentials for a sustainable wine production based on the carbon footprint and the water footprint of locally grown grapes and wine locally produced and consumed. III) METHODS: Two wineries (A and B) were investigated, both of which grow the same white (Riesling) and the same red grape (Pinot Noir/Spätburgunder) on the same rootstock in the Rhine river valley of Germany. The study was based on PAS 2050-1 (BSI) and comprised 99% primary data derived from historical farm records. System boundaries ranged from planting of the grapevines to eventual disposal of a typical 0.75 L glass bottle, which served as the functional unit (FU). IV) RESULTS: The product carbon footprint (PCF) was 1.91 ± 0.3 kg CO2eq/bottle (A) or 1.69 ± 0.3 (B) kg CO2eq/bottle of white wine and 1.86 ± 0.3 kg CO2eq/bottle of red wine for both wineries. These results were attributed to the consumer behaviour (22-30%), followed by the use and production of glass bottles (20-27%). Grapevine cultivation amounted to 0.3-0.4 kg CO2eq/bottle; grape processing caused ca. 0.05-0.06 kg CO2eq/bottle, packaging 0.5-0.6 kg CO2eq/bottle, distribution 0.2-0.4 kg CO2eq/bottle, while use and disposal of the glass bottles emitted 0.5-0.6 kg CO2eq/bottle. The plant protection chemicals caused only ca. 1.4% and organic fertilizer ca. 2.8% of the product carbon footprint (PCF). Red and white wine appeared commensurate in their PCF within 3-8% in both vineyards. The water footprint was ca. 5.7 ± 0.6 (A) and 2.1 ± 0.4 (B) L blue water/bottle for both red and white wine. V) DISCUSSION: The results are discussed with higher carbon footprint values for wine from overseas. We have identified the following reduction potentials such as the following management strategies: VI) RECOMMENDATIONS: a) reduction of fossil fuels for gas heating of the premises and for farm vehicles, b) the use of lightweight glass bottles and c) alternative means of transport for the consumer purchase at the winery when using a private vehicle.


Production of Coenzyme Q10 by microbes: an update.
Coenzyme Q10 (CoQ10) is the main CoQ species in human and is used extensively in food, cosmetic and medicine industries because of its antioxidant properties and its benefit in prophylactic medicine and therapy for a variety of diseases. Among various approaches to increase the production of CoQ10, microbial fermentation is the most effective. As knowledge of the biosynthetic enzymes and regulatory mechanisms modulating CoQ10 production increases, opportunities arise for metabolic engineering of CoQ10 in microbial hosts. In this review, we present various strategies used up to date to improve CoQ10 production and focus on metabolic engineering of CoQ10 overproduction in microbes. General strategies of metabolic engineering include providing sufficient precursors for CoQ10, increasing metabolic fluxes, and expanding storage capacity for CoQ10. Based on these strategies, CoQ10 production has been significantly improved in natural CoQ10 producers, as well as in heterologous hosts.


Optimization of carbon dioxide and nitrogen fixation by the blue-green alga Anabaena in freshwater blooms.
In the bloom-forming filamentous blue-green algae Anabaena, both carbon dioxide and nitrogen fixation share a dependence on light. During daylight, A. reduces direct competition between these processes for light-generated reductant by optimizing carbon fixation during late morning hours while optimizing nitrogen fixation during afternoon hours.Sequential optimization was examined from both biochemical and ecological perspectives. Biochemically, it is sound to optimize carbon prior to nitrogen fixation, due to the higher sensitivity of the former to afternoon increases in dissolved oxygen levels which commonly occur in blooms. It is also advantageous to first assure adequate supplies of fixed carbon prior to incorporating fixed nitrogen. Ecologically, the sequence represents optimal use of radiant energy. A. is able to shift energy flow from a highly inhibited to a less inhibited process, thereby maintaining a sink for photo-generated reductant. Both A. and a non-nitrogen fixing diatom community show similar carbon fixation efficiencies during morning and midday hours. During afternoon however, A. diverts significant portions of photo-reductant from carbon to nitrogen fixation. This allows A. to optimize carbon fixation while maintaining access to nitrogen during periods of ambient nitrogen shortage. Accordingly, A. blooms usually appear during summer months when both nitrogen starvation and photosynthetically-active radiation inputs are maximal.


Apoptosis of peripheral T cells in rodent cardiac allograft recipients induced by donor-specific transfusion with impaired inducible costimulator/B7 homologous protein allorecognition.
To investigate apoptosis of the CD8(+) T cells (Tc) subpopulation in rodent cardiac allograft recipients, which were treated by donor specific transfusion combined with blockade of Inducible costimulator (ICOS)/B7 homologous protein (B7h) costimulation. Donor hearts were heterotopically transplanted into the necks of recipient mice using Chen's technique. Postoperative graft survival was recorded. Both the percentage of CD3(+)CD8(+)ICOS(+) Tc in recipients' peripheral blood and the apoptosis of CD8(+) Tc in recipient draining lymph nodes were detected by flow cytometry analysis. In comparison with the allogeneic group, the survival of cardiac grafts was prolonged by combined treatment with 5 × 10(6) ICOS-Fc-targeted B cells on day 0 of transplantation and 10 mg/kg/d ICOS-Fc on days 0 to 6 (84.38 ± 29.14 days versus 7.00 ± 0.76 days, P < .01). The treatment group showed a stable CD8(+)Tc clone size in recipient peripheral blood (49.4% ± 3.11% versus 50.0% ± 2.46%, P > .05); however, the percentage of CD3(+)CD8(+)ICOS(+) Tc decreased significantly compared with the allogeneic group (7.5% ± 2.02% versus 14.0% ± 3.03%, P < .05). Compared with allogeneic group, apoptosis of the CD8(+) Tc subpopulation in recipient draining lymph nodes was up-regulated significantly at postoperative 7 days in the treatment group (19.53% ± 5.10% versus 8.70 ± 3.14%, P < .05). Apoptosis of CD8(+) Tc in recipient draining lymph nodes was enhanced by pretreatment with donor specific transfusion and impaired ICOS/B7h allorecognition, which may have been associated with the variation in the CD3(+)CD8(+)ICOS(+) Tc subpopulation in peripheral blood and at least partially contributed to unresponsiveness toward cardiac allograft.


MYB36 regulates the transition from proliferation to differentiation in the Arabidopsis root.
Stem cells are defined by their ability to self-renew and produce daughter cells that proliferate and mature. These maturing cells transition from a proliferative state to a terminal state through the process of differentiation. In the Arabidopsis thaliana root the transcription factors SCARECROW and SHORTROOT regulate specification of the bipotent stem cell that gives rise to cortical and endodermal progenitors. Subsequent progenitor proliferation and differentiation generate mature endodermis, marked by the Casparian strip, a cell-wall modification that prevents ion diffusion into and out of the vasculature. We identified a transcription factor, MYB DOMAIN PROTEIN 36 (MYB36), that regulates the transition from proliferation to differentiation in the endodermis. We show that SCARECROW directly activates MYB36 expression, and that MYB36 likely acts in a feed-forward loop to regulate essential Casparian strip formation genes. We show that myb36 mutants have delayed and defective barrier formation as well as extra divisions in the meristem. Our results demonstrate that MYB36 is a critical positive regulator of differentiation and negative regulator of cell proliferation.


Host-dependent variations in the seasonal prevalence and intensity of heterophyid encysted metacercariae (Digenea: Heterophyidea) in brackish water fish in Egypt.
The prevalence of heterophyid (Digenea: Heterophyidae) encysted metacercariae (EMC) in its second intermediate host, the fish Mugil spp. and Tilapia spp. was studied in a subtropical permanent Lake in northeastern Egypt. Seasonal changes in the occurrence of the EMC in different fish hosts were monitored in a longitudinal field survey lasting 12 months from June 2006 to May 2007. This study tested two hypotheses; (i) prevalence and intensity of heterophyid EMC fluctuate seasonally throughout the year and (ii) variation in the prevalence and intensity of heterophyid EMC is host-dependent. A total of 832 fish specimens comprising 5 species collected from Manzala Lake, northeastern Egypt were examined by artificial gastric juice digestion for EMC. All five species of brackish water fish examined were found to harbor the EMC of the family Heterophyidae in their muscles. The overall infection prevalence of EMC over 12 months was 23.2%. The adult flukes recovered from puppies experimentally infected with morphologically different metacercariae from different fish species were compatible with six species belong to five genera of Heterophyidae, namely, Heterophyes heterophyes, Heterophyes aequalis, Pygidiopsis genata, Phagicola sp., Haplorchis sp. and Stictodora sp. EMC of H. heterophyes were most abundant, detected in 56% of the total fish examined. P. genata was ranked second, followed by Phagicola sp., H. aequalis, Haplorchis sp., and Stictodora sp., respectively. Seasonal differences in infection were observed for all heterophyid species studied in all fish species examined. Heterophyid infections reached peak prevalences during the summer season 38.2% followed by spring 26.6% and autumn 19.3% seasons, whereas the lowest prevalence was recorded in the winter 8.7%. Intensity of heterophyid EMC followed the same seasonal pattern, being high during summer months and low in winter months. All fish species were infected with all the heterophyid digeneans, but with different prevalence. Possible reasons for these findings are discussed with reference to host, climatic and biotic factors.


[Comparison study on uterine and umbilical artery blood flow during pregnancy at high altitude and at low altitude].
To evaluate the effect of high altitude on uterine and umbilical artery blood flow dynamics during normal pregnancy. Uterine artery blood flow parameters of the pregnant (34) and nonpregnant (37) subjects and umbilical artery blood flow parameters of 119 subjects living at high altitude or at low altitude were measured with color Doppler flow imaging system. Uterine artery diameter, blood flow volume increased during pregnancy at both altitude, and uterine artery blood flow volume and diameter were smaller at high altitude than at low altitude [(0.35 +/- 0.04) cm vs (0.45 +/- 0.04) cm, (280 +/- 48) ml/min vs (425 +/- 55) ml/min, P < 0.01]. Umbilical artery blood flow velocity systolic to diastolic (S/D) value, resistant index of different pregnant period were greater at high altitude than at low altitude (P < 0.01). High altitude has effect on placental and infant blood flow that causes the decrease of placental blood infusion and the increase of uterine and umbilical artery flow velocity S/D and reactive index.


Optometric use of a teleophthalmology service in rural Western Australia: comparison of two prospective audits.
Lions Outback Vision provides a telehealth service ('the telehealth service') to rural and remote communities in Western Australia aiming to deliver timely ophthalmic care to this underserved population. A number of barriers to its use were identified by an initial prospective audit. A multifaceted intervention was designed to increase the use of the telehealth service by optometrists. Optometrists referred patients from rural and remote Western Australia to the telehealth service. Two five-month prospective audits of the telehealth service were compared. The first, in 2012, was prior to the implementation of the intervention. The second, in 2014, was during the period of the intervention, which included logistical support, remuneration to optometrists, a more user-friendly referral pathway and awareness raising. The outcome measures were the number of consultations conducted during the two audit periods and other quantitative changes to the telehealth service. After implementation of the intervention, use of the telehealth service increased 3.5 fold. A greater percentage of referrals were for non-urgent conditions (145 [69 per cent] versus 16 [32 per cent], p < 0.001) and less consultations recommended follow up with an ophthalmologist in clinic (42 [20 per cent] versus 17 [28 per cent], p = 0.04). Imaging studies were frequently used to supplement information provided by the referrer to the specialist during both audit periods. Optometrists used the telehealth service more frequently after the implementation of an intervention that addressed the barriers to its use. This has a number of potential benefits to rural and remote ocular health service provision in Australia.


Bowel Functional Outcomes After Long-Course or Short-Course Radiation for Advanced Rectal Cancers: A Propensity-Matched Analysis.
Despite short-course radiation and chemotherapy gaining popularity because of similar or better oncological outcomes, functional outcomes relative to long-course radiation have not been evaluated. To compare bowel function outcomes after long-course or short-course radiation and delayed operation for advanced rectal cancers. Propensity-matched analysis. This study was conducted at a single tertiary cancer center. Patients were operated on between 2014 and 2020. The study included patients with locally advanced, nonmetastatic, mid, and low rectal cancers who underwent low anterior resection with stapled anastomosis and diverting ostomy. Extended or beyond total mesorectal excisions and lateral node dissections were excluded. Long-course radiation delivered as a radiation dose of 50 Gy in 25 fractions or short-course radiation (5 Gy in 5 fractions) and delayed surgery after 4 to 6 weeks with or without chemotherapy. One-time assessment of low anterior resections syndrome and Wexner incontinence scores at least 6 months after stoma reversal. After matching 124 patients in the 1:2 ratio between short- and long-course radiations, 93 patients were included for analysis. Any low anterior resection syndrome was found in 90.3% of short-course patients compared to 54.8% after long-course radiation (p < 0.001). Major incontinence was detected in 6.5% after short-course radiation as opposed to 8.1% of patients after long-course radiation (p = 0.781). On multivariate logistic regression, short-course radiation predicted the development of any low anterior resection syndrome with an OR of 4.4. Selection and misclassification biases from retrospective recruitment. For patients with locally advanced, nonmetastatic, mid, and low rectal cancers who underwent preoperative radiation followed by stapled low anterior resection, short-course radiation had higher probability of developing low anterior resection syndrome than long-course radiation. See Video Abstract at http://links.lww.com/DCR/C37. ANTECEDENTES:A pesar de que la radiación de corta duración y la quimioterapia están ganando popularidad debido a resultados oncológicos similares o mejores, los resultados funcionales en relación con la radiación de larga duración no han sido evaluado.OBJETIVO:Comparar resultados de la función intestinal después de la radiación de ciclo largo o corto y cirugía diferida para los en cáncer de recto avanzado.DISEÑO:Análisis emparejado de propensión.ENTORNO CLINICO:Centro único de cáncer terciario. Pacientes operados entre 2014 y 2020.PACIENTES:Cánceres de recto medio y bajo localmente avanzados, no metastásicos, que se sometieron a resección anterior baja con anastomosis grapada y ostomía de derivación. Se excluyeron las escisiones total de mesorecto extendidas o más allá del plano y las disecciones de los ganglios laterales.INTERVENCIONES:Radiación de ciclo largo administrada como 50 Gy en 25 fracciones o radiación de ciclo corto (5 Gy en 5 fracciones) y cirugía diferida después de 4 a 6 semanas con o sin quimioterapia.PRINCIPALES MEDIDAS DE RESULTADO:Evaluación única del síndrome de reseccion anterior baja y escala de Wexner de incontinencia al menos seis meses después de la restitución del tránsito intestinal.RESULTADOS:Después de emparejar 124 pacientes en la proporción 1:2 entre radiación de ciclo corto y largo, se incluyeron 93 pacientes para el análisis. Se encontró cualquier síndrome de resección anterior baja en el 90,3% de los pacientes de ciclo corto en comparación con el 54,8% después de la radiación de ciclo largo (p < 0,001). Se detectó incontinencia grave en el 6,5% después de un tratamiento de corta duración frente al 8,1% de los pacientes que recibieron un tratamiento de radiación de larga duración (p = 0,781). En la regresión logística multivariable, la radiación de corta duración predijo el desarrollo de cualquier síndrome de resección anterior baja con una probabilidad de 4,4.LIMITACIONES:Sesgos de selección y clasificación errónea de reclutamiento retrospectivo.CONCLUSIONES:Para los cánceres de recto medio e inferior localmente avanzados, no metastásicos, que se sometieron a radiación preoperatoria seguida de resección anterior baja con grapas, curso corto tuvo una mayor probabilidad de desarrollar síndrome de resección anterior baja en comparación con radiación de curso largo. Consulte Video Resumen en http://links.lww.com/DCR/C37. (Traducción- Dr. Francisco M. Abarca-Rendon).


Does prolonged thromboprophylaxis improve outcome in patients undergoing surgery?
Patients undergoing major abdominal surgery, particularly for malignancy, are at increased risk of venous thromboembolism. Haemostatic markers of coagulation are raised for several weeks after surgery. A higher dose of low-molecular-weight heparin than normally used for thromboprophylaxis is effective in preventing post-surgical VTE in patients with cancer with no compromise on bleeding. Four weeks' of thromboprophylaxis with the LMWH dalteparin is significantly more effective than standard (1 week) thromboprophylaxis in preventing proximal DVT. A meta-analysis of studies comparing 4 weeks' with 1 week of thromboprophylaxis showed that prolonged thromboprophylaxis with LMWH following major abdominal surgery for malignancy significantly reduces the risk of late occurring DVT.


Duplication of the parotid duct: a previously unreported anomaly.
A hitherto unreported duplication of the parotid duct in a 63-year-old man is reported. The ducts were found in the right cheek during cadaver dissection. The surrounding connective tissue of the ducts was removed and a photograph was taken. These two parotid ducts were then removed and fixed in a 10% formalin solution, embedded in paraffin blocks and the sections stained with hematoxylin eosin. The histologic findings showed that both had the normal ductal columnar epithelium. There was only one parotid duct in the left cheek.


Walking speed, unilateral leg loading, and step symmetry in young adults.
The purpose of this study was to examine the effects of gait speed and unilateral lower limb loading on step time and step length symmetry in healthy adults. Spatiotemporal gait data were collected from 22 healthy subjects (11 men, 11 women), using the GaitRite walkway, under four randomly sequenced test conditions: self-selected speed (SS), fast speed (F), self-selected speed with the right leg loaded (LSS), and the fastest attainable speed with the right leg loaded (LF). The symmetry index, calculated with the formula [((R-L)/0.5 × (R+L)) × 100], was used to quantify step time and step length symmetry. It was found that over-ground gait speed had no significant effects on the symmetry of step time or step length. Unilateral lower limb loading significantly increased step time asymmetry, with longer step time for the loaded leg. Step symmetry was further compromised and became more asymmetrical when, in addition to unilateral leg loading, subjects maximized their gait speed. This effect of fast speed with unilateral leg loading was particularly prominent in relation to step length, with its shortening in the unloaded leg and lengthening in the loaded leg. These observations in healthy subjects may serve as a reference for the assessment of gait symmetry in patients with unilateral lower limb pathologies.


Intermolecular Interactions of Myosin Subfragment 1 Induced by the N-Terminal Extension of Essential Light Chain 1.
We applied dynamic light scattering (DLS) to compare aggregation properties of two isoforms of myosin subfragment 1 (S1) containing different "essential" (or "alkali") light chains, A1 or A2, which differ by the presence of an N-terminal extension in A1. Upon mild heating (up to 40°C), which was not accompanied by thermal denaturation of the protein, we observed a significant growth in the hydrodynamic radius of the particles for S1(A1), from ~18 to ~600-700 nm, whereas the radius of S1(A2) remained unchanged and equal to ~18 nm. Similar difference between S1(A1) and S1(A2) was observed in the presence of ADP. In contrast, no differences were observed by DLS between these two S1 isoforms in their complexes S1-ADP-BeFx and S1-ADP-AlF4- which mimic the S1 ATPase intermediate states S1*-ATP and S1**-ADP-Pi. We propose that during the ATPase cycle the A1 N-terminal extension can interact with the motor domain of the same S1 molecule, and this can explain why S1(A1) and S1(A2) in S1-ADP-BeFx and S1-ADP-AlF4- complexes do not differ in their aggregation properties. In the absence of nucleotides (or in the presence of ADP), the A1 N-terminal extension can interact with actin, thus forming an additional actin-binding site on the myosin head. However, in the absence of actin, this extension seems to be unable to undergo intramolecular interaction, but it probably can interact with the motor domain of another S1 molecule. These intermolecular interactions of the A1 N-terminus can explain unusual aggregation properties of S1(A1).


Consistency and variability in human performance during simulate infant CPR: a reliability study.
Positive outcomes from infant cardiac arrest depend on the effective delivery of resuscitation techniques, including good quality infant cardiopulmonary resuscitation (iCPR) However, it has been established that iCPR skills decay within weeks or months after training. It is not known if the change in performance should be considered true change or inconsistent performance. The aim of this study was to investigate consistency and variability in human performance during iCPR. An experimental, prospective, observational study conducted within a university setting with 27 healthcare students (mean (SD) age 32.6 (11.6) years, 74.1% female). On completion of paediatric basic life support (BLS) training, participants performed three trials of 2-min iCPR on a modified infant manikin on two occasions (immediately after training and after 1 week), where performance data were captured. Main outcome measures were within-day and between-day repeated measures reliability estimates, determined using Intraclass Correlation Coefficients (ICCs), Standard Error of Measurement (SEM) and Minimal Detectable Change (MDC95%) for chest compression rate, chest compression depth, residual leaning and duty cycle along with the conversion of these into quality indices according to international guidelines. A high degree of reliability was found for within-day and between-day for each variable with good to excellent ICCs and narrow confidence intervals. SEM values were low, demonstrating excellent consistency in repeated performance. Within-day MDC values were low for chest compression depth and chest compression rate (6 and 9%) and higher for duty cycle (15%) and residual leaning (22%). Between-day MDC values were low for chest compression depth and chest compression rate (3 and 7%) and higher for duty cycle (21%) and residual leaning (22%). Reliability reduced when metrics were transformed in quality indices. iCPR skills are highly repeatable and consistent, demonstrating that changes in performance after training can be considered skill decay. However, when the metrics are transformed in quality indices, large changes are required to be confident of real change.


Inductive line tunneling FET using epitaxial tunnel layer with Ge-source and charge enhancement insulation.
In this paper, we propose an inductive line tunneling FET using Epitaxial Tunnel Layer with Ge-Source and Charge Enhancement Insulation (CEI ETL GS-iTFET). The CEI ETL GS-iTFET allows full overlap between the gate and source regions, thereby enhancing the line tunneling. In addition, a germanium layer is introduced on the source side to form a heterojunction, effectively improving the device's conduction current. An ETL is incorporated to combat point tunneling leakage, resulting in a steeper subthreshold swing. Furthermore, a CEI consisting of Si3N4 is introduced between the germanium source and the Schottky metal, which effectively reduces carrier losses in the inversion layer and improves the overall device performance. This study presents a calibration-based approach to simulations, taking into account practical process considerations. Simulation results show that at VD = 0.2 V, the CEI ETL GS-iTFET achieves an average subthreshold swing (SSavg) of 30.5 mV/dec, an Ion of 3.12 × 10-5 A/μm and an Ion/Ioff ratio of 1.81 × 1010. These results demonstrate a significantly low subthreshold swing and a high current ratio of about 1010. In addition, the proposed device eliminates the need for multiple implantation processes, resulting in significant manufacturing cost reductions. As a result, the CEI ETL GS-iTFET shows remarkable potential in future low-power device competition.


3D-MRI of the ankle with optimized 3D-SPACE.
To assess the use of 3-dimensional (3D) MR imaging of the ankle with the 3D-turbo-spin-echo-sequence 3D-"Sampling Perfection with Application optimized Contrast using different flip angle Evolutions" (SPACE), as compared with 2-dimensional-turbo-spin-echo-sequence. After internal review board's approval and informed consent, 15 healthy volunteers and 45 consecutive patients were examined at 3 T with isotropic fat-saturated moderately T2-weighted 3D-SPACE (voxel size: 0.6(3) mm(3)/acquisition time: 6:43 minutes) featuring radial k-space reordering for optimized contrast. Signal- and contrast-to-noise ratios (SNR; CNR, respectively) were calculated with the subtraction method. Using free 3D reconstructions, 2 radiologists independently assessed depiction of cartilage, ligaments, and tendons, as well as detection and grading of abnormalities of these structures (5-point Likert scale) compared with conventional 2-dimensional-TSE-sequences (voxel size: 0.4 × 0.4 × 3 mm(3)/total acquisition time: 11 minutes). Statistical analysis was performed with Wilcoxon signed rank tests, 95% and 99% confidence intervals and weighted κ coefficients. SNR and CNR of fluid/cartilage were significantly higher for 3D-SPACE (P < 0.05). The isotropic voxel size facilitated improved depiction of the medial and lateral ankle ligaments with significant differences for the calcaneofibular ligament and the anteromedial ligament complex (P < 0.05). In the patient cohort, cartilage and spring ligaments were also significantly better depicted (P < 0.05). However, there were no significant differences in the number or in the diagnostic confidence of detected cartilage, ligament, or tendon abnormalities. Interreader correlation was good (κ = 0.69-0.71) for both sequences. The correlation between the 2 sequences was excellent (κ = 0.84-0.85). 3D-SPACE allows 3D acquisition and assessment of the ankle and facilitates depiction of the complex ankle anatomy at sufficient SNR and CNR.


Use of molecular markers to determine postremission treatment in acute myeloid leukemia with normal cytogenetics.
Most patients with acute myeloid leukemia can be induced into complete remission, but postremission treatment is required for cure. The choice of postremission therapy in a majority of nonelderly patients, between intensive chemotherapy and allogeneic hematopoietic cell transplantation, is largely determined by the results of conventional cytogenetic analysis. In 45% of patients with a normal karyotype, the presence or absence of specific molecular mutations should be used to determine the prognosis and postremission treatment. In addition, the identification of mutations may indicate a role for targeted intervention, including following transplantation.


Thoracoscopic rib resection using a Gigli saw.
When a conventional approach is used to perform a rib resection, a skin incision longer than the rib to be resected must be made. As a result, a conventional rib resection leaves a rather large and esthetically unfavorable scar. After considering pain management, esthetics, and quality of life, we devised a new technique for thoracoscopic rib resection that uses a Gigli saw. This new technique was performed on an overweight woman with a solitary metastatic bone tumor of the right eighth rib, whose case is described herein. The patient's postoperative course was satisfactory. Since this technique does not require a long skin incision, pain management and aesthetic results are improved compared with conventional techniques.


[Birth readiness of the uterine cervix. II. Cervix readiness score and its problems because of the variability of individual criteria].
Cervical ripeness was scored in nulliparous and parous women not in labor at term according to Bishop's pelvic score. The frequency distributions of the scores for the single criteria as well as of the total score reveal the problems of all those scoring systems caused by the grouping process as sequelae of the choice of width of the classes as well as of their limits. E.g. for cervical dilatation in none case 2 or 3 points had been reached and similar findings had to be stated concerning station of the presenting part. An other point of discussion erases from the results of the analysis for linear correlation of the single criteria between each other and between the single criteria and the total score. The total score is mostly influenced by the consistency (r = 0,81 in nulliparous and parous women) and the effacement (r = 0,80 and r = 0,81) of the cervix, whereas for dilatation and station lower correlation coefficients were found. In contrast, when labor had started spontaneously, even if the status of cervix was not advanced, a significant change in the correlative influence of the total score by the single criteria could be stated with high correlation coefficients for dilatation and station and lower one's for consistency and effacement.


External auditory exostoses and early Neolithic aquatic resource procurement in Cyprus: Results from Cypro-PPNB Kissonerga-Mylouthkia in regional context.
This research is designed to evaluate the occurrence of external auditory exostoses (EAEs) in skeletal remains from the oldest known water wells in the world (Kissonerga-Mylouthkia, Cyprus, 8,200-7,200 BCE). Six individuals (MNI = 6), five fragmentary temporalia, two preserved auditory canals. Macroscopic and microscopic (up to x30) observation, with illumination; presence, type, side, severity, occlusion, number, and position of bony growths recorded. Bony growths within two auditory canals were discovered. Differential diagnosis includes osteomata and external auditory exostoses, with the latter consistent with the bony growths (Grade 1 EAEs, two adult males, one with single, another with two EAEs). The emergence of the Neolithic in Southwest Asia is thought to involve increases in dietary breadth among foraging societies (Broad-Spectrum Revolution). EAEs likely indicate maritime activity in this context, given the lack of freshwater bodies, and zooarchaeological evidence points to dietary and other uses of maritime organisms. This EAE evidence is the oldest known in maritime contexts in Eastern Mediterranean and the Middle East, and first in Cyprus. It contributes towards understanding the initial colonization events by Neolithic farming communities in the 9th millennium BC, and the emergence of broad-spectrum economies at the dawn of the Neolithic in Southwest Asia, crucial for re-considerations of paradigms on the transition to the Neolithic way of life in the Near East. Only a few skeletal remains from these prehistoric contexts were available for observation. Further intensive review of Cypriot skeletal collections for EAEs is advised.