Repair of soft tissue and extensor tendon defects on the dorsum of the hand by transfer of dorsal foot flap and extensor digitorum brevis tendon in a 3-year-old child: A case report.
Repair of soft tissue defects on the dorsum of the hand with accompanying tendon defects is a challenging problem in clinical practice. Here, we describe the case of a 3-year-old boy with a 1-week old soft tissue injury with infection due to a soft tissue defect on the dorsum of his right hand, and further describe its treatment. A diagnosis of a soft tissue defect of the dorsum with extensor tendon defects in the fore, middle, ring, and little fingers of the right hand was made. The defects were repaired using a dorsal foot flap combined with the extensor digitorum brevis tendon, under spinal anesthesia, and a small dose of the sedative phenobarbital (Lumina) was administered via pump injection after the surgery. The patient was followed-up for 6 months. The shape of the dorsal hand flap recovered satisfactorily and the skin color was almost normal. Protective sensation was restored and the tendon graft functioned well in vivo. Satisfactory outcomes were achieved in the flexion and extension of each finger. This case study provides evidence that for soft tissue defects on the dorsum of the hand with tendon defects, 1-stage transfer of a dorsal foot flap with the extensor digitorum brevis tendon can be effective for recovery of appearance and extensor function. In case of infant patients, postoperative use of low-dose sedation can effectively reduce the risk of vascular crisis, thus promoting survival of the flap graft, and ensuring the success of the operation.


Afferent mechanisms for the reflex response to imposed ankle movement in chronic spinal cord injury.
We have reported earlier that externally imposed ankle movements trigger ankle and hip flexion reflexes in individuals with spinal cord injury (SCI). In order to examine the afferent mechanisms underlying these movement-triggered reflexes, controlled ankle movements were imposed in 17 SCI subjects. In 13 of these subjects, reflex torques were recorded at the hip, knee and ankle in response to 5 ankle movement ranges, and 4 movement speeds. Subjects were tested using both ankle plantarflexion and dorsiflexion movements. The principal outcome measure, peak hip flexion torque of the induced reflexes, was used for comparing the effects of movement range and speed on the reflex response. We found that movement-triggered reflexes were sensitive to the angular range of ankle deflection, but insensitive to the velocity of the movement. Movement amplitudes sufficient to trigger hip and ankle flexion were routinely associated with increases in ankle passive force, suggesting that force-sensitive receptors participated in the reflex response. However, increases in angular range also corresponded to increases in muscle length, making it difficult to distinguish whether the response was triggered by a load-sensitive receptor (e.g., Golgi tendon organ or muscle free nerve ending) or a position-sensitive receptor responsive to absolute ankle angle (e.g., muscle spindle secondary afferent). The absence of velocity dependence of the reflex suggested that spindle Ia afferents were not major contributors. These results suggest movement-triggered reflexes originate in muscle receptors that are sensitive to either absolute muscle length, to muscle force or to both. Although receptors that are sensitive to absolute muscle length cannot be excluded with certainty, the finding that reflex responses require that ankle movements elicit an increase in passive force argues for a prominent role of nonspindle mechanoreceptors, such as group III/IV muscle afferents. These afferents are activated preferentially as muscles are stretched to near maximum length, and they appear to have potent reflex effects in spinal cord injury.


Construction of the miRNA-mRNA regulatory network and analysis of hub genes in oral squamous cell carcinoma.
Oral squamous cell carcinoma (OSCC) severely affects the quality of life and the 5-year survival rate is low. Exploring the potential miRNA-mRNA regulatory network and analyzing hub genes and clinical data can provide a theoretical basis for further elucidating the pathogenesis of OSCC. The miRNA expression datasets of GSE113956 and GSE124566 and mRNA expression datasets of GSE31056, GSE37991 and GSE13601 were obtained from the Gene Expression Omnibus databases. The differentially expressed miRNAs (DEMs) and mRNAs (DEGs) were screened using GEO2R. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed by DAVID database. The PPI network was established through STRING database and the hub genes were preliminarily screened out by Cytoscape software. After identifying the hub genes in the TCGA database, we predicted the potential DEM transcription factors, constructed a miRNA-mRNA regulatory network, and analyzed the relationship between the hub genes and clinical data. A total of 28 DEMs and 764 DEGs were screened out, which were composed of 285 up-regulated genes and 479 down-regulated genes. Enrichment analysis showed that up-regulation of DEGs were mainly enriched in extracellular matrix organization and cancer-related pathway, while down-regulation of DEGs were mainly enriched in muscular system process and adrenaline signal transduction. After preliminary screening by PPI network and identification in TCGA, the up-regulated FN1, COL1A1, COL1A2, AURKA, CCNB1, CCNA2, SPP1, CDC6, and down-regulated ACTN2, TTN, IGF1, CAV3, MYL2, DMD, LDB3, CSRP3, ACTA1, PPARG were identified as hub genes. The miRNA-mRNA regulation network showed that hsa-miR-513b was the DEM with the most regulation, and COL1A1 was the DEG with the most regulation. In addition, CDC6, AURKA, CCNB1 and CCNA2 were related to overall survival and tumor differentiation. The regulatory relationship of hsa-miR-513b/ CDC6, CCNB1, CCNA2 and the regulatory relationship of hsa-miR-342-5p /AURKA were not only verified in the miRNA-mRNA regulatory network but also related to overall survival and tumor differentiation. These results indicated that they participated in the cellular regulatory process, and provided a molecular mechanism model for the study of pathogenesis.


Tanning bed and nail lamp use and the risk of cutaneous malignancy: a review of the literature.
Malignant melanoma (MM) and non-melanoma skin cancer (NMSC) are increasingly common and both can be fatal. In 2009 the World Health Organization (WHO) classified the whole ultraviolet spectrum and tanning beds as carcinogenic to humans, placing them in the same category as asbestos and tobacco. Despite this, the trend for indoor tanning continues. A growing body of evidence has now associated indoor tanning with an increased risk of MM and NMSC. As a result, there has been an upsurge in regulations in the tanning industry ranging from age restrictions to complete bans on commercial tanning. This article examines the evidence and strengthens the case for a complete ban of a recognised modifiable risk factor for cutaneous malignancy.


Real-time quantitative PCR for the detection of Streptococcus pneumoniae in the middle ear fluid of children with acute otitis media.
PCR based on the amplification of pneumolysin gene fragments has previously been applied to demonstrate Streptococcus pneumoniae in clinical specimens. Here, a real-time PCR method for the detection and quantification of pneumococci by amplifying a 206-bp fragment of the pneumolysin-encoding gene is described. The amplified fragments were detected simultaneously using fluorescent-labeled sequence-specific hybridization probes. The applicability of the assay to clinical samples was evaluated by studying 50 middle ear fluid (MEF) specimens from children with acute otitis media. Twenty-six of the MEF samples were positive by real-time PCR and the numbers of genome equivalents detected varied from 90 to 88,000/microl in 17 culture-positive samples and from 1 to 1,200/microl in 9 culture-negative samples. The results were compared to culture findings and to results obtained by using agarose gel electrophoresis or Europium-labeled hybridization probes for the detection of amplification products of conventional PCR. The sensitivity and specificity of the real-time PCR assay developed in the present study compared to culture were 100 and 73%, and to conventional PCR with agarose gel and/or TRF detection 93 and 96%, respectively. The real-time PCR assay was found to be rapid, easy to use, and sensitive in detecting and quantifying pneumococci.


Development of retrospective quantitative and qualitative job-exposure matrices for exposures at a beryllium processing facility.
To construct a job-exposure matrix (JEM) for an Ohio beryllium processing facility between 1953 and 2006 and to evaluate temporal changes in airborne beryllium exposures. Quantitative area- and breathing-zone-based exposure measurements of airborne beryllium were made between 1953 and 2006 and used by plant personnel to estimate daily weighted average (DWA) exposure concentrations for sampled departments and operations. These DWA measurements were used to create a JEM with 18 exposure metrics, which was linked to the plant cohort consisting of 18,568 unique job, department and year combinations. The exposure metrics ranged from quantitative metrics (annual arithmetic/geometric average DWA exposures, maximum DWA and peak exposures) to descriptive qualitative metrics (chemical beryllium species and physical form) to qualitative assignment of exposure to other risk factors (yes/no). Twelve collapsed job titles with long-term consistent industrial hygiene samples were evaluated using regression analysis for time trends in DWA estimates. Annual arithmetic mean DWA estimates (overall plant-wide exposures including administration, non-production, and production estimates) for the data by decade ranged from a high of 1.39 μg/m(3) in the 1950s to a low of 0.33 μg/m(3) in the 2000s. Of the 12 jobs evaluated for temporal trend, the average arithmetic DWA mean was 2.46 μg/m(3) and the average geometric mean DWA was 1.53 μg/m(3). After the DWA calculations were log-transformed, 11 of the 12 had a statistically significant (p < 0.05) decrease in reported exposure over time. The constructed JEM successfully differentiated beryllium exposures across jobs and over time. This is the only quantitative JEM containing exposure estimates (average and peak) for the entire plant history.


Chemical and Biochemical Characterization of Essential Oils and Their Corresponding Hydrolats from Six Species of the Lamiaceae Family.
Many plants belonging to the Lamiaceae family are rich in essential oils (EOs) which are intensively used for aromatherapy, food and beverage flavoring, alternative medicine, cosmetics, and perfumery. Aerial parts of Thymus vulgaris L., Thymus pannonicus All., Lavandula angustifolia L., Lavandula x intermedia, Origanum vulgare L., and Origanum vulgare var. aureum L. were subjected to hydrodistillation, and both resulting fractions were analyzed. The purpose of this study was to determine the chemical composition, antioxidant activity, and total phenolic content of six essential oils and their corresponding hydrolats (HDs) through GC-MS and spectrophotometric analyses. Overall, 161 compounds were identified, some found exclusively in essential oils and others in hydrolats, making them individual products with specific end purposes. The total phenolic content was the highest for the Thymus vulgaris L. EOs (3022 ± mg GAE L-1), because of its high phenolic oxygenated monoterpenes content (thymol and carvacrol) and the smallest for the Lavandula angustifolia L. EOs (258.31 ± 44.29 mg GAE L-1), while hydrolats varied from 183.85 ± 0.22 mg GAE L-1 for Thymus vulgaris L. HD and 7.73 mg GAE L-1 for Thymus pannonicus All. HD. Significant antioxidant effects determined through DPPH• and ABTS•+ assays were also observed in samples with higher hydrophilic compounds. The highest antioxidant activity was determined for Thymus vulgaris L. EO and its corresponding HD. Although EOs are the principal traded economic product, HDs represent a valuable by-product that could still present intense antiseptic activities, similar to their corresponding EOs (thyme and oregano), or have multiple aromatherapy, cosmetics, and household applications (lavender and lavandin).


Minodronate suppresses prostaglandin F2alpha-induced vascular endothelial growth factor synthesis in osteoblasts.
In our previous study, we showed that prostaglandin F2alpha (PGF2alpha) stimulates vascular endothelial growth factor (VEGF) synthesis via activation of p44/p42 mitogen-activated protein (MAP) kinase via protein kinase C (PKC) in osteoblast-like MC3T3-E1 cells. In addition, we demonstrated that incadronate amplified, and tiludronate suppressed PGF2alpha-induced VEGF synthesis among bisphosphonates, while alendronate or etidronate had no effect. In the present study, we investigated the effects of minodronate, a newly developed bisphosphonate, on PGF (2alpha)-induced VEGF synthesis in MC3T3-E1 cells. Minodronate significantly reduced VEGF synthesis induced by PGF2alpha dose-dependently at levels between 3 and 100 microM. PGF2alpha-stimulated phosphorylation of Raf-1, MEK1/2 and p44/p42 MAP kinase were suppressed by minodronate. 12-O-tetradecanoylphorbol-13-acetate (TPA), a direct activator VEGF synthesis induced by PKC, was inhibited by minodronate. Minodronate inhibited Raf-1, MEK1/2 and p44/p42 MAP kinase phosphorylation induced by TPA. Mevalonate failed to affect the suppressive effect of minodronate on PGF2alpha-induced VEGF synthesis. Taken together, these results indicate that minodronate suppresses PGF2alpha-stimulated VEGF synthesis at the point between PKC and Raf-1 in osteoblasts.


Synthesis of monocarbenepalladium(0) complexes and their catalytic behavior in cross-coupling reactions of aryldiazonium salts.
The first monocarbenepalladium(0) complexes with benzoquinone and naphthoquinone as additional ligands have been prepared. As demonstrated by NMR spectroscopy and X-ray analysis, the complexes show a unique coordination mode giving quinone-bridged dimers. The monocarbenepalladium(0) complexes allow efficient cross-coupling reactions of aryldiazonium salts with olefins (Heck reaction) and arylboronic acids (Suzuki reaction).


[Psychiatric morbidity in connection with surgical treatment of epilepsy. A short-term follow-up of patients with amygdalohippocampectomy].
The aim of the study was to examine the occurrence of psychiatric disorders in epilepsy patients who had received surgical treatment, especially amygdalohippocampectomy (AHE), for the relief of medically intractable seizures. Forty-seven subjects, treated during the period 1987-1991 in the Danish epilepsy surgery programme (EPIKIR), entered a retrospective interview study. Of these, 37 had undergone AHE. Preoperative psychiatric morbidity was assessed through interview and available case notes, including a routine psychiatric interview. Postoperative psychiatric morbidity was assessed by the use of the Present State Examination. A total of six subjects (five AHE subjects) developed depressive disorders of various duration and severity after operation. In three subjects this occurred "de novo". No paranoid-hallucinatory psychoses developed within the follow-up period (a minimum of one year), and the presence of psychiatric disorders could not be associated with either lateralization of cerebral dominance of histopathological findings. Thus, depression appears to be the most frequent psychiatric problem following epilepsy surgery. Although the present study mainly deals with AHE, this finding is in accordance with the results of recent findings concerning anterior temporal lobe resection.


Pulmonary function at peak exercise in patients with chronic heart failure.
Various respiratory abnormalities are associated with chronic heart failure (CHF). However, changes in inspiratory capacity (IC) and breathing pattern from rest to exercise in patients with CHF have not been thoroughly investigated in these patients. Seventy seven (66 male/11 female) patients with clinical stable CHF (age: 52+/-11 years) were studied. All the patients underwent pulmonary function tests, including measurements of IC and maximal inspiratory pressure (Pimax) at rest and then a maximal cardiopulmonary exercise testing (CPET) on a treadmill. During the CPET, IC was measured every 2 min. Pimax was measured again after the end of CPET. Percent predicted forced expiratory volume in 1 s (FEV1) was 91+/-12, %predicted forced vital capacity (FVC) was 92+/-13, %FEV1/FVC was 81+/-4, and %predicted IC was 85+/-18. Peak exercise IC was lower than resting (2.4+/-0.6 vs. 2.6+/-0.6 l, p<0.001). Analysis of variance between Weber's groups revealed statistically significant differences in peak exercise IC (p<0.001), VE/VCO2slope (p<0.001), resting Pimax (p=0.005) and post-exercise Pimax (p<0.001). At rest, there was a statistically significant difference in end-tidal CO2 (P(ETCO2)) (p=0.002), in breathing frequency (p=0.004), in inspiratory time (Ti) (p=0.04) and in total respiratory time (T(Tot)) (p=0.004) among Weber's groups. At peak exercise there was a statistically significant decrease in minute ventilation (VE) (p<0.001), tidal volume (VT) (p<0.001), respiratory cycle (VT/TI) (p<0.001) and P(ETCO2) (p<0.001). Peak IC was correlated with peak VO2 (r=0.72, p<0.001), anaerobic threshold (r=0.71, p<0.001), VO2/t slope (r=0.54, p<0.0001), and post-exercise Pimax (r=0.62, p<0.001). In patients with CHF, peak exercise IC is reduced in parallel with disease severity, which is probably due to respiratory muscle dysfunction.


A case of bilateral carpal tunnel syndrome with palmaris longus and FDS anomalies.
We report a case of bilateral carpal tunnel syndrome due to two distinct muscular anomalies coexisting with trigger finger deformity. Many muscular anomalies in association with carpal tunnel syndrome have been described so far. But such a unique case of bilateral carpal tunnel syndrome with two different muscular anomalies, flexor digitorum superficialis anomaly on one side and palmaris longus anomaly on the other side has not been described. Even rare, muscular anomalies should be considered in the aetiology of carpal tunnel syndrome.


Mutation of the zebrafish glass onion locus causes early cell-nonautonomous loss of neuroepithelial integrity followed by severe neuronal patterning defects in the retina.
Mutation of the glass onion locus causes drastic neuronal patterning defects in the zebrafish retina and brain. The precise stratified appearance of the wild-type retina is absent in the mutants. The glass onion phenotype is first visible shortly after the formation of optic primordia and is characterized by the rounding of cells and disruption of the ventricular surface in the eye and brain neuroepithelia. With exception of the dorsal- and ventral-most regions of the brain, neuroepithelial cells lose their integrity and begin to distribute ectopically. At later stages, the laminar patterning of retinal neurons is severely disrupted. Despite the lack of lamination, individual retinal cell classes differentiate in the glass onion retina. Mosaic analysis reveals that the glass onion mutation acts cell nonautonomously within the retina and brain, as neuroepithelial cell morphology and polarity in these tissues are normal when mutant cells develop in wild-type hosts. We conclude that the glass onion mutation affects cell-cell signaling event(s) involved in the maintenance of the neuroepithelial cell layer shortly after its formation. The disruption of neuroepithelial integrity may be the cause of the neuronal patterning defects following neurogenesis. In addition, the expression of the glass onion phenotype in a subset of neuroepithelial cells as well as its onset following the initial formation of the neuroepithelial sheets indicate the presence of genetically distinct temporal and spatial subdivisions in the development of this histologically uniform tissue.


Glycine transporters (glycine transporter 1 and glycine transporter 2) are expressed in retina.
The amino acid glycine is an inhibitory neurotransmitter in the spinal cord, brain stem, and vertebrate retina. The effective synaptic concentrations of glycine are regulated by at least two transporters: glycine transporter 1 and glycine transporter 2. Here, we show retinal expression of glycine transporter 1 by in-situ hybridization and of glycine transporter 2 by reverse transcriptase-PCR and in-situ hybridization. In-situ hybridization signals were observed in the ganglionar and inner nuclear layer as well as in the outer nuclear layer of the frog and rat retinas. In addition, accumulation of H-glycine was observed in isolated photoreceptor cells. The expression of these transporters in nonglycinergic cells suggests that they may also modulate electrical signals.


[An assay for anti-factor Xa activity of low molecular weight heparins by high performance liquid size exclusion chromatography].
The "gold standard" assay for monitoring low molecular weight heparins (LMWHs) activity is the chromogenic-based anti-factor Xa assay. The methodology of an anti-factor Xa assay is that LMWH is added to a known amount of excess factor Xa and excess antithrombin. It will bind to antithrombin and form a triplet complex with factor Xa, inhibiting the activity of factor Xa. However, the residual factor Xa can still hydrolyze chromogenic peptide substrate, releasing the chromophore for photometric detection. The absorbance is inversely proportional to the amount of heparin/LMWH. The results are given in anticoagulant concentration in units/ mL of anti-factor Xa, such that high values indicate high levels of anticoagulation and low values indicate low levels of anticoagulation. Herein, a novel assay method for anti-FXa activity of LMWHs using high performance liquid size exclusion chromatography (SEC) is reported, in which antithrombin III (AT Ill ) was diluted by the buffer solution contained LMWHs. Subsequently, exogenous FXa and p-nitroaniline coupled peptide substrate were added and incubated for a period, separately. The resulting mixture was separated based on size by SEC, and the free chromophore p-nitroaniline can be detected at an absorption maximum of 385 nm without interference from the absorbance of p-nitroanilide substrates. Moreover, the measurements are not influenced by sample opacity or turbidity, so it is possible to test various complex samples, such as plasma. The assay is robust, sensitive, and cost effective.


Alkylation of phenylglycinol-derived oxazolopiperidone lactams. Enantioselective synthesis of beta-substituted piperidines.
The stereochemical outcome of the alkylation of a variety of phenylglycinol-derived oxazolopiperidone lactams is studied. The influence of the configuration of the C-8a stereocenter and the effect of the substituents at the C-8 and C-8a positions on the stereoselectivity of the reaction are discussed. The synthetic utility of these alkylation reactions is illustrated with the synthesis of cis and trans 3,5-disubstituted, 2,5-disubstituted, and 2,3,5-trisubstituted enantiopure piperidines, and the indole alkaloids 20R- and 20S-dihydrocleavamine.


AlN passivation layer-mediated improvement in tensile failure of flexible ZnO:Al thin films.
AlN passivation layer-mediated improvement in tensile failure of ZnO:Al thin films on polyethersulfone substrates is investigated. ZnO:Al films without any passivation layer were brittle with a crack-initiating bending strain εc of only about 1.13% with a saturated crack density ρs of 0.10 μm(-1) and a fracture energy Γ of 49.6 J m(-2). On passivation by an AlN overlayer, the fracture energy of the system increased considerably and a corresponding improvement in εc was observed. AlN layers deposited at higher discharge powers yielded higher fracture energy and exhibited better performance in terms of εc and ρs.


The effects of symmetric and asymmetric foot placements on sit-to-stand joint moments.
The purpose of this study was to determine the effects of symmetric and asymmetric foot placements on joint moments during sit-to-stand movements. Three symmetric (foot-neutral, foot-back, and foot-intermediate) and three asymmetric foot placements (preferred stagger, nonpreferred stagger, and intermediate stagger) were tested. Standard (46 cm) and low (41 cm) seat heights were chosen to represent an average public seat height and a 10% lower seat height. Using inverse dynamics, maximum ankle plantarflexion, knee extension, hip extension, and hip abduction moments were calculated. Hip extension moments were significantly increased when using foot-neutral as compared to foot-back. Ankle plantarflexion and knee extension moments were significantly increased when a foot was placed in the posterior position as compared to the anterior position for preferred and nonpreferred stagger. Knee extension moments were significantly increased at the low seat height as compared to the standard seat height. When shifting the feet anterior or posterior for symmetric placements during sit-to-stand, the most dramatic effect was an increase in hip extension moments when the feet are shifted anteriorly. Utilizing asymmetric foot placements during sit-to-stand produced increases in ankle plantarflexion and knee extension moments for the posteriorly placed limb, with reductions in the anteriorly placed limb.


Powerful haplotype-based Hardy-Weinberg equilibrium tests for tightly linked loci.
Recently, there have been many case-control studies proposed to test for association between haplotypes and disease, which require the Hardy-Weinberg equilibrium (HWE) assumption of haplotype frequencies. As such, haplotype inference of unphased genotypes and development of haplotype-based HWE tests are crucial prior to fine mapping. The goodness-of-fit test is a frequently-used method to test for HWE for multiple tightly-linked loci. However, its degrees of freedom dramatically increase with the increase of the number of loci, which may lack the test power. Therefore, in this paper, to improve the test power for haplotype-based HWE, we first write out two likelihood functions of the observed data based on the Niu's model (NM) and inbreeding model (IM), respectively, which can cause the departure from HWE. Then, we use two expectation-maximization algorithms and one expectation-conditional-maximization algorithm to estimate the model parameters under the HWE, IM and NM models, respectively. Finally, we propose the likelihood ratio tests LRT[Formula: see text] and LRT[Formula: see text] for haplotype-based HWE under the NM and IM models, respectively. We simulate the HWE, Niu's, inbreeding and population stratification models to assess the validity and compare the performance of these two LRT tests. The simulation results show that both of the tests control the type I error rates well in testing for haplotype-based HWE. If the NM model is true, then LRT[Formula: see text] is more powerful. While, if the true model is the IM model, then LRT[Formula: see text] has better performance in power. Under the population stratification model, LRT[Formula: see text] is still more powerful. To this end, LRT[Formula: see text] is generally recommended. Application of the proposed methods to a rheumatoid arthritis data set further illustrates their utility for real data analysis.


Updated meta-analysis of randomized controlled trials comparing conventional excisional haemorrhoidectomy with LigaSure for haemorrhoids.
To compare the surgical outcome of haemorrhoidectomy performed using LigaSure bipolar diathermy with conventional haemorrhoidectomy. Only randomized and alternate allocated studies were included from the major electronic databases using the search terms "ligasure" and "haemorrhoids". Duration of operation, blood loss during operation, postoperative pain score, wound healing, in-hospital stay, time to return to normal activities and complications were assessed. The 11 trials contained a total of 1,046 patients; the largest study was based on 273 patients and two earlier studies were based on 34 patients. No significant gender mismatch between the groups was reported in any of the studies. The patients' ages were similar between groups in the studies, as was disease severity. All 11 studies reported a shorter duration of the operation when using LigaSure compared to the conventional technique (p<0.001). The postoperative pain score (p=0.001) and blood loss during operation (p=0.001) were significantly reduced. After LigaSure haemorrhoidectomy wound healing (p=0.004) and the return to normal activities (p=0.001) were significantly faster than after conventional haemorrhoidectomy. However, the overall incidence of complications reported was not significantly different (p=0.056). LigaSure is an effective instrument for haemorrhoidectomy which results in less blood loss, quicker wound healing and earlier return to work.


Safety of thoracentesis in mechanically ventilated patients.
As practicing intensivists, we frequently diagnose pleural effusions in mechanically ventilated patients and routinely perform thoracentesis even when the patient is on positive end-expiratory pressure (PEEP). In light of a recent report, we have reviewed our experience. It is of interest that all thoracenteses were performed with patients in the lateral decubitus position.


Idiopathic chronic fatigue and chronic fatigue syndrome: a comparison of two case-definitions.
The aim of the study was to compare the signs and symptoms of individuals meeting two different definitions of chronic fatigue syndrome (CFS). Ninety-four patients fitting the eligibility criteria for idiopathic fatigue were enrolled into the study. Of the 94 patients, 48 met the 1988 definition of CFS, 20 the 1994 (but not the 1988) definition of CFS, and 26 met neither definition. The 1994 defined cases were more likely than 1988 defined cases, and non-syndromal individuals to be male, married, and high school educated. The 1994 cases were less likely than 1988 cases to present acute onset, self reported sore throat, mild fever lymphadenopathy, pharyngitis. In conclusion, the 1994 criteria increased the number of patients classified as CFS; however, those who fit only the 1994 criteria were less likely to have an acute symptomatic onset and signs and symptoms suggestive of an infectious process.


Higher physical fatigue predicts adherence to a 12-week exercise intervention in women with elevated blood pressure.
To investigate predictors of exercise adherence to a 12-week exercise intervention for sedentary women and men with elevated blood pressure (BP). Fifty-one otherwise healthy and unmedicated adults (27 women and 24 men) with elevated BP (≥120/80 mmHg but <179/109 mmHg) participated in a 12-week exercise intervention involving cardiovascular and strength training. Participants kept weekly exercise logs detailing minutes spent exercising each week. The following were assessed before and after the intervention: cardiorespiratory fitness (in mL/kg/min), body mass index (BMI), level of habitual physical activity, physical fatigue, self-efficacy for exercise habits, and social support. Regression analysis revealed that mean exercise minutes/week were predicted by higher age (p < .05), higher cardiorespiratory fitness (p < .05), and a gender by physical fatigue interaction (p < .01; R2 = 0.34, F = 3.248, p < .01). Women who reported higher physical fatigue prior to the intervention spent more time exercising during the 12-week intervention than those with lower levels of physical fatigue. This relationship persisted after controlling for age, BMI, cardiorespiratory fitness, level of habitual physical activity prior to the intervention, self-efficacy for exercise habits, and social support (p < .01). The gender by physical fatigue interaction explained 13.9% of the variance in mean minutes exercised/week above and beyond the effects of covariates. Both gender and fatigue should be considered when developing exercise interventions, such that more initial physical fatigue in women is associated with a tendency to devote greater amounts of time to exercising.


Comparison of Lewis Score and Capsule Endoscopy Crohn's Disease Activity Index in Patients with Crohn's Disease.
Small bowel capsule endoscopy (SBCE) is used to visualize mucosal inflammatory changes in the small intestine of patients with Crohn's disease (CD). The Lewis score (LS) and Capsule Endoscopy Crohn's Disease Activity Index (CECDAI) are used to evaluate the visualized images. We determined the score disagreement between LS and CECDAI in patients with CD. We evaluated 184 SBCE procedures in 102 CD patients with small bowel lesions. Patients were classified according to the Montreal classification. LS and CECDAI were calculated, and cases with disagreement between the two scores were identified. We investigated the characteristics of disagreement, and analyzed the relationships with the Crohn's Disease Activity Index (CDAI) and C-reactive protein. LS (504 ± 1160) correlated strongly with CECDAI (6 ± 5.4) (Spearman's rank correlation coefficient ρ = 0.81, p < 0.0001). LS values of 135 and 790 were equivalent to CECDAI values of 4.9 and 6.9, respectively. The inflammatory changes by LS were significantly observed in several tertiles in the CECDAI discrepancy group (LS < 135, CECDAI ≥ 4.9) compared with the normal agreement group (LS < 135, CECDAI < 4.9) (p < 0.0001). In both groups, CDAI was also significantly different between Montreal L1 and L3 groups (p = 0.0232, p = 0.0196, respectively). LS inflammation score was 0 in six cases in the LS discrepancy group (LS ≥ 135, CECDAI ≤ 4.9, n = 10); the high LS scores were in patients with high stricture scores. Discrepancies between the LS and CECDAI scores were observed in some patients. Cases with high CECDAI alone exhibited extensive inflammation and high disease activity (clinical symptoms and biomarker levels). CECDAI seems to better reflect active intestinal inflammation than LS.


[A case of teratoma of the urachus].
The paper reports a case of teratoma of the urachus in a 53-year-old patient. The difficulties of diagnosing this pathology are underlined, in particular in relation to the rarity of the site of which no other examples have been reported in the literature.


[Variability of sinus rhythm and cardiac failure].
Under pathological conditions, the autonomic nervous system, which continually regulates cardiac function, may have adverse effects on pump function and electrical activation. The sinus rhythm is an indirect marker of the different components of the autonomic nervous system and changes in the heart rate reflect the permanent variation of vagal and sympathetic tone. Analysis of variability in the temporal or frequential domaines, provides information about the modulation of the different components of the autonomic nervous system. In the post-infarction period, studies have shown that the heart rate variability is an independent predictive factor of cardiovascular mortality. The data available in patients with cardiac failure is limited. There is a decrease in heart rate variability and this decrease seems to be associated with a higher risk.


Basic principles on toe-to-hand transplantation.
Within the last three decades, toe-to-hand transplantation has become a well-established method for function and appearance reconstruction after trauma and in congenital hand anomalies. An otherwise healthy and cooperative patient is the ideal candidate for toe transplantation after trauma. In such patient, even primary toe transplantation is possible, if the stump is clean and viable. If secondary reconstruction after completed wound healing is considered, emphasis should be laid on tissue sacrifice during the acute management of non-replantable amputations at the hand. Specific considerations regarding selection of toe(s) to be transplanted, technique of toe harvest and inset, sequence of transplantations if more than one digit is to be reconstructed such as in the metacarpal hand, and postoperative regimen are important to achieve satisfying functional and aesthetic results on both recipient and donor sites. A trimmed great toe is ideal for thumb reconstruction if the amputaiton is located at or distal to the middle metacarpal shaft. However, in more proximal amputations a second toe may be more suitable as it allows transmetatarsal harvest without increasing donor site morbidity. Distal finger reconstruction with partial toe or second toe warp around flap gives most gratifing result to those patients who are critically concerned about their body images and also those who need distal fingers for jobs or recreation activities. Combined second and third toe or third and fourth toe transplantations are particular useful in metacarpal hand reconstruction to provide tripod pinch. The role of toe-to-hand transplantation in the new millenium assuming progress in tissue engineering, gene transfer, and the development of new immunosuppressive drugs is discussed.


Improvements and limits of anti SARS-CoV-2 antibodies assays by WHO (NIBSC 20/136) standardization.
A few CLIA automated immunoassays for the recognition of anti S1-RBD SARS-CoV-2 antibodies have recently been placed on the market. Preliminary data demonstrate a high correlation between methods but wide differences in absolute concentrations. A new WHO international standard for anti-SARS-CoV-2 immunoglobulin, NIBSC code 20/136, has been recently introduced to reduce the differences. The aim of this study is thus to verify the harmonization made by NIBSC 20/136 on Ab anti S1-RBD measurement on real samples. The following assays were studied: LIAISON® SARS-CoV-2 TrimericS IgG (DiaSorin); Elecsys® anti-SARS-CoV-2 S (ROCHE); Atellica IM SARS-CoV-2 IgG (sCOVG) (Siemens); MAGLUMI® SARS-CoV-2 S-RBD IgG (Snibe), measuring 210 samples from 70 health workers with no previous SARS-CoV2 infection, during their Pfizer-BioNTech's BNT162b2 vaccination period. The recalculation of concentrations based on the NIBSC 20/136 standardization improve the analytical and diagnostic comparability but do not cancel this variability between methods: recalibrated results remain different across methods, both in terms of tendency and single data. The recalculation of concentrations based on the NIBSC 20/136 standardization improves the analytical and diagnostic comparability but does not cancel the differences between methods: recalibrated results remain different across methods, both in terms of tendency and single data.


Didelphis albiventris as a carrier of Leptospira sp. in the central nervous tissue in the semiarid region of Northeast, Brazil.
Leptospirosis has been investigated in several species of wild animals. The white-eared opossum (Didelphis albiventris) is a mammal common in the brazilian semi-arid, so, this study aimed to investigate its role in the occurrence of the leptospirosis in the region Northeast of Brazil. 12 animals were used, from which samples were collected for the attempt of isolation, molecular detection and serological examination. There was no microbial growth, nor were any anti-Leptospira sp. antibodies found in the serological samples. The PCR detected leptospiric DNA in the central nervous system (CNS) of five animals (41.7 %). The gene in one of the samples was sequenced and showed identity with Leptospira interrogans. The presence of Leptospira sp. in the CNS of Didelphis albiventris does not allow the characterization of the studied animals as reservoirs with potential for transmission of the pathogen in the region, however it represents a site that needs to be further investigated.


Criteria for prediabetes and posttransplant diabetes mellitus after kidney transplantation: A 2-year diagnostic accuracy study of participants from a randomized controlled trial.
Posttransplant diabetes mellitus (PTDM) and prediabetes (impaired glucose tolerance [IGT] and impaired fasting glucose [IFG]) are associated with cardiovascular events. We assessed the diagnostic performance of fasting plasma glucose (FPG) and HbA1c as alternatives to oral glucose tolerance test (OGTT)-derived 2-hour plasma glucose (2hPG) using sensitivity and specificity in 263 kidney transplant recipients (KTRs) from a clinical trial. Between visits at 6, 12, and 24 months after transplantation, 28%-31% of patients switched glycemic category (normal glucose tolerance [NGT], IGT/IFG, PTDM). Correlations of FPG and HbA1c against 2hPG were lower at 6 months (r = 0.59 [FPG against 2hPG]; r = 0.45 [HbA1c against 2hPG]) vs. 24 months (r = 0.73 [FPG against 2hPG]; r = 0.74 [HbA1c against 2hPG]). Up to 69% of 2hPG-defined PTDM cases were missed by conventional HbA1c and FPG thresholds. For prediabetes, concordance of FPG and HbA1c with 2hPG ranged from 6%-9%. In conclusion, in our well-defined randomized trial cohort, one-third of KTRs switched glycemic category over 2 years and although the correlations of FPG and HbA1c with 2hPG improved with time, their diagnostic concordance was poor for PTDM and, especially, prediabetes. Considering posttransplant metabolic instability, FPG's and HbA1c 's diagnostic performance, the OGTT remains indispensable to diagnose PTDM and prediabetes after kidney transplantation.


Vasodilators in hypertension--a review with special emphasis on the combined use of vasodilators and beta-adrenoceptor blockers.
This paper presents a review of studies dealing with combined beta-adrenoceptor blockade and vasodilatation in the treatment of hypertension. This therapy can be achieved either through the combined use of conventional beta-adrenoceptor blocking compounds given together with vasodilator drugs or with agents which show multiple action of this kind. From a hemodynamic point of view this therapeutic approach is quite logical since most forms of established hypertension are characterized by increased vascular resistance. It can therefore be concluded that combined beta-adrenoceptor blockade and vasodilation offers a rational and useful treatment of hypertension.


A GPU-based multi-criteria optimization algorithm for HDR brachytherapy.
Currently in HDR brachytherapy planning, a manual fine-tuning of an objective function is necessary to obtain case-specific valid plans. This study intends to facilitate this process by proposing a patient-specific inverse planning algorithm for HDR prostate brachytherapy: GPU-based multi-criteria optimization (gMCO). Two GPU-based optimization engines including simulated annealing (gSA) and a quasi-Newton optimizer (gL-BFGS) were implemented to compute multiple plans in parallel. After evaluating the equivalence and the computation performance of these two optimization engines, one preferred optimization engine was selected for the gMCO algorithm. Five hundred sixty-two previously treated prostate HDR cases were divided into validation set (100) and test set (462). In the validation set, the number of Pareto optimal plans to achieve the best plan quality was determined for the gMCO algorithm. In the test set, gMCO plans were compared with the physician-approved clinical plans. Our results indicated that the optimization process is equivalent between gL-BFGS and gSA, and that the computational performance of gL-BFGS is up to 67 times faster than gSA. Over 462 cases, the number of clinically valid plans was 428 (92.6%) for clinical plans and 461 (99.8%) for gMCO plans. The number of valid plans with target [Formula: see text] coverage greater than 95% was 288 (62.3%) for clinical plans and 414 (89.6%) for gMCO plans. The mean planning time was 9.4 s for the gMCO algorithm to generate 1000 Pareto optimal plans. In conclusion, gL-BFGS is able to compute thousands of SA equivalent treatment plans within a short time frame. Powered by gL-BFGS, an ultra-fast and robust multi-criteria optimization algorithm was implemented for HDR prostate brachytherapy. Plan pools with various trade-offs can be created with this algorithm. A large-scale comparison against physician approved clinical plans showed that treatment plan quality could be improved and planning time could be significantly reduced with the proposed gMCO algorithm.


Challenges in the Diagnosis of Beta-thalassemia Syndrome: The Importance of Molecular Diagnosis.
Patients with heterozygous β-thalassemia are generally asymptomatic. However, the intermediate phenotype is uncommon, and patients require further investigation to confirm the diagnosis. We describe a 32-year-old woman (gravida 3, para 2) with heterozygous β-thalassemia who presented with symptomatic anemia and had a history of frequent blood transfusion in each pregnancy. Physical examination was unremarkable. Laboratory results at presentation showed hypochromic microcytic anemia with reticulocytosis. Molecular study revealed intermedia phenotypes resulting from coinheritance of heterozygous β-globin chain mutation (IVS1-5) and a rare heterozygous α-globin triplication (αααanti-3.7). In this case report, we discuss the laboratory diagnostic approaches and the challenges faced in investigating this case.


Bispectral index and the clinically evaluated anaesthetic depth in dogs.
This study investigated whether the bispectral index (BIS monitor) corresponded with the clinical assessment of anaesthetic depth in dogs. Prospective clinical study. Sixty-five dogs undergoing anaesthesia for surgery. Dogs were assigned to one of three different anaesthetic techniques. A three point scale was devised to determine the clinical depth of anaesthesia (CDA); CDA 1 represented light, CDA 2 surgical and CDA 3 excessive depth of anaesthesia. BIS values were recorded and CDA assessed at specific times and points throughout surgery. Data were statistically analysed using mixed model regression. Clinical depth of anaesthesia was assessed as CDA 1 on 68, 2 on 748 and 3 on four occasions. The BIS recorded for CDA 1 differed significantly from that for CDA 2 (p<0.001). However, individual BIS values measured at light and surgical levels of anaesthesia overlapped considerably. The sensitivities and specificities calculated for BIS to diagnose CDA 1 compared to CDA 2 in the three anaesthetic protocols were 28-86% and 55-85%. The accompanying positive predictive value was 0.08-0.29 and the negative predictive value was 0.95-0.97. End-tidal isoflurane concentrations (anaesthetic techniques 1 and 3) and propofol infusion (technique 2) at CDA 1 was significantly lower than those at CDA 2 (p=0.001). Although BIS values overall distinguished between CDA scores, the calculated specificities, sensitivities and predictive values were low, and there were anomalous results in individual cases. The use of the BIS as the sole method to determine anaesthetic depth in dogs is imprudent.


Structural studies of the lipid components of bile.
The lipid-rich molecular aggregates responsible for the transport of cholesterol in bile include mixed micelles and bilayer vesicles. In this review, the molecular conformations of the individual lipid components of biliary micelles and vesicles (phospholipids, bile salts and cholesterol) obtained by high-resolution x-ray crystallographical analysis are described. The key conformational/packing features relevant to lipid organization, molecular interactions and cholesterol solubility in bile are discussed. The structure of cholesterol monohydrate, the major component in cholesterol gallstones, is described and problems relevant to cholesterol crystal nucleation/growth processes are briefly discussed.


[Pulmonary infection with Coccidioides immitis].
A man aged 42 who was referred to the outpatient department for Pulmonary Diseases because of a cough of two weeks' standing and fever up to 40 degrees C, had recently spent 10 days in the desert (San Joaquin Valley, California). Physical examination revealed no distinct abnormalities. Radiologically, an infiltrative lesion in the left upper lobe of the lung was established, as well as swollen lymph nodes near the pulmonary hilus. Blood testing revealed leukocytosis and eosinophilia. Possibilities considered were tuberculosis and, because the patient had been in California, coccidioidomycosis. The Mantoux test and several Ziehl-Neelsen preparations were negative. However, the immunodiffusion test for Coccidioides immitis antibodies was positive. Also, C. immitis was cultured from the sputum. The diagnosis read ¿pulmonary coccidioidomycosis with eosinophilia'. Because of aggravation of the pulmonary lesions and eosinophilia, treatment with ketoconazole was instituted. This was the first time in the Netherlands that a human infection with the fungus C. immitis could be confirmed serologically as well.


In vitro exposure to sodium fluoride does not modify activity or proliferation of human osteoblastic cells in primary cultures.
The anabolic effects of sodium fluoride (NaF) on trabecular bone mass in osteoporosis is now well established. In vivo histologic studies performed in humans and other animals have shown that fluoride induces an increase in osteoblast number at the tissue level. To determine the mechanisms of action of fluoride on osteoblasts, we studied the effects of NaF on short- and long-term cultures of human osteoblastic cells derived from bone explants obtained from 21 donors. In short-term experiments, bone-derived cells were exposed to NaF for 4 days. At doses ranging from 10(-11) to 10(-5) M, NaF did not modify the alkaline phosphatase (AP) activity or osteocalcin secretion. In long-term experiments, half the bone samples from 15 donors were cultured for 4 months in the presence of 10(-5) M NaF and the other half were maintained in NaF-free medium. Observations by light and electron microscopy disclosed no morphologic modification in bone explants after 4 months of exposure to NaF, despite an increase in the bone fluoride content. After the first month of culture, slight but not significant increases were noted in 6 of 10 cases for AP activity, 4 of 10 for osteocalcin secretion, and 5 of 7 for [3H]thymidine incorporation. After 4 months of culture in the presence of NaF, no change in AP activity or cell proliferation was noted. In contrast, the osteocalcin secretion significantly decreased (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Age at Diagnosis and Baseline Myelomalacia Sign Predict Functional Outcome After Spinal Meningioma Surgery.
Objective: Spinal meningioma (SM) accounts for 12% of all meningiomas. Clinical and immunohistochemical factors were analyzed with regard to functional outcome, surgical adverse events, and tumor recurrence. Methods: One-hundred and twenty-three consecutive SM patients underwent surgery and were retrospectively reviewed with regard to demographic parameters, imaging features, neurological function, and immunohistochemical items. Neurological function was graded according to the Modified McCormick Scale (MMS) and dichotomized as "good (grade I + II)" and "poor (grade III-V)" function. Results: One-hundred and fourteen (92.7%) WHO grade I and 9 (7.3%) WHO grade II SM were included in this study. Univariate analysis identified a baseline T2 hyperintensity of the spinal cord, baseline symptom duration ≥4 weeks, age ≥66 years, and dural tail sign as predictors of poor MMS. Baseline T2 hyperintensity of the spinal cord [Odds ratio (OR) = 13.3, 95% CI = 3.4-52.1, p < 0.001] and age ≥66 years (OR = 10.3, 95% CI = 2.6-41.1, p = 0.001) were independent predictors of a poor MMS grade at discharge after SM surgery in the multivariate binary logistic regression analysis. The 12- and 24-month recurrence-free survival rates were 98.7 % (1/80) and 94.7% (2/38), respectively. In those patients with tumor recurrence of the SM, highly increased MIB-1 (≥5%) labeling indices were observed. Conclusion: Baseline T2 hyperintensity, especially in the elderly patients, is a strong predictor of poorer recovery after spinal meningioma surgery. SMs with high proliferative activity should be followed-up closely despite maximal safe resection.


Bethesda proposals for classification of nonlymphoid hematopoietic neoplasms in mice.
The hematopathology subcommittee of the Mouse Models of Human Cancers Consortium recognized the need for a classification of murine hematopoietic neoplasms that would allow investigators to diagnose lesions as well-defined entities according to accepted criteria. Pathologists and investigators worked cooperatively to develop proposals for the classification of lymphoid and nonlymphoid hematopoietic neoplasms. It is proposed here that nonlymphoid hematopoietic neoplasms of mice be classified in 4 broad categories: nonlymphoid leukemias, nonlymphoid hematopoietic sarcomas, myeloid dysplasias, and myeloid proliferations (nonreactive). Criteria for diagnosis and subclassification of these lesions include peripheral blood findings, cytologic features of hematopoietic tissues, histopathology, immunophenotyping, genetic features, and clinical course. Differences between murine and human lesions are reflected in the terminology and methods used for classification. This classification will be of particular value to investigators seeking to develop, use, and communicate about mouse models of human hematopoietic neoplasms.


A magnetic resonance study of early schizophrenia.
Patients with untreated first schizophrenic episodes and others who had made varying degrees of recovery from such episodes were blindly compared with normal volunteers in terms of the periventricular appearances on spin echo magnetic resonance scans. Significant differences were not found.


Feeding value of wood sugar concentrate for feedlot cattle.
Six crossbred steers (344 kg) with "T" cannulas in the rumen and proximal duodenum (6 cm from the pyloric sphincter) were used in a crossover experiment to evaluate the feeding value of wood sugar concentrate (WSC) in a finishing diet for feedlot steers. Composition of WSC was as follows: DM, 49.5%; ash, 19.2%; N, .1%; hydrolyzable sugars, 38.9% and lignosulfonate, 28.8%. Dietary treatments consisted of a finishing diet based on steam-flaked corn supplemented or not supplemented with 10.5% WSC (DM basis). Adding WSC to the diet increased (P less than .10) passage of OM to the small intestine. However, passage of N constituents (non-ammonia N, microbial N and feed N) was not affected (P greater than .10). Postruminal digestion of OM and N was depressed (P less than .05) 11.5% and 6.7%, respectively, with WSC supplementation. Total tract digestibilities of OM and GE were depressed (P less than .01) 4.1 and 4.2%, respectively. Adjusting for constituent passage of the basal diet, estimated digestible OM and DE values for WSC used in this trial were 42.7% and 2.02 Mcal/kg. WSC (DM basis) had 76% and 64%, respectively, of the energy value of hemicellulose extract (masonex) and cane sugar molasses. Because a high level (10% of diet DM) of WSC depressed postruminal N digestion, WSC levels of feedlot diets that are marginal in protein should not exceed 5% of diet DM.


Accelerating Cementite Precipitation during the Non-Isothermal Process by Applying Tensile Stress in GCr15 Bearing Steel.
In this work, the non-isothermal process of GCr15 bearing steel after quenching and tempering (QT) under different tensile stress (0, 20, 40 MPa) was investigated by kinetic analysis and microstructural observation. The Kissinger method and differential isoconversional method were employed to assess the kinetic parameters of the microstructural evolution during the non-isothermal process with and without applied stress. It is found that the activation energy of retained austenite decomposition slightly increases from 109.4 kJ/mol to 121.5 kJ/mol with the increase of tensile stress. However, the activation energy of cementite precipitation decreases from 179.4 kJ/mol to 94.7 kJ/mol, proving that tensile stress could reduce the energy barrier of cementite precipitation. In addition, the microstructural observation based on scanning and transmission electron microscopy (SEM and TEM) shows that more cementite has formed for the specimens with the applied tensile stress, whereas there is still a large number of ε carbides existing in the specimens without stress. The results of X-ray diffraction (XRD) also verify that carbon in martensite diffuses more and participates in the formation of cementite under the applied tensile stress, which thus are in good agreement with the kinetic analysis. The mechanisms for the differences in cementite precipitation behaviors may lie in the acceleration of carbon atoms migration and the reduction of the nucleation barrier by applying tensile stress.


Two non-vesicular ATP release pathways in the mouse erythrocyte membrane.
Erythrocytes are exceptionally suited for analysis of non-exocytotic release mechanisms of ATP, because these cells under physiological conditions lack vesicles. Previous studies have indicated, that Pannexin1 (Panx1) provides a key ATP permeation pathway in many cell types, including human and frog erythrocytes. Here we show that erythrocytes of Panx1(-/-) mice lend further support to this conclusion. However, ATP release, although attenuated, was still observed in Panx1(-/-) mouse erythrocytes. In contrast to Panx1(+/+) cells, this release was not correlated with uptake of extracellularly applied dyes, was insensitive to Panx1 channel blockers, and was inhibited by dipyridamole and stimulated by iloprost. Thus, in erythrocytes, two independent pathways mediate the release of ATP. We also show that glyburide is a strong inhibitor of Panx1 channels.


The amino acid sequence of coagulogen isolated from southeast Asian horseshoe crab, Tachypleus gigas.
The amino acid sequence of coagulogen isolated from Southeast Asian horseshoe crab (Tachypleus gigas) has been determined. The NH2-terminal sequence of the first 51 residues was obtained by automated Edman degradation. The intact protein was then treated with a Tachypleus clotting enzyme, to form a gel and to remove an internal peptide C (28 residues) located near the NH2-terminal portion. The gel protein, which consisted of A chain (18 residues) and B chain (129 residues), was S-alkylated and the resulting two chains were separated by acetone precipitation. Among these segments, A chain and peptide C were assigned to the NH2-terminal portion of whole coagulogen, as judged from their amino acid compositions. On the other hand, the covalent structure of B chain was determined by sequencing the peptides obtained from its tryptic digest. The alignments of the tryptic peptides were deduced from the sequence homology in comparison with the previously established B chain sequence of Japanese horseshoe crab (T. tridentatus) coagulogen. T. gigas coagulogen had a total of 175 amino acids and a calculated molecular weight of 19,770. When the sequence was compared with those of Japanese and American horseshoe crab (Limulus polyphemus) coagulogens, extensive structural homology was found: T. tridentatus/T. gigas, 87% and L. polyphemus/T. gigas, 67%. This comparison suggests that Japanese and Southeast Asian horseshoe crabs have a crab, based on amino acid sequence data.


Development of Neutral and Nearly Neutral Theories
A short history of the major features of neutral theories of molecular evolution is presented. Emphasis is placed on the nearly neutral theory, as this version of the neutral theory has explained the widest range of phenomena. The shift of interest from protein to DNA evolution is chronicled, leading to the modern view that silent and replacement substitutions are responding to different evolutionary forces. However, the exact nature and magnitude of these forces remains controversial, as all current theoretical models suffer either from assumptions that are not quite realistic or from an inability to account readily for all phenomena. Although the gathering of sequence data has been the main effort of contemporary population genetics, further exploration of theoretical models of molecular evolution would provide a more coherent framework for data analysis.


Policy and public communication methods among U.S. state prisons during the first year of the COVID-19 pandemic.
Throughout the first year of the COVID-19 pandemic, our research team monitored and documented policy changes in United States (U.S.) prison systems. Data sources included prison websites and official prison social media accounts. Over 2500 data sources relevant to the COVID-19 pandemic in U.S. prisons were located and summarized in to five different categories: 1) prevention, 2) case identification and intervention, 3) movement, 4) social communication and connection, and 5) programming, recreation, and privileges. All state prison systems reportedly enacted multiple policies intended to limit the spread of COVID-19 during the pandemic. Document analysis revealed that the most commonly released policies were restrictions on social contacts and privileges, basic preventive measures (e.g., distribution of masks), and basic case identification measures (e.g., verbal screening and temperature checks). Utilization of social media for policy communication varied significantly across states, though relevant data was more often released on Facebook than Twitter. Together, our work provides foundational knowledge on the wide breadth of policies that were reportedly enacted in the first year of the pandemic that may be used as a base for quantitative work on policy effectiveness and examinations of implementation.


Management of neurogenic bowel dysfunction.
There are several modalities for treating neurogenic bowel dysfunction (NBD), including conservative treatments (diet, medications, biofeedback, transanal irrigation, massage, electrical stimulation, anal plug). When conservative treatments fail, clinicians can choose from a variety of therapeutic options, including colostomies, Malone anterograde continence enemas, sacral anterior root stimulator implantations, graciloplasties, and artificial bowel sphincters. We reviewed the various treatments for constipation and/or fecal incontinence in patients with NBD and propose over-reaching stepwise algorithms for the management of NBD. Our review included English language articles, randomized controlled studies, cohort studies, case-control studies, and retrospective studies (if necessary) that assessed the management of NBD. Our literature search identified 577 articles, of which 79 met our inclusion criteria. There is little evidence for the success of conservative but non-pharmacological treatments. There is strong evidence for the success of pharmacological interventions (i.e., prokinetic agents) in the treatment of chronic constipation. While surgical interventions may be considered, there is little evidence of their effectiveness. Bowel management programs for patients with neurologic diseases require a multi-faceted approach. While a range of medical and surgical treatments are available, there is little evidence for their effectiveness, with the exception of pharmacological interventions.


Conservation of structure and expression of the c-yes and fyn genes in lower vertebrates.
The src-gene family in mammals and birds consists of 9 closely related protein tyrosine kinases. We have cloned the c-yes and fyn homologues of the src-family from the teleost fish Xiphophorus helleri. Both genes show a high degree of sequence conservation and exhibit all structural motifs diagnostic for functional src-like protein tyrosine kinases. Sequence comparisons revealed three domains (exon 2, exons 3-6, exons 7-12) which evolve at different rates. Both genes exhibit an identical expression pattern, with preferential expression in neural tissues. No transcripts of c-yes were found in liver which is contrary to the situation in higher vertebrates. In malignant melanoma, elevated levels of c-yes and fyn were detected indicating a possible function during secondary steps of tumor progression for src-related tyrosine kinases.


Repulsive Backbone-Backbone Interactions Modulate Access to Specific and Unspecific Binding Sites on Surface-Bound Mucins.
Mucin glycoproteins are the matrix-forming key components of mucus, the innate protective barrier protecting us from pathogenic attack. However, this barrier is constantly challenged by mucin-degrading enzymes, which tend to target anionic glycan chains such as sulfate groups and sialic acid residues. Here, we demonstrate that the efficiency of both unspecific and specific binding of small molecules to mucins is reduced when sulfate groups are enzymatically removed from mucins; this is unexpected because neither of the specific mucin-binding partners tested here targets these sulfate motifs on the mucin glycoprotein. Based on simulation results obtained from a numerical model of the mucin macromolecule, we propose that anionic motifs along the mucin chain establish intramolecular repulsion forces which maintain an elongated mucin conformation. In the absence of these repulsive forces, the mucin seems to adopt a more compacted structure, in which the accessibility of several binding sites is restricted. Our results contribute to a better understanding on how different glycans contribute to the broad spectrum of functions mucin glycoproteins have.


Atorvastatin therapy during the peri-infarct period attenuates left ventricular dysfunction and remodeling after myocardial infarction.
Although statins impart a number of cardiovascular benefits, whether statin therapy during the peri-infarct period improves subsequent myocardial structure and function remains unclear. Thus, we evaluated the effects of atorvastatin on cardiac function, remodeling, fibrosis, and apoptosis after myocardial infarction (MI). Two groups of rats were subjected to permanent coronary occlusion. Group II (n = 14) received oral atorvastatin (10 mg/kg/d) daily for 3 wk before and 4 wk after MI, while group I (n = 12) received equivalent doses of vehicle. Infarct size (Masson's trichrome-stained sections) was similar in both groups. Compared with group I, echocardiographic left ventricular ejection fraction (LVEF) and fractional area change (FAC) were higher while LV end-diastolic volume (LVEDV) and LV end-systolic and end-diastolic diameters (LVESD and LVEDD) were lower in treated rats. Hemodynamically, atorvastatin-treated rats exhibited significantly higher dP/dt(max), end-systolic elastance (Ees), and preload recruitable stroke work (PRSW) and lower LV end-diastolic pressure (LVEDP). Morphometrically, infarct wall thickness was greater in treated rats. The improvement of LV function by atorvastatin was associated with a decrease in hydroxyproline content and in the number of apoptotic cardiomyocyte nuclei. We conclude that atorvastatin therapy during the peri-infarct period significantly improves LV function and limits adverse LV remodeling following MI independent of a reduction in infarct size. These salubrious effects may be due in part to a decrease in myocardial fibrosis and apoptosis.


Superhydrophobic micro/nano dual-scale structures.
In this paper, we present superhydrophobic micro/nano dual structures (MNDS). By KOH-etching of silicon, well-designed microstructures, including inverted pyramids and V-shape grooves, are first fabricated with certain geometry sizes. Nanostructures made of high-compact high-aspect-ratio nanopillars are then formed atop microstructures by an improved controllable deep reactive ion etching (DRIE) process without masks, thus forming MNDS. Resulting from both the minimized liquid-solid contact area and the fluorocarbon layer atop deposited during the DRIE process, the MNDS show a reliable superhydrophobicity. The contact angle and contact angle hysteresis are -165 degrees and less than 1 degrees, respectively. This superhydrophobicity of MNDS is very stable according to squeezing and dropping test, even in high voltage conditions with the electrowetting threshold voltage of -300 V. Therefore, this micro/nano dual-scale structure has strong potential applications to the self-cleaning surface and superhydrophobic micro/nano fluidics.


Comparison of the proportion method with mycobacteria growth indicator tube and E-test for susceptibility testing of Mycobacterium tuberculosis.
The aim of this study was to investigate the correlation between proportion method with mycobacteria growth indicator tube (MGIT) and E-test for Mycobacterium tuberculosis. Forty clinical isolates were tested. MGIT and E-test with the first line antituberculous drugs correlated with the proportion method. Our results suggested that MGIT and E-test methods can be routinely used instead of the proportion method.


Novel insights into the dissemination route of Japanese apricot (Prunus mume Sieb. et Zucc.) based on genomics.
Japanese apricot (Prunus mume) is an attractive fruit tree originating from China, and its cultivation history dates back 7000 years. In this study, we investigated the genetic diversity, population structure, and genetic relationship of Japanese apricots in different regions of China and Japan. The analyses of the genetic variation between wild and cultivated populations improved our understanding of the general mechanisms of domestication and improvement. A total of 146 accessions of Japanese apricot from different geographic locations were sequenced. The genetic diversity of wild and domesticated accessions (3.60 × 10-3 and 3.51 × 10-3 , respectively) from China was high, and the effect of artificial selection pressure on domesticated accessions was small; however, the genetic diversity of artificially bred accessions decreased significantly (2.68 × 10-3 ) compared to domesticated accessions, which had an obvious improvement bottleneck effect. The chloroplast genome results showed that 41 haplotypes were detected, and Japanese apricots from the Yunnan region had the most haplotypes and the highest genetic diversity. The results revealed the dissemination route of Japanese apricot, not only along the Yangtze River basin system (from southwest China to Hunan, Jiangxi, and Anhui, and finally to the Jiangsu, Zhejiang, and Shanghai areas). Additionally, we discovered a second route for Japanese apricot dispersion, which was mostly in the Pearl River basin system, from southwest China to Libo of Guizhou and then to the Guangdong, Fujian, and Taiwan areas. This also showed that Japanese-bred accessions originated from Zhejiang, China. In addition, selective sweep analysis showed that most of the high-impact single nucleotide polymorphisms were identified in genes related to glucose metabolism, aromatic compound metabolism, flowering time, dormancy, and resistance to abiotic stress during the domestication and improvement of Japanese apricot.


Asparagus officinalis extract controls blood glucose by improving insulin secretion and β-cell function in streptozotocin-induced type 2 diabetic rats.
The aim of the present study was to evaluate the anti-diabetic mechanism of Asparagus officinalis, a dietary agent used for the management of diabetes. Streptozotocin (90 mg/kg) was injected in 2-d-old Wistar rat pups to induce non-obese type 2 diabetes. After confirmation of diabetes on the 13th week, diabetic rats were treated with a methanolic extract of A. officinalis seeds (250 and 500 mg/kg per d) or glibenclamide for 28 d. After the treatment, fasting blood glucose, serum insulin and total antioxidant status were measured. The pancreas was examined by haematoxylin-eosin staining and immunostained β- and α-cells were observed using a fluorescence microscope. Treatment of the diabetic rats with the A. officinalis extract at doses of 250 and 500 mg/kg suppressed the elevated blood glucose in a dose- and time-dependent manner. The 500 mg/kg, but not 250 mg/kg, dose significantly improved serum insulin levels in the diabetic rats. The insulin:glucose ratio was significantly increased at both doses in the A. officinalis-treated rats. Both qualitative and quantitative improvements in β-cell function were found in the islets of the A. officinalis-treated rats. The extract showed potent antioxidant activity in an in vitro assay and also improved the total antioxidant status in vivo. In most cases, the efficacy of A. officinalis (500 mg/kg) was very similar to a standard anti-diabetic drug, glibenclamide. Thus, the present study suggests that A. officinalis extract exerts anti-diabetic effects by improving insulin secretion and β-cell function, as well as the antioxidant status.


The Degradation Products of Ascorbic Acid Inhibit Amyloid Fibrillation of Insulin and Destabilize Preformed Fibrils.
Ascorbic acid (AsA) is an important antioxidant and enzyme cofactor in many biochemical processes. Most biological activities of AsA are closely related to its redox properties. Recent investigations have demonstrated that AsA is associated with amyloid-related diseases and can inhibit amyloid aggregation of polypeptides. In the present study, we determined the kinetics of AsA degradation and investigated the anti-amyloidogenic activities of AsA and its degradation products by utilizing insulin as a model polypeptide. The results showed that the half-life of AsA varied with the pH of the medium and the incubation temperature. The degradation products of AsA inhibited insulin fibrillation, with an activity positively correlated to the degree of AsA degradation. The degradation species, compared with intact AsA, also showed a stronger disruptive effect on mature amyloid fibrils and significantly decreased fibrillar cytotoxicity. Dehydroascorbic acid and diketogulonic acid, two key intermediates in AsA degradation, had similar anti-amyloidogenic activity toward the degradation species of AsA. The results of this work indicate that degradation of natural antioxidants must be considered when evaluating their anti-amyloidogenic effects. These insights into the action of AsA may also provide a novel route to understand its physiological/pharmacological roles in amyloid-related diseases.


Site-directed mutagenesis of the heme axial ligands in the hemoflavoenzyme cellobiose dehydrogenase.
Cellobiose dehydrogenase (CDH) from Phanerochaete chrysosporium is an extracellular 90-kDa hemoflavoenzyme, organized into an N-terminal heme domain and a C-terminal flavin domain. The amino acid residues Met65 and His114 or His163 were suggested to be heme iron ligands. Mutations of these residues were made and mutant proteins were characterized. H114A mutant cultures produce a stable hemoflavoenzyme with spectral and kinetic characteristics similar to those of wild-type CDH. The M65A and H163A transformants secrete a 90-kDa hemoflavoenzyme, which oxidizes cellobiose in the presence of 2,6-dichlorophenol-indophenol (DCPIP), but is unable to reduce cytochrome c. The heme domains of the M65A and H163A CDH variants are, however, unstable and susceptible to degradation, both yielding a 70-kDa cellobiose-oxidizing flavoenzyme. The spectral and kinetic characteristics of these truncated variants suggest that they contain only their respective flavin domains. The yield of the 90-kDa proteins was low and the proteins could not be purified to homogeneity; however, absorption spectra indicate that the 90-kDa proteins do contain the heme domain. Like the truncated flavoenzymes, the 90-kDa variants reduce DCPIP but are unable to transfer electrons to cytochrome c, in contrast to wild-type CDH. These findings suggest that H163 and M65 are the axial heme ligands and that both ligands are required for the reactivity and structural integrity of the heme domain.


Role of the CDC25 homology domain of phospholipase Cepsilon in amplification of Rap1-dependent signaling.
Phospholipase Cepsilon (PLCepsilon) is a novel class of phosphoinositide-specific PLC characterized by possession of CDC25 homology and Ras/Rap1-associating domains. We and others have shown that human PLCepsilon is translocated from the cytoplasm to the plasma membrane and activated by direct association with Ras at its Ras/Rap1-associating domain. In addition, translocation to the perinuclear region was induced upon association with Rap1.GTP. However, the function of the CDC25 homology domain remains to be clarified. Here we show that the CDC25 homology domain of PLCepsilon functions as a guanine nucleotide exchange factor for Rap1 but not for any other Ras family GTPases examined including Rap2 and Ha-Ras. Consistent with this, coexpression of full-length PLCepsilon or its N-terminal fragment carrying the CDC25 homology domain causes an increase of the intracellular level of Rap1.GTP. Concurrently, stimulation of the downstream kinases B-Raf and extracellular signal-regulated kinase is observed, whereas the intracellular level of Ras.GTP and Raf-1 kinase activity are unaffected. In wild-type Rap1-overexpressing cells, epidermal growth factor induces translocation of PLCepsilon to the perinuclear compartments such as the Golgi apparatus, which is sustained for at least 20 min. In contrast, PLCepsilon lacking the CDC25 domain translocates to the perinuclear compartments only transiently. Further, the formation of Rap1.GTP upon epidermal growth factor stimulation exhibits a prolonged time course in cells expressing full-length PLCepsilon compared with those expressing PLCepsilon lacking the CDC25 homology domain. These results suggest a pivotal role of the CDC25 homology domain in amplifying Rap1-dependent signal transduction, including the activation of PLCepsilon itself, at specific subcellular locations such as the Golgi apparatus.


Cerebral blood flow and blood volume in response to O2 and CO2 changes in normal humans.
Changes in cerebral blood volume (CBV) after head injury may be an important determinant of intracranial pressure (ICP). To determine the normal response of CBV to hypoxemia, hypercapnia, and hypocapnia, eight normal subjects (5 males and 3 females; ages 25 to 43) were studied under these conditions. Cerebral blood volume was measured using an external collimated gamma detector to determine 99m-Tc-labeled red blood cell (RBC) activity in the intracranial vascular pool, and cerebral blood flow (CBF) was determined by internal carotid artery duplex scanning. Hypocapnia (Paco2 = 26.0 +/- 1.7 mm Hg, mean +/- SE) was achieved by hyperventilation, hypercapnia (Paco2 = 47.8 +/- 1.5 mm Hg) was achieved by inhalation of 6% CO2, and hypoxemia (Pao2 = 38.1 +/- 1.1 mm Hg, O2 saturation = 76.7 +/- 2.0%) was achieved by inhalation of 10% O2. Changes in CBF and CBV were determined by comparing the values in each condition to the immediately preceding period of normoxia and normocapnia. For conditions of hypocapnia, hypercapnia, and hypoxemia, the percentage of change in CBV was: -7.2 +/- 0.01, 12.8 +/- 0.01, and 5.2 +/- 0.03, respectively. The simultaneous percentage of change in CBF for the same conditions was -30.7 +/- 4.0, 29.5 +/- 9.2, and 18.4 +/- 6.9, respectively. For all conditions, changes in CBF were greater than changes in CBV; however, this was most pronounced during hypocapnia induced by hyperventilation. Because the change in CBV reflects the potential change in ICP in response to treatment, therapeutic hyperventilation may impair CBF to a greater degree than it reduces ICP.(ABSTRACT TRUNCATED AT 250 WORDS)


An Expanded View of Joint Attention: Skill, Engagement, and Language in Typical Development and Autism.
This study provides an expanded view of joint attention and its relation to expressive language development. A total of 144 toddlers (40 typically developing, 58 with autism spectrum disorder [ASD], 46 with developmental delay [DD]) participated at 24 and 31 months. Toddlers who screened positive for ASD risk, especially those subsequently diagnosed with ASD, had poorer joint attention skills, joint engagement during parent-toddler interaction, and expressive language. Findings highlight the dynamic relation between joint attention and language development. In the ASD and DD groups, joint engagement predicted later expressive vocabulary, significantly more than predictions based on joint attention skills. Joint engagement was most severely impacted when toddlers did not talk initially and improved markedly if they subsequently began to speak.


Development of a scale to measure discomfort during pregnancy.
During pregnancy fundamental changes occur in a woman's body that make physical discomforts almost unavoidable. Extensive literature searches revealed that there was no psychometrically acceptable tool available to assess accurately maternal physical discomfort. This paper presents the procedures undertaken to develop the Maternal Physical Discomfort Scale (MPDS), an assessment instrument designed to quantify the type and number of maternal physical discomforts. The MPDS, a scale consisting of 36 items, was developed and psychometrically evaluated using factor analysis, item response theory and reliability measures. The initial version of the scale was validated by a sample of 307 pregnant women. Based on the result from this sample, the MPDS was modified to 33 items and validated by a further sample of 125 pregnant women. The MPDS developed in this study was demonstrated to have content and construct validity and to be reliable.


Interim Estimates of 2021-22 Seasonal Influenza Vaccine Effectiveness - United States, February 2022.
In the United States, annual vaccination against seasonal influenza is recommended for all persons aged ≥6 months except when contraindicated (1). Currently available influenza vaccines are designed to protect against four influenza viruses: A(H1N1)pdm09 (the 2009 pandemic virus), A(H3N2), B/Victoria lineage, and B/Yamagata lineage. Most influenza viruses detected this season have been A(H3N2) (2). With the exception of the 2020-21 season, when data were insufficient to generate an estimate, CDC has estimated the effectiveness of seasonal influenza vaccine at preventing laboratory-confirmed, mild/moderate (outpatient) medically attended acute respiratory infection (ARI) each season since 2004-05. This interim report uses data from 3,636 children and adults with ARI enrolled in the U.S. Influenza Vaccine Effectiveness Network during October 4, 2021-February 12, 2022. Overall, vaccine effectiveness (VE) against medically attended outpatient ARI associated with influenza A(H3N2) virus was 16% (95% CI = -16% to 39%), which is considered not statistically significant. This analysis indicates that influenza vaccination did not reduce the risk for outpatient medically attended illness with influenza A(H3N2) viruses that predominated so far this season. Enrollment was insufficient to generate reliable VE estimates by age group or by type of influenza vaccine product (1). CDC recommends influenza antiviral medications as an adjunct to vaccination; the potential public health benefit of antiviral medications is magnified in the context of reduced influenza VE. CDC routinely recommends that health care providers continue to administer influenza vaccine to persons aged ≥6 months as long as influenza viruses are circulating, even when VE against one virus is reduced, because vaccine can prevent serious outcomes (e.g., hospitalization, intensive care unit (ICU) admission, or death) that are associated with influenza A(H3N2) virus infection and might protect against other influenza viruses that could circulate later in the season.


A novel effective method for the assessment of microvascular function in male patients with coronary artery disease: a pilot study using laser speckle contrast imaging.
Evaluation of microvascular endothelial function is essential for investigating the pathophysiology and treatment of cardiovascular and metabolic diseases. Although laser speckle contrast imaging technology is well accepted as a noninvasive methodology for assessing microvascular endothelial function, it has never been used to compare male patients with coronary artery disease with male age-matched healthy controls. Thus, the aim of this study was to determine whether laser speckle contrast imaging could be used to detect differences in the systemic microvascular functions of patients with established cardiovascular disease (n=61) and healthy age-matched subjects (n=24). Cutaneous blood flow was assessed in the skin of the forearm using laser speckle contrast imaging coupled with the transdermal iontophoretic delivery of acetylcholine and post-occlusive reactive hyperemia. The maximum increase in skin blood flow induced by acetylcholine was significantly reduced in the cardiovascular disease patients compared with the control subjects (74 vs 116%; P<0.01). With regard to post-occlusive reactive hyperemia-induced vasodilation, the patients also presented reduced responses compared to the controls (0.42±0.15 vs 0.50±0.13 APU/mmHg; P=0.04). In conclusion, laser speckle contrast imaging can identify endothelial and microvascular dysfunctions in male individuals with cardiovascular disease. Thus, this technology appears to be an efficient non-invasive technique for evaluating systemic microvascular and endothelial functions, which could be valuable as a peripheral marker of atherothrombotic diseases in men.


Synthesis, Molecular Docking, and Antimalarial Activity of Hybrid 4-Aminoquinoline-pyrano[2,3-c]pyrazole Derivatives.
Widespread resistance of Plasmodium falciparum to current artemisinin-based combination therapies necessitate the discovery of new medicines. Pharmacophoric hybridization has become an alternative for drug resistance that lowers the risk of drug-drug adverse interactions. In this study, we synthesized a new series of hybrids by covalently linking the scaffolds of pyrano[2,3-c]pyrazole with 4-aminoquinoline via an ethyl linker. All synthesized hybrid molecules were evaluated through in vitro screenings against chloroquine-resistant (K1) and -sensitive (3D7) P. falciparum strains, respectively. Data from in vitro assessments showed that hybrid 4b displayed significant antiplasmodial activities against the 3D7 strain (EC50 = 0.0130 ± 0.0002 μM) and the K1 strain (EC50 = 0.02 ± 0.01 μM), with low cytotoxic effect against Vero mammalian cells. The high selectivity index value on the 3D7 strain (SI > 1000) and the K1 strain (SI > 800) and the low resistance index value from compound 4b suggested that the pharmacological effects of this compound were due to selective inhibition on the 3D7 and K1 strains. Molecular docking analysis also showed that 4b recorded the highest binding energy on P. falciparum lactate dehydrogenase. Thus, P. falciparum lactate dehydrogenase is considered a potential molecular target for the synthesized compound.


Effectiveness of dispatcher instructions-dependent or independent bystander cardiopulmonary resuscitation on neurological survival among patients with out-of-hospital cardiac arrest.
We evaluated the association between survival and bystandercardiopulmonary resuscitation (CPR) with or without dispatcher instructions (DI) considering the time from emergency call receipt by the dispatch center to emergency medical services (EMS) personnel's contact with the patient (i.e. time to EMS arrival). This prospective study conducted in Osaka City, Japan, from 2009 to 2015 included patients with medical cause-related out-of-hospital cardiac arrest who were ≥18 years old. The primary outcome was one-month favorable neurological survival. Using multiple logistic regression models, the adjusted odds ratios (AOR) of independent and DI-dependent CPR for the primary outcome were compared with no CPR. Adjustments were made for patients' age, sex, activities of daily living before the cardiac arrest, year of cardiac arrest, location, presence or absence of witnesses, etiology of cardiac arrest, and the time from EMS contact with the patient to patient's arrival at the hospital. The effective estimated "time to EMS arrival" was also calculated. For analyses 10,925 individuals were eligible. Independent CPR had a significantly higher one-month favorable neurological survival than no CPR whereas there was no significant difference between DI-dependent CPR and no CPR (AOR, 1.90 [1.47-2.46] and 1.16 [0.91-1.47], respectively). The estimated "time to EMS arrival" for a one-month favorable neurological survival after independent CPR was ≤13min. Bystander CPR that did not need DI was associated with significantly higher one-month favorable neurological survival than no CPR, with an effective estimated "time to EMS arrival" of ≤13min.


Perceived Need for Mental Health Care and Associated Factors and Outcomes in Older Adults Consulting in Primary Care.
To assess the individual and health system factors and health-related outcomes associated with perceived need for mental health care in older adults consulting in primary care. This longitudinal cohort study was conducted among 771 cognitively intact older adults aged ≥65 years recruited in primary care practices in Quebec between 2011 and 2013 and followed 4 years later. Predisposing, enabling and need factors were based on Andersen's framework on help-seeking behaviors. Health-related outcomes included course of common mental disorders (CMDs), change in quality of life and societal costs. Perceived need for care (PNC) was categorized as no need, met and unmet need. Multinomial regression analyses were conducted to assess the association between study variables and PNC in the overall and the subsample of participants with a CMD at baseline. As compared with individuals reporting no need, those with an unmet need were more likely to have cognitive decline and lower continuity of care; while those with a met need were more likely to report decreased health-related quality of life. As compared with individuals with an unmet need, those reporting a met need were more likely to report ≥ 3 physical diseases and an incident and persistent CMD, and less likely to show cognitive decline. In participants with a CMD, individuals reporting a met as compared with no need were more likely to be categorized as receiving minimally adequate care and a persistent CMD. Need for care was not associated with societal costs related to health service use. Overall, physicians should focus on individuals with cognitive impairment and lower continuity of care which was associated with unmet mental health need. Improved follow-up in these populations may improve health care needs and outcomes.


Comparison of captopril-thiazide and enalapril-thiazide combinations in the management of mild to moderate black hypertensive patients: how important is diuretic dose and duration of action of the ACE-inhibitor?
A double-blind, randomized, parallel-group study was performed to compare the efficacy and tolerability of captopril-thiazide and enalapril-thiazide combinations. After a 3-week placebo run-in period, 47 Black patients with mild to moderate essential hypertension (mean 24-hour diastolic blood pressure (BP) > 90 mmHg and < 115 mmHg) were randomized to receive 1 of 2 combination tablets: captopril 50 mg plus hydrochlorothiazide 25 mg (CAP, n = 24) or enalapril 20 mg plus hydrochlorothiazide 12.5 mg (COR, n = 23) once daily. After 12 weeks of active treatment the mean 24-hour ambulatory BP was reduced from 152 +/- 11/99 +/- 6 to 133 +/- 13/86 +/- 7 mmHg (p < 0.005) in the CAP group and 157 +/- 15/100 +/- 6 to 141 +/- 18/90 +/- 12 in the COR group (p < 0.005). Target BP (24-hour diastolic BP < 90 mmHg) was achieved in 75% (18/24) of patients on CAP and 48% (11/23) on COR (p = n.s.). 24-hour BP load fell significantly with both CAP (from 69% to 34%, p < 0.001) and COR (from 67% to 37%, p < 0.001). Left ventricular mass index decreased by 7% with CAP and 11% with COR. Cardiac index and fractional shortening remained essentially unchanged in both groups. Both treatments were well tolerated and overall incidence of side effects was very low. It is concluded that both CAP and COR are effective, safe first-line antihypertensive choices in Black patients with mild to moderate hypertension with the former showing a trend towards greater efficacy than the latter.


Midwifery-led care can lower caesarean section rates according to the Robson ten group classification system.
Midwifery-led care is recognised as the best choice of maternity care for low-risk women. Robson's Ten Group Classification System (TGCS) is an internationally recognised audit tool, however there is no midwifery-led service presenting their statistics in this way. The objective of this study was to analyse caesarean section rates for the women attending midwifery-led care at the National Maternity Hospital Dublin, Ireland, using the Robson TGCS. This is a retrospective study of electronic records for a total of 1097 women who were booked to attend the community midwife team in the National Maternity Hospital, during 2016 and 2017. The rate of caesarean section in low-risk nulliparous women (Robson Group 1) was under 6%, without affecting the perinatal outcome. The induction rate in nulliparous women (Group 2) was 36%, less than the national average the cesarean rates were quadruple in this group. Low-risk women who attend midwifery-led services, have a low caesarean section rate in this study. This was achieved with continuity of care, good antenatal preparation, and support throughout labour and birth by a dedicated team of midwives. Outcomes can only be truly compared if we use the same criteria to measure them. The TGCS demonstrates the effectiveness of midwifery-led care.


A test for determining endurance capacity in fencers.
Until now endurance in fencers has been tested by non-specific ergometer tests even though the movement patterns during fencing are considerably different. The aim of the study was to evaluate a newly developed fencing-specific endurance test (FET). 2 studies were carried out: 28 fencers were tested by FET with fencing-specific footwork and incremental tests on cycle (CE) and treadmill ergometer (TM) in a random order. Afterwards fencing bouts (BOU) were conducted to determine specific physical load. Blood lactate and heart rates were measured. In a second study another group of 18 international and 20 national level fencers conducted FET to explore differences between groups. Comparison of CE, TM, FET and BOU revealed a significant correlation between FET and BOU (r=0.80, p<0.01), heart rates during CE and TM were significantly lower than in bouts (p<0.01). Performance at CE and TM hardly correlated with FET (r=0.30, p<0.05; r=0.31, p<0.05). Elite-fencers showed significantly better performance than non-elite fencers in FET (p<0.01). FET was suitable for determining specific endurance in fencers, allows a better assessment of physical demands during bouts than conventional ergometry and can be used to distinguish between fencers of different levels.


Dissection of the genetic architecture of peduncle vascular bundle-related traits in maize by a genome-wide association study.
The peduncle vascular system of maize is critical for the transport of photosynthetic products, nutrients, and water from the roots and leaves to the ear. Accordingly, it positively affects the grain yield. However, the genetic basis of peduncle vascular bundle (PVB)-related traits in maize remains unknown. Thus, 15 PVB-related traits of 386 maize inbred lines were investigated at three locations (Yongcheng, 17YC; Kaifeng, 20KF; and Yuanyang, 20YY). The repeatability for the 15 traits ranged from 35.53% to 92.13%. A genome-wide association study was performed and 69 non-redundant quantitative trait loci (QTL) were detected, including 9, 41, and 27 QTL identified at 17YC, 20KF, and 20YY, respectively. These QTL jointly explained 4.72% (SLL) to 37.30% (NSVB) of the phenotypic variation. Eight QTL were associated with the same trait at two locations. Furthermore, four pleiotropic QTL were identified. Moreover, one QTL (qPVB44), associated with NSVB_20KF, was co-localized with a previously reported locus related to kernel width, implying qPVB44 may affect the kernel width by modulating the number of small vascular bundles. Examinations of the 69 QTL identified 348 candidate genes that were classified in five groups. Additionally, 26 known VB-related homologous genes (e.g. VLN2, KNOX1, and UGT72B3) were detected in 20 of the 69 QTL. A comparison of the NSVB between a Zmvln2 EMS mutant and its wild type elucidated the function of the candidate gene ZmVLN2. These results are important for clarifying the genetic basis of PVB-related traits and may be useful for breeding new high-yielding maize cultivars.


Efficiency and accuracy of disease monitoring systems: application of capture-recapture methods to injury monitoring.
Capture-recapture methods were employed to determine the most accurate and efficient approaches to monitor adolescent injuries. Multiple sources were used to ascertain cases of adolescent injuries that occurred between September 1 and December 31, 1991, in a single school district in metropolitan Pittsburgh, Pennsylvania. Eliminating the duplicate cases between the sources revealed 144 verified injuries; 127 (88.2%) were identified by student monthly recalls, 33 (22.9%) by daily attendance records, 58 (40.3%) by medical excuses, and 72 (50.0%) by a 4-month student recall. Capture-recapture analyses were undertaken to assess potential dependencies between the sources, to estimate the degree of underascertainment in the population, and to evaluate the efficiency of the individual sources and the combinations between them. It was estimated that 91% of the cases in the population were ascertained when all four methods of case finding were utilized. Furthermore, the analysis indicated that accurate injury estimates could be achieved using combinations of only two or three of the sources. An analysis of the efficiency of the methods of ascertainment revealed a trade-off between effort (the number of hours needed to identify cases) and the precision (coefficient of variation) of the injury estimates. Capture-recapture analysis not only provided an approach to evaluate and adjust for undercount but also offered a formal means to evaluate the most efficient combination of the sources to maximize completeness while minimizing effort. The use of these techniques has the potential to evaluate and improve injury surveillance as well as other disease monitoring systems.