Chronic kidney disease among greenhouse workers and field workers in China.
Agricultural workers are at increased risk of developing chronic kidney disease of non-traditional etiology (CKDnt). The environment in solar greenhouse has high-intensity agricultural hazard factors. However, the association between solar greenhouse work and CKDnt remains unknown. We aimed to evaluate the relationship among solar greenhouse work, field work, and CKDnt risk, and to explore gender differences in CKDnt risk among solar greenhouse workers. Solar greenhouse workers and field workers were selected as the greenhouse worker and field worker groups in a cross-sectional study. Individuals with an estimated glomerular filtration rate (eGFR) of <60 ml/min per 1.73 m2 were defined as CKDnt patients. Binary logistic regression and generalized linear regression models were used to estimate the association among solar greenhouse workers, field workers and CKDnt. Furthermore, gender differences in CKDnt were also analyzed. A total of 638 solar greenhouse workers and 231 field workers were included. The prevalence of CKDnt was 2.8% in the solar greenhouse workers and 0.4% in the field workers, and the prevalence of CKDnt was higher in female solar greenhouse workers than in males. The eGFR reduced by 20.0% (19.74 ml/min per 1.73 m2) in the greenhouse worker group compared with that in the field worker group (p < 0.05). Generalized linear analysis showed that the level of eGFR was lower in women than that in men after adjusting for parameters (β = -10.99 [-12.79, -9.10]). Solar greenhouse workers may be at an increased risk of CKDnt, and women are more vulnerable.


Coadministration of gallic acid abates zearalenone-mediated defects in male rat's reproductive function.
As gallic acid (GA) role in zearalenone (ZEN); mediated reproductive dysfunction has not been studied, we report on GA's effect on reproductive dysfunction in rats treated with ZEN-100 µg/kg alone, or with GA-40 mg/kg; for 4 weeks. The mycotoxin ZEN contaminates crops, causing toxicity on ingestion, economic losses, and alters reproductive function. Relative to control, GA reversed ZEN-induced reduction of rats' testicular function enzymes and reproductive hormones and improved ZEN-impaired sperm quality. GA significantly (p < 0.05) increased rats antioxidant status, inhibited (p < 0.05) reactive oxygen and nitrogen species and lipid peroxidation levels, and abated (p < 0.05) proinflammatory biomarkers in the examined organs: hypothalamus, testis, and epididymis. Histopathology revealed that GA facilitated the preservation of testicular and epididymal cytoarchitecture significantly altered in rat cohorts treated with ZEN alone. Conclusively, GA protected against ZEN-induced toxicity in the rats' organs examined, enhanced endogenous antioxidative protective mechanism, and abated proinflammatory responses. GA further averted a decline in circulatory, reproductive enzymes, hormone levels. GA also protected against reproductive tissue damage and improved parameters of sperm functionality.


The organization of the sphingosine 1-phosphate signaling system.
The understanding of the role of the sphingosine 1-phosphate signaling system in immunology and host defense has deepened exponentially over the past 12 years since the discovery that lymphocyte egress was reversibly modulated by sphingosine 1-phosphate receptors, and with the development of fingolimod, a prodrug of a nonselective S1P receptor agonist, for therapeutic use in the treatment of relapsing, remitting multiple sclerosis. Innovative genetic and chemical approaches, together with structural biology, now provide a more detailed molecular understanding of a regulated lysophospholipid ligand with a variety of autocrine, paracrine, and systemic effects in physiology and pathology, based upon selective interactions with a high affinity and selective evolutionary cluster of G-protein-coupled receptors.


AHR agonistic effects of 6-PN contribute to potential beneficial effects of Hops extract.
Hops (Humulus lupulus) is used as an alternative to hormone replacement therapy due to the phytoestrogen, 8-prenylnaringenin (8-PN). To examine the potential risks/benefits of hops extract and its compounds (8-PN and 6-prenylnaringenin, 6-PN), we aimed to evaluate the estrogen receptor α (ERα) and aryl hydrocarbon receptor (AHR) signaling pathways in human endometrial cancer cells. Hops extract, 8-PN and 6-PN showed estrogenic activity. Hops extract and 6-PN activated both ERα and AHR pathways. 6-PN increased the expression of the tumor suppressor gene (AHRR), and that of genes involved in the estrogen metabolism (CYP1A1, CYP1B1). Although 6-PN might activate the detoxification and genotoxic pathways of estrogen metabolism, hops extract as a whole only modulated the genotoxic pathway by an up-regulation of CYP1B1 mRNA expression. These data demonstrate the relevant role of 6-PN contained in the hops extract as potential modulator of estrogen metabolism due to its ERα and AHR agonist activity.


Combined Diagnostic Significance of Preoperative Serum β2-Microglobulin and Routine Blood Test in Patients with High-grade Glioma and Solitary Brain Metastasis.
High-grade glioma (HGG) and solitary brain metastasis (sBM) patients show similar symptoms in clinical practice, and accurately differential diagnosis directly affects the management and prognosis of patients. The aim of this study was to distinguish two entities by preoperative serum β2-microglobulin (β2-m) and routine blood test-associated inflammatory indexes including, white blood cell (WBC), neutrophils, lymphocytes, monocytes, and platelets count, red cell distribution width (RDW), platelet distribution width (PDW), neutrophil/lymphocyte ratio (NLR) and monocyte/lymphocyte ratio (MLR). A retrospective analysis was performed in the Cancer Hospital of the University of Chinese Academy of Sciences from January 2015 to December 2019, including 127 patients of newly pathologically diagnosed with HGG and 174 patients with sBM. Clinical information including age, gender, pathological diagnosis, preoperative serum β2-m and routine blood tests were collected, and NLR and MLR were calculated. The diagnostic significance of these markers for HGG and sBM was assessed by receiver operating characteristic (ROC) curves. The patients with sBM had significantly higher values of preoperative age, β2-m, NLR and MLR as well as lower lymphocytes count than patients with HGG. Besides, the area under the curve (AUC) in differentiating HGG from sBM was 0.625 (95%CI: 0.561-0.689) for age, 0.655 (0.594-0.717) for β2-m, 0.634 (0.571-0.698) for NLR and 0.622 (0.559-0.686) for MLR, and the combination of Age+β2-m+NLR+MLR showed the best diagnostic performance with AUC of 0.731 (0.675-0.788) and 0.048*Age+0.001*β2-m+0.201*NLR+0.594*MLR>5.813 could indicate sBM rather than HGG. The Age+β2-m+NLR+MLR combination was revealed as an inexpensive and noninvasive biomarker for differentiating between HGG and sBM before surgery.


Spastic paraplegia as the only symptom in two adult-onset patients carrying a novel pathogenic variant in PYCR2.
A novel pathogenic PYCR2 variant and corresponding brain images in two patients characterized by spastic paraplegia.


Erratum: Factors influencing patient falls in a private hospital group in the Cape Metropole of the Western Cape.
[This corrects the article DOI: 10.4102/hsag.v25i0.1392.].


Improving health care delivery for persons with multiple sclerosis.
Persons with multiple sclerosis (MS) have a close-to-normal life span and can look forward to a high level of consumption of health care services for an average of 40 to 50 years. As expensive new treatments for MS are developed and better rehabilitation techniques are implemented, lifetime health care costs for MS patients can be very great. This article discusses ways in which these costs can be managed.


Adding ReputationRank to member promotion using skyline operator in social networks.
To identify potential stars in social networks, the idea of combining member promotion with skyline operator attracts people's attention. Some algorithms have been proposed to deal with this problem so far, such as skyline boundary algorithms in unequal-weighted social networks. We propose an improved member promotion algorithm by presenting ReputationRank based on eigenvectors as well as Influence and Activeness and introduce the concept of skyline distance. Furthermore, we perform skyline operator over non-skyline set and choose the infra-skyline as our candidate set. The added ReputationRank helps a lot to describe the importance of a member while the skyline distance assists us to obtain the necessary condition for not being dominated so that some meaningless plans can be pruned. Experiments on the DBLP and WikiVote datasets verify the effectiveness and efficiency of our proposed algorithm. Treating the infra-skyline set as candidate set reduces the number of candidates. The pruning strategies based on dominance and promotion cost decrease the searching space.


Impact of Functional vs Anatomic Complete Revascularization in Coronary Artery Bypass Grafting.
This study was conducted to evaluate the impact of functional and anatomic complete revascularization on long-term clinical outcomes after coronary artery bypass grafting (CABG). Of 2034 patients who underwent primary isolated CABG between 2006 and 2017, 1162 patients who underwent off-pump CABG for 3-vessel disease and for whom data on functional and anatomic completeness of revascularization were available on the basis of preoperative myocardial single photon emission computed tomography and early postoperative graft angiography were enrolled. The median follow-up duration was 82.4 months (interquartile range, 50.8-122.4 months). Univariate and multivariate analyses were performed to evaluate the impact of the functional and anatomic completeness of revascularization on long-term survival. Of 1162 patients, anatomic complete revascularization was achieved in 1014 patients (87.3%), whereas functional complete revascularization was achieved in 1077 patients (92.7%). Early mortality occurred in 7 patients. Late death occurred in 322 of 1155 early survivors. The 5- and 10-year overall survival rates were 84.3% and 66.7%, respectively. Univariate analyses demonstrated that functional completeness of revascularization was a statistically significant risk factor (P = .038), whereas anatomic completeness was not (P = .859). The multivariate analysis showed that functional completeness of revascularization (hazard ratio, 1.54; 95% CI, 1.08-2.22; P = .019) and age, underweight status, diabetes mellitus, chronic kidney disease, chronic obstructive pulmonary disease, and left ventricular dysfunction were significant factors associated with long-term survival. Functional rather than anatomic completeness of revascularization has a significant impact on the long-term survival in patients who undergo CABG.


[Characteristics of the action of an acidic sulfated polysaccharide on global blood coagulation in vitro. Preliminary study in various species of mammals and in man].
An acid sulphated polysaccharide, isolated from a red marine seaweed, Asparagopsis armata ( Harv .), increases the coagulation time of the plasma in vitro studies. This property, compared with the anticoagulant activity of pentosan polysulphate and heparin, pr esents , with concentration and temperature, some variations in man and other mammals . The rat and human plasma seem to behave in the same way with this substance.


Progressive multifocal leukoencephalopathy associated with a lymphoproliferative disorder treated with pembrolizumab.
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease affecting the central nervous system as a result of reactivation of the John Cunningham (JC) polyomavirus and occurs almost exclusively in immunosuppressed individuals. The disease course of PML is variable but usually progressive and often fatal. Treatment is predominantly focused on immune restoration, although this is difficult to do outside of human immunodeficiency virus-associated PML. A recent case series demonstrated a potential role for programmed cell death protein 1 (PD-1) inhibitors, such as pembrolizumab, to contain and/or clear JC virus. Herein, we discuss the first reported Australian case of a 61-year-old female with PML secondary to chemoimmunotherapy demonstrating complete clearance of JC virus as well as clinical and radiological stabilisation following pembrolizumab treatment.


The effects of growth inhibitory peptide on follicular thyroid cancer cell growth, migration, and invasion.
Thyroid cancer is the most common endocrine neoplasm worldwide. Although differentiated thyroid cancers are associated with a favorable survival, the prognosis worsens dramatically for patients with distant metastasis. Metastases from follicular thyroid carcinoma (FTC) occur earlier and are more aggressive than those from papillary thyroid carcinoma. For FTC that is resistant to radioactive iodine, new treatments are urgently needed. Human alpha-fetoprotein (HAFP) is a tumor-associated fetal protein that has been demonstrated to regulate tumorigenesis. Growth inhibitory peptide (GIP), a synthetic 34-mer peptide isolated from the third domain of HAFP, has been shown to have antitumor growth ability in various human cancers. However, the effects of GIP in FTC have not yet been studied. The aim of this study was to investigate the antitumor ability of GIP in FTC. Using both PBS and GIP control peptide as a negative control, the antiproliferative activity of GIP in the WRO human FTC cell line was determined using a tetrazolium-based colorimetric assay. In addition, cell migration and invasion assays were used to measure tumor metastasis inhibition effects in vitro. GIP did not inhibit WRO cell proliferation in a time- or dose-dependent manner. However, in WRO cells treated with GIP for 4 days, migration was significantly inhibited at concentrations of 50 and 100 microM (33.3% and 19.5%, respectively; both P <0.05). Cell invasion was also significantly inhibited at 50 and 100 microM (67.1% and 39.0%, respectively; both P<0.05). Although GIP failed to suppress FTC cell growth, it effectively interrupted both FTC cell migration and invasion abilities in vitro. Further validation in an animal model and elucidation of the underlying mechanisms will be required. GIP may potentially serve as an anti-FTC metastasis agent aiding current chemotherapy regimens.


Design of a breast phantom for quantitative MRI.
We present a breast phantom designed to enable quantitative assessment of measurements of T1 relaxation time, apparent diffusion coefficient (ADC), and other attributes of breast tissue, with long-term support from a national metrology institute. A breast phantom was created with two independent, interchangeable units for diffusion and T1 /T2 relaxation, each with flexible outer shells. The T1 unit was filled with corn syrup solution and grapeseed oil to mimic the relaxation behavior of fibroglandular and fatty tissues, respectively. The diffusion unit contains plastic tubes filled with aqueous solutions of polyvinylpyrrolidone (PVP) to modulate the ADC. The phantom was imaged at 1.5T and 3.0T using magnetic resonance imaging (MRI) scanners and common breast coils from multiple manufacturers to assess T1 and T2 relaxation time and ADC values. The fibroglandular mimic exhibited target T1 values on 1.5T and 3.0T clinical systems (25-75 percentile range: 1289 to 1400 msec and 1533 to 1845 msec, respectively) across all bore temperatures. PVP solutions mimicked the range of ADC values from malignant tumors to normal breast tissue (40% PVP median: 633 × 10(-6) mm(2) /s to 0% PVP median: 2231 × 10(-6) mm(2) /s) at temperatures of 17-24°C. The interchangeable phantom units allowed both the diffusion and T1 /T2 units to be tested on the left and right sides of the coil to assess any variation. This phantom enables T1 and ADC measurements, fits in a variety of clinical breast coils, and can serve as a quality control tool to facilitate the standardization of quantitative measurements for breast MRI. J. Magn. Reson. Imaging 2016;44:610-619.


Sequential class switching is required for the generation of high affinity IgE antibodies.
IgE antibodies with high affinity for their antigens can be stably cross-linked at low concentrations by trace amounts of antigen, whereas IgE antibodies with low affinity bind their antigens weakly. In this study, we find that there are two distinct pathways to generate high and low affinity IgE. High affinity IgE is generated through sequential class switching (μ→γ→ε) in which an intermediary IgG phase is necessary for the affinity maturation of the IgE response, where the IgE inherits somatic hypermutations and high affinity from the IgG1 phase. In contrast, low affinity IgE is generated through direct class switching (μ→ε) and is much less mutated. Mice deficient in IgG1 production cannot produce high affinity IgE, even after repeated immunizations. We demonstrate that a small amount of high affinity IgE can cause anaphylaxis and is pathogenic. Low affinity IgE competes with high affinity IgE for binding to Fcε receptors and prevents anaphylaxis and is thus beneficial.


Rapid increase of cytosolic content of acetyl-CoA carboxylase isoforms in H9c2 cells by short-term treatment with insulin and okadaic acid.
Mammalian acetyl-CoA carboxylase (ACC) is present in two isoforms, alpha and beta, both of which catalyze formation of malonyl-CoA by fixing CO2 into acetyl-CoA. ACC-alpha is highly expressed in lipogenic tissues whereas ACC-beta is a predominant form in heart and skeletal muscle tissues. Even though the tissue-specific expression pattern of two ACC isoforms suggests that each form may have a distinct function, existence of two isoforms catalyzing the identical reaction in a same cell has been a puzzling question. As a first step to answer this question and to identify the possible role of ACC isoforms in myogenic differentiation, we have investigated in the present study whether the expression and the subcellular distribution of ACC isoforms in H9c2 cardiac myocyte change so that malonyl-CoA produced by each form may modulate fatty acid oxidation. We have observed that the expression levels of both ACC forms were correlated to the extent of myogenic differentiation and that they were present not only in cytoplasm but also in other subcellular compartment. Among the various tested compounds, short-term treatment of H9c2 myotubes with insulin or okadaic acid rapidly increased the cytosolic content of both ACC isoforms up to 2 folds without affecting the total cellular ACC content. Taken together, these observations suggest that both ACC isoforms may play a pivotal role in muscle differentiation and that they may translocate between cytoplasm and other subcellular compartment to achieve its specific goal under the various physiological conditions.


Building a quality index for soils impacted by proximity to an industrial complex using statistical and data-mining methods.
Differences in soil quality indices, in terms of the inherent properties of loess parent material and the potential for Zn, Pb and Cd contamination from the emissions of an adjacent large industrial complex, were determined. A set of independent variables was established for the soils, using principal component analysis (PCA) and a random forest (RF) method. The quality indices of 140 topsoil samples from the environs of an industrial complex were compared with those of reference soils taken from around the borders of the study area. Potential driving factors for the Zn, Pb and Cd concentrations were dehydrogenase activity (DHA), urease (Ure) activity and invertase activity (IA), C, N, K2O, MgO, P2O5 and soil clay content. Maps were generated to show the spatial distributions of the Zn, Pb and Cd contamination. Enrichment factors and potential ecological risks were calculated. We established that, in general, concentrations of Zn, Pb and Cd in the topsoil decreased with increasing distance from the industrial complex, and the levels of Zn and Cd exceeded established intervention values, even in some soils on arable land. The arable land was enriched in P2O5, while the highest values for K2O and MgO were found in wasteland soils. The mean C content of all the soils was about 2%, with N (about 0.2%), C/N ratio (about 12) and pH (about 6.9) in the order: arable land<meadow<wasteland. The highest DHA and Ure activity was determined in the reference (unpolluted) soils, while much higher IA was present in the wasteland soils. PCA model focused on factors connected with different soil uses, while RF model emphasised the natural resistance of the studied soils to degradation. Our results indicate that the driving factors of the soil quality index were controlled by the inherent properties of the loess parent material, rather than soil pollution.


Lack of age effects on human brain potentials preceding voluntary movements.
We examined age effects on Movement related potentials (MRPs) in 13 young (mean age = 29.3 years) and 13 old (mean age = 67.2 years) normal adults in right, left and bimanual self-paced button press conditions. Both the groups generated a slowly rising readiness potential (RP) at about 1000 ms, a negative shift (NS') at about 450 ms and a motor potential (MP) at about 100 ms prior to movement. The RP was symmetrical, bilaterally distributed and maximal at the vertex in all conditions in both the groups. Both the groups produced contralaterally enhanced NS' and MP components in unimanual conditions. In contrast to prior reports, topographical distribution, onset latency and mean amplitude were comparable between young and old subjects for the RP, NS' and MP components of the MRP. The results indicate that motor programming as indexed by MRPs is unaffected by normal aging.


Axillary node status in breast cancer patients prior to surgery by imaging with Tc-99m humanised anti-PEM monoclonal antibody, hHMFG1.
In early breast cancer axillary nodes are usually impalpable and over 50% of such patients may have an axillary clearance when no nodes are involved. This work identifies axillary node status by imaging with a Tc-99m radiolabelled anti-Polymorphic Epithelial Mucin, humanised monoclonal antibody (human milk fat globule 1), prior to surgery in 30 patients. Change detection analysis of image data with probability mapping is undertaken. A specificity of 93% and positive predictive value of 92% (both 100% if a second cancer in the axilla with negative nodes is considered) were found. A strategy for combining negative imaging with the sentinel node procedure is presented.


Congenital pigmented and vascular lesions in newborn infants.
The incidence of congenital cutaneous lesions was ascertained by a single dermatologist in each of 830 sequential newborn infants over a 3-month period at the Oklahoma Teaching Hospitals. Lesions were observed in 57% of infants (77% of blacks and 49% of nonblacks). Vascular lesions were the most frequent, occurring in 44% of neonates. Pigmented lesions other than mongolian spots were observed in 15.8% of blacks and in 1.6% of whites. Clinical criteria do not readily distinguish nevus cell nevi from other pigmented lesions. Wood's light examination did not enhance the identification of congenital lesions. Inadequate examination of infants and marked underreporting of congenital lesions in newborn infants are widespread.


Noradrenergic neurotoxin suppresses gonadotropin-releasing hormone (GnRH) and GnRH receptor gene expression in ovariectomized and steroid-treated rats.
The present study was designed to investigate whether noradrenergic neurotransmission regulates the gene expression of gonadotropin-releasing hormone (GnRH) in the preoptic area and GnRH receptor in the pituitary. To this end, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4, 50 mg/kg), an intraperitoneal (i.p.) injection of selective noradrenergic neurotoxin, was administered 1 h before progesterone (1 mg) treatment in ovariectomized and estradiol-treated prepubertal rats. Treatment with DSP4 effectively blocked the progesterone-induced increase in hypothalamic noradrenaline content, but not dopamine content, indicating that DSP4 selectively inhibits noradrenergic neurotransmission. DSP4 significantly blocked progesterone-induced increase in serum luteinizing hormone (LH) concentrations as well as GnRH release from hypothalamic fragments incubated in vitro. DSP4 concomitantly down-regulated GnRH mRNA levels in the preoptic area, as determined by competitive reverse transcription-polymerase chain reaction. DSP4 also clearly down-regulated progesterone-induced GnRH receptor mRNA levels in the pituitary, whereas it failed to alter LHbeta mRNA levels. In summary, blockade of noradrenergic neurotransmission with DSP4 resulted in profound reductions of hypothalamic GnRH and pituitary GnRH receptor gene expression.


On-the-Edge Anchor Placement May Be Protective Against Glenoid Rim Erosion After Arthroscopic Bankart Repair Compared to On-the-Face Anchor Placement.
This retrospective study aimed to compare the effects of 2 different anchoring placements on glenoid rim erosion after arthroscopic Bankart repair (ABR). Shoulders that underwent ABR from January 2013 to July 2020 were divided into 2 groups according to anchor placement (on-the-face, group F; on-the-edge, group E). We retrospectively calculated the percent change of glenoid width (Δ) on the first postoperative computed tomography scan (CT; performed within 6 months) and second postoperative CT (performed at 6 to 12 months) relative to the width on the preoperative CT and compared percent changes between the 2 groups. Also, we investigated the influence of preoperative glenoid structures (normal, erosion, bony Bankart) and the postoperative recurrence rate. We examined 225 shoulders in 214 patients (group F, n = 151; group E, n = 74). At first CT, anchoring placement was significantly associated with postoperative decrease of glenoid width (group F, -7.6% ± 7.9%; group E, -0.1% ± 9.7%; P < .0001). The difference between groups F and E was significant in shoulders with a preoperative glenoid defect (bony Bankart, -6.6% ± 8.8% vs 2.5% ± 11.2%, respectively; P < .0001; erosion, -6.6% ± 6.2% vs -2.6% ± 5.3%, respectively; P = .03). In 112 shoulders, CT was performed twice; Δ was -6.9% ± 7.3% in group F (n = 64) and -1.7% ± 10.1% in group E (n = 48; P = .005) at the first CT and -3.2% ± 10.0% and 1.0% ± 10.6% (P = .10), respectively, at the second CT, indicating recovery of glenoid width in both groups. The postoperative recurrence rate in patients with at least 2 years' follow-up was 14.7% in group F and 14.6% in group E. In the early stage after ABR, on-the-edge glenoid anchor placement was associated with less glenoid rim erosion than on-the-face anchor placement. Level III, retrospective comparative trial.


A neuronal subsystem in the cat's area 18 lacks retinotopy.
Single neurones were recorded extracellularly in the visual cortex of anaesthetized and paralyzed cats. In all parts of area 18, neurones with diffuse receptive fields (DRFs) were found. DRFs measured at least 50 degrees in diameter and always included the area centralis and large parts of the ipsi- and contralateral hemifeld; some DRFs even covered the entire visual field. DRF neurones gave phasic responses to diffuse light, and to light spots either presented stationary or moved rapidly across the field; they were not orientation- or direction-sensitive. In contrast to the majority of area 18 neurones, which are part of a retinotopically organized system, DRF neurones constitute a subsystem with only poor retinotopy, or no retinotopy at all. This system might be suitable for detecting sudden changes in global illumination.


Stimulatory and inhibitory effects of hydrogen peroxide, diamide and vitamin K-5 on sugar transport in rat soleus muscle.
The experiments examined the stimulatory effects of H2O2, diamide and vitamin K-5 on the uptake of D-[U-14C]xylose by rat soleus muscle. All three oxidants stimulated sugar transport to the same extent, which was 30-40% of the maximal stimulatory effect of insulin (0.1 U/ml). Maximum stimulation was achieved with vitamin K-5 (0.01-0.1 mM), diamide (0.3 mM) and H2O2 (5-10 mM); at these concentrations the oxidants did not affect muscle ATP levels. Cytochalasin B (5 microM) abolished oxidant-stimulated xylose uptake. Catalase (20 U/ml) abolished the stimulatory effect of H2O2, but did not affect diamide- or vitamin K-5-stimulated transport. The ability of oxidants to stimulate sugar transport in anaerobic muscle could be demonstrated in short term (30 min) experiments, where muscle contained about 50% of its original ATP, but not after 120 min, when ATP levels were depleted. Oxidant-stimulated sugar transport was diminished and even abolished at supra-optimal oxidant concentrations; at these higher concentrations muscle ATP levels were lowered. All three oxidants inhibited the stimulatory effect of 2,4-dinitrophenol on sugar transport; this effect could be demonstrated using those oxidant concentrations which induced maximal stimulation of basal xylose uptake and which did not affect muscle ATP. It is concluded that: (1) H2O2, diamide and vitamin K-5 stimulate stereospecific sugar transport in soleus muscle by some mechanism other than lowering of ATP levels; (2) stimulation of sugar transport by oxidants is an ATP-dependent process; (3) some oxidant-sensitive sulphydryl group is critically involved in the process which activates muscle sugar transport.


Discovery of a highly potent CECR2 bromodomain inhibitor with 7H-pyrrolo[2,3-d] pyrimidine scaffold.
Cat eye syndrome chromosome region candidate 2 (CECR2) bromodomain is a module of CECR2-containing remodeling factor (CERF), which is a chromatin remodeling complex correlating with transcriptional control and adjustment of chromatin architecture. Potent chemical probes would be beneficial to gain insights into the biochemical and pharmacological functions of CECR2 BRD. Herein, we report the discovery of a series of CECR2 BRD inhibitors with 7H-pyrrolo[2,3-d] pyrimidine scaffold based on molecular docking model of TP-248 and CECR2 BRD. The most potent inhibitor of this series, DC-CBi-22 with IC50 of 8.0 ± 1.4 nM against CECR2 BRD and selectivity over BPTF BRD up to 24.9-fold. The SARs were detailed according to molecular docking. DC-CBi-22 would serve as a useful chemical probe for the study of CECR2.


Prognostic significance of E-cadherin and Cox 2 expression in Tunisian patients with colorectal mucinous adenocarcinoma.
Mucinous colorectal carcinoma (MC) is a rare subtype of colorectal adenocarcinoma known to be associated with bad prognosis. Lately, research has turned to identify new prognostic markers allowing the use of targeted therapy. The aim of our study is to evaluate the prognostic impact of E-cadherin and Cox-2expression in MC. A total of 40 formalin-fixed, paraffin-embedded MC specimens were collected within a period of 13 years and were studied for the expression of the two proteins. We used SPSS 22 software to study associations with clinicopathological parameters and overall survival (OS). A reduced or absent E-cadherin expression was noted in 52.5% of cases. It was associated with distant metastases (p = 0.049) and venous invasion (p = 0.049). Cox-2 was overexpressed in 17.5% of cases. It was associated with negative lymph node status (p = 0.020) and with early stage tumor (p = 0.020). A significant association between the two proteins was also noted (p = 0.04). No significant association with OS was found; However, there was an improvement in the survival of patients overexpressing Cox-2 (p = 0.16). Our findings link the loss of E-cadherin expression with spread and aggressiveness in MC and Cox-2 overexpression with better prognosis and survival. Because MC has a distinct genetic pathway we encourage the analysis of MSI and Cox-2 expression in all MC. Cox-2 inhibitors may not be effective chemopreventative agents in the setting of defective DNA mismatch repair. More molecular studies are needed to better understand the role of these markers and their prognostic significance in MC.


Positive words or negative words: whose valence strength are we more sensitive to?
The present study investigates the human brains' sensitivity to the valence strength of emotionally positive and negative chinese words. Event-Related Potentials were recorded, in two different experimental sessions, for Highly Positive (HP), Mildly Positive (MP) and neutral (NP) words and for Highly Negative (HN), Mildly Negative (MN) and neutral (NN) words, while subjects were required to count the number of words, irrespective of word meanings. The results showed a significant emotion effect in brain potentials for both HP and MP words, and the emotion effect occurred faster for HP words than MP words: HP words elicited more negative deflections than NP words in N2 (250-350 ms) and P3 (350-500 ms) amplitudes, while MP words elicited a significant emotion effect in P3, but not in N2, amplitudes. By contrast, HN words elicited larger amplitudes than NN words in N2 but not in P3 amplitudes, whereas MN words produced no significant emotion effect across N2 and P3 components. Moreover, the size of emotion-neutral differences in P3 amplitudes was significantly larger for MP compared to MN words. Thus, the human brain is reactive to both highly and mildly positive words, and this reactivity increased with the positive valence strength of the words. Conversely, the brain is less reactive to the valence of negative relative to positive words. These results suggest that human brains are equipped with increased sensitivity to the valence strength of positive compared to negative words, a type of emotional stimuli that are well known for reduced arousal.


Carotid endarterectomy without angiography does not compromise operative outcome.
Carotid angiography is associated with a 2% risk of stroke and, since the advent of colour-duplex ultrasound, its role in the assessment of patients with carotid disease has been the subject of debate. The aim of this study was to evaluate a policy of adopting routine duplex supplemented by selective angiography on operative outcome over a 5-year period. A prospective audit of the results of carotid endarterectomy without routine angiography from January 1992 to December 1996. Angiography was performed only if the ultrasonography was concerned about the distal or proximal extent of disease or to assess subocclusion. During the study period, 494 carotid endarterectomies were performed but only 35 patients underwent carotid angiography. The indications for angiography were subocclusion/string sign in 22 patients, to assess the limits of proximal or distal disease in 12 and abnormal anatomy in one. During the 5-year study period the overall perioperative death and/or stroke rate was 4.2%. By 1997, the perioperative stroke rate had fallen to 1.3%. In no case in this series was the operation abandoned due to unexpected findings. Although concerns exist about the precise duplex criteria for diagnosing a severe stenosis, this study has shown that a policy of selective angiography does not compromise patient safety or operability and avoids the unnecessary mortality, morbidity and costs associated with routine angiography.


Unified theoretical framework for black carbon mixing state allows greater accuracy of climate effect estimation.
Black carbon (BC) plays an important role in the climate system because of its strong warming effect, yet the magnitude of this effect is highly uncertain owing to the complex mixing state of aerosols. Here we build a unified theoretical framework to describe BC's mixing states, linking dynamic processes to BC coating thickness distribution, and show its self-similarity for sites in diverse environments. The size distribution of BC-containing particles is found to follow a universal law and is independent of BC core size. A new mixing state module is established based on this finding and successfully applied in global and regional models, which increases the accuracy of aerosol climate effect estimations. Our theoretical framework links observations with model simulations in both mixing state description and light absorption quantification.


Drp1 knockdown represses apoptosis of rat retinal endothelial cells by inhibiting mitophagy.
Diabetic retinopathy (DR) is the leading clinical cause of blindness in diabetic patients. Mitophagy participates in the pathogenesis of DR. Dynamin related protein 1 (Drp1) is associated with mitophagy. Here, we investigated whether Drp1 can regulate mitophagy to affect the progression of DR. We constructed DR rat model by administration of streptozocin. Primary rat retinal endothelial cells (RECs) were treated with high glucose (HG) as a DR cell model. Drp1 was highly expressed in the retinal tissues of DR rats and HG-treated RECs. Drp1 knockdown inhibited HG-mediated increase of reactive oxygen species (ROS) levels and apoptosis in RECs. Moreover, Drp1 silencing inhibited the expression of autophagy-related proteins LC3-II/LC3-1 and Beclin-1 and reduced LC3 puncta in HG-treated RECs. The expression of mitochondrial marker Tom20 was reduced and the levels of mitophagy were increased in the HG-treated RECs, which was rescued by Drp1 silencing. Drp1 knockdown repressed LC3-II expression in HG-treated RECs, indicating that autophagy flux was inhibited. Rapamycin (autophagy activator) enhanced ROS levels and apoptosis in HG-treated RECs by activating autophagy, which was rescued by Drp1 knockdown. In conclusion, these data demonstrated that Drp1 knockdown repressed apoptosis of rat retinal endothelial cells by inhibiting mitophagy. Thus, this work suggests that targeted regulation of Drp1 may become a treatment for DR.


Structure and function of the respiratory system of the dystrophic hamster.
The BIO 14.6 dystrophic hamster has been used extensively over the past 30 years as an animal model in which to study the mechanisms responsible for the development of cardiomyopathy and skeletal muscle dysfunction associated with muscular dystrophy. More recently, structural and functional aspects of the respiratory system of this animal model have been investigated. This review summarizes our current knowledge of ventilation, lung morphometry and mechanics, the structure and function of the diaphragm, tracheal and pulmonary vascular smooth muscle, and pulmonary macrophages in the BIO 14.6 dystrophic hamster. We conclude that many aspects of the structure and function of the respiratory system of this hamster warrant further investigation, including the development of alveolar hypoventilation, the causes of pulmonary vascular hyporeactivity, and the potential contribution of abnormal pulmonary macrophages to the pathogenesis of life-threatening respiratory disease in muscular dystrophy.


Bacteriology of infected burn wounds in the burn wards of a teaching hospital in Southwest Nigeria.
Burns are characterized by the loss of varying proportions of the protective layers of the skin, depression of immune responses, and increased wound susceptibility to infection. Wound infection is a major cause of morbidity and mortality in burn cases. This study characterizes those factors that predispose burn wounds to infection and the bacteriology of the microorganisms in our environment. Prospective study of burns patients that were admitted and treated at the Lagos State University Teaching Hospital (LASUTH), Ikeja-Lagos, Nigeria between January 1 and May 31, 2010 was carried out. Information about the demographics, aetiology/mechanism of burns, interval between the time of injury and admission, microbial studies, and antibiotic therapy were collected and analyzed. A total of 74 patients consisting of 43 males and 31 females were seen. The ages range between one week and 95 ± 22.42 years. Wound infections were confirmed in 28 patients (infection rate of 37.84 per 100 patients). Delayed presentation at LASUTH and length of hospital stay were significantly related to the development of wound infection. Pseudomonas aeruginosa and Proteus mirabilis were the most common infective organisms occurring in 53.6 and 10.7 percentages respectively. The isolated organisms were resistant to the beta-lactam antibiotics and mostly sensitive to carbapenem and aztreonam preparations. Factors predisposing to invasive wound infections in our environment were highlighted and suggestions made on methods that could reduce the infections and thus reduce morbidity and mortality in burns.


Soft lenses to protect the cornea after Fasanella ptosis surgery.
Soft lenses are used continuously for a prolonged period as a corneal protective device following unique under-lid surgery for ptosis correction. Until this procedure was employed, this excellent surgical technique had been all but abandoned.


Green preparation of activated carbon from pomegranate peel coated with zero-valent iron nanoparticles (nZVI) and isotherm and kinetic studies of amoxicillin removal in water.
In present research, the activated carbon was prepared by a green approach from pomegranate peel coated with zero-valent iron nanoparticles (AC-nZVI) and developed as adsorbent for the removal of amoxicillin from aqueous solution. The physicochemical properties of the AC-nZVI were investigated using XRD, FTIR, and FESEM techniques. The optimal values of the parameters for the best efficiency (97.9%) were amoxicillin concentration of 10 mg/L, adsorbent dose of 1.5 g/L, time of 30 min, and pH of 5, respectively. The adsorption equilibrium and kinetic data were fitted with the Langmuir monolayer isotherm model (qmax 40.282 mg/g, R2 0. 0.999) and pseudo-first order kinetics (R2 0.961). The reusability of the adsorbent also revealed that the adsorption efficiency decreased from 83.54 to 50.79% after five consecutive repetitions. Overall, taking into account the excellent efficiency, availability, environmental friendliness, and good regeneration, AC-nZVI can be introduced as a promising absorbent for amoxicillin from aquatic environments.


Changes in aortic endothelium ultrastructure in male rats following castration, replacement with testosterone and administration of 5alpha-reductase inhibitor.
To investigate the relationship between low androgen level and ultrastructure of vascular endothelium. Forty-eight male Sprague-Dawley rats were randomly divided into four groups: group A, normal rats with sham castration; group B, castrated rats; group C, castrated rats given testosterone (T) undecanoate; and group D, intact rats treated with 5alpha-reductase inhibitor. After 10 weeks of treatment or castration, rats in different groups were killed and serum T, free T (FT) and dihydrotestosterone (DHT) were measured. The aortic endothelia were scanned under electron microcopy and the Vascular Endothelium Structure Score (VESS) was computed. Serum T and FT concentrations of rats in group B were significantly lower than those of the other three groups (P < 0.01); DHT concentrations of group D rats were significantly decreased (P < 0.01) when compared with those of groups A and C. Rats in groups B and D rats (with low androgen levels) had obvious damage to their endothelial surfaces, which appeared crimpled, rough, adhesive and ruptured, and had high destruction of VESS. These results suggest that low concentrations of T and DHT are associated with ultrastructural damage of the aortic endothelia in male rats.


Androgens and transforming growth factor beta modulate the growth response to epidermal growth factor in human prostatic tumor cells (LNCaP).
Treatment of LNCaP human prostatic cancer cells with 0.1 nM of the synthetic androgen, R1881, resulted in a three-fold stimulation of growth in 6 days. Of several growth factors tested (epidermal growth factor (EGF), platelet-derived growth factor, insulin-like growth factor, and insulin) only EGF (1 ng/ml) stimulated cell growth (two-fold). This stimulatory effect of EGF was inhibited for approximately 70% by 0.02 ng transforming growth factor beta (TGF beta)/ml. EGF (1 ng/ml) acted synergistically with R1881 (0.1 nM) on LNCaP cells to induce cell proliferation (seven-fold increase in cell growth). The synergistic effect of androgen and EGF was inhibited by TGF beta (0.05 ng/ml). human prostatic LNCaP cells are sensitive to EGF. Androgen increases and TGF beta decreases the growth response to EGF. This effect of TGF beta on an androgen-responsive system has not been observed before.


CoVnita, an end-to-end privacy-preserving framework for SARS-CoV-2 classification.
Classification of viral strains is essential in monitoring and managing the COVID-19 pandemic, but patient privacy and data security concerns often limit the extent of the open sharing of full viral genome sequencing data. We propose a framework called CoVnita, that supports private training of a classification model and secure inference with the same model. Using genomic sequences from eight common SARS-CoV-2 strains, we simulated scenarios where the data was distributed across multiple data providers. Our framework produces a private federated model, over 8 parties, with a classification AUROC of 0.99, given a privacy budget of [Formula: see text]. The roundtrip time, from encryption to decryption, took a total of 0.298 s, with an amortized time of 74.5 ms per sample.


Community mental health ideology of preprofessional students.
Adherence to the ideology of mental health was measured in a cluster sample of preprofessional students in four majors: psychology, social work, rehabilitation and health education. Mean inventory scores for the four groups did not differ significantly.


The identification of glycoproteins associated with elastic-tissue microfibrils.
Cell cultures derived from foetal bovine ligamentum nuchae accumulate extracellular fibrils morphologically identical with elastic-tissue microfibrils. Two glycoproteins synthesized by the ligament cells are closely related to the matrix microfibrils as assessed by immunological and chemical extraction techniques.


Successful treatment of comorbid obsessive-compulsive disorder with aripiprazole in three patients with bipolar disorder.
Data on the efficacy of aripiprazole in obsessive-compulsive disorder (OCD), compared to data on the efficacy of other atypical antipsychotics, are inadequate. This report presents the successful treatment of concurrent OCD with aripiprazole in three patients with bipolar disorder (BD). Assessments performed with the Yale-Brown Obsessive-Compulsive Scale revealed significant reductions in OCD symptoms. Aripiprazole may be a beneficial psychotropic agent for the treatment of BD and OCD comorbidity, which is an important problem in clinical practice.


Antidromic-rectifying gap junctions amplify chemical transmission at functionally mixed electrical-chemical synapses.
Neurons communicate through chemical synapses and electrical synapses (gap junctions). Although these two types of synapses often coexist between neurons, little is known about whether they interact, and whether any interactions between them are important to controlling synaptic strength and circuit functions. By studying chemical and electrical synapses between premotor interneurons (AVA) and downstream motor neurons (A-MNs) in the Caenorhabditis elegans escape circuit, we found that disrupting either the chemical or electrical synapses causes defective escape response. Gap junctions between AVA and A-MNs only allow antidromic current, but, curiously, disrupting them inhibits chemical transmission. In contrast, disrupting chemical synapses has no effect on the electrical coupling. These results demonstrate that gap junctions may serve as an amplifier of chemical transmission between neurons with both electrical and chemical synapses. The use of antidromic-rectifying gap junctions to amplify chemical transmission is potentially a conserved mechanism in circuit functions.


Transcriptional activation of bacteriophage T4 middle promoters by the motA protein.
Transcriptional activation of middle genes in bacteriophage T4 requires the phage-encoded motA protein. Many middle genes are involved in deoxyribonucleotide biosynthesis and phage DNA replication. In the absence of motA, the gene products that are required for DNA synthesis are transcribed from other, upstream promoters. Using primer extension sequencing on RNA templates isolated from T4 motA+ and motA- infected cells, we have characterized 14 motA-dependent transcripts. The T4 middle promoters have a consensus sequence of nine base-pairs, (a/t)(a/t)TGCTT(t/c)A, spaced 11 to 13 nucleotides away from the Escherichia coli--10 consensus sequence, TAnnnT. The motA protein also can act as a transcriptional repressor for at least one early gene. Furthermore, the phage-encoded motA protein can activate in trans a middle promoter resident on a plasmid.


Expression of K2P channels in sensory and motor neurons of the autonomic nervous system.
Several types of neurons within the central and peripheral somatic nervous system express two-pore-domain potassium (K2P) channels, providing them with resting potassium conductances. We demonstrate that these channels are also expressed in the autonomic nervous system where they might be important modulators of neuronal excitability. We observed strong mRNA expression of members of the TRESK and TREK subfamilies in both the mouse superior cervical ganglion (mSCG) and the mouse nodose ganglion (mNG). Motor mSCG neurons strongly expressed mRNA transcripts for TRESK and TREK-2 subunits, whereas TASK-1 and TASK-2 subunits were only moderately expressed, with only few or very few transcripts for TREK-1 and TRAAK (TRESK ≈ TREK-2 > TASK-2 ≈ TASK-1 > TREK-1 > TRAAK). Similarly, the TRESK and TREK-1 subunits were the most strongly expressed in sensorial mNG neurons, while TASK-1 and TASK-2 mRNAs were moderately expressed, and fewer TREK-2 and TRAAK transcripts were detected (TRESK ≈ TREK-1 > TASK-1 ≈ TASK-2 > TREK-2 > TRAAK). Moreover, cell-attached single-channel recordings showed a major contribution of TRESK and TREK-1 channels in mNG. As the level of TRESK mRNA expression was not statistically different between the ganglia analysed, the distinct expression of TREK-1 and TREK-2 subunits was the main difference observed between these structures. Our results strongly suggest that TRESK and TREK channels are important modulators of the sensorial and motor information flowing through the autonomic nervous system, probably exerting a strong influence on vagal reflexes.


MEK inhibition induces caspases activation, differentiation blockade and PML/RARalpha degradation in acute promyelocytic leukaemia.
The hallmark of acute promyelocytic leukaemia (APL) is the reciprocal translocation t(15;17), which leads to the expression of the promyelocytic leukaemia/retinoic acid receptor alpha (PML/RARalpha) fusion protein and a cell differentiation blockade at the promyelocytic stage. PML/RARalpha is directly targeted by all-trans-retinoic acid (ATRA), which degrades the oncoprotein and induces complete remission of malignancies. The aberrant function of PML/RARalpha, together with the constitutive activation of the mitogen-activated protein/extracellular signal-regulated kinase (MEK/ERK) signalling pathway, regulates the ability of haematopoietic cells to proliferate, differentiate, and escape from apoptotic episodes. The role of the MEK/ERK pathway in PML/RARalpha expression, differentiation, proliferation and apoptosis in APL cells was analysed using specific MEK inhibitors. The blockade of MEK/ERK pathway resulted in caspase-dependent degradation of PML/RARalpha, and attenuation of the cell differentiation induction. To our knowledge, this is the first report to show that PML/RARalpha was suppressed by MEK/ERK inhibition, through a mechanism dependent on caspase activation. ATRA co-operated with MEK inhibitor to increase degradation of PML/RARalpha and exhibited a convergence point in caspase activation with MEK inhibitors. Taken together, our data suggest a new role of MEK/ERK pathway in the pathogenesis of APL, thus supporting the use of MEK/ERK inhibitors as an efficient therapeutic strategy for this haematological malignancy.


A simplified lysis method allowing the use of biotinylated probes in colony hybridization.
A method is described for the lysis of bacterial cells grown on nitrocellulose filters which allows the use of nonradioactive (biotin labeled) probes in colony hybridization. Used in conjunction with a colorimetric assay involving streptavidin and alkaline phosphatase this lysis method allows the detection of clones containing a target nucleic acid sequence. Sites of positive hybridization produce dark blue-purple signals, while nonreacting clones give very light blue signals. The occurrence of false-positive and background signals is minimal. With pBR322 as the target sequence it was possible to detect approximately 20 clones in the presence of 10(5) plasmid-free cells. It was also possible to detect low-frequency plasmid-free cells in a population of clones containing the target sequence.


Human memory T cell responses to SARS-CoV E protein.
E protein is a membrane component of severe acute respiratory syndrome coronavirus (SARS-CoV). Disruption of E protein may reduce viral infectivity. Thus, the SARS-CoV E protein is considered a potential target for the development of antiviral drugs. However, the cellular immune responses to E protein remain unclear in humans. In this study, we found that peripheral blood mononuclear cells (PBMCs) from fully recovered SARS individuals rapidly produced IFN-gamma and IL-2 following stimulation with a pool of 9 peptides overlapping the entire E protein sequence. Analysis of the immune responses by flow cytometry showed that both CD4+ and CD8+T cells were involved in the SARS-CoV E-specific immune responses after stimulation with SARS-CoV E peptides. Moreover, the majority of IFN-gamma+CD4+T cells were central memory cells expressing CD45RO+CCR7+CD62L-; whereas IFN-gamma+CD8+ memory T cells were mostly effector memory cells expressing CD45RO-CCR7-CD62L-. The results of T-cell responses to 9 individual peptides indicated that the E protein contained at least two major T cell epitopes (E2 amino acid [aa] 9-26 and E5-6: aa 33-57) which were important in eliciting cellular immune response to SARS-CoV E protein in humans.


Low calcium diet in dogs causes a greater increase in parathyroid function measured with an intact hormone than with a carboxylterminal assay.
The influence of low calcium diets (0.08%) with or without a deficiency in vitamin D (D) on the parathyroid function was studied in two groups of six dogs. The animals were first studied on a normal diet and then again after 3 weeks of the experimental diet. Blood tests, urine tests and a functional evaluation of the parathyroid glands via i.v. infusions of CaCl2 and NaEDTA were performed on both occasions. PTH was measured with an intact hormone assay (I) and with a carboxylterminal assay (C). Since similar results were observed on the D deficient and D normal diets at 3 weeks, data were combined for final analysis. We observed an increase in fasting serum PTH (I, 3.2 +/- 2.0 vs. 4.3 +/- 3.3 pmol/l, P less than 0.05; C, 23.4 +/- 13.9 vs. 30.7 +/- 15.5 pmol/l, P less than 0.005) and in stimulated serum PTH (I, 11.7 +/- 2.7 vs. 18.3 +/- 4.5 pmol/l, P less than 0.0005; C, 67.7 +/- 22 vs. 90.4 +/- 31.1 pmol/l, P less than 0.0005) after 3 weeks of a low calcium diet. Fasting ionized calcium concentrations (1.36 +/- 0.03 vs. 1.36 +/- 0.02 mmol/l), 25(OH)D concentrations (94.8 +/- 28 vs. 86.7 +/- 23.1 nmol/l) and 1,25(OH)2D concentrations (101.1 +/- 19.3 vs. 110.9 +/- 27.6 pmol/l) did not change. The increase in parathyroid function measured with I (60.4 +/- 39%) was greater than that measured with C (33.7 +/- 14.2%, P less than 0.05) and the ratio of maximum carboxylterminal PTH to maximum intact PTH decreased from 5.98 +/- 2.17 to 4.95 +/- 1.21 (P less than 0.05) at 3 weeks. These results suggest that reduced catabolism of intact PTH was involved in the increased parathyroid function. The stimulus responsible for the increased parathyroid function remains to be identified.


The economic burden of noncervical human papillomavirus disease in the United States.
The purpose of this study was (1) to estimate the direct medical costs of 7 major noncervical human papillomavirus (HPV)-related conditions that include genital cancers, mouth and oropharyngeal cancers, anogenital warts, and juvenile-onset recurrent respiratory papillomatosis, and (2) to approximate the economic burden of noncervical HPV disease. For each condition, we synthesized the best available secondary data to produce lifetime cost per case estimates, which were expressed in present value. Using an incidence-based approach, we then applied these costs to develop an aggregate measure of economic burden. The economic burden that was associated with noncervical HPV-6-, -11-, -16-, and -18-related conditions in the US population in the year 2003 approximates $418 million (range, $160 million to $1.6 billion). The economic burden of noncervical HPV disease is substantial. Analyses that assess the value of investments in HPV prevention and control programs should take into account the costs and morbidity and mortality rates that are associated with these conditions.


Leveraging thoughtful quality metric selection for individual and system improvements: the atypical category and use of dashboards.
Quality management is integral to the practice of cytopathology, especially given the heavily manual workflows and expanding ancillary testing requirements inherent to the cytopathology laboratory. Monitoring quality data like turnaround time, specimen unsatisfactory rates, and diagnostic category utilization rates allows for better understanding of performance with opportunities for targeted improvement if there are variations from that which is expected. However, there are costs to quality monitoring including the time and resources needed, and, in already taxed systems, quality management risks being viewed as just another box to check. While there are mandated quality metrics that must be collected by cytology laboratories, thoughtful selection of key performance indicators can be of tremendous benefit in helping to better understand complex laboratory processes and directing improvement endeavors where needed. The following short communication is a discussion on quality management in the cytopathology laboratory from 3 Cytopathology Quality Management Directors. The discussion focuses on monitoring the atypical reporting category with an emphasis on how trending and visualizing quality metrics can provide laboratories with key data.


Detection of daptomycin-nonsusceptible strains using the Neo-Sensitab prediffusion method.
Two prediffusion methods with daptomycin (DAP) Neo-Sensitabs were evaluated against a challenge set of 30 Staphylococcus aureus isolates and 30 enterococci. DAP Neo-Sensitabs were prediffused for either 8 or 20 h on Mueller-Hinton agar. Inhibition zones were plotted versus Etest MIC values determined on the same prediffused agar. A generalization to the genus level of the manufacturer's suggested Neo-Sensitabs breakpoints for staphylococci and enterococci was used to interpret the results. DAP-susceptible and DAP-nonsusceptible enterococci, Enterococcus faecium in particular, were not reliably discriminated using a 20-h prediffusion method and the manufacturer's suggested breakpoints. Further development of this testing methodology, such as changing the format to a susceptibility screen followed by a confirmatory MIC, is needed to accurately categorize the DAP susceptibility of enterococcal isolates. Prediffusion for either 8 or 20 h with DAP Neo-Sensitabs discriminated between susceptible and nonsusceptible S. aureus with minimal errors. Both prediffusion methods also detected changes in MIC values between isogenic pairs of susceptible and nonsusceptible S. aureus. These results suggest that a multisite evaluation of either prediffusion method with DAP Neo-Sensitabs against a larger collection of S. aureus is warranted.


Quantitative multi-parameter assessment of age- and gender-related variation of back extensor muscles in healthy adults using Dixon MR imaging.
Investigate sex differences in age-related back extensor muscle degeneration using Dixon MRI and analyze the relationship between quantitative muscle parameters and back muscle strength in healthy adults. 105 healthy subjects underwent lumbar Dixon MRI. Fat fraction (FF), cross-sectional area (CSA), functional CSA (FCSA), and relative FCSA (RFCSA) of multifidus muscle (MF) and erector spinae (ES) were quantified. Back extension muscle strength was measured using an external fixation dynamometer. ANOVA with post hoc Tukey correction was used for age group comparisons. Partial and Spearman's correlation analyzed relationships between age, muscle parameters, and muscle strength. MF and ES FF significantly increased with age in both genders (r = 0.55-0.85; p < 0.001). Muscle FF increased prominently for females (40-49 years, MF and 50-59 years, ES) and males (60-73 years, MF and ES). In females, total ES FCSA and RFCSA (r = - 0.42, - 0.37; p < 0.01) correlated with age. While in males, all MF and ES muscle size parameters, except total MF CSA, correlated with age (r = - 0.30 to - 0.58; p < 0.05). Back extension muscle strength correlated with mean FF, total CSA, and total FCAS for MF and ES individually (p < 0.001). The combined MF + ES FCSA correlation coefficient (r = 0.63) was higher than FF (r = - 0.51) and CSA (r = 0.59) (p < 0.001). Age-related back extensor muscle degeneration varies by muscle type and sex. FCSA has the highest association with back muscle strength compared to FF and CSA. The investigation of sex differences in age-related back extensor muscle degeneration utilizing Dixon imaging may hold significant implications for evaluating spine health and enabling earlier intervention. Muscles' FCSA could contribute to acquiring additional evidence for reflecting muscle function change. • The multifidus muscle (MF) and erector spinae (ES) fat fraction (FF) increased with age at all lumbar disc levels in females and males. • Age-related changes in muscle morphological quantitative parameters of healthy adults were specific by muscle type and gender. • The muscle functional cross-sectional area (FCSA) measured by Dixon imaging may better monitor back extensor muscle strength changes than muscle FF and cross-sectional area (CSA).


Effects of a virtual reality intervention on dementia care education among acute care nurses in Japan: A non-randomised controlled trial.
This study aimed to evaluate the effects of a virtual reality intervention for dementia care education in Japanese acute care nurses. Non-randomised controlled trial was used to assess the effectiveness of the intervention pre- and post-intervention and at a 1-month follow-up. This study enrolled 20 and 19 nurses in the intervention and control groups, respectively. Generalized estimating equation analyses revealed significant differences in scores on the Dementia Nursing Competency Scale in Acute Hospitals and Staff Experiences of Working with Dementia Residents questionnaire in the intervention group. A post hoc test revealed significantly higher scores on the Dementia Nursing Competency Scale in Acute Hospitals at 1 month after compared with pre-intervention. Staff Experiences of Working with Dementia Residents questionnaire scores were significantly lower at pre- than that at post-intervention and 1 month after intervention. These findings could improve competency of dementia nursing care and attitudes toward people with dementia.


When and How I Add Trochleoplasty in the Treatment of Recurrent Patella Instability.
Long experience and recent evidence suggest that trochleoplasty is needed in very few patella stabilization surgeries. As trochleoplasty adds risk, this author recommends it only in patients with high degrees of dysplasia, prominent supratrochlear spurs, ligamentous laxity, and more dramatic J signs.


Increased expression of the MBP mRNA binding protein HnRNP A2 during oligodendrocyte differentiation.
Heterogeneous nuclear ribonucleoprotein (hnRNP) A2, a trans-acting factor that mediates intracellular trafficking of myelin basic protein (MBP) mRNA to the myelin compartment in oligodendrocytes, is most abundant in the nucleus, but shuttles between the nucleus and cytoplasm. In the cytoplasm, it is associated with granules that transport mRNA from the cell body to the processes of oligodendrocytes. We found that the overall level of hnRNP A2 increased in oligodendrocytes as they differentiated into MBP-positive cells, and that this augmentation was reflected primarily in the cytoplasmic pool of hnRNP A2 present in the form of granules. The extranuclear distribution of hnRNP A2 was also observed in brain during the period of myelination in vivo. Methylation and phosphorylation have been implicated previously in the nuclear to cytoplasmic distribution of hnRNPs, so we used drugs that block methylation and phosphorylation of hnRNPs to assess their effect on hnRNP A2 distribution and mRNA trafficking. Cultures treated with adenosine dialdehyde (AdOx), an inhibitor of S-adenosyl-L-homocysteine hydrolase, or with 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB), a drug that inhibits casein kinase 2 (CK2), maintained the preferential nuclear distribution of hnRNP A2. Treatment with either drug affected the transport of RNA trafficking granules that remained confined to the cell body.


Gamma-irradiated dry fruits. An example of a wide variety of long-time dependent EPR spectra.
EPR spectra of dry, sugar containing fruits--raisins, sultanas, figs, dates, peaches, blue plums and chokeberry recorded before and after irradiation with gamma-rays, are reported. It is shown that weak singlet EPR line with 2.0031+/-0.0005 can be recorded before irradiation of seeds, stones or skin of chokeberry, figs and raisins as well as flesh of blue plum, raisins and peaches. EPR signals of various shape are distinguished after irradiation in different parts of the fruits, as well as in randomly cut pieces of them: As a result, randomly cut pieces of dry fruits suitable for EPR studies, containing various constituents, exhibit different in shape and intensity EPR spectra. Kinetic studies followed for 1 year on the time stability of all reported EPR signals indicate that intensity ratio between the simultaneously appearing EPR signals in particular fruit varies from 1:20 immediately after irradiation to 1:0.5 at the end of the period. These observations open a new possibility for identification of irradiated fruits - using the magnitude of the intensity ratio to find the approximate date of radiation processing in the first ca. 30-100 days.


SBDS interacts with RNF2 and is degraded through RNF2-dependent ubiquitination.
Shwachman-Diamond syndrome (SDS) is an autosomal recessive disorder caused by mutation in the Shwachman-Bodian-Diamond syndrome (SBDS) gene that has a variety of clinical features, including exocrine pancreatic insufficiency and hematological dysfunction. The SBDS protein is considered to be involved in ribosome biogenesis, ribosomal RNA metabolism, stabilization of mitotic spindles and cellular stress responses, yet the function of SBDS in detail is still incompletely understood. The multiple functions imply that certain proteins might associate with SBDS and affect its function. In this study, we identified Ring finger protein 2 (RNF2) as a candidate for the SBDS interactor by yeast two-hybrid screening. Moreover, we confirmed the interaction by GST-pull down assay using recombinant proteins and co-immunoprecipitation in HEK293T cells overexpressing RNF2. In addition, it is shown that RNF2 ubiquitinates SBDS and promotes its proteasomal degradation in HEK293T cells. These findings provide new insights into the regulation of SBDS.


A service evaluation of parent adherence with dysphagia management therapy guidelines: reports from family carers supporting children with complex needs in Greece.
Purpose: Many children with complex needs exhibit eating, drinking, and/or swallowing disorders (dysphagia). These children often have associated learning needs, and require assistance from carers for daily tasks such as eating and drinking. The aim of this study was to identify which strategies to manage dysphagia were challenging for family carers, and reasons for any non-adherence.Method: In this service evaluation researchers observed carers during mealtimes, and investigated carer opinions of strategies used to minimise the risks of dysphagia. Eight children with complex needs aged 3.4-7.5 years and their primary family caregiver participated.Results: Adherence with speech and language pathologists' dysphagia recommendations overall was over 50% in all but one case. For specific strategies, the highest adherence was observed for diet modifications of foods (89%), communication during the mealtime (83%), amount of food to present (81%), and the pacing of fluids and foods (81%). Lower levels of adherence were identified in relation to postural management (58%), environmental changes (58%), utensils (56%), and preparatory strategies (49%).Conclusions: Adherence with use of strategies to support mealtimes was over 50% in all but one case. Findings suggest that support is essential to promote safe mealtimes, reduce family carers' stress and increase knowledge, confidence, and adherence in implementing dysphagia guidelines in the family home. Implications for rehabilitationDifficulties with eating, drinking and swallowing (dysphagia) can impact on the parent-child mealtime experience.Mealtime strategies as recommended by a speech-language pathologist can support children who have difficulties eating, drinking, and swallowing.Some strategies to support eating, drinking, and swallowing are easier for carers to adhere to than others.


Long-term follow-up of allergic bronchopulmonary aspergillosis treated with glucocorticoids: A study of 182 subjects.
The long-term outcomes of allergic bronchopulmonary aspergillosis (ABPA) are poorly characterised. We retrospectively included treatment-naïve subjects of acute stage ABPA-complicating asthma from three randomised trials. All the subjects received oral prednisolone for 4 months and were monitored every 6 weeks for 6 months and then every 6 months. Our primary objective was to estimate the incidence rate and the frequency of subjects experiencing ABPA exacerbation. The key secondary objectives were to evaluate the factors predicting ABPA exacerbation and the changes in serum total IgE seen during treatment. We included 182 subjects. Eighty-one (44.5%) patients experienced 120 exacerbations during 512 patient-years of follow-up. The incidence rate of ABPA exacerbations was 234/1000 patient-years. Most (73/81, 90.1%) subjects experienced ABPA exacerbation within three years of stopping therapy. On multivariate logistic regression analysis, peripheral blood eosinophil count ≥1000 cells/μL (adjusted odds ratio [aOR] 2.43; 95% confidence interval (CI), 1.26-4.67), the extent of bronchiectasis (aOR 1.10; 95% CI, 1.03-1.18), age (aOR 0.97; 95% CI, 0.94-0.99), and female sex (aOR 2.16; 95% CI, 1.10-4.24) independently predicted ABPA exacerbation after adjusting for serum total IgE and high-attenuation mucus. The best cut-off for serum total IgE after 6 weeks for identifying treatment response and ABPA exacerbations was a 20% decline and a 50% increase, respectively. ABPA exacerbations were common within 3 years of stopping treatment. Age, female sex, peripheral blood eosinophilia and the extent of bronchiectasis predicted ABPA exacerbations. The optimal serum total IgE cut-off for defining ABPA response and exacerbations is a 20% decline and a 50% increase, respectively.


Efficient and highly selective iron-catalyzed reduction of nitroarenes.
Pyrolysis of iron-phenanthroline complexes supported on carbon leads to highly selective catalysts for the reduction of structurally diverse nitroarenes to anilines in 90-99% yields. Excellent chemoselectivity for the nitro group reduction is demonstrated.


Parathyroid hormone-related protein (PTHrP) gene expression in solid tumours associated with normocalcaemia and hypercalcaemia.
Parathyroid hormone-related protein (PTHrP) is an important humoral factor in the syndrome of humoral hypercalcaemia of malignancy (HHM) and its importance is evident by the many studies examining either PTHrP mRNA expression, intracellular peptide, or circulating PTHrP levels in patients with malignancy. However, the relationship between PTHrP mRNA expression, intracellular localization of peptide, and circulating PTHrP levels in the same group of patients with malignancy has not been examined. This study was carried out to explore this relationship in a group of patients with solid tumours associated with either normocalcaemia or hypercalcaemia. PTHrP mRNA and peptide were localized by in situ hybridization and immunohistochemistry respectively in 26 squamous carcinomas and 15 adenocarcinomas from patients who were either hypercalcaemic or normocalcaemic. Plasma PTHrP1-86 and serum PTH1-84 concentrations were measured by two-site immunoradiometric assays. PTHrP mRNA and peptide were localized in 11 (100 per cent) and 10 (91 per cent) of 11 squamous tumours from hypercalcaemic patients, all of whom had detectable circulating PTHrP levels, and in 14 (97 per cent) and 11 (73 per cent) respectively of 15 squamous tumours from normocalcaemic patients. PTHrP mRNA and peptide were localized in only two (28 per cent) and four (57 per cent) respectively of seven adenocarcinomas associated with hypercalcaemia. Since the majority of squamous tumours synthesized PTHrP irrespective of the calcium status of the patient, this suggests that the clinical expression of tumour-derived PTH-like bioactivity may depend on the rate of secretion of PTHrP rather than gene expression, and that the bioactivity of secreted PTHrP may be modulated by post-translational processing.


Association of Retinal Microvascular Signs with Incident Atrial Fibrillation: The Multi-Ethnic Study of Atherosclerosis.
Microvascular diseases may contribute to the occurrence of atrial fibrillation (AF). Retinal microvascular signs that are similar to other microvasculature in the body and can be visualized directly via ophthalmoscopy may provide insights into such a relationship. Prospective, longitudinal, multiethnic study. We examined the association between retinal microvascular signs and incident AF in 4994 participants 47 to 86 years of age and free of prior AF who underwent fundus photography from 2002 through 2004 and were followed up through 2015 in the Multi-Ethnic Study of Atherosclerosis (MESA). Retinal microvascular signs evaluated include central retinal arteriolar equivalent and central retinal venular equivalent (CRVE) and presence of any retinopathy signs (e.g., retinal microaneurysms or hemorrhages). A multivariate Cox regression analysis was used to determine the relationship while adjusting for traditional risk factors, alcohol intake, body mass index, diabetes status, chronic kidney disease status, hemoglobin A1c level, C-reactive protein level, medications, and prevalent cardiovascular diseases or heart failure. Incident AF events were identified using 12-lead electrocardiographic findings, hospital discharge records, and Medicare claims data. During a median follow-up of 14.1 years, 643 AF events were identified. No association was found between any retinal microvascular signs and incident AF except for retinal focal arteriolar narrowing (hazard ratio, 1.75; 95% confidence interval, 1.06-2.87) in the overall population. However, in the subgroup analyses by gender, wider CRVE was associated with a higher risk of incident AF in women, but not in men (hazard ratio for every 10-μm increase in CRVE, 1.08 [95% confidence interval, 1.01-1.15] and 0.97 [95% confidence interval, 0.92-1.03], respectively; P = 0.041 for interaction). No consistent pattern of association was found between retinal microvascular signs and incident AF. We observed an association in women, but not in men, of wider retinal venular calibers with incidence of AF. The reasons for a possible interaction are incompletely understood.


Prefrontal cortex and decision making in a mixed-strategy game.
In a multi-agent environment, where the outcomes of one's actions change dynamically because they are related to the behavior of other beings, it becomes difficult to make an optimal decision about how to act. Although game theory provides normative solutions for decision making in groups, how such decision-making strategies are altered by experience is poorly understood. These adaptive processes might resemble reinforcement learning algorithms, which provide a general framework for finding optimal strategies in a dynamic environment. Here we investigated the role of prefrontal cortex (PFC) in dynamic decision making in monkeys. As in reinforcement learning, the animal's choice during a competitive game was biased by its choice and reward history, as well as by the strategies of its opponent. Furthermore, neurons in the dorsolateral prefrontal cortex (DLPFC) encoded the animal's past decisions and payoffs, as well as the conjunction between the two, providing signals necessary to update the estimates of expected reward. Thus, PFC might have a key role in optimizing decision-making strategies.


Evaluation of Dosimetry Formalisms in Intraoperative Radiation Therapy of Glioblastoma.
The intraoperative radiotherapy in newly diagnosed glioblastoma multiforme (INTRAGO) clinical trial assesses survival in patients with glioblastoma treated with intraoperative radiation therapy (IORT) using the INTRABEAM. Treatment planning for INTRABEAM relies on vendor-provided in-water depth dose curves obtained according to the TARGeted Intraoperative radioTherapy (TARGIT) dosimetry protocol. However, recent studies have shown discrepancies between the estimated TARGIT and delivered doses. This work evaluates the effect of the choice of dosimetry formalism on organs at risk (OAR) doses. A treatment planning framework for INTRABEAM was developed to retrospectively calculate the IORT dose in 8 INTRAGO patients. These patients received an IORT prescription dose of 20 to 30 Gy in addition to external beam radiation therapy. The IORT dose was obtained using (1) the TARGIT method; (2) the manufacturer's V4.0 method; (3) the CQ method, which uses an ionization chamber Monte Carlo (MC) calculated factor; (4) MC dose-to-water; and (5) MC dose-to-tissue. The IORT dose was converted to 2 Gy fractions equivalent dose. According to the TARGIT method, the OAR dose constraints were respected in all cases. However, the other formalisms estimated a higher mean dose to OARs and revealed 1 case where the constraint for the brain stem was exceeded. The addition of the external beam radiation therapy and TARGIT IORT doses resulted in 10 cases of OARs exceeding the dose constraints. The more accurate MC calculation of dose-to-tissue led to the highest dosimetric differences, with 3, 3, 2, and 2 cases (out of 8) exceeding the dose constraint to the brain stem, optic chiasm, optic nerves, and lenses, respectively. Moreover, the mean cumulative dose to brain stem exceeded its constraint of 66 Gy with the MC dose-to-tissue method, which was not evident with the current INTRAGO clinical practice. The current clinical approach of calculating the IORT dose with the TARGIT method may considerably underestimate doses to nearby OARs. In practice, OAR dose constraints may have been exceeded, as revealed by more accurate methods.


Establishing the computer-patient working alliance in automated health behavior change interventions.
Current user interfaces for automated patient and consumer health care systems can be improved by leveraging the results of several decades of research into effective patient-provider communication skills. A research project is presented in which several such "relational" skills - including empathy, social dialogue, nonverbal immediacy behaviors, and other behaviors to build and maintain good working relationships over multiple interactions - are explicitly designed into a computer interface within the context of a longitudinal health behavior change intervention for physical activity adoption. Results of a comparison among 33 subjects interacting near-daily with the relational system and 27 interacting near-daily with an identical system with the relational behaviors ablated, each for 30 days indicate, that the use of relational behaviors by the system significantly increases working alliance and desire to continue working with the system. Comparison of the above groups to another group of 31 subjects interacting with a control system near-daily for 30 days also indicated a significant increase in proactive viewing of health information.


Factors complicating interpretation of capnography during advanced life support in cardiac arrest--a clinical retrospective study in 575 patients.
End tidal carbon dioxide (ETCO(2)) monitoring during advanced life support (ALS) using capnography, is recommended in the latest international guidelines. However, several factors might complicate capnography interpretation during ALS. How the cause of cardiac arrest, initial rhythm, bystander cardiopulmonary resuscitation (CPR) and time impact on the ETCO(2) values are not completely clear. Thus, we wanted to explore this in out-of-hospital cardiac arrested (OHCA) patients. The study was carried out by the Emergency Medical Service of Haukeland University Hospital, Bergen, Norway. All non-traumatic OHCAs treated by our service between January 2004 and December 2009 were included. Capnography was routinely used in the study, and these data were retrospectively reviewed together with Utstein data and other clinical information. Our service treated 918 OHCA patients, and capnography data were present in 575 patients. Capnography distinguished well between patients with or without return of spontaneous circulation (ROSC) for any initial rhythm and cause of the arrest (p<0.001). Cardiac arrests with a respiratory cause had significantly higher levels of ETCO(2) compared to primary cardiac causes (p<0.001). Bystander CPR affected ETCO(2)-recordings, and the ETCO(2) levels declined with time. Capnography is a useful tool to optimise and individualise ALS in cardiac arrested patients. Confounding factors including cause of cardiac arrest, initial rhythm, bystander CPR and time from cardiac arrest until quantitative capnography had an impact on the ETCO(2) values, thereby complicating and limiting prognostic interpretation of capnography during ALS.


Conformational changes in bacteriorhodopsin studied by infrared attenuated total reflection.
We report on a new method based on Fourier transform infrared (FTIR)-difference spectroscopy for studying the conformational changes occurring during the photocycle of bacteriorhodopsin. Previous studies have been made by measuring the absorbance of an infrared (IR) beam transmitted through a thin hydrated purple membrane film. In contrast, the present study utilizes the technique of attenuated total reflection (ATR). Purple membrane is fixed on the surface of a germanium internal reflection crystal and immersed in a buffer whose pH and ionic composition can be varied. Measurements of the amide I and II absorbance with light polarized parallel and at 45 degrees to the crystal surface reveals that the membrane is highly oriented. An ATR-FTIR-difference spectrum of the light to dark (bR570 to bR548) transition is similar but not identical to the transmittance FTIR-difference spectrum. This disagreement between the two methods is shown to be due in the ATR case to the absorption of transition moments oriented predominantly out of the membrane plane. Raising the pH of La3+ substituted purple membrane films from 6.8 to 8.0 slows the M-decay rate sufficiently so that a bR570 to M412 difference spectrum can be obtained with steady state illumination at room temperature. A comparison of this difference spectrum with that obtained at -23 degrees C using the transmittance method reveals several changes that cannot be attributed to out-of-plane transition moments. An increase in the intensity of peaks in the amide I and II regions agrees with recent time-resolved kinetic FTIR-difference measurements and indicates that a localized protein conformational change involving the peptide backbone of bR occurs which is not evident at the lower temperature.


[Effects of jingqianshu granule on expression of 5-HT(1A)R of PMS model rats with liver-qi stagnation].
To research the effect of the Jingqianshu granule (JQS) on the expression of serotonin receptor-1A (5-HT(1A)R) in hippocampus and hypothalamus of premenstrual syndrome (PMS) model rats with Liver-qi depression. The PMS model rats with Liver-qi depression were induced by bandaging the limbs. The model rats were treated with JQS, and evaluated by open-field test. The expression of 5-HT(1A)R in hippocampus and hypothalamus was analysed by the method of RT-PCR and Western blot. After the JQS were administered, the open field scores, the expression of 5-HT(1A)R mRNA and protein in hippocampus and hypothalamus of rats increased significantly. The JQS granule can up-regulate the expression of 5-HT(1A)R in hippocampus and hypothalamus, which maybe one of the mechanism to treat PMS with liver-qi depression.


Services for people at high risk improve outcomes in patients with first episode psychosis.
About one-third of patients referred to services for people at high risk for psychosis may have already developed a first episode of psychosis (FEP). We compared clinical outcomes in FEP patients who presented to either high risk or conventional mental health services. Retrospective study comparing duration of hospital admission, referral-to-diagnosis time, need for compulsory hospital admission and frequency of admission in patients with FEP who initially presented to a high-risk service (n = 164) to patients with FEP who initially presented to conventional mental health services (n = 2779). Regression models were performed, controlling for several confounders. FEP patients who had presented to a high-risk service spent 17 fewer days in hospital [95% CI: -33.7 to (-0.3)], had a shorter referral-to-diagnosis time [B coefficient -74.5 days, 95% CI: -101.9 to -(47.1)], a lower frequency of admission [IRR: 0.49 (95% CI: 0.39-0.61)] and a lower likelihood of compulsory admission [OR: 0.52 (95% CI: 0.34-0.81)] in the 24 months following referral, as compared to FEP patients who were first diagnosed at conventional services. Services for people at high risk for psychosis are associated with better clinical outcomes in patients who are already psychotic.


Immunization of salmonids against Yersinia ruckeri: significance of humoral immunity and cross protection between serotypes.
Brook trout (Salvelinus fontinalis) were immunized with bacterins containing either Serotype 1 or 2 isolates of Yersinia ruckeri to determine the relative degree of cross-protection afforded when the fish were challenged with the homologous or heterologous serotype. While fish immunized with pH-lysed bacterins produced highly specific agglutinins that did not cross-react with antigens derived from a heterologous serotype of Y. ruckeri all fish were protected against experimental challenge, regardless of which serotype was used for bacterin production and experimental challenge. Other experiments indicated that brook trout injected intraperitoneally with highly specific antibodies could not be passively immunized against experimental challenge.


Improving blood pressure estimation through internal and environmental feedback.
Different bodily sensations and situational factors covary with changes in systolic blood pressure (SBP). The present experiment explored whether an awareness of SBP-related cues could help individuals to estimate their own SBP levels more accurately. Sixty-four adults (53 women and 11 men) participated in two experimental sessions 3 months apart. Immediately following each of 13 task and intervening baseline periods of each of the two sessions, subjects estimated their SBP and rated the degree to which they were experiencing each of 10 physical symptoms and moods (i.e., internal cues). In addition, independent judges rated the extent to which various situational factors were present during each task and baseline. Within-subject correlations between internal and situational cues with SBP served as the basis for subjects' receiving one of four randomly assigned types of feedback: no feedback, internal cue feedback, situational cue feedback, or biosituational feedback based on both internal and situational cues. In the second experimental session 3 months later, subjects in the biosituational feedback condition were significantly better at estimating SBP than were individuals in any of the other conditions. Implications of biosituational feedback as an alternative to traditional biofeedback are discussed.


Electrocardiograph abnormalities in intracerebral hemorrhage.
This study investigated the prevalence and type of electrocardiography (ECG) abnormalities, and their possible association with the clinical/radiological findings in 118 consecutive patients with non-traumatic, non-neoplastic intracerebral hemorrhage (ICH). ECG frequently demonstrates abnormalities in patients with ischemic stroke and subarachnoid hemorrhage, but little is known of ECG changes in ICH patients. Clinical and radiological information was retrospectively reviewed. ECG recordings that were obtained within 24 hours of the initial hemorrhage were analyzed. Sixty-six patients (56%) had one or more ECG abnormalities. The most frequent was ST depression (24%), followed by left ventricular hypertrophy (20%), corrected QT interval (QTc) prolongation (19%), and T wave inversion (19%). The logistic regression analysis demonstrated the following: insular involvement was an independent predictive factor of ST depression (p<0.001; odds ratio OR 10.18; 95% confidence interval [CI] 2.84-36.57); insular involvement (p<0.001; OR 23.98; 95% CI 4.91-117.11) and presence of intraventricular hemorrhage (p<0.001; OR 8.72; 95% CI 2.69-28.29) were independent predictive factors of QTc prolongation; deep hematoma location (p<0.001; OR 19.12; 95% CI 3.82-95.81) and hematoma volume >30 ml (p=0.001; OR 6.58; 95% CI 2.11-20.46) were independent predictive factors of T wave inversion. We demonstrate associations between ECG abnormalities and detailed characteristics of ICH.


Fetal sex dependent hormone levels in early pregnant women with elevated maternal serum alpha-fetoprotein.
Maternal serum and amniotic hormone levels have been investigated in two groups of women in pregnancy weeks 18-21. One group (B) was composed of women with high alpha-fetoprotein levels in serum without fetal abnormality, and a matched control group (A) with normal alpha-fetoprotein levels in serum. Amongst group B women were four pregnancy complications: two spontaneous abortions, one premature delivery, and one cesarean section due to fetal asphyxia. Group B women were significantly different from group A women. Thus, higher maternal serum levels of total estriol (P = 0.030), testosterone (P = 0.016), and alpha-fetoprotein (P = 0.018) were noted in the presence of male fetuses; and higher hPL (P = 0.004), FSH (P = 0.037), and alpha-fetoprotein (P = 0.002) concentrations in women carrying female fetuses, who were accompanied by lower total estriol concentrations (P = 0.045). Differences between groups B and A in terms of amniotic fluid analyses were only related to female fetal sex. Thus, group B showed higher hPL (P = 0.028), testosterone (P = 0.020), and FSH (P = 0.006) levels, and lower alpha-fetoprotein (P = 0.013) concentrations. It is concluded that elevated maternal serum levels of alpha-fetoprotein are accompanied in female fetuses by an endocrine milieu different from that of matched controls. This difference may put the conceptus at a disadvantage, but the majority of the girls were born on time without signs of small-for-date.


Cochlear implants in deaf children.
This investigation was aimed to determine the current status of sensorineural hearing loss in children from the provinces of the Kingdom Saudi Arabia and to report on those with severe to profound hearing loss who are in need of cochlear implant. A comprehensive survey of 9540 Saudi children was carried out from September 1997 through to May 2000. The subjects were randomly selected from the 4 main provinces of the country. The main objective was to screen these children for hearing impairment. A survey team included an ear, nose and throat specialist, a nurse, a social worker and an audiologist. A questionnaire was completed; clinical examination and audiological assessment was performed. Those confirmed and in doubt cases were referred for further audiological and clinical assessment including computerized tomography scan and auditory brain stem response. The over all prevalence of hearing impairment was 13% (1241 out of 9540). Those with sensorineural hearing loss was 142 (1.5%) and those with severe to profound (76-100 decibels loss) was 68 (0.7%) 7 of them suffered from unilateral while 135 suffered from bilateral sensorineural hearing loss. The prevalence rate of severe to profound sensorineural hearing loss is high in our country compared to developed countries. Cochlear implant is a useful procedure for those with severe and profound sensorineural hearing loss but hearing aids must be tried first. There is definitely a requirement for additional hearing and speech centers to be available, which, are at least accessible in the big cities in each province.


Clinical evaluation of low-temperature thermoplasticized injectable gutta-percha: a preliminary report.
An injectable thermoplasticized gutta-percha system (Ultrafil) was used to fill 50 teeth which were monitored radiographically over a period of 24 months. An equal number of teeth were filled with the lateral condensation technique and used as controls. Radiographic evidence of success was determined at a 24-month recall. The results were subjected to a 2 x 2 analysis of variance (control versus experimental/before and after treatment. There was a significant amount of repair irrespective of obturation procedure (p greater than 0.0001). Thirteen teeth in the experimental group randomly filled with sealer showed that the sealer did not influence repair.


Immune complex transfer enzyme immunoassay for antibody IgM to HIV-1 p17 antigen.
The immune complex transfer enzyme immunoassay for antibody IgM to HIV-1 p17 antigen is described. Serum samples containing antibody IgM to HIV-1 p17 antigen were incubated simultaneously with 2,4-dinitrophenyl-bovine serum albumin-recombinant p17 (rp17) conjugate and rp17-beta-D-galactosidase conjugate, and the immune complex formed comprising the three components was trapped onto colored polystyrene beads coated with affinity-purified (anti-2,4-dinitrophenyl group) IgG. Subsequently, the immune complex was transferred to white polystyrene beads coated with monoclonal mouse (antihuman IgM) IgG in the presence of excess of epsilonN-2,4-dinitrophenyl-L-lysine. The signal for antibody IgM to p17 antigen was the fluorescence intensity by fluorometric assay of beta-D-galactosidase activity bound to the white polystyrene beads. The periods of time required for the formation, trapping, and transferring of the immune complex comprising the three components were more than 4 hr, 2 hr, and 3 hr, respectively. The immunoassay developed was shown to be specific by inhibition of transferring the immune complex in the presence of excess of nonspecific IgM but not IgG. Signals for antibody IgM to p17 antigen with serum samples of HIV-1 seroconversion serum panels,--that is, with serum samples in early stages of the infection--tended to be higher than those with serum samples from HIV-1 asymptomatic carriers probably long after the infection and patients with ARC and AIDS. In contrast, signals for antibody IgG to p17 antigen with serum samples of HIV-1 seroconversion serum panels tended to be higher than signals for antibody IgM to p17 antigen but were much lower than signals for antibody IgG to p17 antigen with serum samples from HIV-1 asymptomatic carriers and patients with ARC and AIDS.


Dietary intake of n-3 polyunsaturated fatty acids is inversely associated with CRP levels, especially among male smokers.
To examine whether dietary intake of n-3 polyunsaturated fatty acid (n-3PUFA) is associated with serum C-reactive protein (CRP) levels with regard to smoking status in the Japanese general population in a cross-sectional study. A total of 14,191 participants aged 40-69 years were enrolled and divided into quartile groups according to their intake of n-3PUFA. Multivariate-adjusted logarithm-transformed CRP levels were compared between the quartile groups with regard to smoking status after adjusting for traditional risk factors and intake of saturated fatty acids. Adjusted CRP levels were inversely associated with dietary intake of n-3PUFA for both the male subjects and female subjects (p<0.05 for trend). A linear trend was not seen between intake of n-3PUFA and adjusted CRP levels in male nonsmokers. Adjusted CRP level in the lowest quartile group of n-3PUFA was significantly higher than the levels in other groups in male smokers. Sufficient dietary intake of n-3PUFA may attenuate inflammatory reaction and this effect is more evident among high-risk populations such as male smokers although the small numbers of female ex-smokers and nonsmokers limited statistical power to draw strong conclusions about these groups.


Osteoid osteoma of the femoral neck: excision through medial approach.
An 11-year-old girl with osteoid osteoma of the medial femoral neck underwent excision of the lesion through a medial adductor approach. A satisfactory result was achieved without unsightly scarring or internal fixation. The medial adductor approach should be considered when osteoid osteoma of the femoral neck is encountered.