The Effects of Different Brain Regions on fNIRS-based Task-state Detection in Speech Imagery.
Brain-computer interface (BCI) based on speech imagery can decode users' verbal intent and help people with motor disabilities communicate naturally. Functional near-infrared spectroscopy (fNIRS) is a commonly used brain signal acquisition method. Asynchronous BCI can response to control commands at any time, which provides great convenience for users. Task state detection, defined as identifying whether user starts or continues covertly articulating, plays an important role in speech imagery BCIs. To better distinguish task state from idle state during speech imagery, this work used fNIRS signals from different brain regions to study the effects of different brain regions on task state detection accuracy. The imagined tonal syllables included four lexical tones and four vowels in Mandarin Chinese. The brain regions that were measured included Broca's area, Wernicke's area, Superior temporal cortex and Motor cortex. Task state detection accuracies of imagining tonal monosyllables with four different tones were analyzed. The average accuracy of four speech imagery tasks based on the whole brain was 0.67 and it was close to 0.69, which was the average accuracy based on Broca's area. The accuracies of Broca's area and the whole brain were significantly higher than those of other brain regions. The findings of this work demonstrated that using a few channels of Broca's area could result in a similar task state detection accuracy to that using all the channels of the brain. Moreover, it was discovered that speech imagery with tone 2/3 tasks yielded higher task state detection accuracy than speech imagery with other tones.


A chemogenomic screening identifies CK2 as a target for pro-senescence therapy in PTEN-deficient tumours.
Enhancement of cellular senescence in tumours triggers a stable cell growth arrest and activation of an antitumour immune response that can be exploited for cancer therapy. Currently, there are only a limited number of targeted therapies that act by increasing senescence in cancers, but the majority of them are not selective and also target healthy cells. Here we developed a chemogenomic screening to identify compounds that enhance senescence in PTEN-deficient cells without affecting normal cells. By using this approach, we identified casein kinase 2 (CK2) as a pro-senescent target. Mechanistically, we show that Pten loss increases CK2 levels by activating STAT3. CK2 upregulation in Pten null tumours affects the stability of Pml, an essential regulator of senescence. However, CK2 inhibition stabilizes Pml levels enhancing senescence in Pten null tumours. Taken together, our screening strategy has identified a novel STAT3-CK2-PML network that can be targeted for pro-senescence therapy for cancer.


Educational Cadaveric Module for Teaching Percutaneous and Intranasal Osteotomies in Rhinoplasty.
Lateral osteotomies are essential to rhinoplasty and are performed through percutaneous or intranasal approaches. Both techniques are difficult to teach as they rely on tactile feedback. Thus, it is critical to understand trainee learning curves to minimize complications. Herein, we aim to (1) demonstrate an educational module for teaching lateral osteotomies and (2) examine potential differences in outcomes between the 2 surgical approaches when performed by trainees. After a hands-on cadaveric laboratory, trainees (n = 24) reported increased confidence in performing both types of osteotomies ( P < .0001). Completion of the bony cut was similar between intranasal and percutaneous osteotomies (96% vs 75%, P = .097), as was correct placement of the osteotomy (75% vs 67%, P = .53). Intranasal osteotomies were more likely to cause periosteal disruption ( P = .02). This pilot study demonstrates that cadaveric laboratories are an effective way to teach lateral osteotomies and that percutaneous osteotomies may be less likely to cause periosteal disruption in trainees' hands.


Expression of the Voltage-Gated Potassium Channel Kv1.3 in Lesional Skin from Patients with Cutaneous T-Cell Lymphoma and Benign Dermatitis.
The voltage-gated potassium channel Kv1.3 (KCNA3) is expressed by effector memory T cells (TEM) and plays an important role in their activation and proliferation. Mycosis fungoides (MF), the most common subtype of cutaneous T-cell lymphoma (CTCL), was recently proposed to be a malignancy of skin-resident TEM. However, the expression of Kv1.3 in CTCL has not been investigated. This study aims to examine the expression of Kv1.3 in situ and in vitro in CTCL. The expression of Kv1.3 was examined by immunohistochemistry in skin lesions from 38 patients with MF, 4 patients with Sézary syndrome (SS), and 27 patients with benign dermatosis. In 4 malignant T-cell lines of CTCL (Myla2059, PB2B, SeAx, and Mac2a) and a non-malignant T-cell line (MyLa1850), the expression of Kv1.3 was determined by flow cytometry. The proliferation of those cell lines treated with various concentrations of Kv1.3 inhibitor ShK was measured by 3H-thymdine incorporation. Half of the MF patients (19/38) displayed partial Kv1.3 expression including 1 patient with moderate Kv1.3 positivity, while the other half (19/38) exhibited Kv1.3 negativity. An almost identical distribution was observed in patients with benign conditions, that is, 44.4% (12/27) were partially positive for Kv1.3 including 1 patient with moderate Kv1.3 positivity, while 55.6% (15/27) were Kv1.3 negative. In contrast, 3 in 4 SS patients displayed partial Kv1.3 positivity including 2 patients with weak staining and 1 with moderate staining, while 1 in 4 SS patients was Kv1.3 negative. In addition, all malignant T-cell lines, and a non-malignant T-cell line, displayed low Kv1.3 surface expression with a similar pattern. Whereas 2 cell lines (PB2B and Mac2a) were sensitive to Kv1.3 blockade, the other 2 (Myla2059 and SeAx) were completely resistant. We provide the first evidence of a heterogeneous Kv1.3 expression in situ in CTCL lesions.


Antiarrhythmic drugs for pharmacological cardioversion of atrial fibrillation and sex differences: Insights from the CANT II Study.
Data on sex differences in terms of action of antiarrhythmic agents (AADs) are limited. This study aimed to evaluate the clinical profile of patients with atrial fibrillation (AF), and efficacy and safety of AADs used for pharmacological cardioversion (PCV) of AF. This research was a sub-analysis of the retrospective multicenter Cardioversion with ANTazoline II (CANT) registry, which comprised 1365 patients with short-duration AF referred for urgent PCV with the use of AAD. Patients were categorized according to and compared in terms of clinical parameters and PCV outcomes. The primary endpoint was return of sinus rhythm within 12 hours after drug infusion, and the composite safety endpoint involved bradycardia <45 bpm, hypotension, syncope, or death. The sex distribution of patients qualified for PCV was even (men, n = 725; 53.1%). Females were older and more symptomatic and had higher CHA2DS2-VASc scores, higher prevalence of tachyarrhythmia, and higher use of chronic anticoagulation. The overall efficacy (71.4% vs. 70.1%; P = 0.59) and safety (5.2% vs. 4.6%; P = 0.60) of PCV was comparable in men and women. Amiodarone (68.3% vs. 65.9%; P = 0.66) and antazoline (77.1% vs. 80.0%; P = 0.19) had similar efficacy in men and women, but propafenone had a lower rate of rhythm conversion in men (64.7% vs. 79.3%; P = 0.046). None of the assessed AADs differed in terms of safety profile in both sexes. Female patients with AF have different clinical profiles but similar efficacy and safety of AADs as compared to male participants. Propafenone has significantly lower efficacy in men, which requires further investigation.


Prevalence and burden of illness for asthma and related symptoms among kindergartners in Chicago public schools.
Asthma mortality rates in poor communities of Chicago are among the highest in the country. Possible explanations include increased asthma prevalence, increased severity, and suboptimal health care. To estimate the prevalence of asthma and asthma-related symptoms among inner-city kindergarten children, and to characterize their burden of illness, asthma-related health care access, and pharmacologic treatment. Cross-sectional survey of parents of kindergartners was conducted in 11 randomly selected Chicago elementary schools. A self-administered 16-item questionnaire was given to parents of kindergartners. Parents who reported doctor-diagnosed asthma or at least one of several key asthma-related symptoms were then interviewed with a supplemental questionnaire examining asthma-related health care and medication use. Based on data from 638 children [mean age 5.7 (SD = 0.6) years], the prevalence of diagnosed asthma was 10.8%. Sixteen percent of the respondents reported that their child had wheezed in the past year. The prevalence of asthma-related symptoms unassociated with a diagnosis of asthma was 30.1%. The children with diagnosed asthma had evidence of a high burden of illness: over 40% were reported to have had sleep disturbance due to wheezing > or =1 to 2 nights/week and 86.6% reported acute care visits for respiratory symptoms in the past year. Self-reported access to medical care was high. Over 40% of the children with doctor diagnosed asthma were reported to have used a beta2-agonist in the preceding 2 weeks, and 12.2% used an inhaled anti-inflammatory. These data suggest that asthma prevalence in school-aged children in inner-city communities may be higher than US estimates. The burden of illness experienced by these children is substantial. Also, a large proportion of children were reported to have respiratory symptoms consistent with asthma, and no asthma diagnosis, suggesting possible undiagnosed asthma. While measures of health care access appear to indicate that the majority of children with asthma experience no identified barriers to health care, there is evidence to suggest undertreatment.


Sulfonamides incorporating ketene N,S-acetal bioisosteres as potent carbonic anhydrase and acetylcholinesterase inhibitors.
In this study, 15 novel compounds in a series of sulfonamide-based ketenes (7a-o) were synthesized and characterized using Fourier-transform infrared spectroscopy, nuclear magnetic resonance spectroscopy, and mass spectrometry. All compounds were tested for their ability to inhibit the human carbonic anhydrase (hCA) isoforms I and II, and acetylcholinesterase (AChE). The halogen-appended compounds, 7g, 7o, and 7i, exhibited the highest hCA I/II and AChE inhibition, with the KI values in the low nanomolar range (KI = 9.01 ± 0.08, 7.41 ± 0.03, and 7.37 ± 0.31 nM, respectively), as compared with their corresponding parent 2-[2,2-dicyano-1-(phenylamino)vinylthio]-N-(4-sulfamoylphenyl)acetamide analogs 7a-o. Besides, derivatives 7c and 7e selectively inhibited the isoform hCA I, whereas compounds 7m and 7n selectively inhibited isoform hCA II. These findings indicated that all compounds can inhibit metabolic dysfunctions, such as edema, epilepsy, glaucoma, and Alzheimer's disease, by specifically targeting both the hCA isoforms and AChE expression. Herein, also the interactions between ligands and receptors were highlighted through in silico molecular docking studies. The molecular mechanics-generalized Born surface area method was utilized to compute the binding free energy and the energy contribution of the critical residues in the active site was estimated. All these results would help us to perfectly understand the relationship between activity and structural characteristics of derivatives and to further improve newly and highly effective analogs targeting hCA and AChE.


Testicular fat deposition attenuates reproductive performance via decreased FSH level and sperm meiosis and testosterone synthesis in mouse.
Testicular fat deposition has been reported to affect animal reproduction. However, the underlying mechanism remains poorly understood. The present study explored whether sperm meiosis and testosterone synthesis contribute to mouse testicular fat deposition-induced reproductive performance. High fat diet (HFD)-induced obesity CD1 mice (DIO) were used as a testicular fat deposition model. The serum hormone test was performed by agent kit. The quality of sperm was assessed using a Sperm Class Analyzer. Testicular tissue morphology was analyzed by histochemical methods. The expression of spermatocyte marker molecules was monitored by an immuno-fluorescence microscope during meiosis. Analysis of the synthesis of testosterone was performed by Real-time PCR and reagent kit. It was found that there was a significant increase in body weight among DIO mice, however, the food intake showed no difference compared to control mice fed a normal diet (CTR). The number of offspring in DIO mice decreased, but there was no significant difference from the CTR group. The levels of FSH were lower in DIO mice and their LH levels were similar. The results showed a remarkable decrease in sperm density and motility among DIO mice. We also found that fat accumulation affected the meiosis process, mainly reflected in the cross-exchange of homologous chromosomes. In addition, overweight increased fat deposition in the testis and reduced the expression of testosterone synthesis-related enzymes, thereby affecting the synthesis and secretion of testosterone by testicular Leydig cells. Fat accumulation in the testes causes testicular cell dysfunction, which affects testosterone hormone synthesis and ultimately affects sperm formation.


Atelocollagen-delivered siRNA targeting the FABP5 gene as an experimental therapy for prostate cancer in mouse xenografts.
The gene FABP5 encodes cutaneous fatty acid binding protein (C-FABP) that is up-regulated in prostate cancer where it acts as a putative oncogene. To test the hypothesis that siRNA to FABP5 delivered to the external environment of a prostate cancer would reduce the level of C-FABP in vivo, experiments were established whereby siRNA to FABP5 suspended in atelocollagen was injected around tumour masses produced by PC-3M cells in Balb/c nude mice and compared with the effect of non-specific scrambled siRNA in atelocollagen. At autopsy, the average size of tumours from the groups treated with 10 and 15 microM siRNA in atelocollagen was significantly (p=0.02) reduced by more than 3-fold, when compared to the controls. In contrast, when compared to the tumours produced by the group treated with scrambled siRNA, treatment with 10 microM FABP5 siRNA in buffer and 1 or 5 microM siRNA in atelocollagen did not produce significant differences. Although the dosage of 15 microM siRNA produced a greater reduction in tumour sizes when compared with 10 microM, this difference was not significant (p=0.9). Immunohistochemistry and Western blotting revealed that the levels of C-FABP expression in tumours from mice treated with 10 and 15 microM dosages were lower than those from the other groups. These data demonstrate that FABP5 siRNA delivered by atelocollagen to the external environment surrounding a tumour mass can effectively inhibit prostate cancer cell growth in nude mice when administered in a dose-dependent manner at concentrations of >10 microM.


Inducible podocyte injury and proteinuria in transgenic zebrafish.
Damage or loss of podocytes causes glomerulosclerosis in murine models, and mutations in podocyte-specific genes cause nephrotic syndrome in humans. Zebrafish provide a valuable model for kidney research, but disruption of pronephroi leads to death within a few days, thereby preventing the study of CKD. In this study, we generated an inducible model of podocyte injury in zebrafish (pod::NTR-mCherry) by expressing a bacterial nitroreductase, which converts metronidazole to a cytotoxin, specifically in podocytes under the control of the zebrafish nphs2/podocin promoter. Application of the prodrug metronidazole to the transgenic fish induces acute damage to the podocytes in pronephroi of larval zebrafish and the mesonephroi of adult zebrafish, resulting in foot-process effacement and podocyte loss. We also developed a functional assay of the glomerular filtration barrier by creating transgenic zebrafish expressing green fluorescent protein (GFP)-tagged vitamin D-binding protein (VDBP) as a tracer for proteinuria. In the VDBP-GFP and pod::NTR-mCherry double-transgenic fish, induction of podocyte damage led to whole-body edema, and the proximal tubules reabsorbed and accumulated VDBP-GFP that leaked through the glomeruli, mimicking the phenotype of human nephrotic syndrome. Moreover, expression of wt1b::GFP, a marker for the developing nephron, extended into the Bowman capsule in response to podocyte injury, suggesting that zebrafish have a podocyte-specific repair process known to occur in mammalian metanephros. These data support the use of these transgenic zebrafish as a model system for studies of glomerular pathogenesis and podocyte regeneration.


Rotavirus VP6 expressed by PVX vectors in Nicotiana benthamiana coats PVX rods and also assembles into viruslike particles.
The rotavirus major inner capsid protein (VP6) has been expressed in Nicotiana benthamiana plants using vectors based on potato virus X (PVX). VP6 was expressed either as a fusion with the PVX coat protein or from an additional subgenomic promoter inserted to enable both VP6 and PVX coat protein to be expressed independently. Both approaches yielded VP6, which retained the ability to form trimers. VP6 expressed from the subgenomic promoter assembled into paracrystalline sheets and tubes. Expression as a fusion protein yielded PVX rods that presented an external "overcoat" of VP6, but unexpectedly, some rotavirus protein also assembled into icosahedral viruslike particles (VLPs). The assembly of viral protein into VLPs suggests that prior display of VP6 on the flexuous PVX rod facilitates the subsequent assembly of VP6 into stable icosahedral particles.


Incidence of sexual dysfunction associated with antidepressant agents: a prospective multicenter study of 1022 outpatients. Spanish Working Group for the Study of Psychotropic-Related Sexual Dysfunction.
Antidepressants, especially selective serotonin reuptake inhibitors (SSRIs), venlafaxine, and clomipramine, are frequently associated with sexual dysfunction. Other antidepressants (nefazodone, mirtazapine, bupropion, amineptine, and moclobemide) with different mechanisms of action seem to have fewer sexual side effects. The incidence of sexual dysfunction is underestimated, and the use of a specific questionnaire is needed. The authors analyzed the incidence of antidepressant-related sexual dysfunction in a multicenter, prospective, open-label study carried out by the Spanish Working Group for the Study of Psychotropic-Related Sexual Dysfunction. The group collected data from April 1995 to February 2000 on patients with previously normal sexual function who were being treated with antidepressants alone or antidepressants plus benzodiazepines. One thousand twenty-two outpatients (610 women, 412 men; mean age = 39.8 +/- 11.3 years) were interviewed using the Psychotropic-Related Sexual Dysfunction Questionnaire, which includes questions about libido, orgasm, ejaculation, erectile function, and general sexual satisfaction. The overall incidence of sexual dysfunction was 59.1% (604/1022) when all antidepressants were considered as a whole. There were relevant differences when the incidence of any type of sexual dysfunction was compared among different drugs: fluoxetine, 57.7% (161/279); sertraline, 62.9% (100/159); fluvoxamine, 62.3% (48/77); paroxetine, 70.7% (147/208); citalopram, 72.7% (48/66); venlafaxine, 67.3% (37/55); mirtazapine, 24.4% (12/49); nefazodone, 8% (4/50); amineptine, 6.9% (2/29); and moclobemide, 3.9% (1/26). Men had a higher frequency of sexual dysfunction (62.4%) than women (56.9%), although women had higher severity. About 40% of patients showed low tolerance of their sexual dysfunction. The incidence of sexual dysfunction with SSRIs and venlafaxine is high, ranging from 58% to 73%, as compared with serotonin-2 (5-HT2) blockers (nefazodone and mirtazapine), moclobemide, and amineptine.


Antibody to parietal cells in patients with duodenal ulcer, and relationship to pernicious anaemia.
Of 160 patients with pernicious anaemia, none had current duodenal ulceration, whereas in a random population of similar age and sex distribution some 5% would be expected to have a duodenal ulcer. Parietal-cell antibody was detected in serum from 8 of 169 men (4-7%) and from 2 to 31 women (6-4%) with duodenal ulceration. None of the 200 duodenal ulcer patients had antibody to intrinsic factor. The prevalence of these antibodies in duodenal ulcer patients was not significantly different from that in control subjects of similar age and sex distribution. The decreased prevalance of duodenal ulcer in pernicious anaemia patients implies that pernicious anaemia must be less prevalent in duodenal ulcer patients than in a random population; but it appears that this cannot be attributed to an absence of gastric autoimmunity in patients with duodenal ulcer. To resolve this disrepancy, we suggest that pernicious anaemia is determined not only by autoimmune reactions, but also by independent genetic and environmental factors which influence the state of the gastric mucosa.


Delivery route in bone marrow cell transplantation should be optimized according to the etiology of heart disease.
Recent studies have revealed that bone marrow cell (BMC) transplantation is effective not only for myocardial infarction (MI), but also for dilated cardiomyopathy (DCM). However, the method of administering donor cells remains unknown, and may differ between MI and DCM. In the present study, intramyocardial (IM) injection and intravenous (IV) delivery of BMC were compared in each etiological model. MI was induced in 72 mice and DCM in another 36 mice by doxorubicin. BMCs were administered IV or IM in an acute MI (AMI), old MI (OMI) or DCM model. In the AMI model, left ventricular (LV) remodeling was reduced in both the IM- and IV-groups, but only in the IM-group in the OMI model. In the DCM model, the LV dimension of the IV-group was smaller than that of the IM-group. Histological examination showed that green fluorescent protein (GFP) cells were equally distributed in the infarct area of the IV- and IM-groups in AMI, and in the IM-group in the OMI model. In the DCM model, GFP cells were diffusely scattered throughout the ventricular wall in the IV-group, but were confined to the injection site in the IM-group. In OMI, IM delivery of BMCs was more effective than IV; however, IV delivery was superior in DCM. Delivery route should be selected according to the etiology of heart disease to optimize the efficacy of BMC transplantation.


A case of alpha-fetoprotein-producing gastric cancer.
A case of alpha-fetoprotein (AFP)-producing gastric cancer is described in a 57-year-old Chinese woman. She presented with bleeding tendency and bone pain, and was found to have haematological evidence of disseminated intravascular coagulation and spinal metastasis. Her tumour markers, including AFP, Ca 19-9 and carcinoembryonic antigen (CEA) were elevated. In view of the elevated tumour markers, there was an exhaustive search for a primary lesion in the gastrointestinal tract, liver and ovaries. There was no radiological evidence to suggest any lesion in the chest, liver or pelvis. Lectin affinity electrophoresis of the AFP showed AFP-L2 and AFP-L3 bands, which are suggestive of a non-hepatoma malignancy. Gastroscopy showed a gastric ulcer and she developed bleeding after the gastric biopsy which required urgent surgery. Intraoperatively she was found to have carcinomatous peritone and a malignant ulcer in the greater curve of the stomach. Histology confirmed a linitis plastica like adenocarcinoma which stains for AFP. She died from multi-organ failure 3 days after surgery. AFP-producing adenocarcinoma of the stomach is not uncommon. Lectin affinity electrophoresis of AFP is helpful in the differentiation between hepatoma and non-hepatoma malignancies.


The relationship between serum fatty acids and depressive symptoms in obese adolescents.
Depression and obesity are highly prevalent and are considered inflammatory pathologies; in addition, they are also associated with dietary patterns including types of fatty acids (FA). Changes in the FA composition in the brain are determined by changes in the content and quality of dietary and serum FA. The aim of this study was to verify the relationships between serum-free FA, inflammatory processes and depressive symptoms in obese adolescents. This was a cross-sectional study that analysed a database composed of 138 post-pubertal adolescents. Data regarding the depressive symptoms, body composition, glucose metabolism, lipid profile, FA profile, leptin concentration, as well as adiponectin, IL-A, IL-6, IL-10, TNF-α, C-reactive protein and plasminogen activator inhibitor-1 levels of the subjects were collected. A total of 54·6 % of the adolescents presented with depressive symptoms, and there were positive correlations between depressive symptoms and serum saturated fatty acids (SFA) content, body fat, and inflammatory adipokines, such as leptin, IL-6, and the leptin/adiponectin ratio. Moreover, the content of n-3 polyunsaturated fatty acids (PUFA) was negatively correlated with depressive symptoms, suggesting that eicosatrienoic acid (C20:2n6) and dihomo-γ-linolenic acid (C20:3n-6) are independently associated with depressive symptom scores and can be critical predictors of poor mental health in humans. These results point to the relationship between SFA and depressive symptoms in obese adolescents. However, longitudinal studies are needed to confirm the causality between dietary SFA and depression in obese individuals.


Consumer managed care appeals: are the available procedural protections fundamentally fair?
Managed care incentives to reduce costs have also resulted in incentives to deny care. Anecdotes concerning managed care denials of care have led to a consumer outcry for protection either through the use of procedural due process or by the establishment of patient rights that would include appeal and grievance protections. This Article reviews the procedural protections of constitutional due process, the Consumer Due Process Protocol, and the Patient Bill of Rights. The Article then extensively discusses the availability of these procedural protections in various public and private forums. The discussion of public forums includes proposals contained in recent national legislative initiatives. The author then reviews relevant federal and state law, as well as Uniform Law proposals. Next, the Article analyzes the protections provided by accreditation agencies, dispute resolution organizations, professional organizations, and health insurers. Finally, the author recommends criteria to be used to determine whether a procedure is fundamentally fair.


201Tl myocardial perfusion imaging.
Despite predictions that 201Tl imaging would be completely supplanted by the new 99mTc perfusion agents, thallium perfusion imaging is alive and well. In fact, in the past year, important new information on thallium imaging continued to emerge. Among the new data, the reinjection of a "booster" dose of 201Tl after the redistribution images has been heralded as a breakthrough that would equal positron-emission tomography in the prediction of myocardial viability. Pharmacologic coronary vasodilation has been increasingly popular, especially since the approval of intravenous dipyridamole by the Food and Drug Administration and in view of recent studies showing that adenosine is a very attractive alternative to dipyridamole in patients who cannot exercise. Beyond the undisputed diagnostic value of dipyridamole-thallium imaging, data on risk stratification continue to accumulate for patients receiving peripheral vascular surgeries as well as for those recovering from a myocardial infarction. The advent of single-photon emission CT in combination with 201Tl imaging allows improved quantification of jeopardized myocardium. This technique has now been used increasingly to complement the information obtained from coronary angiography by the determination of the functional significance of known coronary stenoses. Recent studies have shown marked heterogeneity in the extent of jeopardized myocardium in patients with coronary artery disease. Equally important have been recent reports on the high prevalence of silent ischemia in patients undergoing 201Tl exercise scintigraphy. Technical progress has also enhanced the diagnostic capability of 201Tl imaging, allowing sharper identification of perfusion defects and quantification of reversible myocardial ischemia precipitated by exertion. Finally, one of the most exciting areas of research in thallium scintigraphy is its established prognostic value in patients with stable angina or those recovering from a myocardial infarction. Recently, these prognostic data have also been extended to patients with unstable angina or those receiving thrombolytic therapy.


Analysis of survival rates and cellular fatty acid profiles of Listeria monocytogenes treated with supercritical carbon dioxide under the influence of cosolvents.
In the present study, we identified several process variables that significantly affect the efficiency of supercritical carbon dioxide inactivation of the food-borne pathogen Listeria monocytogenes. Treatment with SC-CO(2) completely disabled the colony-forming activity of the cells (8-log reduction) within specific treatment time (10-50 min), pressure (80-150 bar), and temperature ranges (35-45 degrees C). Microorganism inactivation rates increased proportionally with pressure and temperature, but the inactivation rate decreased significantly when cells were suspended in phosphate-buffered saline rather than in physiological saline. Additionally, when the microbial cell suspension was 80-100% (w/w) of water, the SC-CO(2)-mediated reduction in CFU ml(-1) was 4-8 log higher at the same treatment conditions than in typical cell suspensions (a water content of 800-4000% [w/w]) or dry preparations that had only 2-10% (w/w) of water. The addition of a fatty acid, oleic acid, decreased the effectiveness of the microbial inactivation by SC-CO(2), but the addition of a surfactant, sucrose monolaurate, increased the effectiveness. Therefore, cosolvents for SC-CO(2), including water, a fatty acid, and a surfactant in this study, were found to greatly influence on the inactivation effectiveness. The extraction of cellular substances, such as nucleic acid- and protein-like materials and fatty acids, was monitored by spectrophotometry and GC/MS and increased with SC-CO(2) treatment time. Additionally, using scanning and transmission electron microscopies, we investigated morphological changes in the SC-CO(2)-treated cells. The effects of the variables we have described herein represent a significant contribution to our current knowledge of this method of inactivating food-borne pathogens.


Understanding the roles of plasmonic Au nanocrystal size, shape, aspect ratio and loading amount in Au/g-C3N4 hybrid nanostructures for photocatalytic hydrogen generation.
Hybrid photocatalysts containing plasmonic metal and semiconductor building blocks can alleviate charge carrier recombination and broaden the range of light absorption of the semiconductor. In this work, plasmonic Au nanocrystals of different sizes and shapes (spheres and rods) are attached on graphitic carbon nitride (g-C3N4) nanosheets through electrostatic attraction. The effects of the morphology and loading amount of the Au nanocrystals are carefully studied for understanding and optimizing the hybrid photocatalysts. The optimized 18 nm-sized Au nanospheres/g-C3N4 photocatalyst exhibits a superior activity for H2 evolution at a rate of 540 μmol g-1 h-1 under visible light (λ > 420 nm), exceeding those produced over larger-sized Au nanospheres/g-C3N4, Au nanorods/g-C3N4 and photodeposited Au nanoparticles/g-C3N4 photocatalysts. The excellent activity for H2 evolution is attributed to the electron sink and plasmonic effects of the Au nanocrystals in different spectral regions, as evidenced by photocurrent measurements. The introduced plasmonic Au nanocrystals not only enhance the photocatalytic activity, but they also endow the hybrid photocatalysts with an extended light absorption range. Our results and understanding will be useful for the design of efficient plasmonic photocatalysts for solar to fuel energy conversion as well as for other plasmon-driven chemical reactions.


A Peptide-Based Virus Inactivator Protects Male Mice Against Zika Virus-Induced Damage of Testicular Tissue.
Zika virus (ZIKV) was a re-emerging arbovirus associated with Guillain-Barré Syndrome in adult and congenital Zika syndrome in fetus and infant. Although ZIKV was mainly transmitted by mosquito bites, many sexual transmission cases have been reported since the outbreak in 2015. ZIKV can persist in testis and semen for a long time, causing testicular tissue damage and reducing sperm quality. However, no drug has been approved for prevention or treatment of ZIKV infection, especially infection in male testicular tissue. Previously reported peptide Z2 could inactivate ZIKV, inhibiting ZIKV infection in vitro and in vivo. Importantly, Z2 could inhibit vertical transmission of ZIKV in pregnant mice, reducing ZIKV infection in fetus. Here we showed that intraperitoneally administered Z2 could also be distributed to testis and epididymis, resulting in the reduction of ZIKV RNA copies in testicular tissue and protection of testis and epididymis against ZIKV-induced pathological damage and poor sperm quality in type I interferon receptor-deficient A129 mice. Thus, Z2, a ZIKV inactivator, could serve as an antiviral agent for treatment of ZIKV infection and attenuation of ZIKV-induced testicular tissue damage.


Subcutaneous tissue oxygen pressure: a reliable index of peripheral perfusion in humans after injury.
The usual initial life-threatening effect of injury is hypovolemic shock. In the hierarchical physiologic response to hypovolemia, perfusion of peripheral tissues is sacrificed early and restored late. But the usual hemodynamic and metabolic measurements of blood pressure, urine output, and base deficit are not reliable indices of peripheral perfusion. Although the Clark electrode can quantitate tissue oxygen pressure and thereby serve as an index of perfusion, its use is compromised by several technical deficiencies. Recently, an optical method (optode) using fluorescent technology has been developed for measurement of oxygen tension in subcutaneous tissue (P sgO2). Our studies compared this device with the Clark electrode in the laboratory and tested its value in both animal and clinical studies of hypovolemic shock. The results of these several studies demonstrated that: (1) the new oximeter tracked a rapid fall or rapid rise of oxygen tension between room air (150 mm Hg) and 0 mm Hg ( a glucose oxidase/catalase solution) as well as the Clark electrode without encountering its technical problems; (2) with an acute hemorrhage to 20% of base line, the PsgO2 was found to decline rapidly in parallel with the decline of mean arterial pressure (MAP). Although the MAP rapidly returned to normal after immediate complete return of all shed blood, the PsgO2 did not reach normal levels for at least 2 hours, suggesting persistent peripheral vasoconstriction. (3) Studies in progress suggest that between 35 and 78% of trauma patients (n = 18) adequately resuscitated for hypovolemia b customary criteria have a decreased level of PsgO2 for as long as 60 hours after resuscitation for injury. If care is taken to prevent other causes of catecholamine induced vasoconstriction such as pain, fear, cold, and arterial hypoxia, these several results suggest that a certain number of injured patients are inadequately resuscitated despite the return to normal of conventional hemodynamic measurements. The serial analysis of PsgO2 may assist in managing patients and promote better understanding of the responses to injury.


Comparison of a polymeric pseudostationary phase in EKC with ODS stationary phase in RP-HPLC.
Poly(stearyl methacrylate-co-methacrylic acid) (P(SMA-co-MAA)) was induced as pseudostationary phase (PSP) in electrokinetic chromatography (EKC). The n-octadecyl groups in SMA were the same as that in octadecylsilane (ODS) C18 column. Thus, the present work focused on the comparison of selectivity between polymeric PSP and ODS stationary phase (SP), and the effect of organic modifiers on the selectivity of polymeric PSP and ODS SP. 1-butanol could directly interacted with PSP as a Class I modifier, and improved both of the methylene selectivity and polar group selectivity. When the analysis times were similar, the polymeric PSP exhibited better methylene selectivity and polar group selectivity. Although the hydrophobic groups were similar, the substituted benzenes elution order was different between polymeric PSP and ODS SP. Linear solvation energy relationships (LSER) model analysis found that polymeric PSP and ODS SP exhibited two same key factors in selectivity: hydrophobic interaction and hydrogen bonding acidity. But polymeric PSP exhibited relatively strong n- and π-electrons interaction to the analytes.


Open pulled straw vitrification and slow freezing of sheep IVF embryos using different cryoprotectants.
The aim of the present study was to evaluate the post-thaw survival and hatching rates of sheep blastocysts using different cryoprotectants. In Experiment 1, Day 6 sheep embryos were cryopreserved by a slow freezing protocol using 10% ethylene glycol (EG), 10% dimethyl sulfoxide (DMSO) or a mixture of 5% EG and 5% DMSO. Hatching rates were higher in the 10% EG group than in the 10% DMSO or EG + DMSO groups (30% vs 18% and 20%, respectively). In Experiment 2, embryos were cryopreserved by open pulled straw (OPS) vitrification using either 33% EG, 33% DMSO or a mixture of 16.5% EG + 16.5% DMSO. Re-expansion and hatching rates in the EG + DMSO group (79.16% and 52.74%, respectively) were higher than those in the EG group (64.28% and 30.02%, respectively), whereas the outcomes for the DMSO group were the lowest (45.18% and 8.6%, respectively). In Experiment 3, embryos were cryopreserved by OPS vitrification using either 40% EG, 40% DMSO or a mixture of 20% EG + 20% DMSO. Re-expansion and hatching rates were highest in the EG group than in the EG + DMSO and DMSO groups (92.16% vs 76.30% and 55.84% re-expansion, respectively; and 65.78% vs 45.55% and 14.46% hatching, respectively). In conclusion, OPS vitrification was found to be more efficient for cryopreservation of in vitro-developed sheep embryos than traditional freezing.


Changing Paradigms in the Diagnosis of Ischemic Heart Disease by Multimodality Imaging.
Coronary artery disease (CAD) represents the most common cardiovascular disease, with high morbidity and mortality. Historically patients with chest pain of suspected coronary origin have been assessed with functional tests, capable to detect haemodynamic consequences of coronary obstructions through depiction of electrocardiographic changes, myocardial perfusion defects or regional wall motion abnormalities under stress condition. Stress echocardiography (SE), single-photon emission computed tomography (SPECT), positron emission tomography (PET) and cardiovascular magnetic resonance (CMR) represent the functional techniques currently available, and technical developments contributed to increased diagnostic performance of these techniques. More recently, cardiac computed tomography angiography (cCTA) has been developed as a non-invasive anatomical test for a direct visualisation of coronary vessels and detailed description of atherosclerotic burden. Cardiovascular imaging techniques have dramatically enhanced our knowledge regarding physiological aspects and myocardial implications of CAD. Recently, after the publication of important trials, international guidelines recognised these changes, updating indications and level of recommendations. This review aims to summarise current standards with main novelties and specific limitations, and a diagnostic algorithm for up-to-date clinical management is also proposed.


Mechanisms of herpes simplex virus infectivity enhanced by ultracentrifugal inoculation.
Ultracentrifugation of very dilute suspensions of herpes simplex virus directly onto monolayer cells grown in centrifuge tubes was studied. Enhanced infectivity by ultracentrifugation was similar at 4 degrees C and at 35 to 37 degrees C. The high infectivity levels of cultures centrifuged at 4 degrees C were further examined by infectious center assays. At 4 degrees C, the numbers of infectious centers in control (noncentrifuged) cultures were almost 100-fold fewer than in control cultures at 37 degrees C. However, the numbers of infectious centers in cultures ultracentrifuged at 4 degrees C were similar to those ultracentrifuged at 37 degrees C. The great difference in the numbers of infectious centers between 4 and 37 degrees C control cultures, in contrast to the similarity between 4 and 37 degrees C ultracentrifuged cultures, indicated that ultracentrifugation at 4 degrees C enhanced infectivity possibly by facilitation of herpes simplex virus penetration into monolayer cells.


Beliefs about mental disorder treatment and prognosis: comparison of health professionals with the Australian public.
In the 1990s, large differences in beliefs about the helpfulness of treatments for mental disorders were observed between the Australian public and health professionals. This study evaluates whether gaps in public and professional beliefs remain by comparing beliefs of the public and health professionals on the helpfulness of interventions and likely prognosis for six mental health problems: depression, depression with suicidal thoughts, early schizophrenia, chronic schizophrenia, social phobia, and post-traumatic stress disorder. Mental health literacy surveys based around a vignette of a person with a mental disorder were carried out in a nationally representative sample of the Australian public (n=6019) in 2011 and samples of Australian general practitioners, psychiatrists, and psychologists (n=1536) in 2012. Respondents were asked to rate the helpfulness of a range of interventions and the likely outcome with or without appropriate professional treatment. Differences between groups were examined with chi-square tests. There were many significant differences in treatment beliefs, but most of these were small in size. Medium-sized differences tended to be consistent across vignettes and relate to the greater belief by the public in the helpfulness of close family or friends, a counsellor, vitamins and minerals, a special diet or avoiding certain foods, and having an occasional alcohol drink to relax. In contrast, professionals showed a greater belief in psychotherapy and cognitive behaviour therapy for depression and anxiety, and antipsychotics for schizophrenia. Findings on prognosis showed mostly small differences in beliefs. Overall, the results indicate that the views of the public and professionals are more aligned than in the 1990s. There are now few large gaps in treatment beliefs, but there remain some areas that could be improved.


Strategies to improve 3D whole-body PET image reconstruction.
An algorithm is described for three-dimensional whole-body (3DWB) image reconstruction in positron emission tomography. For whole-body applications, improvements to the popular fixed-axial-acceptance-angle technique are achieved by combining axially adjacent projection data available with a long-axis data set. Time-consuming reprojection of unmeasured oblique lines of response is reduced or eliminated by axial overlap of bed positions, while pixel variance and reconstructed axial resolution are made more uniform by the overlap. Improvements in noise and resolution uniformity are accompanied by gains in reconstruction efficiency, and may be optimized against increased acquisition-time due to overlapping acquisition segments and reduced axial coverage. An 11-detector-ring overlap improves axial uniformity in coronal images of a long, uniform cylinder from 23% to 8% with uniform axial resolution. Associated with a 37% improvement in reconstruction time is a 34% reduction in axial coverage for four bed positions. A smaller degree of overlap is found to provide the best trade-off between image uniformity, total scan duration, and reconstruction time because of a proportionally greater reduction in reprojected lines of response. Using a sample optimization scheme, we find a three-ring overlap is best for a 60 cm axial field of view and a five-ring overlap for an 80 cm axial field of view.


Occurrence of longitudinal stent compression before stent deployment: Two case studies.
Several recent reports have described the occurrence of longitudinal stent deformation (LSD, defined as the distortion or shortening of a stent along the longitudinal axis), following its successful deployment. However, few reports have described LSD prior to any stent deployment. This previously unrecognized complication is the result of modifications to stent design. It has been noted that the new-generation stent platforms have a reduced number of connectors, which in turn causes a reduction in longitudinal stent strength. To corroborate previous findings by our lab and others (Vijayvergiya et al, 2013), we describe here two cases of LSD prior to stent deployment that occurred due to crushing of the proximal stent edge by the guide catheter while attempting to withdraw the crimped stent. In addition, we discuss the associated risk factors, such as the length of the stent, and specific management strategies, including technical guidelines and use of fluoroscopic guidance for maneuvering the stent during the procedure.


Willingness to Take a Free Home HIV Test and Associated Factors among Internet-Using Men Who Have Sex with Men.
Online HIV prevention studies have been limited in their ability to obtain biological specimens to measure study outcomes. We describe factors associated with willingness of men who have sex with men (MSM) to take a free home HIV test as part of an online HIV prevention study. Between March and April 2009, we interviewed 6163 HIV-negative MSM and assessed the willingness to test for HIV infection using a home collection kit. Men reported being very likely (3833; 62%) or likely (1236; 20%) to accept a home HIV test as part of an online HIV prevention study. The odds of being willing to home test were higher for men who were offered incentives of $10 or $25, were black, had unprotected anal intercourse in the past 12 months, and were unaware of their HIV status. Home testing offered as part of online HIV prevention research is acceptable overall and in important subgroups of high-risk MSM.


[The role of hypothermia in brain protection by adenosine receptor agonists].
Agonists of A1 adenosine receptors induce a profound hypothermia that is correlated with a considerable increase in tolerance with respect to the global cerebral ischemia. Thermal irradiation of the head considerably decreases and the thermoneutral temperature completely prevents (i) the development of hypothermia in the body and, especially, in the cortex and (ii) the neuroprotection, so that a correlation of these two effects disappears. The induction of hypothermia is the most important but not single mechanism of neuroprotective action of A1-receptor agonists. Other A-agonists are much less active.


Liver function recovery of COVID-19 patients after discharge, a follow-up study.
Objective: The aim of this study was to observe the liver function recovery of COVID-19 patients after discharge. Patients and Methods: A total of 253 discharged COVID-19 patients in Shenzhen city, China were selected. The clinical characteristics of these patients were assessed. A 2-month follow-up and laboratory hematology test were performed to examine the status of patients' liver function. Results: Patients combined with liver diseases, especially fatty liver, are more likely to progress to severe condition (P<0.05). Patients in severe condition and those with liver diseases have higher rates of liver injuries during hospitalization, characterized by a significant increase in alanine aminotransferase (ALT) and aspartate aminotransferase (AST, P<0.01). The ALT, AST/ALT, gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), total protein (TP), albumin (ALB), and A/G levels showed significant differences in comparison with the control group (P<0.05, and P<0.001); and the outlier ratio of A/G, ALT, GGT and ALP of patients remained abnormal higher within 14 days after discharge (P<0.001). Liver injuries of COVID-19 patients may be related to the epidemiological characteristics, clinical indexes, basic diseases, symptoms, drug treatment during hospitalization and the complications. Indicators of liver function were correlated with cardiac function, renal function, thyroid function, lipid metabolism, glucose metabolism, immune index, leukocyte, erythrocyte, hemoglobin and platelet related indexes. The outlier ratio of TP, ALB and GLB remained extremely low throughout the follow-up period; the outlier ratio of ALT, AST and GGT decreased below 10% from a high level at 40 days after discharged. However, the outlier ratio of A/G, AST/ALT and ALP remained high during the follow-up period. Conclusions: Abnormal liver function might indicate worse recovery of COVID-19 patients. Changes in liver function should be emphasized during long-term follow-up of COVID-19 patients after hospital discharge; the necessity of employing appropriate interventions for liver function repair should be emphasized.


Conceptualizing and measuring community preparedness within public health preparedness and response: complexities and lessons learned.
Since 2001, the Centers for Disease Control and Prevention's Public Health Emergency Preparedness cooperative agreement has supported state, territorial, and local public health departments in preparing for and responding to public health emergencies. This conceptual article describes complexities identified and lessons learned in developing community preparedness performance measures for the Centers for Disease Control and Prevention's public health preparedness program. Challenges arose in (a) defining community; (b) measuring meaningful community engagement; and (c) determining a strategy for collecting, aggregating, and analyzing data from diverse state, territorial, and local health departments. This article contributes to prior work describing conceptual challenges in developing standardized measures of performance at the federal level and suggests ways to potentially mitigate general performance measurement challenges as well as measurement complexities specific to community preparedness. It may be informative for those state, territorial, and local health departments currently implementing (or contemplating implementing) community preparedness activities and for individuals more generally engaged in performance measurement.


Complete and sustained resolution of calcinosis universalis in a juvenile dermatomyositis case with mycophenolate mofetil.
Çakan M, Karadağ ŞG, Aktay Ayaz N. Complete and sustained resolution of calcinosis universalis in a juvenile dermatomyositis case with mycophenolate mofetil. Turk J Pediatr 2019; 61: 771-775. Juvenile dermatomyositis (JDM) is a rare, multisystemic, idiopathic vasculopathy mainly affecting the muscles and the skin. Gastrointestinal system, lungs, joints and heart may also be involved. Characteristic skin findings are heliotrope rash and Gottron papules but extensive skin involvement as large necrotic lesions are rarely reported. Calcinosis is one of the major issues in the long term. Delay in diagnosis, inadequate therapy at the initial phase, prolonged persistent disease activity are considered as major risk factors for the development of calcinosis. Treatment of calcinosis is also a major issue because no single treatment modality has been found to reproducibly stop or reverse calcification. A 5-year-old girl was admitted to our clinic with typical signs and symptoms of JDM. She was initially treated with high-dose corticosteroids, methotrexate and intravenous immunoglobulin (IVIG). Soon after, she developed necrotic ulcerative skin lesions and cyclosporine was added to her treatment regimen. By this treatment all muscle and skin manifestations were controlled but on the first year of follow-up she developed superficial calcification plaques on the upper extremities and calcinosis universalis like calcifications on the lower extremities. Calcifications did not respond to bisphosphonate (pamidronate) and IVIG treatment but mycophenolate mofetil resulted in rapid and sustained resolution of all calcification plaques.


Effects of AFQ056 on language learning in fragile X syndrome.
FXLEARN, the first-ever large multi-site trial of effects of disease-targeted pharmacotherapy on learning, was designed to explore a new paradigm for measuring effects of mechanism-targeted treatment in fragile X syndrome (FXS). In FXLEARN, the effects of mGluR5 negative allosteric modulator (NAM) AFQ056 on language learning were evaluated in 3-6 year-old children with FXS, expected to have more learning plasticity than adults, where prior trials of mGluR5 NAMs have failed. After a 4-month single-blind placebo lead-in, participants were randomized 1:1 to AFQ056 or placebo, with 2 months of dose optimization to the maximum tolerated dose, then 6 months of treatment during which a language learning intervention was implemented for both groups. The primary outcome was a centrally scored videotaped communication measure, the Weighted Communication Scale (WCS). Secondary outcomes were objective performance-based and parent-report cognitive and language measures. FXLEARN enrolled 110 participants, randomized 99, and 91 completed the placebo-controlled period. Although both groups made language progress and there were no safety issues, the change in WCS score during the placebo-controlled period was not significantly different between the AFQ056 and placebo-treated groups, nor were there any significant between-group differences in change in any secondary measures. Despite the large body of evidence supporting use of mGluR5 NAMs in animal models of FXS, this study suggests that this mechanism of action does not translate into benefit for the human FXS population and that better strategies are needed to determine which mechanisms will translate from pre-clinical models to humans in genetic neurodevelopmental disorders. ClincalTrials.gov NCT02920892 FUNDING. This study was supported by NeuroNEXT network NIH grants U01NS096767, U24NS107200, U24NS107209, U01NS077323, U24NS107183, U24NS107168, U24NS107128, U24NS107199, U24NS107198, U24NS107166, U10NS077368, U01NS077366, U24NS107205, U01NS077179, and U01NS077352, NIH grant P50HD103526 and Novartis IIT grant AFQ056X2201T for provision of AFQ056.


Changes of trabecular meshwork pigmentation in patients with pigment dispersion syndrome: A 15-year study.
To report the changes of trabecular meshwork (TM) pigmentation and clinical outcomes of patients with pigment dispersion syndrome (PDS) after resolution of reverse pupillary block.Twenty one eyes of 11 PDS patients were followed up periodically for 15 years after resolution of reverse pupillary block with either Nd: YAG laser peripheral iridotomy (LPI) or trabeculectomy. Visual acuity (VA), best-corrected visual acuity (BCVA), slit lamp examination, intraocular pressure (IOP), Humphrey visual field analysis (VFA), gonioscopy and stereoscopic funduscopy were performed on admission and every 6 months postoperatively. TM pigmentation was quantitatively evaluated and graded every 5 years after the treatment, in which the circumference of anterior chamber angle was divided into 4 quadrants: superior, inferior, nasal and temporal. Postoperative IOP, VA, BCVA, VFA, TM pigmentation and adjunctive anti-glaucoma medications were main outcome measurements and compared with baseline.Eleven patients (9 males, 2 females) were identified as PDS according to the diagnostic criteria, with average age of 38.25 ± 6.93 years (range, 31-55 years) at initial diagnosis. The mean IOP level was 33.1 ± 9.8 mmHg (range, 22-56 mmHg) at diagnosis. Ten PDS eyes received LPI, and the other eleven eyes underwent uneventful trabeculectomy. The median TM pigmentation score of the 21 PDS eyes was 16 (interquartile range [IQR], 15-16) on admission, which changed to 14 (IQR, 13-15), 13 (IQR, 12-14), 12(IQR, 10.5-12) at 5-, 10-, 15-year follow-up visits respectively. The decrease rate of TM pigmentation was 37% in inferior quadrant, while in nasal, temporal, and superior quadrant the reduction rate was 28%, 23%, and 18%, respectively, at the last follow-up visit. Majority of these enrolled eyes (19/21) had stable VA and BCVA with average endpoint IOP of 15.1 ± 3.4 mmHg.TM pigmentation in PDS patients attenuates with time after reverse pupillary block was resolved, in which the inferior quadrant seems faster than the other quadrants.


Object recognition using three-dimensional information.
This paper describes an approach to the recognition of stacked objects with planar and curved surfaces. The system works in two phases. In the learning phase, a scene containing a single object is shown one at a time. The range data of a scene are obtained by a range finder. The description of each scene is built in terms of properties of regions and relations between them. This description is stored as an object model. In the recognition phase, an unknown scene is described in the same way as in the learning phase. Then the description is matched to the object models so that the stacked objects are recognized sequentially. Efficient matching is achieved by a combination of data-driven and model-driven search processes. Experimental results for blocks and machine parts are shown.


Biodentine Pulpotomy in Mature Permanent Molar: A Case Report.
Irreversible pulpitis is the most common reason for endodontic treatment in primary and permanent teeth. Root canal therapy and extraction are the two viable and most documented treatment options for the same. Studies with regards to management of mature permanent teeth with carious exposure and treatment with vital pulp therapies such as adult permanent tooth pulpotomy are scarce. However, permanent tooth pulpotomy with the new calcium-silicate based cements (Mineral Trioxide Aggregate and Biodentine) can help preserve the tooth pulp vitality and promote healing and repair foregoing the more invasive root canal therapy procedure. A 12-year old male patient with irreversible pulpitis in right mandibular first permanent molar was treated with complete coronal pulpotomy with placement of Biodentine in the pulp chamber and a full coronal coverage using stainless steel crown. Clinical and radiographic examinations were performed at three, six, twelve and eighteen months. At the end of 18 months, the patient was completely asymptomatic and the tooth was free of any clinical and radiographic signs of inflammation and infection.


ANALYZING SECOND ORDER STOCHASTICITY OF NEURAL SPIKING UNDER STIMULI-BUNDLE EXPOSURE.
Conventional analysis of neuroscience data involves computing average neural activity over a group of trials and/or a period of time. This approach may be particularly problematic when assessing the response patterns of neurons to more than one simultaneously presented stimulus. in such cases the brain must represent each individual component of the stimuli bundle, but trial-and-time-pooled averaging methods are fundamentally unequipped to address the means by which multiitem representation occurs. We introduce and investigate a novel statistical analysis framework that relates the firing pattern of a single cell, exposed to a stimuli bundle, to the ensemble of its firing patterns under each constituent stimulus. Existing statistical tools focus on what may be called "first order stochasticity" in trial-to-trial variation in the form of unstructured noise around a fixed firing rate curve associated with a given stimulus. our analysis is based upon the theoretical premise that exposure to a stimuli bundle induces additional stochasticity in the cell's response pattern in the form of a stochastically varying recombination of its single stimulus firing rate curves. We discuss challenges to statistical estimation of such "second order stochasticity" and address them with a novel dynamic admixture point process (DAPP) model. DAPP is a hierarchical point process model that decomposes second order stochasticity into a Gaussian stochastic process and a random vector of interpretable features and facilitates borrowing of information on the latter across repeated trials through latent clustering. We illustrate the utility and accuracy of the DAPP analysis with synthetic data simulation studies. We present real-world evidence of second order stochastic variation with an analysis of monkey inferior colliculus recordings under auditory stimuli.


Validation of an automated surveillance approach for drain-related meningitis: a multicenter study.
OBJECTIVE Manual surveillance of healthcare-associated infections is cumbersome and vulnerable to subjective interpretation. Automated systems are under development to improve efficiency and reliability of surveillance, for example by selecting high-risk patients requiring manual chart review. In this study, we aimed to validate a previously developed multivariable prediction modeling approach for detecting drain-related meningitis (DRM) in neurosurgical patients and to assess its merits compared to conventional methods of automated surveillance. METHODS Prospective cohort study in 3 hospitals assessing the accuracy and efficiency of 2 automated surveillance methods for detecting DRM, the multivariable prediction model and a classification algorithm, using manual chart review as the reference standard. All 3 methods of surveillance were performed independently. Patients receiving cerebrospinal fluid drains were included (2012-2013), except children, and patients deceased within 24 hours or with pre-existing meningitis. Data required by automated surveillance methods were extracted from routine care clinical data warehouses. RESULTS In total, DRM occurred in 37 of 366 external cerebrospinal fluid drainage episodes (12.3/1000 drain days at risk). The multivariable prediction model had good discriminatory power (area under the ROC curve 0.91-1.00 by hospital), had adequate overall calibration, and could identify high-risk patients requiring manual confirmation with 97.3% sensitivity and 52.2% positive predictive value, decreasing the workload for manual surveillance by 81%. The multivariable approach was more efficient than classification algorithms in 2 of 3 hospitals. CONCLUSIONS Automated surveillance of DRM using a multivariable prediction model in multiple hospitals considerably reduced the burden for manual chart review at near-perfect sensitivity.


Time Series Complexities and Their Relationship to Forecasting Performance.
Entropy is a key concept in the characterization of uncertainty for any given signal, and its extensions such as Spectral Entropy and Permutation Entropy. They have been used to measure the complexity of time series. However, these measures are subject to the discretization employed to study the states of the system, and identifying the relationship between complexity measures and the expected performance of the four selected forecasting methods that participate in the M4 Competition. This relationship allows the decision, in advance, of which algorithm is adequate. Therefore, in this paper, we found the relationships between entropy-based complexity framework and the forecasting error of four selected methods (Smyl, Theta, ARIMA, and ETS). Moreover, we present a framework extension based on the Emergence, Self-Organization, and Complexity paradigm. The experimentation with both synthetic and M4 Competition time series show that the feature space induced by complexities, visually constrains the forecasting method performance to specific regions; where the logarithm of its metric error is poorer, the Complexity based on the emergence and self-organization is maximal.


Statistically correcting dynamical electron scattering improves the refinement of protein nanocrystals, including charge refinement of coordinated metals.
Electron diffraction allows protein structure determination when only nanosized crystals are available. Nevertheless, multiple elastic (or dynamical) scattering, which is prominent in electron diffraction, is a concern. Current methods for modeling dynamical scattering by multi-slice or Bloch wave approaches are not suitable for protein crystals because they are not designed to cope with large molecules. Here, dynamical scattering of nanocrystals of insulin, thermolysin and thaumatin was limited by collecting data from thin crystals. To accurately measure the weak diffraction signal from the few unit cells in the thin crystals, a low-noise hybrid pixel Timepix electron-counting detector was used. The remaining dynamical component was further reduced in refinement using a likelihood-based correction, which was introduced previously for analyzing electron diffraction data of small-molecule nanocrystals and was adapted here for protein crystals. The procedure is shown to notably improve the structural refinement, in one case allowing the location of solvent molecules. It also allowed refinement of the charge states of bound metal atoms, an important element in protein function, through B-factor analysis of the metal atoms and their ligands. These results clearly increase the value of macromolecular electron crystallography as a complementary structural biology technique.


Morphine and promethazine as intravenous premedicants.
Two hundred seventy patients received morphine 5 mg or 10 mg alone or with promethazine 6.25 mg, 12.5 mg, or 25 mg. Promethazine 25 mg alone also was studied. All drugs were given intravenously. Anxiety relief, sedation, patient acceptance, lack of recall, and side effects were the variables examined. Promethazine improved relief of anxiety, sedation, and patient acceptance when added to morphine. Doses of promethazine larger than 12.5 mg intravenously failed to improve these effects. Memory remained unaffected by any of the drugs.


Effect of Hyperbaric Oxygen on Neurologic Sequelae and All-Cause Mortality in Patients with Carbon Monoxide Poisoning: A Meta-Analysis of Randomized Controlled Trials.
BACKGROUND Hyperbaric oxygen (HBO) is used in patients with carbon monoxide (CO) poisoning to prevent the occurrence of delayed neurological sequelae. However, inconsistent results were obtained regarding the treatment effects of HBO. Therefore, the current meta-analysis was conducted based on published randomized controlled trials (RCTs) to determine the effect of HBO on neurologic sequelae and all-cause mortality in patients with CO poisoning. MATERIAL AND METHODS Electronic databases MedLine, EmBase, and the Cochrane Library were searched for relevant RCTs from inception to March 1, 2019. The pooled relative risks (RRs) and weighted mean differences (WMDs) with corresponding 95% confidence intervals (CIs) were calculated to evaluate the outcomes by using a random-effects model. Sensitivity, subgroup, and publication bias analyses were also conducted. RESULTS Seven RCTs, including 9 cohorts and a total of 2023 patients with CO poisoning, were enrolled in this study. The summary results revealed that HBO showed an association with lower risk of memory impairment compared to patients receiving normobaric oxygen (NBO), whereas 2 sessions of HBO showed an association with higher risk of memory impairment compared to those who received 1 session of HBO. Moreover, HBO was associated with increased neuropsychologic scores of block design and trail making when compared with NBO. No other significant differences regarding the treatment effects of HBO were observed. CONCLUSIONS These results indicate that HBO therapy significantly reduces the risk of memory impairment compared to NBO, but 2 sessions of HBO might not be better for memory impairment than 1 session of HBO.


A rapid and non-destructive identification for paper cup evidence based on shifted-excitation Raman difference spectroscopy and SOM clustering.
In order to achieve rapid, non-destructive, efficient, and accurate classification of paper cup samples, we propose a classification model that integrates shifted-excitation Raman difference spectroscopy (SERDS) with self-organizing map (SOM) and Bayesian optimization-support vector machine (BO-SVM). We collected differential Raman data from 52 paper cup samples using SERDS, with an excitation wavelength range of 784-785 nm, a laser power of 440 mW, an integration time of 10 s, and a spectral range spanning from 280 to 2700 cm-1 . Subsequently, principal component analysis (PCA) was applied to reduce the dimensionality of the data. The SOM clustering outcomes were utilized as the foundation for constructing the discriminant analysis (FDA) and BO-SVM classification models. The primary constituent of the paper cup samples was identified as cellulose, while additional fillers such as talc, calcium carbonate, and kaolin were also present. The SOM clustering categorized the samples into seven distinct groups. The FDA model achieved a classification accuracy of 92.3%, and the BO-SVM model reached a classification accuracy of 96.2%. The SOM clustering effectively discerned samples with different fillers, as evidenced by distinct peak numbers and shapes in the differential Raman spectra, thereby underscoring the practical significance of SOM clustering. In comparison with FDA, BO-SVM exhibited enhanced classification accuracy and exceptional performance in handling outliers and linearly inseparable data, indicating its superior generalization capabilities.


Different prognostic impact of recurrent gene mutations in chronic lymphocytic leukemia depending on IGHV gene somatic hypermutation status: a study by ERIC in HARMONY.
Recent evidence suggests that the prognostic impact of gene mutations in patients with chronic lymphocytic leukemia (CLL) may differ depending on the immunoglobulin heavy variable (IGHV) gene somatic hypermutation (SHM) status. In this study, we assessed the impact of nine recurrently mutated genes (BIRC3, EGR2, MYD88, NFKBIE, NOTCH1, POT1, SF3B1, TP53, and XPO1) in pre-treatment samples from 4580 patients with CLL, using time-to-first-treatment (TTFT) as the primary end-point in relation to IGHV gene SHM status. Mutations were detected in 1588 (34.7%) patients at frequencies ranging from 2.3-9.8% with mutations in NOTCH1 being the most frequent. In both univariate and multivariate analyses, mutations in all genes except MYD88 were associated with a significantly shorter TTFT. In multivariate analysis of Binet stage A patients, performed separately for IGHV-mutated (M-CLL) and unmutated CLL (U-CLL), a different spectrum of gene alterations independently predicted short TTFT within the two subgroups. While SF3B1 and XPO1 mutations were independent prognostic variables in both U-CLL and M-CLL, TP53, BIRC3 and EGR2 aberrations were significant predictors only in U-CLL, and NOTCH1 and NFKBIE only in M-CLL. Our findings underscore the need for a compartmentalized approach to identify high-risk patients, particularly among M-CLL patients, with potential implications for stratified management.


Physicochemical descriptors in property-based drug design.
The contribution of physicochemical descriptors to lipophilicity, water solubility, and intestinal absorption and oral bioavailability in humans is considered. Partitioning in the octanol/water system is presented as a competition between two opposing effects: volume and hydrogen bond acceptor ability. Water solubilities of liquid compounds are roughly equal to their reciprocal logP values. However, there is also a detectable contribution of H-bond donor ability to water solubility. The main problem in predicting the solubilities of solid chemicals and drugs is the estimation of their crystal lattice energies. QSAR approaches that add terms such as melting point, and the product of H-bond donor and acceptor parameters are not sufficient to make these predictions practical. Human intestinal absorption for passively transported drugs is almost completely correlated with hydration processes that are determined by H-bond acceptor and donor abilities. It is emphasized that structural features of drug molecules have significant influences on their properties. Classic QSAR approaches are not enough to create stable, predictive models for diverse drugs. A combination of Similarity and QSAR approaches is one possibility to take all physicochemical properties in addition to structural features into account.


Water Adsorption on Mica Surfaces with Hydrophilicity Tuned by Counterion Types (Na, K, and Cs) and Structural Fluorination.
The stability of adsorbed water films on mineral surfaces has far-reaching implications in the Earth, environmental, and materials sciences. Here, we use the basal plane of phlogopite mica, an atomically smooth surface of a natural mineral, to investigate water film structure and stability as a function of two features that modulate surface hydrophilicity: the type of adsorbed counterions (Na, K, and Cs) and the substitution of structural OH groups by F atoms. We use molecular dynamics simulations combined with in situ high-resolution X-ray reflectivity to examine surface hydration over a range of water loadings, from the adsorption of isolated water molecules to the formation of clusters and films. We identify four regimes characterized by distinct adsorption energetics and different sensitivities to cation type and mineral fluorination: from 0 to 0.5 monolayer film thickness, the hydration of adsorbed ions; from 0.5 to 1 monolayer, the hydration of uncharged regions of the siloxane surface; from 1 to 1.5 monolayer, the attachment of isolated water molecules on the surface of the first monolayer; and for >1.5 monolayer, the formation of an incipient electrical double layer at the mineral-water interface.


Preoperative risk factors of malnutrition for cardiac surgery patients.
Malnutrition (MN) is prevalent in cardiac surgery, but there are no specific preoperative risk factors of MN. The aim of this study is to assess the clinically relevant risk factors of MN for cardiac surgery patients. The nutritional state of the patients was evaluated one day prior to surgery using a bioelectrical impedance analysis phase angle (PA). Two groups of patients were generated according to low PA: malnourished and well nourished. Risk factors of MN were divided into three clinically relevant groups: psychosocial and lifestyle factors, laboratory findings and disease-associated factors. Variables in each different group were entered into separate multivariate logistic regression models. A total of 712 patients were included in the study. The majority of them were 65-year old men after a CABG procedure. Low PA was present in 22.9% (163) of patients. The analysis of disease-related factors of MN revealed the importance of heart functions (NYHA IV class OR: 3.073, CI95%: 1.416-6.668, p = 0.007), valve pathology (OR: 1.825, CI95%: 1.182-2.819, p = 0.007), renal insufficiency (OR: 4.091, CI95%: 1.995-8.389, p < 0.001) and body mass index (OR: 0.928, CI95%: 0.890-0.968, p < 0.001). Laboratory values related to MN were levels of haemoglobin (OR: 0.967, CI95%: 0.951-0.983, p < 0.001) and C-reactive protein (OR: 1.015, CI95%: 1.002-1.028, p = 0.0279). The lifestyle variables that qualified as risk factors concerned the intake of food (OR: 3.030, CI95%: 1.353-6.757, p = 0.007) and mobility (OR: 2.770, CI95%: 1.067-7.194, p = 0.036). MN risk factors comprise three different clinical groups: psychosocial and lifestyle factors, laboratory findings and disease-associated factors. The patients who are most likely to be malnourished are those with valve pathology, severe imparted heart function, insufficient renal function and high inflammatory markers. Also these patients have decreased mobility and food intake.


Detection and identification of Xanthomonas pathotypes associated with citrus diseases using comparative genomics and multiplex PCR.
In Citrus cultures, three species of Xanthomonas are known to cause distinct diseases. X. citri subsp. citri patothype A, X. fuscans subsp. aurantifolii pathotypes B and C, and X. alfalfae subsp. citrumelonis, are the causative agents of cancrosis A, B, C, and citrus bacterial spots, respectively. Although these species exhibit different levels of virulence and aggressiveness, only limited alternatives are currently available for proper and early detection of these diseases in the fields. The present study aimed to develop a new molecular diagnostic method based on genomic sequences derived from the four species of Xanthomonas. Using comparative genomics approaches, primers were synthesized for the identification of the four causative agents of citrus diseases. These primers were validated for their specificity to their target DNA by both conventional and multiplex PCR. Upon evaluation, their sensitivity was found to be 0.02 ng/µl in vitro and 1.5 × 104 CFU ml-1 in infected leaves. Additionally, none of the primers were able to generate amplicons in 19 other genomes of Xanthomonas not associated with Citrus and one species of Xylella, the causal agent of citrus variegated chlorosis (CVC). This denotes strong specificity of the primers for the different species of Xanthomonas investigated in this study. We demonstrated that these markers can be used as potential candidates for performing in vivo molecular diagnosis exclusively for citrus-associated Xanthomonas. The bioinformatics pipeline developed in this study to design specific genomic regions is capable of generating specific primers. It is freely available and can be utilized for any other model organism.


A forensic neuropsychiatric approach to traumatic brain injury, aggression, and suicide.
Aggression is a common neuropsychiatric sequela of traumatic brain injury (TBI), one which interferes with rehabilitation efforts, disrupts social support networks, and compromises optimal recovery. Aggressive behavior raises critical safety concerns, potentially placing patients and care providers in harm's way. Such aggression may be directed outwardly, manifesting as assaultive behavior, or directed inwardly, resulting in suicidal behavior. Given the frequency of TBI and posttraumatic aggression and the potential medicolegal questions surrounding the purported causal relationships between the two, forensic psychiatrists need to understand and recognize posttraumatic aggression. They also must be able to offer cogent formulations about the relative contributions of neurotrauma versus other relevant neuropsychiatric factors versus combinations of both to any specific act of violence. This article reviews the relationships between TBI and aggression and discusses neurobiological and cognitive factors that influence the occurrence and presentation of posttraumatic aggression. Thereafter, a heuristic is offered that may assist forensic psychiatrists attempting to characterize the relationships between TBI and externally or internally directed violent acts.


Pre-onset risk characteristics for mania among young people at clinical high risk for psychosis.
Psychosis and mania share conceptual, genetic and clinical features, which suggest the possibility that they have common antecedents. Participants identified to be at-risk for psychosis might also be at-risk for mania. We aimed to identify the rate and predictors of transition to mania in a cohort of youth with clinical or familial risk for psychosis. Among a cohort of 416 young people with an at-risk mental state for psychosis defined using the Ultra-High-Risk (UHR) criteria, 74.7% were followed up between 5 and 13years from their baseline assessment. We undertook a matched case-control examination of those who developed mania over the follow-up period compared to those who did not develop mania or psychosis. Transition to mania was determined using either a structured clinical interview, or diagnoses from a state-wide public mental health contact registry. Clinical characteristics and risk factors were examined at baseline using information from structured interviews, clinical file notes, rating scales and unstructured assessments. Eighteen participants developed mania (UHR-Manic transition or UHR-M, 4.3%). In comparison with participants matched on age, gender and baseline-study who developed neither mania nor psychosis, more UHR-M participants had subthreshold manic symptoms or were prescribed antidepressants at baseline. They also had lower global functioning. In addition to the UHR criteria, features such as subthreshold manic symptoms and antidepressant use may help identify at-risk groups that predict the onset of mania in addition to transition to psychosis. Presence of manic symptoms may also indicate syndrome specificity early in the prodromal phase.


Referral to physiotherapy as part of a general practitioner's management of back pain.
The aim of this survey was to investigate how general practitioners (GPs) manage their back pain patients and if they refer them for physiotherapy. The research instrument was a self-administered postal questionnaire. This was sent to 580 GPs, one quarter of the GPs in the Republic of Ireland. Two hundred and ninety three questionnaires (n=293)were returned, which constituted a 50.5% response rate. Two hundred and sixty one questionnaires (n=261) were usable. The main findings of the study were that the respondents consider that physiotherapy has a major role in the management of back pain. However there was limited availability of physiotherapy for the GPs' public patients. One hundred and thirteen GPs (over 43% of respondents) have referred back pain patients to alternative practitioners for manipulation. One hundred and forty four respondents (52%) believe that physiotherapists should not treat back pain patients without the patient first consulting their doctor.


The NLRB decisions on appropriate bargaining units.
It appears that the NLRB's lack of familiarity with the health care industry and particularly with the day-to-day functioning of a hospital led it to search for touchstones such as the status of an RN or the certification of technicians that would enable it to make easy but illogical distinctions. As the cases are reviewed in the judicial system, the separate units for RNs, technical employes, and business office clerical employes will be closely scrutinized. Finally, the bargaining units as outlined and the placement of particular groups of employes based on their formal status will necessarily have an impact on the functional integration of hospital activities.


Symptomatic root compression by a free fat transplant after hemilaminectomy. Case report.
The authors report a case in which a free fat graft, placed at the operative site after hemilaminectomy for lumbar disc herniation, was forced into the spinal canal by action of the paraspinal muscles and behaved as a symptomatic space-occupying lesion. The patient recovered satisfactorily after the graft was removed. The pathogenetic mechanism is discussed and guidelines to avoid this complication are outlined.


Bilateral ureteral reimplantation at primary bladder exstrophy closure.
We present the outcomes of children who underwent concurrent complete primary repair of bladder exstrophy and bilateral ureteral reimplantation vs those undergoing bladder exstrophy repair alone, focusing on the rate of postoperative febrile urinary tract infections. We performed complete primary repair of bladder exstrophy with bilateral ureteral reimplantation using a cephalotrigonal technique in 15 patients (group 1) and without bilateral ureteral reimplantation in 23 patients (group 2). Postoperative assessment included ultrasound and voiding cystourethrogram in all patients. Outcome measurements included postoperative febrile urinary tract infections, hydronephrosis and presence of vesicoureteral reflux. Mean followup was 34 months (range 6 to 54) for group 1 and 70 months (23 to 117) for group 2. Median age at surgery was 3 days for both groups (range 1 to 140). There were 10 boys and 5 girls in group 1, and 11 boys and 12 girls in group 2. Two of 15 patients (13%) in group 1 had hydronephrosis postoperatively compared to 10 of 23 (43%) in group 2 (p = 0.05). One patient in group 1 (7%) had a febrile urinary tract infection vs 11 (48%) in group 2 (p = 0.01). No patients in group 1 had postoperative vesicoureteral reflux compared to 17 (74%) in group 2 (p = 0.04). There were no complications related to ureteral reimplantation. Bilateral ureteral reimplantation can be safely and effectively performed during primary closure of bladder exstrophy in newborns, potentially reducing postoperative febrile urinary tract infections and hydronephrosis by early correction of vesicoureteral reflux.


The reinnervation of regenerated hair cells in the basilar papilla of chicks after kanamycin ototoxicity.
When newly hatched chicks were injected with kanamycin on 8 successive days, the hair cells were destroyed completely in the area 0.4 to 0.8 mm from the proximal end of the basilar papilla. At this time, and 1 and 7 days following the completion of 10 days of injections, the nerve fibres in the basilar papilla of chicks show no sign of injury. On the first day following 10 days kanamycin administration the regenerated hair cells obtained not only afferent innervation, but also efferent innervation. At 15 days following drug cessation, afferent innervation of the regenerated hair cells was already similar to the controls, and the thresholds measured at this time were significantly better than those at 1 and 7 days. The chalice efferent terminals did not appear until the 60th day of drug cessation. Efferent innervation of the regenerated hair cells also approached maturity at this time. Compared with the half month after the completion of drug injection, the hearing of birds had no evident increase. It was obvious that afferent innervation of the regenerated hair cells was related more to the recovery of hearing than efferent innervation. The regenerated hair cells beginning reinnervation early and maturing were important factors influencing the recovery of the birds' hearing function after kanamycin ototoxicity.


[Spontaneous animal models for insulin-dependent diabetes (type 1 diabetes)].
Insulin dependent (type 1) diabetes in humans is a polygenic, auto-immune disease that is characterized, among other things, by the infiltration of the islets of Langerhans by immune cells (insulite) as well as many serum auto-antibodies (including islet cell antibodies: ICA). The medical goal is to diagnose the condition at a sub-clinical stage and then to prevent the disease from developing. Spontaneous diabetic rodent models, in particular the NOD mouse and BB rat are invaluable to the continuing progress of the work aimed at better understanding the human disease. In addition to these models, the study of type 1 diabetes in larger animals, having a longer life-span would also be helpful. In dogs and cats, certain minor kinds of diabetes appear to be of type 1. The classification of diabetes types in carnivores remains poorly defined, however, epidemiological, genetic and metabolic studies are required before these diabetes can be used as operational models for the human pathology. Even if the classification of these diseases is clarified, the ethical and social considerations involved with the use of companion animals, will limit the use of these animals as models for spontaneous diabetes. The selection of a specific line of diabetic dogs should perhaps be considered.


Ragweed skin test responsiveness correlates with specific immunoglobulin E levels.
Evaluation for allergic rhinitis requires an objective measure of atopy. Serum eosinophils, total and specific immunoglobulin E (IgE), and skin testing have been used as this measure. The objective of our study was to examine the relationship between in vitro allergy tests and in vivo responsiveness. We compared eosinophil counts, total IgE, and the specific IgE radioallergosorbent test (RAST) measurements to end point skin test titrations with ragweed. Forty subjects > or = 18 years of age with at least a 2-year history of moderate to severe ragweed-allergic rhinitis and a positive skin-prick test to ragweed participated in this study with 33 subjects having data for all measurements. End point skin tests were performed by intradermal injection of 0.03 mL of threefold dilutions of standardized short ragweed extract into the forearm. Ragweed-specific IgE was significantly correlated to end point wheal and erythema concentrations. The results were similar whether the endpoint wheal (r = -0.714; p < 0.001) or erythema (r = 0.862; p < 0.001) concentration was used, and the correlation between these two values was significant (r = 0.97; p < 0.001). However, 8 of 33 subjects had a negative specific IgE RAST value for ragweed. There was a significant relationship between ragweed-specific IgE and total IgE (r = 0.72; p < 0.01). No significant correlations were found between blood eosinophils and either total IgE, ragweed-specific IgE, and end point wheal or erythema concentrations. Skin test responsiveness to ragweed correlated with in vitro ragweed-specific IgE levels, but these tests are not equivalent indicators of the degree of IgE-mediated sensitivity.


Congenital chloride diarrhea needs to be distinguished from Bartter and Gitelman syndrome.
Pseudo-Bartter/Gitelman syndrome (p-BS/GS) encompasses a clinically heterogeneous group of inherited or acquired disorders similar to Bartter syndrome (BS) or Gitelman syndrome (GS), both renal salt-losing tubulopathies. Phenotypic overlap frequently occurs between p-BS/GS and BS/GS, which are difficult to diagnose based on their clinical presentation and require genetic tests for accurate diagnosis. In addition, p-BS/GS can occur as a result of other inherited diseases such as cystic fibrosis, autosomal dominant hypocalcemia, Dent disease, or congenital chloride diarrhea (CCD). However, the detection of the variants in genes other than known BS/GS-causing genes by conventional Sanger sequencing requires substantial time and resources. We studied 27 cases clinically diagnosed with BS/GS, but with negative genetic tests for known BS/GS genes. We conducted targeted sequencing for 22 genes including genes responsible for tubulopathies and other inherited diseases manifesting with p-BS/GS symptoms. We detected the SLC26A3 gene variants responsible for CCD in two patients. In Patient 1, we found the SLC26A3 compound heterozygous variants: c.354delC and c.1008insT. In Patient 2, we identified the compound heterozygous variants: c.877G > A, p.(Glu293Lys), and c.1008insT. Our results suggest that a comprehensive genetic screening system using targeted sequencing is useful for the diagnosis of patients with p-BS/GS with alternative genetic origins.


A Review on Molecular Mechanism of Flavonoids as Antidiabetic Agents.
The development of drugs possessing anti-diabetic activities is a long pursued goal in drug discovery. It has been shown that deregulated insulin mediated signaling, oxidative stress, obesity, and β-cell dysfunction are the main factors responsible for the disease. With the advent of new and more powerful screening assays and prediction tools, the idea of a drug that can effectively treat diabetes by targeting different pathways has re-bloomed. Current anti-diabetic therapy is based on synthetic drugs that very often have side effects. For this reason, there is an instantaneous need to develop or search new alternatives. Recently, more attention is being paid to the study of natural products. Their huge advantage is that they can be ingested in everyday diet. Here, we discuss various causes, putative targets, and treatment strategies, mechanistic aspects as well as structural features with a particular focus on naturally occurring flavonoids as promising starting points for anti-diabetic led development.


M-free: scoring the reference bias in sub-tomogram averaging and template matching.
Cryo-electron tomography provides a snapshot of the cellular proteome. With template matching, the spatial positions of various macromolecular complexes within their native cellular context can be detected. However, the growing awareness of the reference bias introduced by the cross-correlation based approaches, and more importantly the lack of a reliable confidence measurement in the selection of these macromolecular complexes, has restricted the use of these applications. Here we propose a heuristic, in which the reference bias is measured in real space in an analogous way to the R-free value in X-ray crystallography. We measure the reference bias within the mask used to outline the area of the template, and do not modify the template itself. The heuristic works by splitting the mask into a working and a testing area in a volume ratio of 9:1. While the working area is used during the calculation of the cross-correlation function, the information from both areas is explored to calculate the M-free score. We show using artificial data, that the M-free score gives a reliable measure for the reference bias. The heuristic can be applied in template matching and in sub-tomogram averaging. We further test the applicability of the heuristic in tomograms of purified macromolecules, and tomograms of whole Mycoplasma cells.


Purification of a high-molecular-weight somatoliberin (growth-hormone-releasing factor) from pig hypothalami.
Preliminary observations [Sykes & Lowry (1980) J. Endocrinol. 85, 42P-43P] had suggested that the major hypothalamic somatoliberin (growth-hormone-releasing factor) was a larger peptide than the other characterized hypothalamic factors, with an elution position on Sephadex G-50 between those of neurophysin and corticotropin. The present paper reports the isolation and preliminary characterization of pig hypothalamic somatoliberin. Acid extracts of pig stalk median eminence were purified by gel filtration and preparative and analytical high-pressure liquid chromatography to yield a preparation that was specific in the release of somatotropin (growth hormone) in vitro, giving a steep dose--response curve at doses in the range 0.20-3.0 ng. Amino acid analysis revealed a non-cysteine-containing peptide with a high number of glutamate (or glutamine) and aspartate (or asparagine) residues. The peptide had about 56-57 amino acid residues and an apparent molecular weight of 6400, in keeping with its elution position on a column of Sephadex G-50.


Impact of spatial aggregation error on the spatial scan analysis: a case study of colorectal cancer.
The paper aims to estimate the level and impact of spatial aggregation error for spatial scan statistics where disaggregated data below the zip code level are not available. Data on colorectal cancer cases in Cook county, Illinois, USA with a 5-year interval were used. An innovative procedure using SAS and Java was designed to make SaTScan auto-run. Characteristics of clusters at each reference level were compared to those at zip code level to observe differences related to spatial aggregation. The comparison reveals that spatial scan statistic at the zip code level can generate reliable clusters in areas with a large number of cases, but fail to detect clusters in areas where there are a sparse number of cases, since the spatial aggregation error is minimised in areas with sizeable numbers of cases. Without localised cancer data, zip code level data can be used effectively to identify dominant clusters. However, smaller clusters located in low-density areas may be missed.


Battle casualities.
Eighty casualities, mainly due to explosive devices, sustained over a period of 3 1/2 months by the armed forces of the Sultan of Oman in counterinsurgency operations are analysed and their management by a British field surgical team is described. Of the 73 who reached the surgical centre alive, 56 per cent had suffered major injuries, yet all but 2 survived, giving an overall survival rate of 88.75 per cent (71/80). The effects of first aid and rapid evacuation on survival and their influence on the surgical work load and on the facilities required for treatment are assessed, together with their relevance to the planning of military and civilian accident services.


Update on the distribution of Aedes albopictus (Diptera: Culicidae) in Misiones, Argentina.
The Asian tiger mosquito ( Aedes albopictus, Diptera: Culicidae) has spread rapidly in the last 30 years from its native region in Southeast Asia. In Argentina, studies on its potential distribution suggest that this species could be found in temperate zones of the province of Buenos Aires. However, since its initial detection in 1998 Ae. albopictus is bounded to the subtropical province of Misiones. To evaluate the presence and abundance of Ae. albopictus in the Northeast of Argentina, we preliminarily evaluated the presence of this vector by analyzing its presence in tires of 20 cities belonging to the province of Misiones and four cities in Northern Corrientes, and then performed an evaluation of the vector in the towns where the vector was detected. Aedes albopictus was present only in two cities of Misiones: Eldorado and Colonia Aurora. Aedes aegypti and Ae . albopictus accounted for 86% of the individuals collected in the domiciles of both towns. In Colonia Aurora both species were in similar abundances suggesting a co-dominance. The present study extends the austral distribution of Ae. albopictus in Argentina to the city of Colonia Aurora where the highest abundance recorded in Argentina was detected. Nevertheless, the reasons of its bounded distribution in the region are not known.