Interlateral asymmetry in the time course of the effect of a peripheral prime stimulus.
Evidence exists that both right and left hemisphere attentional mechanisms are mobilized when attention is directed to the right visual hemifield and only right hemisphere attentional mechanisms are mobilized when attention is directed to the left visual hemifield. This arrangement might lead to a rightward bias of automatic attention. The hypothesis was investigated by testing male volunteers, wherein a "location discrimination" reaction time task (Experiments 1 and 3) and a "location and shape discrimination" reaction time task (Experiments 2 and 4) were used. Unilateral (Experiments 1 and 2) and unilateral or bilateral (Experiments 3 and 4) peripheral visual prime stimuli were used to control attention. Reaction time to a small visual target stimulus in the same location or in the horizontally opposite location was evaluated. Stimulus onset asynchronies (SOAs) were 34, 50, 67, 83 and 100 ms. An important prime stimulus attentional effect was observed as early as 50 ms in the four experiments. In Experiments 2, 3 and 4, this effect was larger when the prime stimulus occurred in the right hemifield than when it occurred in the left hemifield for SOA 100 ms. In Experiment 4, when the prime stimulus occurred simultaneously in both hemifields, reaction time was faster for the right hemifield and for SOA 100 ms. These results indicate that automatic attention tends to favor the right side of space, particularly when identification of the target stimulus shape is required.


Influenza A M2 Channel Clustering at High Protein/Lipid Ratios: Viral Budding Implications.
Protein dynamics in crowded environments is important for understanding protein functions in vivo and is especially relevant for membrane proteins because of the roles of protein-protein interactions in membrane protein functions and their regulation. Here, using solid-state NMR spectroscopy in combination with coarse-grained molecular dynamics simulations, we report that the rotational correlation time for the transmembrane domain of the influenza A M2 proton channel in lipid bilayers increases dramatically at an elevated protein/lipid ratio. This increase is attributable to persistent protein-protein interactions, thus revealing for the first time, to the best of our knowledge, extensive cluster formation of the M2 tetrameric channel. Such clustering appears to have direct biological relevance during budding of the nascent influenza virus, which does not use the endosomal sorting complexes required for transport machinery. Indeed, initial coarse-grained molecular dynamics simulations of the longer M2 construct known as the conductance domain suggest clustering-induced membrane curvature formation.


Lack of effect of captopril on preglomerular renal microvascular prostanoid biosynthesis.
Extensive research has focused on the mechanisms by which converting enzyme inhibitors, such as captopril, lower the systemic blood pressure. In addition to inhibiting the conversion of angiotensin I to angiotensin II, these agents have been proposed to influence other systems which might affect vascular resistance including the kinins and the prostanoids. This study was designed to evaluate whether captopril has any direct effect to increase the synthesis of endogenous vasodilator prostanoids in either freshly isolated rabbit renal preglomerular microvessels or in endothelial cells derived from them. The results indicate that captopril, in a variety of doses, had no effect on the synthesis of either prostacyclin or PGE2 by renal preglomerular microvessels. Bradykinin, on the other hand, increased prostanoid production significantly in the same tissue preparations. Finally, captopril had no effect in altering bradykinin-induced increases in renovascular prostanoid biosynthesis. Thus, captopril appears to have no ability to enhance the production of vasodilator prostanoids in rabbit renal preglomerular resistance vessels. These data question the role of prostanoid-related mechanisms in the non-renin-related antihypertensive actions of captopril.


Low-level viraemia among people living with HIV in Nigeria: a retrospective longitudinal cohort study.
HIV transmission can occur with a viral load of at least 200 copies per mL of blood and low-level viraemia can lead to virological failure; the threshold level at which risk for virological failure is conferred is uncertain. To better understand low-level viraemia prevalence and outcomes, we analysed retrospective longitudinal data from a large cohort of people living with HIV on antiretroviral therapy (ART) in Nigeria. In this retrospective cohort study using previously collected longitudinal patient data, we estimated rates of virological suppression (≤50 copies per mL), low-level viraemia (51-999 copies per mL), virological non-suppression (≥1000 copies per mL), and virological failure (≥2 consecutive virological non-suppression results) among people living with HIV aged 18 years and older who initiated and received at least 24 weeks of ART at 1005 facilities in 18 Nigerian states. We analysed risk for low-level viraemia, virological non-suppression, and virological failure using log-binomial regression and mixed-effects logistic regression. At first viral load for 402 668 patients during 2016-21, low-level viraemia was present in 64 480 (16·0%) individuals and virological non-suppression occurred in 46 051 (11·4%) individuals. Patients with low-level viraemia had increased risk of virological failure (adjusted relative risk 2·20, 95% CI 1·98-2·43; p<0·0001). Compared with patients with virological suppression, patients with low-level viraemia, even at 51-199 copies per mL, had increased odds of low-level viraemia and virological non-suppression at next viral load; patients on optimised ART (ie, integrase strand transfer inhibitors) had lower odds than those on non-integrase strand transfer inhibitors for the same low-level viraemia range (eg, viral load ≥1000 copies per mL following viral load 400-999 copies per mL, integrase strand transfer inhibitor: odds ratio 1·96, 95% CI 1·79-2·13; p<0·0001; non-integrase strand transfer inhibitor: 3·21, 2·90-3·55; p<0·0001). Patients with low-level viraemia had increased risk of virological non-suppression and failure. Programmes should revise monitoring benchmarks and targets from less than 1000 copies per mL to less than 50 copies per mL to strengthen clinical outcomes and track progress to epidemic control. None.


Beyond "Disconnected Youth": Characterizing Developmental Heterogeneity in School or Work Connections During Emerging Adulthood.
Prior research on disconnected youth has defined connectedness to school or work during emerging adulthood as an either/or outcome, conflicting with research on emerging adulthood, which suggests varied, individualized pathways. This study used a growth mixture model method with data from the Panel Study of Income Dynamics Transition into Adulthood Supplement to elucidate developmental heterogeneity in connectedness to school or work during emerging adulthood (n = 1,977). Results indicated distinct subgroups of connectedness to school or work with additional variation within groups. Racialized group and parenting status differentiated between being fully connected or not but did not explain differences among those with less consistent connectedness. Policy implications include that the timing and duration of policies targeting disconnected youth may be missing a substantial minority of young people. Re-thinking supports for disconnected youth can be further informed by future research focused on examining factors related to individual differences in the timing and nature of connectedness to school or work.


Echocardiographic Evaluation of the Mitral Valve in Cavalier King Charles Spaniels.
This prospective cross-sectional study aimed to: (1) characterize echocardiographic features of mitral valve in MMVD affected Cavalier King Charles Spaniels (CKCS), focusing on dogs classified as American College of Veterinary Internal Medicine (ACVIM) class B1; (2) compare echocardiographic data in ACVIM B1 dogs divided on the basis of age at time of MMVD diagnosis, in order to understand if different aged subjects had different echocardiographic patterns. Length (AMVL), width (AMVW) and area (AMVA) of the anterior mitral valve leaflet, mitral valve prolapse, diameters of the mitral valve annulus in diastole (MVAd) and systole (MVAs) of 90 CKCS in different ACVIM classes, 64 of which in class B1, were measured. Valvular measurements were indexed to body weight using Wesselowski's scaling exponents. The presence of heart murmur did not discriminate between A and B1 classes (p = 0.128). Heart enlargement was more frequent in males (r2 = 0.07, p = 0.013). Within class B1, older subjects showed significantly higher values of AMVA, AMVW, MVAd, MVAs and lower sphericity index (SI). Since many CKCS with MMVD have no murmur and their mitral valve has peculiarities, a specifically designed echocardiographic screening should be realized. In addition, different aged B1 dogs have different echocardiographic patterns that may imply different genetic and prognostic profiles.


Interaction between gene A-positive Helicobacter pylori and human leukocyte antigen II alleles increase the risk of Graves disease in Chinese Han population: an association study.
The current study explored the correlation of Helicobacter pylori and the polymorphisms of human leukocyte antigen II (HLA-II) alleles with Graves disease (GD). A total of 216 patients with GD were recruited. 102 healthy volunteers constituted the control group. Levels of H. pylori immunoglobulin G (IgG) antibodies and H. pylori cytotoxin-associated gene A (CagA) IgG antibodies were detected using enzyme-linked immunosorbent assays. Molecular typing of the HLA-II alleles was conducted using polymerase chain reaction with sequence specific primers. H. pylori, particularly CagA-positive strains, HLA-DQA1 0201, and HLA-DQA1 0501 were associated with GD (P=0.015, OR=1.811; P=0.000, OR=3.085; P=0.000, OR=0.315; and P=0.004, OR=2.844, respectively). Patients with CagA-positive H. pylori and negative HLA-DQA1 0201 or positive HLA-DQA1 0501 were more likely exposed to GD compared with those with only one of these indices. CagA-positive H. pylori, negative HLA-DQA1 0201, or positive HLA-DQA1 0501 may increase the risk of GD.


Adrenaline in cardiac arrest: Prefilled syringes are faster.
Standard ampoules and prefilled syringes of adrenaline are widely available in Australasian EDs for use in cardiac arrest. We hypothesise that prefilled syringes can be administered more rapidly and accurately when compared with the two available standard ampoules. This is a triple arm superiority study comparing the time to i.v. administration and accuracy of dosing of three currently available preparations of adrenaline. In their standard packaging, prefilled syringes were on average more than 12 s faster to administer than the 1 mL 1:1000 ampoules and more than 16 s faster than the 10 mL 1:10,000 ampoules (P < 0.01 in both comparisons). With packaging removed, the time to administration was equal for the 1 mL (1:1000) ampoule and the prefilled syringe. Accuracy of dosing was excellent with both the 10 mL (1:10 000) ampoules and prefilled syringes. The 1 mL (1:1000) ampoules delivered a small number of markedly inaccurate doses, but these did not reach statistical significance. The speed of administration of adrenaline utilising a Minijet (CSL Limited, Parkville, Victoria, Australia) is faster than using adrenaline in glass ampoules presented in their plastic packaging. Removing the plastic packaging from the 1 mL (1 mg) ampoule might result in more rapid administration similar to the Minijet. Resuscitation personnel requiring rapid access to adrenaline should consider storing it as either Minijets or ampoules devoid of packaging. These results might be extrapolatable to other clinical scenarios, including pre-hospital and anaesthesia, where other drugs are required for rapid use.


Intraventricular Wenckebach conduction and localized reentry in a case of right ventricular dysplasia with recurrent ventricular tachycardia.
Serial electrophysiologic studies were performed in a patient with recurrent ventricular tachycardia of left bundle branch configuration whose course and noninvasive evaluation are consistent with a diagnosis of right ventricular dysplasia. The localization of slowed conduction to the right ventricular apex, the reproducible initiation and termination of tachycardia with programmed extrastimuli and the presence of continuous electrical activity during tachycardia suggest a reentrant mechanism for this arrhythmia. Antiarrhythmic drugs further prolong the already fragmented apical electrogram and result in Wenckebach conduction within the abnormal portion of the right ventricle during pacing and tachycardia. Electrophysiologic findings are remarkably similar in studies performed 32 months apart.


Noninvasive assessment of left ventricular diastolic function by pulsed Doppler echocardiography in patients with hypertrophic cardiomyopathy.
Hypertrophic cardiomyopathy is a primary myocardial disease in which symptoms may frequently result from impaired left ventricular relaxation, filling and compliance. In the present investigation, Doppler echocardiography was utilized to measure transmitral flow velocity and thereby assess left ventricular diastolic performance noninvasively in a group of 111 patients representative of the broad clinical spectrum of hypertrophic cardiomyopathy. In patients with hypertrophic cardiomyopathy, all Doppler indexes of diastolic relaxation and filling differed significantly (p less than 0.001) from those obtained in 86 control subjects without heart disease, namely, prolongation of isovolumic relaxation (94 +/- 24 versus 78 +/- 12 ms) and of the early diastolic peak of flow velocity (244 +/- 55 versus 220 +/- 28 ms), as well as slower deceleration (3.4 +/- 1.4 versus 4.9 +/- 1.3 m/s2) and reduced maximal flow velocity in early diastole (0.5 +/- 0.2 versus 0.6 +/- 0.1 m/s). As an apparent compensation for impaired relaxation and early diastolic filling, the atrial contribution to left ventricular filling was increased, as shown by increased late diastolic flow velocity (0.4 +/- 0.3 versus 0.3 +/- 0.1 m/s) and reduced ratio of maximal flow velocity in early diastole to that in late diastole (1.4 +/- 0.8 versus 2.1 +/- 0.9). The vast majority of patients with hypertrophic cardiomyopathy (91 [82%] of 111) showed evidence of impaired left ventricular diastolic performance, as assessed from the Doppler waveform. Abnormal Doppler diastolic indexes were identified with similar frequency in patients with (78%) or without (83%) left ventricular outflow obstruction, as well as in patients with (84%) or without (80%) cardiac symptoms. However, patients with nonobstructive hypertrophic cardiomyopathy showed more severe alterations in the Doppler indexes of diastolic function than did patients with obstruction. Thus, abnormal diastolic performance as assessed by Doppler echocardiography was apparent in the vast majority of the study patients with hypertrophic cardiomyopathy, independent of the presence or absence of cardiac symptoms or a subaortic pressure gradient. The high frequency with which diastolic abnormalities are identified in asymptomatic patients with hypertrophic cardiomyopathy suggests that impaired diastolic performance may be present at a time in the natural history of the disease when functional limitation is not yet evident.


[Zuclopenthixol benzoate poisoning in a child: evidence from chromatography].
Zuclopenthixol is a thioxanthene-based neuroleptic. It may cause acute intoxication in children with neurological and consciousness disorders. Immunochromatography is unable to identify the molecule and diagnosis requires mass spectroscopy and HP chromatography. The short time needed for this technique significantly improves the exploration and treatment of Clopixol(®) poisoning.


Role of central angiotensin II receptors in cold-induced hypertension.
Earlier studies from this laboratory showed that central angiotensin II (AngII) receptors are upregulated by chronic cold exposure. The purpose of this study was to determine whether central AngII receptors may play a role in the development of cold-induced hypertension. Four groups of rats (six rats each) were used. Two groups were exposed to cold (5 degrees C) and the other two groups were kept at 25 degrees C. One cold-exposed and one warm-adapted group were treated chronically, via osmotic minipumps, with AngII type 1 (AT1) receptor blocker (losartan, 6.0 microg/2.5 microL/h, intracerebroventricularly) at the beginning of cold exposure. Systolic blood pressure (BP) of the cold-exposed untreated group increased during week 1 of cold exposure and rose to 160+/-4 mm Hg by week 4, whereas BP of the losartan-treated group in cold did not increase and remained at 121+/-3 mm Hg. Cold-induced increases in drinking response to AngII, plasma renin activity, and urine norepinephrine output disappeared in the treated rats, indicating blockade of central AngII receptors. Withdrawal of losartan at 4 weeks resulted in an increase in BP of this group to the cold-exposed untreated level, which was accompanied by an increase in the above parameters. Significant increases in AngII-induced drinking response and hypothalamic AT1 receptor mRNA content of the cold-exposed rats indicate upregulation of AngII receptors during chronic cold exposure. Hypothalamic AngII level was not affected by cold exposure. Upregulation of brain AT1 receptors plays a role in the development of cold-induced hypertension.


Assessing cancer in people with profound and multiple disabilities.
Cancers are as common in individuals with intellectual disabilities as in the general population (GP). For the subgroup of people with profound and multiple disabilities (PMD) who present with both severe intellectual disability and major motor disorders, the frequency and distribution of cancers are currently not known, preventing proper cancer surveillance. We carried out a systematic and synthetic review of the medical literature, including a focused search of Japanese data. The total risk of cancer in individuals with PMD is thought to be lower than in the GP, possibly due to a shorter life expectancy. They have reduced exposure to cancer risk factors, such as alcohol, tobacco, sunlight, human papillomavirus infection, occupational toxins, and being overweight. On the other hand, individuals with PMD present a greater frequency of gastroesophageal reflux disease, Helicobacter pylori gastritis, chronic cystitis, and cryptorchidism, which increase the risk for cancer of the esophagus, stomach, urinary bladder, and testes. In addition, certain genetic disorders underlying compromised motor and cognitive functions are associated with higher risk of childhood cancers. An analysis of 135 cancers in persons with PMD in Japan suggested that they present a particular tumor profile, with certain cancers rarer than in the GP, whereas cancers of the digestive tract are frequent. Cancers of the digestive tract occurred significantly earlier than in the GP (colon: average age 48.3 years vs. 71.3 years in the GP, esophagus: 39 years vs. 72 years in the GP). An increasing number of therapeutic successes in children and adults with PMD have been reported in different countries when cancers are discovered early. Individuals with PMD must be appropriately monitored for cancer. Screenings for breast and colon cancer, as well as regular monitoring of the esophagus, stomach, urinary bladder, and testicles, are necessary. Population-based epidemiological studies are needed to better understand risk factors, frequency, and distribution of cancers in the PMD population.


LEA proteins in higher plants: structure, function, gene expression and regulation.
Late embryogenesis abundant (LEA) proteins are mainly low molecular weight (10-30 kDa) proteins, which are involved in protecting higher plants from damage caused by environmental stresses, especially drought (dehydration). These findings and the fact that the breeding of drought tolerant varieties would be of great value in agriculture, form the basis of search for anti-drought inducible genes and their characterization. LEA proteins are generally classified into six groups (families) according to their amino acid sequence and corresponding mRNA homology, which are basically localized in cytoplasm and nuclear region. LEA protein synthesis, expression and biological activities are regulated by many factors (e.g. developmental stages, hormones, ion change and dehydration), signal transduction pathways and lea genes. No tissue-specific lea gene expression has been considered as one main regulatory mechanism on the basis of extensive studies with the model plant, Arabidopsisthaliana. The study of the regulatory mechanism of lea gene expression is an important feature of modern plant molecular biology.


Claude Beck and cardiac resuscitation.
The problem of sudden death due to derangement of the cardiac mechanism remained poorly defined into the 20th century. The physiologist Carl J. Wiggers proposed maintenance of the circulation by manual massage of the heart, followed by electrical defibrillation at a suitable time. His surgical colleague Claude S. Beck, with several associates, defined a precise sequence of steps for management of cardiac arrest in the operating room and was able to apply them clinically with complete success. Subsequently, patients were resuscitated outside the operating room as well; and finally, massage and defibrillation across the intact chest have made cardiac resuscitation available at any place or time.


How do parents deal with their children's chronic kidney disease? A qualitative study for identifying factors related to parent's adaptation.
Parents' adaptation affects the health outcomes of children with chronic kidney diseases (CKD). Identifying factors that affect parents' adaptation is necessary to understand their adaptation status. This study aims to explore factors related to the adaptation of parents who have children with CKD. This was a qualitative study with a content analysis approach. Seventeen parents of children with CKD were selected by using purposive sampling. The leading researcher performed semi-structured, in-depth, face-to-face interviews to collect data. Conventional content analysis was used to analyze data. Two main categories extracted from the data were "adaptation facilitators" and "adaptation barriers." Adaptation facilitators were supported by three sub-categories: "social support", "family capability" and "spiritual beliefs". Four sub-categories of "adaptation barriers" were revealed as: "family-related barriers," "mental stress by others," "the chronic nature of the disease," and "unfavorable treatment conditions." Identifying the factors influencing parental adaptation helps the medical staff to make the necessary interventions to support the parents. According to this study, increasing parent access to the required information, supporting them financially and emotionally, and helping them identify support resources can facilitate their adaptation to their child's chronic illness. Also, identifying and eliminating adaptation barriers can help parents deal better with their child's chronic disease.


The relationship between seropositivity against Chlamydia pneumoniae and stroke and its subtypes in a Latvian population.
Serological evidence of infection with Chlamydia pneumoniae has been associated with cardiovascular diseases, but the relationship with stroke and its risk factors remains not completely understood. The aim of this study was to determine whether serological evidence of infection with Chlamydia pneumoniae was associated with the risk of ischemic stroke and any of investigated stroke subtypes. Confirmed stroke cases (n=102) were compared with gender- and age-matched control patients (n=48). The patients with stroke were divided into 3 groups according to the TOAST criteria: atherothrombotic (n=36), cardioembolic (n=47), and of undetermined etiology (n=19). Plasma levels of IgG antibodies to Chlamydia pneumoniae were measured by enzyme-linked immunosorbent assay. There was a significant association between seropositivity to Chlamydia pneumoniae and stroke. Anti-Chlamydia pneumoniae IgG antibodies were detected in 64 case patients (62.7%) and 17 control patients (35.4%) (χ(2)=9.8; df=1; P=0.002). IgG seropositivity to Chlamydia pneumoniae was linked to all the analyzed etiological subtypes of stroke. This study showed that IgG seropositivity to Chlamydia pneumoniae was associated with stroke and all the analyzed etiological subtypes of stroke.


Expression of EMMPRIN in adenoid cystic carcinoma of salivary glands: correlation with tumor progression and patients' prognosis.
Extracellular matrix metalloproteinase inducer (EMMPRIN) plays a critical role in the progression of malignancies by stimulating expression of metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) in stromal cells. However, the expression of EMMPRIN in adenoid cystic carcinoma (ACC) of salivary glands, and its correlation with patients' prognosis have never been investigated thus far. In the present study, the expression of EMMPRIN was examined in 72 ACCs and 20 normal salivary gland tissues by immunohistochemistry. The expression of MMP-2, MMP-9, VEGF, Ki-67 index, and microvessel density (MVD) labeled by CD31 were also assessed by immunohistochemistry in ACCs. The positivity of EMMPRIN in ACCs was 62.5%, which was significantly higher than that in normal salivary gland tissues (P<0.01). EMMPRIN expression was positively correlated with tumor size, histotypes, clinical stage, perineural invasion, vascular invasion, metastasis, expression of MMP-2, MMP-9, VEGF, Ki-67 index, and MVD (P<0.05), but not with gender, age, tumor site or recurrence (P>0.05). Multivariate analysis showed that EMMPRIN expression, Ki-67 index, and solid histotype had an independent prognostic effect on overall survival (P<0.05). According to our findings, EMMPRIN might actively be involved in the growth, angiogenesis, invasion and metastasis of ACCs. Measurement of EMMPRIN may be helpful in predicting patients' prognosis and understanding the malignant behaviors of ACCs.


Stages in the dissolution of human enamel crystals in dental caries.
Various stages in monocrystal dissolution occurring during human enamel were studied by high resolution transmission electron microscopy. After the development of a central core lesion, two mechanisms by which the dissolution spread laterally to the (100) faces of the crystal could be demonstrated on the basis of the systematic orientation of the crystallographic axes. In the first case, the destruction was developing parallel to (120) planes and the borders were limited by (100) planes. In the second type, the development of the lateral side lesion was observed parallel to (100) planes. The carious destruction of the enamel monocrystal occurred as a result of the development of several lateral side dissolutions of the two types described, proceeding along the entire central core lesion.


A highly selective and colorimetric assay of lysine by molecular-driven gold nanorods assembly.
In this contribution, a simple, rapid, colorimeteric and selective assay for lysine was achieved by a controllable end-to-end assembly of gold nanorods (AuNRs) in the presence of Eu(3+) and lysine. This one-pot end-to-end assembly of 11-mercaptoundecanoic acid (MUA) modified AuNRs was occurred in Britton-Robinson buffer of pH 6.0, which involves the coordination binding between Eu(3+) and COO(-) groups as well as the electrostatic interaction of the COO(-) groups of MUA with the -NH(3)(+) group of lysine. As monitored by absorption spectra, scanning electron microscopic (SEM) images and dynamic light scattering (DLS) measurement, the end-to-end chain assembly results in large red-shift in the longitudinal plasmon resonance absorption (LPRA), giving red-to-blue color change of AuNRs. Importantly, it was found that the red-shift of LPRA is linearly proportional to the concentrations of lysine in the range of 5.0×10(-6)-1.0×10(-3)M with the limit of detection (LOD) being 1.6×10(-6)M (3σ/k). This red-shift of LPRA is highly selective, making it possible to develop a rapid, selective and visual assay for lysine in food samples.


High-performance liquid chromatographic determination of ampicillin and its metabolites in rat plasma, bile and urine by post-column degradation with sodium hypochlorite.
A high-performance liquid chromatographic method has been developed for the determination of ampicillin (1) and its metabolites [(5R,6R)-ampicilloic acid (2), the (5S,6R)-epimer (3) and the corresponding (2R)-piperazine-2',5'-dione (4)] in rat plasma, bile and urine. The method involves the separation of 1-4 from the background components of the biological fluids on a reversed-phase C18 column, using sodium heptanesulphonate as an ion-pairing agent and methanol in the mobile phase, followed by post-column degradation with 1.5 M sodium hydroxide-0.02% sodium hypochlorite solution at ambient temperature, and detection of the degradation product(s) of each compound at 270 nm. The detection limits were about 25 ng for each compound at a signal-to-noise ratio of 3. At concentrations of 2-5 micrograms/ml of each compound, the within- and between-run precisions (relative standard deviation) were 0.77-7.15% and 1.76-5.96%, respectively. The plasma, biliary and urinary levels of 1 and its metabolites were determined by the proposed method after intravenous administration of 1 to rats.


Emerging Roles of Coblation in Rhinology and Skull Base Surgery.
Coblation is a technology that incorporates bipolar radiofrequency energy to ablate tissue at relatively low temperatures. Its use for sinonasal surgery is actively being investigated, including applications for turbinate reduction, sinus surgery, skull base surgery, and adenoidectomy. Potential benefits include reduction in blood loss, improved endoscopic surgical visualization, and reduction in postoperative pain. The main drawbacks are its relatively high cost, potential adverse effects on functional epithelium, and relative paucity of long-term outcomes.


Laparoscopic resection for splenic artery aneurysm using the lateral approach: report of two cases.
We report two cases of successful laparoscopic surgery for splenic artery aneurysm. In case 1, a 59-year-old man who had hypertension was admitted to the hospital with complaints of slight back pain. CT scan showed a winding splenic artery and an aneurysm behind the pancreas body. In case 2, a 71-year-old woman with hypertension consulted us and was diagnosed with splenic artery aneurysm. Her aneurysm increased from 1.2 mm to 20 mm at the 1-year follow-up. In both cases, we performed laparoscopic splenectomy, using the left lateral approach, to resect the aneurysm. Splenectomy was performed after the spleen had changed color. The operating times were 210 and 259 min, respectively and the bleeding was 60 and 100 mL, respectively. The postoperative course was uneventful. By using the lateral approach from the left side, we were able to precisely resect the splenic artery aneurysm under a stable laparoscopic view.


Whatever happened to symptom substitution?
Symptom substitution is a theoretical consequence of the psychodynamic model of psychopathology and symptom formation that contrasts markedly with behavioral models. Symptom substitution was a major scientific and clinical question about a half century ago that was abandoned rather than answered partly because it did not seem to occur and partly because perceived methodological problems impeded empirical research. The contemporary relevance of symptom substitution is that the psychodynamic model of psychopathology and symptom formation from which the prediction of symptom substitution stems continues to be widely taught and to broadly inform clinical practice. This article revisits the psychodynamic model of symptom formation and substitution, restates perceived methodological limitations to its empirical study, demonstrates that symptom substitution is an empirically testable prediction, reviews the relevant empirical literature, and discusses implications for the science and practice of clinical psychology including a proposed research design for certifying bona fide psychoanalytic symptoms.


Decrease in the fatigue resistance of nickel-titanium rotary instruments after clinical use in curved root canals.
The changes in fatigue resistance of nickel-titanium rotary ProFile instruments after clinical use for shaping 10 curved molar root canals were evaluated in this study. Twenty-five sets of files #20, #25, and #30 and tapers .04 and .06 were divided into 2 groups, one with 10 sets of new files that were tested in a fatigue test bench device as a control. The other, experimental group, with 15 sets of clinically used files, was tested in the same device. The Student t test was employed to compare mean values of the measured parameters. A statistically significant decrease in the number of cycles to failure was determined for the clinically used files, as compared with the new ones. The fracture point was the same for all files tested. The clinical use of ProFile instruments for shaping curved canals reduces their fatigue resistance.


Efficacy of Visual Retraining in the Hemianopic Field after Stroke: Results of a Randomized Clinical Trial.
To evaluate the efficacy of motion discrimination training as a potential therapy for stroke-induced hemianopic visual field defects. Clinical trial. Forty-eight patients with stroke-induced homonymous hemianopia (HH) were randomized into 2 training arms: intervention and control. Patients were between 21 and 75 years of age and showed no ocular issues at presentation. Patients were trained on a motion discrimination task previously evidenced to reduce visual field deficits, but not in a randomized clinical trial. Patients were randomized with equal allocation to receive training in either their sighted or deficit visual fields. Training was performed at home for 6 months, consisting of repeated visual discriminations at a single location for 20 to 30 minutes daily. Study staff and patients were masked to training type. Testing before and after training was identical, consisting of Humphrey visual fields (Carl Zeiss Meditech), macular integrity assessment perimetry, OCT, motion discrimination performance, and visual quality-of-life questionnaires. Primary outcome measures were changes in perimetric mean deviation (PMD) on Humphrey Visual Field Analyzer in both eyes. Mean PMDs improved over 6 months in deficit-trained patients (mean change in the right eye, 0.58 dB; 95% confidence interval, 0.07-1.08 dB; mean change in the left eye 0.84 dB; 95% confidence interval, 0.22-1.47 dB). No improvement was observed in sighted-trained patients (mean change in the right eye, 0.12 dB; 95% confidence interval, -0.38 to 0.62 dB; mean change in the left eye, 0.10 dB; 95% confidence interval, -0.52 to 0.72 dB). However, no significant differences were found between the alternative training methods (right eye, P = 0.19; left eye, P = 0.10). To date, no widely accepted therapy is available to treat HH. This study evaluated the efficacy of a promising potential treatment, visual perceptual training. We failed to find a difference between treatment training within the deficit field and control training within the sighted field when performed in a home environment.


Meet the author: Professor Zhijian Cai.
In this Q&A, Cell Metabolism's Scientific Editor Rosalind Mott talks to Prof. Zhijian Cai about his paper "UBE2M-mediated neddylation of TRIM21 regulates obesity-induced inflammation and metabolic disorders" and his experience with publishing through Cell Press Community Review.


Study on impact dynamic characteristics of semi-autogenous mill liner based on improved multivariable method.
The impact resistance of semi-autogenous mill liner has an important influence on the reliable operation of the system. The complex dynamic characteristics in the process of collision with abrasive medium are studied by the improved multivariable method proposed in this paper. Firstly, based on manifold element method, the deformation of abrasive medium and lining plate in the contact area is expressed by the coordinates of first-order manifold element basis function, while the deformation of the non-contact region is described by modal coordinates to improve the traditional multivariable method, and the displacement constraint equations as well as the acceleration constraint equations of the collision system are derived, then the Lagrange method is used to establish the impact dynamic equation of abrasive medium and lining plate system. Secondly, a collision test rig between abrasive medium and lining plate was built to verify the correctness and accuracy of the proposed method. Finally, the influence of structural parameters and motion parameters of abrasive medium and lining plate on the dynamic characteristics of collision system is analyzed by parameter analysis method. It is found that when the Poisson's ratio of abrasive medium to lining plate material exceeds 1.0, the increase amplitude of stress becomes smaller. The increase amplitude of displacement, velocity, acceleration and stress at the collision contact point decreases when the initial velocity of abrasive medium exceeds 3.0 m/s. The stress at the collision contact point changes greatly, and the maximum acceleration occurs in advance when the radius of abrasive medium exceeds 20 mm. When the thickness of liner exceeds 40 mm, the time of maximum acceleration to reach is almost unchanged. The results show that compared with the traditional multivariable method, the improved multivariable method can increase the modeling efficiency and solving accuracy, and lay a theoretical foundation for optimizing the structure of the liner and raising the service life of the system.


Acute kidney injury after cardiac arrest: a systematic review and meta-analysis of clinical studies.
The prevalence of and the risk factors for acute kidney injury (AKI) after cardiac arrest (CA), and the association of AKI with outcome have not been systematically investigated so far. In this systematic review and meta-analysis, studies on adult patients (dating from January 1966 to August 2015) published as full-text articles were screened. Two authors independently extracted data and assessed study quality using the Quality Assessment Tool of the U.S. National Institute of Health. Data were summarized using weighted means. Eight studies (total 1693 patients; 68% males) were included. The incidence of AKI was 37%. In six studies where a standard AKI definition (RIFLE, AKIN or KDIGO) was used, the incidence for AKI stage 1 or higher was 52%. AKI occurred at a median of 1-2 days from cardiac arrest in 6/8 studies. Renal replacement therapy (RRT) was used in 239 AKI patients (33%), of whom five (2%) still needed RRT at 30 days after CA. An initial non-shockable rhythm, a longer duration of arrest, higher creatinine levels on admission, and the presence of shock or higher blood lactate after resuscitation were significant predictors of AKI occurrence. Hospital mortality was significantly higher in AKI vs. non-AKI patients (OR 2.63 [1.86-3.68]; P<0.0001). post-arrest AKI has an early onset, occurs in more than 50% of CA patients, and it is associated with increased mortality. Decreased renal function on admission, an initial non-shockable rhythm and both pre-arrest and post-arrest markers of hypoperfusion are associated with increased risk of AKI in this setting.


Carotid body grafts induce chemosensitivity in muscle nerve fibers of the cat.
The ability of carotid body parenchymal cells to change the physiological properties of nerve fibers was tested in 8 cats by transplanting the carotid body to the tenuissimus muscle and reinnervating the organ with the muscle nerve. Ninety-five to 174 days after the transplant, electrophysiological recordings were obtained from the reinnervating tenuissimus nerves. Forty percent of the regenerating nerve fibers having spontaneous activity responded to muscle stretch, hypoxia, NaCN, ACh, nicotine and dopamine, apparently because of dual innervation of glomus cells and muscle spindles. Five of 6 transplants, examined electron microscopically, contained viable glomus cells innervated by axon terminals. Neither the normal tenuissimus nerve nor the same nerve regenerating into adipose tissue grafts or to one non-viable carotid body transplant showed chemosensory properties although these grafts contained numerous, small myelinated axons indicative of extensive nerve regeneration. It is concluded that carotid body cells are capable of inducing chemosensory properties in axons that, normally, subserve a mechanosensory function.


Correlation of Tumor Budding With Known Clinicopathological, Histomorphological and Hormonal Receptor Status in Patients With Invasive Breast Carcinoma.
Introduction: Tumor blossoming may be a predictive indicator for a variety of cancers. At the invasive origin of the tumor, cells get detached from the original tumor mass. Aims & objectives: Studying breast cancer tumor budding, as well as its link to other prognostic indicators, such as clinicopathological features and hormone receptor status, will be the focus of this study. Materials & methods: Over six years, 110 cases of invasive breast cancer were examined. Ten high-power fields were used to analyze H&E-stained slices for tumor sprouting. It was determined that the tumor buds were divided into low and high grades. Tumor budding and other prognostic factors were compared using the chi-square test. It was considered significant if the p-value was less than or equal to 0.05. Results: There were 110 cases of invasive ductal carcinoma, which accounts for more than half of the total cases (88.18%). A total of 144 tumors were present, of which 74 displayed strong budding and 36 displayed poor budding. A correlation between tumor budding and tumor size, lymph node metastasis, and tumor stage is statistically significant (P = 0.0099). Conclusion: Tumor budding in breast cancer is an easily visible in microscopy, novel prognostic indicator. A new prognostic element may be added to the reporting process.


Prevention of nitroimidazole resistance in Campylobacter pylori by coadministration of colloidal bismuth subcitrate: clinical and in vitro studies.
One hundred patients with duodenal ulceration and Campylobacter pylori in their stomach were entered into a double blind placebo controlled prospective study. Treatment schedules were cimetidine and placebo, or cimetidine and tinidazole, or colloidal bismuth subcitrate (CBS) and placebo, or CBS and tinidazole. Seventeen per cent of isolates of C pylori obtained at the first endoscopy were resistant to tinidazole and 70% of the second isolates from patients given cimetidine and tinidazole became tinidazole resistant. Suspensions of nitroimidazole sensitive cultures of C pylori showed that three of 22 isolates had a nitroimidazole resistant subpopulation. In patients who healed and remained free of C pylori after treatment ulcers recurred less often than in patients who healed but retained C pylori (23% v 73% over 12 months, p less than 0.001).


Perilymphatic application of alpha-melanocyte stimulating hormone ameliorates hearing loss caused by systemic administration of cisplatin.
It has previously been demonstrated that ototoxicity induced by systemic administration of cisplatin is reduced by concomitant systemic administration of alpha-melanocyte stimulating hormone (alpha-MSH). In this study we investigated the effects of cochlear, perilymphatic application of alpha-MSH during intraperitoneal administration of cisplatin. Guinea pigs, implanted with a round-window electrode, allowing daily monitoring of the compound action potential (CAP), and also implanted with a mini-osmotic pump, pumping at a rate of 0.25 microl/h either physiological saline or alpha-MSH solution (0.02, 2, and 20 microg/ml), were treated daily with a bolus injection of cisplatin (2 mg/kg) until the electrocochleogram showed a persistent decrease in CAP amplitude (> or = 40 dB threshold shift at 8 kHz). Then, cisplatin treatment was stopped, but intracochlear perfusion of alpha-MSH or physiological saline was continued for 10 days to evaluate possible effects of alpha-MSH on the expected recovery. On day 10, the animals were killed and the cochleas were fixed and processed for histological analysis. All groups required 6-7 days of cisplatin to reach the criterion CAP threshold shift. Ten days after cessation of the cisplatin treatment, recovery of the CAP was observed in all groups and at all frequencies, although it was more pronounced at the lower frequencies. With respect to recovery, small statistically significant differences were found between the saline and the alpha-MSH co-treated groups. Histological results showed significantly less outer hair cell (OHC) loss in the group co-treated with 2 microg/ml alpha-MSH as compared to the group co-treated with saline. Since alpha-MSH was directly delivered to the cochlea, the ameliorating effect of alpha-MSH on OHC survival is likely to involve a cochlear target.


Exploration of Factors Associated With Surgeon Deviation From Practice Guidelines for Management of Inguinal Hernias.
Despite availability of evidence-based guidelines for surgery, many patients receive guideline-discordant care. Reasons for this are largely unknown. For example, evidence-based guidelines recommend a minimally invasive approach for persons with bilateral or recurrent unilateral inguinal hernias. Benefits are also noted for primary unilateral inguinal hernia. However, findings from previous quantitative research indicate that only 26% of patients receive this treatment and only 42% of surgeons offer a minimally invasive approach, even for recurrent or bilateral hernias. To explore factors associated with surgeon choice of approach (minimally invasive vs open) in inguinal hernia repair as a tool to gain an understanding of guideline-discordant care. Qualitative study performed as part of a larger explanatory sequential mixed methods design. Purposive sampling was used to recruit 21 practicing surgeons from a large statewide quality collaborative who were diverse with regard to practice type, geographic location, and surgical specialty. Qualitative interviews consisted of a clinical vignette, followed by semi-structured interview questions. Through thematic analysis using qualitive data analysis software, patterns within the data were located, analyzed, and identified. All data were collected between April 24 and July 31, 2018. Clinical vignette as part of the qualitative interviews. Capture of surgical approaches and factors motivating decision-making for inguinal hernia repair. Of the 21 participating surgeons, 17 (81%) were men, 18 (86%) were White, and all were 35 years of age or older. Data revealed 3 dominant themes: surgeon preference and autonomy (eg, favoring one approach over the other), access and resources (eg, availability of robot), and patient characteristics (eg, age, comorbidities). Decision-making for the approach to inguinal hernia repair is largely influenced by surgeon preference and access to resources rather than patient factors. Although a one-size-fits-all approach is not recommended, the operative approach should ideally be informed by patient factors, including hernia characteristics. Addressing surgeon preference and available resources with a clinician-facing decision aid may provide an opportunity to optimize care for patients undergoing inguinal hernia repair.


Zinc deficiency manifested by dermatitis and visual dysfunction in a patient with Crohn's disease.
We report a case of Crohn's disease with low serum zinc concentration in a 26-year-old woman. She demonstrated acrodermatitis enteropathica and decreased visual acuity during total parenteral nutrition. Subsequent intravenous zinc supplementation resulted in alleviation of the skin lesions and improvement of visual acuity. This case supports the notion that depressed serum zinc in Crohn's disease may cause clinical manifestations, such as acrodermatitis enteropathica and retinal dysfunction, which may be correctable with zinc supplementation.


Clinical assessment of a flow-through fluorometric blood gas monitor.
We performed an observational study to evaluate a flow-through fluorometric instrument (Gas-STAT) that continuously measures the carbon dioxide tension (PCO2), oxygen tension (PO2), and pH of blood in the cardiopulmonary bypass circuit. Setup and calibration of the instrument typically required 20 minutes. During bypass, 129 blood samples were drawn from 16 patients for comparison with conventional measurements obtained with a blood gas machine. Data for each variable, within each sensor, were analyzed by linear regression. The ranges of the standard errors of the estimate were 0.7 to 4.2 mm Hg for PCO2, 18.3 to 78.7 mm Hg for the high PO2 range, 1.4 to 7.1 mm Hg for the low PO2 range, and 0.008 to 0.049 for pH. The regression lines differed from the identity line (P less than 0.05) in at least one variable in most patients, and large deviations from the line of identity in both slope and intercept were common. Among 58 sensors evaluated, failures occurred in 5 (2.9%) of the 174 optodes, and minor leakage occurred in 2 (3.4%) of the flow-through cells. We conclude that although this flow-through fluorometric instrument is an adequate monitor of trends in blood gases during cardiopulmonary bypass, it is not accurate enough to supplant conventional laboratory measurements.


Future directions in imaging pouches.
The sections of this special issue on the ileal pouch demonstrate that in the nearly 45 years since the ileal pouch has been utilized to treat patients with colitis and familial adenomatous polyposis, a substantial number of patients experience both short- and long-term morbidity and that imaging plays an important role in their management. Further, referral centers are encountering an increasing number of patients with pouch and peri-pouch complications and dysfunction. Many of these patients have had their pouches for years, and many have experienced a reduced quality of life as a result of their symptoms.As we look to the future, what are the specific questions that arise from this compilation of experience from institutions that see large numbers of patients with an ileal pouch? In what areas are we deficient? In what areas are we using the wrong methods? What should we be doing differently?


Anterior chamber depth during hemodialysis.
Exacerbation of chronic glaucoma or acute glaucoma is occasionally observed in patients undergoing hemodialysis (HD) because of anterior chamber depth changes during this therapy. To evaluate anterior chamber depth and axial length in patients during HD sessions. A total of 67 eyes of 35 patients were prospectively enrolled. Axial length and anterior chamber depth were measured using ultrasonic biometry, and these measures were evaluated at three different times during HD sessions. Body weight and blood pressure pre- and post-HD were also measured. There was no difference in the axial length between the three measurements (P = 0.241). We observed a significantly decreased anterior chamber depth (P = 0.002) during HD sessions. Our results support the idea that there is a change in anterior chamber depth in HD sessions.


Hemoperfusion with an immobilized polymyxin B fiber column inhibits activation of vascular endothelial cells.
Involvement of the activation of neutrophils and vascular endothelial cells in the pathology of sepsis has recently been reported. We therefore investigated whether direct hemoperfusion (DHP) with a polymyxin B immobilized fiber column (PMX) could reduce the level of plasminogen activator inhibitor-1 (PAI-1), an index of vascular endothelial cell activation. Twelve sepsis patients satisfying the following criteria were enrolled in the study: (i) stable global oxygen metabolism (oxygen delivery index>500 mL/min/m2 and oxygen consumption index>120 mL/min/m2); (ii) abnormal tissue oxygen metabolism (PCO2 gap: gastric mucosal PCO2 minus arterial PCO2 difference>8 mm Hg); and (iii) mean blood pressure>or=60 mm Hg. Direct hemoperfusion with PMX was performed twice (for 3 h each time) within 24 h. Plasminogen activator inhibitor-1 was measured a total of 5 times: before PMX-DHP, immediately after the first DHP with PMX session (3 h after the start), and 24, 48, and 72 h afterward. The PAI-1 value was 150+/-30.0 ng/mL before DHP with PMX, 178+/-60.0 ng/mL immediately after DHP with PMX, 90+/-22.1 ng/mL at 24 h after, 65+/-21.0 ng/mL at 48 h after, and 64+/-18.3 ng/mL 72 h after. The values were significantly lower from 48 h onward compared with baseline. These data suggest that DHP with PMX inhibits vascular endothelial cell activation.


Denitrification performance of sulfur-based autotrophic denitrification and biomass‑sulfur-based mixotrophic denitrification in solid-phase denitrifying reactors using novel composite filters.
Both the elemental sulfur-based autotrophic denitrification (ESAD) and the biomass‑sulfur-based mixotrophic (simultaneous autotrophic and heterotrophic) denitrification processes (BSMD) are efficient methods for removing nitrate from wastewater. However, a comparative analysis of the denitrification capacity of the BSMD and ESAD in the packed bed reactors is still lacking. In this paper, corncob powder was selected as the biomass source to prepare biomass‑sulfur-based composite filter (BSCF) for the BSMD process. The denitrification performances of the three identical lab-scale bioreactors packed with varying elemental sulfur-based composite filters (ESCFs) were compared under varying loading conditions, and the optimal ESCF of the ESAD system was 2:1 by weight ratio of sulfur powder to shell powder. In pilot-scale experiments, the results showed that BSCF could decrease the sulfate productivity and gave better denitrification performance than the ESCF with the optimal nitrate removal rate (NRR) of 504 ± 12.3 mg NO3--N·L-1·d-1. In addition, the two-stage flushing strategy (for the removal of aged sludge) can effectively improve the denitrification capacity, while the denitrification will be inhibited when the influent dissolved oxygen concentration was higher than 4.5 mg L-1. Moreover, the heterotrophs and autotrophs were abundant in the reactors. Over time, the abundance of autotrophs increased while that of heterotrophs decreased. Overall, BSCF could be a promising and economic technology to improve the effluent quality.


Pathogenic mechanisms of osteogenesis imperfecta, evidence for classification.
Osteogenesis imperfecta (OI) is a connective tissue disorder affecting the skeleton and other organs, which has multiple genetic patterns, numerous causative genes, and complex pathogenic mechanisms. The previous classifications lack structure and scientific basis and have poor applicability. In this paper, we summarize and sort out the pathogenic mechanisms of OI, and analyze the molecular pathogenic mechanisms of OI from the perspectives of type I collagen defects(synthesis defects, processing defects, post-translational modification defects, folding and cross-linking defects), bone mineralization disorders, osteoblast differentiation and functional defects respectively, and also generalize several new untyped OI-causing genes and their pathogenic mechanisms, intending to provide the evidence of classification and a scientific basis for the precise diagnosis and treatment of OI.


A divided attention experiment with pervasively hyperactive children.
Task performance of 12 pervasive hyperactives and controls was studied in a divided attention reaction time experiment. The two groups differed with respect to task efficiency. The hyperactives were slower than controls, had more variable reaction times, and made more frequent errors. Task inefficiency could not be explained by a deficiency in divided attention or impulsive responding in the hyperactive group. Further, the observed differences in IQ between the groups could not account for the differential performance finding. It is concluded that input and/or output processes, probably in combination with energetical factors, might be disturbed in hyperactive children.


Complete Genome Sequences of Five Isolated Pseudomonas Strains that Catabolize Pentose Sugars and Aromatic Compounds Obtained from Lignocellulosic Biomass.
We report on complete genome sequences of five Pseudomonas soil isolates that are capable of metabolizing pentose sugars and aromatic monomers. These complete genome sequence data provide insight into possible alternative hosts for the production of biofuels and bio-based chemicals from lignocellulosic feedstock.


Mechanical limits of bacterial flagellar motors probed by electrorotation.
We used the technique of electrorotation to apply steadily increasing external torque to tethered cells of the bacterium Escherichia coli while continuously recording the speed of cell rotation. We found that the bacterial flagellar motor generates constant torque when rotating forward at low speeds and constant but considerably higher torque when rotating backward. At intermediate torques, the motor stalls. The torque-speed relationship is the same in both directional modes of switching motors. Motors forced backward usually break, either suddenly and irreversibly or progressively. Motors broken progressively rotate predominantly at integral multiples of a unitary speed during the course of both breaking and subsequent recovery, as expected if progressive breaking affects individual torque-generating units. Torque is reduced by the same factor at all speeds in partially broken motors, implying that the torque-speed relationship is a property of the individual torque-generating units.


COVID-19 one year on: identification of at-risk groups for psychological trauma and poor health-protective behaviour using a telephone survey.
This study examined the profiles and correlates of psychological trauma, compliance with preventative measures, vaccine acceptance and participation in voluntary testing during the novel coronavirus disease 2019 (COVID-19) pandemic among the adult population in Hong Kong (n = 3,011). Data were collected through a telephone survey between December 2020 and February 2021, using measures of psychological trauma, compliance with preventative measures, reading news reports on COVID-19, vaccine acceptance and willingness to participate in voluntary testing. The prevalence of possible post-traumatic stress disorder was found to be 12.4%. Respondents were generally compliant with routine preventative measures, and approximately half had accepted vaccination and voluntary testing. Participants who had lower levels of education, were unemployed or had no income showed greater psychological trauma symptoms, whereas female, older and more educated participants showed greater compliance with preventative measures. Participants who spent more time watching news reports of COVID-19 had greater psychological trauma, but also greater compliance. Participants who were male, older, had lower education levels or were married showed greater acceptance of vaccination and participation in voluntary testing. Socio-demographic factors affected both psychological trauma and engagement in health-protective measures at one year after the onset of the pandemic. The theoretical and practical implications of these findings are discussed.


Development of a field enhanced photocatalytic device for biocide of coliform bacteria.
A field enhanced flow reactor using bias assisted photocatalysis was developed for bacterial disinfection in lab-synthesized and natural waters. The reactor provided complete inactivation of contaminated waters with flow rates of 50mL/min. The device consisted of titanium dioxide nanotube arrays, with an externally applied bias of up to 6V. Light intensity, applied voltage, background electrolytes and bacteria concentration were all found to impact the device performance. Complete inactivation of Escherichia coli W3110 (~8×10(3)CFU/mL) occurred in 15sec in the reactor irradiated at 25mW/cm(2) with an applied voltage of 4V in a 100ppm NaCl solution. Real world testing was conducted using source water from Emigration Creek in Salt Lake City, Utah. Disinfection of natural creek water proved more challenging, providing complete bacterial inactivation after 25sec at 6V. A reduction in bactericidal efficacy was attributed to the presence of inorganic and organic species, as well as the increase in robustness of natural bacteria.


Study to investigate the prevalence of human papillomavirus in Barrett's oesophagus using a novel screening methodology.
Human papillomavirus (HPV) is strongly associated with Barrett's dysplasia and oesophageal cancer suggesting a role in carcinogenesis. HPV persistence predicts treatment failure after endotherapy for Barrett's dysplasia. This pilot study applies a novel HPV screening tool (previously only used in the oropharynx) to detect HPV DNA directly and determine the prevalence rates in Barrett's oesophagus (BO). DNA was extracted from 20 formalin-fixed BO samples. HPV DNA was detected using real-time PCR and gel electrophoresis. 5 out of 20 patients were identified as positive for HPV. Prevalence was 25% in patients with BO. This method can be used in BO's tissue to determine HPV infection. Adoption of this as a screening test could potentially revolutionise future research in this area. If a clear link between HPV and Barrett's dysplasia can be confirmed, this qPCR method has the potential to aid in monitoring and/or dysplasia detection by stratifying those most at risk and aid in the development of new therapies.


Characterization of dihydroartemisinin-resistant colon carcinoma HCT116/R cell line.
Dihydroartemisinin (DHA) is an important artemisinin derivative and presents profound anti-tumor potential. A DHA-resistant cell line named HCT116/R derived from colon carcinoma cell line HCT116 was established in our previous study. Herein, we found that HCT116/R cells were much more resistant to DHA- or artesunate-induced proliferation inhibition and more tolerant to DHA-induced cell cycle arrest and apoptosis compared with those of the parent HCT116 cells. The protein levels of P-glycoprotein and MDR-associated protein 1 and the accumulation of doxorubicin in cells were similar in both cell lines. Moreover, HCT116/R cells were still sensitive to camptothecin- and doxorubicin-induced cell growth inhibition. To further explore the characterization of HCT116/R cell line, a proteomic study employing two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry was performed. Eight different expressed proteins between the two cell lines were identified including some heat shock proteins, annexins, etc. This study not only indicates that exposure to DHA may not induce a tumor multi-drug-resistant phenotype but also affords new clues for the further investigation of the anti-cancer mechanisms of DHA and other artemisinin derivatives.


Mercury as a serious health hazard for children in gold mining areas.
In many developing countries, mercury is used to extract gold from ore in small-scale mining areas. Exposure through mercury in these small-scale mining communities is a serious health hazard, especially to the children living and working there. Many children begin working with immediate contact to mercury from the very early age of seven. In Indonesia and Zimbabwe, 166 children were clinically examined for mercury. The mercury concentration in the blood, urine, and hair was analyzed. Compared to the control groups, the exposed children showed typical symptoms of mercury intoxication, such as ataxia. The children working with mercury had high levels of this substance in the various biomonitors. The exposure derives mainly from the liquid mercury used to bind gold, forming an amalgam. The amalgam is heated and the smelting amalgam releases mercury vapor plus the wanted gold. Mercury vapor in contrast to liquid mercury is highly toxic. This elemental, vaporized mercury is the main form of exposure. Since in over 50 countries children live in small-scale gold mining areas and are exposed in a similar way to mercury, immediate action is needed to reduce this severe chemical health hazard for children. Child labor with hazardous substances such as mercury must be stopped.


Recommendations for Radiotherapy Technique and Dose in Extra-nodal Lymphoma.
Extra-nodal sites may be involved in around 40% of patients with non-Hodgkin lymphoma. The general principles for target volume delineation in this setting are presented, together with specific examples. In general, the entire organ affected should be encompassed in the clinical target volume with an expansion of at least 10 mm, increased in some instances to account for patterns of potential lymphatic flow. Adjacent lymph nodes may be treated using standard techniques for nodal irradiation. Doses for extra-nodal lymphoma follow the same principles as nodal lymphoma, delivering 30 Gy in 15 fractions for Hodgkin and aggressive non-Hodgkin lymphoma and 24 Gy in 12 fractions for indolent lymphomas, with the exception of certain palliative situations, mycosis fungoides, central nervous system lymphoma and natural killer/T-cell lymphoma.


Evaluation of Neel Temperatures from Fully Self-Consistent Broken-Symmetry GW and High-Temperature Expansion: Application to Cubic Transition-Metal Oxides.
Using fully self-consistent thermal broken-symmetry GW, we construct effective magnetic Heisenberg Hamiltonians for a series of transition metal oxides (NiO, CoO, FeO, and MnO), capturing a rigorous but condensed description of the magnetic states. Then applying high-temperature expansion, we find the decomposition coefficients for spin susceptibility and specific heat. The radius of convergence of the found series determines the Neel temperature. The NiO, CoO, and FeO contain a small ferromagnetic interaction between the nearest neighbors (NNs) and the dominant antiferromagnetic interaction between the next-nearest neighbors (NNNs). For them, the derived Neel temperatures are in good agreement with experiment. The case of MnO is different because both NN and NNN couplings are antiferromagnetic and comparable in magnitude, for which the error in the estimated Neel temperature is larger, which is a signature of additional effects not captured by electronic structure calculations.


2019 Canadian Cardiovascular Society Position Statement for Transcatheter Aortic Valve Implantation.
Transcatheter aortic valve implantation (TAVI) or replacement has rapidly changed the treatment of patients with severe symptomatic aortic stenosis. It is now the standard of care for patients believed to be inoperable or at high surgical risk, and a reasonable alternative to surgical aortic valve replacement for those at intermediate surgical risk. Recent clinical trial data have shown the benefits of this technology in patients at low surgical risk as well. This update of the 2012 Canadian Cardiovascular Society TAVI position statement incorporates clinical evidence to provide a practical framework for patient selection that does not rely on surgical risk scores but rather on individual patient evaluation of risk and benefit from either TAVI or surgical aortic valve replacement. In addition, this statement features new wait time categories and treatment time goals for patients accepted for TAVI. Institutional requirements and recommendations for operator training and maintenance of competency have also been revised to reflect current standards. Procedural considerations such as decision-making for concomitant coronary intervention, antiplatelet therapy after intervention, and follow-up guidelines are also discussed. Finally, we suggest that all patients with aortic stenosis might benefit from evaluation by the heart team to determine the optimal individualized treatment decision.


Protocol for ridge preservation at severely compromised extraction sockets: Consecutive case series.
The physiologic bone remodeling accompanying tooth extraction is a phenomenon well described in the dental literature. Extraction sockets severely compromised by local infection, trauma, iatrogenesis, or other factors may exhibit enhanced reduction in alveolar dimensions during healing. The purpose of this report is to present an alveolar ridge preservation (ARP) protocol specifically intended for use at severely compromised sites. Seven patients presented to the Department of Periodontics, Army Postgraduate Dental School, Fort Gordon, Georgia, requiring extraction of teeth with partial or near-complete loss of the facial/buccal cortex. At each site, a cross-linked bovine collagen membrane was used to prevent collapse of the facial/buccal soft tissue and maintain space, a freeze-dried bone allograft was applied in the socket, and a dense polytetrafluoroethylene membrane covered the occlusal aspect. All sites healed uneventfully and resulted in favorable alveolar ridge dimensions for implant placement. Few authors have proposed specific ARP methods for managing severely deficient extraction sockets. The predominant recommendation has been staged reconstruction of the site applying hard and soft tissue augmentation. Observations reported herein suggest that staged reconstruction is avoidable at some extraction sockets exhibiting severe alveolar compromise. Controlled clinical investigation of this protocol appears warranted. Few authors have proposed alveolar ridge preservation (ARP) methods specifically intended for use at severely compromised extraction sockets. The prevailing recommendation at such sites is a staged protocol involving tooth extraction with delayed hard and soft tissue augmentation. The presented bilaminar ARP technique may eliminate the need for staged reconstruction at some severely compromised extraction sockets.


Anti-infectives in Drug Delivery-Overcoming the Gram-Negative Bacterial Cell Envelope.
Infectious diseases are becoming a major menace to the state of health worldwide, with difficulties in effective treatment especially of nosocomial infections caused by Gram-negative bacteria being increasingly reported. Inadequate permeation of anti-infectives into or across the Gram-negative bacterial cell envelope, due to its intrinsic barrier function as well as barrier enhancement mediated by resistance mechanisms, can be identified as one of the major reasons for insufficient therapeutic effects. Several in vitro, in silico, and in cellulo models are currently employed to increase the knowledge of anti-infective transport processes into or across the bacterial cell envelope; however, all such models exhibit drawbacks or have limitations with respect to the information they are able to provide. Thus, new approaches which allow for more comprehensive characterization of anti-infective permeation processes (and as such, would be usable as screening methods in early drug discovery and development) are desperately needed. Furthermore, delivery methods or technologies capable of enhancing anti-infective permeation into or across the bacterial cell envelope are required. In this respect, particle-based carrier systems have already been shown to provide the opportunity to overcome compound-related difficulties and allow for targeted delivery. In addition, formulations combining efflux pump inhibitors or antimicrobial peptides with anti-infectives show promise in the restoration of antibiotic activity in resistant bacterial strains. Despite considerable progress in this field however, the design of carriers to specifically enhance transport across the bacterial envelope or to target difficult-to-treat (e.g., intracellular) infections remains an urgently needed area of improvement. What follows is a summary and evaluation of the state of the art of both bacterial permeation models and advanced anti-infective formulation strategies, together with an outlook for future directions in these fields.


Relentlessly Progressive Sweet Syndrome of the Eye with Scleritis and Choroidal Infiltration.
To describe a case of Sweet syndrome, a dermatologic inflammatory disease, with progressive, unrelenting ocular findings. Case report. A 73-year-old male was evaluated with a six-month history of Sweet syndrome, manifesting as cutaneous erythematous edematous papules on the dorsal arms and shins and confirmed with biopsy demonstrating neutrophil infiltration with nuclei fragmentation and lack of vasculitis. He initially noted a unilateral red eye with ocular pain and was found to have scleritis and choroidal infiltration. The patient's ocular disease progressed despite treatment with systemic corticosteroids, intraocular Ozurdex ®, systemic dapsone, and subtenons triamcinolone. Systemic evaluation was negative for malignancy or other inflammatory syndromes. Following 7 months of non-manageable ocular pain enucleation was offered to the patient, but he declined. Sweet syndrome, a dermatologic condition, can be associated with unilateral scleritis and choroidal infiltration that are relentlessly progressive despite maximal systemic and ocular corticosteroid therapy.


The West Haven Yale Multidimensional Pain Inventory: Reliability and validity of the Turkish version in individuals with cancer.
Pain is a complex, multidimensional and subjective phenomenon that is common in patients with cancer. The translation of existing pain measurement scales is considered important in producing internationally comparable measures for evidence based practice. In measuring the pain experience, the WHYMPI is a widely used instrument to measure assessment of clinical pain, and it has not been validated in Turkey. The present study aimed to assess the reliability and validity of the Turkish version of the West Haven Yale Multidimensional Pain Inventory (WHYMPI). In this methodological study, the scale was translated into simplified Turkish by the cross-culture translation method, and 520 participants with cancer were assessed. The internal consistency, item analysis, and test-retest methods were used to determine the reliability of the Turkish WHYMPI. Content validity, criterion validity, convergent/divergent validity, and exploratory factor analysis were used to test the construct validity of the Turkish WHYMPI. Cronbach's alpha and item-total correlations results suggested that there was good internal reliability. The Cronbach's alpha for internal consistency of the pain experience, responses by significant others, and daily activities were 0.85, 0.60, and 0.83, respectively. The internal consistency coefficient for test-retest reliability of the pain experience, responses by significant others, and daily activities were acceptable: 0.82, 0.66, and 0.81, respectively. Factor loadings were significant, with standardised loadings ranging from 0.40 to 0.92. WHYMPI is reliable and valid instrument for the measurement of pain in patients with cancer in Turkey. Its use is recommended for clinical and research purposes.


Developments and quality assurance in rectal cancer surgery.
One of the main problems in the treatment of rectal cancer is the development of local recurrences. In the last decades, major improvements have been realized in the surgical treatment of rectal cancer. The introduction of TME-surgery has led to a large reduction in local recurrence rates and improved survival. TME-based operations are now established as the standard of care for rectal cancer, and should form the basis for trials concerning the role of (neo)adjuvant therapy. However, training and quality control are prerequisites to obtain good results in all surgeons' hands. Furthermore, standardization in the description of operations and reporting of pathology specimens should be implemented as important features of quality control. In general, it is thought that high volume and specialist care produces superior results to low volume and non-specialist care, especially for those less frequent forms of cancer and in technically difficult operations, like those for rectal cancer. However, limiting the performance of rectal cancer surgery to highly specialized surgeons or to only those general surgeons who perform more than a certain volume is impractical in view of the prevalence of rectal cancer. This article reviews developments in the treatment of especially mobile rectal cancer and pays attention to variability in outcomes and quality assurance of surgery.


The Intention of Inhaled Medication Adherence Scale (IMAS): The Development of a New Instrument for Assessing Inhaled Medication Adherence Among Patients with Chronic Obstructive Pulmonary Disease (COPD) Using Theory of Planned Behavior.
Inhaled medication adherence is an important issue for patients with chronic obstructive pulmonary disease (COPD) because adhering to inhaled medications could substantially improve their health. However, patients with COPD may not be always adhere to the prescribed inhaled medications. Therefore, understanding the underlying reasons for patients with COPD adhering to inhaled medications is important. The present study used Theory of Planned Behavior (TPB) as a theoretical framework to develop the Intention of Inhaled Medication Adherence Scale (IMAS) and assess its psychometric properties. After reviewing papers using the TPB to design psychometric scales and the TPB scale development guidelines, 28 items were generated for expert evaluation. Eight experts reported that the 28 items all had good content validity (content validity index ranged from 0.88 to 1.00 at item-level; and from 0.981 to 0.987 at scale-level) comprising four factors. Following initial development, 235 patients with COPD (mean age 73.12 years; 93.6% males) completed the IMAS via interview with a respiratory therapist and a research assistant. The four-factor structure of the IMAS was evaluated using confirmatory factor analysis (CFA). Nine IMAS items were removed because of low factor loadings or offending estimates. The 19-item IMAS was confirmed as having a four-factor structure supported by the CFA results (comparative fit index=1.00; Tucker-Lewis index=1.00; root mean square error of approximation=0.00; standardized root mean square residual=0.06). The 19-item IMAS had satisfactory psychometric properties in construct validity. The 19-item IMAS is an instrument that could help healthcare providers understand potential factors associated with adherence to inhaled medications among people with COPD.


Spinal epidural metastasis from cervical cancer: Report of two cases and literature review.
Spinal epidural metastasis(SEM) from cervical cancer is extremely rare, with only 6 cases reported in the literature, including our reported 2 cases. SEM mostly occurs in poorly differentiated carcinoma. Hematogenous spread is the primary mechanism of SEM from cervical cancer. The patients with SEM usually present with a range of clinical manifestations of nervous system because of spinal cord compression. SEM from cervical cancer indicates a late event with a poor prognosis. Local treatments mainly include surgery decompression and radiotherapy. Combining local and systemic therapy might be a better choice to prolong survival.


Construction of a subtractive library from hexavalent chromium treated winter flounder (Pseudopleuronectes americanus) reveals alterations in non-selenium glutathione peroxidases.
Chromium is released during several industrial processes and has accumulated in some estuarine areas. Its effects on mammals have been widely studied, but relatively little information is available on its effects on fish. Gene expression changes are useful biomarkers that can provide information about toxicant exposure and effects, as well as the health of an organism and its ability to adapt to its surroundings. Therefore, we investigated the effects of Cr(VI) on gene expression in the sediment dwelling fish, winter flounder (Pseudopleuronectes americanus). Winter flounder ranging from 300 to 360 g were injected i.p. with Cr(VI) as chromium oxide at 25 microg/kg chromium in 0.15N KCl. Twenty-four hours following injections, winter flounder were euthanized with MS-222 and the livers were excised. Half of the livers were used to make cytosol and the other half were used to isolate mRNA for subtractive hybridization. Subtractive clones obtained were spotted onto nylon filters, which revealed several genes with potentially altered expression due to Cr(VI), including an alpha class GST, 1-Cys peroxiredoxin (a non-selenium glutathione peroxidase), a P-450 2X subfamily member, two elongation factors (EF-1 gamma and EF-2), and complement component C3. Semi-quantitative RT-PCR was performed and confirmed that Cr(VI) down-regulated complement component C3, an EST, and two potential glutathione peroxidases, GSTA3 and 1-Cys peroxiredoxin. In addition, cytosolic GSH peroxidase activity was reduced, and silver stained SDS-PAGE gels from glutathione-affinity purified cytosol demonstrated that a 27.1 kDa GSH-binding protein was down-regulated greater than 50%. Taken together, Cr(VI) significantly altered the expression of several genes including two potential glutathione peroxidases in winter flounder.


Soft tissue effects of the holmium-YSGG laser in the canine trachea.
A holmium-yttrium scandium gallium garnet laser is a pulsed mid-infrared crystalline laser (wavelength, 2.1 microns), which is easily transmissible through flexible quartz fibers. With use of a 300-microns fiber delivery system, this laser was applied in the canine trachea to create a standard 5-mm diameter lesion through mucosa and submucosa. Power settings of 400 mJ and 600 mJ per pulse at 2 pulses per second were used, and wound healing was studied over a 2-week period. Excellent control of depth of tissue ablation was noted, with uncomplicated wound repair. Although healing was somewhat slower compared with healing when the CO2 laser was used, less granulation and fewer inflammatory changes were noted. Further studies need to be performed to determine ideal laser dosimetry before this laser is applied clinically.


Comparative study of vitrectomy with and without vein decompression for branch retinal vein occlusion: a pilot study.
To report the clinical outcomes in patients undergoing pars plana vitrectomy with and without vein decompression for treatment of branch retinal vein occlusion (BRVO). Thirty-five eyes with macular edema and visual acuity worse than 20/100 secondary to BRVO were prospectively evaluated. Vitrectomy with posterior hyaloid removal and vein decompression at the arteriovenous crossing was performed on 15 eyes (Group 1); consecutively, the same technique without vein decompression was performed on 20 eyes (Group 2). Primary outcome was visual acuity and secondary outcomes were resolution of macular edema and development of neovascularization. No differences were found between groups in either patient age (p = 0.566) or preoperative visual acuity (p = 0.505). No differences were found in visual acuity at 3 (p = 0.651), 6 (p = 0.697), 9 (p = 0.763), 12 (p = 0.881), or 18 (p = 0.748) months. Mean time for macular edema resolution and visual acuity improvement was 9 months in both groups, with a mean improvement of 3.5 +/- 2.35 lines in Group 1 and 3.2 +/- 2.97 lines in Group 2. No eyes in either group developed new vessels. Results suggest that vitrectomy with posterior hyaloid removal without vein decompression can resolve macular edema, improve vision, and prevent development of new vessels in BRVO.


Influence of PDZK1 on lipoprotein metabolism and atherosclerosis.
PDZK1 is a scaffold protein containing four PDZ protein interaction domains, which bind to the carboxy termini of a number of membrane transporter proteins, including ion channels (e.g., CFTR) and cell surface receptors. One of these, the HDL receptor, scavenger receptor class B type I (SR-BI), exhibits a striking, tissue-specific dependence on PDZK1 for its expression and activity. In PDZK1 knockout (KO) mice there is a marked reduction of SR-BI protein expression (approximately 95%) in the liver, but not in steroidogenic tissues or, as we show in this report, in bone marrow- or spleen-derived macrophages, or lung-derived endothelial cells. Because of hepatic SR-BI deficiency, PDZK1 KO mice exhibit dyslipidemia characterized by elevated plasma cholesterol carried in abnormally large HDL particles. Here, we show that inactivation of the PDZK1 gene promotes the development of aortic root atherosclerosis in apolipoprotein E (apoE) KO mice fed with a high fat/high cholesterol diet. However, unlike complete SR-BI-deficiency in SR-BI/apoE double KO mice, PDZK1 deficiency in PDZK1/apoE double knockout mice did not result in development of occlusive coronary artery disease or myocardial infarction, presumably because of their residual expression of SR-BI. These findings demonstrate that deficiency of an adaptor protein essential for normal expression of a lipoprotein receptor promotes atherosclerosis in a murine model. They also define PDZK1 as a member of the family of proteins that is instrumental in preventing cardiovascular disease by maintaining normal lipoprotein metabolism.


On the shape and origins of the freshwater species-area relationship.
The species-area relationship (SAR) has over a 150-year-long history in ecology, but how its shape and origins vary across scales and organisms remains incompletely understood. This is the first subcontinental freshwater study to examine both these properties of the SAR in a spatially explicit way across major organismal groups (diatoms, insects, and fish) that differ in body size and dispersal capacity. First, to describe the SAR shape, we evaluated the fit of three commonly used models, logarithmic, power, and Michaelis-Menten. Second, we proposed a hierarchical framework to explain the variability in the SAR shape, captured by the parameters of the SAR model. According to this framework, scale and species group were the top predictors of the SAR shape, climatic factors (heterogeneity and median conditions) represented the second predictor level, and metacommunity properties (intraspecific spatial aggregation, γ-diversity, and species abundance distribution) the third predictor level. We calculated the SAR as a sample-based rarefaction curve using 60 streams within landscape windows (scales) in the United States, ranging from 160,000 to 6,760,000 km2 . First, we found that all models provided good fits (R2 ≥ 0.93), but the frequency of the best-fitting model was strongly dependent on organism, scale, and metacommunity properties. The Michaelis-Menten model was most common in fish, at the largest scales, and at the highest levels of intraspecific spatial aggregation. The power model was most frequent in diatoms and insects, at smaller scales, and in metacommunities with the lowest evenness. The logarithmic model fit best exclusively at the smallest scales and in species-poor metacommunities, primarily fish. Second, we tested our framework with the parameters of the most broadly used SAR model, the log-log form of the power model, using a structural equation model. This model supported our framework and revealed that the SAR slope was best predicted by scale- and organism-dependent metacommunity properties, particularly spatial aggregation, whereas the intercept responded most strongly to species group and γ-diversity. Future research should investigate from the perspective of our framework how shifts in metacommunity properties due to climate change may alter the SAR.


Population structure of Adenostoma fasciculatum in mature stands of chamise chaparral in the southern Sierra Nevada, California.
In the low elevation chaparral areas of Sequoia National Park, California, pure stands of chamise (Adenostoma fasciculatum) are periodically rejuvenated by fire. Mature stands showed considerable variability in density and total biomass even though a positive correlation exists between the two. Mature stands showed a preponderance of individuals in the smaller size classes (inverse-J shape distribution). Dead shrubs found in mature stands also tended to be in the smaller size classes. This relatively high mortality of small individuals is important to post-fire stand development. In addition, resprout and seedling biomass one year after fire both showed inverse-J shaped size-class structures. A positive correlation existed between the preburn basal area of a shrub and its first year resprout biomass. Shrub biomass and distance to nearest neighbor were poorly correlated. A significant correlation existed between stand density and a stand's variance-to-mean ratio, indicating a trend toward more regular spacing as density increases. Pre-burn and fire-induced mortality tended to move the stand towards a more clumped distribution. Seedlings replaced dead individuals after a fire and thus restored regular spacing.


Sex Differences in Affective Expression Among Individuals with Psychometrically Defined Schizotypy: Diagnostic Implications.
The present investigation uses facial electromyography (fEMG) to measure patterns of affective expression in individuals with psychometrically defined schizotypy during presentation of neutral and negative visual images. Twenty-eight individuals with elevated schizotypal features and 20 healthy controls observed a series of images from the International Affective Picture System (IAPS) and provided self-report ratings of affective valence and arousal while their physiological responses were recorded. The groups were evenly divided by sex. A three-way interaction in fEMG measurement revealed that while males with psychometrically defined schizotypy demonstrated the expected pattern of blunted/constricted facial affective expression relative to male controls in the context of negative images, females displayed the opposite pattern. That is, females with psychometrically defined schizotypy demonstrated significant elevations in negative facial affective expression relative to female controls while viewing negative images. We argue that these findings corroborate previously reported impressions of sex differences in affective expression in schizotypy. We discuss implications for assessment and diagnostic procedures among individuals with disorders along the schizophrenia spectrum.


First-line treatment of metastatic or locally advanced unresectable soft tissue sarcomas with conatumumab in combination with doxorubicin or doxorubicin alone: a phase I/II open-label and double-blind study.
Conatumumab is a fully human monoclonal agonist antibody that binds to death receptor 5 and induces apoptosis in sensitive cells. This study evaluated the safety and efficacy of doxorubicin ± conatumumab as first-line systemic therapy for metastatic or locally advanced/unresectable soft-tissue sarcoma. In Phase I, six patients received doxorubicin (75 mg/m2) with conatumumab (15 mg/kg) every 3 weeks. In Phase II, patients were randomised (2:1) to receive doxorubicin with either double-blind conatumumab 15 mg/kg (conatumumab-doxorubicin; n=86) or placebo (placebo-doxorubicin; n=42). Patients who progressed on placebo-doxorubicin could receive open-label conatumumab monotherapy post-chemotherapy (n=21). The expected histopathologic subtypes (e.g. leiomyosarcoma, liposarcoma, others) were represented in this trial. No unexpected adverse events were noted in either Phase I or II. Median progression-free survival in Phase II was 5.6 and 6.4 months in the conatumumab-doxorubicin and placebo-doxorubicin arms, respectively (stratified HR: 1.00; p=0.973), with more early progressions noted in the first 3.5 months in the conatumumab-doxorubicin arm. Median overall survival was not reached after 8.6 months median follow-up in either arm. Common adverse events were nausea (conatumumab-doxorubicin: 66%; placebo-doxorubicin: 80%), alopecia (55%; 63%), fatigue (60%; 38%) and neutropenia (32%; 50%). Post-chemotherapy results were not notably improved by conatumumab dosing. Addition of conatumumab to doxorubicin appeared to be safe but did not improve disease control in a heterogeneous unselected group of patients with soft tissue sarcomas. The results of this trial are very useful for estimating the outcomes of first-line therapy of sarcoma patients treated with standard doxorubicin.


The oncological safety of hysteroscopy in the diagnosis of early-stage endometrial cancer: An Israel gynecologic oncology group study.
To compare survival measures of women with early-stage endometrial cancer who underwent either hysteroscopy or a non-hysteroscopic procedure as a diagnostic procedure. An Israel Gynecologic Oncology Group multicenter study of 1324 patients with stage I endometrial cancer who underwent surgery between 2002 and 2014. Patients were divided into two groups: hysteroscopy and non-hysteroscopy (curettage or office endometrial biopsy). Clinical, pathological, and survival measures were compared between the groups. There were 355 patients in the hysteroscopy group and 969 patients in the non-hysteroscopy group. The median follow-up was 52 months (range 12-120 months). There were no differences between the groups in the 5-year recurrence-free survival (90.2% vs. 88.2%; p = 0.53), disease-specific survival (93.4% vs. 91.7%; p = 0.5), and overall survival (86.2% vs. 80.6%; p = 0.22). Our findings affirm that hysteroscopy does not compromise the survival of patients with early-stage endometrial cancer.


Pharmacological characterization of the cannabinoid CB₁ receptor PET ligand ortholog, [³H]MePPEP.
MePPEP ((3R,5R)-5-(3-methoxy-phenyl)-3-((R)-1-phenyl-ethylamino)-1-(4-trifluoromethyl-phenyl)-pyrrolidin-2-one) is an inverse agonist shown to be an effective PET ligand for labeling cannabinoid CB₁ receptors in vivo. [¹¹C]MePPEP and structurally related analogs have been reported to specifically and reversibly label cannabinoid CB₁ receptors in rat and non-human primate brains, and [¹¹C]MePPEP has been used in human subjects as a PET tracer. We have generated [³H]MePPEP, an ortholog of [¹¹C]MePPEP, to characterize the molecular pharmacology of the cannabinoid CB₁ receptor across preclinical and clinical species. [³H]MePPEP demonstrates saturable, reversible, and single-site high affinity binding to cannabinoid CB₁ receptors. In cerebellar membranes purified from brains of rat, non-human primate and human, and cells ectopically expressing recombinant human cannabinoid CB₁ receptor, [³H]MePPEP binds cannabinoid CB₁ receptors with similar affinity with K(d) values of 0.09 nM, 0.19 nM, 0.14 nM and 0.16 nM, respectively. Both agonist and antagonist cannabinoid ligands compete [³H]MePPEP with predicted rank order potency. No specific binding is present in autoradiographic sections from cannabinoid CB₁ receptor knockout mouse brains, demonstrating that [³H]MePPEP selectively binds cannabinoid CB₁ receptors in native mouse tissue. Furthermore, [³H]MePPEP binding to anatomical sites in mouse and rat brain is comparable to the anatomical profiles of [¹¹C]MePPEP in non-human primate and human brain in vivo, as well as the binding profiles of other previously described cannabinoid CB₁ receptor agonist and antagonist radioligands. Therefore, [³H]MePPEP is a promising tool for translation of preclinical cannabinoid CB₁ receptor pharmacology to clinical PET ligand and cannabinoid CB₁ receptor inverse agonist therapeutic development.


Distribution of multi-resistant Gram-negative versus Gram-positive bacteria in the hospital inanimate environment.
We prospectively studied the difference in detection rates of multi-resistant Gram-positive and multi-resistant Gram-negative bacteria in the inanimate environment of patients harbouring these organisms. Up to 20 different locations around 190 patients were surveyed. Fifty-four patients were infected or colonized with methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant enterococci (VRE) and 136 with multi-resistant Gram-negative bacteria. The environmental detection rate for MRSA or VRE was 24.7% (174/705 samples) compared with 4.9% (89/1827 samples) for multi-resistant Gram-negative bacteria (P<0.001). Gram-positive bacteria were isolated more frequently than Gram-negatives from the hands of patients (P<0.001) and hospital personnel (P=0.1145). Environmental contamination did not differ between the intensive care units (ICUs) and the general wards (GWs), which is noteworthy because our ICUs are routinely disinfected twice a day, whereas GWs are cleaned just once a day with detergent. Current guidelines for the prevention of spread of multi-resistant bacteria in the hospital setting do not distinguish between Gram-positive and Gram-negative isolates. Our results suggest that the inanimate environment serves as a secondary source for MRSA and VRE, but less so for Gram-negative bacteria. Thus, strict contact isolation in a single room with complete barrier precautions is recommended for MRSA or VRE; however, for multi-resistant Gram-negative bacteria, contact isolation with barrier precautions for close contact but without a single room seems sufficient. This benefits not only the patients, but also the hospital by removing some of the strain placed on already over-stretched resources.


Elucidating the tight-binding mechanism of two oral anticoagulants to factor Xa by using induced-fit docking and molecular dynamics simulation.
Communicated by Ramaswamy H. Sarma.