Socioeconomic variation and prostate specific antigen testing in the community: a United Kingdom based population study.
We examined the association of prostate specific antigen testing with prostate cancer incidence, tumor differentiation and mortality according to socioeconomic status. Participants were 96,484 men between 40 and 99 years old without preexisting prostate cancer who were registered with a general practitioner in the Tayside region of Scotland, United Kingdom, between January 1, 2003 and December 31, 2008. We performed a retrospective cohort analysis using anonymized health data, including biochemistry data on prostate specific antigen tests, Scottish Index of Multiple Deprivation, cancer registry data set and General Register Office for Scotland death records. Main outcome measures were prostate specific antigen testing, prostate cancer incidence and death. Men in the most affluent Scottish Index of Multiple Deprivation quintile had a greater chance of undergoing a prostate specific antigen test (OR 1.48, 95% CI 1.40-1.57, p <0.001) and having prostate cancer (OR 1.48, 95% CI 1.15-1.91, p = 0.002) than men in the most deprived quintile, adjusting for age. There was no association between deprivation index quintile and prostate cancer death. Increased affluence was associated with a higher likelihood of a prostate specific antigen test and a higher incidence of prostate cancer. However, there were no observed differences by social class of the likelihood of a positive prostate specific antigen test or prostate cancer related death.


Group testing via hypergraph factorization applied to COVID-19.
Large scale screening is a critical tool in the life sciences, but is often limited by reagents, samples, or cost. An important recent example is the challenge of achieving widespread COVID-19 testing in the face of substantial resource constraints. To tackle this challenge, screening methods must efficiently use testing resources. However, given the global nature of the pandemic, they must also be simple (to aid implementation) and flexible (to be tailored for each setting). Here we propose HYPER, a group testing method based on hypergraph factorization. We provide theoretical characterizations under a general statistical model, and carefully evaluate HYPER with alternatives proposed for COVID-19 under realistic simulations of epidemic spread and viral kinetics. We find that HYPER matches or outperforms the alternatives across a broad range of testing-constrained environments, while also being simpler and more flexible. We provide an online tool to aid lab implementation: http://hyper.covid19-analysis.org .


Persistent cerebrovascular effects of MDMA and acute responses to the drug.
Acutely, 3,4,-methylenedioxymethamphetamine (MDMA) induces cerebrovascular dysfunction [Quate et al., (2004)Psychopharmacol., 173, 287-295]. In the longer term the same single dose results in depletion of 5-hydroxytrptamine (5-HT) nerve terminals. In this study we examined the cerebrovascular consequences of this persistent neurodegeneration, and the acute effects of subsequent MDMA exposure, upon the relationship that normally exists between local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCMRglu). Dark agouti (DA) rats were pre-treated with 15 mg/kg i.p. MDMA or saline. Three weeks later, rats from each pre-treatment group were treated with an acute dose of MDMA (15 mg/kg i.p.) or saline. Quantitative autoradiographic imaging was used to measure LCBF or LCMRglu with [(14)C]-iodoantipyrine and [(14)C]-2-deoxyglucose, respectively. Serotonergic terminal depletion was assessed using radioligand binding with [(3)H]-paroxetine and immunohistochemistry. Three weeks after MDMA pre-treatment there were significant reductions in densities of 5-HT transporter (SERT)-positive fibres (-46%) and [(3)H]-paroxetine binding (-47%). In animals pre-treated with MDMA there were widespread significant decreases in LCMRglu, but no change in LCBF indicating a persistent loss of cerebrovascular constrictor tone. In both pre-treatment groups, acute MDMA produced significant increases in LCMRglu, while LCBF was significantly decreased. In 50% of MDMA-pre-treated rats, random areas of focal hyperaemia indicated a loss of autoregulatory capacity in response to MDMA-induced hypertension. These results suggest that cerebrovascular regulatory dysfunction resulting from acute exposure to MDMA is not diminished by previous exposure, despite a significant depletion in 5-HT terminals. However, there may be a sub-population, or individual circumstances, in which this dysfunction develops into a condition that might predispose to stroke.


Anaesthesia Management of Caesarean Section in Two Patients with Eisenmenger's Syndrome.
Recently two parturients with Eisenmenger's syndrome underwent caesarean section at our hospital. They were managed by a multidisciplinary team during their perioperative period. The caesarean sections were uneventfully performed, one under general anaesthesia and one with epidural anaesthesia, with delivery of two newborns with satisfactory Apgar scores. One patient died in the post-partum period, and the other did well. We discuss the anaesthetic considerations in managing these high-risk patients.


Simultaneous separation of chlorinated/brominated dioxins, polychlorinated biphenyls, polybrominated diphenyl ethers and their methoxylated derivatives from hydroxylated analogues on molecularly imprinted polymers prior to gas/liquid chromatography and mass spectrometry.
Polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs), polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are important contaminants in the environment. In recent years also polybrominated dibenzo-p-dioxins/dibenzofurans (PBDD/Fs) have been reported as emerging environmental stressors. It has been suggested that hydroxylated polybrominated biphenyl ethers (OH-BDEs) are important - may be even the most important - precursors of brominated dioxins/furans. The aim of this study was to develop a robust, time-saving analytical procedure to collectively separate in animal tissues such compounds prior to determination of individual substances with a gas/liquid chromatograph coupled to an ion trap/time-of-flight mass spectrometer (GC/IT-MS or UPLC/TOF-MS). Two OH-CB/BDE separation methods including alkaline extraction and molecularly imprinted polymers (MIP) were compared. Performance of both methods was validated: absolute recovery values were in the 47-90% range depending on the compound, while recovery relative standard deviation was below 20% in most cases. Levels of the studied compounds have been assessed in some real life samples.


Oxidative stress in paroxysmal nocturnal hemoglobinuria and other conditions of complement-mediated hemolysis.
The complement (C') system and redox status play important roles in the physiological functioning of the body, such as the defense system, but they are also involved in various pathological conditions, including hemolytic anemia. Herein, we review the interaction between the C' and the redox systems in C'-mediated hemolytic anemias, paroxysmal nocturnal hemoglobinuria (PNH) and autoimmune hemolytic anemia, including acute hemolytic transfusion reaction. Blood cells in these diseases have been shown to have increased oxidative status, which was further elevated by interaction with activated C'. The results suggest that oxidative stress, in conjunction with activated C', may cause the underlying symptoms of these diseases, such as intra- and extravascular hemolysis and thrombotic complications. Antioxidants ameliorate oxidative stress by preventing generation of free radicals, by scavenging and preventing their accumulation, and by correcting their cellular damage. Antioxidants have been shown to reduce the oxidative stress and inhibit hemolysis as well as platelet activation mediated by activated C'. This raises the possibility that treatment with antioxidants might be considered as a potential therapeutic modality for C'-mediated hemolytic anemias. Currently, eculizumab, a humanized monoclonal antibody that specifically targets the C' protein C5, is the main treatment modality for PNH. However, because antioxidants are well tolerated and relatively inexpensive, they might be considered as potential adjuvants or an alternative therapeutic modality for PNH and other C'-mediated hemolytic anemias.


Arginine vasopressin effects on membrane potentials of preoptic area temperature-sensitive and -insensitive neurons in rat hypothalamic tissue slices.
Arginine vasopressin (AVP) plays a hypothermic regulatory role in thermoregulation and is an important endogenous mediator in this mechanism. In the preoptic area (POA), AVP increases the spontaneous firing and thermosensitivity of warm-sensitive neurons and decreases those of cold-sensitive and temperature-insensitive neurons. Because POA neurons play a crucial role in precise thermoregulatory responses, these findings indicate that there is an association between the hypothermia and changes in the firing activity of AVP-induced POA neurons. However, the electrophysiological mechanisms by which AVP controls this firing activity remain unclear. Therefore, in the present study, using in vitro hypothalamic brain slices and whole-cell recordings, we elucidated the membrane potential responses of temperature-sensitive and -insensitive POA neurons to identify the applications of AVP or V1a vasopressin receptor antagonists. By monitoring changes in the resting potential and membrane potential thermosensitivity of the neurons before and during experimental perfusion, we observed that AVP increased the changes in the resting potential of 50% of temperature-insensitive neurons but reduced them in others. These changes are because AVP enhances the membrane potential thermosensitivity of nearly 50% of the temperature-insensitive neurons. On the other hand, AVP changes both the resting potential and membrane potential thermosensitivity of temperature-sensitive neurons, with no differences between the warm- and cold-sensitive neurons. Before and during AVP or V1a vasopressin receptor antagonist perfusion, no correlation was observed between changes in the thermosensitivity and membrane potential of all neurons. Furthermore, no correlation was observed between the thermosensitivity and membrane potential thermosensitivity of the neurons during experimental perfusion. In the present study, we found that AVP induction did not result in any changes in resting potential, which is unique to temperature-sensitive neurons. The study results suggest that AVP-induced changes in the firing activity and firing rate thermosensitivity of POA neurons are not controlled by resting potentials.


Differential effects of castration and testosterone replacement on basal and LHRH-stimulated cAMP and cGMP accumulation and on gonadotropin release from the pituitary of the male rat.
Castration of male rats decreased cAMP levels, and increased cGMP levels and gonadotropin release from anterior pituitaries incubated in vitro. Testosterone (T) replacement via silastic tubes filled with the steroid increased cAMP and decreased cGMP levels and gonadotropin release. Incubation of hemipituitaries from intact males with luteinizing hormone releasing hormone (LHRH, 5 nM for 2 h) resulted in increased cAMP and cGMP accumulation and gonadotropin release. Castration abolished LHRH-induced cAMP accumulation, but increased the effect of LHRH on cGMP accumulation and gonadotropin release. Testosterone replacement restored cAMP stimulation by LHRH but decreased LHRH-induced elevation of cGMP levels and gonadotropin release. These data illustrate parallel increases by castration of LHRH-induced cGMP accumulation and of gonadotropin release. Furthermore, these two parameters are influenced in the opposite direction by replacement therapy. These results support the concept of a role for cGMP in LHRH action as well as providing evidence of a link between the feedback action of T and cGMP in the pituitary gland.


The surgical management of megaureters in duplex systems: the efficacy of ureteral tapering and common sheath reimplantation.
We describe 6 children with renal duplication associated with megaureter(s) who underwent ureteral tapering and common sheath reimplantation. Of the patients 4 had complete duplication with reflux into 1 or both ureters and 2 had incomplete duplication with a short distal segment that was obstructed at the ureterovesical junction. All obstructed or refluxing ureteral segments were dilated to a degree that tapering was required at the time of common sheath reimplantation. Megaureter repair in the presence of a duplicate collecting system proved to be safe and reliable.


Effects of salpingitis simulation on the morphology and expression of inflammatory-related genes of oviduct in laying hens.
This study was conducted to simulate salpingitis of laying hens by observing the morphology and expression of inflammatory genes in the oviduct. A total of one hundred twenty 81-wk-old Roman Pink laying hens in good physical condition without the oviduct disease with an average egg production rate of 76% were fed a basal diet for 2 wks and then randomly allocated into 4 groups (6 replicates/group, 5 birds/replicate). The experimental treatments were as follows: 1) Control group (treated with PBS); 2) Organic chemical reagent (OCR) group; 3) Lipopolysaccharide (LPS) group; 4) LPS + OCR group. First, the chickens were kept upside down to make ectropion and exposure of the apertura uterinae; then prepared reagents were poured into the uterine part of the fallopian tube by using the chicken vas deferens (1 mL/layer); finally, the chickens were kept in the inverted position for 5 to 10 min. The fallopian tube samples (the magnum, isthmus, and uterus) were collected after 48 h of treatment. Compared with the control, treatment with LPS+OCR decreased (P < 0.05) the secondary villus length and primary villus area in magnum and villus length in isthmus (P < 0.05). An increase (P < 0.05) of the intervillous space of uterus was observed in LPS + OCR group compared with the control. The expressions of interleukin-6 mRNA of magnum and interferon-γ (IFN-γ) of isthmus in the LPS and LPS+OCR treatments were higher (P < 0.05) than that in control. Compared with the control, treatment with LPS+OCR increased (P < 0.05) the expressions of IFN-γ mRNA of magnum and IFN-γ, tumor necrosis factor-α and inducible nitric oxide synthase mRNA of uterus in laying hens. In conclusion, the results of morphological damage of fallopian tube tissue and increased expression of inflammatory factors in LPS + OCR treatment group suggested that LPS+OCR treatment can provide data basis to establish salpingitis model in laying hens for studying the pathogenesis of it.


Can the long-term effects of beach cleaning heavy duty machinery on aeolian sedimentary dynamics be detected by monitoring of vehicle tracks? An applied and methodological approach.
Beach-dune systems are fragile ecosystems vulnerable to changes, especially those associated to human activities. This study focuses on El Inglés beach (Canary Islands, Spain), which is located on the eastern limit of the Maspalomas dunefield. This is the sediment input to the dunefield, and vehicles that provide urban-touristic services circulate every day, most notably heavy duty machinery responsible for beach cleaning. The aim of this study is to make a first methodological approach and a quantitative and empirical analysis of the long-term environmental effects, especially on the topography and geomorphology, that mechanical beach cleaning services could have on the aeolian dynamics, using as an indicator the vehicles tracks mapping. The methodology is divided into four sections: i) a spatiotemporal study of vehicle tracks on the beach; ii) a field campaign to observe beach cleaning activities in situ and compile data; iii) an interview with the local team responsible for beach cleaning; and iv) a general analysis of the aeolian dynamics over the almost last two decades. Results shown not only a high correlation between vehicle tracks and heavy duty machinery tracks, but also the variation in vehicle track density was proven to follow changes in the management process and the number of tourists. Different track densities varied depending on the intensity of the presence of visitors and hence the intensity of beach use, which is not homogeneous throughout the beach. A study of the deflation surfaces as erosion process found that they not only remain steady but even increase in some areas with high vehicle track densities, with no sedimentary gain. Although management activities like cleaning and levelling may not have a direct impact on the dunefield, they were positively correlated to deflation surfaces, increasing sediment loss in the beach area. These activities could be leading an artificially-maintained steady beach contrary to documented sedimentary loss in the dunefield. In conclusion, the pioneer approach of analysing the vehicle traffic through tracks monitoring, especially beach cleaning activities, has shown the viability to detect long-term effects on the sedimentary dynamics, including sediment loss to the foredune and, therefore, inside the system.


Use of ketamine and esketamine for depression: an overview of systematic reviews with meta-analyses.
To summarize the evidence of efficacy and safety of the use of ketamine and esketamine for depression. A literature search was performed in Medline, the Cochrane Library, LILACS, and CRD until November 2020. We included systematic reviews with meta-analyses of randomized controlled trials on the use of ketamine and esketamine in adult patients with depression. Two authors independently performed the study selection and data extraction. The AMSTAR-2 tool was used to appraise the quality of included reviews. A total of 118 records were identified, and 11 studies fully met the eligibility criteria. Compared to control, ketamine improved the clinical response at 40 min to 1 week and clinical remission at 80 min to 72 h, and esketamine improved both outcomes at 2 h to 4 weeks. Ketamine and esketamine also had a beneficial effect on the depression scales score and suicidality. For adverse events, oral ketamine did not show significant change compared to control, while intranasal esketamine showed difference for any events, such as dissociation, dizziness, hypoesthesia, and vertigo. Most reviews were classified as "critically low quality," and none of them declared the source of funding of the primary studies and assessed the potential impact of risk of bias in primary studies. Ketamine and esketamine showed a significant antidepressant action within a few hours or days after administration; however, the long-term efficacy and safety are lacking. In addition, the methodological quality of the reviews was usually critically low, which may indicate the need for higher quality evidence in relation to the theme.


Energetic aspects of inotropic interventions in rat myocardium.
Contractile force of the myocardium can be increased by different molecular mechanisms, and therefore different energetic consequences may result. The influence of the inotropic substances isoproterenol and UDCG-115 on myocardial energetics in isometrically contracting left ventricular rat papillary muscles was investigated by means of highly sensitive antimony bismuth thermopiles. Isoproterenol increased total heat and initial heat by 147% (p less than 0.01) and 69% (p less than 0.02) when normalized to tension-time integral, respectively. No significant change of both heat terms occurred due to UDCG-115. Initial heat was separated into tension-independent heat ("calcium cycling") and tension-dependent heat ("cross-bridge cycling") by means of a new method using 2,3-butanedione monoxime. Both tension-dependent heat per tension-time integral and tension-independent heat increased significantly, due to isoproterenol, from 4.9 +/- 1.17 to 7.6 +/- 2.72 mu cal/g.cm.s (p less than 0.05) and from 0.15 +/- 0.06 to 0.22 +/- 0.04 mcal/g (p less than 0.01). UDCG-115 influenced neither tension-independent heat nor tension-dependent heat per tension-time integral significantly. Thus, the economy of force development was not significantly altered due to UDCG-115 whereas isoproterenol significantly increased the energy necessary for activation, i.e. calcium cycling, and the energy necessary for force production, i.e. cross-bridge cycling. The basic mechanisms of these energetic changes are discussed.


[Intraorbital foreign body].
Perforative intraorbital injuries can be potentially serious, and management depends on the type of projectile and its intraorbital trajectory. Medical imaging is an imperative part of the initial assessment. We report the case of a wooden intraorbital foreign body (arrow), with no functional or anatomical consequences, with a remarkable intraorbital trajectory analyzed by CT. The two main risks of these injuries are first mechanical, with possible bulb, nerve, muscle or bone complications, and second infectious. The CT scan or better yet MRI imaging provide a detailed analysis of the projectile's intraorbital trajectory in the orbital cavity. Infectious complications are promoted by the fat cells present in the orbit and must be systematically controlled with wide-spectrum antibiotics.


An ERP study of agreement features in Spanish.
The goal of the present study was to investigate whether two morphological agreement features, Person and Number, play a different role in the agreement process. According to the Feature Hierarchy hypothesis, different nominal agreement features have different degrees of cognitive strength (e.g., Person>Number). Event-related potentials (ERPs) were collected from Spanish speakers while they read sentences in which either Person Disagreement (PD; e.g., Tú salto en el patio [You (2ndPerSing) jump (1stPerSing) in the backyard]), Number Disagreement (ND; e.g., Nosotros salto en el patio [We (1stPerPl) jump (1stPerSing) in the backyard]) or both Person and Number Disagreement (NPD; e.g., Ustedes salto en el patio [You (2ndPerPl) jump (1stPerSing) in the backyard]) relationships were manipulated. ND, PD and NPD all elicited an anterior negativity (AN) and P600 pattern. An AN effect was only found in the NPD with a different topography from the classic LAN effect as it was lateralized to right and central sites. The P600 effect elicited by the NPD condition was larger than the agreement condition and that of ND and PD in the first window 500-700, while the three disagreement conditions elicited larger P600 amplitudes than the agreement condition in the second window 700-900. There were no differences between the processing of person and number. Thus, the combination of number and person disagreement could be solved in parallel through an additive mechanism of the two features. These results do not support the Feature Hierarchy hypothesis.


Misuses of biology in the context of the paranormal.
Public suspicion of science stems from science's challenging of perceptions and myths about reality, and a public fear of new technology. The result is a susceptibility to pseudoscience. In claiming that creation 'science' is as valid as evolution the creationists misquote scientists and seek to spread their own 'scientific' myths concerning a young age for the earth, an act of creation based on a particular literalist interpretation of the Christian Bible and a single worldwide flood. They use methods of debate and politics, rather than scientific research. A selection of their arguments is examined and the nature of the evidence for evolution is discussed. Problems with the creation 'science' model are noted. In the myth of the hundredth monkey phenomenon, original research is misquoted to denigrate scientific research and support sentimental ideas of paranormal events. The misuse of science is seen as damaging to society because it reduces the effective gathering and application of scientific information. However, pseudoscience provides a valuable guide to gaps in public scientific education.


Trends in inequalities in the prevalence of dementia in the United States.
This paper presents estimates of the prevalence of dementia in the United States from 2000 to 2016 by age, sex, race and ethnicity, education, and a measure of lifetime earnings, using data on 21,442 individuals aged 65 y and older and 97,629 person-year observations from a nationally representative survey, the Health and Retirement Study (HRS). The survey includes a range of cognitive tests, and a subsample underwent clinical assessment for dementia. We developed a longitudinal, latent-variable model of cognitive status, which we estimated using the Markov Chain Monte Carlo method. This model provides more accurate estimates of dementia prevalence in population subgroups than do previously used methods on the HRS. The age-adjusted prevalence of dementia decreased from 12.2% in 2000 (95% CI, 11.7 to 12.7%) to 8.5% in 2016 (7.9 to 9.1%) in the 65+ population, a statistically significant decline of 3.7 percentage points or 30.1%. Females are more likely to live with dementia, but the sex difference has narrowed. In the male subsample, we found a reduction in inequalities across education, earnings, and racial and ethnic groups; among females, those inequalities also declined, but less strongly. We observed a substantial increase in the level of education between 2000 and 2016 in the sample. This compositional change can explain, in a statistical sense, about 40% of the reduction in dementia prevalence among men and 20% among women, whereas compositional changes in the older population by age, race and ethnicity, and cardiovascular risk factors mattered less.


Postpartum ovarian vein thrombosis.
Ovarian vein thrombosis (OVT) is a rare but potentially serious postpartum complication, which occurs in 0.05% to 0.18% of pregnancies and is diagnosed on the right side in 80% to 90% of the cases. A 32-year-old woman presented at 15 days postpartum to our emergency department with severe abdominal pain, fever, and abdominal distension. Abdominal examination revealed right lower quadrant pain with rebound tenderness. The plain abdominal radiography evidenced a diffuse fecal stasis; abdominal ultrasound showed the presence of free fluid in the Douglas' pouch and between small bowel loops. Diagnosis of acute appendicitis was made. The patient immediately underwent explorative laparoscopy; at surgery, a woody tumoration consistent with right ovarian vein thrombosis was found. Laparoscopic ultrasound confirmed the diagnosis. Anticoagulation therapy and antibiotics were instituted. CT-scan confirmed the presence of thrombosis up to the vena cava. The patient was discharged on postoperative day 4. At 1-month follow-up, she remained stable and symptom free. Even though postpartum ovarian vein thrombosis is rare, recognition and treatment is needed to institute adequate therapy and avoid potential serious sequelae. The diagnosis can be established by ultrasound, CT scan, and MRI examinations, although, as in the case described, the limitation of ultrasound includes obscuration of the gonadic vein by overlying bowel gas. OVT should be considered in any woman in the postpartum period with lower abdominal pain, fever, and leucocytosis.


The uptake and elimination of 1,1,1-trichloroethane during and following inhalation exposures in rats.
The pharmacokinetics of 1,1,1-trichloroethane (TRI) was studied in male Sprague-Dawley rats in order to characterize and quantify TRI uptake and elimination oby direct measurements of the inhaled and exhaled compound. Fifty or 500 ppm TRI was inhaled for 2 hr through a one-way breathing valve by unanesthetized rats of 325-375 g. Repetitive samples of the separate inhaled and exhaled breath streams, as well as arterial blood, were collected concurrently both during and following TRI inhalation and analyzed for TRI by gas chromatography. Respiratory rates and volumes were continuously monitored during and following exposure and were used in conjunction with the pharmacokinetic data to characterize profiles of uptake and elimination. TRI was very rapidly absorbed from the lung, in that substantial levels were present in arterial blood at the first sampling time (i.e., 2 min). Blood and exhaled breath concentrations of TRI increased rapidly after the initiation of exposure, approaching but not reaching steady state during the 2-hr exposures. The blood and exhaled breath concentrations were directly proportional to the exposure concentration during the exposures. Percentage uptake of TRI decreased 30-35% during the first hour of inhalation, diminishing to approximately 45-50% by the end of the exposure. Total cumulative uptake in the 50 and 500 ppm groups over the 2-hr inhalation exposures was determined to be 6 and 48 mg/kg body wt, respectively. By the end of the exposure period, 2.1 and 20.8 mg, respectively, of inhaled TRI was eliminated from rats inhaling 50 and 500 ppm TRI. A physiological pharmacokinetic model for TRI inhalation was utilized to predict blood and exhaled breath concentrations for comparison with observed experimental values. Overall, values predicted by the physiological pharmacokinetic model for TRI levels in the blood and exhaled breath were in close agreement with measured values both during and following TRI inhalation.


Hyaluronic acid pretreatment for Sendai virus-mediated cochlear gene transfer.
Gene therapy with viral vectors is one of the most promising strategies for sensorineural hearing loss. However, safe and effective administration of the viral vector into cochlear tissue is difficult because of the anatomical isolation of the cochlea. We investigated the efficiency and safety of round window membrane (RWM) application of Sendai virus, one of the most promising non-genotoxic vectors, after pretreatment with hyaluronic acid (HA) on the RWM to promote efficient viral translocation into the cochlea. Sendai virus expressing the green fluorescent protein reporter gene was detected throughout cochlear tissues following application combined with HA pretreatment. Quantitative analysis revealed that maximum expression was reached 3 days after treatment. The efficiency of transgene expression was several 100-fold greater with HA pretreatment than that without. Furthermore, unlike the conventional intracochlear delivery methods, this approach did not cause hearing loss. These findings reveal the potential utility of gene therapy with Sendai virus and HA for treatment of sensorineural hearing loss.


Systematic Review of Randomized Controlled Trials in Australian Nursing Homes from 2000 to 2018.
High-quality research provides an evidence base for optimal practice care in clinical settings, yet, little is known about the nature and extent of randomized control trials (RCTs) conducted in Australian nursing homes (NHs). Research from other settings and other countries is not necessarily transferable to the Australian NH sector. We sought to identify and describe RCTs conducted in Australia which investigated interventions targeted at improving care for NH residents. The design of this study comprised a systematic literature search with a narrative review. Studies were included if they were RCTs published after 2000, conducted in an Australian NH, and evaluated a health intervention which may have directly or indirectly benefitted the NH resident. Australian NHs. Nursing home residents. Jurisdiction (state or territory where the study was conducted), number of NHs recruited in each trial, number of residents included in each trial, intervention characteristics, comparator characteristics, and characteristics of outcome. Only 43 articles reporting on 39 RCTs were identified. In contrast, 30 Australian musculoskeletal RCTs were published in just 2 years (2011-2012). Most of the RCTs identified were conducted in New South Wales (n = 14), Queensland (n = 10), and Victoria (n = 9). The mean number of NHs included in each trial was 22.4 (standard deviation (SD) = 27.0), with a median of 14.5 (interquartile range (IQR) = 27.8), while the mean number of residents included was 412.4 (SD = 921) with a median of 187 (IQR = 341.0). The most common interventions targeted: managing dementia (n = 20), prevention of falls (n = 7), and addressing mental health issues (n = 6). This review provides evidence of the paucity of high-quality research in the form of RCTs, in the Australian NH setting and demonstrates the need for Australia to improve its research capability in the NH sector.


Comprehensive evaluation model for health grade of multi-component compound release materials based on fuzzy comprehensive evaluation with grey relational analysis.
The selection of materials is a complex and elusive process due to the multiple factors related to health. For the effective selection of materials, a comprehensive model for evaluating the health grade of materials was proposed with the mathematical method of the fuzzy comprehensive evaluation (FCE) and grey relational analysis (GRA). A health evaluation procedure scheme of the AgBB as well as standards of the forestry industry of the People's Republic of China and standards of the health industry of the People's Republic of China were referred to during the process. Based on Qt technology, a computer program was developed to calculate the compound comprehensive evaluation models. The data of Choerospondias axillaris with different lacquers were used as practical examples firstly, and then, the emission and odor characteristics of Xylosma racemosum (Sieb. et Zucc.) Miq. with PU, UV, and waterborne coating were explored with the technology of GC-MS/O. Results showed that: a total of 21 odorants were identified from Xylosma racemosum with PU, UV, and waterborne coating. The health grade of three Xylosma racemosum samples was UV > waterborne > PU, with the health grade of UV coating being "A", and the boards with PU and the waterborne coating were "N", with a fuzzy comprehensive index of PPU = 0.5151, Pwaterborne coatings=0.4950. Based on the results, it is proved that the establishment of the comprehensive evaluation model based on FCE and GRA successfully converts qualitative evaluation into quantitative evaluation; in addition, effectively evaluates the health grade of materials. This study provides a better understanding of materials' health grades, which will aid consumers in reducing indoor air pollution and using their products properly.


Further evidence for entry of infectious bovine rhinotracheitis virus into bovine kidney cells.
The penetration of bovine kidney cells by infectious bovine rhinotracheitis virus, a member of the herpesvirus group, was investigated using the direct immunoferritin labeling technique. Electron microscopic examination of infected cells after 10 min at 37°C revealed fusion between viral envelope and cell membrane; the former reacted with the ferritin particles conjugated with antiviral antibody. However, shortly after penetration of the nucleocapsid, viral-specific antigenic sites on the plasma membrane were not detected by the immunoferritin technique. Antigenically reactive structures in a disorganized array were frequently detected extracellularly, situated above the penetration sites as indicated by the internalized nucleocapsids.


Cross-reactivity trends when selecting scFv antibodies against snake toxins using a phage display-based cross-panning strategy.
Antibodies with cross-reactive binding and broad toxin-neutralizing capabilities are advantageous for treating indications such as infectious diseases and animal envenomings. Such antibodies have been successfully selected against closely related antigens using phage display technology. However, the mechanisms driving antibody cross-reactivity typically remain to be elucidated. Therefore, we sought to explore how a previously reported phage display-based cross-panning strategy drives the selection of cross-reactive antibodies using seven different snake toxins belonging to three protein (sub-)families: phospholipases A2, long-chain α-neurotoxins, and short-chain α-neurotoxins. We showcase how cross-panning can increase the chances of discovering cross-reactive single-chain variable fragments (scFvs) from phage display campaigns. Further, we find that the feasibility of discovering cross-reactive antibodies using cross-panning cannot easily be predicted by analyzing the sequence, structural, or surface similarity of the antigens alone. However, when antigens share the (exact) same functions, this seems to increase the chances of selecting cross-reactive antibodies, which may possibly be due to the existence of structurally similar motifs on the antigens.


FK506 impairs neutrophil migration that results in increased polymicrobial sepsis susceptibility.
This study aimed to investigate the effects of FK506 on experimental sepsis immunopathology. It investigated the effect of FK506 on leukocyte recruitment to the site of infection, systemic cytokine production, and organ injury in mice with sepsis. Using a murine cecal ligation and puncture (CLP) peritonitis model, the experiments were performed with wild-type (WT) mice and mice deficient in the gene Nfat1 (Nfat1-/-) in the C57BL/6 background. Animals were treated with 2.0 mg/kg of FK506, subcutaneously, 1 h before the sepsis model, twice a day (12 h/12 h). The number of bacteria colony forming units (CFU) was manually counted. The number of neutrophils in the lungs was estimated by the myeloperoxidase (MPO) assay. The expression of CXCR2 in neutrophils was determined using flow cytometry analysis. The expression of inflammatory cytokines in macrophage was determined using ELISA. The direct effect of FK506 on CXCR2 internalization was evaluated using HEK-293T cells after CXCL2 stimulation by the BRET method. FK506 treatment potentiated the failure of neutrophil migration into the peritoneal cavity, resulting in bacteremia and an exacerbated systemic inflammatory response, which led to higher organ damage and mortality rates. Failed neutrophil migration was associated with elevated CXCL2 chemokine plasma levels and lower expression of the CXCR2 receptor on circulating neutrophils compared with non-treated CLP-induced septic mice. FK506 did not directly affect CXCL2-induced CXCR2 internalization by transfected HEK-293 cells or mice neutrophils, despite increasing CXCL2 release by LPS-treated macrophages. Finally, the CLP-induced response of Nfat1-/- mice was similar to those observed in the Nfat1+/+ genotype, suggesting that the FK506 effect is not dependent on the NFAT1 pathway. Our data indicate that the increased susceptibility to infection of FK506-treated mice is associated with failed neutrophil migration due to the reduced membrane availability of CXCR2 receptors in response to exacerbated levels of circulating CXCL2.


Affinity and hydrophobic chromatography of Escherichia coli aspartate transcarbamoylase.
Chromatography of aspartate transcarbamoylase from Escherichia coli on agarose-immobilized dyes and alkyl-agaroses of differing carbon length were investigated. The bacterial aspartate transcarbamoylase was bound by Procoin red HE3B-agarose and Cibacron blue F3GA-agarose nearly completely under the conditions chosen relative to other agarose-coupled dyes. The aspartate transcarbamoylase holoenzyme was eluted from the Procion red HE3B-agarose slightly later than from the Cibacron blue F3GA-agarose during salt gradient elution. The catalytic trimer of the enzyme as well as its regulatory dimer were eluted by a lower salt concentration from both dye-agarose gels than the concentration required to elute the holoenzyme. The interaction of the catalytic trimer with the Procion red HE3B-agarose and Cibacron blue F3GA-agarose gels may be a determinant in the holoenzyme being retained on these resins. Of those alkyl-agaroses tested, the ethyl-, propyl- and hexyl-agarose gels bound the majority of aspartate transcarbamoylase activity. Chromatography of aspartate transcarbamoylase on ethyl-agarose found it to be eluted by a low salt concentration. A purification scheme for relatively small amounts of aspartate transcarbamoylase utilizing Procion red HE3B-agarose and ethyl-agarose is presented. This purification scheme is particularly useful for mutant versions of aspartate transcarbamoylase which cannot be purified by literature procedures.


Three-Dimensional Bio-Printed Autologous Omentum Patch Ameliorates Unilateral Ureteral Obstruction-Induced Renal Fibrosis.
Recent advances in the field of tissue engineering and regenerative medicine have contributed to the repair of damaged tissues and organs. Renal dysfunctions such as chronic kidney disease (CKD) are considered intractable owing to its cellular heterogeneity. In addition, the absence of definitive treatment options other than dialysis or kidney transplantation in advanced CKD. In this study, we investigated therapeutic effects of a three-dimensional (3D) bio-printed omentum patch as treatment source. Because omentum contains a lot of biological sources for immune regulation and tissue regeneration, it has been used in clinic for >100 years. By using autologous tissue as a bio-ink, the patch could minimize the immune response. The mechanically micronized omentum without any additives became small enough to print, but the original components could be preserved. Then, the 3D printed omentum patch was transplanted under renal subcapsular layer in unilateral ureteral obstruction (UUO) rat model. After 14 days of patch transplantation, the kidneys were analyzed through bulk RNA sequencing and histopathological staining. From the results, decreased tubular injury was observed in the omentum patch group. In addition, the omentum patch significantly altered biological process of gene ontology such as fibrosis-related gene and growth factors. RNA sequencing confirmed the antifibrotic effect by inhibiting fibrosis-inducing mechanisms within PI3K-AKT and JAK-STAT pathways. In conclusion, the omentum patch showed the effect of antitubular injury and antifibrosis on UUO kidneys. In particular, the omentum patch is expected to protect the organ from further degeneration and loss of function by inhibiting the progression of fibrosis. The omentum patch can be a novel therapeutic option for renal dysfunction. Impact statement Many studies and clinical trials are being conducted to develop new treatments for kidney disease. However, there are no newly developed renal replacement therapies. In this study, we developed a new treatment that can ameliorate renal interstitial fibrosis using three-dimensional (3D) bio-printed autologous omentum patch. The 3D printer enables precise patch printing, and the bio-ink made of autologous tissue minimizes the immune response after transplantation. The whole kidneys were analyzed by RNA sequencing and histopathological staining 14 days after transplantation. From the results, the omentum patch had the effect of relieving tubular injury in the injured state. Also, the omentum patch significantly altered biological process of gene ontology. In particular, genes related to fibrosis were observed to be downregulated by the omentum patch. RNA sequencing confirmed that the antifibrotic effect was owing to inducing mechanisms of PI3K-AKT and JAK-STAT pathways. The findings reported in this study represent a significant advancement in the application of 3D bio-printer to damaged organ treatments, especially fibrosis-related diseases.


Three-Dimensional Interactions Analysis of the Anticancer Target c-Src Kinase with Its Inhibitors.
Src family kinases (SFKs) constitute the biggest family of non-receptor tyrosine kinases considered as therapeutic targets for cancer therapy. An aberrant expression and/or activation of the proto-oncogene c-Src kinase, which is the oldest and most studied member of the family, has long been demonstrated to play a major role in the development, growth, progression and metastasis of numerous human cancers, including colon, breast, gastric, pancreatic, lung and brain carcinomas. For these reasons, the pharmacological inhibition of c-Src activity represents an effective anticancer strategy and a few compounds targeting c-Src, together with other kinases, have been approved as drugs for cancer therapy, while others are currently undergoing preclinical studies. Nevertheless, the development of potent and selective inhibitors of c-Src aimed at properly exploiting this biological target for the treatment of cancer still represents a growing field of study. In this review, the co-crystal structures of c-Src kinase in complex with inhibitors discovered in the past two decades have been described, highlighting the key ligand-protein interactions necessary to obtain high potency and the features to be exploited for addressing selectivity and drug resistance issues, thus providing useful information for the design of new and potent c-Src kinase inhibitors.


Tracheal stenosis depends on the extent of cartilaginous injury in experimental canine model.
To test the hypothesis that the development of tracheal stenosis would depend on the extent of tracheal cartilaginous injury, either 90 degrees (n=6) or 180 degrees (n=6) of anterior wall of 4 tracheal rings were cauterized in 12 mongrel dogs using Nd-YAG laser. Beginning at 3 weeks after cauterization, 180 degrees tracheal injury resulted in life-threatening tracheal stenosis whereas 90 degrees injury did not. Gross and microscopic examinations showed that after 180 degrees injury, tracheal stenosis was accompanied by the loss of tracheal cartilage and dense fibrosis. These results indicate that tracheal stenosis depends on the extent of tracheal injury in experimental canine model.


Peptidylprolyl isomerase A (PPIA) as a preferred internal control over GAPDH and beta-actin in quantitative RNA analyses.
A good internal control is critical in all quantitative analyses of gene expression. Levels of bet-actin, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and peptidylprolyl isomerase A (PPIA) were analyzed in 78 samples (data obtained from our laboratory and from a publicly available database at http://www.ncbi.nlm.nih.gov/SAGE/). These libraries included cell lines and tissues from brain, breast, colon, kidney, ovary, pancreas, prostate, skin, and vascular origin. The level of PPIA mRNA is the most constant among the three genes. Hence, our study suggests that PPIA is a better internal control than beta-actin or GAPDH, the two most commonly used internal controls.


Characteristics of IgG antiphospholipid antibodies in patients with systemic lupus erythematosus and syphilis.
To evaluate the similarities and differences of antiphospholipid antibodies (aPL) in systemic lupus erythematosus (SLE) and syphilis, we studied 20 SLE and 16 syphilis high titer IgG aPL sera for antibody isotype, avidity, phospholipid specificity, light chain and IgG subclass. Syphilis aPL had lower avidity, with kappa light chain and IgG1 and IgG3 predominance, in contrast to higher avidity, with lambda light chain and IgG2 and IgG4 predominance in SLE aPL. Phospholipid specificities were similar. SLE and syphilis aPL both recognize phospholipid epitopes but differ in important antibody characteristics.


Human trial using the novel bioprosthetic VenoValve in patients with chronic venous insufficiency.
Chronic venous insufficiency (CVI) is a disease characterized by failure of the venous valves that allow blood from the lower limbs to return to the heart. The more severe types of CVI (C4b-C6 disease) significantly influence patients' quality of life (QOL). The treatment options for CVI of the deep system are limited. The present study is the first-in-human study using a prosthetic venous valve, VenoValve, to initially evaluate patient outcomes. We evaluated the feasibility, initial safety, and performance outcomes of the VenoValve. Ten patients with C5-C6 CVI of the deep venous system secondary to postthrombotic syndrome had had a VenoValve surgically implanted into the femoral vein in Bogota, Colombia, under approval of the local ethics committee and Colombian National Food and Drug Surveillance Institute, national health care regulatory body, or the Colombian National Food and Drug Surveillance Agency. Follow-up examinations were conducted postoperatively at 2 and 14 days and then every 30 days for 6 months. The results of the assessments for adverse events, reflux time, disease severity (venous clinical severity scores), pain scores (visual analog scale), and QOL (VEINES-QOL/Sym [venous insufficiency epidemiological and economic study-QOL/symptoms] questionnaire) were documented. Ten patients underwent successful implantation of the VenoValve into the femoral vein as outpatients (100% technical success rate). Of the 10 patients, 9 had undergone VenoValve placement under regional anesthesia and 1 under local anesthesia. Six patients had required bovine patch angioplasty of the vein. Four adverse events occurred, including one case of hematoma at the incision site that was aspirated, 2 cases of superficial wound infection in C6 patients treated with antibiotics, and 1 case of a bleeding complication due to warfarin anticoagulation. One patient's VenoValve had thrombosed at 5 months due to nontherapeutic anticoagulation. Improvements in all 5 patients who had reached the 6-month follow-up mark with the VenoValve were demonstrated during the study period by decreases in the venous clinical severity scores (61% decrease from baseline), visual analog scale for pain scores (57% decrease), and reflux time (40% decrease) and a statistically significant improvement in the VEINES-QOL/Sym questionnaire. The patient with the occluded VenoValve had experienced improvements in all areas except for the reflux time. The latter patient had shown improvement because her ulcer had nearly healed before the occurrence of the thrombosis. The early results of the first-in-human trial using the VenoValve appear promising, with improvements in clinical outcomes and QOL. The VenoValve is the first prosthetic valve that has shown success at 6 months of follow-up. These findings offer insight for creating better outcomes for these highly disabled patients.


Design of a novel molecular beacon: modification of the stem with artificially genetic alphabet.
A molecular beacon that incorporates components of an artificially expanded genetic information system (Aegis) in its stem is shown not to be opened by unwanted stem invasion by adventitious standard DNA; this should improve the "darkness" of the beacon in real-world applications.


The genetics and biology of DISC1--an emerging role in psychosis and cognition.
In the developing field of biological psychiatry, DISC1 stands out by virtue of there being credible evidence, both genetic and biological, for a role in determining susceptibility to schizophrenia and related disorders. We highlight the methodologic paradigm that led to identification of DISC1 and review the supporting genetic and biological evidence. The original finding of DISC1 as a gene disrupted by a balanced translocation on chromosome 1q42 that segregates with schizophrenia, bipolar disorder, and recurrent major depression has sparked a number of confirmatory linkage and association studies. These indicate that DISC1 is a generalizable genetic risk factor for psychiatric illness that also influences cognition in healthy subjects. DISC1 has also been shown to interact with a number of proteins with neurobiological pedigrees, including Ndel1 (NUDEL), a key regulator of neuronal migration with endo-oligopeptidase activity, and PDE4B, a phosphodiesterase that is critical for cyclic adenosine monophosphate signaling and that is directly linked to learning, memory, and mood. Both are potential "drug" targets. DISC1 has thus emerged as a key molecular player in the etiology of major mental illness and in normal brain processes.


Primary states of consciousness: A review of historical and contemporary developments.
Primary states of consciousness are conceived as phylogenetically older states of consciousness as compared to secondary states governed by sociocultural inhibition. The historical development of the concept in psychiatry and neurobiology is reviewed, along with its relationship to theories of consciousness. We suggest that primary states of consciousness are characterized by a temporary breakdown of self-control accompanied by a merging of action, communication, and emotion (ACE fusion), ordinarily segregated in human adults. We examine the neurobiologic basis of this model, including its relation to the phenomenon of neural dedifferentiation, the loss of modularity during altered states of consciousness, and increased corticostriatal connectivity. By shedding light on the importance of primary states of consciousness, this article provides a novel perspective on the role of consciousness as a mechanism of differentiation and control. We discuss potential differentiators underlying a gradient from primary to secondary state of consciousness, suggesting changes in thalamocortical interactions and arousal function. We also propose a set of testable, neurobiologically plausible working hypotheses to account for their distinct phenomenological and neural signatures.


A pinusolide derivative, 15-methoxypinusolidic acid from Biota orientalis inhibits inducible nitric oxide synthase in microglial cells: implication for a potential anti-inflammatory effect.
The inhibitory effect of 15-methoxypinusolidic acid (15-MPA) isolated from Biota orientalis (Cupressaceae) on lipopolysaccharide (LPS)-induced inflammation in microglial BV2 cells was investigated. 15-MPA significantly reduced the expression of inducible nitric oxide synthase (iNOS), the activity of iNOS, and the production of nitric oxide (NO) in LPS-stimulated BV2 cells. In addition, 15-MPA significantly suppressed the expressions of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and cyclooxygenase (COX)-2. However, 15-MPA did not affect LPS-induced degradation of inhibitor kappaB-alpha (IkappaB-alpha) and translocation of nuclear factor-kappaB (NF-kappaB) into the nucleus. LPS-activated p38 MAPK, extracellular signal-regulated kinase (ERK)-1/2, and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) were not affected by 15-MPA. Taken together, this study demonstrates that 15-MPA inhibits LPS-induced iNOS expression and NO production, independent on MAPK and NF-kappaB, suggesting a potential anti-inflammatory effect of the compound on microglial cells.


Relevant proteins for the monitoring of engraftment phases after allogeneic hematopoietic stem cell transplantation.
Hematopoietic Stem Cell Transplant (HSCT) has been successfully used as standard therapy for hematological disorders. After conditioning therapy, patients undergoing allogeneic HSCT, present three different phases of engraftment: early pre-engraftment, early post-engraftment, and late engraftment. Severe complications are associated with morbidity, mortality, and malignancies in these phases, which include effects on the oral cavity. The changes in the salivary composition after HSCT may contribute to identifying relevant proteins that could map differences among the phases of diseases, driven for personalized diagnostics and therapy. Unstimulated whole saliva was collected from patients submitted to HSCT. The samples were submitted to trypsin digestion for a Mass spectrometry analysis. MaxQuant processed the Data analysis, and the relevant expressed proteins were subjected to pathway and network analyses. Differences were observed in the most identified proteins, specifically in proteins involved with the regulation of body fluid levels and the mucosal immune response. The heatmap showed a list of proteins exclusively expressed during the different phases of HSCT: HBB, KNG1, HSPA, FGB, APOA1, PFN1, PRTN3, TMSB4X, YWHAZ, CAP1, ACTN1, CLU and ALDOA. Bioinformatics analysis implicated pathways involved in protein processing in the endoplasmic reticulum, complement and coagulation cascades, apoptosis signaling, and cholesterol metabolism. The compositional changes in saliva reflected the three phases of HSCT and demonstrated the usefulness of proteomics and computational approaches as a revolutionary field in diagnostic methods.


Correlation of morphology, immunophenotype, and flow cytometry with remission induction and survival in high grade non-Hodgkin's lymphoma.
A series of cases of high grade non-Hodgkin's lymphomas has been studied by morphology (110 cases), immunocytochemistry (90 cases), using reagents reactive in fixed paraffin-embedded tissue, and flow cytometry (77 cases). B-cell tumours constituted 67.0 per cent of the total, T-cell tumours 22.0 per cent, and unclassified cases 8.8 per cent. Immunocytochemistry revealed two anaplastic carcinomas. Of the 77 cases studied by flow cytometry, 67.5 per cent were diploid and 32.5 per cent DNA aneuploid. T-cell tumours were more likely to be diploid than B-cell tumours, though the difference did not reach statistical significance. T-cell tumours had a significantly lower proliferative index (%S + G2) than B-cell tumours (P = 0.002). The overall remission induction rate was 68 per cent and actuarial 3-year survival 47 per cent. There was a trend for cases with %S + G2 less than 22 per cent to survive longer (P = 0.07). This trend became statistically significant when aneuploid cases were added to the high PI group (P = 0.04). No correlation was seen between morphological or immunophenotypic groups and remission induction rates or survival.


Selective Priming of Tumor Blood Vessels by Radiation Therapy Enhances Nanodrug Delivery.
Effective drug delivery is restricted by pathophysiological barriers in solid tumors. In human pancreatic adenocarcinoma, poorly-permeable blood vessels limit the intratumoral permeation and penetration of chemo or nanotherapeutic drugs. New and clinically viable strategies are urgently sought to breach the neoplastic barriers that prevent effective drug delivery. Here, we present an original idea to boost drug delivery by selectively knocking down the tumor vascular barrier in a human pancreatic cancer model. Clinical radiation activates the tumor endothelial-targeted gold nanoparticles to induce a physical vascular damage due to the high photoelectric interactions. Active modulation of these tumor neovessels lead to distinct changes in tumor vascular permeability. Noninvasive MRI and fluorescence studies, using a short-circulating nanocarrier with MR-sensitive gadolinium and a long-circulating nanocarrier with fluorescence-sensitive nearinfrared dye, demonstrate more than two-fold increase in nanodrug delivery, post tumor vascular modulation. Functional changes in altered tumor blood vessels and its downstream parameters, particularly, changes in Ktrans (permeability), Kep (flux rate), and Ve (extracellular interstitial volume), reflect changes that relate to augmented drug delivery. The proposed dual-targeted therapy effectively invades the tumor vascular barrier and improve nanodrug delivery in a human pancreatic tumor model and it may also be applied to other nonresectable, intransigent tumors that barely respond to standard drug therapies.


Corrigendum: Matching different-structured advertising pictorial metaphors with verbalization forms: incongruity-based evoked response potentials evidence.
[This corrects the article DOI: 10.3389/fpsyg.2023.1131387.].


Comparison of cannabis and tobacco withdrawal: severity and contribution to relapse.
This naturalistic telephone survey study compared perceptions of withdrawal severity in 67 daily cannabis users and 54 daily tobacco cigarette smokers who made quit attempts during the prior 30 days. A Withdrawal Symptom Checklist assessed the severity of abstinence symptoms and a Likert scale assessed perceived relations between abstinence symptoms and relapse. A composite Withdrawal Discomfort Score did not differ significantly between groups (M = 13.0 for cannabis, vs. M = 13.2 for tobacco). Individual symptom severity ratings were also of similar magnitude, except craving and sweating were slightly higher for tobacco. Both groups reported that withdrawal contributed substantially to relapse, and the strength of these ratings was similar across groups. The diverse convenience sample examined in this study adds external validity and generalizability to prior studies that included only users not planning to quit or excluded many common types of cannabis users. The comparable withdrawal experience from these heterogeneous cannabis and tobacco users supports previous findings from controlled laboratory studies and indicates that real-world, frequent cannabis users perceive that withdrawal symptoms negatively affect their desire and ability to quit.


Pre-procedural ACE-activity does not predict symptomatic in-stent restenosis.
Several studies indicate that ACE-activity is related to atherosclerosis. We investigated the correlation between ACE-activity, in plasma as well as in the atherosclerotic plaque, and in-stent restenosis. ACE-activity was measured in blood samples from 178 patients who underwent a percutaneous coronary intervention with stent placement. During 8 months follow-up, 51 of these patients had an adverse clinical event. ACE-activity did not differ between patients with or without adverse events (21.5 vs. 23.1 nM/ml/min; P=0.36). Tissue samples were obtained with an atherectomy catheter before elective stent placement in another group of 13 patients with de novo stenosis. In this tissue, we determined the ACE-content immunohistologically. These patients were scheduled for follow-up quantitative coronary angiography after 12 months. In this group, the quantity of ACE was not correlated to the late luminal loss (0.31 vs. 0.38 mm; P=0.76). In this study, pre-procedural ACE-activity, in plasma as well as in the atherosclerotic plaque, does not predict the occurrence of in-stent restenosis.


siRNA-Encapsulated Hybrid Nanoparticles Target Mutant K-ras and Inhibit Metastatic Tumor Burden in a Mouse Model of Lung Cancer.
There is an unmet need in the development of an effective therapy for mutant K-ras-expressing non-small-cell lung cancer (NSCLC). Although various small molecules have been evaluated, an effective therapy remains a dream. siRNAs have the potential to downregulate mutant K-ras both at the protein and mRNA levels. However, a safe and effective delivery of siRNAs to tumors remains a limitation to their translational application in the treatment of this highly debilitating disease. Here we developed a novel hybrid nanoparticle carrier for effective delivery of anti-mutant K-ras to NSCLC (AKSLHN). The ability of this treatment modality to regress lung tumors in mouse models was evaluated as a monotherapy or as a combination treatment with erlotinib. Further, the toxicity of this treatment modality to healthy tissues was evaluated, along with its ability to elicit immune/inflammatory reactions. The results suggest that this treatment modality is a promising prospect for the treatment of mutant K-ras-expressing NSCLC without any accompanying toxicity. However, further understanding of the cellular-level interaction between AHSLHN and erlotinib needs to be attained before this promising treatment modality can be brought to the bedside.


Prevention of meningitis in a day-care center: management of an outbreak of Haemophilus influenzae type b.
The care of infants and toddlers in nursery school and day-care centers in increasingly large numbers over the past decade poses special problems with respect to communicable disease control. This age group is particularly susceptible to those infectious agents (bacterial, viral, and parasitic) spread by close personal contact. This study describes an outbreak of Haemophilus influenzae type b meningitis in a large nursery school in Westchester County, New York. Organized efforts to control the outbreak through recommendation of rifampin prophylaxis were undertaken and evaluated. Compliance following the first case of meningitis was unacceptably low (45% of children and 33% of staff). Following the second case, however, compliance rose to 90% among child attendees and 79% among staff. Recommended procedures for implementation of control measures are described.


Assessment of aberrations on chromosome 8 in prostatic atrophy.
To systematically examine the genetic alterations on chromosome 8 in prostate epithelia deriving from atrophic areas, and to compare these alterations with those of cells derived from prostatic intraepithelial neoplasia (PIN) and prostate cancer in the same organ. Tissue microarrays were constructed from 50 patients with histologically different tissues, including normal, PIN, atrophy and cancer lesions. Control samples were obtained from 10 patients who died from causes other than prostate cancer. Multicolour DNA probes for 8p22, centromere 8 and 8q24 were used to detect genetic alterations by fluorescence in situ hybridisation analysis. Chromosomal alterations were detected on chromosome 8 in all analysed tissues. Including all observed signal patterns, a gradual increase of nuclei with loss of 8p22 was detected in normal (16%), in atrophy (21%), in PIN (25%) and in cancer tissue (31%), and there was gain in 8q24 in normal tissue (10%), in atrophy lesions (19%), in PIN (21%) and in cancer (27%). Generally, in all three lesion types the percentage of cells with 8q24 gain was significantly lower than the percentage of cells with loss of 8p22. This investigation confirms the presence of severe chromosomal aberrations in the epithelium of the atrophic glands of the prostate. The aberrations are the same those that can be found in PIN and in prostate cancer. These findings confirm the genetic instability of the cells in the atrophic areas of the prostate, which can be a target for further injuries, leading to prostate cancer.


A case of postoperative Sphingomonas paucimobilis endophthalmitis after cataract extraction.
To report a case of an acute onset of delayed postoperative endophthalmitis that was caused by Sphingomonas paucimobilis. This case demonstrates an acute onset of delayed postoperative endophthalmitis at 3 months after uneventful cataract extraction and posterior chamber intraocular lens implantation. We performed vitrectomy, intraocular lens and capsular bag removal, and intravitreal antibiotics injection. On the smear stains from the aspirated vitreous humor, gram-negative bacilli were detected and S. paucimobilis was found in culture. At three months after vitrectomy, the best corrected visual acuity was 20/300. Fundus examination showed mild pale color of optic disc and macular degeneration. Vitrectomy with intravitreal ceftazidime injection had contributed to the favorable result in case of an acute onset of delayed postoperatire endophthalmitis caused by S. paucimobilis.


Efficient, Antibiotic Marker-Free Transformation of a Dicot and a Monocot Crop with Glutamate 1-Semialdehyde Aminotransferase Selectable Marker Genes.
Antibiotic-free, efficient in vitro selection in plant genetic engineering can improve risk perception and speed up pre-market scrutiny of genetically modified crops. We provide a protocol for genetic transformation of two important crops, durum wheat and alfalfa, using a bacterial and a plant-derived selectable marker gene encoding mutated, gabaculine-insensitive glutamate 1-semialdehyde aminotransferase (GSA) enzymes. These methods can potentially be applied, with minor adaptations, to many other monocot and dicot crop plants.


Crab shell amendments enhance the abundance and diversity of key microbial groups in sulfate-reducing columns treating acid mine drainage.
Substrate amendments composed of crab shell (CS) waste materials have been shown to significantly improve the longevity and performance of acid mine drainage (AMD) treatment systems containing spent mushroom compost (SMC), yet the development of key microbial populations within these systems has not been investigated. To better understand the effects of CS on microbial dynamics in these systems, clone libraries and real-time quantitative PCR (qPCR) were performed on materials from a laboratory-scale AMD treatment system containing SMC and 0 to 100% CS substrate after receiving a continuous flow of AMD for 148 days (428 pore volumes). The proportion of CS in the substrate positively correlated with the diversity of sulfate-reducing bacteria (SRB) and archaeal clones, but negatively correlated with fungal diversity. CS also impacted microbial community structure, as revealed in Unifrac significance and principal coordinate analysis tests. The column containing 100% CS substrate supported 7 different genera of SRB-the most ever observed in an AMD treatment system. Moreover, the copy numbers of functional genes representing fermenters, sulfate reducers, and chitin degraders increased with increasing proportions of CS. These observations agree well with the chemical performance data, further validating that by supporting more abundant key microbial groups, chitinous substrates may provide benefits for improving both the longevity and performance of AMD treatment systems, and may provide similar benefits for the treatment of other environmental contaminants that are amenable to anaerobic bioremediation.Key points• Crab shell improves the longevity and performance of acid mine drainage treatment.• The diversity of sulfate-reducing bacteria is enhanced with crab shell amendments.• Crab shell supports more abundant key microbial groups than spent mushroom compost.


Prognostic risk factors for conversion in laparoscopic cholecystectomy.
Laparoscopic cholecystectomy (LC) is the gold standard technique for the treatment of gallbladder disease. However, in some cases, conversion to open surgery is still necessary. Identification of patients with high risk of conversion is of great importance to prepare the surgical scenario and to anticipate the convalescence. The objective of this study is to identify the factors that may predict a conversion to an open procedure. A total of 1386 LC were performed in Dr. Manuel Gea González General Hospital, from January 2009 to May 2013. A retrospective analysis of 41 parameters in these patients was performed, including demographic variables, clinical history, laboratory studies, ultrasound results and intraoperative findings. Subsequently, a multivariate logistic regression analysis was used to determine the predictive variables for conversion. Fourteen patients required conversion (1%). The multivariate analysis revealed that the factor that was most associated with conversion was emergency surgery (OR 4.9, CI 95% 2.3-2.4), as well as dilatation > 6 mm of the common bile duct in ultrasound (OR 1.8, CI 95% 1.1-1.7), hepatomegaly (OR 1.3, CI 95% 0.3-4.9), diagnosis of chronic cholecystitis associated to previous biliary colics (OR 2.8, CI 95% 1.0-21) and elevated alanine aminotransaminase (OR 1.2, CI 95% 1.0-2.1). Patients with acute symptoms, with dilatation of the bile duct, cholestasis history and hepatomegaly have a higher risk of a conversion surgery. These factors may warn both the patient and the surgeon for a complex surgery and possible complications.


Pure laparoscopic right hepatectomy in the semi-prone position using the intrahepatic Glissonian approach and a modified hanging maneuver to minimize intraoperative bleeding.
Although laparoscopic liver resection has been widely adopted, performing a pure laparoscopic right hepatectomy remains a challenging procedure. The aim of this report is to evaluate the efficiency of a pure laparoscopic right hepatectomy (PLRH) in the semi-prone position using the intrahepatic Glissonian approach and a modified hanging maneuver. Pure laparoscopic right hepatectomy was performed in the semi-prone position with the use of an intrahepatic Glissonian approach and modified hanging maneuver for patients with primary liver cancer (n = 3) and metastatic liver cancer (n = 1). The intraoperative total blood loss was only 95-140 g (mean: 126.2 g). None of the patients required a blood transfusion, and no serious complications were encountered. The durations of the surgeries ranged from were 308 to 445 min (mean: 394.8 min). The postoperative hospital stay was 8-11 days (mean 9.5 days). Pure laparoscopic right hepatectomy in the semi-prone position using the intrahepatic Glissonian approach and a modified hanging maneuver is thus considered to be a safe modality, which minimizes intraoperative bleeding.


Significant ophthalmoarthropathy associated with ectodermal dysplasia in a child with Marshall-Stickler overlap: a case report.
The Marshall-Stickler phenotype is an autosomal dominant trait comprising ocular abnormalities, sensorineural hearing loss, craniofacial anomalies, and anhidrotic ectodermal dysplasia. A 5-year-old boy from non-consanguineous family in Austria was born with features of Pierre-Robin association (cleft palate, micrognathia, and glossoptosis). Radiological examination at birth revealed coronal clefts of the vertebrae, platyspondyly, and flaring of the metaphyses of the long bones (features suggestive of the Weissenbacher-Zweymuller syndrome). Significant features of ectodermal dysplasia such as sparse hair, defective dentition, dysplastic nails, and deficient sweating associated with bouts of unexplained hyperthermia were present. These features not shared by Stickler syndrome, Wagner syndrome, or Weissenbacher - Zweymuller syndrome, all of which are conditions often confused with Marshall syndrome. There is continuing debate over the clinical overlap and differential diagnosis of Marshall and Stickler syndromes. We compared similar disorders, such as Weissenbacher-Zweymuller, and Wagner syndromes, and conclude that our present patient manifests Marshall-Stickler overlap. Focussing on subtle facial and ectodermal features may detract from recognising the serious outcome of congenital vitreous/myopia anomaly. Retinal detachment with subsequent blindness is a major risk in our current patient.


Inhibitors of antibiotic efflux in resistant Enterobacter aerogenes and Klebsiella pneumoniae strains.
In Enterobacter aerogenes and Klebsiella pneumoniae, efflux provides efficient extrusion of antibiotics and contributes to the multidrug resistance phenotype. One of the alkoxyquinoline derivatives studied here, 2,8-dimethyl-4-(2'-pyrrolidinoethyl)-oxyquinoline, restores noticeable drug susceptibility to resistant clinical strains. Analyses of energy-dependent chloramphenicol efflux indicate that this compound inhibits the efflux pump mechanism and improves the activity of structurally unrelated antibiotics on multidrug-resistant E. aerogenes and K. pneumoniae isolates.


BAIAP2L2 promotes the progression of gastric cancer via AKT/mTOR and Wnt3a/β-catenin signaling pathways.
Gastric cancer is third leading cause of cancer-related deaths worldwide and remarkably threatens human health and life. BAIAP2L2 is an epithelial-specific BAR domain protein that considered to be closely related to cell migration. In this study, we explored the specific role of BAIAP2L2 in human gastric cancer. BAIAP2L2 expression was analyzed via online database and immunohistochemistry. The proliferation was detected using CCK8 and colony formation assay. The migration and invasion was confirmed by transwell assay, and the apoptosis of gastric cancer cells was detected by flow cytometry. BAIAP2L2 was highly expressed in tumour tissues and its expression significantly correlated with tumor diameter, T stage, pTNM stage and lymph node metastasis, respectively. Compared with GES-1 cells, SGC7901, MKN28, MKN45, AGS and BGC-823 tumor cells were all presented a high-expression of BAIAP2L2. The in vitro results showed that knockdown of BAIAP2L2 inhibited the proliferation, migration and invasion, and induced the apoptosis of gastric cancer cell. Further, knockdown of BAIAP2L2 inhibited the expression of the related proteins of AKT/mTOR and Wnt3a/β-catenin signaling pathways. BAIAP2L2 is upregulated in gastric cancer, and knockdown of BAIAP2L2 inhibited the proliferation and metastasis through the inactivation of AKT/mTOR and Wnt3a/β-catenin signaling pathways.


Effect of output variation with dose rate on the Virtual Wedge factor.
Siemens Virtual Wedge factor may drift significantly due to increase in output as dose rate decreases. This variation of output is caused by defective sample and hold boards in the dosimetry circuit due to radiation damage. In this note, we present a simple model based on the principle of Virtual Wedge operation and the measured output variation with dose rate to quantitatively describe Virtual Wedge factor drift as a function of field size and wedge angle. Our results support the recommendation that VWF be measured for large field sizes (e.g., 20 ' 20 cm2) and large wedge angles (e.g., 60 degrees) as a part of routine quality assurance.


Spinal-supraspinal serotonergic circuits regulating neuropathic pain and its treatment with gabapentin.
Not all neuropathic pain patients gain relief from current therapies that include the anticonvulsant, gabapentin, thought to modulate calcium channel function. We report a neural circuit that is permissive for the effectiveness of gabapentin. Substance P-saporin (SP-SAP) was used to selectively ablate superficial dorsal horn neurons expressing the neurokinin-1 receptor for substance P. These neurons project to the brain as shown by retrograde labelling and engage descending brainstem serotonergic influences that enhance spinal excitability via a facilitatory action on 5HT(3) receptors. We show the integrity of this pathway following nerve injury contributes to the behavioural allodynia, neuronal plasticity of deep dorsal horn neurons and the injury-specific actions of gabapentin. Thus SP-SAP attenuated the tactile and cold hypersensitivity and abnormal neuronal coding (including spontaneous activity, expansion of receptive field size) seen after spinal nerve ligation. Furthermore the powerful actions of gabapentin after neuropathy were blocked by either ablation of NK-1 expressing neurones or 5HT(3) receptor antagonism using ondansetron. Remarkably, 5HT(3) receptor activation provided a state-dependency (independent of that produced by neuropathy) allowing GBP to powerfully inhibit in normal uninjured animals. This circuit is therefore a crucial determinant of the abnormal neuronal and behavioural manifestations of neuropathy and importantly, the efficacy of gabapentin. As this spino-bulbo-spinal circuit contacts areas of the brain implicated in the affective components of pain, this loop may represent a route by which emotions can influence the degree of pain in a patient, as well as the effectiveness of the drug treatment. These hypotheses are testable in patients.


Knockout Zbtb33 gene results in an increased locomotion, exploration and pre-pulse inhibition in mice.
The Zbtb33 gene encodes the Kaiso protein-a bimodal transcriptional repressor. Here, the effects of Zbtb33 gene disruption on the brain and behaviour of the Kaiso-deficient (KO) and C57BL/6 (WT) male mice were investigated. Behaviour was studied using the open field, novel object, elevated plus maze and acoustic startle reflex tests. Brain morphology was investigated with magnetic resonance imaging. Biogenic amine levels and gene expression in the brain were measured with high-performance liquid chromatography and quantitative real-time RT-PCR, respectively. Zbtb33 gene mRNA was not detected in the brain of KO mice. KO mice exhibited increased locomotion, exploration in the open field, novel object and elevated plus-maze test. At the same time, Zbtb33 gene disruption did not alter anxiety-related behaviour in the elevated plus-maze test. KO mice showed elevated amplitudes and pre-pulse inhibitions of the acoustic startle reflex. These behavioural alterations were accompanied by significant reductions in the volumes of the lateral ventricles without significant alterations in the volumes of the hippocampus, striatum, thalamus and corpus callosum. Norepinephrine concentration was reduced in the hypothalami and hippocampi in KO mice, while the levels of serotonin, dopamine, their metabolites as well as mRNA of the gene coding brain-derived neurotrophic factor were not altered in the brain of KO mice compared to WT mice. This study is the first to reveal the involvement of the Zbtb33 gene in the regulation of behaviour and the central nervous system.


Acute hepatic failure.
Acute hepatic failure is characterized by a sudden catastrophic compromise of hepatic failure that causes clinical signs such as anorexia, depression, vomiting, diarrhea, icterus, and encephalopathy. Injurious hepatotoxins, drugs, infectious agents, or metabolic disturbances can cause acute hepatic failure; however, in many cases, the inciting cause is not determined. Treatment is aimed at controlling complications such as fluid-electrolyte imbalances, hepatic encephalopathy, hypoglycemia, bleeding diathesis, gastric ulcer, sepsis, and endotoxemia, in order to provide time for liver regeneration and recovery.


How common is natural conception in women who have had a livebirth via assisted reproductive technology? Systematic review and meta-analysis.
What is the proportion of women who experience natural conception after a livebirth via assisted reproductive technology (ART)? Current evidence suggests that natural conception pregnancy may occur in at least one in five women after having a baby via IVF or ICSI. It is widely known that some women having babies via ART go on to conceive naturally. This reproductive history is of media interest and often described as 'miracle' pregnancies. A systematic review with meta-analysis was carried out. Ovid Medline, Embase, and PsycINFO were searched until 24 September 2021 for English language, human studies from 1980. Search terms were used for the concepts of natural conception pregnancy, assisted reproduction, and livebirth. The inclusion criterion was studies with an outcome measure of the proportion of women experiencing natural conception pregnancy after an ART livebirth. Quality of studies was assessed using the Critical Appraisal Skills Programme cohort study checklist or AXIS Appraisal tool for cross-sectional studies, and a risk of bias assessment was carried out. No studies were excluded based on quality. Random-effects meta-analyses were adopted to produce a pooled effect estimate of the proportion of natural conception pregnancy after ART livebirth. A total of 1108 distinct studies were identified, resulting in 54 studies after screening by title and abstract. Eleven studies including 5180 women were selected for this review. The included studies were mostly of moderate quality with a maximum follow-up period ranging from 2 to 15 years. Four studies reported natural conception livebirths which were used as known underestimates of natural conception pregnancies. The pooled estimate for the proportion of women having natural conception pregnancies after ART livebirth was 0.20 (95% CI, 0.17-0.22). The studies varied widely according to methodology, population, cause of subfertility, type and outcome of fertility treatment, and length of follow-up, leading to potential bias relating to confounding, selection bias, and missing data. Current evidence suggests that contrary to widely held views, natural conception pregnancy after ART livebirth is far from rare. National, data-linked studies are needed to provide more accurate estimates of this incidence and analysis of associated factors and trends over time to facilitate tailored counselling of couples considering further ART. This work was conducted as part of an academic clinical fellowship awarded to AT by the National Institute for Health Research (NIHR). NIHR has had no input into the study design, data collection, and analysis, nor the writing of this study. No authors have any conflicts of interest. PROSPERO (CRD42022322627).


Documentation of ED patient pain by nurses and physicians.
The purpose of this study was to evaluate ED documentation of patient pain in light of the Joint Commission of Accreditation of Healthcare Organization's emphasis on pain assessment and management. A prospectively designed pain management survey was offered to patients on ED discharge. Documentation of pain intensity by ED nurses and physicians was retrospectively reviewed. Of 302 patients surveyed, 261 (86%) complete charts were available for review. Initial pain assessments were noted on 94% of the charts, but a pain scale was used for only 23% of the patients. Documentation of pain subsequent to therapy was noted on 39% of the charts, but a pain scale was used only 19% of the time. Subsequent to therapy, nurses were 2.2 x more likely to document pain assessments than physicians (30% vs 16%, P <.001). Patients with severe pain on arrival (46% vs 31%, odds ratio [OR] = 1.9, P <.02), chest pain (72% vs 32%, OR = 5.4, P <.001), or those receiving powerful analgesics (62% vs 32%, 3.5, P <.001) were more likely to receive a documented subsequent pain assessment than other patients. Pain severity is not consistently documented in ED patients, especially after therapy has been provided. Patients with severe pain and those receiving powerful analgesics were more likely to have a pain assessment subsequent to ED therapy.


Microalbuminuria is independently associated with deep or infratentorial brain microbleeds in hypertensive adults.
Brain microbleeds (BMBs) detected on gradient echo T2*-weighted magnetic resonance imaging (GE-MRI) may be pathophysiologically linked to ischemic cerebral small-vessel disease (SVD) and increased risk of future hemorrhagic stroke. Chronic kidney disease (CKD) has been associated with the presence of BMBs in stroke patients. However, the relationship between CKD markers and BMBs in stroke-free populations is unknown. Two hundred and eighty-five hypertensive subjects (mean age 68.6 years) without neurological symptoms were enrolled from a hospital-based outpatient clinic and all participants underwent GE-MRI. We calculated urinary albumin/creatinine ratio (UACR) from morning spot urine and the estimated glomerular filtration rate (eGFR) in serum samples. Multivariate logistic regression analysis was used to evaluate the association between these kidney biomarkers and the presence and location of BMBs, controlling for age, sex, use of antihypertensive or antithrombotic drugs, and MRI findings. BMBs were observed in 48 (16.8%) patients. Median UACRs were significantly higher in patients with deep or infratentorial BMBs than in patients with pure lobar BMBs (54 vs. 17 mg/g creatinine, P = 0.04). No significant differences were found between eGFR levels and the location of BMBs. Microalbuminuria (UACR >30- ≤300 mg/g creatinine), but not low eGFR level was significantly associated with higher prevalence of deep or infratentorial BMBs (odds ratio (OR): 3.16, 95% confidence interval (CI): 1.34-7.44, P = 0.009) even after adjustment for potential confounding factors. Microalbuminuria is closely associated with the prevalence of deep or infratentorial BMBs in hypertensive patients. Our findings provide new insights into the association between risk factors and the distribution of BMBs.


Aerobic Ru-catalyzed direct C2-olefination of N-heteroarenes with alkenes directed by a removable N-dimethylcarbamoyl group.
A highly efficient and selective Ru-catalyzed direct C2-olefination of indoles, pyrroles, and carbazoles assisted by a removable N-dimethylcarbamoyl group has been developed by using O2 as the terminal oxidant. Both electron-deficient and unactivated alkenes are applicable to the protocol.


Is the LDL receptor involved in cortical amyloid protein clearance?
This article puts forward the hypothesis that the Low Density Lipid Receptor (LDLR) is one of the molecules that is involved in the clearance of amyloid proteins in the brain and that it may play a role in Alzheimer's Disease (AD) via its up-regulation by statins. The hypothesis is built on the following observations: a-statins (which have been shown to increase LDLR in astrocytes, see below) have a beneficial role in AD, b-defects in the LDL receptor gene are found in AD, c-molecules with similar structure to the LDLR have been shown to clear amyloid protein from the brain.


Number representation is influenced by numerical processing level: an ERP study.
The same numerical magnitude can be manifested in different physical notations. However, how the numbers with distinct notations are mentally represented is still unclear. Here, we hypothesized that how the number is mentally represented is influenced by the numerical processing level of the tasks. If the task only needed a low-level processing, the representation would be dependent on the surface forms of the numbers, exhibiting a numerical notation-dependent effect. By contrast, if the task required a deeper magnitude processing, the processing would utilize an abstract numerical format whose effects are notation independent. To test this hypothesis, we manipulated the notation type and the numerical processing level of the tasks. An ERP component N270 was taken to index the mismatch between the internal representation and the probed number. The results showed that N270 was enhanced when the magnitude was mismatched between two numbers. More importantly, under the task requiring a low-level processing (e.g., magnitude comparison), compared with the same notations, the latency of N270 difference wave was delayed by different notations, exhibiting a notation-dependent effect. However, in the task involving a deeper processing (e.g., magnitude addition), the N270 latencies were earlier for probes having distinct notations (Mandarin or Arabic number) than for probes having the same notations as in the addition operation (Mahjong). Moreover, no difference was found on N270 latencies between the two distinct notations but with similar degree of familiarity. Taken together, these results support our hypothesis that the numerical processing level affects the number representation.


Non-quantal release of acetylcholine in rat atrial myocardium is inhibited by noradrenaline.
In the mammalian myocardium, ACh, which is the main neurotransmitter of cardiac parasympathetic postganglionic fibres, can be released via both quantal (vesicular) and non-quantal (non-vesicular) mechanisms of secretion. Non-quantal release is continuous and independent of vagus activity and exocytosis of ACh-containing vesicles. During the incubation of myocardium in the presence of acetylcholinesterase (AChE) inhibitors, non-quantal ACh release leads to accumulation of ACh in the myocardium and cholinergic effects, which are proportional to the intensity of non-quantal secretion. The aim of the present study was to reveal whether non-quantal release of ACh can be modulated by another major cardioregulator, noradrenaline, or whether it represents uncontrolled leakage of ACh from cholinergic fibres. Cholinergic changes of electrical activity induced by the AChE inhibitor paraoxon (5 × 10(-6) M) in isolated rat right atrial preparations were determined by means of a standard microlectrode technique and used as a measure of the intensity of non-quantal release. Noradrenaline (10(-7) and 10(-6) M) substantially suppressed, but did not abolish, effects of paraoxon via stimulation of α-adrenoceptors, because all experiments were conducted in the presence of the β-blocker propranolol (5 × 10(-6) M). A blocker of ganglionic transmission, hexamethonium bromide (10(-4) M), failed to alter the inhibitory effect of noradrenaline, indicating that only non-quantal ACh release is suppressed by this neurotransmitter. The effects of noradrenaline could be reduced by the α2-antagonist yohimbine (10(-6) M). However, both the α1-agonist phenylephrine (10(-6) M) and the α2-agonist clonidine (10(-6) M) significantly inhibited the cholinergic effects of paraoxon, indicating the possible involvement of both α-adrenoceptor subtypes in mediation of the adrenergic inhibition of non-quantal ACh release. Thus, cardiac non-quantal ACh release can be negatively regulated by noradrenaline, providing another facet of sympathetic-parasympathetic interaction in the heart.


Increased protected sex and abstinence among Namibian youth following a HIV risk-reduction intervention: a randomized, longitudinal study.
To evaluate an HIV risk-reduction intervention among Namibian adolescents. A randomized trial of a 14-session face-to-face intervention emphasizing abstinence and safer sexual practices conducted among 515 youths (median age 17 years and median grade 11) attending 10 secondary schools located in two districts in Namibia. Youths were randomly assigned to the intervention or control condition at the level of the individual. HIV risk behaviours, intentions and perceptions were assessed at baseline, immediately post-intervention and at 6 and 12 months post-intervention. Among all 515 youths who enrolled in the programme, rates of either abstinence or sex with a condom were not different between control and intervention youths at baseline or in the follow-up period. However, analyses conducted among the subset of youths who were sexually inexperienced at baseline (n = 255) revealed that a higher percentage of intervention youths (17%) than control youths (9%, P<0.05) remained sexually inexperienced one year later. Moreover, in the immediate post-intervention period, among baseline virgins who subsequently initiated sex, intervention youths were more likely than control youths to use a condom (18 versus 10%, P<0.05). Additional HIV-related risk behaviours (failure to discuss previous HIV risk exposure with one's sexual partner and alcohol use), intentions to use condoms, and perceptions of the ability to use condoms were positively affected by the intervention. There is evidence that the 'My Future is My Choice' (MFMC) intervention is reducing HIV risk behaviours among sexually inexperienced participants aged 15-18. Related risk behaviours and perceptions are also positively impacted by the intervention.


Susceptibility to antifungal agents and enzymatic activity of Candida haemulonii and Cutaneotrichosporon dermatis isolated from soft corals on the Brazilian reefs.
Candida is a common fungus with the capacity to cause infections in humans. However, most studies have concentrated on clinical isolates and little is known about the identity, ecology and drug resistance of free living species/strains. Here, we isolate eight strains of Candida haemulonii and four strains of Cutaneotrichosporon dermatis from three marine cnidarian zoanthids species (Palythoa caribaeorum, Palythoa variabilis and Zoanthus sociatus) collected from Brazilian coral reefs. Strains were identified by sequencing of the D1/D2 domain LSU rDNA and ITS region. We tested these environmental isolates for their capacity to grow in media with increasing concentration of NaCl, capacity to grow in different temperatures, enzymatic activity and antifungal susceptibility. For C. haemulonii, all strains strongly produced gelatinase, esterase and albuminase and were either able to express lipase, phospholipase and keratinase, but not express urease and DNase. The strains were able to grow at 37 °C, but not at 39 °C, and except for LMS 40, all of them could grow in a 10 % NaCl medium. All isolates were resistant to all antifungals tested, with exception for ketoconazole and tioconazole (MIC = 2 µg/mL). For C. dermatis, all strains could grow at 39 °C and could not express phospholipase, keratinase or gelatinase. However, all were capable of expressing urease, lipase and esterase. Three out of four strains could grow in a 10 % NaCl medium, but none grew in a 30 % NaCl medium. The strains showed high values of minimal inhibitory concentration. LMPV 90 was resistant to tioconazole, terbinafine, fluconazole and posaconazole, and LMS 38 was resistant to all antifungal agents tested. We discuss the characterization of C. haemulonii and C. dermatis as a possible emerging pathogen due to its animal-related enzymatic arsenal and antifungal resistance.


Nicotine dependence and self-esteem in adolescents with mental disorders.
Recent studies in adolescents have found a weak association between lower self-esteem and smoking. However, this association has not been investigated in a psychiatric setting. In 223 inpatient adolescents [140 girls (16.5 years) and 83 boys (16.4 years)], self-esteem was measured with Coopersmith's self-esteem inventory (SEI), and smoking dependence with the Fagerström Test for Nicotine Dependence (FTND). DSM-IV categories included major depression (n=35), anxiety disorders (n=35), psychotic disorders (n=31), eating disorders (n=9), and conduct disorders (n=113). There were 101 smokers and 122 nonsmokers. Self-esteem scores were lower in smokers than in nonsmokers (p=0.039). Self-esteem scores were very significantly lower in smokers showing moderate or high nicotine dependence (i.e., FTND score>or=4) when compared with nonsmokers (p=0.002). Smoking with moderate or high nicotine dependence was associated with lower self-esteem in both girls and boys, whereas smoking with no or low nicotine dependence was associated with lower self-esteem only in girls. Smoking was associated with lower self-esteem in all diagnostic categories, except in eating disorders. Interventions targeted on self-esteem might be used to prevent smoking in adolescents with mental disorders.


Can compassionate healthcare be measured? The Schwartz Center Compassionate Care Scale™.
Assess psychometric characteristics of an instrument to measure patient ratings of treating physicians' compassionate care in a recent hospitalization. We used Cronbach's alpha to examine scale reliability, exploratory and confirmatory factor analysis to examine scale structure of two sets of items on compassionate care. We used Mokken analysis to determine if items in each set belonged to a unidimensional scale. Results indicated that both sets of items had strong reliability when used to rate individual physicians (Cronbach's α=.97 and .95). A one factor model was a good fit to both sets of items. Mokken analysis supported unidimensional scales. Both sets of items correlated with an overall measure of patient satisfaction with physicians and even more strongly with an item measuring emotional support. A patient-rated scale reliably measured hospital physicians' compassion and correlated significantly with an item measuring overall patient satisfaction and a specific measure of satisfaction with emotional support. Measurement of compassionate healthcare should be included in research, educational assessment, and quality improvement programs. Clinicians should participate in efforts to enhance their ability to demonstrate compassionate care including eliciting and sharing information and acting collaboratively to ameliorate patients' socioemotional concerns and needs.