Category fluency, latent semantic analysis and schizophrenia: a candidate gene approach.
Category fluency is a widely used task that relies on multiple neurocognitive processes and is a sensitive assay of cortical dysfunction, including in schizophrenia. The test requires naming of as many words belonging to a certain category (e.g., animals) as possible within a short period of time. The core metrics are the overall number of words produced and the number of errors, namely non-members generated for a target category. We combine a computational linguistic approach with a candidate gene approach to examine the genetic architecture of this traditional fluency measure. In addition to the standard metric of overall word count, we applied a computational approach to semantics, Latent Semantic Analysis (LSA), to analyse the clustering pattern of the categories generated, as it likely reflects the search in memory for meanings. Also, since fluency performance probably also recruits verbal learning and recall processes, we included two standard measures of this cognitive process: the Wechsler Memory Scale and California Verbal Learning Test (CVLT). To explore the genetic architecture of traditional and LSA-derived fluency measures we employed a candidate gene approach focused on SNPs with known function that were available from a recent genome-wide association study (GWAS) of schizophrenia. The selected candidate genes were associated with language and speech, verbal learning and recall processes, and processing speed. A total of 39 coding SNPs were included for analysis in 665 subjects. Given the modest sample size, the results should be regarded as exploratory and preliminary. Nevertheless, the data clearly illustrate how extracting the meaning from participants' responses, by analysing the actual content of words, generates useful and neurocognitively viable metrics. We discuss three replicated SNPs in the genes ZNF804A, DISC1 and KIAA0319, as well as the potential for computational analyses of linguistic and textual data in other genomics tasks.


Somatosensory Plasticity in Pediatric Cerebral Palsy following Constraint-Induced Movement Therapy.
Cerebral palsy (CP) is predominantly a disorder of movement, with evidence of sensory-motor dysfunction. CIMT1 is a widely used treatment for hemiplegic CP. However, effects of CIMT on somatosensory processing remain unclear. To examine potential CIMT-induced changes in cortical tactile processing, we designed a prospective study, during which 10 children with hemiplegic CP (5 to 8 years old) underwent an intensive one-week-long nonremovable hard-constraint CIMT. Before and directly after the treatment, we recorded their cortical event-related potential (ERP) responses to calibrated light touch (versus a control stimulus) at the more and less affected hand. To provide insights into the core neurophysiological deficits in light touch processing in CP as well as into the plasticity of this function following CIMT, we analyzed the ERPs within an electrical neuroimaging framework. After CIMT, brain areas governing the more affected hand responded to touch in configurations similar to those activated by the hemisphere controlling the less affected hand before CIMT. This was in contrast to the affected hand where configurations resembled those of the more affected hand before CIMT. Furthermore, dysfunctional patterns of brain activity, identified using hierarchical ERP cluster analyses, appeared reduced after CIMT in proportion with changes in sensory-motor measures (grip or pinch movements). These novel results suggest recovery of functional sensory activation as one possible mechanism underlying the effectiveness of intensive constraint-based therapy on motor functions in the more affected upper extremity in CP. However, maladaptive effects on the less affected constrained extremity may also have occurred. Our findings also highlight the use of electrical neuroimaging as feasible methodology to measure changes in tactile function after treatment even in young children, as it does not require active participation.


Iatrogenic Teratoma Rupture during TVOR Complicated with Peritonitis, Pleuritis, and Septic Shock.
To obtain a better understanding of the clinical course and the subsequent complications of teratoma rupture. We report a rare case of chemical peritonitis and pleuritis caused by teratoma rupture during ultrasonographically guided transvaginal oocyte retrieval (TVOR). The patient initially presented with nonspecific and digestive symptoms after TVOR, but the condition deteriorated rapidly after three weeks with peritonitis and septic shock. Thus, exploratory laparoscopy was performed with the findings of a ruptured teratoma at left adnexa, severe adhesions, and purulent fluid in her peritoneal cavity. Bilateral pleuritis was also noted after the operation, which was suspected to be caused by chemical irritation of the spilled contents of the teratoma. The patient's condition improved after surgical treatment and was discharged 28 days after admission. Our case showed that the timing of peritoneal irritation caused by teratoma rupture converting to severe chemical peritonitis was approximately 3 weeks. Physicians should avoid cyst puncture during TVOR and closely observe or even perform surgical treatment when iatrogenic teratoma ruptures are suspected.


Sensitivity of two biomarkers for biomonitoring exposure to fluoride in children and women: A study in a volcanic area.
The natural enrichment of water with fluoride is related to natural sources such as volcanic activity, with it being documented that fluorosis, an endemic and widespread disease in volcanic areas, is associated to the ingestion of high levels of fluoride through water. Thus, in this study, we aimed to define the fluoride concentration in drinking waters of volcanic origin and compare the sensitivity of urine and nail clippings as biomarkers for fluoride exposure in adults and children. Samples of drinking water from four villages in São Miguel Island (Azores) were used and the fluoride concentration was determined, as well the fluoride content in urine and toenails clippings from 66 children and 63 adults from these villages. A validated diet questionnaire, assessing sources of fluoride, was recorded for each participant. The fluoride determination in urine and nail clipping samples was made using a fluoride-specific electrode. A positive correlation was found between the fluoride daily intake and fluoride content in children urine (rs = 0.475; p < 0.001) and in their nail clippings (rs = 0.475; p < 0.001), while in adult women, the fluoride daily intake correlated positively with fluoride content nail clippings (rs = 0.495, p < 0.001). This reveals that nail clippings are more reliable as biomarkers of chronic exposure to fluoride than urine for populations of different ages (children vs. adults). Furthermore, nail clippings are more suitable than urine fluoride levels to assess long term exposure to fluoride in areas where the exposure to fluoride in drinking water is considered within, or slightly above, the recommended legal values.


Oxygen sensitivity of reporter genes: implications for preclinical imaging of tumor hypoxia.
Reporter gene techniques have been applied toward studying the physiologic phenomena associated with tumor hypoxia, a negative prognostic indicator. The purpose of this study was to assess the potential adverse effects of hypoxic conditions on the effectiveness of four commonly used reporter genes: Renilla luciferase, monomeric red fluorescent protein, thymidine kinase, and lacZ. Tumor-forming A375 cells expressing a trifusion reporter consisting of Renilla luciferase, monomeric red fluorescent protein, and thymidine kinase were subjected to decreasing oxygen tensions and assayed for reporter expression and activity. A375 cells expressing beta-galactosidase were similarly exposed to hypoxia, with activity of the reporter monitored by cleavage of the fluorescent substrate 7-hydroxy-9H-(1,3-dichloro-9,9-dimethylacridin-2-one)-beta-galactoside (DDAOG). Generation of signal in in vivo tumor models expressing bioluminescent or beta-galactosidase reporters were also examined over the course of hypoxic stresses, either by tumor clamping or the antivascular agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA). Our findings indicate that bioluminescent and fluorescent reporter activity are decreased under hypoxia despite minimal variations in protein production, whereas beta-galactosidase reporter activity per unit protein was unchanged. These results demonstrate that combining beta-galactosidase with the DDAOG optical probe may be a robust reporter system for the in vivo study of tumor hypoxia.


The Preconception Period analysis of Risks and Exposures Influencing health and Development (PrePARED) consortium.
Preconception health may have intergenerational influences. We have formed the PrePARED (Preconception Period Analysis of Risks and Exposures influencing health and Development) research consortium to address methodological, conceptual, and generalisability gaps in the literature. The consortium will investigate the effects of preconception exposures on four sets of outcomes: (1) fertility and miscarriage; (2) pregnancy-related conditions; (3) perinatal and child health; and (4) adult health outcomes. A study is eligible if it has data measured for at least one preconception time point, has a minimum of selected core data, and is open to collaboration and data harmonisation. The included studies are a mix of studies following women or couples intending to conceive, general-health cohorts that cover the reproductive years, and pregnancy/child cohort studies that have been linked with preconception data. The majority of the participating studies are prospective cohorts, but a few are clinical trials or record linkages. Data analysis will begin with harmonisation of data collected across cohorts. Initial areas of interest include nutrition and obesity; tobacco, marijuana, and other substance use; and cardiovascular risk factors. Twenty-three cohorts with data on almost 200 000 women have combined to form this consortium, begun in 2018. Twelve studies are of women or couples actively planning pregnancy, and six are general-population cohorts that cover the reproductive years; the remainder have some other design. The primary focus for four was cardiovascular health, eight was fertility, one was environmental exposures, three was child health, and the remainder general women's health. Among other cohorts assessed for inclusion, the most common reason for ineligibility was lack of prospectively collected preconception data. The consortium will serve as a resource for research in many subject areas related to preconception health, with implications for science, practice, and policy.


Antispasmodic and relaxant effects of the hidroalcoholic extract of Pimpinella anisum (Apiaceae) on rat anococcygeus smooth muscle.
The present work describes the mechanisms involved in the muscle relaxant effect of ethanol:water (40:60, 60:40 and 80:20) aerial parts extracts of Pimpinella anisum. Three hidroalcoholic extracts in which the proportion of ethanol was 40% (HA(40%)), 60% (HA(60%)) or 80% (HA(80%)) were tested for activity in the rat anococcygeus smooth muscle. The three extracts (50 microg/mL) inhibited acetylcholine-induced contraction. The extract HA(60%) (5-50 microg/mL) concentration dependently relaxed acetylcholine-pre-contracted tissues (31.55+/-3.56%). Conversely, HA(40%) and HA(80%) did not exert relaxant action. Pre-incubation of the preparations with N(G)-nitro-L-arginine methyl ester (L-NAME, 100 microM), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 3 microM) and oxyhemoglobin (10 microM) reduced the relaxation induced by HA(60%) (percentage of relaxation: 6.81+/-1.86%, 13.13+/-5.87% and 2.12+/-1.46%, respectively). Neither indomethacin (10 microM) nor tetraethylammonium (1 mM) affected the relaxation induced by HA(60%). Incubation of the tissues with L-NAME significantly enhanced the maximal contraction induced by acetylcholine, indicating an inhibitory role for NO in the modulation of the contractile response of anococcygeus smooth muscle to acetylcholine. However, simultaneous addition of L-NAME and HA(60%) resulted in an effect similar to that observed with L-NAME alone, further confirming the observation that Pimpinella anisum acts by realizing NO. Additionally, HA(60%) did not alter CaCl(2)-induced contraction. Collectively, our results provide functional evidence that the effects elicited by the hidroalcoholic extract of Pimpinella anisum involve the participation of NO and subsequent activation of the NO-cGMP pathway. The relaxant action displayed by Pimpinella anisum justifies its use in the folk medicine as an antispasmodic agent.


Genetics of endometriosis.
Endometriosis is a heritable complex disorder that is influenced by multiple genetic and environmental factors. Identification of these genetic factors will aid a better understanding of the underlying biology of the disease. In this article, we describe different methods of studying genetic variation of endometriosis, summarize results from genetic studies performed to date and provide recommendations for future studies to uncover additional factors contributing to the heritable component of endometriosis.


MYC-induced epigenetic activation of GATA4 in lung adenocarcinoma.
Human lung cancer is a disease with high incidence and accounts for most cancer-related deaths in both men and women. Metastasis is a common event in non-small cell lung carcinoma (NSCLC), diminishing the survival chance of the patients with this type of tumor. It has been shown that MYC is involved in the development of metastasis from NSCLC, but the mechanism underlying this switch remained to be identified. Here, we focus on GATA4 as a MYC target in the development of metastasis with origin in lung adenocarcinoma, the most common type of NSCLC. Epigenetic alterations at the GATA4 promoter level were observed after MYC expression in lung adenocarcinoma in vivo and in vitro. Such alterations include site-specific demethylation that accompanies the displacement of the MYC-associated zinc finger protein (MAZ) from the GATA4 promoter, which leads to GATA4 expression. Histone modification analysis of the GATA4 promoter revealed a switch from repressive histone marks to active histone marks after MYC binding, which corresponds to active GATA4 expression. Our results thus identify a novel epigenetic mechanism by which MYC activates GATA4 leading to metastasis in lung adenocarcinoma, suggesting novel potential targets for the development of antimetastatic therapy.


Circumcision and risk of HIV infection in Australian homosexual men.
To assess circumcision status as a risk factor for HIV seroconversion in homosexual men. The Health in Men (HIM) study was a prospective cohort of homosexual men in Sydney, Australia. HIV-negative men (n = 1426) were recruited primarily from community-based sources between 2001 and 2004 and followed to mid-2007. Participants underwent annual HIV testing, and detailed information on sexual risk behaviour was collected every 6 months. HIV incidence in circumcised compared with uncircumcised participants, stratified by whether or not men predominantly practised the insertive role in anal intercourse. There were 53 HIV seroconversions during follow-up; an incidence of 0.78 per 100 person-years. On multivariate analysis controlling for behavioural risk factors, being circumcised was associated with a nonsignificant reduction in risk of HIV seroconversion [hazard ratio 0.78, 95% confidence interval (CI) 0.42-1.45, P = 0.424]. Among one-third of study participants who reported a preference for the insertive role in anal intercourse, being circumcised was associated with a significant reduction in HIV incidence after controlling for age and unprotected anal intercourse (UAI) (hazard ratio 0.11, 95% CI 0.03-0.80, P = 0.041). Those who reported a preference for the insertive role overwhelmingly practised insertive rather than receptive UAI. Overall, circumcision did not significantly reduce the risk of HIV infection in the HIM cohort. However, it was associated with a significant reduction in HIV incidence among those participants who reported a preference for the insertive role in anal intercourse. Circumcision may have a role as an HIV prevention intervention in this subset of homosexual men.


Microorganisms surviving for 5300 years.
Recently, the well-preserved corpse of a prehistoric man with an age of approximately 5300 years bp was discovered in the Central European Alps. Analysis of materials associated with the individual has revealed the presence of microorganisms which are believed to have survived since the time of death. So far, two fungi have been isolated and identified as species of the genera Chaetomium and Absidia, respectively. In addition, we have obtained one bacterial isolate which we have identified as a Streptomyces species. Our findings demonstrate that microorganisms can remain viable under appropriate circumstances for thousands of years. The isolates may enable us to study evolutionary trends within microorganisms.


Dual-comb spectroscopy using frequency-doubled combs around 775 nm.
Two frequency-doubled combs are generated by nonlinear frequency conversion to realize spectroscopic measurements around 775 nm. Frequency-doubled interferograms are corrected in real-time by monitoring the relative instabilities between the combs at their fundamental frequency. Rubidium absorption lines are used to demonstrate the technique's accuracy and serve as absolute references to calibrate the frequency grid of computed spectra. The method allows frequency-doubled interferograms to be averaged without distortion during long periods of time. The calibrated frequency grid is validated by the measurement of the oxygen A-band. Moreover, the measurement analysis of the acetylene ν(1) + 3ν(3) overtone band has revealed some discrepancies with previous publications.


Prevalence and Predictors of Ocular Complications in Obstructive Sleep Apnea Patients: A Cross-sectional Case-control Study.
This study sought to identify the magnitude and the possible risk factors of ocular complications in patients with Obstructive Sleep Apnea (OSA). A hospital-based cross-sectional study with a nested case-control design was conducted. Qualifying study subjects were patients who had been diagnosed with moderate to severe OSA (AHI index of ≥ 5, n=80), and control subjects (n=20) who had an AHI index of ≤ 5 ("normal"). Study participants were recruited from Mansoura University Hospital's Sleep Disorders Clinic in Mansoura, Egypt.Selected subjects were assessed for ocular complications at Mansoura Univerity Hospital Ophthalmic Center, (Mansoura), Egypt. An ophthalmic history was recorded, and opthalmic testing was carried out. The testing included unaided visual acuity measurement, refraction, best-corrected visual acuity measurement, slit lamp bio-microscopic evaluation of the anterior segment and anterior segment photography, dilated fundus examination, intraocular pressure measurement, fundus photo, and fluorescein angiography, and visual field assessment. Various tests of OSA symptoms were also monitored, including the AHI, lowest oxygen concentrations and desaturation index plus the overall severity index. . It was found that OSA patients n=28 (35%), n=24 (30%), n=4 (5%) had senile cataract, normal tension glaucoma, and retinal ischemia, respectively, with an overall prevalence of 45%. Additionally, the OSA group had seven times greater risk (OR=7.36, 95%CI: 1.6-33.86) of vision-threatening disorders compared to the controls. OSA patients were observed to be at a greater risk of senile cataract 28 (35%), normal tension glaucoma 24 (30%), retinal ischemia 4 (5%) and conjunctival hyperemia and dry eye (OR=3.77, 95%CI: 1.02-13.95, OR=4.36, 95%CI: 1.26-17.08). Also, multivariate logistic regression analysis testing showed that the lowest oxygen saturation index was the only significant predictor negatively associated with vision-threatening disorders (OR=0.84, 95%CI: 0.75-0.93). The risk of vision-threatening and non-threatening ocular disorders is higher among OSA cases. The lowest oxygen saturation index was the only significant predictor of vision-threatening disorders. These findings support the recommendation that a full ophthalmic examination should be carried out on patients with confirmed OSA.


Many Hands Working Together: Adapting Hospital Care to Support Autistic Children's Mental Health.
Hospitals pose a threat to autistic children's mental health. Adapting hospitals to meet children's needs can address this issue. To determine the impact of an interprofessional program (Adaptive Care) to support autistic children's mental health on nursing staff's knowledge, efficacy, and confidence. Pretest-posttest, quasi-experimental design. Large pediatric hospital. Nursing staff were the first participants in the program implementation. Approximately 300 nursing staff received training through the program, and 107 completed program evaluation surveys. Of these, 18 nursing staff completed both the pretest and posttest surveys approximately 1 yr apart. Occupational therapy practitioners and other professionals developed and implemented the program, which consists of staff training and resources to adapt hospital physical and social environments and to ultimately improve patients' hospital experiences. Researcher-developed, pilot-tested, online survey to assess knowledge, perceived effectiveness, confidence, and strategies that staff used while caring for autistic children in the hospital. Respondents had increased effectiveness and confidence working with autistic children in the hospital after program implementation. Respondents reported significantly more strategies to care for autistic children. Interprofessional collaboration and programming can positively affect social environments in the hospital by enhancing nursing staff's self-efficacy, confidence, and strategies to support mental health and to enhance health care for autistic children. What This Article Adds: The Adaptive Care program is an example of occupational therapy practitioners and other interprofessional team members adapting physical and social health care environments to support autistic children's mental health. This program was effective at increasing nursing staff's self-efficacy, confidence, and strategies while caring for autistic children in the hospital. Positionality Statement: This article uses the identity-first language autistic people. This nonableist language describes their strengths and abilities and is a conscious decision. This language is favored by autistic communities and self-advocates and has been adopted by health care professionals and researchers (Bottema-Beutel et al., 2021; Kenny et al., 2016).


Identification of conserved gene expression features between murine mammary carcinoma models and human breast tumors.
Although numerous mouse models of breast carcinomas have been developed, we do not know the extent to which any faithfully represent clinically significant human phenotypes. To address this need, we characterized mammary tumor gene expression profiles from 13 different murine models using DNA microarrays and compared the resulting data to those from human breast tumors. Unsupervised hierarchical clustering analysis showed that six models (TgWAP-Myc, TgMMTV-Neu, TgMMTV-PyMT, TgWAP-Int3, TgWAP-Tag, and TgC3(1)-Tag) yielded tumors with distinctive and homogeneous expression patterns within each strain. However, in each of four other models (TgWAP-T121, TgMMTV-Wnt1, Brca1Co/Co;TgMMTV-Cre;p53+/- and DMBA-induced), tumors with a variety of histologies and expression profiles developed. In many models, similarities to human breast tumors were recognized, including proliferation and human breast tumor subtype signatures. Significantly, tumors of several models displayed characteristics of human basal-like breast tumors, including two models with induced Brca1 deficiencies. Tumors of other murine models shared features and trended towards significance of gene enrichment with human luminal tumors; however, these murine tumors lacked expression of estrogen receptor (ER) and ER-regulated genes. TgMMTV-Neu tumors did not have a significant gene overlap with the human HER2+/ER- subtype and were more similar to human luminal tumors. Many of the defining characteristics of human subtypes were conserved among the mouse models. Although no single mouse model recapitulated all the expression features of a given human subtype, these shared expression features provide a common framework for an improved integration of murine mammary tumor models with human breast tumors.


Identifying economically viable tidal sites within the Alderney Race through optimization of levelized cost of energy.
Costs of tidal stream energy generation are anticipated to fall considerably with array expansion and time. This is due to both economies of volume, where arrays comprising of large numbers of turbines can split fixed costs over a greater number of devices, and learning rates, where the industry matures and so arrays of the same size become cheaper due to lessons learned from previous installations. This paper investigates how tidal energy arrays can be designed to minimize the levelized cost of energy (LCOE), by optimizing not only the location but also the number of devices, to find a suitable balance between decreased costs due to economies of volume and diminishing returns due to global blockage effects. It focuses on the Alderney Race as a case study site due to the high velocities found there, making it a highly suitable site for large-scale arrays. It is demonstrated that between 1 and 2 GW could be feasibly extracted as costs in the tidal industry fall, with the LCOE depending greatly on the assumed costs. A Monte-Carlo analysis is undertaken to account for variability in capital and operational cost data used as inputs to the array optimization. Once optimized, the estimated P50 LCOE of an 80 MW array is £110/MWh. This estimate aligns closely with the level of subsidy considered for tidal stream projects in the Alderney Race in the past. This article is part of the theme issue 'New insights on tidal dynamics and tidal energy harvesting in the Alderney Race'.


An approach to the arsenic status in cardiovascular tissues of patients with coronary heart disease.
Among non-cancer effects of arsenic, cardiovascular diseases have been well documented; however, few are known about the arsenic fate in cardiovascular tissues. We studied the analytic bioinorganic arsenic behaviour in cardiovascular tissues from an arsenic exposure coronary heart disease patient group from Antofagasta-Chile against a small unexposed arsenic coronary heart patient group. Total arsenic concentrations were measured in pieces of cardiovascular tissues of the arsenic-exposed and unexposed coronary heart patient groups by hydride generation atomic absorption spectrometry (HG-AAS); speciation analysis was made by high performance liquid chromatography-inductively coupled plasma-mass spectrometry (HPLC-ICP-MS). Pieces of auricle (AU), mammary artery (MAM), saphenous vein (SAP) and fat residuals (FAT) were considered in this study. The arsenic concentrations in AU and MAM tissues were significantly different between both groups of patients. Also, it was demonstrated that the AU is an 'As(3+) target tissue.' Otherwise, linking of the total concentrations of arsenic with conditional variables and variables related to medical geology factors allowed us to infer that the latter are more important for the cardiovascular risk of arsenic exposure in the Antofagasta region. Knowledge of total arsenic and the prevalence of the trivalent ion (As(3+)) in the AU of patients could contribute to understanding the effect of arsenic on cardiovascular diseases.


[Spinal cord magnetic resonance imaging in multiple sclerosis: importance of determining degree of atrophy as a marker of disease course].
Spinal cord magnetic resonance imaging (MRI) is of particular interest in the management of multiple sclerosis (MS) especially in primary progressive forms. Most of the demyelinating lesions are located in the cervical or dorsal cord. Spinal cord area reduction has been recently correlated with the progression of disability (Losseff et al., 1996, Lycklama a Nijeholt et al., 1998). The aim of this study was to confirm this first result, to assess the reproducibility of this method and to correlate demyelinating lesions with spinal cord area reduction. Fifty two patients were included and compared with 15 controls (normal subjects). T2 Sagittal and axial plane images were performed to localized hypersignal lesions. Spinal cord area was obtained by a volume acquired inversion prepared fast spoiled gradient echo acquisition (MP-Rage) sequence. We compared the mean area value with clinical parameters (age, course of the disease, expanded disability status scale ¿EDSS) and with the number and location of demyelinating lesions. Demyelinating lesions were found in 82p.100 of MS patients and in none of controls. Mean spinal cord area was closely similar to Losseff et al. (1996) results and was reduced compared with controls (p<0.001). Spinal cord reduction was correlated with disability, studied by the EDSS. Furthermore, no correlation was found between demyelinating lesions and spinal cord area reduction. This study confirms the interest of spinal cord area mesurement in MS. Spinal cord atrophy is a reliable marker for axonal loss. This method should be of particular interest for the follow-up of axonal loss in thepeutic trials especially in primary progressive MS.


Using an F(2) screen to monitor frequency of resistance alleles to Bt cotton in field populations of Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae).
In an effort to control the most devastating cotton pest, Helicoverpa armigera (Hübner), in Qiuxian County (Hebei, China), Bt cotton has been planted almost exclusively since 1998 in this area. Owing to the high insecticidal selection pressures in this region, monitoring of Bt resistance in H. armigera is necessary so that proactive actions can be implemented before field control measures fail. From 2003 to 2005, an F(2) screen was conducted in order to monitor Bt resistance in H. armigera populations collected from this area. The F(2) screen showed that 15 out of 278 isofemale lines carried resistance alleles to Bt cotton. The resistance allele frequency in field populations of H. armigera ranged from 0.0119 to 0.0297, with an overall frequency of 0.0146 and a 95% confidence interval of 0.0084-0.0225 for the 3 year period. This value is greater than the value reported from 1999 (P < 0.05). A fluctuating but overall increase in resistance allele frequency was detected in the field populations of H. armigera in Qiuxian County from 1999 to 2005. To prevent further increases in Bt resistance frequency in this pest, it is necessary to introduce Bt cotton expressing multiple Bt toxins and integrate this technology with other tactics for management of this key pest.


SWI5 instability may be necessary but is not sufficient for asymmetric HO expression in yeast.
Homothallic haploid yeast cells divide to produce a mother cell that switches mating type and a daughter cell that does not. This pattern is the result of HO endonuclease transcription exclusively in mother cells, and there only transiently in late G1 as cells undergo Start. SWI5 encodes an HO transcription factor that is expressed during the S, G2, and M phases of the cell cycle. The lack of synthesis of SWI5 during G1 is essential to prevent HO transcription in daughter cells. Thus, HO must be activated by SWI5 protein synthesized in the previous cell cycle if it is to be properly regulated. SWI5 is inherited by both mother and daughter cells, and we show here that most of it is rapidly degraded during early G1. More stable mutant SWI5 proteins cause daughter cells to switch mating type, suggesting that SWI5 destruction is necessary to prevent HO expression in daughters. We show further that mother cells can still express HO when stimulated to undergo Start after arrest in early G1 for several hours. We propose that a small fraction of the SWI5 protein inherited by mother cells is extremely stable and that the crucial difference between mothers and daughters with regard to HO transcription is their differential ability to sequester SWI5 in a stable form, possibly as a component of transcription complexes on the HO promoter.


Antihyperlipidemic and Antioxidant Effects of C-phycocyanin in Golden Syrian Hamsters Fed with a Hypercholesterolemic Diet.
Hyperlipidemia and oxidation play major roles upon cardiovascular diseases (CVDs). C-phycocyanin (CPC), the major component in blue-green algae, possesses antiinflammatory and radical scavenging properties. Herein we aimed to investigate the effect of CPC upon lipid metabolism and its antioxidant effects. Golden Syrian hamsters were randomly assigned to five groups: (1) control; (2) 0.2% cholesterol; (3) 0.2% cholesterol+ 1% lopid; (4) 0.2% cholesterol+ 0.25% CPC; and (5) 0.2% cholesterol+ 1.25% CPC. All animals were sacrificed after 8-week feeding. Serum cholesterol, triglyceride (TG), low-density lipoprotein (LDL), glutamate-oxaloacetate transaminase (GOT), and glutamate-pyruvate transaminase (GPT) were examined. The diene conjugation in the Cu(2+)-mediated oxidation of LDL was measured. The protein levels of several antioxidative enzymes including catalase (CAT), superoxide dismutases (SOD), and glutathione peroxidase (GPx) of liver were assayed. HepG2 cells were cultured in medium containing various concentrations of CPC (0, 1, 15, and 30 μM). The mRNA concentrations of LDL receptor, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG CoA) reductase, SOD-1 and GPx of HepG2 cells in each group were analyzed. CPC was effective in lowering serum cholesterol, total cholesterol (TC), TG, LDL, GOT, and GPT. CPC was found to decrease the malondialdehyde (MDA) equivalents and delay the diene conjugation in the Cu(2+)-mediated oxidation of LDL. CPC increase the enzyme expressions of CAT, SOD, and GPx. CPC concentrations were positively correlated with the mRNA level of LDL receptor while the mRNA levels of HMG CoA reductase, SOD-1, and GPx in HepG2 cells were not affected. The lipid-lowering and antioxidation effects of CPC suggest its roles in prevention of CVD and atherosclerotic formation.


Evaluation of a Conceptual Model for Gas-Particle Partitioning of Polycyclic Aromatic Hydrocarbons Using Polyparameter Linear Free Energy Relationships.
A model for gas-particle partitioning of polycyclic aromatic hydrocarbons (PAHs) was evaluated using polyparameter linear free energy relationships (ppLFERs) following a multiphase aerosol scenario. The model differentiates between various organic (i.e., liquid water-soluble (WS)/organic soluble (OS) organic matter (OM), and solid/semisolid organic polymers) and inorganic phases of the particulate matter (PM). Dimethyl sulfoxide and polyurethane were assigned as surrogates to simulate absorption into the above-mentioned organic phases, respectively, whereas soot, ammonium sulfate, and ammonium chloride simulated adsorption processes onto PM. The model was tested for gas and PM samples collected from urban and nonurban sites in Europe and the Mediterranean, and the output was compared with those calculated using single-parameter linear free energy relationship (spLFER) models, namely Junge-Pankow, Finizio, and Dachs-Eisenreich. The ppLFER model on average predicted 96 ± 3% of the observed partitioning constants for semivolatile PAHs, fluoranthene, and pyrene, within 1 order of magnitude accuracy with root-mean-square errors (RMSE) of 0.35-0.59 across the sites. This was a substantial improvement compared to Finizio and Dachs-Eisenreich models (37 ± 17 and 46 ± 18% and RMSE of 1.03-1.40 and 0.94-1.36, respectively). The Junge-Pankow model performed better among spLFERs but at the same time showed an overall tendency for overestimating the partitioning constants. The ppLFER model demonstrated the best overall performance without indicating a substantial intersite variability. The ppLFER analysis with the parametrization applied in this study suggests that the absorption into WSOSOM could dominate the overall partitioning process, while adsorption onto salts could be neglected.


Adult alveolar epithelial cells express multiple subtypes of voltage-gated K+ channels that are located in apical membrane.
Whole cell perforated patch-clamp experiments were performed with adult rat alveolar epithelial cells. The holding potential was -60 mV, and depolarizing voltage steps activated voltage-gated K(+) (Kv) channels. The voltage-activated currents exhibited a mean reversal potential of -32 mV. Complete activation was achieved at -10 mV. The currents exhibited slow inactivation, with significant variability in the time course between cells. Tail current analysis revealed cell-to-cell variability in K(+) selectivity, suggesting contributions of multiple Kv alpha-subunits to the whole cell current. The Kv channels also displayed steady-state inactivation when the membrane potential was held at depolarized voltages with a window current between -30 and 5 mV. Analysis of RNA isolated from these cells by RT-PCR revealed the presence of eight Kv alpha-subunits (Kv1.1, Kv1.3, Kv1.4, Kv2.2, Kv4.1, Kv4.2, Kv4.3, and Kv9.3), three beta-subunits (Kvbeta1.1, Kvbeta2.1, and Kvbeta3.1), and two K(+) channel interacting protein (KChIP) isoforms (KChIP2 and KChIP3). Western blot analysis with available Kv alpha-subunit antibodies (Kv1.1, Kv1.3, Kv1.4, Kv4.2, and Kv4.3) showed labeling of 50-kDa proteins from alveolar epithelial cells grown in monolayer culture. Immunocytochemical analysis of cells from monolayers showed that Kv1.1, Kv1.3, Kv1.4, Kv4.2, and Kv4.3 were localized to the apical membrane. We conclude that expression of multiple Kv alpha-, beta-, and KChIP subunits explains the variability in inactivation gating and K(+) selectivity observed between cells and that Kv channels in the apical membrane may contribute to basal K(+) secretion across the alveolar epithelium.


Iminosugar glycosidase inhibitors: structural and thermodynamic dissection of the binding of isofagomine and 1-deoxynojirimycin to beta-glucosidases.
The design and synthesis of transition-state mimics reflects the growing need both to understand enzymatic catalysis and to influence strategies for therapeutic intervention. Iminosugars are among the most potent inhibitors of glycosidases. Here, the binding of 1-deoxynojirimycin and (+)-isofagomine to the "family GH-1" beta-glucosidase of Thermotoga maritima is investigated by kinetic analysis, isothermal titration calorimetry, and X-ray crystallography. The binding of both of these iminosugar inhibitors is driven by a large and favorable enthalpy. The greater inhibitory power of isofagomine, relative to 1-deoxynojirimycin, however, resides in its significantly more favorable entropy; indeed the differing thermodynamic signatures of these inhibitors are further highlighted by the markedly different heat capacity values for binding. The pH dependence of catalysis and of inhibition suggests that the inhibitory species are protonated inhibitors bound to enzymes whose acid/base and nucleophile are ionized, while calorimetry indicates that one proton is released from the enzyme upon binding at the pH optimum of catalysis (pH 5.8). Given that these results contradict earlier proposals that the binding of racemic isofagomine to sweet almond beta-glucosidase was entropically driven (Bülow, A. et al. J. Am. Chem. Soc. 2000, 122, 8567-8568), we reinvestigated the binding of 1-deoxynojirimycin and isofagomine to the sweet almond enzyme. Calorimetry confirms that the binding of isofagomine to sweet almond beta-glucosidases is, as observed for the T. maritima enzyme, driven by a large favorable enthalpy. The crystallographic structures of the native T. maritima beta-glucosidase, and its complexes with isofagomine and 1-deoxynojirimycin, all at approximately 2.1 A resolution, reveal that additional ordering of bound solvent may present an entropic penalty to 1-deoxynojirimycin binding that does not penalize isofagomine.


What the electroconvulsive therapy practitioner needs to know about obstructive sleep apnea.
Obstructive sleep apnea (OSA) is common and increasingly so in countries experiencing an epidemic of obesity. The rate of OSA is likely as high or higher in psychiatric patients and patients receiving electroconvulsive therapy (ECT) as compared with the general population. Obstructive sleep apnea can be detected by maintaining a high degree of suspicion in patients with risk factors, symptoms, and typical physical findings. Failure to detect OSA can lead to serious long-term problems with cardiovascular health, excessive sleepiness, and increased risk of motor vehicle accidents. It is unknown whether failure to treat OSA could promote failure to respond to ECT or greater cognitive problems with ECT, but failure to recognize and manage the risk for OSA in patients receiving ECT might expose them to anesthetic difficulties. Ideally, patients with suspected OSA should have a sleep laboratory evaluation and a definitive treatment plan in place before ECT, but, sometimes, psychiatric urgency and lack of access to resources in developing countries would make this unworkable. At a minimum, steps can be taken during the ECT procedure to manage airway obstruction in suspected or known patients with OSA.


RORA and posttraumatic stress trajectories: main effects and interactions with childhood physical abuse history.
Longitudinal studies of posttraumatic stress (PTS) have documented environmental factors as predictors of trajectories of higher, versus lower, symptoms, among them experiences of childhood physical abuse. Although it is now well-accepted that genes and environments jointly shape the risk of PTS, no published studies have investigated genes, or gene-by-environment interactions (GxEs), as predictors of PTS trajectories. The purpose of this study was to fill this gap. We examined associations between variants of the retinoid-related orphan receptor alpha (RORA) gene and trajectory membership among a sample of predominantly non-Hispanic Black urban adults (N = 473). The RORA gene was selected based on its association with posttraumatic stress disorder (PTSD) in the first PTSD genome wide association study. Additionally, we explored GxEs between RORA variants and childhood physical abuse history. We found that the minor allele of the RORA SNP rs893290 was a significant predictor of membership in a trajectory of consistently high PTS, relatively to a trajectory of consistently low PTS. Additionally, the GxE of rs893290 with childhood physical abuse was significant. Decomposition of the interaction showed that minor allele frequency was more strongly associated with membership in consistently high or decreasing PTS trajectories, relative to a consistently low PTS trajectory, among participants with higher levels of childhood physical abuse. The results of the study provide preliminary evidence that variation in the RORA gene is associated with membership in trajectories of higher PTS and that these associations are stronger among persons exposed to childhood physical abuse. Replication and analysis of functional data are needed to further our understanding of how RORA relates to PTS trajectories.


ATP-activated channels in rat and bullfrog sensory neurons: concentration dependence and kinetics.
The concentration dependence and kinetics of ionic currents activated by extracellular adenosine 5'-triphosphate (ATP) were studied in voltage-clamped dorsal root ganglion neurons from rats and bullfrogs. About 40% of neurons of both species responded to ATP with an increase in membrane conductance. The ATP-activated currents were similar in the 2 species, except that currents in rat neurons desensitized faster. In bullfrog neurons, the conductance was half-maximally activated by about 3 microM ATP; at low concentrations, the conductance increased 3- to 7-fold for a doubling in [ATP], suggesting that several ATP molecules must bind in order to activate the current. A steeper concentration-response relationship than expected from 1:1 binding was also seen in rat neurons. The current activated quickly upon application of ATP and decayed quickly when ATP was removed. Activation kinetics were faster at higher [ATP], with time constants decreasing from about 200 msec at 0.3 microM ATP to about 10 msec at 100 microM ATP. Deactivation kinetics (tau approximately 100-200 msec) were independent of the ATP concentration. The rapid activation and deactivation make it seem likely that the ATP-activated current is mediated by direct ligand binding rather than by a second-messenger system. The experimental observations can be mimicked by a simple model in which ATP must bind to 3 identical, noninteracting sites in order to activate a channel. The potency and kinetics of ATP action were voltage-dependent, with hyperpolarization slowing deactivation and increasing ATP's potency. Deactivation kinetics were also sensitive to the concentration of external Ca, becoming faster in higher Ca.


The utility of a tissue slice model system to determine breast cancer infectivity by oncolytic adenoviruses.
Due to advances in viral design, oncolytic adenoviruses have emerged as a promising approach for treatment of breast cancer. Tumor tissue slices offer a stringent model system for preclinical evaluation of adenovirus therapies, since the slices retain a morphology and phenotype that more closely resembles the in vivo setting than cell line cultures, and this system has been shown to have utility in the evaluation of viral infectivity and replication. In this study, we evaluated the efficacy of viral infection and replication using a tropism-modified oncolytic adenovirus. Breast tumor tissue slices were infected with a tropism-modified oncolytic adenovirus, and a wild-type adenovirus for comparison. Efficiency of infection was evaluated using fluorescent microscopy, as the viruses used have been modified to express red fluorescent protein. Replication of the viruses was evaluated with quantitative real-time polymerase chain reaction (PCR) to assay viral E4 genome copy number, a surrogate indicator for the number of virions. The breast tumor tissue slices were evaluated for the expression of CD46 expression by immunohistochemistry. Infection and replication of our tropism modified oncolytic virus has been observed in the breast cancer tissue slice model system and is comparative to wild-type virus. A qualitative increase in the number of cells showing red fluorescent protein (RFP) expression was observed correlating with increasing multiplicity of infection. Higher relative infectivity of the virus was observed in tumor tissue compared with normal breast tissue. Replication of the virus was demonstrated through increases in E4 copy number at 48 and 72 h after infection in human breast tumor slices. We have shown that a tropism modified oncolytic adenovirus can infect and replicate in breast cancer tissue slices, which may be an important preclinical indicator for its therapeutic utility.


The mosaic structure of the symbiotic plasmid of Rhizobium etli CFN42 and its relation to other symbiotic genome compartments.
Symbiotic bacteria known as rhizobia interact with the roots of legumes and induce the formation of nitrogen-fixing nodules. In rhizobia, essential genes for symbiosis are compartmentalized either in symbiotic plasmids or in chromosomal symbiotic islands. To understand the structure and evolution of the symbiotic genome compartments (SGCs), it is necessary to analyze their common genetic content and organization as well as to study their differences. To date, five SGCs belonging to distinct species of rhizobia have been entirely sequenced. We report the complete sequence of the symbiotic plasmid of Rhizobium etli CFN42, a microsymbiont of beans, and a comparison with other SGC sequences available. The symbiotic plasmid is a circular molecule of 371,255 base-pairs containing 359 coding sequences. Nodulation and nitrogen-fixation genes common to other rhizobia are clustered in a region of 125 kilobases. Numerous sequences related to mobile elements are scattered throughout. In some cases the mobile elements flank blocks of functionally related sequences, thereby suggesting a role in transposition. The plasmid contains 12 reiterated DNA families that are likely to participate in genomic rearrangements. Comparisons between this plasmid and complete rhizobial genomes and symbiotic compartments already sequenced show a general lack of synteny and colinearity, with the exception of some transcriptional units. There are only 20 symbiotic genes that are shared by all SGCs. Our data support the notion that the symbiotic compartments of rhizobia genomes are mosaic structures that have been frequently tailored by recombination, horizontal transfer and transposition.


Clinical Features of 4 Novel NOTCH3 Mutations of Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy in China.
BACKGROUND This study aimed to identify NOTCH3 mutations and describe the genetic and clinical features and magnetic resonance imaging results in 11 unrelated patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) from Henan province in China. MATERIAL AND METHODS NOTCH3 was directly sequenced in 11 unrelated patients of Chinese descent. The clinical presentations and magnetic resonance imaging features were retrospectively analyzed in the 11 index patients with a definite diagnosis. RESULTS Seven different mutations were identified in 11 unrelated patients, including 4 novel mutations (p.P167S, p.P652S, p.C709R, and p.R1100H) in China and 3 reported mutations (p.C117R, p.R578C, and p.R607C). Four novel mutations (p.P167S, p.P652S, p.C709R, and p.R1100H) were predicted to be probably pathogenic using an online pathogenicity prediction program through comprehensive analysis. Clinical presentations in symptomatic patients included stroke, cognitive decline, psychiatric disturbances, and migraine. Multiple lacunars infarcts and leukoaraiosis were detected on MRI in most symptomatic patients, while white-matter lesions were identified in the temporal pole or the external capsule in all affected patients. CONCLUSIONS The mutation spectrum of CADASIL patients from Henan province in China displayed some differences from that of those reported previously. DNA sequencing was used to diagnose all 11 patients as having CADASIL, and we found 4 novel mutations. The present results further contribute to the enrichment of NOTCH3 mutation databases.


The ageing and myasthenic thymus: a morphometric study validating a standard procedure in the histological workup of thymic specimens.
The thymus is believed to play an important role in the pathogenesis of myasthenia gravis (MG). The 80% of MG patients with anti-acetylcholine receptor autoantibodies fall into three clinical subgroups: 1) thymoma; 2) early-onset MG (<age of 40; EOMG) and 3) late-onset (LOMG; onset after 40). Thymectomy is widely used in EOMG, but its benefits have not been established in randomized controlled trials. A multicenter international trial (MGTX) currently seeks to determine whether thymectomy reduces corticosteroid requirements, and to look for correlations with thymic histology. We here describe the validated, standardized histological workup and reporting system used in this trial.


The modality shift effect and the effectiveness of warning signals in different modalities.
Which is better, a visual or an auditory warning signal? Initial findings suggested that an auditory signal was more effective, speeding reaction to a target more than a visual warning signal, particularly at brief foreperiods [Bertelson, P., & Tisseyre, F. (1969). The time-course of preparation: confirmatory results with visual and auditory warning signals. Acta Psychologica, 30. In W.G. Koster (Ed.), Attention and Performance II (pp. 145-154); Davis, R., & Green, F. A. (1969). Intersensory differences in the effect of warning signals on reaction time. Acta Psychologica, 30. In W.G. Koster (Ed.), Attention and Performance II (pp. 155-167)]. This led to the hypothesis that an auditory signal is more alerting than a visual warning signal [Sanders, A. F. (1975). The foreperiod effect revisited. Quarterly Journal of Experimental Psychology, 27, 591-598; Posner, M. I., Nissen, M. J., & Klein, R. M. (1976). Visual dominance: an information-processing account of its origins and significance. Psychological Review, 83, 157-171]. Recently [Turatto, M., Benso, F., Galfano, G., & Umilta, C. (2002). Nonspatial attentional shifts between audition and vision. Journal of Experimental Psychology: Human Perception and Performance, 28, 628-639] found no evidence for an auditory warning signal advantage and showed that at brief foreperiods a signal in the same modality as the target facilitated responding more than a signal in a different modality. They accounted for this result in terms of the modality shift effect, with the signal exogenously recruiting attention to its modality, and thereby facilitating responding to targets arriving in the modality to which attention had been recruited. The present study conducted six experiments to understand the cause of these conflicting findings. The results suggest that an auditory warning signal is not more effective than a visual warning signal. Previous reports of an auditory superiority appear to have been caused by using different locations for the visual warning signal and visual target, resulting in the target arriving at an unattended location when the foreperiod was brief. Turatto et al.'s results were replicated with a modality shift effect at brief foreperiods. However, it is also suggested that previous measures of the modality shift effect may still have been confounded by a location cuing effect.


Influencing and modifying children's energy intake: the role of portion size and energy density.
Childhood obesity is of concern worldwide. The portion size (PS) and energy density (ED) of food are two major determinants of children's energy intake (EI). Trends towards increasing PS are most apparent and best documented in the USA, where PS of numerous food products have increased in the marketplace over the past three decades, particularly high-energy dense foods. Analyses of population-level dietary surveys have confirmed this trend in children for both in- and out-of-home eating, and a plethora of observational evidence positively associates PS, ED and adiposity in children. A limited number of intervention studies provide clear evidence that children, even as young as 2 years, respond acutely to increasing PS, with some studies also demonstrating the additive effects of increased ED in promoting excessive EI. However, most of the evidence is based on children aged 3-6 years and there is a paucity of data in older children and adolescents. It is unclear whether decreasing PS can have the opposite effect on children's EI but recent acute studies have demonstrated that the incorporation of lower energy dense foods, such as fruit and vegetables, into children's meals down-regulates EI. Although a direct causal link between PS and obesity remains to be established, the regular consumption of larger PS of energy dense foods do favour obesity-promoting eating behaviours in children. Further research is required to establish the most feasible and effective interventions and policies to counteract the deleterious impact of PS and ED on children's EI.


Preparation of membrane rafts.
The concept that biological membranes contain microdomains of specialized lipid and protein composition has attracted great attention in recent years. Initially, the focus in the field was very much on the characterization of cholesterol-and sphingolipid-rich plasma membrane microdomains that were resistant to solubilization in the cold non-ionic detergent Triton X-100. Such detergent-insoluble membrane domains were of low buoyant density and could be readily purified on sucrose equilibrium density gradients. The intrinsic buoyancy of the detergent-insoluble domains gave rise to the term "lipid rafts." Cholesterol- and sphingolipid-rich rafts at the plasma membrane have been implicated in a wide range of cellular processes, including pathogen invasion, receptor signaling, and endocytosis. However, work with other non-ionic detergents such as Lubrol WX and Brij-98 has revealed the existence of various raft subtypes with differing lipid compositions and proposed functions. More recently, there has been some focus on isolating lipid rafts from intracellular organelles, in particular membranes from the Golgi-endosomal pathway, where raft lipids have been proposed to function in processes such as the sorting of vesicular cargo and the processing of amyloid precursor protein. While there remains a large degree of controversy surrounding the purity, the physiological importance, and even the existence of different types of lipid rafts in intact cells, the ability to routinely purify such domains has led to significant progress in understanding the functional architecture of biological membranes. We describe a number of widely used methods to prepare rafts, based on early preparations of caveolae by density gradient ultracentrifugation and immunoaffinity precipitation.


Introduction to computational causal inference using reproducible Stata, R, and Python code: A tutorial.
The main purpose of many medical studies is to estimate the effects of a treatment or exposure on an outcome. However, it is not always possible to randomize the study participants to a particular treatment, therefore observational study designs may be used. There are major challenges with observational studies; one of which is confounding. Controlling for confounding is commonly performed by direct adjustment of measured confounders; although, sometimes this approach is suboptimal due to modeling assumptions and misspecification. Recent advances in the field of causal inference have dealt with confounding by building on classical standardization methods. However, these recent advances have progressed quickly with a relative paucity of computational-oriented applied tutorials contributing to some confusion in the use of these methods among applied researchers. In this tutorial, we show the computational implementation of different causal inference estimators from a historical perspective where new estimators were developed to overcome the limitations of the previous estimators (ie, nonparametric and parametric g-formula, inverse probability weighting, double-robust, and data-adaptive estimators). We illustrate the implementation of different methods using an empirical example from the Connors study based on intensive care medicine, and most importantly, we provide reproducible and commented code in Stata, R, and Python for researchers to adapt in their own observational study. The code can be accessed at https://github.com/migariane/Tutorial_Computational_Causal_Inference_Estimators.


Unusual treatment of Kasabach-Merritt syndrome secondary to hepatic hemangioma: embolization with bleomycin.
Kasabach-Merritt syndrome (KMS) is a rare complication of cavernous hemangiomas characterized with anemia, thrombocytopenia, and consumption coagulopathy. This syndrome usually develops due to superficial soft tissue hemangiomas in infancy and childhood. KMS developing secondarily to hepatic hemangioma is very rare. In this report, we aimed to present the treatment of KMS developing secondarily to giant cavernous hemangioma of the liver with transarterial chemoembolization using bleomycin.


Crispene E, a cis-clerodane diterpene inhibits STAT3 dimerization in breast cancer cells.
Crispene E, a new clerodane-type diterpene, inhibited STAT3 dimerization in a cell-free fluorescent polarisation assay and was found to have significant toxicity against STAT3-dependent MDA-MB 231 breast cancer cell line and selectively inhibited the expression of STAT3 and STAT3 target genes cyclin D1, Fascin and bcl-2. Molecular docking studies suggest the molecule inhibits STAT3 by interacting with its SH2 domain. The compound has been isolated from Tinospora crispa and characterized using standard spectroscopic techniques.


Trophic complexity and the adaptive value of damage-induced plant volatiles.
Indirect plant defenses are those facilitating the action of carnivores in ridding plants of their herbivorous consumers, as opposed to directly poisoning or repelling them. Of the numerous and diverse indirect defensive strategies employed by plants, inducible volatile production has garnered the most fascination among plant-insect ecologists. These volatile chemicals are emitted in response to feeding by herbivorous arthropods and serve to guide predators and parasitic wasps to their prey. Implicit in virtually all discussions of plant volatile-carnivore interactions is the premise that plants "call for help" to bodyguards that serve to boost plant fitness by limiting herbivore damage. This, by necessity, assumes a three-trophic level food chain where carnivores benefit plants, a theoretical framework that is conceptually tractable and convenient, but poorly depicts the complexity of food-web dynamics occurring in real communities. Recent work suggests that hyperparasitoids, top consumers acting from the fourth trophic level, exploit the same plant volatile cues used by third trophic level carnivores. Further, hyperparasitoids shift their foraging preferences, specifically cueing in to the odor profile of a plant being damaged by a parasitized herbivore that contains their host compared with damage from an unparasitized herbivore. If this outcome is broadly representative of plant-insect food webs at large, it suggests that damage-induced volatiles may not always be beneficial to plants with major implications for the evolution of anti-herbivore defense and manipulating plant traits to improve biological control in agricultural crops.


Getting under the skin of the primary care consultation using video stimulated recall: a systematic review.
Video stimulated recall (VSR) is a method of enhancing participants' accounts of the consultation using a video recording of the event to encourage and prompt recall in a post consultation interview. VSR is used in education and education research, and to a lesser extent in medical and nursing research. Little is known about the sort of research questions that lend themselves best to the use of VSR or the impact of the specific VSR procedure on study quality. This systematic review describes studies in primary care that have used the method and aims to identify the strengths, weaknesses and role of VSR. A systematic literature search has been conducted to identify primary care consultation research using VSR. Two authors undertook data extraction and quality appraisal of identified papers and a narrative synthesis has been conducted to draw together the findings. In addition, theory on classifying VSR procedures derived from other disciplines is used as a lens through which to assess the relevance of VSR technique. Twenty eight publications were identified that reported VSR in primary care doctor-patient consultation research. VSR was identified as a useful method to explore specific events within the consultation, mundane or routine occurrences, non-spoken events and appears to particularly add value to doctor's post consultation accounts. However, studies frequently had insufficient description of methods to properly evaluate both the quality of the study, and the influence of VSR technique on findings. VSR is particularly useful for study of specific consultation events when a 'within case' approach is used in analysis, comparing and contrasting findings from the consultation and post-consultation interview. Alignment of the choice of VSR procedure and sampling to the study research question was established as particularly important in the quality of studies. Future researchers may consider the role of process evaluation to understand further the impact of research design on data yielded and the acceptability of the method to participants.


Ten new species of Oreophryne (Anura, Microhylidae) from Papua New Guinea.
Oreophryne presently represents the second-most-diverse genus of microhylid frogs, with 57 named species, most occurring on New Guinea and its satellite islands. Nonetheless, a diversity of species remains to be described. Using morphological, color-pattern, and advertisement-call data, I describe ten new species of Oreophryne from the Papuan Peninsula of New Guinea and adjacent islands, which together form the East Papuan Composite Terrane. All but two of these species can be placed into two species groups based on call type. I refer to these species groups as the O. anser group and the O. equus group, both being based on species described herein. Members of the O. anser group produce calls reminiscent of a goose honk, whereas members of the O. equus group produce calls reminiscent of a horse's whinny. Description of three new species in the O. anser group requires me to first rediagnose O. loriae, which has previously been interpreted as including the frogs named herein as O. anser sp. nov. The honk call type has not previously been reported within Oreophryne, and the whinny call may be novel as well, although it is possibly derived from other New Guinean species having calls consisting of a slower series of peeps. Based on their unique call types, I hypothesize that both species groups are monophyletic. If true, each would appear endemic to the East Papuan Composite Terrane. Only five additional species of Oreophryne are known from this region that do not belong to one or the other of these two species groups; hence, these newly identified species groups represent the majority of diversity in Oreophryne from the Papuan Peninsula and its satellite islands.


Xylose Improves Antibiotic Activity of Chloramphenicol and Tetracycline against K. pneumoniae and A. baumannii in a Murine Model of Skin Infection.
Increased resistance to antimicrobials in clinically important bacteria has been widely reported. The major mechanism causing multidrug resistance (MDR) is mediated by efflux pumps, proteins located in the cytoplasmic membrane to exclude antimicrobial drug. Some efflux pumps recognize and expel a variety of unrelated antimicrobial agents, while other efflux pumps can expel only one specific class of antibiotics. Previously, we have reported that xylose decreases the efflux-mediated antimicrobial resistance in Salmonella typhimurium, Pseudomonas aeruginosa, and Acinetobacter baumannii in vitro. In this work, we assessed the effectiveness of combining xylose with antibiotics to kill resistant Acinetobacter baumannii and Klebsiella pneumoniae in a murine model of skin infection. Skin infections were established by seeding 109 bacteria onto eroded skin of mice. Mice treated with the antibiotic alone or with a mixture of glucose and antibiotics or xylose and antibiotics were compared to a control group that was infected but received no further treatment. We observed that the mixtures xylose-tetracycline and xylose-chloramphenicol produced a decrease of at least 10 times viable Acinetobacter baumannii and Klebsiella pneumoniae recovered from infected skin, compared with mice treated with the antibiotic alone. Our results show that xylose improves the antibiotic activity of tetracycline and chloramphenicol against efflux-mediated resistance Acinetobacter baumannii and Klebsiella pneumoniae, in a murine model of skin infection. We envision these combined formulations as an efficient treatment of skin infections with bacteria presenting efflux-mediated resistance, in both humans and animals.


Effects of a supported speed treadmill training exercise program on impairment and function for children with cerebral palsy.
To compare the effects of a supported speed treadmill training exercise program (SSTTEP) with exercise on spasticity, strength, motor control, gait spatiotemporal parameters, gross motor skills, and physical function. Twenty-six children (14 males, 12 females; mean age 9y 6mo, SD 2y 2mo) with spastic cerebral palsy (CP; diplegia, n=12; triplegia, n=2; quadriplegia n=12; Gross Motor Function Classification System levels II-IV) were randomly assigned to the SSTTEP or exercise (strengthening) group. After a twice daily, 2-week induction, children continued the intervention at home 5 days a week for 10 weeks. Data collected at baseline, after 12-weeks' intervention, and 4 weeks after the intervention stopped included spasticity, motor control, and strength; gait spatiotemporal parameters; Gross Motor Function Measure (GMFM); and Pediatric Outcomes Data Collection Instrument (PODCI). Gait speed, cadence, and PODCI global scores improved, with no difference between groups. No significant changes were seen in spasticity, strength, motor control, GMFM scores, or PODCI transfers and mobility. Post-hoc testing showed that gains in gait speed and PODCI global scores were maintained in the SSTTEP group after withdrawal of the intervention. Although our hypothesis that the SSTTEP group would have better outcomes was not supported, results are encouraging as children in both groups showed changes in function and gait. Only the SSTTEP group maintained gains after withdrawal of intervention.


TLR4 expression on monocyte subsets in myocardial infarction.
Monocyte toll-like receptor 4 (TLR4) has been implicated in the pathogenesis of atherosclerosis with increased levels in myocardial infarction. The aim of this study was to assess the numbers of TLR4(+) monocytes in each monocyte subset in MI, the expression of TLR4 and association with markers of monocyte activation, inflammation, myocardial damage and postmyocardial infarction (MI) cardiac contractility. Surface expression of TLR4 and numbers of TLR4-expressing monocytes were quantified by flow cytometry of venous blood in 50 patients with ST-elevation MI (STEMI), 48 with non-STEMI (NSTEMI) and 40 with stable coronary artery disease (CAD). These parameters were measured on days 1, 3, 7 and 30 post-MI in STEMI patients. Three monocyte subsets were defined as CD14(++) CD16(-) CCR2(+) (Mon1), CD14(++) CD16(+) CCR2(+) (Mon2) and CD14(+) CD16(++) CCR2(-) (Mon3). Plasma inflammatory cytokines were assessed using cytometric bead arrays. There was a significant increase in counts of TLR4(+) Mon1 and Mon2 in STEMI patients and TLR4(+) Mon2 in NSTEMI patients compared with controls with CAD. Monocyte TLR4(+) expression was similar between the groups, and was not changed during follow-up in STEMI patients. Plasma interleukin-6 (IL6) levels correlated positively with TLR4(+) Mon2 count (r = 0.54, P < 0.001), but negatively with TLR4 expression on Mon2 (r = -0.33, P = 0.021). Following treatment of acute MI, TLR4 expression by individual monocyte subsets is unchanged. An increase in TLR4(+) Mon1 and Mon2 count in patients with STEMI and TLR(+) Mon2 count in those with NSTEMI is due to an increase in monocyte subset count and not to changes in TLR4 expression. Monocyte counts but not TLR4 expression correlate positively with plasma IL6 levels. We suggest that TLR4 expression may not be a reliable marker of monocyte activation in MI.


Adaptations to climate-mediated selective pressures in sheep.
Following domestication, sheep (Ovis aries) have become essential farmed animals across the world through adaptation to a diverse range of environments and varied production systems. Climate-mediated selective pressure has shaped phenotypic variation and has left genetic "footprints" in the genome of breeds raised in different agroecological zones. Unlike numerous studies that have searched for evidence of selection using only population genetics data, here, we conducted an integrated coanalysis of environmental data with single nucleotide polymorphism (SNP) variation. By examining 49,034 SNPs from 32 old, autochthonous sheep breeds that are adapted to a spectrum of different regional climates, we identified 230 SNPs with evidence for selection that is likely due to climate-mediated pressure. Among them, 189 (82%) showed significant correlation (P ≤ 0.05) between allele frequency and climatic variables in a larger set of native populations from a worldwide range of geographic areas and climates. Gene ontology analysis of genes colocated with significant SNPs identified 17 candidates related to GTPase regulator and peptide receptor activities in the biological processes of energy metabolism and endocrine and autoimmune regulation. We also observed high linkage disequilibrium and significant extended haplotype homozygosity for the core haplotype TBC1D12-CH1 of TBC1D12. The global frequency distribution of the core haplotype and allele OAR22_18929579-A showed an apparent geographic pattern and significant (P ≤ 0.05) correlations with climatic variation. Our results imply that adaptations to local climates have shaped the spatial distribution of some variants that are candidates to underpin adaptive variation in sheep.


Improving plant transient expression through the rational design of synthetic 5' and 3' untranslated regions.
The growing field of plant molecular farming relies on expression vectors that allow high yields of recombinant proteins to be produced through transient gene expression. While numerous expression vectors currently exist for this purpose, there are very few examples of systematic efforts to improve upon these. Moreover, the current generation of expression systems makes use of naturally-occurring regulatory elements, typically selected from plant viruses, to maximise yields. This study aims to use rational design to generate synthetic sequences that can rival existing ones. In this work, we present the rational design of novel synthetic 5' and 3' untranslated regions (UTRs) which can be used in various combinations to modulate accumulation levels of transiently-expressed recombinant proteins. Using the pEAQ-HT expression vector as a point of comparison, we show that pre-existing expression systems can be improved by the deployment of rationally designed synthetic UTRs. Notably, we show that a suite of short, synthetic 5'UTRs behave as expression enhancers that outperform the HT 5'UTR present in the CPMV-HT expression system. Furthermore, we confirm the critical role played by the 3'UTR of cowpea mosaic virus RNA-2 in the performance of the CPMV-HT system. Finally, we use the knowledge obtained from these results to develop novel expression vectors (named pHRE and pHREAC) that equal or outperform pEAQ-HT in terms of recombinant protein yield. These new vectors are also domesticated for the use of certain Type IIS restriction enzymes, which allows for quicker cloning and straightforward assessment of different combinations of UTRs. We have shown that it is possible to rationally design a suite of expression modulators in the form of synthetic UTRs. We have created novel expression vectors that allow very high levels of recombinant protein expression in a transient expression context. This will have important consequences for future efforts to develop ever-better plant transient overexpression vectors for research or industrial applications.


Takayasu Arteritis Mistaken for Epilepsy: A Case Presenting With Convulsive Syncope.
Takayasu arteritis (TA) is a chronic inflammatory disease characterized by granulomatous vasculitis that predominantly manifests as panaortitis. This occlusive thromboaortopathy lacks pathognomonic features often resulting in a diagnostic dilemma leading to its under-recognition, misdiagnosis and delayed management. Although neurological manifestations are not uncommon in TA, convulsive syncope as an initial clinical presentation is extremely rare. We report a case of convulsive syncope as a manifesting symptom of TA. A 17-year-old male patient of African origin was referred to us from an upcountry regional hospital with a diagnosis of medically intractable epilepsy for cardiovascular review. He presented with a 28-week history of generalized tonic-clonic seizures followed by loss of consciousness. He denied history of recurrent headaches, fever, visual disturbances, arthralgias, claudication or unintentional weight loss. Physical examination revealed feeble left-sided brachial and radial pulses, elevated blood pressure, differences in blood pressure between arms and left-sided carotid and vertebral bruits. Computed tomography angiogram of his thoracic and abdominal aorta revealed changes suggestive of a diffuse arteritis. Additionally, magnetic resonance angiogram of the brain revealed total occlusion of the left common carotid, left internal carotid, left external carotid and left vertebral arteries. Based on the physical examination and radiological findings, we reached a diagnosis of TA. He was prescribed dexamethasone, methotrexate, acetylsalicylic acid and amlodipine. He had a remarkable recovery and was seizure-free for the last 5 months after discharge. TA may manifest with convulsive syncope mimicking epilepsy. Despite its rarity, presentations of this nature continue to challenge clinicians resulting in delayed diagnosis with irreversible life-threatening consequences to patients. In view of this, physicians should strive to take detailed history and perform thorough physical examination so as to timely pick the characteristic signs of TA especially in patients presenting with unanticipated symptoms.


Stability and fibril formation properties of human and fish transthyretin, and of the Escherichia coli transthyretin-related protein.
Human transthyretin (hTTR) is one of several proteins known to cause amyloid disease. Conformational changes in its native structure result in aggregation of the protein, leading to insoluble amyloid fibrils. The transthyretin (TTR)-related proteins comprise a protein family of 5-hydroxyisourate hydrolases with structural similarity to TTR. In this study, we tested the amyloidogenic properties, if any, of sea bream TTR (sbTTR) and Escherichia coli transthyretin-related protein (ecTRP), which share 52% and 30% sequence identity, respectively, with hTTR. We obtained filamentous structures from all three proteins under various conditions, but, interestingly, different structures displayed different tinctorial properties. hTTR and sbTTR formed thin, curved fibrils at low pH (pH 2-3) that bound thioflavin-T (thioflavin-T-positive) but did not stain with Congo Red (CR) (CR-negative). Aggregates formed at the slightly higher pH of 4.0-5.5 had different morphology, displaying predominantly amorphous structures. CR-positive material of hTTR was found in this material, in agreement with previous results. ecTRP remained soluble at pH 2-12 at ambient temperatures. By raising of the temperature, fibril formation could be induced at neutral pH in all three proteins. Most of these temperature-induced fibrils were thicker and straighter than the in vitro fibrils seen at low pH. In other words, the temperature-induced fibrils were more similar to fibrils seen in vivo. The melting temperature of ecTRP was 66.7 degrees C. This is approximately 30 degrees C lower than the melting temperatures of sbTTR and hTTR. Information from the crystal structures was used to identify possible explanations for the reduced thermostability of ecTRP.


Muscle and not neuronal biomarkers correlate with severity in spinal and bulbar muscular atrophy.
To determine whether blood biomarkers of neuronal damage (neurofilament light chain [NfL]), muscle damage (creatine kinase [CK]), and muscle mass (creatinine) are altered in spinal and bulbar muscular atrophy (SBMA) and can be used as biomarkers for disease severity. In this multicenter longitudinal prospective study, plasma and serum were collected from 2 cohorts of patients with SBMA in London, United Kingdom (n = 50), and Padova, Italy (n = 43), along with disease (amyotrophic lateral sclerosis [ALS]) and healthy controls, and levels of plasma and serum NfL, CK, and creatinine were measured. Disease severity was assessed by the SBMA Functional Rating Scale and the Adult Myopathy Assessment Tool at baseline and 12 and 24 months. Blood NfL concentrations were increased in ALS samples, but were unchanged in both SBMA cohorts, were stable after 12 and 24 months, and were not correlated with clinical severity. Normal NfL levels were also found in a well-established mouse model of SBMA. Conversely, CK concentrations were significantly raised in SBMA compared with ALS samples, and were not correlated to the clinical measures. Creatinine concentrations were significantly reduced in SBMA, and strongly and significantly correlated with disease severity. While muscle damage and muscle mass biomarkers are abnormal in SBMA, axonal damage markers are unchanged, highlighting the relevant primary role of skeletal muscle in disease pathogenesis. Creatinine, but not CK, correlated with disease severity, confirming its role as a valuable biomarker in SBMA.


Factors underlying parental decisions about combination childhood vaccinations including MMR: a systematic review.
Suboptimal childhood vaccination uptake results in disease outbreaks, and in developed countries is largely attributable to parental choice. To inform evidence-based interventions, we conducted a systematic review of factors underlying parental vaccination decisions. Thirty-one studies were reviewed. Outcomes and methods are disparate, which limits synthesis; however parents are consistently shown to act in line with their attitudes to combination childhood vaccinations. Vaccine-declining parents believe that vaccines are unsafe and ineffective and that the diseases they are given to prevent are mild and uncommon; they mistrust their health professionals, Government and officially-endorsed vaccine research but trust media and non-official information sources and resent perceived pressure to risk their own child's safety for public health benefit. Interventions should focus on detailed decision mechanisms including disease-related anticipated regret and perception of anecdotal information as statistically representative. Self-reported vaccine uptake, retrospective attitude assessment and unrepresentative samples limit the reliability of reviewed data - methodological improvements are required in this area.


"Everyone Needs a Friend Sometimes" - Social Predictors of Long-Term Remission In First Episode Psychosis.
Background: Predictors of long-term symptomatic remission are crucial to the successful tailoring of treatment in first episode psychosis. There is lack of studies distinguishing the predictive effects of different social factors. This prevents a valid evaluating of their independent effects. Objectives: To test specific social baseline predictors of long-term remission. We hypothesized that first, satisfaction with social relations predicts remission; second, that frequency of social interaction predicts remission; and third, that the effect of friend relationship satisfaction and frequency will be greater than that of family relations satisfaction and frequency. Material and Methods: A sample of first episode psychosis (n = 186) completed baseline measures of social functioning, as well as clinical assessments. We compared groups of remitted and non-remitted individuals using generalized estimating equations analyses. Results: Frequency of social interaction with friends was a significant positive predictor of remission over a two-year period. Neither global perceived social satisfaction nor frequency of family interaction showed significant effects. Conclusions: The study findings are of particular clinical importance since frequency of friendship interaction is a possibly malleable factor. Frequency of interaction could be affected through behavioral modification and therapy already from an early stage in the course, and thus increase remission rates.


Aromatic as well as aliphatic hydrocarbon solvent axonopathy.
Superfund sites that contain mixtures of aromatic and aliphatic solvents represent an undefined health hazard. After prolonged exposure to relatively high levels of certain aliphatic solvents (e.g. n-hexane, 2-hexanone), humans and animals develop a dose-dependent neurodegeneration that occurs clinically as a symmetrical peripheral neuropathy. This is triggered by the action of 2,5-hexanedione (1,2-diacetylethane), a 1,4-diketone (gamma-diketone) metabolite that targets proteins required for the maintenance of neuronal (and testicular Sertoli cell) integrity. Certain aromatic solvents (1,2-diethylbenzene, 1,2,4-triethylbenzene) cause electrophysiological changes consistent with sensorimotor neuropathy in rodents, but the underlying mechanisms and pathogenesis are unclear. Our recent studies show that the o-diacetyl derivative and likely metabolite of 1,2-diethylbenzene, 1,2-diacetylbenzene, behaves as a neurotoxic (aromatic) gamma-diketone of high neurotoxic potency. Rats treated with 1,2-diacetylbenzene develop limb weakness associated with proximal, neurofilament-filled giant axonal swellings comparable to those seen in animals treated with the potent 3,4-dimethyl derivative of 2,5-hexanedione. The blue chromogen induced by treatment with 1,2-diacetylbenzene is under study as a possible urinary biomarker of exposure to aromatic solvents (e.g. 1,2-diethylbenzene, tetralin) with neurotoxic potential. Development and validation of sensitive new biomarkers, especially for non-cancer endpoints, will aid in assessing the health risk associated with exposure to hazardous substances at Superfund sites.


A complete picture of protein unfolding and refolding in surfactants.
Interactions between proteins and surfactants are of relevance in many applications including food, washing powder formulations, and drug formulation. The anionic surfactant sodium dodecyl sulfate (SDS) is known to unfold globular proteins, while the non-ionic surfactant octaethyleneglycol monododecyl ether (C12E8) can be used to refold proteins from their SDS-denatured state. While unfolding have been studied in detail at the protein level, a complete picture of the interplay between protein and surfactant in these processes is lacking. This gap in our knowledge is addressed in the current work, using the β-sheet-rich globular protein β-lactoglobulin (bLG). We combined stopped-flow time-resolved SAXS, fluorescence, and circular dichroism, respectively, to provide an unprecedented in-depth picture of the different steps involved in both protein unfolding and refolding in the presence of SDS and C12E8. During unfolding, core-shell bLG-SDS complexes were formed within ∼10 ms. This involved an initial rapid process where protein and SDS formed aggregates, followed by two slower processes, where the complexes first disaggregated into single protein structures situated asymmetrically on the SDS micelles, followed by isotropic redistribution of the protein. Refolding kinetics (>100 s) were slower than unfolding (<30 s), and involved rearrangements within the mixing deadtime (∼5 ms) and transient accumulation of unfolded monomeric protein, differing in structure from the original bLG-SDS structure. Refolding of bLG involved two steps: extraction of most of the SDS from the complexes followed by protein refolding. These results reveal that surfactant-mediated unfolding and refolding of proteins are complex processes with rearrangements occurring on time scales from sub-milliseconds to minutes.


Neem (Azadirachta Indica A. Juss) Capsules for Prophylaxis of COVID-19 Infection: A Pilot, Double-Blind, Randomized Controlled Trial.
SARS-CoV-2 is a global public-health concern. Interventions to prevent infection are urgently needed. The anti-inflammatory and antiviral effects of neem make it a potential agent for COVID-19 prophylaxis. The study intended to evaluate the prophylactic effects of neem capsules for persons at high risk of COVID-19 infection due to contact with COVID-19 positive patients. The research team designed a prospective, randomized, double-blind, placebo-controlled, parallel-design study. The study was conducted at a single center in India. Participants were 190 healthcare workers at the hospital or relatives of patients with COVID-19 infection. Of the 190 participants, 95 were in the intervention group and 95 in the control group. Participants received 50 mg of a proprietary, patent-pending, neem-leaf extract or a placebo orally in capsules, twice a day for 28 days. The number of individuals positive for COVID-19 between baseline and follow-up on day 56 was the primary outcome measure. Secondary measures included an evaluation of neem's safety and its effects on quality of life (QOL) and changes in biomarkers. The mean age of participants was 36.97 years, and 68.42% were male. Total 13 subjects tested positive during the study. All were asymptomatic. Of the 154 participants who completed the study per-protocol, 11 tested positive, 3 in the intervention group and 8 in the control group. The probability of COVID-19 infection in participants receiving the intervention was 0.45 times that of participants receiving the placebo, a relative risk of 0.45, with the effectiveness of the intervention being around 55%. Treatment-emergent adverse events (TEAEs) in both groups were minimal and were of grade 1 or 2 in severity. Biomarkers and QOL remained stable in both groups. The study found a reduced risk of COVID-19 infection in participants receiving neem capsules, which demonstrates its potential as a prophylactic treatment for the prevention of COVID-19 infection. The findings warrant further investigation in clinical trials.


Delineation of sequences important for efficient packaging of feline immunodeficiency virus RNA.
We have used systematic deletion analysis of the 5' untranslated region (UTR) of the feline immunodeficiency virus (FIV) genome, both in the presence and absence of various amounts of gag, to define the cis-acting sequences responsible for efficient RNA packaging. Our analyses revealed that the primary FIV packaging signal consists of two essential core elements located within the first 90-120 bp of the 5'UTR and the first 90 bp of the gag gene. Interestingly, the region between the major splice donor (SD) and gag, including approximately 130-160 bp upstream of the SD, is dispensable for encapsidation. Finally, other determinants of packaging were found to be present in the viral LTR and/or within the 3' end of the viral genome. Taken together, our results suggest that the primary packaging determinants of FIV are multipartite and discontinuous, composed of two elements within the 5'UTR and gag gene.


Typical integration of emotion cues from bodies and faces in Autism Spectrum Disorder.
Contextual cues derived from body postures bias how typical observers categorize facial emotion; the same facial expression may be perceived as anger or disgust when aligned with angry and disgusted body postures. Individuals with Autism Spectrum Disorder (ASD) are thought to have difficulties integrating information from disparate visual regions to form unitary percepts, and may be less susceptible to visual illusions induced by context. The current study investigated whether individuals with ASD exhibit diminished integration of emotion cues extracted from faces and bodies. Individuals with and without ASD completed a binary expression classification task, categorizing facial emotion as 'Disgust' or 'Anger'. Facial stimuli were drawn from a morph continuum blending facial disgust and anger, and presented in isolation, or accompanied by an angry or disgusted body posture. Participants were explicitly instructed to disregard the body context. Contextual modulation was inferred from a shift in the resulting psychometric functions.Contrary to prediction, observers with ASD showed typical integration of emotion cues from the face and body. Correlation analyses suggested a relationship between the ability to categorize emotion from isolated faces, and susceptibility to contextual influence within the ASD sample; individuals with imprecise facial emotion classification were influenced more by body posture cues.


A recombinant antibody with the antigen-specific, major histocompatibility complex-restricted specificity of T cells.
Specific recognition of peptide/major histocompatibility complex (MHC) molecule complexes by the T-cell receptor is a key reaction in the specific immune response. Antibodies against peptide/MHC complexes would therefore be valuable tools in studying MHC function and T-cell recognition and might lead to novel approaches in immunotherapy. However, it has proven difficult to generate antibodies with the specificity of T cells by conventional hybridoma techniques. Here we report that the phage display technology is a feasible alternative to generate antibodies recognizing specific, predetermined peptide/MHC complexes.


Antimicrobial resistance in aquaculture.
Appropriate antimicrobial therapy represents one of the most effective management responses to emergencies associated with infectious disease epizootics. The use of these agents, however, has the potential to increase the frequencies of bacterial resistance and this would have a negative impact on the subsequent use of these agents to control infectious disease in aquaculture. There is also a possibility that the enrichment of resistant bacteria or genes encoding resistance could have an adverse impact on the use of antimicrobial agents to control diseases in humans and other land-based animals. Attempts to apply formal risk analysis to this problem have been frustrated by the extreme diversity of aquaculture and by the general shortage of relevant data. A central argument made in this paper is, however, that not only do we lack the data this exercise would require; we also lack validated methods for collecting those data in the first place. At the most fundamental level we do not even possess validated methods for determining whether a bacterium isolated from an aquaculture site should or should not be classified as resistant. In the absence of any significant risk assessment, current attempts at risk management are centred on the development of lists of critically important antimicrobials for the various users of these agents. It is argued here that studies of gene ecology and models of gene flow in the environment are urgently required if we are to be able to evaluate this risk management approach, to predict its consequences or to generate more appropriate strategies.


Double-configuration grating monochromator for extreme-ultraviolet ultrafast pulses.
We present the design and characterization of a double-configuration grating monochromator for the spectral selection of extreme-ultraviolet ultrafast pulses. Two grating geometries are joined in an instrument with two interchangeable diffracting stages, both used at grazing incidence: one with the gratings in the off-plane mount (OPM), the other in the classical diffraction mount (CDM). The use of two stages gives great flexibility: the OPM stage is used for sub-50 fs time response and low spectral resolution, while the CDM stage is for 100-200 fs time response and high spectral resolution. The monochromator spectral and temporal performances have been experimentally demonstrated on a high-order laser-harmonics beam line.


The psychology of engagement with indigenous identities: a cultural perspective.
In a questionnaire study among 124 students at Haskell Indian Nations University, the authors investigated the hypothesis that engagement with Indigenous identity--assessed along three dimensions including degree (identification scale), content (panethnic or tribal nation), and context (reservation or nonreservation)--can serve as a psychological resource for well-being and liberation from oppression. Consistent with this hypothesis, degree of identification was positively correlated with community efficacy and perception of racism. Apparently inconsistent with this hypothesis, degree of identification among students who had resided on a reservation was negatively correlated with the Social Self-Esteem subscale of the Current Thoughts Scale. Rather than evidence against the identity-as-resource hypothesis, this pattern may reflect the cultural grounding of self-esteem and tools designed to measure it.


Can the world's favorite fruit, tomato, provide an effective biosynthetic chassis for high-value metabolites?
Tomato has a relatively short growth cycle (fruit ready to pick within 65-85 days from planting) and a relatively high yield (the average for globe tomatoes is 3-9 kg fruit per plant rising to as much as 40 kg fruit per plant). Tomatoes also produce large amounts of important primary and secondary metabolites which can serve as intermediates or substrates for producing valuable new compounds. As a model crop, tomato already has a broad range of tools and resources available for biotechnological applications, either increased nutrients for health-promoting biofortified foods or as a production system for high-value compounds. These advantages make tomato an excellent chassis for the production of important metabolites. We summarize recent achievements in metabolic engineering of tomato and suggest new candidate metabolites which could be targets for metabolic engineering. We offer a scheme for how to establish tomato as a chassis for industrial-scale production of high-value metabolites.