Forest fragmentation and avian nest predation in forested landscapes.
The size of forest fragments, the use of land bordering fragments, and the distance of nests from an edge all affect the frequency of predation upon bird nests in Maine (USA), an area where the forest has been fragmented by roads, but not significantly reduced in area. We placed artificial nests containing quail eggs in forests of different sizes and at various distances from the edge to test which of these factors was most important in describing predation. Predation was greatest in small tracts surrounded completely by land. Large areas and those bordered on at least one side by a large water body had lower predation rates. This suggests that influx of predators from nearby habitats may be responsible for much of the nest predation in forest fragments.


Positive and negative ion mass spectrometry of benzophenones, the acid-hydrolysis products of benzodiazepines.
Positive electron impact (EI), positive chemical ionization (CI), and negative CI mass spectra of 14 benzophenones are presented. In the positive EI mode, intense molecular peaks appeared for most compounds; some other peaks due to splitting at both sides of the carbonyl group also appeared. In the positive CI mode, [M + 1]+ quasi-molecular ions together with [M + C2H5]+ peaks were observed for all compounds; some fragment peaks were common to those in the positive EI mode. In the negative CI mode, the spectra were much simpler than those in the positive EI or CI mode. In the 1 Torr negative CI mode, some spectra showed only single molecular anions; in the 0.01 Torr negative CI mode, halogen or nitro peaks appeared in addition to the molecular anions. An extraction procedure for benzophenones from human urine and plasma after heating in strong acid, and their separation by gas chromatography (GC) are also presented to serve for their actual identification by GC/mass spectrometry.


Submerged anaerobic membrane bioreactor for low-strength wastewater treatment: effect of HRT and SRT on treatment performance and membrane fouling.
Three 6-L submerged anaerobic membrane bioreactors (SAnMBRs) with solids retention times (SRTs) of 30, 60 and infinite days were setup for treating synthetic low-strength wastewater at hydraulic retention times (HRTs) of 12, 10 and 8 h. Total COD removal efficiencies higher than 97% were achieved at all operating conditions. Maximum biogas production rate was 0.056 L CH(4)/g MLVSS d at an infinite SRT. A shorter HRT or longer SRT increased biogas production due to increased organic loading rate or enhanced dominancy of methanogenics. A decrease in HRT enhanced growth of biomass and accumulation of soluble microbial products (SMP), which accelerated membrane fouling. A drop in carbohydrate to protein ratio also inversely affected fouling. At 12-h HRT, the effect of SRT on biomass concentration in SAnMBRs was negligible and membrane fouling was controlled by variant surface modification due to different SMP compositions, i.e., higher carbohydrate and protein concentrations in SMP at longer SRT resulted in higher membrane fouling rate. At 8 and 10-h HRTs, infinite SRT in SAnMBR caused highest MLSS and SMP concentrations, which sped up particle deposition and biocake/biofilm development. At longer SRT, lower extracellular polymeric substances reduced flocculation of particulates and particle sizes, further aggravated membrane fouling.


Correlates of intrusion and avoidance as stress response symptoms in family carers of patients suffering from dementia.
To explore intrusion and avoidance in family carers of dementia patients. We studied 196 family carers of 196 home-dwelling dementia patients. Carers were assessed by the Impact of Events Scale (IES), the Geriatric Depression Scale (GDS), the State Trait Anxiety Inventory (STAI) and the Distress scale of the Neuropsychiatric Inventory (NPI-D), and patients with the Mini Mental State Examination (MMSE), the Disability Assessment for Dementia (DAD), and the Neuropsychiatric Inventory (NPI). Twenty carers (10%) scored above 19 on the intrusion and avoidance subscales of the IES, whereas 90 (47%) scored above 8 on both subscales. This moderate to high stress response was independently explained by being a spouse (OR 3.74 (95% CI 1.81-7.74)), high scores on GDS (OR 1.12 (95% CI 1.06-1.18) per unit increase) and high score on NPI-D (OR 1.05 (95% CI 1.01-1.09) per unit increase). Spouses and other family carers having daily contact with patients with dementia experience moderate to high levels of intrusion and avoidance. These symptoms are associated with symptoms of anxiety, distress and depression and should be taken into account when tailoring interventions for carers.


The effect of flexible acrylic resin on masticatory muscle activity in implant-supported mandibular overdentures: a controlled clinical trial.
It is not yet clear from the current literature to what extent masticatory muscle activity is affected by the use of flexible acrylic resin in the construction of implant-supported mandibular overdentures. To compare masticatory muscle activity between patients who were provided with implant-supported mandibular overdentures constructed from flexible acrylic resin and those who were provided with implant-supported mandibular overdentures constructed from heat-cured conventional acrylic resin. In this clinical trial, 12 completely edentulous patients were selected and randomly allocated into two equal treatment groups. Each patient in Group 1 received two implants to support a mandibular overdenture made of conventional acrylic resin. In Group 2, the patients received two implants to support mandibular overdentures constructed from "Versacryl" flexible acrylic resin. The maxillary edentulous arch for patients in both groups was restored by conventional complete dentures. For all patients, masseter and temporalis muscle activity was evaluated using surface electromyography (sEMG). The results showed a significant decrease in masticatory muscle activity among patients with implant-supported mandibular overdentures constructed from flexible acrylic resin. The use of "Versacryl" flexible acrylic resin in the construction of implant-supported mandibular overdentures resulted in decreased masticatory muscle activity.


Ruptured Ectopic Pregnancy with an Intrauterine Device: Case Report and Sonographic Considerations.
Ectopic pregnancy carries a high morbidity and mortality; patients are at risk for rupture and life-threatening hemorrhage. We present a rare case of ruptured abdominal ectopic pregnancy in a patient with a well-positioned intrauterine device (IUD) and discuss the diagnostic utility that transabdominal point-of-care ultrasound (POCUS) can have when performed at the bedside. While pregnancy with an IUD in place is rare, when it is encountered the emergency provider should maintain a high degree of suspicion for extrauterine pregnancy and perform prompt evaluation for hemorrhagic shock using diagnostic POCUS.


Do the vaccinated perform less distancing, mask wearing and hand hygiene? A test of the risk compensation hypothesis in a representative sample during the COVID-19 pandemic.
The "risk compensation hypothesis" holds that vaccinated individuals may be less motivated to protect themselves using other COVID-19 mitigation behaviors-e.g., masking, distancing and hand hygiene-given that they may perceive their infection risk to be lower. The current investigation provides an empirical test of the risk compensation hypothesis in the COVID-19 context using prospective data from the Canadian COVID-19 Experiences Survey (CCES). The survey comprised 1,958 unvaccinated and fully vaccinated individuals drawn from a representative sample, using quota sampling to ensure substantial representation of unvaccinated individuals. Two waves of data were collected 6 months apart. Findings revealed that vaccinated individuals performed COVID-19 mitigation behaviors significantly more frequently than their unvaccinated counterparts, and they also showed lower rates of attenuation as the pandemic continued. In summary, our findings do not support the risk compensation hypothesis; instead they support the notion that people adopt vaccination and other protective behaviors in parallel.


Evidence against vasoactive intestinal polypeptide (VIP) as a dilator and in favour of substance P as a constrictor in airway neurogenic responses.
Propranolol-resistant neurogenic relaxation persisted in (carbachol-contracted) guinea-pig tracheae already relaxed by supramaximal concentrations of vasoactive intestinal polypeptide (VIP). Also, VIP relaxed preparations that were under neurogenic inhibition. In hilus bronchi, about 60% of a neurogenic contraction was atropine-resistant. (Arg5, D-Trp7.9) SP 5-11 specifically antagonized this contraction and those produced by exogenous substance P. Substance P, but not VIP, seems to be involved in nerve-mediated effects on guinea-pig airway tone.


Clinical results of colectomy for severe constipation.
Subtotal colectomy has been performed in 40 patients with severe constipation. Only one patient was male. Five patients (13 per cent) had a history of a serious psychiatric disorder. Twenty-six patients (65 per cent) could not expel a 100-ml air-filled balloon and 19 patients (48 per cent) had electromyographic evidence of abnormal puborectalis contraction during attempted defaecation before operation. Median preoperative passage of 50 radio-opaque markers over 5 days was 16 per cent. Sixteen patients had had a previous anorectal myectomy to exclude Hirschsprung's disease. Initial resections were subtotal colectomy and ileorectal anastomosis (n = 34), caecorectal (n = 5) or ileosigmoid (n = 1) anastomosis. Secondary operations included restorative proctocolectomy and ileal pouch-anal anastomosis (n = 6) and six patients eventually had an ileostomy. Median bowel frequency per week significantly increased after operation (0.3 (range 0-1) preoperatively to 21 (range 2-70) postoperatively, P less than 0.005), the percentage of patients with abdominal pain fell after operation from 93 to 39 per cent but symptoms of abdominal distension remained the same (86 per cent preoperatively and 82 per cent postoperatively).


Porous Zr-Based Metal-Organic Frameworks (Zr-MOFs)-Incorporated Thin-Film Nanocomposite Membrane toward Enhanced Desalination Performance.
Four different thin-film nanocomposite (TFN) membranes were prepared by adding different concentrations of porous Zr-metal-organic frameworks (MOFs) (UiO-66 and UiO-66-NH2) to piperazine aqueous solution (aqueous phase) or 1,3,5-benzenetricarbonyl trichloride-n-hexane solution (organic phase) by interfacial polymerization. The main purpose is to study the specific effects of different addition methods and addition amounts of nanoparticles on the structure and performance of the TFN membranes by interfacial polymerization. All four TFN membranes exhibited a higher water permeability while maintaining high salt rejection compared to thin-film composite membrane. On the one hand, the TFN membranes behave differently, which are prepared by adding the same kind of nanoparticles to the aqueous phase or organic phase, respectively. The TFN membrane prepared by adding 0.2 w/v% UiO-66 to the organic phase had a high water flux of 87.86 L m-2 h-1, compared to 46.31 L m-2 h-1 of the membrane prepared by adding 0.3 w/v% UiO-66 in the aqueous phase. This is due to the fact that UiO-66 greatly slows the interfacial polymerization rate when UiO-66 is added to the organic phase, resulting in a thinner and wider-aperture polyamide thin-film layer, reducing the water transmission resistance during filtration. Therefore, it is more economical by adding nanoparticles to organic phase than aqueous phase under the same filtering effect. On the other hand, different nanoparticles can also cause differences in performance and structure of the TFN membranes even in the same preparation manner. TFN membrane with UiO-66-NH2 in the aqueous phase has higher water permeance than the one with UiO-66 in the aqueous phase, owing to the good hydrophilicity of the amino group, which improves the water dispersibility of UiO-66-NH2 so that the TFN membrane is more uniform. In addition, UiO-66-NH2 slows down the process of interface polymerization, making the membrane more porous. The monomers in the aqueous phase and organic phase can be adsorbed in the pores of Zr-MOFs, which makes the interfacial polymerization occur both in the pores and on the surface of the pores. Thus, the compatibility between the polyamide and MOFs was enhanced and less defects were formed in the thin-film layer, resulting in a high salt rejection even when the concentration of Zr-MOFs increased. This is the first time to explain that polyamide membrane has not obvious salt rejection attenuation with increasing porous material content using pore adsorption reaction monomer principle. Also, the Zr-MOFs-based TFN membrane exhibited good heat resistance and antifouling property. This work shows that porous Zr-MOFs nanomaterials have significant advantages in the development of nanofiltration membranes with high water flux and rejection.


The effect of reservoir expansion from underground karst cave to surface reservoir on water quality in southwestern China.
Due to the excessive exploitation of traditional energy sources, the attention paid to water energy has increased in recent years. As an important means to effectively utilize water energy, reservoirs play an important role in drinking water, irrigation, flood control, and drought resistance. However, utilizing reservoirs often led to water quality issues resulting from the interaction of nutrients and hydrological conditions, especially due to the special structure of karst areas. Because of the change of hydrological conditions by the effect of dam construction, the dynamic of water quality will be more obvious in karst areas with a fast exchange of water and contaminants between underground and surface streams. In the present study, the change in water quality of a karst reservoir, the Muzhu Reservoir in the Houzhai Catchment, was studied. Long-term monitored datasets (1981-2002) and water quality datasets of more recent years were used to assess the effect on the water quality of reservoir expansion from the underground reservoir to the surface reservoir in a karst area. Long-term series datasets had shown that the hydro-chemistry type had been changed from HCO3-·SO42--Ca2+·Mg2+ type to HCO3--Ca2+ type in the short term after the reservoir's expansion. The chemical components of water originating from a rock background reduced markedly after the reservoir's expansion, whereas the content of the anthropogenic contribution in the water decreased after the expansion, except in April and May. Isotopic characteristics showed that δ15N-NO3- and δ18O-NO3- values were positively correlated before and after the reservoir expansion, but the slope of the linear regression before the expansion was 0.34, while the slope of the linear regression before the expansion was close to 0.7. This indicated that although denitrification and assimilation may occur simultaneously after the reservoir's expansion, the role of denitrification on nitrate removal decreased, which resulted in nitrate accumulation in the karst reservoir. The results highlighted that nitrate accumulation in karst reservoirs should be monitored to decrease nitrate concentration in the future.


The effect of being left home alone at age 3 years on schizotypy and antisocial behavior at ages 17 and 23 years.
Negative home environments are associated with both schizophrenia-spectrum disorders and crime, but whether this is due to the social or cognitive sequelae of such environments is unclear. This study investigates the effect of early home environments on adult mental health. Using data from the Mauritius Child Health Project, a multiple time-point prospective study where all children born in 1969 in two towns (Quatre Bornes and Vacaos) were recruited at age 3 years (N = 1794), a group of children left home alone at age 3 (n = 34) were compared to children cared for by siblings/relatives (n = 222), or by mothers (n = 1498) on antisocial behavior and schizotypal personality at ages 11, 17, and 23 years. Home alone children showed higher scores on psychotic behavior and conduct disorder at age 17, and also schizotypal personality and crime at 23 years compared to the other groups. No negative behavioral or cognitive effects were observed at age 11. Findings were not accounted for by social adversity or ethnicity and appear to be 'sleeper effects' in that they do not emerge until later adolescence and into adulthood. Findings appear to be the first to show the negative effects of dual-parental daytime absence on adult schizotypy and crime, a finding that cannot be accounted for by verbal and spatial cognitive impairments. Results suggest an early common psychosocial denominator to the two comorbid conditions of antisocial behavior and schizotypy.


Aortic stump closure: a new technique.
The usual closure of the aortic stump results in a cul-de-sac which favors secondary rupture. A new procedure utilizing an anterior-posterior suture line in two layers is described which creates a median strut. It allows a secure suture line in a short aortic stump, and may enhance the splitting of blood flow between the renal arteries.


The accuracy of predicting histologic grades of supratentorial astrocytomas on the basis of computerized tomography and cerebral angiography.
This report concerns a group of 49 patients who had been diagnosed as having gliomas on the basis of CT scans plus angiograms and for whom histologic proof was available. Ninety percent were found to be gliomas, 4% were metastases, and histology was unclear in the rest. Combining the CT criteria of inhomogeneous enhancement and surrounding edema with one or more of three angiographic signs (early venous drainage, stain, abnormal vessels) allowed a more confident diagnosis of glioblastoma.


Overexpression of GATA5 Inhibits Prostate Cancer Progression by Regulating PLAGL2 via the FAK/PI3K/AKT Pathway.
Prostate cancer (PCa) is a malignancy with high incidence and the principal cause of cancer deaths in men. GATA binding protein 5 (GATA5) belongs to the GATA gene family. GATA5 has a close association with carcinogenesis, but the role of GATA5 in PCa remains poorly understood. The aim of our present study was to probe into the effect of GATA5 on PCa progression and to elucidate the involved mechanism. The expression of GATA5 was detected in both PCa samples and PCa cell lines. GATA5 overexpression, PLAGL2 knockdown, and overexpression cell models were generated, then Western blotting experiments were utilized to validate the efficiency of transfection. The effects of GATA5 on PCa cell proliferation, metastasis, apoptosis, cell cycle progression, and EMT were detected in vitro or in vivo. Furthermore, the mechanism by which GATA5 inhibits prostate cancer progression through regulating PLAGL2 via the FAK/PI3K/AKT pathway was also explored. GATA5 expression was downregulated in PCa samples and cell lines. GATA5 overexpression inhibited PCa cell proliferation and metastasis but increased the rate of apoptosis. In addition, we confirmed that GATA5 inhibited prostate cancer progression, including EMT, by regulating PLAGL2 via the FAK/PI3K/AKT pathway. We demonstrated that GATA5, as a tumor suppressor in PCa, inhibits PCa progression by regulating PLAGL2. These results showed that the GATA5/PLAGL2/FAK/PI3K/AKT pathway may become a new therapeutic direction for the treatment of PCa.


Etiologic and prognostic value of external carotid artery thrombus detection during endovascular therapy for anterior circulation proximal occlusions.
An early understanding of stroke mechanism may improve treatment and outcome in patients presenting with large vessel occlusion stroke (LVOS) treated with mechanical thrombectomy (MT). We aimed to investigate whether spontaneous external carotid artery (ECA) embolism detection during MT is associated with stroke etiology and clinical outcome. We retrospectively reviewed our prospectively maintained institutional database including consecutive patients with anterior circulation LVOS treated with MT between January 2015 and August 2020. An ECA embolus was detected in 68 of 1298 patients (5.2%). The kappa coefficient for interobserver agreement was 0.89 (95% confidence interval [CI] 0.82-0.95). ECA embolism was significantly associated with intracranial internal carotid artery (ICA) occlusion (p < 0.001), cardioembolic etiology (p < 0.001) and a lower clot burden score (p < 0.001). Day-1 variation of National Institutes of Health Stroke Scale score (adjusted odds ratio [OR] -2.7, 95% CI -4.9 to 0.3; p = 0.021) and delta Alberta Stroke Program Early Computed Tomography Score (adjusted OR 0.9, 95% CI 0.2 to 1.5; p = 0.004) were worse among patients with ECA emboli. There was no significant difference in 90-day functional outcome between groups (adjusted OR 0.8, 95% CI 0.42 to 1.52; p = 0.50). In patients with anterior circulation LVOS treated with MT, ECA embolism was significantly associated with cardioembolic etiology, high thrombus burden and proximal intracranial ICA occlusions. This underexplored angiographic pattern might provide a valuable etiologic clue to the underlying cause of anterior circulation LVOS and may also help determine the appropriate revascularization strategy.


Ganoderma lucidum polysaccharide peptides GL-PPSQ2 alleviate intestinal ischemia-reperfusion injury via inhibiting cytotoxic neutrophil extracellular traps.
Ganoderma lucidum polysaccharides peptides (GLPP) are the main effective ingredients from G. lucidum (Leyss. ex Fr.) Karst with anti-inflammatory, antioxidant, and immunoregulatory activities. We extracted and characterized a novel GLPP, named GL-PPSQ2, which were found to have 18 amino acids and 48 proteins, connected by O-glycosidic bonds. The monosaccharide composition of GL-PPSQ2 was determined to be composed of fucose, mannose, galactose and glucose with a molar ratio of 1:1.45:2.37:16.46. By using asymmetric field-flow separation technique, GL-PPSQ2 were found to have a highly branched structure. Moreover, in an intestinal ischemia-reperfusion (I/R) mouse model, GL-PPSQ2 significantly increased the survival rate and alleviated intestinal mucosal hemorrhage, pulmonary permeability, and pulmonary edema. Meanwhile, GL-PPSQ2 significantly promoted intestinal tight junction, decreased inflammation, oxidative stress and cellular apoptosis in the ileum and lung. Analysis with Gene Expression Omnibus series indicates that neutrophil extracellular trap (NET) formation plays an important role in intestinal I/R injury. GL-PPSQ2 remarkedly inhibited NETs-related protein myeloperoxidase (MPO) and citrulline-Histone H3 (citH3) expression. GL-PPSQ2 could alleviate intestinal I/R and its induced lung injury via inhibiting oxidative stress, inflammation, cellular apoptosis, and cytotoxic NETs formation. This study proves that GL-PPSQ2 is a novel drug candidate for preventing and treating intestinal I/R injury.


Surface Properties of Squalene/Meibum Films and NMR Confirmation of Squalene in Tears.
Squalene (SQ) possesses a wide range of pharmacological activities (antioxidant, drug carrier, detoxifier, hydrating, emollient) that can be of benefit to the ocular surface. It can come in contact with human meibum (hMGS; the most abundant component of the tear film lipid layer) as an endogenous tear lipid or from exogenous sources as eyelid sebum or pharmaceuticals. The aims of this study were to determine (i) if SQ is in tear lipids and (ii) its influence on the surface properties of hMGS films. Heteronuclear single quantum correlation NMR confirmed 7 mol % SQ in Schirmer's strips extracts. The properties of SQ/hMGS pseudo-binary films at the air/water interface were studied with Langmuir surface balance, stress-relaxation dilatational rheology and Brewster angle microscopy. SQ does not possess surfactant properties. When mixed with hMGS squalene (i) localized over the layers' thinner regions and (ii) did not affect the film pressure at high compression. Therefore, tear SQ is unlikely to instigate dry eye, and SQ can be used as a safe and "inert" ingredient in formulations to protect against dry eye. The layering of SQ over the thinner film regions in addition to its pharmacological properties could contribute to the protection of the ocular surface.


Dissection of an inflammatory process induced by CD8+ T cells.
A massive delayed type hypersensitivity (DTH) reaction occurs in the cerebrospinal fluid (CSF) of mice with lymphocytic choriomeningitis (LCM). In this article, Peter Doherty and colleagues analyze this reaction together with the population dynamics of the regional lymph node to give a comprehensive picture of the events underlying this CD8+ T-cell-mediated immunopathological disease. Their findings are of general relevance to the understanding of inflammation.


Psychological perspectives of sex and aging.
Older patients have many assaults on their sexuality. Our culture often discourages sexual interest in older persons. Changes in sexual physiology and the effects of chronic illness and medications can further contribute to negative expectations and can impair sexual performance. The emotional and relational stresses of aging can lead to depression, thus further compounding sexual slowdown. Failure to appreciate psychological factors can result in inappropriate treatment by the physician and actually add to the patient's distress. This report considers the mind/body relationship in sexual performance and offers guidance to the physician in the diagnosis of physical and emotional factors affecting the older person's sexual life.


Functional characterization of two defensins, HlDFS1 and HlDFS2, from the hard tick Haemaphysalis longicornis.
Ticks are second to mosquitoes as vectors of human arthropod-borne diseases. Ticks rely heavily on antimicrobial peptides (AMPs) to defend against microbes and defensins are major components of innate immunity in ticks. Two novel defensin genes, named HlDFS1 and HlDFS2, were identified from a cDNA library of the hard tick Haemaphysalis longicornis collected in southeast China. The peptides encoded by both genes shares typical features of type-2 arthropod defensin superfamily. The expressions of both genes increased in ticks during blood-feeding. The synthetic minimum functional peptides HlDFS1 and HlDFS2 showed broad spectrum antimicrobial activity against various Gram-positive and Gram-negative bacteria. Moreover, HlDFS1 and HlDFS2 exhibit bactericidal activity to some drug resistant bacteria. HlDFS1, but not HlDFS2, showed inhibitory activity against fungus Candida albicans. HlDFS1 and HlDFS2 had no significant hemolysis effect on human erythrocytes at low concentrations and did not impair mammalian cell survival. Finally, HlDFS1 and HlDFS2 significantly protected mice against lethal infection by Staphylococcus aureus and Micrococcus luteus. HlDFS1 and HlDFS2 are two novel functional defensins from the hard tick Haemaphysalis longicornis. They showed bactericidal activity against various Gram-positive and Gram-negative bacteria and significantly protect mice against lethal bacterial infection. Thus, HlDFS1 and HlDFS2 can be introduced to the medical field as new drug candidates with antibacterial activity.


Acquired immunodeficiency syndrome-related lymphoma of the lung presenting as empyema thoracis.
B-cell lymphoma in patients infected with the human immunodeficiency virus is usually a disseminated process that occasionally involves the lungs. Surgical diagnosis is often necessary to distinguish this from other neoplasms or opportunistic infections of the lung. We report a case of pulmonary B-cell lymphoma in a patient infected with human immunodeficiency virus who presented with a left empyema thoracis and an associated left lower lobe abscess secondary to bronchial obstruction. Resection was performed and the patient subsequently recovered from the acute process and survived an additional 6 months. This report demonstrates that surgical intervention may be necessary for both the diagnosis of pulmonary lymphoma and the definitive management of infectious complications that may arise as a result of pulmonary neoplastic disease in patients with acquired immunodeficiency syndrome.


Protein-losing enteropathy as a complication of spontaneous isolated superior mesenteric artery dissection: A case report.
Protein-losing enteropathy and spontaneous isolated superior mesenteric artery dissection are both rare clinically. Protein-losing enteropathy due to superior mesenteric artery dissection is extremely rare. A 46-year-old male with acute abdominal pain and hematochezia was diagnosed with a complete occlusion of the superior mesenteric artery because of dissection. He suffered from diarrhea and hypoproteinemia after an emergency thromboendarterectomy. Based on laboratory tests and capsule endoscopy inspection, a diagnosis of protein-losing enteropathy was made. Endovascular treatment was provided. After stent placement, he quickly recovered without a recurrence of symptoms. Protein-losing enteropathy is a serious complication of an isolated superior mesenteric artery dissection. Restoring the patency of the superior mesenteric artery is keyed for the treatment of this complication.


Biovalorization of spent Konacha tea leaves via single-culture fermentation involving wine yeasts and lactic acid bacteria.
The objective of this study was to explore the potential of fermentation as a biovalorization strategy for spent tea leaves (STL), a major agrifood waste generated from the tea extraction industry. Fermentation by wine yeasts or lactic acid bacteria (LAB) has shown promising results in previous studies across various substrates. Konacha (green tea) STL slurries were inoculated with single strains of wine yeasts or LAB respectively. After a 48-h fermentation, changes in selected nonvolatile and volatile compositions were evaluated. Fermentation by LAB increased organic acid content by 5- to 7-fold (except Lactobacillus fermentum) and modulated the composition of major tea catechins, whereas wine yeast fermentation resulted in a 30% increase in amino acid content. Strain-specific production of specific volatile compounds was also observed such as butanoic acid (L. fermentum), isoamyl acetate (Pichia kluyveri) and 4-ethylphenol (L. plantarum). Both volatile and nonvolatile compound compositions of Konacha STL were successfully modified via wine yeast and LAB fermentation. Our findings indicate that Konacha STL is a suitable medium for biovalorization by wine yeasts or LAB via the generation of commercially useful volatile and nonvolatile compounds. Future optimizations could further render fermentation an economically viable strategy for the upcycling of STL.


Factors Associated with Increased Risk for Pulmonary Embolism After Metabolic and Bariatric Surgery: Analysis of Nearly One Million Patients.
Metabolic and bariatric surgery (MBS) has a low incidence of post-operative morbidity and mortality. Understanding risk factors associated with complications that occur allows surgeons to define at-risk patients and assess the need for preventive and prophylactic measures. To determine risk factors associated with development of pulmonary embolism (PE) within 30 days of MBS and to predict the increased risk for mortality when PE occurs. USA, MBSAQIP database. Analysis of the MBSAQIP database was undertaken. This included information on 966,646 MBS cases from 2015 to 2019 in the USA. Twenty-two risk factors for development of PE post-MBS were identified to be statistically significant. PE is a relatively uncommon complication after MBS. When it does occur, there is a 50.9-fold increased risk for mortality. Patients with significant risk factors for PE may benefit from higher dose perioperative and/or extended VTE prophylaxis after MBS.


Glutathione peroxidase and CT scan abnormalities in schizophrenia.
The search for morphological clues to the etiology of schizophrenia has led to widespread application of computed tomography (CT) scans in the examination of patients. These investigations have resulted in numerous reports over the past several years of brain atrophy and increased ventricle-brain ratios (VBR), suggestive of neuronal tissue damage, associated with the disorder. Altered activity of cellular antioxidant systems have been implicated in the neuronal cell loss that is associated with degenerative diseases of the central nervous system (CNS), but this phenomenon has not been investigated with respect to functional disorders like schizophrenia. A search for such a relationship in schizophrenics with evidence of brain atrophy has been initiated by measuring the activity of the important antioxidant enzyme glutathione peroxidase (GPx) in blood samples from a population of chronic schizophrenics and age- and sex-matched nonschizophrenic mental patients as controls. A strong negative correlation has been found between GPx activity in both isolated platelets and erythrocytes and CT scan measures of brain atrophy and VBR in the schizophrenics, but not in the control population, which exhibited comparable CT scan abnormalities. These observations suggest a unique relationship of GPx to the mechanism of tissue damage in the schizophrenics.


Impact of the 2014 CDC HIV testing guidelines on detection of acute HIV infections.
The Centers for Disease Control and Prevention (CDC) issued updated guidelines for HIV testing in 2014. These guidelines recommend screening using an HIV-1/2 antigen/antibody (Ag/Ab) test and create the ability to identify algorithm-defined acute HIV infections (AHI). The guidelines also recommend laboratory confirmation of preliminary positive point of care (POC) rapid HIV test results and specimens from high-risk individuals who test POC rapid negative. The Florida Public Health Laboratory (FPHL) switched from an antibody-only algorithm to the CDC recommended algorithm April 16, 2012. To analyze the FPHL HIV testing data and evaluate the impact of the CDC recommended algorithm on the identification of AHI, time to result and inconclusive HIV reports. FPHL HIV test data, for the period January 1, 2010 through December 31, 2019, was reviewed to determine the number of AHI cases identified, the number of indeterminate HIV results and the time from specimen receipt to result for tests in the antibody-only and CDC recommended algorithms. In addition, POC rapid results were compared to laboratory-based results for AHI cases for which rapid test results were available. There was no difference in time to result between the antibody-only and CDC recommended algorithms for HIV negative specimens. The time to result for HIV-1 positive specimens decreased from an average of 5 days with the antibody-only algorithm to an average of 1 day with the CDC recommended algorithm. The average number of indeterminate results per month decreased from 6.25 per month with the antibody-only algorithm to an average of 2.5 per month using the CDC recommended algorithm. Despite HIV seropositivity decreasing by 0.5% during the study period (2012 = 3.1% [3,892/124,394]: 2019 = 2.6% [2,456/95,525]), AHI cases increased annually from a total of 4 in 2012 to over 50 in 2019 and cases were identified in 30 of 67 Florida counties. The increase in identification of AHIs is credited to educational efforts with healthcare providers to encourage further testing on individuals with risk factors for HIV and a recent POC HIV-1/2 rapid negative test result. Data indicates that performing HIV testing according to the CDC recommended algorithm decreased time to result for HIV positive results, reduced the number of indeterminate results and identified algorithm-defined AHI. In addition, laboratory-based testing is warranted for high-risk individuals who test negative by POC rapid testing.


Inhibition of ruthenium red-induced Ca2+ efflux from liver mitochondria by the antibiotic X-537A.
It has been reported (Becker, G.L., Fiskum, G. and Lehninger, A.L. (1980) J. Biol. Chem. 255, 9009-9012) that respiring rat liver mitochondria suspended in KC1 medium containing ATP, Mg2+ and phosphate, maintain a steady state extramitochondrial free Ca2+ concentration of about 0.5 microM. The results reported here show that the addition of the antibiotic X-537A, at concentrations far below those required for ionophorous activity, caused a perturbation in this steady state, lowering the extramitochondrial free Ca2+ concentration by about 0.20 microM. This shift in steady state was clarified by a study of X-537A inhibition of the Ca2+ efflux induced by ruthenium red; a half-maximum effect was observed at approximately 25 nM X-537A. No effect on Ca2+ transport through the influx uniporter was observed. The possibility of a generalized stabilizing action of the antibiotic on the mitochondrial membrane seems to be ruled out by its effectiveness at very low concentrations.


Fe-modified biochar enhances microbial nitrogen removal capability of constructed wetland.
To improve the nitrogen removal capability of constructed wetlands, the biochar, produced from bamboo, activated with HCl and coated with Fe (FeCl3·6H2O), and then was added as a substrate into the systems. Three horizontal subsurface flow constructed wetlands (HSCWs) was established to treat the low C/N tailwater from the wastewater treatment plant: C-HSCW (quartz sand + soil), B-HSCW (quartz sand + soil + unmodified biochar), and FeB-HSCW (quartz sand + soil + Fe-modified biochar). Under different combinations of hydraulic retention time and nitrogen loading, the FeB-HSCW revealed extremely effective nitrogen removal, compared to the C-HSCW and B-HSCW. The highest removal efficiencies of NO3--N (95.30%), TN (86.68%), NH4+-N (86.33%), NO2--N (79.35%) and COD (63.36%) were obtained in FeB-HSCW with the hydraulic retention time of 96 h. and low influent nitrogen loading (C/N of 2.5). Nitrogen mass balance analysis showed that microbial processes played the most important role of nitrogen removal in HSCWs and the Fe-modified biochar significantly enhanced the microbial nitrogen removal. A total of 128.40 g nitrogen was removed by microorganisms in FeB-HSCW (average removal rate of 2.52 g N/(m3·d1)), much higher than that in other two HSCWs. The contributions of microorganisms, substrate storage and plant uptake on the total amount of nitrogen removal in the FeB-HSCW was 92.69%, 2.97% and 4.34%, respectively. Moreover, FeB significantly increased the abundances of genes involved in nitrogen removal. The copy numbers of bacterial 16S rRNA and amx, as well as of genes nirS, nirK, nosZ-I, nosZ-II, and hzsA were 1.3- to 27.8-fold higher in the FeB-HSCW than that in the other two HSCWs. Thus, Fe-modified biochar provides a feasible and effective amendment for constructed wetlands to improve the nitrogen removal, particularly nitrate-N, for low C/N wastewaters by enhancing the microbial nitrogen removal capacity (mainly of the denitrification).


Action of substance P on the working rat heart.
The effect of substance P (SP) on the cardiodynamics of the isolated working rat heart perparation was examined. The peptide over the concentration range of 10(-8) to 10(-6) M was found to have no influence on aortic pressure, cardiac output, or cardiac work. However, a 10-15% reduction in coronary flow was observed at 1 x 10(-6) M substance P. Octapeptide substance P (SP4-11) exhibited a similar vasoconstrictive action. The IC50 of SP4-11 was 2 x 10(-13) M compared to an IC50 of 3.5 x 10(-8) M for substance P. Perfusion of the heart in the presence of bacitracin (1 x 10(-4) M), a protease inhibitor, prevented the reduction in coronary flow observed in the presence of substance P. By contrast, the reduction in coronary flow produced by octapeptide substance P was not altered by the presence of bacitracin. Thus, it appears that a C-terminal fragment such as SP4-11 may be responsible for the observed decrease in coronary flow.


Dienogest, a synthetic progestin, inhibits prostaglandin E2 production and aromatase expression by human endometrial epithelial cells in a spheroid culture system.
Prostaglandin E(2) (PGE(2)) is a major mediator in the pathophysiology, and pathogenesis of gynecological diseases associated with abnormal endometrial disease with proliferation and inflammation, such as endometriosis. In this study, we investigated the effect of dienogest, a selective progesterone receptor agonist, on PGE(2) production and the expression of aromatase, an estrogen synthase, in human immortalized endometrial epithelial cells. Compared with monolayer culture, the cells showed enhanced PGE(2) production and expression of the PGE(2) synthases cyclooxygenase-2 (COX-2), and microsomal prostaglandin E(2) synthase-1 (mPGES-1) in a spheroid culture system. Dienogest inhibited PGE(2) production and this effect was reversed by RU486, a progesterone receptor antagonist. Dienogest inhibited the PGE(2) synthases mRNA and protein expression, and the nuclear factor-κB activation. Moreover, the suppressive effect of dienogest on PGE(2) production was sustained 24h after the drug was withdrawn. Dienogest but not COX inhibitors inhibited aromatase expression. These results suggest that progesterone receptor activation reduces the gene expressions of COX-2, mPGES-1, and aromatase. Our findings suggest that the pharmacological mechanism of dienogest includes the direct inhibition of PGE(2) synthase and aromatase expression and may contribute to the therapeutic effect on the progression of endometriosis.


17β-estradiol (E2) in membranes: Orientation and dynamic properties.
Non-genomic membrane effects of estrogens are of great interest because of the diverse biological activities they may elicit. To further our understanding of the molecular features of the interaction between estrogenic hormones and membrane bilayers, we have determined the preferred orientation, location, and dynamic properties of 17β-estradiol (E2) in two different phospholipid membrane environments using (2)H-NMR and 2D (1)H-(13)C HSQC in conjunction with molecular dynamics simulations. Unequivocal spectral assignments to specific (2)H labels were made possible by synthesizing six selectively deuterated E2 molecules. The data allow us to conclude that the E2 molecule adopts a nearly "horizontal" orientation in the membrane bilayer with its long axis essentially perpendicular to the lipid acyl-chains. All four rings of the E2 molecule are located near the membrane interface, allowing both the E2 3-OH and the 17β-OH groups to engage in hydrogen bonding and electrostatic interactions with polar phospholipid groups. The findings augment our knowledge of the molecular interactions between E2 and membrane bilayer and highlight the asymmetric nature of the dynamic motions of the rigid E2 molecule in a membrane environment.


Intraneural perineurioma of the radial nerve in a child.
An intraneural perineurioma is an uncommon solitary neoplasm of major nerve trunks composed of perineurial cells from the peripheral nerve sheath. The typical course of intraneural perineurioma is indolent, with gradual-onset motor loss and presentation for evaluation months to years after onset of symptoms. We report a 9-year-old girl with an intraneural perineurioma of the radial nerve. Diagnosis was confirmed by histology and immunohistochemistry. Resection and nerve graft reconstruction were performed to prevent progression of motor compromise and to allow recovery of motor function. An algorithm for the management of focal intraneural tumors is shown.


Factors influencing the abundance of Japanese encephalitis vectors in ricefields in India--II. Biotic.
The relationship of insect predators and phytoplankton with the abundance of Culex tritaeniorhynchus Giles, Cx. vishnui Theobald and Cx. pseudovishnui Colless mosquito larvae and pupae (Diptera: Culicidae) in ricefields was investigated during three rice growing seasons. Notonectids were the most abundant insect predators, whereas diatoms dominated among phytoplankton. Multiple regression analysis showed that the occurrence of notonectids (both nymphs and adults) was negatively associated with larval abundance. Phytoplankton, especially diatoms and blue green algae (BGA), were found to favour abundance of culicine immatures during Navarai and Kuruvai crops, respectively. Larval gut analysis showed that the intake of algae by late instars was high, with 93%, 58% and 24% of diatoms, BGA and green algae, respectively. Filamentous algae may not necessarily be of nutritive value, but they are observed to form mats, which provide protection to the mosquito immatures from the predators.


Towards a plastic-less planet. Gender and individual responsibility predict the effect of imagery nudges about marine (micro)plastic pollution on R-behavior intentions.
Emerging microplastics (MP) pollution is one of the biggest threats for the oceans today. Consumers could reduce MP pollution adopting R-behaviors such as reducing consumption of plastic, refusing products with MP, replacing them for green products, and recycling. Here we tested the efficiency of online nudges (images and short messages) for promoting MP-conscious behavior in Spain (n = 671). The perceived level of environmental responsibility and the willingness to adopt R-behaviors were measured. Messages about seafood with MP and plastic-polluted marine environment were more efficient than images of animals killed by plastics. Feeling responsible for MP pollution predicted R-behavior intention. Women would adopt more R-behaviors than men, while men were more sensitive than females to the proposed nudges. Raising the sense of environmental responsibility would be priority in education campaigns. For different cultural sensitivities to animal suffering, evoking environmental health instead of threats to wildlife would be generally recommended.


[Congenital ptosis].
Simple congenital ptosis is the most common form, characterised by fatty dystrophy and fibrosis of the levator muscle, which leads to a restricted elevation in upgaze and a lid lag in downgaze. In the complicated form additional changes will be found: fibrosis of extraocular muscles, synkinesia or anomalies of the lids. Moreover, congenital ptosis is relatively often associated with refractive errors and/or disturbance of the binocular vision. Therefore a careful examination is necessary. Therapeutic management includes first prevention of amblyopia either by occlusion or by early surgical intervention. The choice of operation depends on the grade of ptosis, the actual levator function and the presence of lid anomalies as well.


Effect of small coding genes on the circadian rhythms under elevated CO2 conditions in plants.
Increase in atmospheric carbon dioxide (CO2) has a significant effect on plant growth and development. To explore the elevated-CO2 response, we generated transcriptional profiles over a time course (2 h-14 days) of exposure to elevated CO2 in Arabidopsis thaliana. Genes related to photosynthesis were down-regulated and circadian rhythm-related genes were abnormally regulated in the early to middle phase of elevated CO2 exposure. To understand the novel mechanism of elevated CO2 signaling, we focused on 42 unknown small coding genes that showed differential expression patterns under elevated CO2 conditions. Four transgenic plants overexpressing the small coding gene exhibited a growth-defective phenotype under elevated CO2 but not under current CO2. Transcriptome analysis showed that circadian rhythm-related genes were commonly regulated in four transgenic plants. These circadian rhythm-related genes were transcribed in the dark when CO2 concentrations in the leaf was high. Taken together, our identified four small coding genes are likely to participate in elevated CO2 signaling to the circadian rhythm.


PAK-dependent regulation of actin dynamics in breast cancer cells.
Metastatic Breast Cancer has a poor 25% survival rate and currently there are no clinical therapeutics which target metastasis. 'Migrastatics' are a new drug class which target migration pathway effector proteins in order to inhibit cancer cell invasion and metastasis. The p21-activated kinases (PAKs) are essential drivers of breast cancer cell migration and invasion through their regulation of actin cytoskeletal dynamics. Therefore, the PAKs present as attractive migrastatic candidates. Here we review how PAKs regulate distinct aspects of breast cancer actin dynamics focussing on cytoskeletal reorganisation, cell:matrix adhesion, actomyosin contractility and degradative invasion. Lastly, we discuss the introduction of PAK migrastatics into the well-honed breast cancer clinical pipeline.


Evolution of solid phase homochirality for a proteinogenic amino acid.
The inexorable evolution of solid-phase single chirality is demonstrated for the first time for a proteinogenic amino acid. Enantioenrichment is observed both under attrition-enhanced conditions and without the aid of particle grinding. Differences in the form of the conversion profiles for the process under the two sets of conditions provide suggestions concerning the mechanism of the transformation.


Geodynamic evolution of southwestern North America since the Late Eocene.
Slab rollback, lithospheric body forces, or evolution of plate boundary conditions are strongly debated as possible lithospheric driving mechanisms for Cenozoic extension in southwestern North America. By incorporating paleo-topography, lithospheric structure, and paleo-boundary conditions, we develop a complete geodynamic model that quantifies lithospheric deviatoric stresses and predicts extension and shear history since Late Eocene. We show that lithospheric body forces together with influence of change-over from subduction to transtensional boundary conditions from Late Eocene to Early Miocene were the primary driving factors controlling direction and magnitude of extensional deviatoric stresses that produced topographic collapse. After paleo-highlands collapsed, influence of Pacific-North America plate motion and associated deformation style along the plate boundary became increasingly important from Middle Miocene to present. Smaller-scale convection stress effects from slab rollback and associated mantle flow played only a minor role. However, slab rollback guided deformation rate through introduction of melts and fluids that impacted rheology.


Monoclonal immunoglobulin gene rearrangement in peripheral lymphocytes of a patient with multiple myeloma.
We analyzed the immunoglobulin (Ig) heavy chain gene rearrangement in the peripheral blood lymphocytes of a patient with multiple myeloma (MM). Although the morphological and immunological examination did not reveal the presence of circulating plasma cells, a monoclonal Ig gene rearrangement was detected. This observation indicates that a monoclonal expansion of circulating B cells was present in the peripheral lymphocytes of this patient.


Financial control of laboratory animal facilities: partial cost recovery in an academic institution.
The objective of cost management in the animal house is to make efficient use of resources and to regulate the activity of the user. Regular charging of users keeps them aware of their responsibility both ethically and financially. Forward budgetary control is encouraged and regulation of the work load achieved through planned requirements helps to reduce animal wastage.


Analysis of the Diffusion in a Multilayer Structure under a Constant Heating Rate: The Calculation of Activation Energy from the In Situ Neutron Reflectometry Measurement.
Understanding mass transport in micro- and nanostructures is of paramount importance in improving the performance and reliability of the micro- and nanostructures. In this work, we solve the diffusion problem in a multilayer structure with periodic conditions under a constant heating rate via a Fourier series. Analytical relation is established between the coefficients of eigenfunctions and the intensity of X-ray or neutron Bragg peak. The logarithm of temporal variation of the intensity of X-ray or neutron Bragg peak is a linear function of the nominal diffusion time, with the nominal diffusion time being dependent on the heating rate. This linear relation is validated by experimental data. The Taylor series expansion of the linear relation to the first order of the diffusion time yields an approximately linear relation between the logarithm of temporal variation of the intensity of X-ray or neutron peak and the diffusion time for small diffusion times, which can be likely used to calculate the activation energy for the diffusion in a multilayer structure. The validation of such an approach is subjected to the fact that the characteristic time for heat conduction is much less than the characteristic time for the ramp heating as well as the characteristic time for diffusion.


Can 80 W KTP Laser Vaporization Effectively Relieve the Obstruction in Benign Prostatic Hyperplasia?: A Nonrandomized Trial.
There is little data evaluating the changes of severity of bladder outlet obstruction after 80 W-potassium-titanyl-phosphate (KTP) photoselective laser vaporization prostatectomy (PVP) by pressure-flow study. We evaluated the efficacy of PVP to relieve the obstruction in benign prostate hyperplasia (BPH) compared with transurethral resection of the prostate (TURP). This is a prospective, non-randomized single center study. The inclusion criteria were as follows: Men suffering from lower urinary tract symptoms (LUTS) secondary to BPH, age ≥50 years, International Prostatic Symptom Score (IPSS) ≥13, maximum flow rate (Qmax) ≤15 ml/s, and ability to give fully informed consent. Patients with neurogenic cause or detrusor underactivity were excluded. The IPSS, bother score, Qmax, postvoid residual volume (PVR), detrusor pressure at maximum flow rate (PdetQmax), bladder outlet obstruction index (BOOI), and prostate volume were measured before and 6 months after surgery and compared between PVP and TURP. Sixty-seven patients (53 in PVP, 14 in TURP) were evaluable. In both groups, the IPSS, bother score, Qmax, and PVR had significantly improved (p<0.05), and there were no differences between the changes in those parameters. PVP could effectively reduce the PdetQmax, prostate volume, and BOOI from baseline (from 68.7±23.3 to 40.6±11.2 cmH2O, 49.5±16.3 to 31.3±12.1 ml, 49.8±25.6 to 9.8±20.7), similar to TURP. There were no differences in postoperative PdetQmax, prostate volume, or BOOI between the two groups. The percentage of patients with BOOI ≥40 was decreased from 64% to 4% in the PVP group and from 86% to 14% in the TURP group. PVP could reduce the prostate volume effectively and relieve bladder outlet obstruction similar to TURP by the 6-month follow up in men with BPH.


The association between active tumor volume, total lesion glycolysis and levels of S-100B and LDH in stage IV melanoma patients.
The Standardized Uptake Value (SUV) in single lesions on 18F-FDG PET/CT scans and serum S-100B concentrations are inversely associated with disease-free survival in stage IV melanoma. The aim of this study was to assess the association between biomarkers (S-100B, LDH) and the PET-derived metrics SUVmean/max, metabolic active tumor volume (MATV), and total lesion glycolysis (TLG) in stage IV melanoma in order to understand what these biomarkers reflect and their possible utility for follow-up. In 52 stage IV patients the association between PET-derived metrics and the biomarkers S-100B and LDH was assessed and the impact on survival analyzed. S-100B was elevated (>0.15 μg/l) in 37 patients (71%), LDH in 11 (21%). There was a correlation between S-100B and LDH (R2 = 0.19). S-100B was correlated to both MATV (R2 = 0.375) and TLG (R2 = 0.352), but LDH was not. Higher MATV and TLG levels were found in patients with elevated S-100B (p < 0.001) and also in patients with elevated LDH (>250 U/l) (p < 0.001). There was no association between the biomarkers and SUVmean/max. Survival analysis indicated that LDH was the only predictor of melanoma-specific survival. In newly diagnosed stage IV melanoma patients S-100B correlates with 18F-FDG PET/CT derived MATV and TLG in contrast to LDH, is more often elevated than LDH (71% vs. 21%) and seems to be a better predictor of disease load and disease progression. However, elevated LDH is the only predictor for survival. The biomarkers, S-100B and LDH appear to describe different aspects of the extent of metastatic disease and of tumornecrosis.


Evaluation of Factors Affecting the Surgical Outcome in Tympanoplasty.
Tympanoplasty is a standard procedure to repair tympanic membrane perforation. The aim of this study is to evaluate the results of tympanoplasty (hearing improvement and tympanic membrane closure rate) in patients suffering from chronic perforation of the tympanic membrane by considering the prognostic factors. In a prospective study, based on the results of tympanoplasty with temporal graft fascia in 60 patients in the ENT department of the Medical Science University of Tabriz, we evaluated prognostic factors, such as age, sex, smoking, size, and site of perforation, for the outcome of this surgery. The rate of surgical success- integration of the graft- was 93.3%. Improvement of hearing, as demonstrated through audiometry, occurred in 93% of cases. We did not find any factors to be statistically significant to affect surgical outcome. Even by considering the influence of different factors on the results of a tympanoplasty operation, according to the statistical results of this study, there is not a significant difference in the results of the operation, neither in the health of the tympanic membrane after surgery nor in hearing development.


Associations between personality traits, physical activity level, and muscle strength.
Associations among personality as measured by the Five Factor Model, physical activity, and muscle strength were assessed using data from the Baltimore Longitudinal Study of Aging (N = 1220, age: mean = 58, SD = 16). General linear modeling with adjustment for age, sex, race, and body mass index, and bootstrapping for mediation were used. We found neuroticism and most of its facets to negatively correlate with strength. The extraversion domain and its facets of warmth, activity, and positive-emotions were positively correlated with strength, independent of covariates. Mediation analysis results suggest that these associations are partly explained by physical activity level. Findings extend the evidence of an association between personality and physical function to its strength component and indicate health behavior as an important pathway.


The effect of five days' fasting on skeletal muscle enzymes in obese men.
The effect of 120 hours' (five days) fasting on the activity of some enzymes of energy metabolism in skeletal muscles was investigated in six obese young men. The results revealed a significant decline in the activity of the following enzymes: triosophosphate dehydrogenase (by 20%), glycerol-3-phosphate dehydrogenase (by 24%), lactate dehydrogenase (by 13%), citrate synthase (by 20%), hydroxyacyl-CoA dehydrogenase (by 40%), while the hexokinase and malate dehydrogenase activities were not significantly altered. Contrary to muscles of non-obese healthy men (Vondra, Bass, Brodan, Kuhn, Andĕl, Veselková and Vítek 1982), a smaller decline of activities of the investigated enzymes occurred together with a paradoxical change of the enzyme pattern, namely a predominance of carbohydrate catabolism and a decline of the role of fatty acids in muscle energy metabolism.


Nutritional aspects of neuromuscular diseases.
Evidence suggests that individuals with DMD have reduced skeletal development, including decreased linear growth and bone mineral density, compared to normal subjects. Despite their reduced muscle mass, a high percentage of DMD patients are overweight. Body composition measurements can assist with monitoring changes in fat mass and skeletal muscle mass as the disease progresses. Weight management in overweight DMD patients is indicated because excess adiposity burdens mobility and breathing, but only one study in two DMD patients has documented that weight reduction can be done safely. In the latter stages of the disease most DMD subjects become underweight because of an acceleration in skeletal muscle protein degradation relative to its synthesis. Studies of energy, protein and branched chain amino acid supplementation in DMD have yielded promising but inconclusive results, and more well-designed studies are needed in this area. Although there is currently no cure for DMD, studies on the role of nutritional therapy in increasing the quality of life in these patients are urgently needed. Studies in adults with various SP-NMDs indicate a reduction in fat-free mass and an increase in fat mass relative to controls. The newly developed method of air displacement plethysmography for measuring body composition is ideally suited for SP-NMD subjects because it requires very little effort and the measurement procedure is relatively fast. Dual energy x-ray absorptiometry technology has been proposed for distinguishing myogenic from neurogenic SP-NMDs from calculation of the fat-to-lean soft tissue ratio, which is higher in patients with myogenic muscular atrophy. Studies on the energy metabolism of ambulatory SP-NMD subjects indicate that their basal metabolic rate is either similar to or slightly lower than controls, but 24-hour energy expenditure is about 25% lower than controls. This reduction in 24-hour energy expenditure is due to a reduction in physical activity in SP-NMD. Studies examining the roles of energy expenditure, physical activity, and diet in the development of adiposity and risk for secondary chronic diseases in SP-NMD subjects are currently underway.


Cell cycle aberrations by alpha-synuclein over-expression and cyclin B immunoreactivity in Lewy bodies.
alpha-Synuclein is a presynaptic protein that accumulates abnormally in Lewy bodies of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Its physiological function and role in neuronal death remain poorly understood. Recent immunohistochemical studies suggest that cell cycle-related phenomena may play a role in the pathogenesis of Alzheimer's disease and perhaps other neurodegenerative disorders. In this investigation, we examined the effects of alpha-synuclein expression levels on cell cycle indices in PC12 cells engineered to conditionally induce alpha-synuclein expression upon withdrawal of doxycycline. Over-expression of alpha-synuclein resulted in enhanced proliferation rate and enrichment of cells in the S phase of the cell cycle. This was associated with increased accumulation of the mitotic factor cyclin B and down-regulation of the tumor suppressor retinoblastoma 2. Additionally, ERK1/2, key molecules in proliferation signaling, were highly phosphorylated. Immunohistochemical studies on postmortem brains revealed intense cyclin B immunoreactivity in Lewy bodies in cases with DLB and to a lesser extent in PD. We propose that elevated expression of alpha-synuclein causes changes in cell cycle regulators through ERK activation leading to apoptosis of postmitotic neurons. These changes in cell cycle proteins are also associated with ectopic expression of cyclin B in Lewy bodies.


The RNA world on ice: a new scenario for the emergence of RNA information.
The RNA world hypothesis refers to a hypothetical era prior to coded peptide synthesis, where RNA was the major structural, genetic, and catalytic agent. Though it is a widely accepted scenario, a number of vexing difficulties remain. In this review we focus on a missing link of the RNA world hypothesis-primitive miniribozymes, in particular ligases, and discuss the role of these molecules in the evolution of RNA size and complexity. We argue that prebiotic conditions associated with freezing, rather than "warm and wet" conditions, could have been of key importance in the early RNA world.


Negative view of the self and symptoms of depression in adolescents.
Although negative self-evaluation is a common symptom of depression in adolescents, there is little understanding of how the self is associated with depression. Beck (1967) proposed that a negative view of the self was a 'hallmark' of depression. In contrast Linville (1985; 1987) proposed that holding multiple aspects of the self was associated with lower levels of depression. The aim of this paper is to evaluate these two models of self and depression in adolescents. Young people aged 13-18 years (n = 822) reported symptoms of depression (the Mood and Feelings Questionnaire) and completed a measure of self-concept, the Twenty Statements Test (TST). We coded responses to the TST to reflect the valance (positive to negative) and the complexity of their self-concept (number of self-aspects). Valence, but not complexity, of self-concept was significantly associated with severity of depression symptoms. The valance of young people's self-concept accounted for 25% of the variance in depression symptoms. Adolescent's with more positive self-concept tended to have fewer symptoms of depression. The cross-sectional design of this study precludes any conclusions about the causal relationship between depression and negative self-evaluation; experimental and longitudinal research is needed to assess the causal direction of the relationship. The results of this study supported the cognitive model of depression. Negative self-evaluation may constitute a risk factor for depression in adolescents and could offer a potential target for prevention and early intervention in adolescents.


A comparative study of UHPLC/Orbitrap MS metabolomics profiles and biological properties of Asphodeline taurica from Bulgaria and Turkey.
The present investigation attempts to compare the pharmacological properties and phytochemical profile of four extracts (ethyl acetate, dichloromethane, methanol, and water) of Asphodeline taurica (Pall.) Endl. roots from Bulgaria and Turkey. The Bulgarian ethyl acetate extract displayed the highest antioxidant activity in the DPPH, CUPRAC, and phosphomolybdenum assay, and strongest inhibition against α-amylase and α-glucosidase. The Turkish aqueous extract exhibited the strongest ABTS scavenging and ferric reducing power while its methanol extract was the most effective acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitor. On the other hand, the Turkish dichloromethane extract showed the highest lipase inhibition. UHPLC/Orbitrap MS analysis showed a wide array of individual phenolics; six free anthraquinones, two bianthraquinones, three bianthracenes, three anthraquinone glycosides and one bianthracen glycoside were identified. The present data suggest that A. taurica roots can be considered as a valuable source of biologically active phytocompounds with functional properties for the cosmetic and pharmaceutical industries.


Microbial induced calcium precipitation based anaerobic immobilized biofilm reactor for fluoride, calcium, and nitrate removal from groundwater.
In this study, the anaerobic quartz sand fixed biofilm reactor containing Cupriavidus sp. W12 was established to simultaneously remove calcium (Ca2+), fluoride (F-) and nitrate (NO3-N) from groundwater. After 84 days of continuous operation, the optimum operating parameters and defluoridation mechanism were explored, and the microbial community structure under different pH environments were compared and analyzed. Under the optimal operation conditions (HRT of 6 h, initial Ca2+ concentration of 180 mg L-1, and pH of 7.0), the removal efficiencies of Ca2+, F-, and NO3-N were 58.97%, 91.93%, and 100%, respectively. Gas chromatography (GC) results indicate that N2 is the main gas produced by the bioreactor. Three-dimension excitation emission matrix fluorescence spectroscopy (3D-EEM) showed that extracellular polymers (EPS) are produced during bacterial growth and metabolism. The results of Scanning electron microscopy-energy dispersive spectrometer (SEM-EDS), X-ray diffraction (XRD), and Fourier transform infrared spectrometer (FTIR) demonstrated that the defluoridation mechanism is attributed to the synergetic effects of ion exchange, co-precipitation, and chemisorption. The comparative analysis of the microbial community structure under different pH conditions show that Cupriavidus is the dominant bacteria in the bioreactor throughout the experiment, and it shows a prominent advantage at pH of 7.0. This research provides an application foundation for anaerobic microbial induced calcium precipitation (MICP) bioremediation of Ca2+, F-, and NO3-N from groundwater.


Transcriptional patterns of growth factors and proto-oncogenes in human glioblastomas and normal glial cells.
To document over-expression of proto-oncogenes in tumors, it is necessary to determine the level of expression in the progenitor normal tissue. These studies compare the levels of nuclear transcription of a series of growth-factor related genes and proto-oncogenes in human glioblastoma cell lines with those in three normal glial cell populations. The unusual finding was that levels in the three normal glial cell populations varied considerably for several genes and thus overexpression of a specific gene in a tumor cell when compared to just one normal glial cell population would not necessarily represent overexpression. In this study, we compared the level of 17 genes in 7 tumors to the highest level of each gene found in any of three normal glial cell populations. Over-expression of PDGF-B in 4/7 glioblastoma cell lines, EGFR in 1/7, neu in 1/7 IGF-2 in 1/7 and ros in 2/7 was observed. The variation observed in the normal glial cell populations emphasizes the possibility that the normal glial cell populations represent different glial cell lineages and/or stages of differentiation and that the tumors could have arisen from different normal glial cells. Matching lineages of normal and tumor cells, probably by monoclonal antibody reactions, may be required to accurately define over-expression.


Kynurenic acid modulates experimentally induced inflammation in the trigeminal ganglion.
The trigeminal ganglion (TG) plays a central role in cranial pain. Administration of complete Freund's adjuvant (CFA) into the temporomandibular joint (TMJ) elicits activation of TG. Kynurenic acid (KYNA) is an endogenous excitatory amino acid receptor blocker, which may have an anti-inflammatory effect. We hypothesize that KYNA may reduce CFA-induced activation within the TG. A local inflammation was induced by administration of CFA into the TMJ in rats. KYNA and kynurenic acid amide 2 (KYNAA2) were intraperitoneally administered. We investigated changes of mitogen-activated protein kinases (MAPKs as ERK1/2, p38 and SAPK/JNK), NF-κB, CaMKII and DREAM, in addition to calcitonin gene-related peptide (CGRP) and its receptor components calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1) in the TG, with immunohistochemistry and Western blot at 2 and 10 days post-CFA injection. We showed CFA-induces increases in pERK1/2, pp38, CaMKII, NF-κB and DREAM immunohistochemistry after 2 and 10 days. KYNAA2 displayed stronger effects on MAPKs than KYNA. Increased expression of CaMKII, NF-κB and DREAM were found in the neurons. Western blot showed significantly increase in pERK expression at 10 days post-CFA, which decreased after 10 days of KYNA treatment. Two days post-CFA, a significantly increase in pp38 expression was found, which decreased after 2 days of KYNA and KYNAA2 treatment. The CFA-induced inflammatory model for the TG activation provided a time-related expression of MAPK (pERK1/2, pp38) and NF-κB. It involves both the neuronal and glial activation, which points to possible neuron-glia interactions during this process. The administration of the endogenous NMDA-receptor antagonists, KYNA and its derivative KYNAA2, resulted in the inhibition of the induced signaling system of the TG, which further points the importance of the glutamate receptors in this mechanism.


Contrast Pediatric Brain Perfusion: Dynamic Susceptibility Contrast and Dynamic Contrast-Enhanced MR Imaging.
Magnetic resonance (MR) perfusion is a robust imaging technique that assesses the passage of blood through the cerebral vascular network using a variety of techniques. The applications of MR perfusion have been expanded and is well suited to investigate cerebrovascular diseases and cerebral neoplastic processes in pediatric patients. Assessment of brain perfusion can augment the information obtained on conventional MR imaging and provides additional information on the biological and physiologic features of pediatric brain tumors. Similarly, MR perfusion can help guide the management of a variety of pediatric cerebrovascular diseases, including acute ischemic stroke and Moyamoya syndrome.


Cytoarchitecture, fiber connections, and ultrastructure of the nucleus pretectalis superficialis pars magnocellularis (PSm) in carp.
The cytoarchitecture, fiber connections, and ultrastructure of the nucleus pretectalis superficialis pars magnocellularis (PSm) were studied in cypriniform teleosts (Cyprinus carpio). The PSm is an oval nucleus in the pretectum. Medium-sized cells and synaptic glomeruli are the main components of the nucleus. A lesser number of small cells are also present. Most of the medium-sized cells form one or two cell layers on the periphery of the nucleus, and some cells are scattered among synaptic glomeruli in the nucleus. Cell bodies in the peripheral cell layer are pyriform and sprout a thick dendrite directed inward. The dendrite gives off fine dendritic branches, which are postsynaptic elements in synaptic glomeruli. The PSm projects to the ipsilateral corpus mamillare (CM) and sends collaterals to the ipsilateral nucleus lateralis valvulae (NLV). Axons of the PSm neurons have terminals with many varicosities in the CM, and collaterals in the NLV have cup-shaped terminals around the cell bodies of the NLV neurons. Following horseradish peroxidase (HRP) injections into the PSm, HRP-labeled cells are found ipsilaterally in the optic tectum, the nucleus tractus rotundus of Schnitzlein, and the nucleus ruber of Goldstein. The tecto-PSm projections are topographically organized. The rostral optic tectum projects mainly to the rostral portion of the PSm, and the caudal tectum projects to the caudal portion of the PSm. The ventral tectum sends fibers mainly to the ventral part of the PSm. The dorsomedial tectum projects to the medial part of the PSm, and the dorsolateral tectum projects to the lateral part of the PSm. Tectal projection neurons to the PSm are of only one type. The tectal cell body is pyriform and is situated in the superficial part of the ipsilateral stratum periventriculare (SPV). The tectal neurons have a long perpendicular dendrite, which branches out in the stratum opticum (SO). An axon emerges from the branching site in the SO. Judging from the dendritic branching pattern of the tectal projection neurons, we concluded that the PSm receives visual information from the optic tectum.


Platelet aggregation induced in the hamster cheek pouch by a photochemical process with excited fluorescein isothiocyanate-dextran.
Excitation of intravascular fluorescein isothiocyanate (FITC)-dextran by light induces platelet aggregation in arterioles of the hamster cheek pouch. Time to aggregate appearance (TAA) was found to be 45 +/- 5.6 sec in vessels of 10-14 micron diameter. The interindividual differences of TAA are low (coefficient of variance = 12.5%) and the TAA in individual animals can be reproduced for several hours with a coefficient of variance of 14.5%. TAA decreased at higher concentrations of intravascular FITC-dextran (r = 0.98) and with increased energy of the exciting beam. Scavengers of singlet oxygen, sodium azide, and trans-beta-carotene, delayed TAA. A scavenger of hydroxyl radicals, dimethyl sulfoxide, did not influence TAA. Acetylsalicylic acid showed a dose-dependent inhibitory effect from 1 (P less than 0.01) to 100 mg/kg body weight ia. The time-dependent increase of TAA after administration of 100 mg/kg acetylsalicylic acid is demonstrated; the dosage finally delayed TAA to longer than 360 seconds. The findings suggest that platelet formation, initiated by exciting FITC-dextran may involve local production of singlet oxygen. The consequently observed damaging process and the primary role of the endothelial cell damage are described. It is postulated that the described procedure provides a new model of intravascular platelet aggregation, characterized by a good reproducibility. A new damaging mechanism is proposed to study platelet aggregation in vivo.


Systematic change in global patterns of streamflow following volcanic eruptions.
Following large explosive volcanic eruptions precipitation decreases over much of the globe1-6, particularly in climatologically wet regions4,5. Stratospheric volcanic aerosols reflect sunlight, which reduces evaporation, whilst surface cooling stabilises the atmosphere and reduces its water-holding capacity7. Circulation changes modulate this global precipitation reduction on regional scales1,8-10. Despite the importance of rivers to people, it has been unclear whether volcanism causes detectable changes in streamflow given large natural variability. Here we analyse observational records of streamflow volume for fifty large rivers from around the world which cover between two and 6 major volcanic eruptions in the 20th and late 19th century. We find statistically significant reductions in flow following eruptions for the Amazon, Congo, Nile, Orange, Ob, Yenisey and Kolyma amongst others. When data from neighbouring rivers are combined - based on the areas where climate models simulate either an increase or a decrease in precipitation following eruptions - a significant (p<0.1) decrease in streamflow following eruptions is detected in northern South American, central African and high-latitude Asian rivers, and on average across wet tropical and subtropical regions. We also detect a significant increase in southern South American and SW North American rivers. This suggests that future volcanic eruptions could substantially affect global water availability.


Measuring change in the new NHS.
Measurement is an important factor in determining the extent to which clinical care works. This article summarises lessons learnt from the King's Fund Promoting Action on Clinical Effectiveness programme about effective means of gathering and using information to evaluate changes in care.


Meet the authors: Jianong Zhang and Haojie Huang.
Here, Molecular Cell talks to first author Jianong Zhang and co-corresponding author Haojie Huang about their paper, ''A lncRNA from the FTO locus acts as a suppressor of the m6A writer complex and p53 tumor suppression signaling'' (in this issue of Molecular Cell) and their scientific journeys until now.


S Fas in bronchoalveolar lavage fluid of patients with sarcoidosis in relation to cigarette smoking.
Sarcoidosis is a multiorgan granulomatous disease with frequent spontaneous remission. Apoptosis is postulated to participate in the granuloma resolution. Soluble Fas (sFas) is known to inhibit Fas-induced apoptosis. The aim of this study was to determine the sFas concentration in the BALf of ever smoking (S) and never smoking (NS) patients with sarcoidosis. We investigated 57 patients with confirmed SA: 36 NS and 21 S. The sFas concentration was measured by ELISA method. The sFas concentration was lower in the BALf of patients S group compared with NS (median values 68.3 vs. 96.1 pg/mL, p=0.07) and it was significantly lower in active smokers when compared with NS (62.9 vs. 96.1 pg/mL, p=0.03). There was a significant correlation between sFas concentration and proportion of lymphocytes and negative relation with macrophage proportion. Lower concentration of sFas in smoking SA patients may result in higher apoptosis rate of inflammatory cells and hereby promote resolution of granulomas.


Progressive multifocal leukoencephalopathy and the spectrum of JC virus-related disease.
Progressive multifocal leukoencephalopathy (PML) is a devastating CNS infection caused by JC virus (JCV), a polyomavirus that commonly establishes persistent, asymptomatic infection in the general population. Emerging evidence that PML can be ameliorated with novel immunotherapeutic approaches calls for reassessment of PML pathophysiology and clinical course. PML results from JCV reactivation in the setting of impaired cellular immunity, and no antiviral therapies are available, so survival depends on reversal of the underlying immunosuppression. Antiretroviral therapies greatly reduce the risk of HIV-related PML, but many modern treatments for cancers, organ transplantation and chronic inflammatory disease cause immunosuppression that can be difficult to reverse. These treatments - most notably natalizumab for multiple sclerosis - have led to a surge of iatrogenic PML. The spectrum of presentations of JCV-related disease has evolved over time and may challenge current diagnostic criteria. Immunotherapeutic interventions, such as use of checkpoint inhibitors and adoptive T cell transfer, have shown promise but caution is needed in the management of immune reconstitution inflammatory syndrome, an exuberant immune response that can contribute to morbidity and death. Many people who survive PML are left with neurological sequelae and some with persistent, low-level viral replication in the CNS. As the number of people who survive PML increases, this lack of viral clearance could create challenges in the subsequent management of some underlying diseases.


Park-based obesity intervention program for inner-city minority children.
To assess an intervention strategy--a 6-week obesity intervention program, Project KidFIT, at 3 Houston, Texas park centers--to address the obesity epidemic in minority children. Project KidFIT is a physical fitness and nutrition education program aimed at promoting the benefits of physical activity and improving nutrition knowledge in overweight (body mass index [BMI] > or = 95th percentile) minority children. A total of 120 minority children (77 boys and 43 girls; mean age, 10.1 years) were enrolled in the program. Approximately 71% of these children were at risk of overweight (BMI > or = 85th percentile), and 54% were overweight. Decreases in body weight (0.3 +/- 0.2 kg [mean +/- standard error]) and BMI (0.1 +/- 0.1 kg/m2) were detected in the overweight children, whereas increases in body weight (0.4 +/- 0.1 kg) and BMI (0.2 +/- 0.1 kg/m2) were observed in the children with normal body weight (BMI < 85th percentile but > 5th percentile). Significant improvements (P < .05) in flexibility, muscular endurance, and muscular strength were detected in all children, regardless of weight status. The findings suggest that the city park-based KidFIT program might be effective at promoting stabilization for body weight and BMI and improving physical activity performance and nutrition knowledge in overweight minority children.


Bio-evaluation of fluoro and trifluoromethyl-substituted salicylanilides against multidrug-resistant S. aureus.
Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Staphylococcus aureus (VRSA) are primary causes of skin and soft tissue infections worldwide. To address the emergency caused due to increasing multidrug-resistant (MDR) bacterial infections, a series of novel fluoro and trifluoromethyl-substituted salicylanilide derivatives were synthesized and their antimicrobial activity was investigated. MIC data reveal that the compounds inhibited S. aureus specifically (MIC 0.25-64 µg/mL). The in vitro cytotoxicity of compounds with MIC < 1 µg/mL against Vero cells led to identification of four compounds (20, 22, 24 and 25) with selectivity index above 10. These four compounds were tested against MDR S. aureus panel. Remarkably, 5-chloro-N-(4'-bromo-3'-trifluoromethylphenyl)-2-hydroxybenzamide (22) demonstrated excellent activity against nine MRSA and three VRSA strains with MIC 0.031-0.062 µg/mL, which is significantly better than the control drugs methicillin and vancomycin. The comparative time-kill kinetic experiment revealed that the effect of bacterial killing of 22 is comparable with vancomycin. Compound 22 did not synergize with or antagonize any FDA-approved antibiotic and reduced pre-formed S. aureus biofilm better than vancomycin. Overall, study suggested that 22 could be further developed as a potent anti-staphylococcal therapeutic.


Classification criteria for rheumatoid arthritis.
The development of classification schemes for RA in the last 40 years has followed the increasingly precise understanding of the nature of the clinical disease and the recognition of the different requirements of classification methods in clinic and population settings. In published studies of RA in clinic patients the most widely used criteria sets have been the 1958 ARA (ACR) criteria and its 1961 adaptation (the Rome (active) criteria). These sets classified disease as 'classical', 'definite', 'probable' and 'possible' RA based on criteria comprising clinical, serological, radiological and histological features (the latter were dropped from the Rome criteria set because of their impracticality). More recently, a new criteria set (the 1987 ARA criteria) has been developed using statistical techniques. This set was derived using RA cases and controls attending hospital clinics. It is based on the earlier criteria sets but accommodates the characteristic pattern of joint involvement in RA more precisely. The criteria recognize only the single disease category of 'rheumatoid arthritis'. In validation studies, the 1987 criteria set has been found to have enhanced specificity over earlier schemes in clinic-based studies of RA. The sensitivity may, however, be reduced, in particular in studies of early disease. The application of classification criteria for case recognition in the population and family studies of RA has proved more problematic. In these settings, there is the additional requirement to recognize individuals with remitted and inactive disease as RA cases. The 1966 New York criteria were developed for this specific purpose, however their format proved cumbersome and they have not been widely adopted. The 1987 criteria set is insufficiently sensitive to recognize inactive disease if the criteria are applied exactly as they have been defined. The sensitivity of the 1987 criteria set is, however, substantially enhanced if the criteria are adapted to incorporate features of past disease activity, for example by allowing deformity to substitute for swelling and by incorporating data on the past occurrence of rheumatoid factor and rheumatoid nodules. Developments in the immunology and genetics of RA may in the future provide more accurate tools for classification and may lead to recognition of more precise disease subsets. At present, however, the 1987 ARA criteria provide the most appropriate basis for case recognition in both clinic and population-based studies.


USP14 governs CYP2E1 to promote nonalcoholic fatty liver disease through deubiquitination and stabilization of HSP90AA1.
Nonalcoholic fatty liver disease (NAFLD) begins with excessive triglyceride accumulation in the liver, and overly severe hepatic steatosis progresses to nonalcoholic steatohepatitis (NASH), which is characterized by lipid peroxidation, inflammation, and fibrosis. Ubiquitin-specific proteinase 14 (USP14) regulates inflammation, hepatocellular carcinoma and viral infection, but the effect of USP14 on NAFLD is unknown. The aim of this study was to reveal the role of USP14 in the progression of NAFLD and its underlying mechanism. We demonstrated that hepatic USP14 expression was significantly increased in NAFLD in both humans and mice. Hepatic USP14 overexpression exacerbated diet-induced hepatic steatosis, inflammation and fibrosis in mice, in contrast to the results of hepatic USP14 knockdown. Furthermore, palmitic/oleic acid-induced lipid peroxidation and inflammation in hepatocytes were markedly increased by USP14 overexpression but decreased by USP14 knockdown. Notably, in vivo or in vitro data show that USP14 promotes NAFLD progression in a cytochrome p4502E1 (CYP2E1)-dependent manner, which exacerbates hepatocyte oxidative stress, impairs the mitochondrial respiratory chain and inflammation by promoting CYP2E1 protein levels. Mechanistically, we demonstrated by immunoprecipitation and ubiquitination analysis that USP14 inhibits the degradation of heat shock protein 90 alpha family class A member 1 (HSP90AA1) by decreasing its lysine 48-linkage ubiquitination. Meanwhile, upregulation of HAP90AA1 protein promotes CYP2E1 protein accumulation. Collectively, our data indicate that an unknown USP14-HSP90AA1-CYP2E1 axis contributes to NAFLD progression, and we propose that inhibition of USP14 may be an effective strategy for NASH treatment.


NecroX-5 suppresses IgE/Ag-stimulated anaphylaxis and mast cell activation by regulating the SHP-1-Syk signaling module.
IgE/Ag-stimulated mast cells release various pro-allergic inflammatory mediators, including histamine, eicosanoids, and pro-inflammatory cytokines. NecroX-5, a cell permeable necrosis inhibitor, showed cytoprotective effects in both in vitro and in vivo models. However, the anti-allergic effect of NecroX-5 has not yet been investigated. The aims of this study were to evaluate the anti-allergic activity of NecroX-5 in vivo and to investigate the underlying mechanism in vitro. The anti-allergic activity of NecroX-5 was evaluated in vitro using bone marrow-derived mast cells (BMMCs) and IgE receptor-bearing RBL-2H3 or KU812 cells and in vivo using a mouse model of passive anaphylaxis. The levels of histamine, eicosanoids (PGD2 and LTC4 ), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were measured using enzyme immunoassay kits. The mechanism underlying the action of NecroX-5 was investigated using immunoblotting, immunoprecipitation, and gene knockdown techniques. NecroX-5 markedly inhibited mast cell degranulation and the synthesis of eicosanoids, TNF-α, and IL-6 by suppressing the activation of Syk, LAT, phospholipase Cγ1, MAP kinases, the Akt/NF-κB pathway, and intracellular Ca(2+) mobilization via the activation of phosphatase SHP-1. Oral administration of NecroX-5 effectively suppressed mast cell-dependent passive cutaneous and systemic anaphylactic reactions in a dose-dependent manner. NecroX-5 might be a potential candidate for the development of a novel anti-allergic agent that suppresses IgE-dependent mast cells signaling.


Distance between the center of the FAZ measured automatically and the highest foveal bulge using OCT-angiography in elderly healthy eyes.
The center of the fovea, termed the foveola, is the area of highest visual acuity, has the highest density of cone photoreceptors. We investigated the distance between the automatically-determined center of the foveal avascular zone (FAZ) and the manually-determined highest foveal bulge (FB) point using single swept-source optical coherence tomography angiography (OCTA) instrument. This cross-sectional study included 49 eyes of 49 individuals (34 women and 15 men; median age: 68 years) with no history of ocular disorders. The FAZ in the superficial capillary plexus was automatically determined using the Kanno-Saitama macro method, and the center of the FAZ was automatically determined using ellipse approximation. Another candidate foveal center, the highest FB point, was determined manually on the serial cross-sectional B-scan images. As a result, the foveal center was manually identified as the highest FB point on B-scan OCTA images. The center of the FAZ was more likely to be located inferior to the highest FB point (p = 0.031). In participants with a total (linear) distance of more than 50 μm between the center of the FAZ and the highest FB point, the displacement was significantly more in the horizontal direction than in the vertical direction (p = 0.017). These results can be applicable to further studies regarding the spatial relationships between the center of the FAZ and the highest FB point in various macular diseases or previously-treated eyes.


Cytoskeleton-associated Pr65gag and retrovirus assembly.
Our studies have shown a rapid and specific association of Rauscher murine leukemia virus (R-MuLV) precursor polyprotein Pr65gag with cytoskeletal elements in infected mouse fibroblasts. The Pr65gag associated with Nonidet P-40 (NP-40)-insoluble cytoskeletal structures appears to be subphosphorylated in comparison to NP-40-soluble Pr65gag. The association of Pr65gag with skeletal elements can be disrupted by extraction of the cytoskeleton with sodium deoxycholate, an ionic detergent, or with buffers of high ionic strength. Both the skeleton-associated Pr65gag and its NP-40-soluble counterpart can be labeled with [3H]palmitate, indicating their probable association with lipids presumably in the plasma membrane. Pr65gag molecules bound to skeletal elements in the infected cell appear to be more stable to proteolytic processing than NP-40-soluble Pr65gag. While the association of Pr65gag with cytoskeleton elements in the cell is neither increased nor decreased by blocking virus assembly and release with interferon, Pr65gag appears to accumulate in the cytoskeleton-enriched fraction of cells chronically infected with a temperature sensitive mutant of R-MuLV (ts 17) when such cells are grown at the nonpermissive temperature. Based on these and other results, we have proposed a model for the active role of cytoskeleton associated Pr65gag in retrovirus assembly.


[Teaching simulation to trainers].
Many trainers wish to integrate simulation into their teaching. Aside from the learning difficulties associated with some simulators, this practice requires the trainer to receive specific training, in order to avoid any risk of a negative or even harmful, learning experience.


Presurgical assessment of memory-related brain structures: the Wada test and functional neuroimaging.
Medial temporal lobe structures are known to play a major role in memory processing. Recent work has revealed that extratemporal structures (e.g. the frontal lobe and thalamus) may also be important in memory function. In candidates for epilepsy surgery, particularly in those with temporal lobe seizures, presurgical evaluation of memory function is essential, since seizures may originate in the neural substrate that is critical for memory. In this article, we review the tools used for presurgical evaluation and their contribution to the understanding of memory function, focusing on the Wada test, [18F]fluorodeoxy-glucose positron emission tomography ([18F]FDG-PET) and functional magnetic resonance imaging (fMRI). We also explore perspectives on future studies that may elucidate the role of the temporal and extratemporal structures in memory function and the mechanisms of cerebral plasticity.


Use of Lisdexamfetamine or Amphetamine? Interpretation of Chiral Amphetamine Analyses.
Amphetamine is frequently detected in forensic toxicological cases. Differentiating between the two isomers of amphetamine (d-amphetamine and l-amphetamine) and determining their relative proportion are fundamental to correctly interpret the results of toxicological analyses. The aim of this study was to examine the profile of amphetamine as well as storage stability of the isomers in authentic samples from patients chronically treated with lisdexamfetamine (LDX), the most prescribed medical amphetamine product in Sweden. Blood and urine samples were collected from 18 patients. The samples were analyzed with an achiral (racemate) method for quantification of amphetamine and with a chiral method to determine the proportion of each isomer of amphetamine. The median daily dose of LDX was 40 mg (range, 20-70 mg). The median amphetamine concentration was 0.06 µg/g (range, 0.02-0.15 µg/g) in blood and 6 µg/mL (range, 1-22 µg/mL) in urine. Only d-amphetamine was found in the blood and urine samples from the included patients. Furthermore, no formation of l-amphetamine occurred during the storage for 3 months at 4°C, 9 months at -20°C and three freeze-thaw cycles. The results from this study may be helpful in the interpretation of whether the source of identified amphetamine in biological samples is from LDX drug intake or not.


Unlocking bat immunology: establishment of Pteropus alecto bone marrow-derived dendritic cells and macrophages.
Bats carry and shed many emerging infectious disease agents including Ebola virus and SARS-like Coronaviruses, yet they rarely display clinical symptoms of infection. Bat epithelial or fibroblast cell lines were previously established to study the bat immune response against viral infection. However, the lack of professional immune cells such as dendritic cells (DC) and macrophages has greatly limited the significance of current investigations. Using Pteropus alecto (P. alecto) GM-CSF plus IL4, FLT3L and CSF-1, we successfully generated bat bone marrow-derived DC and macrophages. Cells with the phenotype, morphology and functional features of monocyte-derived DC, bona fide DC or macrophages were obtained in GM-CSF/IL4, FLT3L or CSF-1 cultures, respectively. The successful generation of the first bat bone marrow-derived immune cells paves the way to unlocking the immune mechanisms that confer host resilience to pathogens in bats.