Simultaneous Single-staged Repair of Anorectal Malformation with Tracheoesophageal Fistula: Lessons Learned.
Anorectal malformation (ARM) associated esophageal atresia (EA) with tracheoesophageal fistula (TEF) spawns special therapeutic propositions. The outcome of these patients banks on numerous factors. We performed this study with an aim to compare the outcome of single-staged simultaneous primary repair of both anomalies versus staged repair of these disorders. Retrospective review of cases with ARM and associated EA with TEF managed over a period of 5 years from July 2010 to June 2015 after ethical approval was undertaken. Patients were split into two groups based on whether they underwent staged repair (Group A) or single-staged simultaneous primary repair of ARM with TEF (Group B). Patient's records were analyzed for demography, weight, gestational age, associated anomaly, preoperative and postoperative sepsis screen results, early and late postoperative complications (at least up to 1 year of age). Patient's Kelly score for continence at the age of 3 years or more was compared. A total of 28 were included in the study. Among these, 17 were managed with staged procedure for ARM (Group A), whereas 11 underwent simultaneous single-stage repair of ARM with TEF (Group B). No difference in continence score was observed in outcome between the two groups (P = 0.96). Overall mortality in Group A at 1-year follow-up was 52.9% and in Group B was 43.4%. The simultaneous single-staged primary repairs result in better long-term outcome in our setup.


Retrospective evaluation of elevator-related injuries in dogs (2015-2020): 13 cases.
To describe elevator-related injuries in dogs. Retrospective study, August 2015 to October 2020. Four urban referral and emergency veterinary facilities. Thirteen client-owned dogs presenting with injuries sustained while using an elevator. None. Thirteen dogs were treated for elevator-related injuries. The mean age of this population was 4.9 ± 4.1 years. Median body weight was 4.3 kg (range = 1.5-32 kg). Dogs in this study were significantly smaller than dogs presenting for all types of trauma during the same study period found in the Veterinary Committee on Trauma registry (VetCOT) (median = 14.5 kg, range = 0.1-141; P = 0.038). There was no difference in age between this study population and dogs presenting for trauma in the VetCOT registry (median = 4.2 years, range = 0.1-26.4, P = 0.7358). Nine dogs sustained a crush injury (69%), and 7 of these dogs received surgical intervention. Four dogs experienced leash entrapment in the elevator doors (31%), and none required surgical intervention. Two of these 4 dogs required inpatient hospital care. No deaths occurred in either group. Injuries that can be sustained by dogs in an elevator include crush injuries from doors closing on limbs or tails and injury due to leash entrapment in an elevator door. Many elevator-related injuries required surgical intervention, and recovery was often protracted. All dogs survived to hospital discharge in the present study, and none of the injuries in these dogs had serious long-term consequences.


Anemia, an independent predictive factor for amputation and mortality in patients hospitalized for peripheral artery disease.
Anemia is associated with poorer outcome in coronary artery disease (CAD) and heart failure (HF), but data on patients with peripheral artery disease (PAD) are scarce, especially regarding the local (limb) prognosis. It was hypothesized that anemia is associated with poorer prognosis in patients hospitalized for PAD, and this relationship would be proportional to the severity of the anemia. Prospective cohort study. The Cohorte des Patients Artéritiques (COPART) is a multicenter registry of patients hospitalized for PAD in three university hospitals in southwestern France. Clinical and biological data were collected at entry. Patients were followed up to 1 year. Anemia was defined by Hb < 8.2 mmol/L in men and <7.6 mmol/L in women. The primary outcome was 1-year survival free from major amputation. The secondary outcome was 1-year major amputation. Data of 925 consecutive patients (70.7 ± 12.8 years, 29.2% females) were analyzed. Patients were hospitalized either for revascularization or medical therapy, with Rutherford categories 3 (25%), 4 (9.1%), 5 or 6 (55.1%) as well as acute limb ischemia (10.8%). Anemia was present in 471 patients (50.9%). These patients were significantly older, with higher rates of hypertension, diabetes, clinical CAD, HF, chronic kidney disease, and cancer, and with lower rates of smoking and dyslipidemia than their counterparts (p < .05 for all). In multivariate models, anemia was significantly and independently associated (p < 0.001) with death and amputation (HR 1.44; 95% CI 1.15-1.80) with similar findings for secondary outcomes. A lower level of hemoglobin is associated with a higher risk of mortality and amputation (HR 1.20; 95% CI 1.09-1.32). Anemia and its severity are independent predictors of mortality and limb loss in patients hospitalized for PAD.


Drug discrimination studies.
Opioid agonists and agonist/antagonists comprise a heterogeneous body of compounds that can be partitioned into at least three groups on the basis of their discriminative stimulus properties in several animal species: (1) stimulus effects similar to those of morphine or fentanyl and blocked completely by low doses of antagonists, such as naloxone and naltrexone; (2) stimulus effects similar to those of ethylketocyclazocine or nalorphine and blocked by higher doses of antagonists; (3) stimulus effects similar to those N-allylnormetazocine or phencyclidine and not blocked by antagonists. This diversity of stimulus properties is consistent with other evidence that multiple populations of receptors mediate the actions of opioids. In man, drugs in group 1 produce subjective effects that are entirely morphine-like and highly reinforcing whereas drugs in groups 2 and 3 produce dysphoric and psychotomimetic subjective effects. Thus, discriminative stimulus properties of opioids appear to reflect drug actions at the neuronal level that are directly relevant to potential for abuse in man.


Adenocarcinoma in situ arising in vulvar papillary hidradenoma: report of 2 cases.
Adenocarcinoma in situ rarely occurs in vulvar papillary hidradenoma. We encountered 2 cases of adenocarcinoma in situ arising in a papillary hidradenoma of the vulva. Both patients were asymptomatic women, aged 83 and 92 years, who presented with nodules (1.0 and 2.0 cm) on the vulva. Macroscopically, the lesions seemed tan-pink, fleshy, and well circumscribed. One tumor ulcerated the overlying epidermis. On microscopic examination, the tumors showed focal features of benign hidradenoma at the periphery with transitions into areas of increasing cytologic atypia that fulfilled criteria for adenocarcinoma in situ similar to that seen in the breast. One tumor showed a predominant cribriform pattern with moderate atypia and many mitoses; the other showed a mixture of cribriform and micropapillary patterns, mild atypia, and fewer mitotic figures. There was no evidence of destructive invasion or desmoplasia in either tumor. Both lesions show areas strongly immunoreactive for mammaglobin and gross cystic disease fluid protein 15 as well as estrogen and progesterone receptor protein in 1 case. There was no evidence of benign ectopic breast tissue within or adjacent to the neoplasms. Both patients underwent local excision with no evidence of tumor recurrence at 15 and 32 months of follow-up. The fact that these tumors displayed morphologic and immunohistochemical features that resembled ductal carcinoma in situ of the breast demonstrates the close homology between papillary hidradenoma and breast epithelium. In the absence of invasion, our experience suggests that these tumors can be cured by local excision.


Bilateral maxillary canine-first premolar transposition in permanent dentition.
Transposition is a dental anomaly characterized by the exchange of position between two adjacent teeth, especially in relation to their roots, or development and eruption of a tooth in a position normally occupied by a nonadjacent tooth. Transposition of the maxillary canine and first premolar has a low prevalence in the population and it primarily affects maxillary canines and premolars. The aetiology of the transposition remains unclear, although it has been associated with genetic factors. It may also be related to a combination of localised factors such as malformation of adjacent teeth, tooth agenesis, retention of the deciduous canine and a history of local trauma. If uncorrected, the results are often both functionally and esthetically unsatisfactory. This case report presents treatment of a female patient with complete bilateral transposition of maxillary canine and premolar. The patient was treated orthodontically with non-extraction fixed mechanotherapy by simulation of maxillary first premolar as canine bilaterally.


Effects of cyclophosphamide, levamisole and concanavalin A on the in vitro IgE biosynthesis.
The effects of cyclophosphamide (200 microgram/ml), levamisole (1 microgram/ml) and Concanavalin A (10 microgram/ml) on the in vitro IgE biosynthesis of lymphocytes from 2 allergic children and six healthy adults were studied. The capability of the IgE biosynthesis was enhanced by cyclophosphamide in nine allergic children, suppressed by levamisole in three and not changed by Concanavalin A. The three patients who showed in vitro suppressed IgE synthesis by levamisole had been treated with levamisole for more than three months but only one revealed decreased serum IgE.


Psychiatric comorbidities in alcohol use disorder.
Alcohol use disorder is a major contributor to the morbidity and mortality burden worldwide. It often coexists with other psychiatric disorders; however, the nature of this comorbidity is still a matter of debate. In this Series paper, we examine the main psychiatric disorders associated with alcohol use disorder, including the prevalence of co-occurring disorders, the temporal nature of the relationship, and mechanisms that might explain comorbidity across the lifespan. Overall, this disorder co-occurs with a wide range of other psychiatric disorders, especially those disorders involving substance use and violent or aggressive behaviour. The causal pathways between alcohol use disorder and other psychiatric disorders are heterogeneous. Hypotheses explaining these relationships include reciprocal direct causal associations, shared genetic and environmental causes, and shared psychopathological characteristics of broader diagnostic entities (eg, externalising disorders). Efforts to untangle the associations between alcohol use disorder and other disorders across the lifespan remain a crucial avenue of research.


Safe usage of anakinra and dexamethasone to treat refractory hemophagocytic lymphohistiocytosis secondary to acute disseminated histoplasmosis in a patient with HIV/AIDS.
Hemophagocytic lymphohistiocytosis (HLH) is a serious life-threatening disease if not recognised early. In patients with HIV/AIDS, this association has been reported following acute opportunistic infections, including histoplasmosis. However, optimal treatment is not known. We describe a male aged 46 years with AIDS who developed HLH following acute disseminated histoplasmosis. Presenting symptoms included fever, hepatosplenomegaly and pancytopenia. Bone marrow biopsy confirmed HLH. Initially, he was refractory to the treatment with amphotericin B, antiretroviral therapy and intravenous immunoglobulin (IVIG). Anakinra, an interleukin-1 receptor antagonist, and dexamethasone were initiated. He improved clinically, did not exhibit any harmful effects and ultimately was discharged from the hospital. This, we believe, is the first reported treatment of HLH with anakinra in a patient with AIDS and acute disseminated histoplasmosis.


Comparison of bone grafting materials in human extraction sockets: clinical, histologic, and histomorphometric evaluations.
Although there are a number of bone replacement graft materials that are currently available for clinical use, there are few studies that directly compare efficacy among graft treatments before implant placement. The purpose of this report was to compare 3 bone replacement graft materials (PepGen P-15 228 FLOW [DENTSPLY Friadent CeraMed, Lakewood, CO], Puros [Zimmer Dental, Carlsbad, CA], and C-Graft 228 [Clinician's Preference, Golden, CO]) for bone formation by clinical, histologic, and histomorphometric evaluation. In this prospective, intraoral pilot study, 13 maxillary sockets in 2 patients (both smokers) were grafted immediately after tooth extraction with C-Graft 228, Puros, or PepGen P-15 228 FLOW (containing additional PepGen P-15 228 particles; FLOW PUTTY). After 4 months, bone cores were retrieved and analyzed histologically. PepGen P-15 228 FLOW PUTTY produced a significantly (P <0.01) higher amount of vital bone than C-Graft 228 or Puros. The amount of vital bone for FLOW PUTTY was 12-fold higher than for C-Graft 228 and 4-fold higher than Puros. Of 7 FLOW PUTTY treated sites, 7 showed >14% vital bone versus 0 of 3 C-Graft 228 and 0 of 3 Puros treated sites. FLOW PUTTY treated sites showed new vital bone between particles of residual graft. C-Graft 228 treated sites showed residual particles in a background of connective tissue with very little bone. Puros treated sites showed nonvital bone particles in a background of connective tissue, with some new vital bone forming around the nonvital bone. PepGen P-15 228 FLOW PUTTY produced significantly greater vital bone as compared to Puros and C-Graft 228 after 4 months. A larger clinical study is required to confirm these results.


Blue rubber bleb nevus syndrome: extensive small bowel vascular lesions responsible for gastrointestinal bleeding.
Blue Rubber Bleb Nevus Syndrome is a rare condition characterised by multiorgan venous malformations, in particular of cutaneous area and the gastrointestinal (GI) tract. We report here a child with chronic iron deficiency anaemia, melena and skin lesions. She had severe hypochromic microcytic anaemia. Upper and lower endoscopy revealed hundreds of red-bluish polypoid lesions involving the entire GI tract primarily of the small bowel. Due to localisation of the most severe lesions, the patient responded well to surgical treatment, allowing a sustained clinical remission.


Activation of Akt/FoxO signaling pathway contributes to induction of neuroprotection against transient global cerebral ischemia by hypoxic pre-conditioning in adult rats.
It is well established that pre-conditioning protects neuronal injury against ischemia. However, the molecular mechanisms underlying ischemic tolerance are not completely understood. The purpose of the present study was to investigate the role of Akt/forkhead transcription factor, class O (FoxO) pathway in hypoxic pre-conditioning (HPC) using a newly developed HPC to transient global cerebral ischemia (tGCI) model in adult rats. HPC for 30-120 min significantly reduced cell death in the CA1 subregion after 10 min of tGCI. HPC was effective only when applied 1-4 days before ischemia. The maximum protection was observed with 30 min of hypoxia and 1 day interval between hypoxia and ischemia. The phosphorylated Akt and FoxOs measured by western blot and immunohistochemistry were significantly increased after hypoxia-ischemia except for a transient decrease in the HPC group. Lateral ventricular infusion of LY294002 before HPC blocked the increase in phosphorylated Akt and FoxOs and increased neuronal damage in HPC animals. These results suggest that pre-exposure to hypoxia induces protection against tGCI in adult rats. Activation of Akt results in the inactivation of FoxOs which may mediate ischemic tolerance after HPC.


[Are the new drugs for treatment of Alzheimer's disease useful?].
In recent years several acetylcholinesterase inhibitor drugs have been developed for the treatment of Alzheimer s disease. These are expensive and their usefulness is doubtful. OBJECTIVE. We wish to review the evidence available with regard to the efficacy and effectiveness of the anticholinesterase drugs permitted in Spain. DEVELOPMENT. We review the controlled clinical trials, systematic reviews and meta-analysis published on the anticholinesterases permitted in Spain (tacrine, donepezil and rivastingmine), and also the publications on their effectiveness and efficacy. CONCLUSIONS. The evidence available seems to show that these drugs are effective in producing modest but real cognitive improvement in persons with mild and moderate Alzheimer s disease (Type 1 evidence). Cognitive improvement has also been observed in everyday clinical practice. Use of these drugs may be associated with a reduction in the costs associated with this disease. These drugs are useful and should be used in persons with mild or moderate Alzheimer s disease, without any contra-indication.


Can dynamic contour tonometry and ocular pulse amplitude help to detect severe cardiovascular pathologies?
We demonstrate the close relationship between a conspicuous ocular pulse amplitude and severe underlying cardiovascular disease. Two otherwise symptom-free glaucoma patients without any previously diagnosed underlying cardiovascular pathology but with a conspicuous ocular pulse amplitude and who underwent routine examinations in our glaucoma department were referred to the appropriate specialty for further diagnostic procedures. In both patients, the diagnosis of a tachyarrhythmia was made as suspected on dynamic contour tonometry measurements. In addition to medical treatment, one patient underwent electric cardioversion and the second patient was scheduled for pacemaker implantation. A third patient with an unexpected high ocular pulse amplitude despite severe cardiovascular pathology underwent major surgery due to an aortic aneurysm. Carotid stenosis was diagnosed due to side differences in ocular pulse amplitude as well. Ocular pulse amplitude might be a noninvasive and affordable screening tool and could be used to detect severe cardiovascular disease. A prospective study including a larger number of patients is needed to prove this hypothesis.


Measurement of oxygen solubility in fermentation media: a colorimetric method.
Methods of measuring oxygen solubility in culture media are scarce, and those available are tedious to apply. A simple colorimetric assay was developed and applied to the analysis of oxygen solubility during alcoholic fermentation. The method was based on the consumption of oxygen by glucose oxidase activity and the production of the pink quinone of syringaldazine by coupled peroxidase activity. Color formation at 526 nm progressed through an optimum that was a linear function of the oxygen added to the assay. Sensitivity was maximized by operating at pH 7 and limiting the medium sample volume added. Each assay took 10-15 min to prepare and react. Reaction time was minimized by using abundant glucose and enzyme concentrations. Data obtained by the assay developed showed good agreement with published oxygen solubilities in water and selected media at various temperatures. Subsequent analyses of fermentation broths indicated falling sugar concentration to be primarily responsible for increases in oxygen solubility during fermentation. For example, during fermentations started with 230 g/L xylose or glucose, oxygen solubility could increase by 41% due to sugar consumption alone. This procedure can provide the solubility data needed to accurately calibrate in-line electronic probes for monitoring dissolved oxygen concentration during fermentation processes.


[Anaphylactic shock caused by shredded rizinus beans. Case report].
A 66 year old man from Krefeld experienced shock while tearing open a sack full of fertilizer containing shredded castor beans. After emergency treatment of shock, sensitisation to castor bean was later demonstrated by scratch testing.


[Latent structure of depression in the elderly: a taxometric analysis].
This study aimed to investigate the latent structure of depression with a non-clinical sample of elderly, using taxometric analysis. The latter consists of a family of statistical procedures conceived for testing whether a given psychological construct is best represented by categories or dimensions in which individuals vary. The sample consisted of 570 elderly with a mean age of 71.9 years (SD = 7.45), who answered the Brazilian version of the Geriatric Depression Scale, a cognitive test, and demographic questions. Three taxometric procedures were used: Mean Above Minus Below A Cut (MAMBAC), Maximum Eigenvalue (MAXEIG), and Latent Mode (L-mode). Sets of simulated categorical and dimensional data, along with the comparison curve fit indices (CCFI), oriented the study data's interpretation. The results with the three techniques pointed to a better fit with the dimensional format as opposed to the taxonic one, that is, depression represented better as a syndrome in which subjects are distributed along a continuum rather than as a discrete diagnostic entity.


Hemodynamics and epoprostenol use are associated with thrombocytopenia in pulmonary arterial hypertension.
Thrombocytopenia develops in some patients with advanced pulmonary arterial hypertension (PAH) while receiving IV epoprostenol therapy. In this study, we evaluate whether epoprostenol use, other PAH medication use, hemodynamics, or PAH etiology are associated with thrombocytopenia in PAH. Platelet counts were evaluated in 47 PAH patients receiving IV epoprostenol, and in 44 patients with an inadequate response to initial therapy with oral agents in a cross-sectional study. Associations between thrombocytopenia (platelet count < 150,000/mL) and epoprostenol use, hemodynamics, PAH etiology, and use of other PAH medications were evaluated in univariable and multivariable analyses. PAH subtypes included idiopathic (69%), fenfluramine (18%), connective tissue disease (10%), and congenital heart disease (2%)-associated PAH. Thrombocytopenia was observed in 34% of patients treated with epoprostenol, compared with 15% of patients receiving oral therapy (odds ratio [OR], 2.9; p < 0.05), and the association between epoprostenol and thrombocytopenia remained significant after adjustment for differences in hemodynamics (OR, 5.0; p < 0.05). Right atrial pressure (OR, 1.12 per mm Hg; p < 0.05) and mixed venous oxygen saturation (Svo(2)) [OR, 0.92 per percentage; p < 0.05] were also associated with thrombocytopenia in univariable analyses; after logistic regression analysis, both the use of epoprostenol and Svo(2) were independently associated with thrombocytopenia. In a separate analysis including only patients with current or prior epoprostenol use, epoprostenol dose and right atrial pressure were inversely associated with platelet count. Epoprostenol use and severity of hemodynamic abnormalities are associated with thrombocytopenia in PAH, and these effects appear to be independent and additive.


Human electrophysiological and pharmacological properties of XEN-D0101: a novel atrial-selective Kv1.5/IKur inhibitor.
The human electrophysiological and pharmacological properties of XEN-D0101 were evaluated to assess its usefulness for treating atrial fibrillation (AF). XEN-D0101 inhibited Kv1.5 with an IC50 of 241 nM and is selective over non-target cardiac ion channels (IC50 Kv4.3, 4.2 μM; hERG, 13 μM; activated Nav1.5, >100 μM; inactivated Nav1.5, 34 μM; Kir3.1/3.4, 17 μM; Kir2.1, >>100 μM). In atrial myocytes from patients in sinus rhythm (SR) and chronic AF, XEN-D0101 inhibited non-inactivating outward currents (Ilate) with IC50 of 410 and 280 nM, respectively, and peak outward currents (Ipeak) with IC50 of 806 and 240 nM, respectively. Whereas Ilate is mainly composed of IKur, Ipeak consists of IKur and Ito. Therefore, the effects on Ito alone were estimated from a double-pulse protocol where IKur was inactivated (3.5 µM IC50 in SR and 1 µM in AF). Thus, inhibition of Ipeak is because of IKur reduction and not Ito. XEN-D0101 significantly prolonged the atrial action potential duration at 20%, 50%, and 90% of repolarization (AF tissue only) and significantly elevated the atrial action potential plateau phase and increased contractility (SR and AF tissues) while having no effect on human ventricular action potentials. In healthy volunteers, XEN-D0101 did not significantly increase baseline- and placebo-adjusted QTc up to a maximum oral dose of 300 mg. XEN-D0101 is a Kv1.5/IKur inhibitor with an attractive atrial-selective profile.


Mental health service use among Canadian older adults with anxiety disorders and clinically significant anxiety symptoms.
Despite evidence of disproportionate underutilization of mental health services by older adults and by individuals with anxiety disorders, little is known specifically about service use by older adults with anxiety. This study examines the prevalence of mental health service use among older adults with anxiety disorders and clinically significant anxiety symptoms, as well as factors associated with service use. The authors used data from the Canadian Community Health Survey-Mental Health and Well-Being, a nationally representative survey of community-dwelling Canadians. This study examined past-year use of mental health services in both the specialty mental health and general medical sectors by adults aged 55+ (N = 12,792). Logistic regression analyses examined predictors of service use among those with anxiety disorders (N = 279) and clinically significant anxiety symptoms (N = 880). Only 20.8% of older adults with an anxiety disorder and no mood disorder used services in the past year, compared to 43.1% of those with a mood disorder and 72.7% of those with comorbid disorders. In the final logistic regression models, only need variables were significant predictors of service use among older adults with anxiety disorders and among those with significant anxiety symptoms. Findings indicate that anxious older adults are less likely to use mental health services than those who are depressed. While predisposing and enabling factors do not appear to impede service use, the need for help does. Anxious older adults and those they interact with may not be interpreting their anxiety symptoms as warranting services.


Systematic reduction of hyperspectral images for high-throughput plastic characterization.
Hyperspectral Imaging (HSI) combines microscopy and spectroscopy to assess the spatial distribution of spectroscopically active compounds in objects, and has diverse applications in food quality control, pharmaceutical processes, and waste sorting. However, due to the large size of HSI datasets, it can be challenging to analyze and store them within a reasonable digital infrastructure, especially in waste sorting where speed and data storage resources are limited. Additionally, as with most spectroscopic data, there is significant redundancy, making pixel and variable selection crucial for retaining chemical information. Recent high-tech developments in chemometrics enable automated and evidence-based data reduction, which can substantially enhance the speed and performance of Non-Negative Matrix Factorization (NMF), a widely used algorithm for chemical resolution of HSI data. By recovering the pure contribution maps and spectral profiles of distributed compounds, NMF can provide evidence-based sorting decisions for efficient waste management. To improve the quality and efficiency of data analysis on hyperspectral imaging (HSI) data, we apply a convex-hull method to select essential pixels and wavelengths and remove uninformative and redundant information. This process minimizes computational strain and effectively eliminates highly mixed pixels. By reducing data redundancy, data investigation and analysis become more straightforward, as demonstrated in both simulated and real HSI data for plastic sorting.


[Brain monoamine oxidase in prematurely aging OXYS rats].
Rats OXYS with manifestations of genetically determined premature aging and OXYR free from these manifestation were studied. Eight month old OXYS and OXYR rats were characterized by similar brain stem MAO A and MAO B activities and their control at the transcription level. In hemispheres of 8 month old OXYS rats MAO A activity was higher than in OXYR. Emotional stress did not affect either MAO A or MAO B in brain stem of the two strains, and lowered MAO A activity in hemispheres of OXYS rats.


Variational Bayesian methods for cognitive science.
Bayesian inference has become a powerful and popular technique for understanding psychological phenomena. However, compared with frequentist statistics, current methods employing Bayesian statistics typically require time-intensive computations, often hindering our ability to evaluate alternatives in a thorough manner. In this article, we advocate for an alternative strategy for performing Bayesian inference, called variational Bayes (VB). VB methods posit a parametric family of distributions that could conceivably contain the target posterior distribution, and then attempt to identify the best parameters for matching the target. In this sense, acquiring the posterior becomes an optimization problem, rather than a complex integration problem. VB methods have enjoyed considerable success in fields such as neuroscience and machine learning, yet have received surprisingly little attention in fields such as psychology. Here, we identify and discuss both the advantages and disadvantages of using VB methods. In our consideration of possible strategies to make VB methods appropriate for psychological models, we develop the differential evolution variational inference algorithm, and compare its performance with a widely used VB algorithm. As test problems, we evaluate the algorithms on their ability to recover the posterior distribution of the linear ballistic accumulator model and a hierarchical signal detection model. Although we cannot endorse VB methods in their current form as a complete replacement for conventional methods, we argue that their accuracy and speed warrant inclusion within the cognitive scientist's toolkit. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Adolescent femicide: a population-based study.
Homicide is the third leading cause of deaths for girls aged 11 to 14 years and the second leading cause of death for girls aged 15 to 18 years. However, few studies examine the contextual issues of adolescent femicide, especially among 11- to 14-year-old victims. To obtain quantitative and contextual information about adolescent femicide, and to compare the context of femicide in younger vs older adolescents. Data from the North Carolina medical examiner were analyzed for all 11- to 18-year-old female homicide victims during 1990 to 1995. Police interviews were conducted for 1993 to 1995 cases to determine context, the relationship of victim and perpetrator, and criminal histories. There were 90 victims; 63 were aged 15 to 18 years, 55 were killed with firearms, and 40 were behind in school. Of 37 femicides for which law enforcement interviews were conducted, the most common contexts were altercation (n = 9), broken or desired relationship (n = 8), reckless behavior with a firearm (n = 6), retaliation (n = 5), and drug related (n = 3). Most perpetrators were men (89%; n = 33), were older than their victims (mean age difference, 8 years), and had criminal records (59%; n = 21). Seventy-eight percent of victims (n = 29) were killed by an acquaintance or intimate partner. Femicide contexts differed by age. Younger adolescents (aged 11-14 years) were more likely to be killed by a family member in the context of an argument than by an intimate partner or acquaintance in the context of a broken relationship or reckless behavior with a firearm. Many victims were engaged in high-risk behaviors, including dropping out of school, running away from home, using drugs, and dating much older men with criminal records. Intervention specialists targeting high-risk female adolescents should be aware that this population may also be at increased risk of femicide.


Prevalence of amblyopia in ametropias in a clinical set-up.
To find out prevalence of amblyopia in ametropias in a clinical set-up. In this retrospective clinical study children from 4-5 years age group to the young adults who attended the eye clinic in one year period were included after taking history, VA test by Snellen's Vision Chart, cycloplegic refraction by streak retinoscope in children and wet or dry retinospcopy in young adults; and a thorough anterior and posterior segment eye examinations by slit lamp biomicroscope and ophthalmoscope to exclude structural abnormality of the eye or the posterior visual pathway defects. A total of 970 eye patients having diminution of vision with ametropias were identified and patients having reduction of visual acuity of greater than two lines between the eyes or an absolute reduction in acuity below 6/9 either eye in snellen's vision chart which cannot be corrected by refraction were enrolled to find out prevalence of amblyopia. Out of 970 ametropic eye patients amblyopia was present in 56 patients (5.97%) with anisometropias and high bilateral ametropias. The prevalence of amblyopia according to types of ametropias are: hyperopia 6 (10.71%), myopia 2 (3.57%), myopic astigmatism 31 (55.36%), hyperopic astigmatism 11 (19.64%) and mixed astigmatism 6 (10.71%). Sex distribution of amblyopia is male 32 (57.14%) and female 24 (42.86%). Laterality of amblyopia shows: monocular 40 (71.43%) and binocular 16 (28.57%). Out of 970 ametropic eye patients a total of 56 (5.97%) patients have amblyopia. A preschool and school screening program in children in critical period of development of amblyopia must be conducted to find out the ametropias and amblyopia in time; and treat them earlier, by optical correction and amblyopia therapy, effectively and adequately.


Managing health risks in urban agriculture: The effect of vegetable washing for reducing exposure to metal contaminants.
A common, yet poorly evaluated, advice to remove contaminants from urban vegetables is to wash the produce before consumption. This study is based on 63 samples of chard, kale, lettuce and parsley that have grown near a heavily trafficked road in the third largest city in Sweden, with one portion of each sample being analysed without first being washed, and the other portion being subjected to common household washing. Concentrations of 71 elements were analysed by ICP-SFMS after a sample digestion that dissolves both the plant tissues and all potentially adhering particles. The results show that the washing effect, or the fraction removed upon washing, varies significantly between elements: from approximately 0 % for K to 68 % for the ∑REEs. Considering traditional metal contaminants, the efficiency decreased from Pb (on average 56 % lost) to Co (56 %) > Cr (55 %) > As (45 %) > Sb (35 %) > Ni (33 %) > Cu (13 %) > Zn (7 %) > Cd (7 %), and Ba (5 %). A clear negative correlation between the washing effect and the different elements' bioconcentration factors shows that the elements' accessibility for plant uptake is a key controlling factor for the degree to which they are removed upon washing. Based on the average washing efficiencies seen in this study, the average daily intake of Pb would increase by 130 % if vegetables are not washed prior to consumption. For the other contaminant metals this increase corresponds to 126 % (Co), 121 % (Cr), 82 % (As), 55 % (Sb), 50 % (Ni), 16 % (Cu), 8 % (Zn), 7 % (Cd) and 5 % (Ba). The advice to wash vegetables is therefore, for many elements, highly motivated for reducing exposure and health risks. For elements which are only slightly reduced when the vegetables are washed, however, advising should rather focus on reducing levels of contamination in the soil itself.


LatisTM catheter: New technology for thrombectomy of vascular access grafts.
The most common complication of vascular access surgery is thrombosis. This study compared the gold standard Fogarty Thrombectomy Catheter, to the new latis Catheter with an advanced monofilament matrix. 30 patients with thrombosed access grafts were randomly assigned to undergo thrombectomy with the Fogarty or latis catheter. An angioscope measured remaining graft thrombi. Twenty-nine of 30 subjects were successfully thrombectomized. No statistical differences in age, gender, race, or extension graft requirements were found. Catheter use in the latis group was: 1 in 14 procedures, and 2 in 1 procedure; Fogarty group: 1 in 10 procedures, 2 in 3 procedures, and 3 in 2 procedures. The average number of catheter passes was: latis 3.06 (1-6 passes) and Fogarty 4.13 (1-9 passes). A trend in favor of the latis catheter was demonstrated; however, statistical significance was not reached (p = 0.067). The overall 6-month primary patency rates were latis (40%) and Fogarty (30%). The estimated patency at the 50th percentile for latis is 120 days and Fogarty 108 days. Statistical significance was not reached with a p-value of the Log-Rank statistic of 0.68 and a p-value of the Wilcoxon statistic of 0.78. The latis and Fogarty catheters are very similar. However, the latis balloon is more rugged with fewer catheters used and reduced number of passes. A difference in primary patency could not be demonstrated. The angioscope identified significant residual thrombus despite no returning thrombus from the catheter. Consequently, our protocol is modified to include the angioscope.


Long-term culture of microvascular endothelial cells derived from Mongolian gerbil brain.
A method for long-term culture of microvascular endothelial cells from Mongolian gerbil brain and their biologic properties in vitro are described. Microvessels were isolated from Mongolian gerbil brain by a combination of enzymatic treatment, filtration, and centrifugation and were seeded onto a gelatin-coated dish. A morphologically homogeneous cell plaque showing a cobblestone appearance was removed 2 to 3 weeks after the seeding, and the cells were subcultured. The cultured cells grew as monolayers of flat polygonal cells and were carried for more than 20 passages without morphologic change. These cells synthesized prostacyclin and retained an endothelial specific marker, factor VIII-related antigen. When the cells were cultured in a collagen gel, they rapidly formed capillarylike tubular structures without endothelial cell growth factor or special substrata. Long-term culture of purified microvascular endothelial cells derived from Mongolian gerbil brain will facilitate the study of the function of microvascular endothelial cells in human brain under normal and pathologic conditions.


A Minireview on Brain Models Simulating Geometrical, Physical, and Biochemical Properties of the Human Brain.
There is a growing body of evidences that brain surrogates will be of great interest for researchers and physicians in the medical field. They are currently mainly used for education and training purposes or to verify the appropriate functionality of medical devices. Depending on the purpose, a variety of materials have been used with specific and accurate mechanical and biophysical properties, More recently they have been used to assess the biocompatibility of implantable devices, but they are still not validated to study the migration of leaching components from devices. This minireview shows the large diversity of approaches and uses of brain phantoms, which converge punctually. All these phantoms are complementary to numeric models, which benefit, reciprocally, of their respective advances. It also suggests avenues of research for the analysis of leaching components from implantable devices.


In Vitro Wound Healing Potential of Photobiomodulation Is Possibly Mediated by Its Stimulatory Effect on AKT Expression in Adipose-Derived Stem Cells.
Increasing evidence suggests that adipose-derived stem cells (ADSCs) serve as a therapeutic approach for wound healing. The aim of this study was to determine the effect of photobiomodulation (PBM) on antioxidant enzymes in ADSCs. Four ADSC cell models, namely, normal, wounded, diabetic, and diabetic wounded, were irradiated with 660 nm (fluence of 5 J/cm2 and power density of 11.2 mW/cm2) or 830 nm (fluence of 5 J/cm2 and power density of 10.3 mW/cm2). Nonirradiated cells served as controls. Cell morphology and wound migration were determined using light microscopy. Cell viability was determined by the trypan blue exclusion assay. The enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of antioxidants (superoxide dismutase (SOD), catalase (CAT), and heme oxygenase (HMOX1)). AKT activation and FOXO1 levels were determined by immunofluorescence and western blotting. The gaps (wound) in PBM-treated wounded and diabetic wounded cell models closed faster than the controls. PBM treatment significantly increased antioxidant levels in all cell models. This reflects that oxidative stress is reduced on the counterpart of increased antioxidant levels. This might be due to the activation of the AKT signaling pathway as evidenced by the increased AKT signals via western blotting and immunofluorescence. This data suggests that PBM promotes wound healing by increasing antioxidant levels by activating AKT signaling.


Lipoic acid prevention of neural tube defects in offspring of rats with streptozocin-induced diabetes.
Increased oxidant stress has been suggested to play a role in the pathogenesis of disturbed embryogenesis in diabetic pregnancies. The present study was conducted to determine whether administration of lipoic acid, a naturally occurring antioxidant, would reduce the incidence of diabetic embryopathy in the streptozocin-induced diabetic rat model. After conception, rats were randomly distributed to 5 groups. From day 1, rats were daily injected intraperitoneally with either lipoic acid, 30 mg/kg, or vehicle. At day 6, rats from groups 3, 4, and 5 were made diabetic by a single intraperitoneal injection of streptozocin. Group 4 rats were injected with lipoic acid from day 1 to day 6, after vehicle treatment until day 17. At day 17 of gestation, rats were killed. The fetuses were released from the yolk sacs and surrounding decidua and were examined for size, resorption rate, and neural tube defects. Pregnant diabetic rats treated with vehicle lost weight during pregnancy (-3.2 +/- 1.9 g/d), as opposed to normal pregnancy-related weight gain (3.5 +/- 0.5 g/d). Treatment with lipoic acid protected against diabetes-induced weight loss, without a measurable effect on fed-state glucose concentrations. Daily treatment with lipoic acid (pregnancy days 1 to 17) was efficient in reducing the resorption rate from 24.0% +/- 9.5% in vehicle-treated diabetic rats to 10.2% +/- 4.8% in lipoic acid-treated diabetic rats (P <.05). The rate of neural tube defects in diabetic rats treated with lipoic acid throughout the pregnancy was reduced from 26.0% +/- 7.0% to 10.2% +/- 3.2% (P <.05). In rats treated only during pregnancy days 1 to 5 (before diabetes induction), lipoic acid failed to exert its protective effects against neural tube defects, which emphasizes the importance of the presence of lipoic acid during the organogenesis period. The atherosis of placental vasculature demonstrated in the vehicle-treated diabetic rats was absent from placentas obtained from lipoic acid-treated diabetic animals. Our data demonstrate a protective effect of lipoic acid against diabetic embryopathy, fetal losses, and ultrastructural alteration of diabetic placentas.


Catalytic [2 + 2 + 2] cycloaddition with indium(iii)-activated formaldimines: a practical and selective access to hexahydropyrimidines and 1,3-diamines from alkenes.
Catalytic [2 + 2 + 2] cycloaddition with imines has, for the first time, been developed as a practical and selective approach for direct construction of hexahydropyrimidine derivatives from various alkenes. With formaldimines as reagents and simple InCl3 as the catalyst, this ionic [2 + 2 + 2] approach is applicable for a wide scope of alkenes and allenes with various electronic and steric properties, as well as substitution patterns. Through facile hydrolysis of the resulting hexahydropyrimidines, this catalytic process also provides a new synthetic strategy for the aminomethylamination of alkenes and allenes to practically access 1,3-diamine derivatives.


Bilateral tibial agenesis and syndactyly in a cat.
A three-year-old cat was referred to the Veterinary Teaching Hospital, University of Naples, Italy. The cat had severe pelvic limb deformity, and abnormal development of all four paws. Radiographs revealed bilateral tibial agenesis, syndactyly, and digital hypoplasia. No treatment was instituted because of the severity of the injury, the adaptation of the cat to the abnormal condition, and the owner's refusal to permit any treatment. Congenital limb deformities are rarely reported in the cat and tibial agenesis is considered a very rare disease. This congenital anomaly is well documented and classified in man, and it has been associated with other abnormalities in more complex syndromes. This paper reports clinical and radiographic findings in a cat affected by bilateral complete tibial agenesis associated with other congenital anomalies.


DNA repair XRCC1 Arg399Gln polymorphism alone, and in combination with CYP2E1 polymorphisms significantly contribute to the risk of development of childhood acute lymphoblastic leukemia.
It is now well established that genetic polymorphisms impairing the DNA repair capacity can disrupt the genomic integrity and potentially modulate individual's susceptibility to various cancers. In this study, we investigated the possible association of X-ray repair cross-complimenting group 1 (XRCC1) Arg399Gln and Arg194Trp variants with the risk of incidence of childhood acute lymphoblastic leukemia (ALL) in Turkish population comprised of 190 healthy controls and 167 ALL patients. For Arg399Gln polymorphism, the heterozygous (Arg/Gln) and homozygous mutant (Gln/Gln) genotypes were significantly more common in the ALL patients than the controls (OR: 1.6, p=0.04). Particularly, the Gln399Gln genotype significantly increased the risk of disease up to 2.0-fold (OR: 2.0, p=0.04). Besides, Gln399Gln genotype has been found to be associated with considerably increased risk of ALL among females (OR=2.9, p=0.03). In case of codon 194 polymorphism, no significant associations have been found with risk of childhood ALL. In addition, none of the combinations of XRCC1 codon 194 and 399 polymorphisms have been found to be significantly associated with childhood ALL risk. In the scope of this study, we have also showed that the co-presence of XRCC1 codon 399 and CYP2E1*5B and *6 polymorphisms (data for CYP2E1 polymorphisms drawn from previously published study conducted in our lab) in the same individuals considerably increased the risk for childhood ALL to 3.7-fold with borderline significance (p=0.049). The observed combined effect was considerably more prominent among females (OR=17.4, p=0.001) and need to further investigation. This is the first study showing combined associations of XRCC1 399Gln, CYP2E1*5B and *6 alleles with the risk of development of childhood ALL.


Receptor structure for F1C fimbriae of uropathogenic Escherichia coli.
F1C fimbriae are correlated with uropathogenic Escherichia coli strains. Although F1C fimbriae mediate binding to kidney tubular cells, their receptor is not known. In this paper, we demonstrate for the first time specific carbohydrate residues as receptor structure for F1C-fimbria-expressing E. coli. The binding of the F1C fimbriated recombinant E. coli strain HB101(pPIL110-54) and purified F1C fimbriae to reference glycolipids of different carbohydrate compositions was evaluated by using thin-layer chromatography (TLC) overlay and solid-phase binding assays. TLC fimbrial overlay analysis revealed the binding ability of purified F1C fimbriae only to glucosylceramide (GlcCer), beta1-linked galactosylceramide 2 (GalCer2) with nonhydroxy fatty acids, lactosylceramide, globotriaosylceramide, paragloboside (nLc(4)Cer), lactotriaosylceramide, gangliotriaosylceramide (asialo-GM(2) [GgO(3)Cer]) and gangliotetraosylceramide (asialo-GM(1) [GgO(4)Cer]). The binding of purified F1C fimbriae as well as F1C fimbriated recombinant E. coli strain HB101(pPIL110-54) was optimal to microtiter plates coated with asialo-GM(2) (GgO(3)Cer). The bacterial interaction with asialo-GM(1) (GgO(4)Cer) and asialo-GM(2) (GgO(3)Cer) was strongly inhibited only by disaccharide GalNAcbeta1-4Galbeta linked to bovine serum albumin. We observed no binding to globotetraosylceramide or Forssman antigen (Gb(5)Cer) glycosphingolipids or to sialic-acid-containing gangliosides. It was demonstrated that the presence of a GalCer or GlcCer residue alone is not sufficient for optimal binding, and additional carbohydrate residues are required for high-affinity adherence. Indeed, the binding efficiency of F1C fimbriated recombinant bacteria increased by 19-fold when disaccharide sequence GalNAcbeta1-4Galbeta is linked to glucosylceramide as in asialo-GM(2) (GgO(3)Cer). Thus, it is suggested that the disaccharide sequence GalNAcbeta1-4Galbeta of asialo-GM(2) (GgO(3)Cer) which is positioned internally in asialo-GM(1) (GgO(4)Cer) is the high-affinity binding epitope for the F1C fimbriae of uropathogenic E. coli.


Adenomatous polyposis coli-stimulated GEF 1 (Asef1) is a negative regulator of excitatory synaptic function.
Guanine nucleotide exchange factors (GEFs) play important roles in many cellular processes, including regulation of the structural plasticity of dendritic spines. A GEF protein, adenomatous polyposis coli-stimulated GEF 1 (Asef1, ARHGEF4) is highly expressed in the nervous system. However, the function of Asef1 has not been investigated in neurons. Here, we present evidence showing that Asef1 negatively regulates the synaptic localization of postsynaptic density protein 95 (PSD-95) in the excitatory synapse by inhibiting Staufen-mediated synaptic localization of PSD-95. Accordingly, Asef1 expression impairs synaptic transmission in hippocampal cultured neurons. In addition, neuronal activity facilitates the dissociation of Asef1 from Staufen in a phosphoinositide 3 kinase (PI3K)-dependent manner. Taken together, our data reveal Asef1 functions as a negative regulator of synaptic localization of PSD-95 and synaptic transmission.


Kinetic Visualization of Single-Cell Interspecies Bacterial Interactions.
Polymicrobial communities are ubiquitous in nature, yet studying their interactions at the single-cell level is difficult. Thus, a microscopy-based method has been developed for observing interspecies interactions between two bacterial pathogens. The use of this method to interrogate interactions between a motile Gram-negative pathogen, Pseudomonas aeruginosa and a non-motile Gram-positive pathogen, Staphylococcus aureus is demonstrated here. This protocol consists of co-inoculating each species between a coverslip and an agarose pad, which maintains the cells in a single plane and allows for visualization of bacterial behaviors in both space and time. Furthermore, the time-lapse microscopy demonstrated here is ideal for visualizing the early interactions that take place between two or more bacterial species, including changes in bacterial species motility in monoculture and in coculture with other species. Due to the nature of the limited sample space in the microscopy setup, this protocol is less applicable for studying later interactions between bacterial species once cell populations are too high. However, there are several different applications of the protocol which include the use of staining for imaging live and dead bacterial cells, quantification of gene or protein expression through fluorescent reporters, and tracking bacterial cell movement in both single species and multispecies experiments.


Lipidome and inflammation interplay: the role of diet in this relationship.
The aim of this review was to provide an overview of the role of novel lipid biomarkers from the circulating lipidome in inflammatory processes and the impact that dietary patterns may have on the lipidome. Inflammation is a process that underlies many acute and chronic diseases, contributing to their development and severity. Finding novel molecules which serve as biomarkers and which are involved in inflammation is very useful, since they offer us both preventive or therapeutic targets and reveal mechanisms of action. Recently, several studies have found circulating lipid molecules that are implicated in inflammatory processes of different diseases, such as cardiovascular diseases, type 2 diabetes, COVID-19 or other respiratory infectious diseases. As such, ceramides, triacylglicerides or lysophosphatidylcholines have been associated with inflammation in a different manner depending on the stage of inflammation. The study of dietary patterns, especially healthy ones as the Mediterranean or the Nordic diets, has shown the impact that dietary habits may have on the lipidomic profile of individuals. Healthy dietary patterns have been suggested to exert beneficial effects in the circulating lipid profile. Studying the circulating lipidome could help to find new biomarkers of underlying inflammation, especially in cases of chronic low-grade inflammatory diseases in which it is more difficult to detect.


Prenatal characteristics of congenital nephrosis: results of a survey.
The purpose of this study was to evaluate the prenatal characteristics of congenital nephrosis of the Finnish type (CNF). Patients presenting with elevated maternal serum and/or amniotic fluid alpha-fetoprotein levels, normal ultrasound examinations and normal fetal karyotypes were included. A retrospective cohort study was conducted using questionnaires sent to all board certified clinical geneticists. Perinatal outcome, including histologic verification of CNF, was obtained. Forty index cases met the above criteria. Ten cases ultimately did not have the diagnosis of CNF, with a median MSAFP level of 7.59 MoM (range 2.7-27.64 MoM) and a median AFAFP level of 10.99 MoM (range 1.47-128.6 MoM). In the affected cohort of index pregnancies, the initial median MSAFP level was 14.49 MoM (range 3.1-38.0 MoM); the median AFAFP level was 40.0 MoM (range 2.4-80.9). MSAFP and AFAFP levels may be lower than previously recognized in patients carrying fetuses with CNF. There is significant overlap between the affected and unaffected patients.


The effect of deferoxamine on ciprofibrate-induced hepatocarcinogenesis in the rat.
Peroxisome proliferators (PP) are proven hepatocarcinogens in rats and mice. The carcinogenic effect of PP has been attributed to the oxidative stress that results from generation of high levels of hydrogen peroxide (H2O2). Since the hydroxyl radical is produced via metal mediated reaction from H2O2 and is DNA reactive, we have examined the effect of deferoxamine, the specific iron chelator, on ciprofibrate-induced hepatocarcinogenesis. Male F-344 rats were fed a diet containing ciprofibrate (0.025%) alone or ciprofibrate plus deferoxamine (0.3% or 0.6%) for 60 to 61 weeks, and the livers were analyzed for the incidence, number and size of the tumors. One hundred percent of rats in all groups developed neoplastic nodules and hepatocellular carcinomas. However, in rats given a higher dose of deferoxamine there was a significant decrease in the number of tumors per liver and the number of tumors larger than 10mm. Although deferoxamine did not prevent tumor development, at the higher dose level it caused a decrease in the number of tumors. These findings indicate that the decreased tumor numbers maybe due to a reduction in the level of hydroxyl radicals.


[Is anaesthesia detrimental to brain development?].
Many experimental studies in mammals, and increasingly also in primates, have shown that almost all anaesthetic agents when administered during a young animal's brain-development phase cause increased neuroapoptosis and changes in dendritic morphology at short term, and later, learning disorders. These findings are being confirmed in increasing numbers of retrospective cohort studies in humans. However, these retrospective cohort studies are considerably influenced by confounding. A current prospective randomized clinical trial comparing general and locoregional (spinal) anaesthesia for hernia repair could provide some clinical evidence. These study results will only provide information on relatively short procedures and will not be available until the first reliable neuropsychological evaluation at age 5 in 2018. Pending this additional data, we should discuss with our surgical colleagues the indications, timing and duration of surgery and - if possible - postpone elective surgery until the child is more mature.


Kecheng Jie.
"A key experience in my education was a visit to Prof. Andrew I. Cooper's group at the University of Liverpool as an exchange PhD student where I started to learn about porous materials and crystal engineering and then got obsessed… The biggest scientific advance of the last decade was artificial intelligence." Find out more about Kecheng Jie in his Introducing… Profile.


Cytologic findings in a fetal intracranial teratoma. A case report.
Fetal neoplasms are very rare. Recently we had the opportunity to examine the fine needle aspiration (FNA) biopsy of a fetal intracranial teratoma. The tumor was found in a 30-week-gestation fetus; the mother was 32 years old, gravida 4, para 1. She presented with a rapid increase in abdominal girth over a two-week period. An ultrasound scan showed severe fetal hydrocephalus and a massive intracranial tumor thought to be a teratoma because of variations in echogenicity and spotty calcification. An FNA biopsy was performed under ultrasound guidance. It showed mainly neuroepithelial cells, so a differential diagnosis of malignant neuroepithelial tumor was considered. At autopsy, several other tissue types were found in the tumor, consistent with a teratoma. Advances in diagnosis of fetal anomalies by ultrasound have been associated with an increase in the use of fetal interventions performed in utero. This includes the availability of fetal surgery in some centers. FNA biopsy of fetal lesions does not appear to be well described. Increased experience with this technique is necessary if its full potential is to be realized.


Current favourable 10-year outcome of patients with early rheumatoid arthritis: data from the ESPOIR cohort.
To report the 10-year outcome of an inception cohort of patients with early rheumatoid arthritis (RA), the ESPOIR cohort, and predictors of outcome. From 2003 to 2005, 813 patients were included if they had early arthritis (<6 months) with a high probability of RA and had never been prescribed DMARDs. Multivariate analysis was used to evaluate predictors of outcome. In total, 521 (64.1%) RA patients were followed up for 10 years; 35 (4.3%) died, which appears to be similar to the French general population. Overall, 480 (92.1%) patients received a DMARD; 174 (33.4%) received at least one biologic DMARD, 13.6% within 2 years. At year 10, 273 (52.4%) patients were in DAS28 remission, 40.1% in sustained remission, 14.1% in drug-free remission, 39.7% in CDAI remission. Half of the patients achieved a health assessment questionnaire-disability index (HAQ-DI) < 0.5. SF-36 physical component and pain were well controlled. Structural progression was weak, with a mean change from baseline in modified Sharp score of 11.0 (17.9). Only 34 (6.5%) patients required major joint surgery. A substantial number of patients showed new comorbidities over 10 years. Positivity for anti-citrullinated peptides antibodies (ACPA) was confirmed as a robust predictor of long-term outcome. We report a very mild 10-year outcome of a large cohort of patients with early RA diagnosed in the early 2000s, which was much better than results for a previous cohort of patients who were recruited in 1993. This current favourable outcome may be related to more intensive care for real-life patients.


Platelet‑derived growth factor‑BB mediates pancreatic cancer malignancy via regulation of the Hippo/Yes‑associated protein signaling pathway.
Platelet‑derived growth factor (PDGF) is a potent mitogen and chemoattractant that serves a role in the development of several types of solid cancer, and abnormal PDGF activity has been reported in numerous human tumors. Tumor‑derived PDGF ligands are considered to act in either a paracrine or autocrine manner, serving roles in the phosphorylation of receptors on tumor and stromal cells in the tumor microenvironment. Despite the well‑established association between PDGF and tumor progression, the precise mechanisms of autocrine PDGF signaling in pancreatic tumor cells remain elusive. Therefore, the present study aimed to analyze the influence of PDGF‑BB in pancreatic cancer. Pancreatic adenocarcinoma BxPC‑3 cells were cultured and treated with recombinant human PDGF‑BB in vitro. Cell proliferation was tested using an MTT assay. Cell apoptosis was measured using flow cytometry. Tumor cell migration and invasion were examined via wound‑healing and Transwell assays, respectively. The expression and subcellular localization of Yes‑associated protein (YAP) was determined using western blotting and immunofluorescence. The transcriptional activity of target genes was tested using a luciferase assay and reverse transcription‑quantitative PCR. The present study revealed that PDGF‑BB significantly promoted cell proliferation in pancreatic adenocarcinoma BxPC‑3 cells and enhanced the aggressiveness of this cell line, as demonstrated by Transwell and wound‑healing assays. Anoikis resistance is an important mechanism by which metastatic cells avoid apoptosis when detaching from adjacent cells or the extracellular matrix. PDGF‑BB treatment inhibited anoikis under anchorage‑independent conditions. Mechanistic experiments revealed that PDGF‑BB promoted the upregulation and activation of the transcriptional coactivator YAP, an effector of the Hippo signaling pathway. RhoA or protein phosphatase‑1 (PP‑1) inhibition partially abolished the accumulation and activation of YAP, suggesting PDGF‑BB‑mediated YAP dephosphorylation and transactivation via the RhoA/PP‑1 cascade. Pharmacologic inhibition of the PDGF receptor directly downregulated YAP activity and the expression levels of downstream genes. Furthermore, verteporfin, a small molecular inhibitor of the Hippo/YAP signaling pathway, partially reversed the effects of PDGF‑BB on cell proliferation, anoikis resistance and cell migration. In conclusion, the present study revealed that the Hippo/YAP signaling pathway may be involved in the tumor‑promoting activity of PDGF‑BB in pancreatic cancer.


Contact and nutrient caregiving effects on newborn infant pain responses.
To understand how the 'caregiving context' could affect responses to procedural pain, the authors sought to determine whether (1) the combined effects of sweet taste and holding (caregiving contact) were greater than the effects of either alone, (2) any combined effects were additive or interactive, and (3) the interventions had similar effects on behavioral (crying and facial activity) and physiological (heart rate, vagal tone) responses to the heel-stick procedure in newborn infants in a randomized two-factorial intervention trial. Eighty-five normally developing newborn infants were studied with a mean gestational age of 39.4 weeks on the 2nd or 3rd day of life. Infants were randomized in blocks of eight to receive (1) no holding and water taste (control participants), (2) no holding and sucrose taste (sucrose group), (3) holding and water taste (holding group), or (4) holding and sucrose taste (holding and sucrose group). Crying was reduced significantly by taste and holding, and the interventions combined additively. Facial activity was only significantly reduced by holding. For physiological measures, the interventions interacted with each other and preintervention levels to reduce heart rate and lower vagal tone more during the procedure in infants in whom heart rate and vagal tone were higher before intervention. Consequently, sweet taste and holding interventions combined in complex ways when acting on different behavioral and physiological response systems to modify stressful pain experiences. The results suggest that providing a caregiving context when painful procedures are performed may be a simple and practical method of reducing pain experience in infants, and that no one measure captures these effects.


Epitope analysis of glycoprotein I of pseudorabies virus.
A panel of 11 monoclonal antibodies (MAbs) raised against pseudorabies virus (PRV) was used to map epitopes on the virus glycoprotein I (gI). We employed three approaches to map epitopes on gI. By a competition binding assay, six groups of MAbs were defined as reacting with distinct antigenic domains on gI. To identify regions along the gI polypeptide chain encompassing the domains recognized by these MAbs, DNA fragments derived from the gI-coding region were cloned into pEX expression plasmids. The antigenic reactivity of the fusion proteins expressed in Escherichia coli was analysed by immunoblotting. Five antigenic domains were mapped within the first 238 amino acids of gI: domains A, B and D were mapped between amino acids 52 and 123 and domains C and E between amino acids 78 and 238. One MAb, representing domain F, did not react with the expressed fusion proteins. To assess the precise location and amino acid sequences of the epitopes, overlapping nonapeptides covering the amino acid sequence 52 to 238 were synthesized. The antibody-binding activity of these peptides was tested by an ELISA (Pepscan-method). Three antigenic domains were mapped: domain A was localized to amino acids 64 to 73 and 75 to 84, domain B to amino acids 52 to 67 and domain D to amino acids 68 to 82. Four MAbs representing antigenic domains C, E and F did not react in the Pepscan. Finally, sera from pigs infected experimentally with PRV reacted with the fusion protein of plasmid ps 1 (amino acids 52 to 238).


Endoscopic Ultrasound-Guided Pancreatic Duct Intervention.
Endoscopic ultrasound-guided pancreatic duct intervention (EUS-PDI) is an emerging endoscopic approach allowing access and intervention to the pancreatic duct (PD) for patients with failed endoscopic retrograde pancreatography (ERP) or patients with surgically altered anatomy. As opposed to biliary drainage for which percutaneous drainage is an alternative following failed endoscopic retrograde cholangiopancreatography (ERCP), the treatment options after failed ERP are very limited. Therefore, endoscopic ultrasound (EUS)-guided access to the PD and options for subsequent drainage may play an important role as an alternative to surgical intervention. However, this approach is technically demanding with a high risk of complications, and should only be performed by highly experienced endoscopists. In this review, we describe an overview of the current endoscopic approaches, basic technical tips, and outcomes using these procedures.


Closing the Gap: cultural safety in Indigenous health education.
The challenge for the future is to embrace a new partnership aimed at closing the gap between Indigenous and non-Indigenous Australians on life expectancy, educational achievement and employment opportunities. Significant improvements in contemporary Indigenous health care can be achieved through culturally safe health education programs for Indigenous students. However, while participation rates of Australian Indigenous students in the higher education sector are increasing, attrition rates are markedly higher than those of the general student population. This paper focuses on a unique degree program that is offered exclusively to Indigenous students in the field of mental health in the School of Nursing, Midwifery and Indigenous Health, Charles Sturt University. This qualitative exploratory study aimed to identify strategies that were especially helpful in sustaining students in the program and to identify and address barriers to the retention of students, to empower students to better prepare for the university environment and to inform academics within the course about areas that could be improved to provide a more culturally safe learning environment. The first stage of the study utilised focus group interviews with 36 Indigenous students across all three years of the program. The findings of the study addressing the issues of culturally appropriate pedagogy, curricula and cultural safety in the mental health degree program are discussed.


In the shadows: parents of seriously ill adult children.
Life-threatening diseases are being diagnosed at younger ages and successfully managed for longer periods of time. Adult patients increasingly will have parents who want to be present and help during treatment. Little is known about how best to include parents of adult children in the nursing plan of care. Healthcare professionals must balance the independence and privacy needs of adult patients with parents' desire to help and provide care.


Functional brain connectomes reflect acute and chronic cannabis use.
Resting state fMRI has been employed to identify alterations in functional connectivity within or between brain regions following acute and chronic exposure to Δ9-tetrahydrocannabinol (THC), the psychoactive component in cannabis. Most studies focused a priori on a limited number of local brain areas or circuits, without considering the impact of cannabis on whole-brain network organization. The present study attempted to identify changes in the whole-brain human functional connectome as assessed with ultra-high field (7T) resting state scans of cannabis users (N = 26) during placebo and following vaporization of cannabis. Two distinct data-driven methodologies, i.e. network-based statistics (NBS) and connICA, were used to identify changes in functional connectomes associated with acute cannabis intoxication and history of cannabis use. Both methodologies revealed a broad state of hyperconnectivity within the entire range of major brain networks in chronic cannabis users compared to occasional cannabis users, which might be reflective of an adaptive network reorganization following prolonged cannabis exposure. The connICA methodology also extracted a distinct spatial connectivity pattern of hypoconnectivity involving the dorsal attention, limbic, subcortical and cerebellum networks and of hyperconnectivity between the default mode and ventral attention network, that was associated with the feeling of subjective high during THC intoxication. Whole-brain network approaches identified spatial patterns in functional brain connectomes that distinguished acute from chronic cannabis use, and offer an important utility for probing the interplay between short and long-term alterations in functional brain dynamics when progressing from occasional to chronic use of cannabis.


Integrins control the positioning and proliferation of follicle stem cells in the Drosophila ovary.
Adult stem cells are maintained in specialized microenvironments called niches, which promote self-renewal and prevent differentiation. In this study, we show that follicle stem cells (FSCs) in the Drosophila melanogaster ovary rely on cues that are distinct from those of other ovarian stem cells to establish and maintain their unique niche. We demonstrate that integrins anchor FSCs to the basal lamina, enabling FSCs to maintain their characteristic morphology and position. Integrin-mediated FSC anchoring is also essential for proper development of differentiating prefollicle cells that arise from asymmetrical FSC divisions. Our results support a model in which FSCs contribute to the formation and maintenance of their own niche by producing the integrin ligand, laminin A (LanA). Together, LanA and integrins control FSC proliferation rates, a role that is separable from their function in FSC anchoring. Importantly, LanA-integrin function is not required to maintain other ovarian stem cell populations, demonstrating that distinct pathways regulate niche-stem cell communication within the same organ.


Trends in beverage prices following the introduction of a tax on sugar-sweetened beverages in Barbados.
A 10% excise tax on sugar sweetened beverages (SSBs) was implemented in Barbados in September 2015. A national evaluation has been established to assess the impact of the tax. We present a descriptive analysis of initial price changes following implementation of the SSB tax using price data provided by a major supermarket chain in Barbados over the period 2014-2016. We summarize trends in price changes for SSBs and non-SSBs before and after the tax using year-on-year mean price per liter. We find that prior to the tax, the year-on-year growth of SSB and non-SSB prices was very similar (approximately 1%). During the quarter in which the tax was implemented, the trends diverged, with SSB price growth increasing to 3% and that of non-SSBs decreasing slightly. The growth of SSB prices outpaced non-SSBs prices in each quarter thereafter, reaching 5.9% compared to <1% for non-SSBs. Future analyses will assess the trends in prices of SSBs and non-SSBs over a longer period and will integrate price data from additional sources to assess heterogeneity of post-tax price changes. A continued examination of the impact of the SSB tax in Barbados will expand the evidence base available to policymakers worldwide in considering SSB taxes as a lever for reducing the consumption of added sugar at the population level.


Prevalence and correlates of problem gambling in people with psychotic disorders.
There are few published studies on the comorbidity of psychosis and problem gambling. This paper provides estimates of the prevalence and clinical correlates of problem gambling in a representative sample of people with psychotic disorders. The second Australian national survey of psychosis was undertaken in 2010 and included adults (18-64 years) attending mental health services. Problem gambling was measured using the Canadian Problem Gambling Index (CPGI) at two sites of this study, with 442 participants providing data suitable for analysis. There were 151 participants who screened positive to past-year gambling. 4.1% of the total sample was classified as low risk gamblers, 6.4% were moderate risk gamblers and 5.8% were problem gamblers. Moderate risk/problem gamblers were more likely to be male, have left school with no qualifications and have sought financial assistance in the last year. There was a significant association with substance use, including alcohol use disorders and use of cannabis and 'other' drugs (excluding cannabis). People with psychosis are four times more likely to have a gambling problem than the general population. The association of gambling with substance use disorders is consistent with community studies, while the increased need for financial assistance suggests that problem gambling increases the likelihood of financial harm for this population. Clinicians should screen for comorbid gambling problems in people with psychosis, while there is also a need for additional research into this area.


Th1 polarization of the immune response in Behçet's disease: a putative pathogenetic role of interleukin-12.
To investigate whether immunologic abnormalities in patients with Behçet's disease (BD) are related to abnormalities of the Th1/Th2 ratio. Th1/Th2 cytokine production by peripheral blood lymphocytes (PBL) from 31 patients with BD, 11 patients with inflammatory arthritis, and 10 healthy blood donors was evaluated by intracellular immunofluorescence staining. Serum interleukin-12 (IL-12) levels were measured using an enzyme amplified-sensitivity immunoassay. The effect of recombinant IL-12 (rIL-12) on spontaneous and Fas-mediated apoptosis of phytohemagglutinin (PHA)-stimulated PBL was evaluated by flow cytometry using propidium iodide (PI) staining and a bromodeoxyuridine (BrdU)/PI procedure. Intracellular immunofluorescence staining of IL-2, IL-4, and interferon-gamma (IFNgamma) in CD3+ lymphocytes from BD patients demonstrated a strong polarization of the immune response toward the Th1 pathway that correlated with the progression of BD. Peripheral Th1 cells were significantly increased in patients with active disease (n = 14) as compared with those in patients in complete remission (n = 17), patients with inflammatory arthritis, and normal donors. In addition, serum IL-12 levels were correlated with peripheral Th1 lymphocytes and disease progression. Apoptotic analysis revealed that PHA-activated PBL from patients with active disease were highly sensitive to spontaneous and Fas-mediated activation-induced cell death. However, addition of rIL-12 to complete medium prevented this spontaneous and Fas-induced apoptosis and enhanced the proliferation of Th1 lymphocytes. Taken together, these results indicate that a strong Th1 immune response occurs in active BD and suggest that IL-12 plays a substantial part in the pathogenesis of BD. By preventing spontaneous and Fas-induced cell death, in fact, it results in an abnormal growth of autoreactive Th1 lymphocytes that could contribute to the prolonged inflammatory autoimmune condition of BD.


Functional Profiling of FSH and Estradiol in Ovarian Granulosa Cell Tumors.
Adult-type granulosa cell tumors (AGCTs) are sex-cord derived neoplasms with a propensity for late relapse. Hormonal modulators have been used empirically in the treatment of recurrent AGCT, albeit with limited success. To provide a more rigorous foundation for hormonal therapy in AGCT, we used a multimodal approach to characterize the expressions of key hormone biomarkers in 175 tumor specimens and 51 serum samples using RNA sequencing, immunohistochemistry, RNA in situ hybridization, quantitative PCR, and circulating biomarker analysis, and correlated these results with clinical data. We show that FSH receptor and estrogen receptor beta (ERβ) are highly expressed in the majority of AGCTs, whereas the expressions of estrogen receptor alpha (ERα) and G-protein coupled estrogen receptor 1 are less prominent. ERβ protein expression is further increased in recurrent tumors. Aromatase expression levels show high variability between tumors. None of the markers examined served as prognostic biomarkers for progression-free or overall survival. In functional experiments, we assessed the effects of FSH, estradiol (E2), and the aromatase inhibitor letrozole on AGCT cell viability using 2 in vitro models: KGN cells and primary cultures of AGCT cells. FSH increased cell viability in a subset of primary AGCT cells, whereas E2 had no effect on cell viability at physiological concentrations. Letrozole suppressed E2 production in AGCTs; however, it did not impact cell viability. We did not find preclinical evidence to support the clinical use of aromatase inhibitors in AGCT treatment, and thus randomized, prospective clinical studies are needed to clarify the role of hormonal treatments in AGCTs.


Time and size at seaward migration influence the sea survival of Salmo salar.
Whether time of seaward migration of young Atlantic salmon Salmo salar influences their subsequent survival and growth was investigated in the River Imsa, south-western Norway. Salmo salar were tagged when moving downstream through a trap near the outlet between 1976 and 2010 and recaptured on their adult return. Most descended as smolts in April and May, but some descended during the other months of the year. Annual variation in timing of the smolt migration was significantly correlated with variation in water temperature during spring. Mean total body length of the descending S. salar varied with month of seaward migration. The sea survival of S. salar emigrating from the River Imsa between January and May was 2·8 times higher than for those descending between June and December. The sea survival of the various cohorts decreased with increasing river temperature in April to May, prior to the smolt migration, and decreasing day number when the smolts moved to sea. The size of smolts descending the river between April and May did not affect the survival at sea as much as it affected the survival of migrants descending in any other month of the year. The majority of the downstream migrating S. salar were 2 years old, but proportionally, more 1 year olds moved downstream in the autumn than in the rest of the year. Mean duration between downstream migration of the young and the return migration of the grilse was shortest (12·7 months) for those descending in July and August and longest for those descending in October (21 months). Mean monthly specific growth rate was highest for those migrating downstream between May and July and lowest for those emigrating in September. Based on the present results, it was hypothesized that S. salar emigrating between April and August migrated directly out into the ocean, while those that emigrated between October and March stayed in the estuary until the subsequent spring.


Maternal sevoflurane exposure induces temporary defects in interkinetic nuclear migration of radial glial progenitors in the fetal cerebral cortex through the Notch signalling pathway.
The effects of general anaesthetics on fetal brain development remain elusive. Radial glial progenitors (RGPs) generate the majority of neurons in developing brains. Here, we evaluated the acute alterations in RGPs after maternal sevoflurane exposure. Pregnant mice were exposed to 2.5% sevoflurane for 6 hours on gestational day 14.5. Interkinetic nuclear migration (INM) of RGPs in the ventricular zone (VZ) of the fetal brain was evaluated by thymidine analogues labelling. Cell fate of RGP progeny was determined by immunostaining using various neural markers. The Morris water maze (MWM) was used to assess the neurocognitive behaviours of the offspring. RNA sequencing (RNA-Seq) was performed for the potential mechanism, and the potential mechanism validated by quantitative real-time PCR (qPCR), Western blot and rescue experiments. Furthermore, INM was examined in human embryonic stem cell (hESC)-derived 3D cerebral organoids. Maternal sevoflurane exposure induced temporary abnormities in INM, and disturbed the cell cycle progression of RGPs in both rodents and cerebral organoids without cell fate alternation. RNA-Seq analysis, qPCR and Western blot showed that the Notch signalling pathway was a potential downstream target. Reactivation of Notch by Jag1 and NICD overexpression rescued the defects in INM. Young adult offspring showed no obvious cognitive impairments in MWM. Maternal sevoflurane exposure during neurogenic period temporarily induced abnormal INM of RGPs by targeting the Notch signalling pathway without inducing long-term effects on RGP progeny cell fate or offspring cognitive behaviours. More importantly, the defects of INM in hESC-derived cerebral organoids provide a novel insight into the effects of general anaesthesia on human brain development.


Safety and efficacy of outpatient endovenous laser ablation in patients 75 years and older: a propensity score-matched analysis.
The purpose of this study was to evaluate the safety and efficacy of endovenous laser ablation (EVLA) in patients 75 years and older in an outpatient setting. In this multicentre retrospective study, we collected the demographic, procedural and outcome data of all consecutive patients with varicose veins class C2 to C6 undergoing EVLA of truncal and accessory saphenous veins. The primary efficacy endpoint was complete ablation of the treated veins diagnosed with duplex ultrasound at 4-week follow up. The primary safety endpoint was endothermal heat-induced thrombosis (EHIT) and deep vein thrombosis (DVT) at 4-week follow up as diagnosed by duplex ultrasound. A secondary endpoint was minor or major bleeding. Between February 2009 and December 2015, a total of 829 patients were treated with EVLA of the truncal and accessory saphenous veins. Among them, 747 were <75 years old (group 1) and 82 were ≥75 years old (group 2). The primary efficacy outcome was reached in 739 patients (98.9%) in group 1 and in 80 patients (97.6%) in group 2 (odd ratio [OR] 0.43, confidence interval [CI] 0.09–2.07; p = 0.295). The number of patients with EHIT type 2 and DVT were 4 (0.5%) and 2 (0.3%), respectively, in group 1, and 2 (2.4%) and 1 (1.2%), respectively, in group 2 (OR 4.64, CI 0.83–25.75; p = 0.079 and OR 4.59, CI 0.41–51.27; p = 0.215, respectively). Minor bleeding events occurred in 36 patients (4.8%) in group 1 and 7 patients (8.9%) in group 2 (OR 1.84, CI 0.79-4.29; p = 0.155). No major bleeding occurred in either group. Propensity score-matched analysis revealed no significant difference in efficacy and safety outcomes. EVLA performed as an outpatient procedure seems to be effective and safe in the elderly population as compared to the younger age group.


Oral-facial-digital syndrome type 1 in males: Congenital heart defects are included in its phenotypic spectrum.
Oral-facial-digital syndrome type 1 (OFD1; OMIM# 311200) is an X-linked dominant ciliopathy caused by mutations in the OFD1 gene. This condition is characterized by facial anomalies and abnormalities of oral tissues, digits, brain, and kidneys. Almost all affected patients are female, as OFD1 is presumed to be lethal in males, mostly in the first or second trimester of pregnancy. Live born males with OFD1 are a rare occurrence, with only five reported patients to date. In four patients the presence of a congenital heart defect (CHD) was observed. Here, we report an affected male fetus with a hemizygous de novo mutation in OFD1 (c.2101C>T; p.(Gln701*)). Ultrasound examination demonstrated severe hydrocephalus, a hypoplastic cerebellum and a hypoplastic left ventricle of the heart. The pregnancy was terminated at 16 weeks of gestation because of poor prognosis. Post-mortem examination of the fetus confirmed severe hypoplasia of the left ventricle of the heart. We emphasize that CHDs should be included in the phenotypic spectrum of OFD1 in males. This justifies molecular analysis of OFD1 when CHD is encountered prenatally in combination with one or more phenotypic features previously described in the OFD1 gene alteration spectrum. The underlying pathogenesis of CHD in OFD1 (and other ciliopathies) probably involves dysfunction of the primary cilia regarding coordination of left-right signalling during early heart development. Whether these CHDs wholly or partly result from defective left right signalling, in which different types of cilia are known to play a critical role, remains a topic of research.


Background-Free Measurement of Ring Currents by Symmetry-Breaking High-Harmonic Spectroscopy.
We propose and explore an all-optical technique for ultrafast characterization of electronic ring currents in atoms and molecules, based on high-harmonic generation (HHG). In our approach, a medium is irradiated by an intense reflection-symmetric laser pulse that leads to HHG, where the polarization of the emitted harmonics is strictly linear if the medium is reflection invariant (e.g., randomly oriented atomic or molecular media). The presence of a ring current in the medium breaks this symmetry, causing the emission of elliptically polarized harmonics, where the harmonics' polarization directly maps the ring current, and the signal is background-free. Scanning the delay between the current excitation and the HHG driving pulse provides an attosecond time-resolved signal for the multielectron dynamics in the excited current (including electron-electron interactions). We analyze the responsible physical mechanism and derive the analytic dependence of the HHG emission on the ring current. The method is numerically demonstrated using quantum models for neon and benzene, as well as through ab initio calculations.


Natural history of sensitizations in atopic dermatitis. A 3-year follow-up in 250 children: food allergy and high risk of respiratory symptoms.
The aim of the study was to define the natural history of sensitization in atopic dermatitis (AD) through cross-sectional (comparison of three age classes) and longitudinal study: 250 children with minor (32.5%), moderate (32.5%), and severe (35%) AD were examined for aeroallergen and food hypersensitivity (skin tests, clinical scoring after allergen elimination, and food challenges). The allergic screening was negative in minor AD and positive in 33% of cases of moderate AD that were concerned with aeroallergen sensitizations with only limited respiratory involvement. This suggests that nonspecific cutaneous hyperreactivity remains an almost exclusive precipitating factor in moderate or minor AD. Severe AD was characterized by a positive allergologic assessment in 100% of patients: food allergens were incriminated as flare factors in 96% of patients, with associated aeroallergen sensitization in 36%. Even at a young age (less than or equal to 2 years), the severe AD group is marked by an extreme frequency of food sensitization (93%) that persists in 73% of children younger than 7 years and 67% younger than 16 years. From the comparison of three age classes, the sequence of food and respiratory sensitization seems to be part of the natural course of AD. Prospective study in 29 children of group 1 (less than 2 years) with a 3-year follow-up confirms the data of the cross-sectional study since 27 had development of aeroallergen sensitization, with respiratory symptoms as early as age 3 years in 23 of these children. The detection of food allergy in a child presenting with AD is likely to indicate a prognosis of severe AD and should be considered by dermatologists as a potentially important predictor of further respiratory symptoms.


Effects of changing forest and impervious land covers on discharge characteristics of watersheds.
Effects of changing patterns of forest and impervious land covers on hydrologic regimes of watersheds were evaluated for urban and rural areas of the lower Cedar River drainage near Seattle, Washington. Land cover characterizations were used in a spatially explicit hydrology model to assess effects of land covers on watershed hydrology during presettlement conditions ("full forest cover"), 1991 and 1998. For the presettlement to 1991 period, urban watersheds showed decreases in forest covers (range 63% to 83%) and increases in impervious surfaces (range 43% to 71%). Rural watersheds showed similar patterns but smaller changes, with forest covers decreasing (range 28% to 34%) and impervious surfaces increasing (range 8% to 15%). For the 1991 and 1998 period, changes in forest covers for urban and rural watershed were <24%, with losses in some watersheds and regeneration in others. Impervious surfaces continued to increase, but increases were larger in rural (range 38% to 60%) than in urban watersheds (range 4% to 27%). Flood-frequency curves indicated that discharge rates (m sec(-1)) for all watersheds were higher in 1991 and 1998 than historical and suggested that chances for floods increase because of changing land covers. The largest increases in discharge rates were in urban watersheds, with rates for 2-year, 10-year, and 25-year recurrence intervals being more than two times greater than the rate during historical conditions. Changes in flow regimes were indicated by presettlement discharge levels of less frequent recurrence intervals (10-year and 25-year) occurring in posturbanization times (1991 and 1998) during more frequent intervals (2-year and 10-year). Normalized flows (m yr(-1)) of watersheds for 2-year, 10-year, and 25-year recurrence intervals indicate how flow regimes in 1991 and 1998 can change as functions of different areas of land covers. During 1991 and 1998, abrupt increases in flows occurred when forest covers were low (range 17% to 37%) and impervious surfaces were >46%. In contrast, the lowest flows occurred when forest covers were most extensive (range 59% to 81%) and impervious surfaces were <23%. We conclude that our use of spatial characterizations of impervious surfaces and forested covers in a spatially explicit hydrology model provides a robust approach for revealing how variations in different types and spatial distributions of land covers can affect flood regimes and flows of different watersheds.


Association of egg consumption and calcified atherosclerotic plaque in the coronary arteries: the NHLBI Family Heart Study.
Eggs are a ubiquitous and important source of dietary cholesterol and nutrients, yet their relationship to coronary heart disease (CHD) remains unclear. While some data have suggested a positive association between egg consumption and CHD, especially among diabetic subjects, limited data exist on the influence of egg consumption on subclinical disease. Thus, we sought to examine whether egg consumption is associated with calcified atherosclerotic plaques in the coronary arteries. In a cross-sectional design, we studied 1848 participants of the NHLBI Family Heart Study without known CHD. Egg consumption was assessed by a semi-quantitative food frequency questionnaire and coronary-artery calcium (CAC) was measured by cardiac CT. We defined prevalent CAC using an Agatston score of at least 100 and fitted generalized estimating equations to calculate prevalence odds ratios of CAC. Mean age was 56.5 years and 41% were male. Median consumption of eggs was 1/week. There was no association between frequency of egg consumption and prevalent CAC. Odds ratios (95% CI) for CAC were 1.0 (reference), 0.95 (0.66-1.38), 0.94 (0.63-1.40), and 0.90 (0.57-1.42) for egg consumption of almost never, 1-3 times per month, once per week, and 2+ times per week, respectively (p for trend 0.66), adjusting for age, sex, BMI, smoking, alcohol, physical activity, income, field center, total calories, and bacon. Additional control for hypertension and diabetes mellitus, or restricting the analysis to subjects with diabetes mellitus or fasting glucose >126 mg/dL did not alter the findings. These data do not provide evidence for an association between egg consumption and prevalent CAC in adult men and women.


Kick the habit: a social marketing campaign by Aboriginal communities in NSW.
Tackling smoking is an integral component of efforts to improve health outcomes in Aboriginal communities. Social marketing is an effective strategy for promoting healthy attitudes and influencing behaviours; however, there is little evidence for its success in reducing smoking rates in Aboriginal communities. This paper outlines the development, implementation and evaluation of Kick the Habit Phase 2, an innovative tobacco control social marketing campaign in Aboriginal communities in New South Wales (NSW). The Aboriginal Health & Medical Research Council worked with three Aboriginal communities and a creative agency to develop locally tailored, culturally relevant social marketing campaigns. Each community determined the target audience and main messages, and identified appropriate local champions and marketing tools. Mixed methods were used to evaluate the campaign, including surveys and interviews with community members and Aboriginal Community Controlled Health Service staff. Community survey participants demonstrated high recall of smoking cessation messages, particularly for messages and images specific to the Kick the Habit campaign. Staff participating in interviews reported an increased level of interest from community members in smoking cessation programs, as well as increased confidence and skills in developing further social marketing campaigns. Aboriginal community-driven social marketing campaigns in tobacco control can build capacity, are culturally relevant and lead to high rates of recall in Aboriginal communities.


Cardiac Mesenchymal Stem Cell-like Cells Derived from a Young Patient with Bicuspid Aortic Valve Disease Have a Prematurely Aged Phenotype.
There is significant interest in the role of stem cells in cardiac regeneration, and yet little is known about how cardiac disease progression affects native cardiac stem cells in the human heart. In this brief report, cardiac mesenchymal stem cell-like cells (CMSCLC) from the right atria of a 21-year-old female patient with a bicuspid aortic valve and aortic stenosis (referred to as biscuspid aortic valve disease BAVD-CMSCLC), were compared with those of a 78-year-old female patient undergoing coronary artery bypass surgery (referred to as coronary artery disease CAD-CMSCLC). Cells were analyzed for expression of MSC markers, ability to form CFU-Fs, metabolic activity, cell cycle kinetics, expression of NANOG and p16, and telomere length. The cardiac-derived cells expressed MSC markers and were able to form CFU-Fs, with higher rate of formation in CAD-CMSCLCs. BAVD-CMSCLCs did not display normal MSC morphology, had a much lower cell doubling rate, and were less metabolically active than CAD-CMSCLCs. Cell cycle analysis revealed a population of BAVD-CMSCLC in G2/M phase, whereas the bulk of CAD-CMSCLC were in the G0/G1 phase. BAVD-CMSCLC had lower expression of NANOG and shorter telomere lengths, but higher expression of p16 compared with the CAD-CMSCLC. In conclusion, BAVD-CMSCLC have a prematurely aged phenotype compared with CAD-CMSCLC, despite originating from a younger patient.


Green materials science and engineering reduces biofouling: approaches for medical and membrane-based technologies.
Numerous engineered and natural environments suffer deleterious effects from biofouling and/or biofilm formation. For instance, bacterial contamination on biomedical devices pose serious health concerns. In membrane-based technologies, such as desalination and wastewater reuse, biofouling decreases membrane lifetime, and increases the energy required to produce clean water. Traditionally, approaches have combatted bacteria using bactericidal agents. However, due to globalization, a decline in antibiotic discovery, and the widespread resistance of microbes to many commercial antibiotics and metallic nanoparticles, new materials, and approaches to reduce biofilm formation are needed. In this mini-review, we cover the recent strategies that have been explored to combat microbial contamination without exerting evolutionary pressure on microorganisms. Renewable feedstocks, relying on structure-property relationships, bioinspired/nature-derived compounds, and green processing methods are discussed. Greener strategies that mitigate biofouling hold great potential to positively impact human health and safety.