OBJECTIVE

Histological studies have provided evidence that carvedilol can prevent cardiac hypertrophy in spontaneously hypertensive-stroke prone rats (SP) fed a high-fat and -salt diet. However, the effects of carvedilol on cardiac function have not been studied in these animals. In addition, the ability of carvedilol to reverse established cardiac hypertrophy and dysfunction under these conditions remains to be determined. Here we have evaluated the ability of carvedilol to prevent and reverse cardiac hypertrophy and progressive dysfunction using echocardiography.

METHODS

Two echocardiology studies were conducted to determine the effects of carvedilol treatment on cardiac hypertrophy and dysfunction. In the first prevention study, four groups of rats were evaluated. SP were fed a high-fat (24.5% in food) and high-salt (1% in water) diet (SFD) without (SP-SFD control group) or with carvedilol (SP-SFD carvedilol group; carvedilol concentration 2,400 parts per million) for 18 weeks. Carvedilol was administered in the food at an optimum concentration (i.e. known to provide clinically relevant blood concentrations and reduce cardiac hypertrophy determined from previous studies). In addition, SP and WKY rats were fed a normal diet (SP normal diet group and WKY normal diet group). These groups are known to not develop the same significant cardiac hypertrophy and dysfunction within this limited time of study, and provided two more normal control groups for comparison. In the second reversal study, one group of SP was fed SFD for 12 weeks (SP-SFD pretreatment period) to induce cardiac hypertrophy. Carvedilol (2,400 parts per million) was then added to the diet for an additional 6 weeks (SP-SFD carvedilol treatment period).

RESULTS

In the first prevention study, carvedilol prolonged longevity (p < 0.05) and prevented left-ventricular hypertrophy and dysfunction (p < 0.05; SP-SFD control vs. SP-SFD carvedilol group). M-mode-measured and -calculated parameters demonstrated that carvedilol treatment in the SP-SFD carvedilol group prevented increases in left-ventricular wall thickness (p < 0.05) and decreases in diastolic chamber diameter and volume, stroke volume, ejection fraction and cardiac output (all p < 0.05) that occurred in the SP-SFD control group. Further, cardiac measurements in the SP-SFD carvedilol group were normalized to levels similar to those in the SP and WKY normal diet groups. All SFD-fed groups exhibited similar, significantly elevated blood pressure during the study. In the second reversal study, carvedilol treatment for 6 weeks reversed the cardiac hypertrophy and dysfunction that developed in SP-fed SFD for 12 weeks prior to carvedilol intervention. Under these conditions, carvedilol improved/normalized left-ventricular wall thickness, diastolic ventricular-chamber diameter and volume, stroke volume, ejection fraction and cardiac output (all p < 0.05).

CONCLUSIONS

These data indicate that carvedilol provides protection from and facilitates reversal of progressive cardiac remodeling and dysfunction in this SP-SFD model of cardiac hypertrophy/heart failure. Since these effects occurred in the absence of effects on blood pressure, other known actions of carvedilol, especially its antioxidant activity, for example, may explain this significant cardiac protection. In addition, research using this SP-SFD model of cardiac hypertrophy/end-organ injury appears to translate well to human cardiovascular disease.

The feasibility of preparing microparticles with high insulin loading suitable for needle-free ballistic drug delivery by spray-freeze-drying (SFD) was examined in this study. The aim was to manufacture dense, robust particles with a diameter of around 50 microm, a narrow size distribution and a high content of insulin. Atomization using ultrasound atomizers showed improved handling of small liquid quantities as well as narrower droplet size distributions over conventional two-fluid nozzle atomization. Insulin nanoparticles were produced by SFD from solutions with a low solid content (<10 mg ml(-1)) and subsequent ultra-turrax homogenization. To prepare particles for needle-free ballistic injection, the insulin nanoparticles were suspended in matrix formulations with a high excipient content (>300 mg ml(-1)) consisting of trehalose, mannitol, dextran (10 kDa) and dextran (150 kDa) (abbreviated to TMDD) in order to maximize particle robustness and density after SFD. With the increase in insulin content, the viscosity of the nanosuspensions increased. Liquid atomization was possible up to a maximum of 250 mg of nano-insulin suspended in a 1.0 g matrix. However, if a narrow size distribution with a good correlation between theoretical and measurable insulin content was desired, no more than 150 mg nano-insulin could be suspended per gram of matrix formulation. Particles were examined by laser light diffraction, scanning electron microscopy and tap density testing. Insulin stability was assessed using size exclusion chromatography (SEC), reverse phase chromatography and Fourier transform infrared (FTIR) spectroscopy. Densification of the particles could be achieved during primary drying if the product temperature (T(prod)) exceeded the glass transition temperature of the freeze concentrate (T(g)') of -29.4 degrees C for TMDD (3331) formulations. Particles showed a collapsed and wrinkled morphology owing to viscous flow of the freeze concentrate. With increasing insulin loading, the d (v, 0.5) of the SFD powders increased and particle size distributions got wider. Insulin showed a good stability during the particle formation process with a maximum decrease in insulin monomer of only 0.123 per cent after SFD. In accordance with the SEC data, FTIR analysis showed only a small increase in the intermolecular beta-sheet of 0.4 per cent after SFD. The good physical stability of the polydisperse particles made them suitable for ballistic injection into tissue-mimicking agar hydrogels, showing a mean penetration depth of 251.3 +/- 114.7 microm.

Powder-injectors use gas propulsion to deposit lyophilised drug or vaccine particles in the epidermal and sub epidermal layers of the skin. We prepared dry-powder (Tg = 45.2 ± 0.5°C) microparticles (58.1 μm) of a MenY-CRM197 glyconjugate vaccine (0.5% wt.) for intradermal needle-free powder injection (NFPI). SFD used ultrasound atomisation of the liquid vaccine-containing excipient feed, followed by lyophilisation above the glass transition temperature (Tg' = - 29.9 ± 0.3°C). This resulted in robust particles (density~ 0.53 ±0.09 g/cm3) with a narrow volume size distribution (mean diameter 58.1 μm, and span = 1.2), and an impact parameter (ρvr ~ 11.5 kg/m·s) sufficient to breach the Stratum corneum (sc). The trehalose, manitol, dextran (10 kDa), dextran (150 kDa) formulation, or TMDD (3:3:3:1), protected the MenY-CRM197 glyconjugate during SFD with minimal loss, no detectable chemical degradation or physical aggregation. In a capsular group Y Neisseria meningitidis serum bactericidal assay (SBA) with human serum complement, the needle free vaccine, which contained no alum adjuvant, induced functional protective antibody responses in vivo of similar magnitude to the conventional vaccine injected by hypodermic needle and syringe and containing alum adjuvant. These results demonstrate that needle-free vaccination is both technically and immunologically valid, and could be considered for vaccines in development.

We aimed to analyze if an overload of saturated fat in maternal diet induced lipid metabolic impairments in livers from rat fetuses that persist in the offspring and to identify potential mechanisms involving fetal leptin resistance. Female rats were fed either a diet enriched in 25% of saturated fat (SFD rats) or a regular diet (controls). Fetuses of 21days of gestation and offspring of 21 and 140days of age were obtained and plasma and liver were kept for further analysis. Livers from a group of control and SFD fetuses were cultured in the presence or absence of leptin. Leptin or vehicle was administered to control fetuses during the last days of gestation and, on day 21, fetal livers and plasma were obtained. Lipid levels were assessed by thin-layer chromatography and mRNA gene expression of CPT1, ACO and PPARα by RT-PCR. Liver lipid levels were increased and CPT1 and ACO were down-regulated in fetuses and offspring from SFD rats compared to controls. After the culture with leptin, control fetal livers showed increased ACO and CPT1 expression and decreased lipid levels, while fetal livers from SFD rats showed no changes. Fetal administration of leptin induced a decrease in ACO and no changes in CPT1 expression. In summary, our results suggest that a saturated fat overload in maternal diet induces fetal leptin resistance in liver lipid catabolism, which might be contributing to liver lipid alterations that are sustained in the offspring.

BACKGROUND

Alzheimer's disease (AD) is the most frequently diagnosed form of dementia resulting in cognitive impairment. Many AD mouse studies, using the methyl donor S-adenosylmethionine (SAM), report improved cognitive ability, but conflicting results between and within studies currently exist. To address this, we conducted a meta-analysis to evaluate the effect of SAM on cognitive ability as measured by Y maze performance. As supporting evidence, we include further discussion of improvements in cognitive ability, by SAM, as measured by the Morris water maze (MWM).

METHODS

We conducted a comprehensive literature review up to April 2014 based on searches querying MEDLINE, EMBASE, Web of Science, the Cochrane Library and Proquest Theses and Dissertation databases. We identified three studies containing a total of 12 experiments that met our inclusion criteria and one study for qualitative review. The data from these studies were used to evaluate the effect of SAM on cognitive performance according to two scenarios: 1. SAM supplemented folate deficient (SFD) diet compared to a folate deficient (FD) diet and 2. SFD diet compared to a nutrient complete (NC) diet. Hedge's g was used to calculate effect sizes and mixed effects model meta-regression was used to evaluate moderating factors.

RESULTS

Our findings showed that the SFD diet was associated with improvements in cognitive performance. SFD diet mice also had superior cognitive performance compared to mice on an NC diet. Further to this, meta-regression analyses indicated a significant positive effect of study quality score and treatment duration on the effect size estimate for both the FD vs SFD analysis and the SFD vs NC analysis.

CONCLUSIONS

The findings of this meta-analysis demonstrate efficacy of SAM in acting as a cognitive performance-enhancing agent. As a corollary, SAM may be useful in improving spatial memory in patients suffering from many dementia forms including AD.

Dome-shaped macula (DSM) was recently described in myopic patients as a convex protrusion of the macula within a posterior pole staphyloma. The pathogenesis of DSM and the development of associated serous foveal detachment (SFD) remain unclear. The obstruction of choroidal outflow and compressive changes of choroidal capillaries have been proposed as causative factors. In this paper, we report two cases of patients with chronic SFD associated with DSM treated with oral spironolactone. After treatment, there was a complete resolution of SFD in both patients. To the best of our knowledge, this is the first report of successful treatment of SFD in DSM by a mineralocorticoid receptor antagonist.

Formulating nanoparticles for delivery to the deep lung is complex and many techniques fail in terms of nanoparticle stability. Spray freeze drying (SFD) is suggested here for the production of inhalable nanocomposite microcarriers (NCM). Different nanostructures were prepared and characterized including polymeric and lipid nanoparticles. Nanoparticle suspensions were co-sprayed with a suitable cryoprotectant into a cooled, stainless steel spray tower, followed by freeze drying to form a dry powder while equivalent compositions were spray dried (SD) as controls. SFD-NCM possess larger specific surface areas (67-77 m(2)/g) and lower densities (0.02 g/cm(3)) than their corresponding SD-NCM. With the exception of NCM of lipid based nanocarriers, SFD produced NCM with a mass median aerodynamic diameter (MMAD) of 3.0±0.5 μm and fine particle fraction (FPF⩽5.2 μm) of 45±1.6% with aerodynamic performances similar to SD-NCM. However, SFD was superior to SD in terms of maintaining the particle size of all the investigated polymeric and lipid nanocarriers following reconstitution (S(f)/S(i) ratio for SFD≈1 versus >1.5 for SD). The SFD into cooled air proved to be an efficient technique to prepare NCM for pulmonary delivery while maintaining the stability of the nanoparticles.

In the present study, crude bacterial extract containing violacein is investigated for the preparation of antimicrobial polyamide fabrics. The optimal culture conditions of Janthinobacterium lividum (JL) for maximum biomass and violacein production were found to be 25°C, pH 7.0, while the addition of ampicillin of 0.2 mg mL-1 in the small scale increased violacein production 1.3-fold. In scale-up trials, the addition of 1% (v/v) glycerol in a fed-batch bioreactor, resulted in fivefold extracted crude violacein increase with final concentration of 1.828 g L-1. Polyamide 6.6 fabrics were dyed following three different processes; through simultaneous fermentation and dyeing (SFD), by incubating the fabric in the sonicated bacterial culture after fermentation and by using cell-free extract containing violacein. Maximum color change (ΔE) and color strength (K/S) obtained for SFD fabrics were 74.81 and 22.01, respectively, while no alteration of fastness and staining of dye at acid and alkaline perspiration or at water was indicated. The dyed fabrics presented significant antifungal activity against Candida albicans, C. parapsilosis, and C. krusei, as well as antibacterial properties against Escherichia coli, Staphylococcus aureus, and the S. aureus MRSA. We have shown that J. lividum cultures can be successfully used for violacein production and for simultaneous dying of fabrics resulting in dyed fabrics with antimicrobial properties without utilization of organic solvents.

OBJECTIVE

According to cognitive-behavioral models of hypochondriasis (HYP), biased attentional and memory processes related to health threat stimuli are crucial for the development and maintenance of severe health anxiety. Little is known about the specificity, temporal stability, and modifiability of these biases via psychotherapy.

METHODS

In an emotional Stroop and subsequent recognition task, the authors compared attention and memory processes for health-related words (illnesses, bodily complaints, and panic-related words) in patients with HYP (n = 32), other somatoform disorders (SFD; n = 27), and panic disorder (PD; n = 25). A control group consisted of 31 healthy participants (CG). All patients were reexamined after 4 months of cognitive-behavioral therapy (CBT).

RESULTS

Patients with HYP showed a significant attentional bias toward all 3 target word categories. Evidence for a specific bias was found only for the PD group. General recognition performance for health threat and neutral words was best in the HYP group. After therapy, attentional bias had clearly decreased in the HYP and SFD patients.

CONCLUSIONS

Patients with HYP can be characterized by attentional bias and more elaborate verbal processing. These irregularities tend to disappear after psychotherapy.

OBJECTIVE

To analyze the genetic test results of probands referred to eyeGENE with a diagnosis of hereditary maculopathy.

METHODS

Patients with Best macular dystrophy (BMD), Doyne honeycomb retinal dystrophy (DHRD), Sorsby fundus dystrophy (SFD), or late-onset retinal degeneration (LORD) were screened for mutations in BEST1, EFEMP1, TIMP3, and CTRP5, respectively. Patients with pattern dystrophy (PD) were screened for mutations in PRPH2, BEST1, ELOVL4, CTRP5, and ABCA4; patients with cone-rod dystrophy (CRD) were screened for mutations in CRX, ABCA4, PRPH2, ELOVL4, and the c.2513G>A p.Arg838His variant in GUCY2D. Mutation analysis was performed by dideoxy sequencing. Impact of novel variants was evaluated using the computational tool PolyPhen.

RESULTS

Among the 213 unrelated patients, 38 had BMD, 26 DHRD, 74 PD, 8 SFD, 6 LORD, and 54 CRD; six had both PD and BMD, and one had no specific clinical diagnosis. BEST1 variants were identified in 25 BMD patients, five with novel variants of unknown significance (VUS). Among the five patients with VUS, one was diagnosed with both BMD and PD. A novel EFEMP1 variant was identified in one DHRD patient. TIMP3 novel variants were found in two SFD patients, PRPH2 variants in 14 PD patients, ABCA4 variants in four PD patients, and p.Arg838His GUCY2D mutation in six patients diagnosed with dominant CRD; one patient additionally had a CRX VUS. ABCA4 mutations were identified in 15 patients with recessive CRD.

CONCLUSIONS

Of the 213 samples, 55 patients (26%) had known causative mutations, and 13 (6%) patients had a VUS that was possibly pathogenic. Overall, selective screening for mutations in BEST1, PRPH2, and ABCA4 would likely yield the highest success rate in identifying the genetic basis for macular dystrophy phenotypes. Because of the overlap in phenotypes between BMD and PD, it would be beneficial to screen genes associated with both diseases.

A spray freeze drying (SFD) method was developed to prepare the composite particles of poorly water-soluble drug. The aqueous solution dissolved drug and the functional polymer was sprayed directly into liquid nitrogen. Then, the iced droplets were lyophilized with freeze-dryer to prepare solid particles. Tolbutamide (TBM) and hydroxypropylmethylcellulose (HPMC) were used as a model drug and water-soluble polymeric carrier in this study, respectively. The morphological observation of particles revealed that the spherical particles having porous structure could be obtained by optimizing the loading amount of drug and polymer in the spray solution. Especially, SFD method was characterized that the prepared particles had significantly larger specific surface area comparing with those prepared by the standard spray drying technique. The physicochemical properties of the resultant particles were found to be dependent on the concentration of spray solution. When the solution with high content of drug and polymer was used, the particle size of the resulting composite particles increased and they became spherical. The specific surface area of the particles also increased as a result of higher concentration of solution. The evaluation of spray solution indicated that these results were dependent on the viscosity of spray solution. In addition, when composite particles of TBM were prepared using the SFD method with HPMC as a carrier, the crystallinity of TBM decreased as the proportion of HPMC increased. When the TBM : HPMC ratio reached 1 : 5, the crystallinity of the particles completely disappeared. The dissolution tests showed that the release profiles of poorly water-soluble TBM from SFD composite particles were drastically improved compared to bulk TBM. The 70% release time T(70) of composite particles prepared by the SFD method in a solution of pH 1.2 was quite smaller than that of bulk TBM, while in a solution of pH 6.8, it was slightly lower. In addition, the release rates were faster than those of standard spray dried (SD) composite particles for solutions of pH 1.2 and 6.8, respectively. When composite particles were prepared from mixtures with various composition ratios, T(70) was found to decrease as the proportion of HPMC increased; the release rate was faster than that of bulk TBM in a solution of pH 6.8, as well as solution of pH 1.2.

To develop resistant starch (RS) nanoparticles, waxy rice starch was hydrolyzed with acid for 10 days, and acid-hydrolyzed waxy rice starch (AHW) was cross-linked with sodium trimetaphosphate. The RS nanoparticles were collected by freeze-drying (FD), freeze-drying after sonication (SFD), and ethanol dehydration after sonication (SE). The particle size distribution, RS level by modified AOAC, zeta potential, and stability of dispersion were assessed. The hydrolysis rate ranged from 44.62% to 49.43%, and AHW particle size decreased as hydrolysis time increased. All AHW and RS nanoparticles showed A type crystallinity. The particle size and zeta potential of the nanoparticles dried by FD, SFD, and SE were 300.0, 211.9, and 459.7 nm and -37.1, -43.0, and -35.4 mV, respectively. The RS levels were increased by cross-linking. The SFD dispersion was the most stable. The results indicate that the RS4 nanoparticles, for applying to liquid foods, can be prepared by acid hydrolysis, cross-linking, and SFD.

Although published studies report that screening for distress (SFD) improves the quality of care for patients with cancer, little is known about how SFD impacts healthcare professionals (HCPs).

This quality improvement project examined the impact of implementing the SFD intervention on HCPs' confidence in addressing patient distress and awareness of person-centered care.

This project involved pre-evaluation and post-evaluation of the impact of implementing SFD. A total of 254 HCPs (cohort 1) were recruited from 17 facilities across the province to complete questionnaires. SFD was then implemented at all cancer care facilities over a 10-month implementation period, after which 157 HCPs (cohort 2) completed post-implementation questionnaires. At regional and community care centers, navigators supported the integration of SFD into routine practice; therefore, the impact of navigators was examined.

HCPs in cohort 2 reported significantly greater confidence in managing patients' distress and greater awareness about person-centered care relative to HCPs in cohort 1. HCPs at regional and community sites reported greater awareness in person-centeredness before and after the intervention, and reported fewer negative impacts of SFD relative to HCPs at tertiary sites. Caring for single or multiple tumor types was an effect modifier, with effects observed only in the HCPs treating multiple tumors.

Implementation of SFD was beneficial for HCPs' confidence and awareness of person-centeredness. Factors comprising different models of care, such as having site-based navigators and caring for single or multiple tumors, influenced outcomes.

The vacuolar-type proton pump of clathrin-coated vesicles is composed of two general domains, a peripheral, catalytic sector (VC) and a transmembranous proton channel (VB). In its native form, the enzyme can hydrolyze both MgATP and CaATP, whereas VC, when separated from VB, loses its MgATPase activity and switches to a state that can hydrolyze only CaATP. Further dissociation of VC results in subcomplexes that are depleted of one or more subunits and lack ATPase activity altogether. Reconstitution of recombinant subunits to these biochemically prepared subcomplexes has demonstrated the necessity of polypeptides of 70, 58, 40, and 33 kDa (subunits A, B, C, and E, respectively) for CaATPase activity of the VC complex. The current studies demonstrate that mixtures of these four recombinant subunits cannot support CaATPase activity in the absence of a biochemically prepared subcomplex. Investigation of the other components required for ATPase activity has led to the identification of three additional polypeptides present in preparations of VC, with apparent molecular masses of 15, 14, and 10 kDa. Each of these proteins was found to activate ATPase activity of mixtures of subunits A, B, C, and E. In addition, ATPase reconstituted from these individual subunits hydrolyses ATP, not only in the presence of Ca2+ but also in the presence of Mg2+. Investigation of the individual properties of these three subunits revealed that the 10-kDa polypeptide is subunit F, as determined by immunoblot analysis. This subunit had no effect on MgATPase activity of VC but stimulated CaATPase activity 6-fold in the presence of subunit D. Under optimal conditions the 14-kDa component resulted in a 10-fold stimulation and the 15-kDa component a 20-fold stimulation of MgATPase activity; based on this observation, the 14- and 15-kDa polypeptides were named subunits G and H, respectively. In addition, proton pumping activity was reconstituted through the reassembly of subunits A-H with VB and SFD, a previously described pump component composed of polypeptides of 50 and 57 kDa (Xie, X.-S, Crider, B.P., Ma, Y. M., and Stone, D. K. (1994) J. Biol. Chem. 269, 25809-25815). Together, these experiments completely define the catalytic center of the vacuolar proton pump of clathrin-coated vesicles.

Myocardial infarction (MI), also referred to as heart attack, occurs when there is an interruption of blood flow to parts of the heart, due to the acute rupture of atherosclerotic plaque, which leads to damage of heart muscle. The heart muscle damage produces changes in the recorded surface electrocardiogram (ECG). The identification of MI by visual inspection of the ECG requires expert interpretation, and is difficult as the ECG signal changes associated with MI can be short in duration and low in magnitude. Hence, errors in diagnosis can lead to delay the initiation of appropriate medical treatment. To lessen the burden on doctors, an automated ECG based system can be installed in hospitals to help identify MI changes on ECG. In the proposed study, we develop a single-channel single lead ECG based MI diagnostic system validated using noisy and clean datasets. The raw ECG signals are taken from the Physikalisch-Technische Bundesanstalt database. We design a novel two-band optimal biorthogonal filter bank (FB) for analysis of the ECG signals. We present a method to design a novel class of two-band optimal biorthogonal FB in which not only the product filter but the analysis lowpass filter is also a halfband filter. The filter design problem has been composed as a constrained convex optimization problem in which the objective function is a convex combination of multiple quadratic functions and the regularity and perfect reconstruction conditions are imposed in the form linear equalities. ECG signals are decomposed into six subbands (SBs) using the newly designed wavelet FB. Following to this, discriminating features namely, fuzzy entropy (FE), signal-fractal-dimensions (SFD), and renyi entropy (RE) are computed from all the six SBs. The features are fed to the k-nearest neighbor (KNN). The proposed system yields an accuracy of 99.62% for the noisy dataset and an accuracy of 99.74% for the clean dataset, using 10-fold cross validation (CV) technique. Our MI identification system is robust and highly accurate. It can thus be installed in clinics for detecting MI.

OBJECTIVE

To report novel TIMP3 mutations, and to characterize the ocular phenotype of Sorsby fundus dystrophy (SFD), including a novel early sign for the disease and to report the effect of anti-VEGF therapy.

METHODS

Twenty-one probands of three unrelated families with SFD were investigated using wide-field imaging, confocal laser scanning ophthalmoscopy with autofluorescence imaging, optical coherence tomography (OCT), indocyanine green-angiography (ICG-A), and molecular diagnostic for causative mutations.

RESULTS

Molecular genetic analysis revealed two novel (p.Tyr174Cys, p.Tyr177Cys) and one previously described (p.Tyr182Cys) missense mutations in TIMP3. In families with p.Tyr177Cys and p.Tyr182Cys, metamorphopsia and/or decrease in visual acuity were the initial symptoms occurring at approximately the sixth decade of life. The p.Tyr174Cys mutation carriers had first symptoms at approximately the third decade with dark adaptation problems and visual field defects. The ocular phenotype included drusen-like deposits, rapidly progressive geographic atrophy, choroidal neovascularization (CNV), and polypoidal choroidal neovascularization (PCV). Late disease manifestations were uniform with widespread chorioretinal atrophy, fibrosis, and choroidal thinning. Three asymptomatic young carriers of a TIMP3 mutation with otherwise normal findings on funduscopy and retinal imaging showed a characteristically reduced fluorescence on late-phase ICG-A images. This phenotypic sign was more pronounced and widespread in later disease stages. Patients with CNV or PCV showed a favorable response to therapy with intravitreally injected bevacizumab.

CONCLUSIONS

This study expands the spectrum of mutations in the TIMP3 gene and associated phenotypic findings. Imaging using late-phase ICG-A may be useful for early identification of individuals at risk for developing SFD. Intravitreal anti-VEGF therapy if initiated timely is effective in SFD patients with CNV.

Snake Fungal Disease (SFD), caused by Ophidiomyces ophiodiicola, is the most recently described fungal disease afflicting wildlife populations across North America and Europe. It has been proposed as a significant conservation threat yielding high mortality and yet much its ecology is unknown. We collected 144 skin swabs from Eastern Massasaugas (Sistrurus catenatus) in 2015 and 2016 to determine document ongoing prevalence and assess differences in microbial assemblages between positive and negative individuals. Alpha diversity of fungi was reduced in SFD positive animals, while beta diversity identified distinct assemblages of microbes between SFD-positive and -negative samples. Ophidiomyces was present on the skin of affected animals, even on body sites distant to lesions indicating that the microbiome on entire surface of the skin is altered. Ophidiomyces was not detected in any non-SFD snake. There were smaller, but significant, influences of year sampled. Bacterial genera Janthinobacterium and Serratia were significantly increased in SFD snakes, while Xylanimicrobium, Cellulosimicrobium, and Rhodococcus were the only bacterial taxa significantly reduced. The relative abundance of fungi within the orders Pleosporales and Canopdiales was reduced in SFD-positive samples, though Pyrenochaetopsis pratorum was the only species found to differ significantly. This is the first study to determine the impact that this fungal pathogen has on the skin microbiome.

There is no commercially available real-time dosimeter that can accurately measure output factors for field sizes down to 4 mm without the use of correction factors. Silicon diode detectors are commonly used but are not dosimetrically water equivalent, resulting in energy dependence and fluence perturbation. In contrast, plastic scintillators are nearly dosimetrically water equivalent. A fibre optic dosimeter (FOD) with a 0.8 mm(3) plastic scintillator coupled to an air core light guide was used to measure the output factors for Novalis/BrainLab stereotactic cones of diameter 4-30 mm and Novalis MLC fields of width 5-100 mm. The FOD data matched the output factors measured by a 0.125 cm(3) Semiflex ion chamber for the MLC fields above 30 mm and those measured with the EBT2 radiochromic film for the cones and MLC fields below 30 mm. Relative detector readings were obtained with four diode types (IBA SFD, EFD, PFD, PTW 60012) for the same fields. Empirical diode correction factors were determined by taking the ratio of FOD output factors to diode relative detector readings. The diodes were found to over-respond by 3%-16% for the smallest field. There was good agreement between different diodes of the same model number.

OBJECTIVE

To investigate the frequency of malformations, fetal growth retardation, cerebral hemorrhage and neonatal withdrawal symptoms in newborns exposed to antiepileptic drugs (AEDs) in utero.

METHODS

Population of the northeastern part of Slovenia (pregnant women and newborns between 1998 and 2002).

METHODS

Data on newborns born between 1998 and 2002 of 37 epileptic mothers taking AEDs in pregnancy, of 32 epileptic mothers not taking AEDs in pregnancy and of 211 mothers healthy in pregnancy were ascertained from hospital obstetric and neonatal records and included in the study. The health status of 270 newborns was assessed.

METHODS

frequency of congenital malformations, growth retardation (SFD), intracranial hemorrhage, feeding problems and withdrawal symptoms.

RESULTS

In the group not exposed to antiepileptic drugs (32 neonates), two (2.9%) had germinal matrix hemorrhage grade I, one (1.4%) was small for date (SFD) and one (1.4%) had feeding problems. In the group exposed to antiepileptic drugs (37 neonates), nine (13%) had germinal matrix hemorrhage grade I, six (8.6%) were SFD, five (7.24%) had feeding problems, four (5.8%) had withdrawal symptoms and three (4.3%) "macro" congenital anomalies. Among neonatal problems in the control non-exposed group of newborns of 211 healthy women we identified 23 (10.9%) newborns who were SFD, 5 (2.4%) cases with germinal matrix hemorrhage grade I, 5 (2.4%) cases with major congenital malformations and 7 (3.3%) cases with feeding problems.

CONCLUSIONS

Prenatal antiepileptic drug exposure in the setting of maternal epilepsy is associated with increased risk of neonatal morbidity. In our study a particularly significant connection was established between carbamazepine therapy during pregnancy and cerebral hemorrhage in the neonates.

In an industrial hospital in India, a 23 per cent prevalence of low birth weight (LBW) was detected, of which 76 per cent were full term small for date (SFD) babies. Hypertensive disorders of pregnancy (HDP) comprised the single most common obstetrical problem associated with term SFD births (31 per cent). Age, parity, booking and socio-economic status were all found to contribute to LBW. Babies weighing between 2.25 and 2.5 kg did not show any significant difference in mortality and morbidity as compared to babies weighing more than 2.5 kg at birth. Despite the lower prevalence of LBW found in this study conducted in a fairly literate urban population, an attempt can be made to further decrease this figure.

Idiopathic environmental intolerance (IEI) represents a functional somatic syndrome marked by diverse bodily complaints attributed to various substances in the environment. Evidence for abnormalities in affective information processing similar to somatoform disorders (SFD) has recently been found in people with IEI. In order to further investigate these cognitive-emotional abnormalities, we compared people with IEI (n=49), SFD only (n=43), and non-somatoform controls (n=54) with respect to their performance in the extrinsic affective Simon task (EAST). This task allowed us to dissociate indicators of automatic affective associations and emotional intrusion effects of both bodily complaints and IEI-trigger words. Negative association effects toward IEI-trigger words were strongest for IEI participants. Emotional intrusion effects of symptom words were larger both in IEI and SFD than in controls. The results of enhanced negative automatic evaluations of IEI-trigger words and greater attention allocation to symptom words support cognitive models of IEI.

OBJECTIVE

The goal of this work was to measure 6MV small field, detector specific, output ratios (OR(det)) using the IBA stereotactic field diode (SFD) and the PTW T60008, T60012, T60016 and T60017 field diodes on both Varian iX and Elekta Synergy accelerators, to establish estimates for the experimental uncertainty and characterize the measurement precision under various conditions.

METHODS

Data were acquired at depths of 1.5, 5.0 and 10.0 cm for square field sizes of 3.0, 1.0, 0.9, 0.8, 0.7, 0.6 and 0.5 cm. Three isocentric measurements comprised of five readings were made to calculate an experimental output ratio OR(det) with respect to a field size of 5.0 cm. The coefficient of variation (CV) was calculated to characterize the precision associated with each detector-linac combination. Another measurement set was made to investigate the influence of jaw position accuracy.

RESULTS

As expected for field sizes smaller than 3.0 cm, the measured OR(det) were not consistent across all detectors. The standard percent uncertainty in measured OR(det) was found to be nearly consistent across all detector-linac combinations: less than ±0.25% for the 3.0 cm field size, increasing to approximately ±1.25% for the smallest field sizes. As the field size was reduced to 0.5 cm the CV increased to 0.10% and 0.15% on the Varian and Elekta linacs, respectively.

CONCLUSIONS

Experimental small field OR(det) measured with the diode detectors used in this study are reproducible to within ±1.25% (standard uncertainty), with the precision of any one set of measurements can be characterized with a CV between 0.10% and 0.15%.

The present study describes a new method for converting a typical point process, such as a train of neuronal action potentials (spikes), into a planar curve which is then processed by means of a fast algorithm to calculate and display the fractal dimension D values of each of a sequence of blocks having an equal and preselectable number of interspike intervals, hence the term sequential fractal dimension D (SFD). This method is fast, does not require special computing facilities, and provides a continuous, high temporal resolution display of the neuronal discharge complexity along the course of spontaneous activity or event relating changes. The method affords insight into short duration changes in neuronal behaviour in a way independent of its discharge rate. SFD analysis of spike trains from spinal dorsal horn neurons suggests that the neuronal response to a given stimulus can be expressed as changes in the discharge pattern complexity, thus revealing a novel sensory coding strategy.