Tumor necrosis factor alpha/cachectin is a growth factor for thymocytes. Synergistic interactions with other cytokines.
Recombinant murine (rm) TNF-alpha but not recombinant human (rh) TNF-alpha induces the proliferation of murine thymocytes in the presence of a comitogenic stimulus. This effect does not appear to be due to the production of significant levels of IL-1, IL-2, or IL-4. although not directly mitogenic (i.e., in the absence of PHA-P) for thymocytes, rmTNF-alpha amplifies the direct mitogenic signals from hIL-1 and rhIL-2 but not rmIL-4. In the presence of PHA-P, thymocytes stimulated with hIL-1, rhIL-2, and rmIL-4 produced significant amounts of TNF-alpha. Although rhTNF-alpha does not induce a proliferative response, it will competitively inhibit the proliferative response of thymocytes to rmTNF-alpha. These data suggest a critical role for TNF-alpha in the intrathymic proliferation of developing T cells.


Functional changes at the preferred retinal locus in subjects with bilateral central vision loss.
Subjects with bilateral central vision loss (CVL) use a retinal region called the preferred retinal locus (PRL) for performing various visual tasks. We probed the fixation PRL in individuals with bilateral macular disease, including age-related macular degeneration (AMD) and Stargardt disease (STGD), for localized sensitivity deficits. Three letter words at the critical print size were presented in the NIDEK MP-1 microperimeter to determine the fixation PRL and its radial retinal eccentricity from the residual fovea in 29 subjects with bilateral CVL. Fixation stability was defined as the median bivariate contour ellipse area (BCEA) from 3 fixation assessments. A standard 10-2 grid (68 locations, 2° apart) was used to determine central retinal sensitivity for Goldmann size II test spots. Baseline and follow-up supra-threshold screening of the fixation PRL for localized sensitivity deficits was performed using high density (0.2° or 0.3° apart) 0 dB Goldmann size II test spots. Custom MATLAB code and a dual bootstrapping algorithm were used to register test-spot locations from the baseline and follow-up tests. Locations where the 0 dB test spots were not seen on either test were labeled as micro-scotomas (MSs). Median BCEA correlated poorly with the radial eccentricity of the fixation PRL. Mean (±SD) sensitivity around the PRL from 10-2 testing was 4.93 ± 4.73 dB. The average percentage of MSs was similar for patients with AMD (25.4%), STGD (20.3%), and other etiologies of CVL (27.1%). The fixation PRL in subjects with bilateral CVL frequently includes local regions of sensitivity loss.


The role of three-dimensional power Doppler ultrasound parameters measured on hCG day in the prediction of pregnancy during in vitro fertilization treatment.
To investigate the value of ultrasound for the assessment of endometrial receptivity during in vitro fertilization (IVF) and embryo transfer (ET). Only those patients in their first IVF cycle, followed a standard long gonadotropin releasing hormone (GnRH) agonist long ovarian stimulation regimen, and had 2 highest scoring embryos transferred on day 3 were included in the study. A 3D ultrasound examination was performed on the day of human chorionic gonadotropin (hCG) injection to determine endometrial thickness, endometrial pattern, peak systolic velocity (PSV), end diastolic velocity (EDV), pulsatility index (PI) and resistance index (RI) of endometrial spiral arteries, endometrial volume, vascularization index (VI), flow index (FI) and vasculariztion flow index (VFI) of endometrial and subendometrial region. Analyses were carried on between pregnant and non-pregnant groups, and miscarriage and ongoing pregnant groups. 435 patients were included in the study, in which 235 (58.8%) got clinical pregnancy, and 49 suffered miscarriage. Patients in both pregnant group and non-pregnant group, and miscarriage and ongoing pregnant group did not show significant difference in endometrial thickness, endometrial volume, endometrial pattern, uterine PI, RI, S/D, endometrial and subendometrial VI, FI and VFI. In relative thin endometrium group, pregnant patients had similar endometrial thickness, endometrial volume, endometrial pattern, uterine PI, RI, S/D, endometrial and subendometrial VI, FI and VFI with non-pregnant patients. 3D PDUS parameters of endometrium measured on hCG day were not good predictors of pregnancy in IVF treatment, neither good predictors of ongoing pregnancy.


Numerical phenetic classification of clinically significant aerobic sporoactinomycetes and related organisms.
Clinically significant aerobic sporoactinomycetes, notably agents of mycetoma, were examined for a balanced set of unit characters and the resultant data analysed using standard numerical taxonomic procedures. All save two of the one hundred and seventy three tested strains were assigned to three multimembered cluster-groups, which encompassed sixteen major (4-7 strains), ten minor (2-3 strains) and forty single membered clusters, in an analysis based on the simple matching coefficient and unweighted pair group method with arithmetic averages algorithm. The three cluster-groups were equated with the genus Actinomadura (including Actinocorallia and Streptomyces somaliensis strains), and the genera Nocardiopsis and Streptomyces, and Thermobifida and Thermomonospora, respectively. In a corresponding principal co-ordinates analysis four multimembered groups corresponding to the genera Actinomadura, Nocardiopsis, Streptomyces, and Thermobifida and Thermomonospora were recognised. The causal agents of actinomycetoma were not only assigned to established taxa, notably, to Actinomadura latina, Actinomadura madurae, Actinomadura pelletieri and Streptomyces somaliensis, but also to additional centres of taxonomic variation which were equated with the rank of species. Most of the streptomycetes isolated from clinical material were assigned to clusters equated with the species Streptomyces albus and Streptomyces anulatus. The numerical taxonomic data were used to generate a frequency matrix designed to facilitate the identification of clinically significant Actinomadura, Nocardiopsis and Streptomyces strains to the species level; rapid enzyme tests accounted for eleven out of the twenty-one diagnostic tests.


Remote ischaemic preconditioning shortens QT intervals during exercise in healthy subjects.
The protective action of remote ischaemic preconditioning (RIPC) has been demonstrated in the context of surgical interventions in cardiology. Application of RIPC to sports performance has been proposed, but its effect on the electrocardiogram (ECG) during exercise remains unknown. This exploratory study aims to measure the changes in ventricular repolarization observed during exercise following RIPC in healthy subjects. In an experimental randomized crossover study, 17 subjects underwent two bouts of constant load exercise tests at 75% and 115% of gas exchange threshold (GET). Prior to exercise, they were allocated to either control or RIPC intervention with four cycles of 5 min of ischaemia followed by 5 min of reperfusion. ECG was continuously recorded during the protocol. QT and RR intervals were measured every 30 s (on an average tracing of the preceding 10 s). Although the time course of RR intervals did not differ between the two interventions (p = .56 at 75% GET and p = .74 at 115% GET), a significant shortening of QT intervals (measured from Q onset to T end) was observed during exercise (mean ± standard deviation of RIPC vs. -32 ± 19 ms at 75% GET (p < .001) and -34 ± 12 ms at 115% GET (p < .001)) as well as during recovery (-21 ± 8 ms at 75% GET (p < .001) and -16 ± 11 ms at 115% GET (p < .001)). This effect was not present at rest. These RIPC-related changes were clearly identifiable on the QT-RR loops after hysteresis reduction. RIPC therefore induces heart rate-independent shortening of QT intervals that is revealed during exercise.


An electron microscopic study of cells with steroid-secreting morphology in the paraaortic lymph node of the hamster.
Clustered cells with steroid-secreting morphology (SH), located within the paraaortic lymph node (PLN) capsules of normal and pregnant female golden hamsters, were examined by light and electron microscopy. Hydroxysteroid dehydrogenase (HD) activity of the SH cell cluster also was examined by histochemical techniques. The cluster was composed of mostly packed SH cells and surrounding mesenchymal cells. Individual SH cells possessed prominent smooth endoplasmic reticulum, well-developed Golgi complexes, some lipid droplets, and numerous mitochondria containing tubulovesicular cristae common to mammalian SH cells. Intermediate-type junctions were often observed between SH cells. The same SH cells were rarely detected in the subcapsular sinus and in the cortical parenchyma of the PLN. Early oophorectomy of the hamster resulted in cytoplasmic degeneration of the SH cell at day 5 after the operation. On the other hand, normal adult male hamsters possessed similar PLNs, but no SH cells were recognized in the nodes. The present histochemical preparation of normal female PLNs revealed moderate-to-strong HD activity, probably associated with SH cell clusters, in the limited regions of the capsules. Based on the present ultrastructural and histochemical findings, it is proposed that the SH cell cluster consists of steroid hormone producing cells.


Plasma folate, methylenetetrahydrofolate reductase (MTHFR), and colorectal cancer risk in three large nested case-control studies.
Few prospective studies have examined the associations between blood levels of folate, in conjunction with methylenetetrahydrofolate reductase (MTHFR) polymorphisms, and colorectal cancer. We evaluated the associations between plasma folate, MTHFR C677T, and A1298C, and colorectal cancer in three large prospective studies: the Nurses' Health Study, the Health Professionals Follow-up Study, and the Physicians' Health Study. A total of 602 incident cases were identified and individually matched to controls who provided blood specimens. We used conditional logistic regression to calculate the relative risk (RR) and 95% confidence interval (95% CI) and then pooled the estimates using a random effects model. We found a lower risk of colorectal cancer among participants with low plasma folate levels: compared with the lowest quartile, RRs (95% CIs) for each successively higher quartile of plasma folate levels were 1.55 (1.14-2.11), 1.37 (1.00-1.88), and 1.47 (1.07-2.01; P for trend = 0.10). For the MTHFR polymorphisms, RRs (95% CIs) were 0.62 (0.44-0.90) for 677TT versus CC/CT and 0.68 (0.31-1.51) for 1298CC versus AC/AA, and these lower-risk genotypes were associated with lower circulating plasma folate levels. When we partitioned the variation in plasma folate levels, variation due to folate intake was not positively associated with colorectal cancer risk. We found that low plasma folate levels were associated with lower risk of colorectal cancer. The reasons underlying a lower risk of colorectal cancer with low plasma folate levels require elucidation because plasma folate levels can reflect dietary intake, genetic influences, and other factors.


Arsenic species in an arsenic hyperaccumulating fern, Pityrogramma calomelanos: a potential phytoremediator of arsenic-contaminated soils.
The fern Pityrogramma calomelanos is a hyperaccumulator of arsenic that grows readily on arsenic-contaminated soils in the Ron Phibun district of southern Thailand. P. calomelanos accumulates arsenic mostly in the fronds (up to 8350 microg As g(-1) dry mass) while the rhizoids contain the lowest concentrations of arsenic (88-310 microg As g(-1) dry mass). The arsenic species in aqueous extracts of the fern and soil were determined by high performance liquid chromatography coupled to an inductively coupled plasma mass spectrometer (HPLC-ICPMS) which served as an arsenic specific detector. Only a small part of the arsenic (6.1-12%) in soil was extracted into water, and most of this arsenic (> 97%) was present as arsenate. The arsenic in the fern rhizoids was approximately 60% water-extractable, 95% of which was present as arsenate. In contrast, arsenic in the fern fronds was readily extracted into water (86-93%) and was present mainly as arsenite (60-72%) with the remainder being arsenate. Methylarsonate and dimethylarsinate were detected as trace constituents in only two fern samples. Preliminary estimates of phytoremediation potential suggest that P. calomelanos might remove approximately 2% of the soil arsenic load per year. With due consideration to the type of arsenic compounds present in the fern, and their water-solubility, the option of disposing high arsenic ferns at sea is raised for discussion.


Proteomic exploration of soft and hard biocorona onto PEGylated multiwalled carbon nanotubes.
In nanomedicine, carbon nanotubes (CNTs) are considered potential candidates as drug delivery systems. The absorption of proteins onto CNTs, after their administration in physiological environment, forms the protein corona or biocorona, which is able to influence their biological properties and biocompatibility. For this reason, characterization of protein corona is a crucial aspect in the research to control CNTs toxicity and capability to target cells. Multiwalled carbon nanotubes (MWCNTs) were functionalized with polyethylene glycol (PEG), chosen considering its well-known biocompatibility, and then incubated in human plasma to create the biocorona. Plasma proteins, which bound around PEGylated CNTs, were detached using five different solutions, grouped into native and denaturant buffers, and used to characterize the two components of biocorona. The proteomic fingerprinting of biocorona was performed by SDS-PAGE and 2D-PAGE separation and mass spectrometry analysis. Native eluents were able to capture proteins of soft corona, characterized by complex secondary structures, and formed by both β-sheet and α-helices domains. Denaturant buffers have eluted many proteins with a high percentage of the α-helix structure that could be involved in specific interactions responsible for the formation of hard corona.


First evidence of microplastic contamination in the freshwater of Lake Guaíba, Porto Alegre, Brazil.
The ubiquitous presence of microplastics in the aquatic environment has raised concern about their potential impacts on and risks to the biota. While the presence of microplastics in a marine environment has been well studied, the impact of microplastic contamination in freshwater bodies is understudied. In the present study, baseline data about contamination with microplastics in Lake Guaíba in southern Brazil are presented. The abundance, distribution, and composition of microplastics in the surface of this freshwater body were investigated, and these parameters were correlated with population density, land occupation, wind, and geohydrologic processes. The samples were collected with a manta net (60 μm mesh size). Microplastics were found in all the samples, with an average of 11.9 ± 0.6 to 61.2 ± 6.1 items m-3, which indicates the widespread contamination of the lake with plastic particles. The most frequent microplastic morphology was the fragment type in the size range of 100 to 250 μm, and the predominant colours were white/transparent and red. Measurement uncertainty of the visual microplastic counts showed that black colour microplastics is more susceptible to be mistaken, which might lead to an underestimation and/or overestimation of the total number of microplastics. Polypropylene and polyethylene together comprised most of the polymer types (98%). Micro-Fourier transform infrared (micro-FTIR) spectroscopy analyses showed that 58% of the analysed polymers were highly oxidised, indicating long residence of this particles in the water. In addition, our data show that the distribution of microplastics is strongly influenced by the geohydrological characteristics of the lake. Therefore, this research may provide information for further investigations of microplastic distribution in Lake Guaíba and can serve as a base to improve the regulations regarding waste management to effectively reduce microplastic pollution in freshwater systems. Additionally, the measurement uncertainty showed that black microplastics are more susceptible to variations in their measurements.


Idiopathic hypereosinophilic syndrome with infiltration of cerebrospinal fluid by immature eosinophils: a case report and literature review.
Idiopathic hypereosinophilic syndrome is characterized by persistent hypereosinophilia with end organ damage and no definite underlying cause. It has been recognized that eosinophils can induce varying degrees of neural damage. There are only a few reports in the literature regarding CSF by eosinophils, and the relationship between hypereosinophilic syndrome and eosinophilic leukemia remains unclear. We report a case of IHS with CSF infiltration by immature eosinophils and significant subdural effusion with underlying brain parenchyma compression. He was treated by inserting a subdural-peritoneal shunt with improvement. Respiratory distress and pulmonary infiltration with eosinophils developed. Imatinib mesylate (Gleevec) was added with improvement, and subsequent CSF study showed normalization of CSF cytology analysis. However, re-collection of subdural fluid developed later and resulted in consciousness disturbance, and the patient died thereafter. Idiopathic hypereosinophilic syndrome remains a serious condition with a poor prognosis for most patients. Cerebrospinal fluid infiltration by immature eosinophils is a rare condition in IHS and may lead to poor prognosis, as observed in this patient, despite improved medical management (steroid and imatinib mesylate) and adequate surgical shunting for the subdural effusion.


Determination of hydroxypropyl-beta-cyclodextrin in plasma and urine by size-exclusion chromatography with post-column complexation.
The analytical method described here provides the appropriate sensitivity and selectivity for the determination of unlabelled hydroxypropyl-beta-cyclodextrin as a parenteral carrier in pharmaceutical formulations. The method may also be used in clinical trials evaluating the fate and pharmacokinetic profile of this compound, which was isolated from the biological matrix by solid-phase extraction with Bond Elut C18 cartridges. The lack of uniformity of the product was circumvented by the use of a size-exclusion chromatographic column. An indirect colorimetric complexation method was used for detection. The detection limit was 0.1 micrograms per 2 ml of biological fluid and the extraction recovery was sufficient (78%).


First outbreak of multidrug-resistant tuberculosis (MDR-TB) in Denmark involving six Danish-born cases.
Denmark is a low-incidence country for tuberculosis (TB) and multidrug-resistant (MDR) TB at 5 and 0.05 cases per 100,000 population, respectively. Until 2018, the transmission of MDR-TB was nonexistent except for a few pairwise related family cases. In this study, we describe the first MDR-TB outbreak in Denmark. On the basis of genotyping of all Mycobacterium tuberculosis (Mtb) culture-positive cases in Denmark spanning 3 decades, 6 molecular- and epidemiologically linked Danish-born cases were identified as the first cluster of an MDR-TB in Denmark. The primary case was diagnosed posthumously in 2010 followed by 5 epidemiologically linked cases from 2018 to 2019. Through a combination of routine Mtb genotyping and clinical epidemiological surveillance data, we identified the first Danish MDR-TB outbreak spanning 10 years and were able to disclose the specific transmission pathways in detail, which helped guide the outbreak investigations. The occurrence of an MDR-TB outbreak in a resource-rich low TB incidence setting such as Denmark highlights the importance of a collaborative control system combining classic contact tracing; timely identification of drug-resistant TB through rapid diagnostics; and a close collaboration between clinicians and classical- and molecular epidemiologists for the benefit of TB control.


Cytochrome P4501A induction and testosterone hydroxylation in cultured hepatocytes of four fish species.
Primary hepatocytes of the rainbow trout (Oncorhynchus mykiss), flounder (Platychthis flesus), dab (Limanda limanda) and lemon sole (Microstomus kitt) were exposed to 3,3'4,4'5 pentachlorobiphenyl (PCB 126) or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for two days. This resulted in a dose-dependent induction of cytochrome P4501A (CYP1A) activity, measured as ethoxyresorufin O-deethylase (EROD), or methoxyresorufin O-deethylase (MROD) activity. In all species, a linear relationship was observed between EROD and MROD activities, suggesting that the same CYP1A enzyme metabolizes the two alkoxy-resorufin substrates. Exposures of hepatocytes of flounder or dab to TCDD, resulted in a 59-fold and 8.2-fold induction of EROD activity, respectively. This did not concur with a change in the in vitro testosterone hydroxylation profiles of both species. These and other in vitro data indicate that TCDD exposure does not influence monooxygenase activities involved in testosterone hydroxylation. Furthermore, CYP1A is of minor importance for testosterone hydroxylation in these fish species.


Perception of eating and exercise in children as a function of child and parent weight status.
The present study assessed the effects of child body weight (obese/lean) and familial loading for obesity (two obese parents/two lean parents) on the psychophysics of sweetness, fatness and exercise workloads, as well as subjective ratings of foods varying in sugar and fat and activities varying in energy expenditure. Children were measured in a baseline state and at 6 months after the obese children had participated in a family-based behavioral weight control program. No differences between obese and lean children in perceptual ratings were observed. However, offspring of obese or lean parents differed on intensity rating, food palatability and activity enjoyment ratings. Intensity ratings for sweetness in offspring of obese parents was increased, with a similar trend for intensity ratings for fatness. Offspring of obese parents rated all foods and activities with lower palatability and enjoyment ratings than offspring of lean parents. After a 6 month family-based behavioral weight loss treatment, obese children had significant decreases in percent overweight while lean children remained stable. Changes in the pattern of food ratings were observed for the obese children, with a reduction in liking for foods high in fat and/or sugar, and an increase in ratings for food slower in fat and sugar. The effects of parental obesity on food and exercise intensity ratings and hedonic ratings were maintained. Overall, these results suggest parental weight influences behavioral factors related to obesity in children.


In quest for method of insulin resistance assessment in everyday clinical practice-Insulin resistance indices.
Insulin resistance (IR) a state of decreased sensitivity of target tissues to insulin is suspected usually in obese so can be overlooked in normal weight subjects thus it is important to find optimal method of IR assessment in clinical practice. HOMA, HOMA2, QUICKI, Matsuda index were calculated using data obtained from medical history of 130 female subjects - patients of the Department of Endocrinology and Metabolic Diseases, in whom oral glucose tolerance test (OGTT) with parallel insulin concentrations assessment was performed. IR correlated positively with body mass index (BMI) in the entire study group, regardless which of four analyzed IR indices was used. Insulin resistance occurred in the obese as well as in normal weight and underweight subjects. The incidences of IR in the study group varied, depending upon chosen method and adopted cut-off values. The need for quantitative assessment of IR in clinical practice is apparent. Proper selection of the best method of IR assessment remains a problem. HOMA appears the method of first choice for clinical use. There is an urgent need to establish universal or, at least, national standard cut-off values for IR, to introduce IR assessment in clinical practice.


Strategies of therapeutic contact: working with children with severe object relationship disturbance.
This article discusses the strategies for making contact with severely disturbed children from the viewpoint of developmental ego psychology. Four stages of object development are described and the strategies for making contact at the various levels of impairment are explained in detail.


Psychosocial Maturity, Autonomy, and Transition Readiness among Young Adults with Congenital Heart Disease or a Heart Transplant.
The population of young adults with congenital heart disease (CHD) or a heart transplant (HTx) is growing rapidly. These survivors require lifelong cardiology care and must assume self-management responsibilities with respect to their health. Accordingly, we sought to assess psychosocial maturity and validity of the Transition Readiness Assessment Questionnaire (TRAQ) in this population. The study was designed as a cross-sectional observational study. The study was set at tertiary-care pediatric and adult cardiology clinics in Edmonton and Toronto, Canada. The patients were 18- to 25-year-olds with moderate or complex CHD or a HTx in childhood. Participants completed validated instruments including the TRAQ, Erickson's Psychosocial Stage Inventory (EPSI), and Kenny's Parental Attachment Questionnaire (PAQ). We enrolled 188 participants (41% women), 109 (58%) having moderate CHD, 64 (34%) complex CHD, and 15 (8%) with a HTx. Mean age for those followed in a pediatric clinic was 21.3 ± 2.3 years, compared with 21.8 ± 2.3 years for those attending an adult clinic (P = 0.20). All questionnaire scores were similar among participants with moderate CHD vs. complex CHD vs. an HTx, and among participants followed in a pediatric clinic vs. an adult clinic. EPSI and PAQ scores were similar to those of healthy populations, though perception of maternal overprotection was common. TRAQ scores increased with age. A response of "not needed for my care" to 5 or more of the 29 TRAQ items was provided by 110 (75%) participants. Age, but not disease severity should be a factor when considering the transition needs of young adults with heart disease. The TRAQ has important limitations in the adult CHD/HTx population and a cardiac-specific measure of transition readiness is needed.


Interpreting the Results of Trials of BCG Vaccination for Protection Against COVID-19.
BCG vaccination has beneficial off-target ("nonspecific") effects on nonmycobacterial infections. On this premise, trials set out to investigate whether BCG provides off-target protection against coronavirus disease 2019 (COVID-19). A literature search identified 11 randomized "BCG COVID-19" trials, with conflicting results. These trials and the differences in their study design are discussed using the PICOT (participants, intervention, control, outcome, and timing) framework to highlight the factors that likely explain their inconsistent findings. These include participant age, sex and comorbid conditions, BCG vaccination strain and dose, outcome measure and duration of follow-up. Understanding how to control these factors to best exploit BCG's off-target effects will be important in designing future trials and intervention strategies.


Inhibition of low density lipoprotein uptake in confluent endothelial cell monolayers correlates with a restricted surface receptor redistribution.
Binding of either low density lipoprotein (LDL) or Concanavalin A (ConA) to actively growing vascular endothelial cells is associated with a redistrubution of the appropriate cell surface receptor sites which form patches and caps. This receptor lateral mobility is greatly restricted when endothelial cells reach confluence and adopt the configuration of a cell monolayer composed of closely apposed and non-overlapping cells. In this case, although the cells still exhibit specific LDL binding to the appropriate cell surface receptor sites, neither the binding of LDL nor of ConA induces a receptor redistribution. The lack of LDL receptor redistribution correlates with a marked decrease in the rate of LDL internalization. In contrast, no such density-dependent changes are observed in cell types which grow on top of each other and form multiple cell layers at confluence. Thus, neither LDL nor ConA induced cap formation in either sparse or confluent smooth muscle cell cultures and the same rate of LDL internalization is observed at both cell densities. Similarly, adsorptive endocytosis of cationized LDL (which enters the cells independently of the LDL receptor sites) was not correlated with a detectable receptor redistribution, nor was it significantly affected by changes in cell density and spatial organization. The formation of a confluent cell monolayer resting on an underlying basement membrane might therefore provide, via a change in membrane dynamics, a mechanism whereby the endothelium of large blood vessels can function as a protective barrier against the high circulating levels of LDL in plasma.


[The clinical characteristics and the treatment of external auditory canal cholesteatoma].
To evaluated the characteristics, stage classification and treatment of external auditory canal cholesteatoma (EACC). Fifty-nine cases (60 ears) with EACC undergoing surgery were retrospectively analyzed in our study. Hearing impairment, otalgia and otorrhea were common symptoms of EACC patients. A total of 60 ears were classified into 4 stages: Stage I (26 ears) underwent canaloplasty, stage II (14 cars) underwent both canaloplasty and tympanoplasty, stage III (19 ears) underwent mastoidectomy, and stage IV (1 ear) required both canaloplasty and neoplasty of capsula articularis articulations temporomandibular. Besides the lesion in external auditory canal, EACC also invaded into the middle ear and the temporal bone. Stage classification by the signs of the temporal bone computed tomography and the patients' clinical findings was helpful for surgery.


The effect of intramuscular stanozolol on fibrinolysis and blood lipids.
The effects of a single 50 mg intramuscular injection of the anabolic steroid stanozolol (Stromba) on fibrinolysis, blood coagulation and lipids was evaluated in 12 healthy male volunteers. Significantly increased plasminogen activator levels (p less than 0.05) was noted 24 hours following the injection and these remained elevated for one week. Plasminogen levels increased significantly by day two (p less than 0.01) and remained elevated for three weeks. HDL cholesterol fell (p less than 0.01) and both total and LDL cholesterol increased (p less than 0.05) when measured one month post injection. Stanozolol appears to have therapeutic potential as an activator of the fibrinolytic system when given by intramuscular injection.


Supervised, individualised exercise reduces fatigue and improves strength and quality of life more than unsupervised home exercise in people with chronic Guillain-Barré syndrome: a randomised trial.
In people in the chronic phase of Guillain-Barré syndrome (GBS), how much more does a supervised, individualised exercise program improve functional independence with activities of daily living than a home-based exercise program? How do the two exercise programs compare regarding their effects on muscle strength, fatigue, pain and quality of life? Randomised controlled trial with concealed allocation, intention-to-treat analysis and blinding of outcome assessors. Sixteen adults with stable residual disability ≥ 6 months after the onset of GBS. Participants in the experimental group were allocated to 60-minute sessions of physiotherapist-supervised strengthening, endurance and breathing exercises, gait training and pain management, two to three sessions/week for 12 weeks. The control group was prescribed a home program of 30-minute sessions of maintenance exercises and education in self-management, two to three sessions/week for 12 weeks. Functional independence in activities of daily living on the 100-point Barthel Index (primary outcome), muscle strength on the 60-point Medical Research Council scale, fatigue on the 0-to-63 Fatigue Severity Scale, a visual analogue scale of pain severity, and quality of life, measured at baseline and months 6 and 12. At month 6, the median between-group difference was 5 (95% CI 0 to 20) for functional independence, 8 (95% CI 4 to 18) for strength, -13 (95% CI -28 to -1) for fatigue, and 12 (95% CI 3 to 13) for the environment domain of quality of life. Estimated effects at month 12 had a similar magnitude, but most of the CIs had greater uncertainty. Supervised, individualised exercise reduced fatigue and improved strength and quality of life more than unsupervised home exercise in people with chronic Guillain-Barré syndrome. CTRI/2016/08/007150.


Involvement of unusual glutamate release in kainate-induced seizures in zinc-deficient adult rats.
Enhanced susceptibility to kainate-induced seizures is linked to a lack of increase in GABA release in zinc-deficient young rats. In the present study, susceptibility to kainate-induced seizures was examined in adult (12-week-old) rats fed a zinc-deficient diet for 4 weeks to evaluate the relationship between the dysfunction of GABAergic neurotransmitter system and seizure susceptibility in zinc deficiency. Susceptibility to kainate-induced seizures was enhanced in zinc-deficient adult rats. Extracellular glutamate concentration in the hippocampus was markedly (>2 times) higher in zinc-deficient adult rats than in the control before and after treatment with kainate. Extracellular zinc concentration in the hippocampus was also higher in zinc-deficient adult rats. Interestingly, it was decreased in both zinc-deficient and control rats after treatment with kainate. In some zinc-deficient adult rats, extracellular GABA concentration in the hippocampus was increased with extracellular glutamate concentration after treatment with kainate. When the capacity for GABA release was examined by excessive stimulation with 100mM KCl, extracellular GABA concentrations were significantly increased even in zinc-deficient adult rats. These results suggest that GABA can be excessively released in zinc-deficient adult rats. An unusual glutamate release may be involved in the enhanced susceptibility to kainate-induced seizures in zinc-deficient adult rats.


Bioluminescence-activated photodynamic therapy for luciferase transfected, grade 4 astrocytoma cells in vitro.
. Grade 4 astrocytoma is incurable due to the diffusely infiltrative nature of the disease. Photodynamic therapy (PDT) is a promising therapeutic option, but external light delivery is not feasible when cancer cells infiltrate unknown areas of normal brain. Hence the search for endogenous sources such as bioluminescence that can generate light at cancer cells. This requires a substrate (a luciferin) and an enabling enzyme (a luciferase), neither seen in mammalian cells. . Preliminary studies confirmed that U87 cells (derived from a human grade 4 astrocytoma) could be killed by conventional PDT using the photosensitizers hypericin or mTHPC. U87 cells were then transfected with firefly and other luciferases and light generating cell lines (U87-luc, U87-hRluc, U87-CBG68luc) identified using the appropriate substrate. Reagent doses and conditions were optimized and U87-luc cells incubated with hypericin or mTHPC with d-luciferin added to initiate bioluminescence activated PDT (bPDT). Cell survival was assessed by MTT assay, haemocytometry and growth assay. Control groups included U87-luc cells with no added active reagents, substrate only, photosensitizer only and non-transfected U87 cells. Results were expressed as a percentage of surviving cells compared with untreated U87-luc controls. . There was no bPDT effect on non-transfected cells. The mean survival of treated transfected cells was 36%, (P<0.001) using hypericin and 35% (P<0.001) using mTHPC, compared with untreated U87-luc cells. bPDT effects were suppressed by the anti-oxidant, lycopene. . bPDT can kill Grade 4 astrocytoma cells transfected with luciferase in vitro. This justifies progression to in vivo studies.


Protective action of intravesical oxybutynin on bladder ultrastructure in rabbits with detrusor overactivity.
To evaluate the protective effect of intravesical oxybutynin on the ultrastructure of rabbits with detrusor overactivity (DO). Seventeen North Folk male rabbits were distributed into three groups: GI (n = 5) used as control, GII (n = 5), and GIII (n = 5) with DO. One animal from GII and one from GIII were excluded because they did not develop DO. In GIII, the animals were treated with daily intravesical application of 0.5 mg/Kg of oxybutynin for 30 days. Bladder weight was significantly higher in animals from GII and GIII as compared to GI. After 30 days, cystometric study revealed that vesical capacity was significantly decreased in GII and GIII. Detrusor pressure was significantly higher in GII. Electron microscopy showed increase of intercellular space, cell junctions and caveolae areas asymmetries, mitochondria and cellular degeneration in GII, while in GIII, these alterations have improved after a 30-day treatment. Animals treated with intravesical oxybutynin presented ultrastructural aspect similar to normal.


Source, transport, and fate of perfluoroalkyl acids (PFAAs) in turbid bay environments: Significant roles of suspended sediment and water column stratification.
The coastal area was the major region receiving pollution from land-based sources into the sea. Perfluoroalkyl acids (PFAAs) in famous bays had aroused wide concern, but the importance of underdeveloped or small bays with notable levels of PFAAs were often neglected. Moreover, the roles of suspended sediment (SPS) and water column stratification on PFAA behaviors were unclear. In this study, PFAAs distribution in multiphase-multilayer in four underdeveloped bays (two urban bays and two island bays) were investigated. The urban bays not only had higher PFAA contamination but also posed a greater threat of short-chain PFAAs in water-SPS-sediment system than the island bays. The major source of PFAAs in water and SPS was domestic sewage in urban bays and was rainfall-runoff in island bays. Water column stratification with higher PFAA partition in water-SPS system in the surface layer than in the bottom layer was only found in the urban bays due to the higher human activity intensity. These provided new perspectives for managing emerging contaminants and establishing water quality criteria in the turbid coastal environment. The key role of SPS as a carrier offered possibilities to accurately differentiate the effects of dissolved and particulate PFAAs on bioavailability.


Multifunctional Catalytic Surface Design for Concerted Acceleration of One-Pot Hydrosilylation-CO2 Cycloaddition.
Silica-supported Rh-ammonium iodide catalyst showed high performance for hydrosilylation-CO2 cycloaddition reaction sequences. The catalyst was prepared by surface grafting of Rh and the silane-coupling reaction of the ammonium iodide moiety. The acceleration of each catalytic reaction was realized due to the concerted catalysis between Rh species, immobilized organic functions, and surface Si-OH groups. As a result, good to excellent yields of silyl carbonates were obtained from epoxyolefins, hydrosilanes, and CO2 under mild reaction conditions.


Induction of labor at 41 weeks of pregnancy among primiparas with an unfavorable Bishop score.
To determine the rate and factors associated with the successful Induction of Labor (IOL) in nulliparous patients undergoing scheduled IOL at 41 weeks of gestational age (GA) with an unfavorable cervix. This was a retrospective analysis that included nulliparous patients who presented to the Labor and Delivery unit at the Bronx Lebanon Hospital Center between 2011 and 2012 for elective IOL at 41 weeks of GA. The Bishop score was assessed upon admission and IOL agents were used in compliance with ACOG guidelines in different combinations, based on the obstetrical team preference. Labor and Delivery Unit of the Bronx Lebanon Hospital. Nulliparous patients with 41 weeks of pregnancy for elective induction of labor. Seventy-six patients were included in the study. GA was confirmed using a combination of the last menstrual period and a dating sonogram during pregnancy. This was a retrospective chart review that included nulliparous patients who presented to the Labor and Delivery unit at the Bronx Lebanon Hospital Center between October 2011 and October 2012 for elective IOL at 41 weeks of gestational age with an unfavorable cervix defined as a Bishop score of 6 or less. The overall successful rate of IOL in a combination of different maternal factors with different agents for induction in nulliparous patients undergoing scheduled IOL with an unfavorable Bishop score at 41 weeks of GA was 51.32 %. Factors associated with successful IOL were younger age [22.3 years vs. 25.1(p = 0.015)], lower BMI [25 vs. 28.1(p = 0.46)] and lower maternal weight [64.75 kg vs. 74.02 (p = 0.28)]. Maternal height was not a contributing factor; the artificial rupture of membranes, epidural anesthesia and the prostaglandins used did not contribute. Use of cervical balloon and oxytocin was associated with failed IOL. Patients undergoing IOL at 41 weeks with an unfavorable cervix had a successful rate of 51.32 %. Younger maternal age, lower weight, and lower BMI were associated with successful IOL.


Anaerobic digestion of thickened waste activated sludge under calcium hypochlorite stress: Performance stability and microbial communities.
Hypochlorite pretreatment has been proven effective in enhancing waste activated sludge (WAS) anaerobic digestion performances recently. In this study, two semi-continuous anaerobic sequencing batch reactors (ASBRs), one fed with Ca(ClO)2 pretreated thickened WAS (TWAS) and one with raw TWAS, were operated at mesophilic conditions (35 °C) for 145 days. Three loading shocks were introduced to each reactor to compare the performance stability and resilience between the digestion of Ca(ClO)2 pretreated TWAS and untreated TWAS. Microbial community shifts were quantified to reveal the microbiome responses to disturbances. The results suggested that 1% Ca(ClO)2 enhanced the digestion of TWAS by inactivating and transforming the biomass to more easily digested substrates. Co-occurrence network analysis revealed that the strongest interactions in the microbial community occurred in the steady state of TWAS anaerobic digestion.


Triarylborane-Appended Anils and Boranils: Solid-State Emission, Mechanofluorochromism, and Phosphorescence.
Herein, the design, synthesis, optical properties, and mechanofluorochromism characteristics of a series of conjugates having covalently linked triarylborane (TAB) and anil/boranil units (TAB-anil: 1 a-3 a and TAB-boranil: 1-3) are reported. The electronic interactions between TAB and anil/boranil in 1 a-3 a and 1-3 were fine-tuned by changing the boryl moiety's position on the phenyl spacer connecting the BMes2 (Mes=mesityl) and anil/boranil units. A boryl moiety at the meta position (1 a) of the phenyl spacer stabilizes the enolic form (E-OH), whereas a boryl moiety at the para position (2 a and 3 a) stabilizes the keto form (Z-NH) in the solid state. However, in solution 1 a, 2 a, and 3 a exhibit keto-enol tautomerism in both ground and excited states. Compounds 1 a-3 a and 1-3 show red-shifted absorption compared with 4 a and 4, which are devoid of TAB moieties, which indicate effective participation of an empty p orbital on the boron center in 1 a-3 a and 1-3. Compounds 1 and 2 showed fluorescence variations in response to external stimuli such as mechanical grinding. Long phosphorescence lifetimes of 18-46 ms were observed for compounds 1-3. The observed optical properties of 1 a-3 a and 1-3 are rationalized in the context of quantum mechanical calculations.


Early-life inflammation primes a T helper 2 cell-fibroblast niche in skin.
Inflammation early in life can prime the local immune milieu of peripheral tissues, which can cause lasting changes in immunological tone that confer disease protection or susceptibility1. The cellular and molecular mechanisms that prompt changes in immune tone in many nonlymphoid tissues remain largely unknown. Here we find that time-limited neonatal inflammation induced by a transient reduction in neonatal regulatory T cells causes a dysregulation of subcutaneous tissue in mouse skin. This is accompanied by the selective accumulation of type 2 helper T (TH2) cells within a distinct microanatomical niche. TH2 cells are maintained into adulthood through interactions with a fibroblast population in skin fascia that we refer to as TH2-interacting fascial fibroblasts (TIFFs), which expand in response to TH2 cytokines to form subcutaneous fibrous bands. Activation of the TH2-TIFF niche due to neonatal inflammation primes the skin for altered reparative responses to wounding. Furthermore, we identify fibroblasts in healthy human skin that express the TIFF transcriptional signature and detect these cells at high levels in eosinophilic fasciitis, an orphan disease characterized by inflammation and fibrosis of the skin fascia. Taken together, these data define a previously unidentified TH2 cell niche in skin and functionally characterize a disease-associated fibroblast population. The results also suggest a mechanism of immunological priming whereby inflammation early in life creates networks between adaptive immune cells and stromal cells to establish an immunological set-point in tissues that is maintained throughout life.


In vitro morphogenesis in zygotic embryo cultures of neem (Azadirachta indica A. Juss.).
Immature zygotic embryo cultures of neem yielded highly regenerative cultures, with the response varying with the embryo stage at culture. Early dicotyledonous stage embryos were the most responsive followed by torpedo stage embryos. The embryo cultures differentiated three types of regenerants: somatic embryos (SEs), shoot buds and neomorphs. SEs exhibited morphological abnormalities such as pluricotyledony, fusion of cotyledons and absence of cotyledons. Although these SEs showed secondary embryogenesis, the occurrence of normal dicotyledonous embryos was extremely rare. On MS basal medium 3% of SEs developed a long tap root but a plumular shoot did not appear. However, it was possible to regenerate plantlets from immature zygotic embryo cultures of neem via neomorph formation and adventitious shoot bud formation. The transplantation survival of these plants was more than 80%.


Antiestrogen binding sites in microsomal fractions of malignant and nonmalignant human breast tissues.
Antiestrogen binding sites (AEBS) were measured in microsomal fractions of 102 malignant breast tumors and 24 nonmalignant breast tissues. The number of AEBS was determined by Scatchard analysis. The cytosol contents of estrogen and progesterone receptors were also analyzed in these tissues. Overall, 50% of the malignant tumors and 33% of the nonmalignant normal breast tissues had detectable contents of AEBS. No correlation was observed between cytosol estrogen receptor (ER) content and microsomal AEBS in the tumors. Detailed data analysis in patients at Stage IV disease revealed that 60% of estrogen receptor positive tumors had no detectable microsomal AEBS contents whereas in the remaining 40% tumors, high affinity AEBS were observed. On the other hand, AEBS were also detected in 35% of ER-poor tumors. Anti-estrogen binding sites were higher in tumors obtained from premenopausal women than in those of postmenopausal women. The incidence of AEBS-positive tumors or AEBS concentration was not influenced by either the patients' obesity or their disease stage.


Synthesis and characterization of 125I-alpha-conotoxin ArIB[V11L;V16A], a selective alpha7 nicotinic acetylcholine receptor antagonist.
The alpha7 nicotinic acetylcholine receptors (nAChRs) are widely expressed both in the central nervous system (CNS) and periphery. In the CNS, 125I-alpha-bungarotoxin is commonly used to identify alpha7 nAChRs specifically. However, alpha-bungarotoxin also interacts potently with alpha1* and alpha9alpha10 nAChRs, two receptor subtypes in peripheral tissues that are colocalized with the alpha7 subtype. [3H]Methyllycaconitine is also frequently used as an alpha7-selective antagonist, but it has significant affinity for alpha6* and alpha9alpha10 nAChR subtypes. In this study, we have developed a highly alpha7-selective alpha-conotoxin radioligand by iodination of a naturally occurring histidine. Both mono- and diiodo derivatives were generated and purified (specific activities were 2200 and 4400 Ci mmol(-1), respectively). The properties of the mono- and diiodo derivatives were very similar to each other, but the diiodo was less stable. For monoidodo peptide, saturation binding to mouse hippocampal membranes demonstrated a K(d) value of 1.15 +/- 0.13 nM, similar to that of 125I-alpha-bungarotoxin in the same preparations (0.52 +/- 0.16 nM). Association and dissociation kinetics were relatively rapid (k(obs) for association at 1 nM was 0.027 +/- 0.007 min(-1); k(off) = 0.020 +/- 0.001 min(-1)). Selectivity was confirmed with autoradiography using alpha7-null mutant tissue: specific binding was abolished in all regions of alpha7(-/-) brains, whereas wild-type mice expressed high levels of labeling and low nonspecific binding. 125I-alpha-conotoxin ArIB[V11L; V16A] should prove useful where alpha7 nAChRs are coexpressed with other subtypes that are also labeled by existing ligands. Furthermore, true equilibrium binding experiments could be performed on alpha7 nAChRs, something that is impossible with 125I-alpha-bungarotoxin.


Hereditary spherocytosis.
Hereditary spherocytosis is a common inherited disorder that is characterised by anaemia, jaundice, and splenomegaly. It is reported worldwide and is the most common inherited anaemia in individuals of northern European ancestry. Clinical severity is variable with most patients having a well-compensated haemolytic anaemia. Some individuals are asymptomatic, whereas others have severe haemolytic anaemia requiring erythrocyte transfusion. The primary lesion in hereditary spherocytosis is loss of membrane surface area, leading to reduced deformability due to defects in the membrane proteins ankyrin, band 3, beta spectrin, alpha spectrin, or protein 4.2. Many isolated mutations have been identified in the genes encoding these membrane proteins; common hereditary spherocytosis-associated mutations have not been identified. Abnormal spherocytes are trapped and destroyed in the spleen and this is the main cause of haemolysis in this disorder. Common complications are cholelithiasis, haemolytic episodes, and aplastic crises. Splenectomy is curative but should be undertaken only after careful assessment of the risks and benefits.


Genetic control of autophagy underlies pathogenesis of inflammatory bowel disease.
Autophagy contributes to cellular homeostasis in the face of nutrient deprivation and other cellular stresses. Cell type-specific functions for autophagy are critical in maintaining homeostasis at both the tissue level and at the whole-organism level. Recent work has highlighted the ways in which human genetic variants modulate autophagy to alter epithelial and immune responses in inflammatory bowel disease.


The peacock's train (Pavo cristatus and Pavo cristatus mut. alba) I. structure, mechanics, and chemistry of the tail feather coverts.
The feathers in the train of the peacock serve not for flying but for sexual display. They are long, slender beams loaded in bending by their own weight. An outer circular conical shell, the cortex, is filled by a closed foam of 7.6% relative density, the medulla, both of feather keratin. Outer diameter and thickness of the cortex decrease linearly from the body toward the tip. This self-similar geometry leads to a division of labor. The cortex (longitudinal Young's modulus 3.3 GPa, transverse modulus 1 GPa) provides 96% of the longitudinal strength and bending rigidity of the feather. The medulla (Young's modulus 10 MPa) provides 96% of the transverse compressive rigidity. Fracture stress of the cortex, both longitudinal and transverse, is 120 MPa.


Perspectives in Genome-Editing Techniques for Livestock.
Genome editing of farm animals has undeniable practical applications. It helps to improve production traits, enhances the economic value of livestock, and increases disease resistance. Gene-modified animals are also used for biomedical research and drug production and demonstrate the potential to be used as xenograft donors for humans. The recent discovery of site-specific nucleases that allow precision genome editing of a single-cell embryo (or embryonic stem cells) and the development of new embryological delivery manipulations have revolutionized the transgenesis field. These relatively new approaches have already proven to be efficient and reliable for genome engineering and have wide potential for use in agriculture. A number of advanced methodologies have been tested in laboratory models and might be considered for application in livestock animals. At the same time, these methods must meet the requirements of safety, efficiency and availability of their application for a wide range of farm animals. This review aims at covering a brief history of livestock animal genome engineering and outlines possible future directions to design optimal and cost-effective tools for transgenesis in farm species.


Synthesis, G-quadruplex stabilisation, docking studies, and effect on cancer cells of indolo[3,2-b]quinolines with one, two, or three basic side chains.
G-quadruplex (G4) DNA structures in telomeres and oncogenic promoter regions are potential targets for cancer therapy, and G4 ligands have been shown to modulate telomerase activity and oncogene transcription. Herein we report the synthesis and G4 thermal stabilisation effects, determined by FRET melting assays, of 20 indolo[3,2-b]quinolines mono-, di-, and trisubstituted with basic side chains. Molecular modelling studies were also performed in an attempt to rationalise the ligands' binding poses with G4. Overall, the results suggest that ligand binding and G4 DNA thermal stabilisation increase with an N5-methyl or a 7-carboxylate group and propylamine side chains, whereas selectivity between G4 and duplex DNA appears to be modulated by the number and relative position of basic side chains. From all the indoloquinoline derivatives studied, the novel trisubstituted compounds 3 d and 4 d, bearing a 7-(aminoalkyl)carboxylate side chain, stand out as the most promising compounds; they show high G4 thermal stabilisation (ΔTm values between 17 and 8 °C) with an inter-G4 ΔTm trend of Hsp90A>KRas21R≈F21T>c-Kit2, 10-fold selectivity for G4 over duplex DNA, and 100-fold selectivity for the HCT116 cancer cell line (IC50 and IC90: <10 μM) over primary rat hepatocytes. Compounds 3 d and 4 d also decreased protein expression levels of Hsp90 and KRas in HCT116 cancer cells.


Long-term outcome of focal segmental glomerulosclerosis after Japanese pediatric renal transplantation.
Focal segmental glomerulosclerosis (FSGS) is known to recur in some patients after renal transplantation. Over a prolonged period, we followed 13 pediatric patients with FSGS who had undergone transplantation from living-related donors, analyzing risk factors for recurrent disease. Native nephrectomies were performed bilaterally in all patients at least 1 month prior to transplantation. Immunosuppressive therapy consisted of cyclosporine (CyA), mizoribine, prednisone, and antilymphocytic globulin or deoxyspergualin. We examined age at onset, time in months between diagnosis and end-stage disease (dialysis or transplantation), the duration of dialysis, age at transplantation, time since nephrectomy, doses of immunosuppressive agents, and HLA mismatch. Five patients (42.8%) developed recurrent disease in the graft; all showed proteinuria within 24 h of transplantation. However, all allografts have functioned well for 34-156 months following transplantation despite the recurrences, although 1 of these patients now shows proteinuria. The remaining 8 patients have had no recurrence for 104.6+/-30.4 months (mean+/-SD). The serum level of creatinine in patients with recurrence and without recurrence was 1.1+/-0.42 mg/dl and 0.98+/-0.29 mg/dl, respectively. The interval from diagnosis to initiation of dialysis was significantly shorter in patients with recurrence than those without recurrence ( P<0.05), but no other variables differed between these two groups. No recurrence of FSGS was observed in the protocol biopsy at 100 days after transplantation. We believe that CyA and native nephrectomy may limit or reverse progression of recurrent FSGS in renal allografts of Japanese pediatric patients, although this is a limited study.


The use of steady-state rate equations to analyse progress curve data.
Analysis of progress curves for enzyme-catalyzed reactions has been made by using a procedure that does not require the derivation of complex integrated rate equations. The method involves conversion of progress curve data to reaction velocities that are then fitted to the appropriate differential rate equation. Application of the procedure to data obtained for the reaction catalyzed by aspartate aminotransferase (L-aspartate:2-oxoglutarate aminotransferase, EC 184.108.40.206), showed that the resulting values for the kinetic parameters agreed well with those obtained by conventional progress curve analysis (Duggleby, R.G. and Morrison, J.F. (1978) Biochim. Biophys. Acta 526, 398--409).


Harnessing harm reduction in Australia: an interview with the Hon. Neal Blewett. Interview by Steve Allsop.
The National Campaign Against Drug Abuse (NCADA) was established in April 1985. Aiming to provide a national framework to minimize the harmful consequences of drug use, the original 3-year programme was extended to 1997. A key figure in the NCADA, Dr Neal Blewett, was interviewed to gain his perspective on the development and implementation of the Campaign over its first 10 years.


Clinical implementation of a multidirectional, angular stable osteosynthesis system in maxillofacial traumatology.
To investigate whether a multidirectional, angular stable osteosynthesis system is suitable for the treatment of mandibular fractures and to compare it with well established available systems. Following preliminary testing in an animal model, the multidirectional angular stable system TiFix 2.3 obtained from Litos (Hamburg, Germany) was utilised for internal fixation of 39 mandibular fractures. These involved four symphyseal fractures, 17 parasymphyseal, 16 of the angle of the mandible and two comminuted fractures. The surgical and postoperative course was closely scrutinised. Radiographs were taken after 6 months and all plates removed under local anaesthesia. Photographs were taken intraoperatively and the plates and surrounding soft tissues were salvaged for histological analysis. Additionally, these operations were compared with treatment of equivalent fractures which were treated with conventional, non-angular stable systems. The relative costs have also been evaluated. In 33 of the 39 fractures one TiFix plate sufficed for osteosynthesis. The plate most often used was a 2-hole plate which was applied in 25 (55.5%) fractures, followed by the 4-hole plates used in 16 (35.5%) fractures. In two comminuted fractures, four 6-hole plates were used (9%). In 17 patients the operation lasted less than 30 min, in 20 patients less than 60 min, in two less than 120 min. In all cases, the operations were shorter, and due to the plates' dimensions fewer screws had to be used, thus reducing the costs. This angular stable system enabled reduction of the amount of the implant material. Also reduced were the operation time and the cost of the procedure. Furthermore, in the future it will allow smaller access incisions and better preservation of the soft tissue integrity.


Durable Lithium Metal Anodes Enabled by Interfacial Layers Based on Mechanically Interlocked Networks Capable of Energy Dissipation.
Solid electrolyte interphase (SEI) has received considerable attention due to its vital role in stabilizing Li anode. However, native and many artificial SEIs often suffer from cracking and fragmentation under dendrite impact or long-term repeated volume variation, causing capacity decay. Herein, a mechanically interlocked network (MIN) was innovatively designed as interfacial layer to protect Li anode by incorporating the unique energy dissipation capability, which helps Li anode survive repeated volume variation during long-term cycling. As a result, symmetric cell with MIN-coated Li anode (MIN@Li) exhibited prolonged cycling life of 1500 hours at 1 mA cm-2 . The full cell using LFP cathode (13.5 mg cm-2 ) cycled stably for 500 cycles with capacity retention over 88 % (1 C). Our results highlight a creative application of MIN in Li anode, and its unique energy dissipation capability promises future success in other battery fields suffering from repeated volume variations.


[Preventive treatment with theophylline of apnea in premature infants: clinical, pharmokinetic and neurophysiological study].
Apnoea is a major problem in the neonatal paediatrics and its prevention is as important as the prevention of neonatal anoxia. The present study has three aims: 1. The strict evaluation of the results of therapy with Theophylline. 2. The determination of the pharmacokinetics of Theophylline and the establishment of the therapeutic protocol. 3. The study of the relationship between blood theophylline levels, apnoea and the states of sleep using prolonged polygraphic recordings.


Robot-assisted Radical Prostatectomy Performed with Different Robotic Platforms: First Comparative Evidence Between Da Vinci and HUGO Robot-assisted Surgery Robots.
In the field of robotic surgery, there is a lack of comparative evidence on surgical and functional outcomes of different robotic platforms. To assess the outcomes of patients receiving robot-assisted radical prostatectomy (RARP) at a high-volume robotic center with daVinci and HUGO robot-assisted surgery (RAS) surgical systems. We analyzed the data of 542 patients undergoing RARP ± extended pelvic lymph node dissection at OLV hospital (Aalst, Belgium) between 2021 and 2023. All procedures were performed by six surgeons using daVinci or HUGO RAS robots; the use of one platform rather than the other did not follow any specific preference and/or indication. Multivariable analyses investigated the association between robotic system (daVinci vs HUGO RAS) and surgical outcomes after adjustment for patient- and tumor-related factors. Urinary continence recovery was defined as the use of no/one safety pad. A total of 378 (70%) and 164 (30%) patients underwent RARP with daVinci and HUGO RAS surgical systems, respectively. Despite a higher rate of palpable disease in the HUGO RAS group (34% vs 25%), baseline characteristics did not differ between the groups (all p > 0.05). After adjusting for confounders, we did not find evidence of a difference between the groups with respect to operative time (estimate: 16.71; 95% confidence interval [CI]: -6.35, 39.78; p = 0.12), estimated blood loss (estimate: 3.12; 95% CI: -67.03, 73.27; p = 0.9), and postoperative Clavien-Dindo ≥2 complications (odds ratio [OR]: 1.66; 95% CI: 0.34, 8.15; p = 0.5). On final pathology, 55 (15%) and 20 (12%) men in, respectively, the daVinci and the HUGO RAS group had positive surgical margins (PSMs; p = 0.5). On multivariable analyses, we did not find evidence of an association between a robotic system and PSMs (OR: 1.08; 95% CI: 0.56, 2.07; p = 0.8). Similarly, the odds of recovering continence did not differ between daVinci and HUGO RAS cases after both 1 mo (OR: 0.78; 95% CI: 0.45, 1.38; p = 0.4) and 3 mo (OR: 1.17; 95% CI: 0.49, 2.79; p = 0.7). Among patients receiving RARP with daVinci or HUGO RAS surgical platforms, we did not find differences in surgical and functional outcomes between the robots. This may be a result of a standardized surgical technique that allowed surgeons to transfer their skills between robotic systems. Awaiting future investigations with longer follow-up, these results have important implications for patients, surgeons, and health care policymakers. We compared surgical and functional outcomes of patients receiving robot-assisted radical prostatectomy with daVinci versus HUGO robot-assisted surgery (RAS) robots. The two platforms were able to achieve similar outcomes, suggesting that the introduction of HUGO RAS is safe and allows for optimal outcomes after radical prostatectomy.


Machine learning in primary biliary cholangitis: A novel approach for risk stratification.
Machine learning (ML) provides new approaches for prognostication through the identification of novel subgroups of patients. We explored whether ML could support disease sub-phenotyping and risk stratification in primary biliary cholangitis (PBC). ML was applied to an international dataset of PBC patients. The dataset was split into a derivation cohort (training set) and a validation cohort (validation set), and key clinical features were analysed. The outcome was a composite of liver-related death or liver transplantation. ML and standard survival analysis were performed. The training set was composed of 11,819 subjects, while the validation set was composed of 1,069 subjects. ML identified four clusters of patients characterized by different phenotypes and long-term prognosis. Cluster 1 (n = 3566) included patients with excellent prognosis, whereas Cluster 2 (n = 3966) consisted of individuals at worse prognosis differing from Cluster 1 only for albumin levels around the limit of normal. Cluster 3 (n = 2379) included young patients with florid cholestasis and Cluster 4 (n = 1908) comprised advanced cases. Further sub-analyses on the dynamics of albumin within the normal range revealed that ursodeoxycholic acid-induced increase of albumin >1.2 x lower limit of normal (LLN) is associated with improved transplant-free survival. Unsupervised ML identified four novel groups of PBC patients with different phenotypes and prognosis and highlighted subtle variations of albumin within the normal range. Therapy-induced increase of albumin >1.2 x LLN should be considered a treatment goal.


Activation of transient receptor potential vanilloid 1 accelerates re-endothelialization and inhibits neointimal formation after vascular injury.
Transient receptor potential vanilloid 1 (TRPV1) is an important regulator of endothelial function, but the effects of TRPV1 on endothelial recovery and neointimal formation after vascular injury remain elusive. We tested the effects of activating TRPV1 using capsaicin on re-endothelialization and neointimal formation after wire-induced injury of the carotid artery in mice. The human umbilical vein endothelial cells (HUVECs) were treated with the TRPV1 agonist capsaicin, its antagonist capsazepine, intracellular calcium chelator BAPTA, or mitofusin 2 (Mfn2)-specific short interfering RNA (siRNA). The migration, proliferation, mitochondrial morphology, membrane potential, and adenosine triphosphate production were measured. The carotid artery wire injury procedure was performed in male TRPV1 knockout mice and C57BL/6J wild-type (WT) mice that were then treated with or without Mfn2 siRNA. The re-endothelialization and neointimal formation were evaluated. Capsaicin significantly enhanced the migration and proliferation of HUVECs. Both capsazepine and BAPTA abolished capsaicin-induced migration and proliferation of HUVECs. In addition, capsaicin stimulated the formation of reticular mitochondria, augmented mitochondrial membrane potential, increased adenosine triphosphate production, and upregulated Mfn2. However, these effects were attenuated by knockdown of Mfn2 with specific siRNA. Dietary capsaicin markedly accelerated re-endothelialization and inhibited neointimal formation in WT mice but not in TRPV1 knockout mice. Moreover, Mfn2 siRNA also attenuated capsaicin-induced enhancement of endothelial recovery and suppression of neointimal hyperplasia in WT mice. Activation of TRPV1 with capsaicin attenuates neointimal formation by accelerating re-endothelialization through upregulation of Mfn2.


QT interval lengthening in cardiac disease relates more to left ventricular systolic dysfunction than to autonomic function.
There are multiple influences on the QTc interval, including the autonomic nervous system. Which influence is the principal determinant of the variation in QTc interval between different cardiac diseases is not yet clear, though some studies have suggested that the QTc interval primarily reflects sympatho-vagal balance. This study investigated this claim further. To determine if autonomic tone was the prime determinant of variation in the QTc interval between subjects with different cardiac diseases. Subjects with different cardiac diseases were studied, QTc interval determined and correlated with three different measures of the autonomic nervous system, that of baroreflex sensitivity, catecholamine levels (epinephrine and norepinephrine) and sympatho-vagal balance as determined by power spectrum analysis. 47 subjects were studied, comprising 17 subjects with heart failure, 14 subjects with left ventricular hypertrophy and 16 control subjects. For the group as a whole there was no relationship between QTc interval and any measure of the autonomic nervous system function, but there was a reasonable relationship between fractional shortening and QTc interval (r=0.47, P<0.003). For subjects with an echocardiographic fractional shortenings less than 0.35 (which correlates with an ejection fraction of <50%), a strong relationship between fractional shortening and QTc interval remained (r=0.57, P<0.002), but in addition a relationship between QTc interval and catecholamine levels developed (for epinephrine: r=0.67, P<0.002; and for norepinephrine: r=0.62, P<0.005). Multiple regression analysis showed that fractional shortening and epinephrine levels were independently related to QTc interval. In subjects with a variety of cardiac diseases, the prime determinant of QTc interval is left ventricular systolic performance rather than the autonomic nervous system, though in subjects with low normal and less fractional shortenings catecholamine levels are independently related to QTc interval.


Effects of school-based physical activity on mathematics performance in children: a systematic review.
The benefits of physical activity (PA) on children's health and wellbeing are well established. However, the benefits of PA on academic performance and particularly on mathematics performance warrant systematic analysis. Mathematics is one of the core subjects in school education globally. We systematically searched, analysed and synthesized the literature on the effects of school-based PA interventions on mathematics performance in children aged 4-16. A total of 29 studies consisting of randomised trials and other interventions with control groups were identified through a systematic search, and 11 of them provided sufficient data and appropriate design for a meta-analysis. Of the 29 studies involving 11,264 participants, positive overall effects of a PA intervention on mathematics performance were found in 13 studies (45%) and neutral overall effects in 15 studies (52%). Only one study reported a significant negative result for a subgroup of children in the first half of the intervention. In a risk-of-bias assessment, 12 studies had low, 17 moderate, and none had a high risk of bias. The meta-analysis of 11 studies suggested an overall small positive effect (ES = 0.23) of the interventions. Only one study in the meta-analysis indicated a negative effect in one of the intervention groups. Adding PA to the school day may enhance children's mathematics performance or has no negative effects on performance. Several types of PA interventions can be recommended to be added to the school day.


Hypothermia severely effects performance of nitinol-based endovascular grafts in vitro.
Nitinol is an alloy that serves as the base for numerous medical devices, including the GORE TAG Thoracic Endoprosthesis (W.L. Gore & Associates, Flagstaff, AZ) thoracic aortic graft device. Given the increasing use of therapeutic hypothermia used during the placement these devices and in post-cardiac arrest situations, we sought to understand the impact of hypothermia on this device. Five 34-mm TAG devices were deployed in a temperature-controlled chamber at 20°C, 25°C, 30°C, 35°, and 37°C (25 total devices). A halographic measurement device was used to measure radial expansive force and normalized to the force at 37°C. Three 34-mm TAG devices were similarly deployed in a temperature-controlled water bath at each of the above temperatures. A laser micrometer was utilized to measure deployed diameter. A statistically significant decrease in expansive force at 20°C, 25°C, and 30°C of 65%, 46%, and 6%, respectively, was noted. A statistically significant decrease in radial diameter at 20°C and 25°C of 17% and 11%, respectively, was noted. Although a 9% difference was noted at 30°C, it was not significant. The nitinol-based TAG device shows marked decreases in radial expansive force and deployed diameter at temperatures at or below 30°C. Surgeons should be aware of the potential implications of placing nitinol-based endoprostheses in hypothermic conditions. In addition, all health care providers should be aware of the changes that occur in nitinol-based endoprostheses during therapeutic hypothermia.


Relative irritancy of free fatty acids of different chain length.
Free fatty acids of human skin surface lipids have previously been implicated in the pathogenesis of acne vulgaris because of their apparent irritant and comedogenic properties. Prior studies on the relative irritancy of free fatty acids revealed the saturated C8 to C14 fatty acids and a C18 dienoic unsaturated fatty acid (linoleic) to be most irritating. Saturated free fatty acids from C3 to C18, and unsaturated C18 free fatty acids were applied daily under occlusive patch tests to human skin until detectable erythema appeared. The most irritating fatty acids were C8 through C12. Of the unsaturated fatty acids tested, only linoleic acid produced irritation.


Pathology and the surgical management of goitre in an endemic area initiating supplementary iodine nutrition.
Goitre in the West African sub-region is caused by iodine deficiency and goitrogens in the diet. Supplementary iodine nutrition on a mass scale was started in Ghana in 1996. In areas where iodine deficiency have been corrected the histological pattern of goitre changes and this influences surgical decision making. Data on the histological types of goitre in our institution is lacking. To define the histopathological types of goitre in this initial period of iodine supplementation and relate this to the types of thyroid surgeries that were performed. It was a prospective study of consecutive patients who underwent thyroidectomy from January 2003-December 2007. Descriptive statistics was employed in analyzing the data Five hundred and twenty eight cases were studied made up of 470 (89%) females and 58 (11%) males with mean age of 41.98 yrs, SD ± 12.90 yrs. The excised mean thyroid tissue weight was 161.4 g, SD ± 116.3 yrs. Hyperplastic goitres were 373 (70.7%), toxic goitre 70 (13.3%), adenoma 37 (7.0%), carcinoma 25 (4.7%) and thyroiditis 23 (4.4%). Papillary carcinoma accounted for 56% (14) cancers. Subtotal thyroidectomy was performed in 278 (52.7%) of patients, near total thyroidectomy 107 (20.3%), lobectomy 98 (18.6%),total thyroidectomy 24 (4.5%), excision or completion thyroidectomy 20 (3.8%) and de-bulking 1 patient. Overall, complications occurred in 32 patients (6.1%) and were made up mostly of haemorrhage in 10 (1.9%), Hypocalcaemia 10 (1.9%), unilateral Recurrent Laryngeal Nerve(RLN) injury 3 (0.57%), Tracheal collapse 3 (0.57%) and Bilateral RLN injury 2 (0.4%). The introduction of iodine supplementation on a mass scale in Ghana is yet to have its fullest impact on thyroid diseases. Goitres are still large and cause pressure effects. Toxic, inflammatory and malignant goitres are gaining prominence, and surgery for malignant goitre was oncologically inadequate.Near total thyroidectomy is recommended as the minimum surgery to avert the need for completion thyroidectomies in view of the lack of preoperative pathological diagnosis of thyroid lesions.


The BTG/TOB family protein TIS21 regulates stage-specific proliferation of developing thymocytes.
As thymocytes undergo differentiation in the thymus, they progress through distinct phases of quiescence and proliferation. Identifying cellular mechanisms that maintain thymocytes in a non-dividing state is critical to fully understand T cell development. A member of the B cell translocation gene/transducer of ErbB-2 (BTG/TOB) family of anti-proliferative proteins was identified as a key mediator of the quiescent state in peripheral anergic and unstimulated T cells. Here, we demonstrate that the BTG/TOB family member TPA-inducible sequence 21 (TIS21) is expressed in quiescent CD44+ CD25- early progenitor thymocytes and CD44- CD25+ cells prior to TCR beta-selection. However, TIS21 expression is decreased in proliferating CD25+ CD44+ progenitor thymocytes and CD25(low) CD44- beta-selected cells, suggesting that its regulated expression may enable thymocytes to remain quiescent in the absence of mitogenic signals. We addressed the role of TIS21 in regulating thymocyte stage-specific expansion by ectopically expressing TIS21 in developing thymocytes and hematopoietic progenitors. Dysregulated expression of TIS21 inhibited the expansion of thymocytes even in the presence of endogenous mitogenic signals, while thymocyte differentiation was unimpeded. These findings imply that the intracellular mechanisms regulating thymocyte differentiation and proliferation, which are induced downstream of developmental cues, function independently during early T cell development.


Endothelial dysfunction induced by hyperhomocyst(e)inemia: role of asymmetric dimethylarginine.
Endothelial function is impaired by hyperhomocyst(e)inemia. We have previously shown that homocyst(e)ine (Hcy) inhibits NO production by cultured endothelial cells by causing the accumulation of asymmetric dimethylarginine (ADMA). The present study was designed to determine if the same mechanism is operative in humans. We studied 9 patients with documented peripheral arterial disease (6 men; 3 women; age, 64+/-3 years), 9 age-matched individuals at risk for atherosclerosis (older adults; 9 men; age, 65+/-1 years), and 5 young control subjects (younger adults; 5 men; age, 31+/-1 years) without evidence of or risk factors for atherosclerosis. Endothelial function was measured by flow-mediated vasodilatation of the brachial artery before and 4 hours after a methionine-loading test (100 mg/kg body weight, administered orally). In addition, blood was drawn at both time points for measurements of Hcy and ADMA concentrations. Plasma Hcy increased after the methionine-loading test in each group (all, P<0.001). Plasma ADMA levels rose in all subjects, from 0.9+/-0.2 to 1.6+/-0.2 micromol/L in younger adults, from 1.5+/-0.2 to 3.0+/-0.4 micromol/L in older adults, and from 1.8+/-0.1 to 3.9+/-0.3 micromol/L in peripheral arterial disease patients (all, P<0.001). Flow-mediated vasodilatation was reduced from 13+/-2% to 10+/-1% in younger adults, from 6+/-1% to 5+/-1% in older adults, and from 7+/-1% to 3+/-1% in peripheral arterial disease patients (all, P<0.001). Furthermore, we found positive correlations between plasma Hcy and ADMA concentrations (P=0.03, r=0.450), as well as ADMA and flow-mediated vasodilatation (P=0.002, r=0.623). Our results suggest that experimental hyperhomocyst(e)inemia leads to accumulation of the endogenous NO synthase inhibitor ADMA, accompanied by varying degrees of endothelial dysfunction according to the preexisting state of cardiovascular health.


Endothelial cells promote smooth muscle cell resilience to H2 O2 -induced cell death in mouse cerebral arteries.
Brain injury produces reactive oxygen species (ROS). However, little is known of how acute oxidative stress affects cell survival in the cerebral vascular supply. We hypothesized that endothelial cells (ECs) are more resilient to H2 O2 and protect vascular smooth muscle cells (SMCs) during acute oxidative stress. Mouse posterior cerebral arteries (PCAs; diameter, ~80 µm) were exposed to H2 O2 (200 µM, 50 min, 37°C). Nuclear staining identified dead and live cells of intact and endothelium-disrupted vessels. SMC [Ca2+ ]i was assessed with Fura-2 fluorescence, and superoxide production was assessed by dihydroethidium and MitoSOX fluorescence. In response to H2 O2 : SMC death (21%) exceeded EC death (5%) and increased following endothelial disruption (to 48%) with a corresponding increase in SMC Ca2+ entry through transient receptor potential (TRP) channels. Whereas pharmacological inhibition of TRPV4 channels prevented SMC death and reduced Ca2+ entry for intact vessels, both remained elevated following endothelial disruption. In contrast, pharmacological inhibition or genetic deletion of TRPC3 prevented SMC death and attenuated Ca2+ entry for both intact and endothelium-disrupted vessels. Inhibiting gap junctions increased EC death (to 22%) while SMC death and [Ca2+ ]i responses were attenuated by inhibiting nitric oxide synthesis or scavenging superoxide/peroxynitrite. Inhibiting NADPH oxidases also prevented SMC Ca2+ entry and death. H2 O2 increased mitochondrial ROS production while scavenging mitochondria-derived superoxide prevented SMC death but not Ca2+ entry. During acute exposure of cerebral arteries to acute oxidative stress, ECs are more resilient than SMCs and the endothelium may protect SMCs by reducing Ca2+ entry through TRPC3 channels.


Preoperative risk factors for discharge to a postacute care facility after shoulder arthroplasty.
Shoulder arthroplasty procedures are becoming increasingly prevalent in the United States due to expanding indications and an aging population. Most patients are discharged home, but a subset of patients is discharged to a postacute care (PAC) facility. The purpose of this study was to identify the risk factors for discharge to a PAC facility after shoulder arthroplasty. The Nationwide Inpatient Sample discharge records from 2011 to 2012 were analyzed for patients who underwent a total shoulder arthroplasty (TSA) or reverse total shoulder arthroplasty (RTSA). Patient and hospital characteristics were identified. Univariate and multivariate analysis were used to determine the statistically significant risk factors for discharge to a PAC facility while controlling for covariates. In 2011 and 2012, 103,798 patients underwent shoulder arthroplasty procedures: 58,937 TSAs and 44,893 RTSAs were identified. RTSA patients were 1.3 times as likely to be discharged to a PAC facility as TSA patients (P = .001). Medicare patients were 2 times as likely to be discharged to a PAC facility than those with private insurance (P < .001). In addition, women and patients presenting with a fracture, older age, or an increasing number of medical comorbidities were more likely to be discharged to a PAC facility (P < .001). The risk factors identified in our study can be used to stratify patients at high risk for postoperative discharge to PAC, allowing for greater improvement in overall care and the facilitation of postoperative discharge planning.


The organization of the salivary gland microcirculation.
1. The microvasculature of the rabbit submandibular salivary gland has been investigated employing in vivo microscopy, blood flow measurements, latex casts, microsphere injections and examination of fixed sections of the gland.2. Two principal microcirculations were distinguished in the living gland, one supplying the acini and the other the intralobular ducts. Parasympathetic nerve stimulation (2, 5 or 10 sec(-1)) elicited different responses in each of the two microcirculations. Flow in the capillaries around the acini slowed initially before increasing. In contrast, flow in the intralobular duct capillaries increased soon after beginning stimulation.3. In some experiments both whole gland flow and microvascular flow were monitored simultaneously. Whole gland flow increased at the same time as flow in the acinar capillaries was decreasing and as flow in the intralobular duct capillaries increased. Flow in acinar capillaries increased about 5 sec after glandular flow started to increase.4. These observations could be explained if either the vascular beds of the acini and the intralobular ducts were arranged in parallel or if arteriovenous anastomoses were to shunt the acinar circulation. No such anastomoses were found in latex casts made of the gland vasculature, and microspheres injected into the artery supplying the gland were not found in the venous effluent.5. The intraglandular distribution of microspheres was measured in histological sections of the injected glands to give an estimate of the distribution of blood flow between the duct and acinar microcirculations. At rest and during maintained stimulation about 55% of the blood flow passed through the intralobular duct microcirculations, whilst during this initial 15 sec of stimulation this proportion was increased to over 70%. This finding is consistent with a parallel arrangement of the two microcirculations.6. The conclusions drawn from these observations are that the duct and acinar microcirculations are arranged in parallel, that there are differences in the way the vasodilatation is mediated in these circulations, and that arterio-venous anastomoses play no significant role in this gland.


Role of hepatitis E virus antigen in confirming active viral replication in patients with acute viral hepatitis E infection.
Demonstration of active viral replication is important in serologically confirmed cases of hepatitis E virus (HEV) infection to assess prognosis. Detection of HEV RNA by reverse transcriptase polymerase chain reaction (rtPCR) is the gold standard for demonstration of active viremia. The present study was designed to compare the diagnostic utility of HEV antigen (Ag) with HEV IgM and HEV rtPCR in detecting the active viral replication. Blood samples from 156 probable cases of acute viral hepatitis (AVH) were collected. Screening for hepatitis B surface antigen (HBsAg), antibody to hepatitis C virus (anti HCV), IgM antibody to hepatitis A virus (HAV IgM) was done on the Architect platform (Abbott Laboratories, IL, USA). HEV IgM ELISA (Wantai Biological, Beijing, China), HEV-Ag ELISA (Wantai Biological, Beijing, China) and HEV rtPCR were done on all the samples. Out of 156 AVH cases in 56 (35.8%) a diagnosis of HEV was confirmed. Positivity being; anti-HEV IgM 44/56, HEV RNA 20/56, and HEV antigen 17/56 in established cases. Male to female ratio was 3:1. The median age was 40 (range 14-71) years. HEV Ag showed a good concordance with HEV RNA (k=0.635, p<0.001). However HEV IgM did not show any concordance with HEV RNA (k=0.14). HEV antigen assay can be used as an additional diagnostic marker to confirm active viral replication in serologically positive samples.


Communicating health information with visual displays.
Well-designed visual displays have the power to convey health messages in clear, effective ways to non-experts, including journalists, patients and policymakers. Poorly designed visual displays, however, can confuse and alienate recipients, undermining health messages. In this Perspective, we propose a structured framework for effective visual communication of health information, using case examples of three common communication tasks: comparing treatment options, interpreting test results, and evaluating risk scenarios. We also show simple, practical ways to evaluate a design's success and guide improvements. The proposed framework is grounded in research on health risk communication, visualization and decision science, as well as our experience in communicating health data.


Bonding and impedance matching of acoustic transducers using silver epoxy.
Silver epoxy was selected to bond transducer plates on glass substrates. The properties and thickness of the bonding medium affect the electrical input impedance of the transducer. Thus, the thickness of the silver epoxy bonding layer was used as a design parameter to optimize the structure for the transducer input impedance to match the 50 Ω output impedance of most radio frequency (RF) generators. Simulation and experimental results show that nearly perfect matching is achieved without using any matching circuit. At the matching condition, the transducer operates at a frequency band a little bit below the half-wavelength resonant frequency of the piezoelectric plate. In experiments, lead titanate (PT) piezoelectric plates were employed. Both full-size, 11.5 mm × 2 mm × 0.4 mm, and half-size, 5.75 mm × 2 mm × 0.4 mm, can be well matched using optimal silver epoxy thickness. The transducer assemblies demonstrate high efficiency. The conversion loss from electrical power to acoustic power in soda-lime glass is 4.3 dB. This loss is low considering the fact that the transducers operate at off-resonance by 12%. With proper choice of silver epoxy thickness, the transducer can be matched at the fundamental, the 3rd and 5th harmonic frequencies. This leads to the possible realization of triple-band transducers. Reliability was assessed with thermal cycling test according to Telcordia GR-468-Core recommendation. Of the 30 transducer assemblies tested, none broke until 2900 cycles and 27 have sustained beyond 4050 cycles.


High rate of occult cancer found in prophylactic mastectomy specimens despite thorough presurgical assessment with MRI and ultrasound: findings from the Hereditary Breast and Ovarian Cancer Registration 2016 in Japan.
Prophylactic surgery is a preemptive strategy for hereditary breast and ovarian cancer (HBOC). Prophylactic mastectomy (PM) reduces breast cancer risk by > 90%. The aim of our study is to analyze the information of the Japanese pedigrees and to utilize the results for clinical practice. We statistically analyzed records of HBOC registrees who had undergone BRCA1/2 genetic testing at seven medical institutions up until 2016. In the cases of PM, we examined breasts with the use of mammography (MMG), ultrasound (US), and magnetic resonance imaging (MRI) before surgery. After PM, the specimens were divided about 1 cm serially and examined in their entirety. Of 1527 registrees who underwent BRCA testing, 1125 (73.7%) were negative for BRCA1/2 mutation, 297 (19.5%) were positive for BRCA1/2 mutation (BRCA1/2MUT+), and 105 (6.9%) had uncertain results. To decide whether to undergo total mastectomy vs. breast-conserving surgery (BCS), 370 registrees underwent presurgical genetic testing. During the follow-up period, four new-onset breast cancers were found among the 55 non-affected BRCA carriers. Among the 73 BRCA1/2MUT+ carriers who underwent BCS, 3 were found to have ipsilateral breast cancer. Of 189 BRCA1/2MUT+ carriers with unilateral breast cancer, 8 were found to have contralateral breast cancer. Of 53 PM specimens, 6 (11.3%) were found to have occult breast cancer despite using MMG, US, and MRI. Our report showed a relatively higher incidence rate of occult cancer at 11.3% in PM specimens despite thorough pre-operative radiological evaluations, which included a breast MRI. Considering the occult cancer rates and the various pathological methods of our study and published studies, we propose the necessity of a histopathological protocol.


Enhancement of atherosclerosis in beta-2-glycoprotein I-immunized apolipoprotein E-deficient mice.
We have previously shown that low density lipoprotein receptor-deficient (LDL-RD) mice immunized with beta2-glycoprotein I (beta2GPI; a target of autoimmune anticardiolipin antibodies) developed enhanced early atherosclerosis, when fed a normal chow diet. The current study was undertaken to evaluate the effect of immunization with beta2GPI and the addition of a high fat diet on the progression of atherosclerosis in the apolipoprotein E (ApoE)-deficient mouse. Six-week-old female ApoE-deficient mice (n = 10) were immunized subcutaneously with either human beta2GPI or with ovalbumin, both emulsified in complete Freund's adjuvant and fed a high fat diet for 6 weeks. The beta2GPI-immunized mice were found to develop accelerated atherosclerosis when compared with their ovalbumin-immunized littermates (aortic lesion area of 137,500 +/- 13,801 vs. 72,444 +/- 14,465 microm2, respectively; p = 0.0067). The beta2GPI-immunized mice developed high titers of anti-beta2GPI antibodies, 10 days after the procedure, which were sustained until the sacrifice. LDL extracted from both study groups displayed similar susceptibility to ex vivo oxidation. These results confirm our previous study in which we found increased atherosclerosis in beta2GPI-immunized LDL-RD mice fed a chow diet. In the current study we show that the proatherogenic effect of beta2GPI immunization is maintained despite high cholesterol levels and is not associated with increased susceptibility of LDL to ex vivo oxidation.


Assessing health-related quality of life after severe brain damage: potentials and limitations.
Assessment of health related quality of life (HRQoL) has been addressed in medicine since more that 20 years. However, little is known about the HRQoL of patients with traumatic brain injury (TBI). The main reason for this seems to be the challenge of attempting to assess HRQoL in the light of the diversity of consequences associated with the condition. Especially in severely brain-damaged patients with altered states of consciousness, patients self-report on own function and well-being seems at least difficult, if not impossible, and the question is whether other persons, like caregivers, might be able to truly judge the patients quality of life. A prerequisite to examining HRQoL in patients with TBI is the availability of appropriate measures. While generic measures are available, the development of condition-specific measures has only recently begun. This chapter reviews conceptual and methodological issues in current HRQoL research, applies these to the area of brain injury and critically summarizes challenges to HRQoL assessment in TBI in terms of potentials and limitations. It is concluded that in spite of recent promising approaches to HRQoL assessment in TBI, much has to be done to understand, measure and finally improve HRQoL in severely brain-damaged patients.


Assessment of Evidence-Based Health and Safety Policies on Sudden Death and Concussion Management in Secondary School Athletics: A Benchmark Study.
Implementation of best-practice health and safety policies has been shown to be effective at reducing the risk of sudden death in sport; however, little is known about the extent to which these policies are required within secondary school athletics. To examine best-practice health and safety policies pertaining to the leading causes of sudden death and to concussion management in sport mandated at the state level for secondary school athletics. Descriptive observational study. State high school athletic associations (SHSAAs), state departments of education, and enacted legislation. United States (including the District of Columbia) SHSAAs. A review of SHSAA health and safety policies for the 2016-2017 academic year, state department of education policies, and enacted legislation was undertaken to assess the polices related to the leading causes of sudden death and concussion management in sport. Current best-practice recommendations used to assess health and safety policies were specific to emergency action plans, automated external defibrillators, heat acclimatization, environmental monitoring and modification, and concussion management. The total number of best-practice recommendations required for each SHSAA's member schools for the aforementioned areas was quantified and presented as total number and percentage of recommendations required. Four of 51 SHSAA member schools were required to follow best practices for emergency action plans, 7 of 51 for access to automated external defibrillators, 8 of 51 for heat acclimatization, and 3 of 51 for management of concussion. At the time of this study, SHSAA member schools were not required to follow all best-practice recommendations for preventing the leading causes of sudden death and for concussion management in sport. Continued advocacy for the development and implementation of best practices at the state level to be required of all secondary schools is needed to appropriately serve the health and well-being of our young student-athletes.


Anatomical patterns of hypoplastic posterior communicating arteries and their implications for cerebrovascular diseases.
A total of 114 undersized posterior communicating arteries (PCoA-s, external diameter less than 1 mm) and 126 larger ones were investigated histologically. Microscopic examination of hypoplastic PCoA-s revealed five different structural patterns. Two of them showed microscopic appearances characteristic of intracranial arteries seen in adults or newborns without vascular disease. Two other types resembled the histologic picture of Moya Moya disease. The last type was thin-walled and dilated. All PCoA-s larger than 1 mm displayed the adult pattern. The PCoA-s with the Moya Moya-like structure and the thin-walled, dilated pattern contained unusually few reticular fibers. It is supposed that Moya Moya disease may be restricted to the PCoA-s. Further, the types of hypoplastic PCoA-s with reticular fiber deficiency are most probably the source of the so-called unexplained subarachnoid hemorrhage regardless of the presence of infundibular widening. The latter statement stems from the observation that the structure of junctional dilatation does not differ from that of other segments of the artery that exhibit this alteration.


A highly selective fluorescent probe for the intracellular measurement of magnesium ion.
Magnesium ion (Mg+2) plays an important role in various biological processes. All the commercial indicators available share a common drawback, i.e., they have a higher affinity towards calcium ions (Ca+2) than Mg+2. In this study, we reported a new robust green fluorescent indicator, Mag-520, for detection of Mg+2 in live cells. Our results showed that Mag-520 has 10 fold higher affinity towards Mg+2 than Ca+2, while mag-fluo-4 has less than 0.5 fold affinity to Mg+2 than Ca+2 under the same conditions using flow cytometry and fluorescence microscopy. The results demonstrated that Mag-520 provides a better tool to measure Mg+2 with less interference from Ca+2.