FGF10 Signaling Enhances Epicardial Cell Expansion during Neonatal Mouse Heart Repair.
Unlike zebrafish and newt hearts, mammalian hearts have limited capacity to regenerate. Upon injury or disease, the adult mammalian hearts form a fibrotic scar. Recently, it was shown that neonatal mouse hearts can regenerate similarly to adult zebrafish hearts. However, this capacity quickly decreases after postnatal day 7 (P7). Understanding the molecular mechanisms underlying neonatal heart regeneration might lead to therapeutic approaches for regenerating adult mammalian hearts. In this study, we utilized an inducible transgenic mouse model to determine the effects of FGF10 growth factor over expression on neonatal mouse heart regeneration/repair. Over expression of FGF10 in myocardium enhanced the expansion of Wt1 positive epicardial cells at 21 days after heart injury through increased proliferation. However, this expansion of epicardial cells did not lead to increased epithelial-to-mesenchymal transition or affect fibroblast formation or fibrosis, as seen by vimentin expression, after heart injury. Furthermore, neither continuous nor transient expression of FGF10 did not affect scar thickness or length after heart injury in neonatal hearts. Our results suggest that FGF10 can regulate epicardial cell expansion of neonatal mouse hearts after injury; however, FGF10 alone is not sufficient to cause beneficial effects on heart repair.


Myocardial viability-State of the art: Is it still relevant and how to best assess it with imaging?
Despite major advances, ischemic cardiomyopathy (ICM) remains a significant cause of death and disability worldwide, with coronary artery disease (CAD) the leading cause of left ventricular (LV) systolic dysfunction. Coronary revascularization may improve LV function, heart failure symptoms and cardiovascular outcomes in high-risk patients with myocardial viability. Multiple imaging modalities have been utilized to detect viable myocardium and predict functional recovery following revascularization. Dobutamine stress echocardiography (DSE), nuclear imaging and cardiac MRI (CMR) are frequently used to assess viability. This review will summarize the extant literature on this topic, describe the role and methods for viability imaging in modern clinical practice, provide a patient-centered perspective regarding the controversies surrounding the current utility of viability imaging, as well as discuss future directions.


The timing of implant exchange in the development of capsular contracture after breast reconstruction.
Capsular contracture is a common complication associated with reconstructive breast surgery. The optimal time interval between the completion of tissue expansion and placement of the permanent implant is arbitrary and incompletely studied in the literature. The aim of the study was to determine whether the time interval between completion of expansion and placement of the permanent implant would affect the incidence of capsular contracture. We conducted a retrospective study of 112 patients with breast cancer, including 140 breasts, who underwent postmastectomy tissue expander placement between 1997 and 2004. All patients underwent replacement of tissue expander with a permanent prosthesis. Data were collected retrospectively, including whether the patient smoked, underwent radiation therapy, had saline or silicone implant reconstruction, required reoperation after tissue expander placement or after permanent implant placement, Baker classification, and the interval between completion of expansion and placement of permanent implant. We used a logistic regression model to incorporate the predictors of capsular contracture. Keeping all other predictors constant, we found that the time interval between implant exchange had no effect on capsular contracture. The only significant predictor of capsular contracture was whether the patient required a reoperation after the permanent implant was placed (P = .0001). Allowing the capsule around a tissue expander to mature does not significantly affect development of capsular contracture. However, a complication that necessitates disrupting the periprosthetic capsule of the permanent implant with an operation significantly increases odds of developing contracture.


High proliferative potential-quiescent cells: a working model to study primitive quiescent hematopoietic cells.
Human adult hematopoietic stem cells are mostly quiescent or slow cycling. We have previously demonstrated that blocking of transforming growth factor-beta1 (TGF-beta1) is able to activate, in the presence of cytokines, primitive quiescent hematopoietic multipotent progenitors which could not grow in a two week semi-solid culture assay (short term culture). We have also shown that anti-TGF-beta1 can up-modulate c-KIT, the receptor of the stem cell factor (steel factor). To elucidate whether TGF-beta1 plays a central role in controlling the quiescence of hematopoietic primitive cells, it was necessary to demonstrate, as detailed in this study, that: (1) whatever the cytokine combination tested, addition of anti-TGF-beta1 releases from quiescence multipotent progenitors with a significantly higher hematopoietic potential than those activated by cytokines alone. (2) Other important cytokine receptors controlling the most primitive hematopoietic cells such as FLT3 and the IL6 receptor (IL6-R) are down-modulated by TGF-beta1 but rapidly up-modulated by anti-TGF-beta1. (3) Anti-TGF-beta1-sensitive multipotent and high proliferative potential progenitors express these cytokine receptors at a low level (FLT3(low) and IL6-Rlow). According to these results, we propose the working model of 'High Proliferative Potential-Quiescent cells' to refer to these primitive hematopoietic multipotent progenitors that are highly sensitive to the growth inhibitory effect of TGF-beta1. This model could be valid not only to study the human hematopoietic quiescent progenitors but also for other somatic stem cell systems.


Analysis of the chromatin landscape and RNA polymerase II binding at SIN3-regulated genes.
The chromatin environment has a significant impact on gene expression. Chromatin structure is highly regulated by histone modifications and RNA polymerase II binding dynamics. The SIN3 histone modifying complex regulates the chromatin environment leading to changes in gene expression. In Drosophila melanogaster, the Sin3A gene is alternatively spliced to produce different protein isoforms, two of which include SIN3 220 and SIN3 187. Both SIN3 isoforms are scaffolding proteins that interact with several other factors to regulate the chromatin landscape. The mechanism through which the SIN3 isoforms regulate chromatin is not well understood. Here, we analyze publicly available data sets to allow us to ask specific questions on how SIN3 isoforms regulate chromatin and gene activity. We determined that genes repressed by the SIN3 isoforms exhibited enrichment in histone H3K4me2, H3K4me3, H3K14ac and H3K27ac near the transcription start site. We observed an increase in the amount of paused RNA polymerase II on the promoter of genes repressed by the isoforms as compared to genes that require SIN3 for maximum activation. Furthermore, we analyzed a subset of genes regulated by SIN3 187 that suggest a mechanism in which SIN3 187 might exhibit hard regulation as well as soft regulation. Data presented here expand our knowledge of how the SIN3 isoforms regulate the chromatin environment and RNA polymerase II binding dynamics.


Refined Frequency Doubling Perimetry Analysis Reaffirms Central Nervous System Control of Chronic Glaucomatous Neurodegeneration.
Refined analysis of frequency doubling perimetric data was performed to assess binocular visual field conservation in patients with comparable degrees of bilateral glaucomatous damage, to determine whether unilateral visual field loss is random, anatomically symmetric, or non-random in relation to the fellow eye. Case control study of 41 consecutive patients with bilaterally mild to severe glaucoma; each right eye visual field locus was paired with randomly-selected co-isopteric left eye loci, performing 690,000 (10,000 complete sets of 69 loci) such iterations per subject. The potential role of anatomic symmetry in bilateral visual field conservation was also assessed by pairing mirror-image loci of the right- and left-eye fields. The mean values of the random co-isopteric and the symmetric mirror pairings were compared with natural point-for-point pairings of the two eyes by paired t-test. Mean unilateral Matrix threshold across the entire 30-degree visual field were 17.0 dB left and 18.4 dB right (average 17.7). The better of the naturally paired concomitant loci yielded binocular equivalent mean bilateral Matrix threshold of 20.9 dB, 1.6 dB higher than the population mean of the 690,000 coisopteric pairings (t = -10.4; P < 10-12). Thus, a remarkable natural tendency for conservation of the binocular Matrix visual field was confirmed, far stronger than explicable by random chance. Symmetric pairings of precise mirror-image loci also produced values higher than random co-isopteric pairings (Δ 1.1 dB; t = -4.0; P = 0.0004). Refined data analysis of paired Matrix visual fields confirms the existence of a natural optimization of binocular visual function in severe bilateral glaucoma via interlocking fields that could only be created by CNS involvement. The disparity of paired Matrix threshold values at mirror-image loci was also highly nonrandom and quantitatively inverse from the expected if anatomic symmetry factors were merely passively contributing systematically to the compensatory binocular Matrix effect. The paired eyes and brain are reaffirmed to function as a unified system in the progressive age-related neurodegenerative condition chronic open angle glaucoma, maximizing the binocular visual field. Given the extensive homology of this disorder with other age-related neurodegenerations, it is reasonable to assume that the brain will similarly resist simultaneous bilateral loss of paired functional zones in both hemispheres in diseases like Alzheimer's and Parkinson's disease. Glaucomatous eyes at all stages of the disease appear to provide a highly accessible paired-organ study model for developing therapeutics to optimize conservation of function in neurodegenerative disorders.


Predicting adolescent alcohol drinking patterns after major injury.
Bedside alcohol counseling provided to injured adolescents during their acute medical care reduces subsequent alcohol consumption and reinjury. This counseling would be even more effective if extended beyond hospitalization to help injured youth return to normal functioning. To enhance this counseling, we first need to know the natural course of adolescent drinking during the year after injury, as well as the predictors of problem drinking during that year. Prospective cohort study that described the natural history of adolescent drinking during the year after traumatic injury and identified predictors of increased alcohol use. Randomly sampled injured adolescents 12 years to 18 years of age, admitted to the surgical services of a Level I trauma center were interviewed to assess alcohol consumption at baseline and 2 months, 5 months, and 12 months after injury admission. Drinking increased steadily over the year, with this increase beginning in the months immediately after injury. Greater preinjury alcohol consumption, greater number of cumulative preinjury traumatic life experiences, and increasing age were independent positive predictors of increased drinking during the year after injury. Increased injury severity was a negative predictor such that the more severe the injury was, the less the adolescent drank during the year after injury. This documented postinjury drinking pattern and its predictors can now identify for the purposes of extended counseling those adolescents most likely to drink heavily during the year after injury.


[Liver cytochrome P-450 system in rats with a varying susceptibility to the development of experimental alcoholism].
The cytochrome P-450-dependent monooxygenase system of the liver was studied in laboratory noninbred male rats selected according to the intensity of their initial alcohol motivation and the dynamics of these parameters was followed up during 10-day alcoholisation. It was shown that in the animals inclined to the development of alcoholism the activity of the monooxygenase system (cytochrome P-450, B5; enzymes: aminopyrine N-demethylase, aniline p-hydroxylase, NADPH-cytochrome c-reductase) is higher than in the animals noninclined to the development of this disease. 10-day alcohol consumption in the free-choice situation between water and 15% ethanol solution did not change the parameters investigated. The only exception was NADPH-cytochrome c-reductase: its activity grew in both the groups of the animals by 40-75%.


Radiology artificial intelligence: a systematic review and evaluation of methods (RAISE).
There has been a large amount of research in the field of artificial intelligence (AI) as applied to clinical radiology. However, these studies vary in design and quality and systematic reviews of the entire field are lacking.This systematic review aimed to identify all papers that used deep learning in radiology to survey the literature and to evaluate their methods. We aimed to identify the key questions being addressed in the literature and to identify the most effective methods employed. We followed the PRISMA guidelines and performed a systematic review of studies of AI in radiology published from 2015 to 2019. Our published protocol was prospectively registered. Our search yielded 11,083 results. Seven hundred sixty-seven full texts were reviewed, and 535 articles were included. Ninety-eight percent were retrospective cohort studies. The median number of patients included was 460. Most studies involved MRI (37%). Neuroradiology was the most common subspecialty. Eighty-eight percent used supervised learning. The majority of studies undertook a segmentation task (39%). Performance comparison was with a state-of-the-art model in 37%. The most used established architecture was UNet (14%). The median performance for the most utilised evaluation metrics was Dice of 0.89 (range .49-.99), AUC of 0.903 (range 1.00-0.61) and Accuracy of 89.4 (range 70.2-100). Of the 77 studies that externally validated their results and allowed for direct comparison, performance on average decreased by 6% at external validation (range increase of 4% to decrease 44%). This systematic review has surveyed the major advances in AI as applied to clinical radiology. • While there are many papers reporting expert-level results by using deep learning in radiology, most apply only a narrow range of techniques to a narrow selection of use cases. • The literature is dominated by retrospective cohort studies with limited external validation with high potential for bias. • The recent advent of AI extensions to systematic reporting guidelines and prospective trial registration along with a focus on external validation and explanations show potential for translation of the hype surrounding AI from code to clinic.


Studies of rheumatoid arthritis among a tribe of Northwest Indians.
Thirty-six women from a Northwest Indian population known to have an increased prevalence of rheumatoid arthritis were studied. The course of the clinical disease was that of erosive rheumatoid arthritis with characteristic involvement of metacarpophalangeal and wrist joints. Rheumatoid factor and antinuclear antibody tests were frequently positive, and reactions to gold therapy were more frequent than in other rheumatoid populations. Viral antibodies were similar in the rheumatoid and the control groups. HL-A W24 and HL-A BW40 were increased in both the diseased and the control Indian populations.


Early weaning and prolonged nursing induce changes in cell proliferation in the gastric epithelium of developing rats.
Food deprivation stimulates cell proliferation in the gastric epithelium of suckling, but not weanling rats. This study was designed to investigate the role of diet on proliferation in developing animals, using early weaning and prolonged nursing models. Rat pups were subjected to these dietary conditions at d 15 and were killed 3 or 7 d afterwards. One day before killing, half of pups were deprived of food. Body weights were recorded. After mitosis blockade, the histologic sections of the stomach were used for the evaluation of cell proliferation and methapasic cell distribution along the gland, and for the measurement of mucosa thickness. Body weight was impaired at 18 d by early weaning and at 22 d by prolonged nursing. Food restriction promoted a 10-15% weight loss regardless of dietary conditions. At 18 d, food deprivation inhibited cell division (P: < 0.01) and reduced the thickness of the mucosa (P: < 0.05) in rats that were weaned early. At 22 d, only the thickness of the mucosa was different between the groups that were subjected to early weaning and prolonged nursing (P: < 0.05), regardless of feeding state. The frequency of dividing cells along the gland was affected by early weaning in 18- and 22-d-old rats. These results suggest the following: 1) food deprivation effects are dependent on dietary condition at 18 d because different proliferative responses were achieved after early weaning and prolonged nursing; 2) the lack of changes after dietary manipulation in 22-d-old rats indicates a nonresponsive period during postnatal development. We conclude that milk is a modulatory factor for cell proliferation in the gastric mucosa of rats.


A data driven epidemic model to analyse the lockdown effect and predict the course of COVID-19 progress in India.
We propose a data driven epidemic model using the real data on the infection, recovery and death cases for the analysis of COVID-19 progression in India. The model assumes continuation of existing control measures such as lockdown and quarantines, the suspected and confirmed cases and does not consider the scenario of 2nd surge of the epidemic due to any reason. The model is arrived after least square fitting of epidemic behaviour model based on theoretical formulation to the real data of cumulative infection cases reported between 24 March 2020 and 30May 2020. The predictive capability of the model has been validated with real data of infection cases reported during June 1-10, 2020. A detailed analysis of model predictions in terms of future trend of COVID-19 progress individually in 18 states of India and India as a whole has been attempted. Infection rate in India, as a whole, is continuously decreasing with time and has reached 3 times lower than the initial infection rate after 6 weeks of lock down suggesting the effectiveness of the lockdown in containing the epidemic. Results suggest that India, as a whole, could see the peak and end of the epidemic in the month of July 2020 and March 2021 respectively as per the current trend in the data. Active infected cases in India may touch 2 lakhs or little above at the peak time and total infected cases may reach over 19 lakhs as per current trend. State-wise results have been discussed in the manuscript. However, the prediction may deviate particularly for longer dates, as assumptions of model cannot be met always in a real scenario. In view of this, a real time application (COV-IND Predictor) has been developed which automatically syncs the latest data from the national COVID19 dash board on daily basis and updates the model input parameters and predictions instantaneously. This real time application can be accessed from the link: https://docs.google.com/spreadsheets/d/1fCwgnQ-dz4J0YWVDHUcbEW1423wOJjdEXm8TqJDWNAk/edit?usp=sharing and can serve as a practical tool for policy makers to track peak time and maximum active infected cases based on latest trend in data for medical readiness and taking epidemic management decisions.


Cost-effectiveness of medical interventions to prevent cardiovascular disease in a sub-Saharan African country--the case of Tanzania.
There is a high and rising prevalence of cardiovascular risk in sub-Saharan Africa, a development typical for countries in epidemiological transition. Contrary to recommendations in treatment guidelines, medical interventions to prevent cardiovascular disease are implemented only on a limited scale in these settings. There is a widespread concern that such treatment is not cost-effective compared to alternative health interventions. The main objectives of this article are therefore to calculate costs-, effects and cost-effectiveness of fourteen medical interventions of primary prevention of cardiovascular disease in Tanzania, including Acetylsalicylic acid, a diuretic drug (Hydrochlorothiazide), a beta-blocker (Atenolol), a calcium channel blocker (Nifedepine), a statin (Lovastatin) and various combinations of these. Effect sizes were derived from systematic reviews or meta-analyses, and calculated as Disability Adjusted Life Years (DALYs). Data on drug costs were calibrated to a Tanzanian setting. Other recurrent and capital costs were derived from previous studies and reviewed by local experts. Expected lifetime costs and health outcomes were calculated using a life-cycle model. Probabilistic cost-effectiveness analysis was performed using Monte Carlo simulation, and results presented as cost-effectiveness acceptability curves and frontiers. The potential impacts of uncertainty in value laden single parameters were explored in one-way sensitivity analyses. The incremental cost-effectiveness ratios for the fourteen interventions and four different levels of risk (totally 56 alternative interventions) ranged from about USD 85 per DALY to about USD 4589 per DALY saved. Hydrochlorothiazide as monotherapy is the drug yielding the most favorable cost-effectiveness ratio, although not significantly lower than when it is combined in duo-therapy with Aspirin or a beta-blocker, in triple-therapy with Aspirin and a beta-blocker, or than Aspirin given as mono-therapy. Preventive cardiology is not cost-effective for any patient group in this setting until willingness to pay exceeds USD 85 per DALY. At this level of willingness to pay, the optimal intervention is Hydrochlorothiazide to patients with very high cardiovascular risk. As willingness to pay for health increase further, it becomes optimal to provide this treatment also to patients with lower cardiovascular risk, and to substitute to more sophisticated interventions.


Lisfranc injury in a west point cadet.
Lisfranc joint injuries are fairly uncommon; however, few injuries hold such an elevated potential for devastating chronic secondary pain and disability. It is imperative when evaluating an injury to the ankle or foot to have a high clinical index of suspicion for Lisfranc injury, as physical examination findings are often subtle. An 18-year-old military cadet reported to a direct-access sports physical therapy clinic with foot pain. Despite negative radiographic findings, there was a high suspicion for Lisfranc injury based on the injury mechanism and physical examination. A computed tomography scan demonstrated an oblique fracture through the base of the third metatarsal, a small marginal fracture at the plantar base of the second metatarsal, and a subtle diastasis. Two days following his injury, he underwent an open reduction and internal fixation, completed subsequent rehabilitation, and returned to full activity approximately 1 year following injury. Early diagnosis of Lisfranc injuries is imperative for proper management and prevention of a poor functional outcome. If a strong clinical suspicion exists, negative radiographic findings are insufficient to rule out a Lisfranc injury, and therefore, advanced imaging is required.


Comparison of oscillation of oxygenation in skeletal muscle between early and late phases in prolonged exercise.
The aim of the present study was to compare the oscillations of oxygenation in skeletal muscle between early and late phases in prolonged exercise. During prolonged exercise at 60 % of peak oxygen uptake (V(.)o(2)) for 60 min and at rest, oxygenated hemoglobin/myoglobin (Hb/MbO(2)) and total Hb/Mb (THb/Mb) were determined by near-infrared spectroscopy in the vastus lateralis. Power spectra density (PSD) for the difference between Hb/MbO(2) and THb/Mb (-HHb/MbO(2): deoxygenation) was obtained by fast Fourier transform at rest, in the early phase (1-6 min) and in the late phase (55-60 min) in exercise. Peak PSD in the early phase was significantly higher than that at rest. There were at least three peaks of PSD in exercise. The highest peak was a band around 0.01 Hz, the next peak was a band around 0.04 Hz, and the lowest peak was a band around 0.06 Hz. PSD in the early phase was not significantly different from that in the late phase in exercise. Heart rate (HR) showed a continuous significant increase from 3 min in exercise until the end of exercise. Skin blood flow (SBF) around the early phase was significantly lower than that around the late phase. It was concluded that oscillation of oxygenation in the muscle oxygen system in the early phase is not different from that in the late phase in prolonged exercise despite cardiovascular drift.


[Bone choristoma of the bilateral choroid and asymmetric microphthalmia].
The authors report a case of associated bilateral asymmetrical microphthalmia and osseous choristoma of the choroid in a seventeen year old young woman. This association, to the author's knowledge, has not been previously reported in the literature. The bone choristoma was present in the eye's posterior poles and the clinical features were studied by electroretinography, fluorescein angiography, A-B scan ultrasonography, computerized axial tomography and nuclear magnetic resonance. The authors hypothesize that a choroid developmental tumor was produced by exposure to the rubella virus during embryonic life.


Vasculitis and Steroid Psychosis: A Case Report and Review of Literature.
Corticosteroids have become the cornerstone of therapy for many pathologies such as vasculitis. Steroid psychosis is a known complication of corticosteroids therapy, although infrequent. We describe a case of psychosis secondary to corticosteroids in a 69-year-old man with large-vessel vasculitis without previous history of psychiatric pathology. He was diagnosed with large-vessel vasculitis and the treatment started with prednisone 1 mg/kg/day. One week later, the patient presented with behavior change: emotional lability, disorientation and aggressiveness. The symptoms worsened for hallucinatory activity and cognitive deficit. After exclusion of other causes, the diagnosis of psychosis secondary to corticosteroids was assumed. It was decided to wean corticosteroids and start new therapy with methotrexate and tocilizumab and introduction of antipsychotic therapy. The patient had a good outcome with disease remission and had no further neuropsychiatric symptomatology. Systemic corticosteroids are widely used, sometimes with a low concern of its potential adverse effects. So it is important that physicians are aware of the potential for their adverse effects and the need to monitor disease activity and drug toxicity.


Pharmacodynamic and urinary metabolomics studies on the mechanism of Schisandra polysaccharide in the treatment of Alzheimer's disease.
Schisandra chinensis (Turcz.) Baill is produced mainly in northeast China, Korea and Japan. Its fruit has been used in food as a nutritional and functional ingredient for centuries. Polysaccharide is an important chemical component in Schisandra. Previous studies have shown that Schisandra polysaccharide (SCP) could be used to improve cognitive function clinically and treat age-related neurodegenerative disorders. In this study, a urinary metabolomics method based on ultra-high-performance liquid chromatography combined with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) was established to investigate the change of endogenous metabolites in an amyloid β-protein (Aβ) 25-35-induced Alzheimer's disease (AD) rat model. Meanwhile, levels of 9 neurotransmitters were evaluated with ultrahigh-performance liquid chromatography-triple-quadrupole mass spectrometry (UHPLC-TQ-MS) to explore the therapeutic mechanisms of SCP on the AD rat model. Additionally, the synthesis of phosphorylated tau protein (p-tau), acetylcholinesterase (AchE) activity and oxidative damage in the brain of the AD rats were assessed using glycogen synthase kinase-3β (GSK3β), AchE and antioxidant assays, NOS (nitric oxide synthase) and SOD (superoxide dismutase), respectively. The results indicated that the AD model was established successfully and the inducement of Aβ25-35 caused the phosphorylation of tau protein and the deposition of Aβ. In the AD model rats, the levels of AchE, GSK-3β and NOS were significantly elevated and SOD activity was reduced. In the hippocampus of the model rats, the contents of γ-aminobutyric acid, acetylcholine, glycine, norepinephrine, taurine, serotonin and dopamine were significantly decreased and the contents of glutamate and aspartic acid were increased significantly. However, SCP could reduce the degree of phosphorylation of tau protein, the deposition of Aβ and oxidative damage and reverse these changes of neurotransmitters in the AD rats. In a metabolomics study, a total of 38 metabolites were finally identified as potential biomarkers of AD and all of them had a significant recovery compared with the AD model after SCP administration. Metabolomics studies have shown that SCP plays a role in protecting the central nervous system, regulating intestinal microbial metabolism, regulating energy metabolism, and promoting antioxidant effects by regulating the levels of endogenous metabolites in related pathways. This is first report of the use of urine metabolomics combined with the evaluation of 9 neurotransmitter levels to investigate the mechanism of SCP on the treatment of AD.


Results of a strategic science study to inform policies targeting extreme thinness standards in the fashion industry.
The appearance pressures experienced by fashion models have been criticized as harmful to their health, as well as increasing eating disorder risk among youth by promoting ideals of extreme thinness. Given recent legislation to protect models, we undertook a strategic science study to assess professional fashion models' perceptions of the potential impact and feasibility of seven policy proposals. A sample of 85 female fashion models, mean age = 22.7 years (SD 3.7) completed an online survey assessing unhealthy weight control behaviors (UWCB), perceived pressure from agencies to lose weight, as well as the perceived impact and feasibility of seven potential policy actions. Chi-squared analyses and multivariable logistic regressions compared UWCB among models who were asked to lose weight and those who were not. Friedman and Kendall's W tests were conducted to examine differences in impact and feasibility ratings across the seven policy proposals. Models reported high levels of pressure to lose weight, which was associated with higher odds of engaging in UWCB. The policy approaches rated as most impactful were those to increase worker protections, though they were rated as only moderately feasible. Requiring employers to provide food and a 30-min break for jobs longer than 6 h was rated as both impactful and feasible. Imposing restrictions on minimum BMI was rated as the least impactful. Approaches providing employment protections and healthier working conditions are most supported by professional models. These findings help to illuminate viable policy approaches from the perspective of key stakeholders.


Dyeing of m-Aramid Fibers in Ionic Liquids.
Aramids represent a class of high-performance fibers with outstanding properties and manifold technical applications, e.g., in flame-retardant protective clothing for firefighters and soldiers. However, the dyeing of aramid fibers is accompanied by several economic and ecological disadvantages, resulting in a high consumption of water, energy and chemicals. In this study, a new and innovative dyeing procedure for m-aramid fibers using ionic liquids (ILs) is presented. The most relevant parameters of IL-dyed fibers, such as tensile strength, elongation and fastness towards washing, rubbing and light, were determined systematically. In summary, all aramid textiles dyed in ILs show similar or even better results than the conventionally dyed samples. In conclusion, we have successfully paved the way for a new, eco-friendly and more sustainable dyeing process for aramids in the near future.


A quantitative and qualitative evaluation of reports of clinical trials published in six Brazilian dental journals indexed in the Scientific Electronic Library Online (SciELO).
Open access publishing is becoming increasingly popular within the biomedical sciences. SciELO, the Scientific Electronic Library Online, is a digital library covering a selected collection of Brazilian scientific journals many of which provide open access to full-text articles.This library includes a number of dental journals some of which may include reports of clinical trials in English, Portuguese and/or Spanish. Thus, SciELO could play an important role as a source of evidence for dental healthcare interventions especially if it yields a sizeable number of high quality reports. The aim of this study was to identify reports of clinical trials by handsearching of dental journals that are accessible through SciELO, and to assess the overall quality of these reports. Electronic versions of six Brazilian dental Journals indexed in SciELO were handsearched at www.scielo.br in September 2008. Reports of clinical trials were identified and classified as controlled clinical trials (CCTs - prospective, experimental studies comparing 2 or more healthcare interventions in human beings) or randomized controlled trials (RCTs - a random allocation method is clearly reported), according to Cochrane eligibility criteria. CRITERIA TO ASSESS METHODOLOGICAL QUALITY INCLUDED: method of randomization, concealment of treatment allocation, blinded outcome assessment, handling of withdrawals and losses and whether an intention-to-treat analysis had been carried out. The search retrieved 33 CCTs and 43 RCTs. A majority of the reports provided no description of either the method of randomization (75.3%) or concealment of the allocation sequence (84.2%). Participants and outcome assessors were reported as blinded in only 31.2% of the reports. Withdrawals and losses were only clearly described in 6.5% of the reports and none mentioned an intention-to-treat analysis or any similar procedure. The results of this study indicate that a substantial number of reports of trials and systematic reviews are available in the dental journals listed in SciELO, and that these could provide valuable evidence for clinical decision making. However, it is clear that the quality of a number of these reports is of some concern and that improvement in the conduct and reporting of these trials could be achieved if authors adhered to internationally accepted guidelines, e.g. the CONSORT statement.


Impact of COVID-19 on cancer service delivery: results from an international survey of oncology clinicians.
To report clinician-perceived changes to cancer service delivery in response to COVID-19. Multidisciplinary Australasian cancer clinician survey in collaboration with the European Society of Medical Oncology. Between May and June 2020 clinicians from 70 countries were surveyed; majority from Europe (n=196; 39%) with 1846 COVID-19 cases per million people, Australia (AUS)/New Zealand (NZ) (n=188; 38%) with 267/236 per million and Asia (n=75; 15%) with 121 per million at time of survey distribution. Medical oncologists (n=372; 74%), radiation oncologists (n=91; 18%) and surgical oncologists (n=38; 8%). Eighty-nine per cent of clinicians reported altering clinical practices; more commonly among those with versus without patients diagnosed with COVID-19 (n=142; 93% vs n=225; 86%, p=0.03) but regardless of community transmission levels (p=0.26). More European clinicians (n=111; 66.1%) had treated patients diagnosed with COVID-19 compared with Asia (n=20; 27.8%) and AUS/NZ (n=8; 4.8%), p<0.001. Many clinicians (n=307; 71.4%) reported concerns that reduced access to standard treatments during the pandemic would negatively impact patient survival. The reported proportion of consultations using telehealth increased by 7.7-fold, with 25.1% (n=108) of clinicians concerned that patient survival would be worse due to this increase. Clinicians reviewed a median of 10 fewer outpatients/week (including non-face to face) compared with prior to the pandemic, translating to 5010 fewer specialist oncology visits per week among the surveyed group. Mental health was negatively impacted for 52.6% (n=190) of clinicians. Clinicians reported widespread changes to oncology services, in regions of both high and low COVID-19 case numbers. Clinician concerns of potential negative impacts on patient outcomes warrant objective assessment, with system and policy implications for healthcare delivery at large.


A novel assay reveals preferential binding between Rabs, kinesins, and specific endosomal subpopulations.
Identifying the proteins that regulate vesicle trafficking is a fundamental problem in cell biology. In this paper, we introduce a new assay that involves the expression of an FKBP12-rapamycin-binding domain-tagged candidate vesicle-binding protein, which can be inducibly linked to dynein or kinesin. Vesicles can be labeled by any convenient method. If the candidate protein binds the labeled vesicles, addition of the linker drug results in a predictable, highly distinctive change in vesicle localization. This assay generates robust and easily interpretable results that provide direct experimental evidence of binding between a candidate protein and the vesicle population of interest. We used this approach to compare the binding of Kinesin-3 family members with different endosomal populations. We found that KIF13A and KIF13B bind preferentially to early endosomes and that KIF1A and KIF1Bβ bind preferentially to late endosomes and lysosomes. This assay may have broad utility for identifying the trafficking proteins that bind to different vesicle populations.


Femoroacetabular impingement syndrome and labral injuries: grading the evidence on diagnosis and non-operative treatment-a statement paper commissioned by the Danish Society of Sports Physical Therapy (DSSF).
This statement summarises and appraises the evidence on diagnostic tests and clinical information, and non-operative treatment of femoroacetabular impingement (FAI) syndrome and labral injuries. We included studies based on the highest available level of evidence as judged by study design. We evaluated the certainty of evidence using the Grading of Recommendations Assessment Development and Evaluation framework. We found 29 studies reporting 23 clinical tests and 14 different forms of clinical information, respectively. Restricted internal hip rotation in 0° hip flexion with or without pain was best to rule in FAI syndrome (low diagnostic effectiveness; low quality of evidence; interpretation of evidence: may increase post-test probability slightly), whereas no pain in Flexion Adduction Internal Rotation test or no restricted range of motion in Flexion Abduction External Rotation test compared with the unaffected side were best to rule out (very low to high diagnostic effectiveness; very low to moderate quality of evidence; interpretation of evidence: very uncertain, but may reduce post-test probability slightly). No forms of clinical information were found useful for diagnosis. For treatment of FAI syndrome, 14 randomised controlled trials were found. Prescribed physiotherapy, consisting of hip strengthening, hip joint manual therapy techniques, functional activity-specific retraining and education showed a small to medium effect size compared with a combination of passive modalities, stretching and advice (very low to low quality of evidence; interpretation of evidence: very uncertain, but may slightly improve outcomes). Prescribed physiotherapy was, however, inferior to hip arthroscopy (small effect size; moderate quality of evidence; interpretation of evidence: hip arthroscopy probably increases outcome slightly). For both domains, the overall quality of evidence ranged from very low to moderate indicating that future research on diagnosis and treatment may alter the conclusions from this review.


An examination of the health and wellbeing of childless women: a cross-sectional exploratory study in Victoria, Australia.
Childlessness among Australian women is increasing. Despite this, little is known about the physical and mental health and wellbeing of childless women, particularly during the reproductive years. The aims of this exploratory study were to: 1) describe the physical and mental health and wellbeing and lifestyle behaviours of childless women who are currently within the latter part of their reproductive years (30 - 45 years of age); and 2) compare the physical and mental health and wellbeing and lifestyle behaviours of these childless women to Australian population norms. A convenience sample of 50 women aged between 30 and 45 years were recruited to participate in a computer assisted telephone interview. The SF-36 Health Survey v2 and lifestyle indicators were collected in regards to women's health and wellbeing. Data were analysed using descriptive statistics, t-tests for independent sample means and 95% confidence intervals for the difference between two independent proportions. Childless women in this study reported statistically significant poorer general health, vitality, social functioning and mental health when compared to the adult female population of Australia. With the exception of vegetable consumption, lifestyle behaviours were similar for the childless sample compared to the adult female population in Australia. Childless women may be at a greater risk of experiencing poor physical and mental health when compared to the Australian population. A woman's health and wellbeing during her reproductive years may have longer term health consequences and as such the health and wellbeing of childless women requires further investigation to identify and address implications for the provision of health (and other social) services for this growing population group.


Comparison of intravenous ketorolac tromethamine and morphine sulfate in the treatment of postoperative pain.
This study compared the efficacy and safety of ketorolac tromethamine and morphine sulfate in alleviating moderate or severe pain immediately after major surgery. One hundred twenty-two patients were randomly assigned to receive single intravenous injections of ketorolac 10 mg, ketorolac 30 mg, morphine 2 mg, or morphine 4 mg; patients could receive a second dose 15 minutes thereafter, upon request, and most received both available doses. Analgesic efficacy was measured by interviewing patients and assessing pain intensity and pain relief for 6 hours after the first medication administration. The two drugs showed a similar onset of action, peaking 1 hour after administration. When placed in order of descending efficacy, the mean scores for most efficacy measures fell into the following sequence: ketorolac 30 mg, ketorolac 10 mg, morphine 4 mg, and morphine 2 mg. There were no statistically significant differences among the two ketorolac doses and the high dose of morphine, but all three of these treatments were significantly superior to the low morphine dose. One patient who took morphine 4 mg withdrew because of drowsiness; other common adverse events reported included nausea, vomiting, somnolence, and dyspepsia. There were no statistically significant differences in the frequency of adverse events among the treatment groups. Intravenous ketorolac is effective for the treatment of postoperative pain.


Comparison of nutritional quality between conventional and organic dairy products: a meta-analysis.
As a contribution to the debate on the comparison of nutritional quality between conventional versus organic products, the present study would like to provide new results on this issue specifically on dairy products by integrating the last 3 years' studies using a meta-analysis approach with Hedges' d effect size method. The current meta-analysis shows that organic dairy products contain significantly higher protein, ALA, total omega-3 fatty acid, cis-9,trans-11 conjugated linoleic acid, trans-11 vaccenic acid, eicosapentanoic acid, and docosapentanoic acid than those of conventional types, with cumulative effect size ( ± 95% confidence interval) of 0.56 ± 0.24, 1.74 ± 0.16, 0.84 ± 0.14, 0.68 ± 0.13, 0.51 ± 0.16, 0.42 ± 0.23, and 0.71 ± 0.3, respectively. It is also observed that organic dairy products have significantly (P < 0.001) higher omega-3 to -6 ratio (0.42 vs. 0.23) and Δ9-desaturase index (0.28 vs. 0.27) than the conventional types. The current regulation on organic farming indeed drives organic farms to production of organic dairy products with different nutritional qualities from conventional ones. The differences in feeding regime between conventional and organic dairy production is suspected as the reason behind this evidence. Further identical meta-analysis may be best applicable for summarizing a comparison between conventional and organic foodstuffs for other aspects and food categories.


Factors that Predict Overall Health and Quality of Life in Non-Ambulatory Individuals with Cerebral Palsy.
It is unknown what role specific tasks associated with personal care, positioning, communication and social interaction, and comfort and emotions play in predicting the overall health and quality of life of individuals with non-ambulatory cerebral palsy (CP). In this study, we prospectively evaluated which of these factors were significant predictors of overall health and quality of life. Parents and guardians of non-ambulatory children, adolescents and young adults with CP were prospectively recruited from the Cerebral Palsy Clinic of a large pediatric academic hospital. Caregivers completed the CP Child Questionnaire®. Univariate analyses were used to identify relationships between overall health, overall quality of life (QOL), and responses in the following categories: personal care and activities of daily living, positioning and transfer mobility, comfort and emotions, and communication and social interaction. Significant predictors of overall health and QOL were then determined via logistic regression. 64 patients ages 0-20 years and Gross Motor Function Classification System levels IV and V were included in our study (mean age 9.16 ±4.96 years). Overall QOL (OR 194.2, 95% CI, 9.5-3964.9) and comfort while sitting (OR 15.9, 95% CI, 1.2-205.3) were significant predictors of overall health. Feelings of unhappiness or sadness (OR 59.9, 95% CI, 1.6-2209.8), difficulty understanding the parent or guardian (OR 29.8, 95% CI, 1.6-543.7), and not attending school (OR 57.2, 95% CI, 2.6-1274.4) were significant predictors of lower overall quality of life. Overall QOL appears to predict overall health. Factors associated with comfort and emotions and communication and social interaction appear to predict overall QOL to a greater extent than personal care and transfer mobility.Level of Evidence: Prognostic II.


Effectiveness of mobilization with movement (Mulligan concept techniques) on low back pain: a systematic review.
To evaluate evidence on the effectiveness of Mulligan techniques on low back pain. PubMed/Medline, Scopus, Ovid, CINAHL, Embase, PEDro, Google Scholar, and Cochrane Library were searched from inception to 31 March 2018 for randomized clinical trials reporting outcomes of pain or disability in adult patients (⩾18 years) with low back pain. Two authors screened the results and extracted data for use in this review. The risk of bias was evaluated using the Cochrane criteria. Basic information and treatment protocols were also extracted. In addition, the level of evidence of each study and strength of conclusion for pain and disability were determined. A total of 20 studies with 693 patients were included. Nine trials focused on sustained natural apophyseal glide, three on spinal mobilization with limb movement and seven on bent leg raise. The results showed that Mulligan techniques can decrease pain and disability and increase range of motion in patients with low back pain; however, the strength of conclusion for pain and disability was moderate. Furthermore, inconclusive results were observed for the effectiveness of Mulligan techniques on movement speed. In this review, eight studies were categorized as low risk of bias, while 12 studies had high risk of bias. Level of evidence analysis revealed that 17 studies were classified as level of evidence B, while three studies were classified as level of evidence A2. Current evidence is insufficient in supporting the benefits of Mulligan techniques on pain, disability, and range of motion in low back pain patients.


Violence and Abuse: A Pandemic Within a Pandemic.
During the COVID-19 pandemic, as society struggled with increasing disease burden, economic hardships, and with disease morbidity and mortality, governments and institutions began implementing stay-at-home or shelter-in-place orders to help stop the spread of the virus. Although well-intentioned, one unintended adverse consequence was an increase in violence, abuse, and neglect. We reviewed the literature on the effect the pandemic had on domestic violence, child and elder abuse and neglect, human trafficking, and gun violence. In this paper we explore common themes and causes of this violence and offer suggestions to help mitigate risk during ongoing and future pandemics. Just as these forms of violence primarily target at-risk, vulnerable populations, so did pandemic-related violence target marginalized populations including women, children, Blacks, and those with lower socioeconomic status. This became, and remains, a public health crisis within a crisis. In early 2021, the American College of Emergency Physicians (ACEP) Public Health and Injury Committee was tasked with reviewing the impact the pandemic had on violence and abuse as the result of a resolution passed at the 2020 ACEP Council meeting. Measures meant to help control the spread of the COVID-19 pandemic had many unintended consequences and placed people at risk for violence. Emergency departments (ED), although stressed and strained during the pandemic, remain a safety net for survivors of violence. As we move out of this pandemic, hospitals and EDs need to focus on steps that can be taken to ensure they preserve and expand their ability to assist victims should another pandemic or global health crisis develop.


[External signals can induce stable increase in frequency of cell death in populations].
Relatively weak radiation and some other external actions, producing no "forced" cell death, trigger some intracellular mechanisms in various unicellular organisms (amoebae, ciliates, yeasts) and in the studied mammalian cells (rat vascular endotheliocytes). These mechanisms provide spasmodic changes: massive transition of cell populations into a stationary alternative state which is characterized by an increased predisposition to cell death, in comparison with the initial level. This phenomenon is considered as a particular, widely spread in nature form of genetic control of cell death frequency populations.


Pharmacological Profile of MP-101, a Novel Non-racemic Mixture of R- and S-dimiracetam with Increased Potency in Rat Models of Cognition, Depression and Neuropathic Pain.
The racemic mixture dimiracetam negatively modulates NMDA-induced glutamate release in rat spinal cord synaptosomal preparations and is orally effective in models of neuropathic pain. In this study, we compared the effects of dimiracetam, its R- or S-enantiomers, and the R:S 3:1 non-racemic mixture (MP-101). In vitro, dimiracetam was more potent than its R- or S-enantiomers in reducing the NMDA-induced [3H]D-aspartate release in rat spinal cord synaptosomes. Similarly, acute oral administration of dimiracetam was more effective than a single enantiomer in the sodium monoiodoacetate (MIA) paradigm of painful osteoarthritis. Then, we compared the in vitro effects of a broad range of non-racemic enantiomeric mixtures on the NMDA-induced [3H]D-aspartate release. Dimiracetam was a more potent blocker than each isolated enantiomer but the R:S 3:1 non-racemic mixture (MP-101) was even more potent than dimiracetam, with an IC50 in the picomolar range. In the chronic oxaliplatin-induced neuropathic pain model, MP-101 showed a significantly improved anti-neuropathic profile, and its effect continued one week after treatment suspension. MP-101 also performed better than dimiracetam in animal models of cognition and depression. Based on the benign safety and tolerability profile previously observed with racemic dimiracetam, MP-101 appears to be a novel, promising clinical candidate for the prevention and treatment of several neuropathic and neurological disorders.


Synthesis and biological activity of analogues of beta-chlornaltrexamine and beta-funaltrexamine at opioid receptors.
beta-Chlornaltrexamine and beta-funaltrexamine analogues 4-7 with different length "arms" to which an electrophilic moiety is attached were synthesized in an effort to obtain affinity labels that would selectively and irreversibly block specific opioid receptor types and subtypes. One of the compounds, 4, was a potent, irreversible blocker of opioid receptors in the guinea pig ileum and mouse vas deferens preparations. The results of this study suggest that nucleophiles that are remote from the recognition locus are capable of alkylation by reactive electrophiles.


Retained Products of Conception Associated with Intravasation of Hysterosalpingogram Contrast and Hysteroscopic Distention Media: A Case Report.
Hysteroscopic resection of retained products of conception has not been previously described to increase the risk for volume overload at the time of hysteroscopy. A 35-year-old woman with a history of recurrent pregnancy loss was evaluated by a hysterosalpingogram that identified retained products of conception with adjacent contrast intravasation. She underwent a hysteroscopic resection of the uterine septum and products of conception. During the 15 minute operating time she developed a fluid deficit of 2,300 cc of 3% sorbitol with resulting hyponatremia despite normal pressure and flow settings on the fluid management equipment. When a hysterosalpingogram demonstrates likely retained products of conception with an accompanying intravasation of contrast media, the provider should consider this finding a potential risk factor for excess intravasation of hysteroscopic distention media and take additional precautions to avoid volume overload.


Interaction between protein kinase C and protein kinase A can modulate transmitter release at the rat neuromuscular synapse.
We used intracellular recording to investigate the functional interaction between protein kinase C (PKC) and protein kinase A (PKA) signal transduction cascades in the control of transmitter release in the neuromuscular synapses from adult rats. Our results indicate that: 1) PKA and PKC are independently involved in asynchronous release. 2) Evoked acetylcholine (ACh) release is enhanced with the PKA agonist Sp-8-BrcAMP and the PKC agonist phorbol ester (PMA). 3) PKA has a constitutive role in promoting a component of normal evoked transmitter release because, when the kinase is inhibited with H-89, the release diminishes. However, the PKC inhibitor calphostin C (CaC) does not affect ACh release. 4) PKA regulates neurotransmission without PKC involvement because, after PMA or CaC modulation of the PKC activity, coupling to the ACh release of PKA can normally be stimulated with Sp-8-BrcAMP or inhibited with H-89. 5) After PKA inhibition with H-89, PKC stimulation with PMA (or inhibition with CaC) does not lead to any change in evoked ACh release. However, in PKA-stimulated preparations with Sp-8-BrcAMP, PKC becomes tonically active, thus potentiating a component of release that can now be blocked with CaC. In normal conditions, therefore, PKA was able to modulate ACh release independently of PKC activity, whereas PKA stimulation caused the PKC coupling to evoked release. In contrast, PKA inhibition prevent PKC stimulation (with the phorbol ester) and coupling to ACh output. There was therefore some dependence of PKC on PKA activity in the fine control of the neuromuscular synaptic functionalism and ACh release.


Change in psychotropic drug use in Norwegian nursing homes between 2004 and 2011.
ABSTRACTBackground:We aimed to assess whether there were any changes in the use of psychotropic drugs in Norwegian nursing homes between 2004 and 2011. Also, we investigated whether the predictors of use of specific psychotropic drug groups have changed. We conducted a secondary analysis of two cohort studies of two Norwegian nursing home samples (2004/05 and 2010/11). Multivariate models were applied. We found a significant decrease in the prescription of antipsychotic drugs between 2004 and 2011 (0.63 OR, 95%CI = 0.49-0.82, p < 0.001) even after adjusting for relevant demographic and clinical variables. There are only minor changes for the other psychotropic drugs. We found that (1) the use of specific psychotropic drug groups as well as the number of psychotropic drugs used was associated with more affective symptoms and (2) the use of specific psychotropic drug groups as well as the number of psychotropic drugs used was associated with lower scores on the Physical Self-Maintenance scale. This is the first study to show a robust decrease in antipsychotic drug use in nursing home patients with dementia unrelated to possible changes in case mix. The change might be explained by treatment recommendations against its use except in the most severe conditions of aggression or psychosis. Our findings indicate that it takes several years to implement scientific knowledge in clinical practice in nursing homes.


Reward maximization justifies the transition from sensory selection at childhood to sensory integration at adulthood.
In a multisensory task, human adults integrate information from different sensory modalities--behaviorally in an optimal Bayesian fashion--while children mostly rely on a single sensor modality for decision making. The reason behind this change of behavior over age and the process behind learning the required statistics for optimal integration are still unclear and have not been justified by the conventional Bayesian modeling. We propose an interactive multisensory learning framework without making any prior assumptions about the sensory models. In this framework, learning in every modality and in their joint space is done in parallel using a single-step reinforcement learning method. A simple statistical test on confidence intervals on the mean of reward distributions is used to select the most informative source of information among the individual modalities and the joint space. Analyses of the method and the simulation results on a multimodal localization task show that the learning system autonomously starts with sensory selection and gradually switches to sensory integration. This is because, relying more on modalities--i.e. selection--at early learning steps (childhood) is more rewarding than favoring decisions learned in the joint space since, smaller state-space in modalities results in faster learning in every individual modality. In contrast, after gaining sufficient experiences (adulthood), the quality of learning in the joint space matures while learning in modalities suffers from insufficient accuracy due to perceptual aliasing. It results in tighter confidence interval for the joint space and consequently causes a smooth shift from selection to integration. It suggests that sensory selection and integration are emergent behavior and both are outputs of a single reward maximization process; i.e. the transition is not a preprogrammed phenomenon.


The severity of whirling disease among wild trout corresponds to the differences in genetic composition of Tubifex tubifex populations in central Colorado.
We analyzed the geographic distribution of Tubifex tubifex from various river drainages in central Colorado by genetic screening with specific mitochondrial 16S ribosomal DNA (mt 16S rDNA) markers. Four distinct mt 16S rDNA lineages are evident. The sites varied with respect to land- and water-use practices. All sites represented habitats presumed capable of supporting oligochaetes. At the locations where whirling disease has had the greatest impact on resident rainbow trout, T. tubifex, representing lineages I and III (genotypes known to be susceptible to Mxyobolus cerebralis), were most commonly found. In contrast, at sites less affected by whirling disease, T. tubifex of lineages V and VI that are more resistant to M. cerebralis infections were more abundant. The predominance of resistant T. tubifex worms (lineages V and VI) at low-impact sites supports the conclusion that when these genotypes are in greater abundance, the potential for more severe effects of whirling disease on wild rainbow trout populations may be diminished.


Nationwide trends in laparoscopic colectomy from 2000 to 2004.
Over the past 5 years, several studies have demonstrated that laparoscopic colon resection is an acceptable and perhaps preferable alternative to open resection for both benign diseases and cancer. The extent to which laparoscopic colon resections are used nationally is not known. The Nationwide Inpatient Sample was used to identify laparoscopic and open elective colon resections performed in the United States each year from 2000 through 2004. The trends in adoption of the laparoscopic technique for each type of colon resection and for the most common diagnoses were identified, and differences in patient and provider characteristics were examined. From 2000 to 2004, the proportion of colon resections performed laparoscopically increased from 3% to 6.5%. The proportion performed for cancer increased from 1.4% to 4.3%, and for benign disease from 4.6% to 8.2%. Patients treated laparoscopically tended to be younger (median age, 61 years vs 66 years; p < 0.001) and to have fewer comorbidities (Charlson score of zero for 58.1% vs 37%; p < 0.001). Laparoscopic colon resections were more widely adopted in teaching versus nonteaching hospitals (5.1% vs 3.7%; p < 0.001) and in urban versus rural hospitals (4.7% vs 2.2%; p < 0.001). Although the proportion of colon resections performed laparoscopically increased in the first half of this decade, it has remained very low. This trend is similar across procedure types and diagnoses. It remains to be seen whether greater patient demand and more recent trials will result in wider adoption of the laparoscopic approach.


Repopulation of different layers of host human Bruch's membrane by retinal pigment epithelial cell grafts.
To determine the morphology of human retinal pigment epithelium (RPE) after reattachment to different ultrastructural layers of human Bruch's membrane (BM). Bruch's membrane explants were prepared from eyes of 23 human donors (age range, 11-89 years). The basal lamina of the RPE, inner collagenous layer, and elastin layer were removed sequentially by mechanical and enzymatic techniques. First-passage cells of human RPE (15,000 cells/6 mm explant) from three donors (ages, 52, 64, and 80 years) were plated onto different layers of human BM, and the explants were examined by scanning and transmission electron microscopy up to 21 days later. RPE flattened and extended footplates 6 hours after plating onto basal lamina. Cells remained round 6 and 24 hours after plating onto the inner collagenous, elastin, or outer collagenous layer. The RPE cells became confluent 14 days after plating onto basal lamina but did not become confluent up to 21 days after plating onto the inner collagenous or elastin layer. Sparse round cells were observed 21 days after plating onto deeper layers, suggesting extensive loss of RPE. The morphology and subsequent behavior of the RPE reattached to BM depends on the anatomic layer of BM available for cell reattachment. The results suggest that the ability of transplanted RPE to repopulate BM in age-related macular degeneration and other disorders may depend on the layer of BM available to serve as a substrate for cell reattachment.


Immunological reactivity in patients with widespread carcinoma of the liver and bile ducts as evaluated on the basis of spleen white pulp morphology.
The morphology of the white pulp of the spleens collected from forty four patients died in widespread carcinoma of the liver and extrahepatic bile ducts was histologically evaluated by utilizing the standardized reporting system previously outlined. As a control material, the same number of age- and sex-matched patients died in myocardial infarction or cerebrovascular accident without signs of any malignancy was used. Special attention was paid to the assessment of the T- and B-lymphocyte populations responsible for the immunological reactivity. Histological characteristics suggesting an active function of both the cell-mediated and humoral immune reactions (central and peripheral lymphoid sheats, respectively) were found to be within the normal range in the control spleens, whereas in the cancer series, both these elements were profoundly deranged. The significance of the histological observations made was discussed in the light of the tumor immunology, and a conclusion was drawn that an impairment of both the humoral and cell-mediated immune responses must exist in patients dying in widespread hepato-biliary carcinoma. The applicability of the standardized reporting system used was advocated.


Hepatic vascular malformations in hereditary hemorrhagic telangiectasia.
Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disorder that can involve the liver diffusely in the form of vascular malformations ranging from small telangiectases to discrete arteriovenous malformations. Anatomically, three different patterns of abnormal vascular communications can occur in liver: portal vein to hepatic vein (portovenous), hepatic artery to hepatic vein (arteriovenous) and hepatic artery to portal vein (arterioportal), with the most common being arteriovenous. Only 5 to 8% of patients with these vascular malformations are symptomatic. When symptomatic, patients present with high-output cardiac failure, biliary ischemia (which, when severe, can progress to biliary and hepatic necrosis and lead to acute liver failure), or portal hypertension. Other less common presentations include portosystemic encephalopathy and abdominal angina. Diagnosis is confirmed by Doppler ultrasonography or multidetector computed tomography. The hallmark findings are intrahepatic hypervascularization and an enlarged common hepatic artery. Focal nodular hyperplasia and nodular regenerative hyperplasia are common findings. Symptomatic patients are treated with intensive medical treatment aimed at the predominant clinical presentation. Patients who fail aggressive medical therapy and those with acute biliary/hepatic necrosis should be considered for liver transplantation.


[Heat transfer in the inferior vena cava and abdominal aorta of the rabbit].
The blood temperature was measured in the abdominal aorta and in the v. cava posterior as blood flowed from the legs to the heart in anesthetised rabbits. The temperature in the v. cava posterior was changed by the influx of blood from various tissues and organs of abdominal cavity and of the body. The temperature was increased by the influx of blood from liver (0.23 degrees C +/- 0.03) and kidneys (0.25 degrees C +/- 0.04). The temperature fall was caused by the influx from subcutaneous veins (0.18 degrees C +/- 0.04). The temperature in the aorta was equal to the temperature in the right heart.


Light-regulated protein and mRNA synthesis in root caps of maize.
Illumination of maize roots initiates changes in mRNA levels and in the activities of proteins within the root cap. Using Northern analysis we showed a 5-6-fold increase in the levels of three specific mRNAs and a 14-fold increase in plastid mRNA. This increase is rapid, occurring within 30 minutes of illumination. With prolonged periods of darkness following illumination, messages return to levels observed in dark, control caps. For two species of mRNA illumination results in a reduction in message levels. Light-stimulated increases in the levels of specific mRNAs are proportionally greater than are increases in the activities of corresponding proteins. We suggest that the light-stimulated increase in protein activity in root caps may be preceded by and occur as a consequence of enhanced levels of mRNA. Our work suggests that photomorphogenesis in roots could involve changes in the levels of a wide variety of mRNAs within the root cap.


Clostridium perfringens Enterotoxin: Action, Genetics, and Translational Applications.
Clostridium perfringens enterotoxin (CPE) is responsible for causing the gastrointestinal symptoms of several C. perfringens food- and nonfood-borne human gastrointestinal diseases. The enterotoxin gene (cpe) is located on either the chromosome (for most C. perfringens type A food poisoning strains) or large conjugative plasmids (for the remaining type A food poisoning and most, if not all, other CPE-producing strains). In all CPE-positive strains, the cpe gene is strongly associated with insertion sequences that may help to assist its mobilization and spread. During disease, CPE is produced when C. perfringens sporulates in the intestines, a process involving several sporulation-specific alternative sigma factors. The action of CPE starts with its binding to claudin receptors to form a small complex; those small complexes then oligomerize to create a hexameric prepore on the membrane surface. Beta hairpin loops from the CPE molecules in the prepore assemble into a beta barrel that inserts into the membrane to form an active pore that enhances calcium influx, causing cell death. This cell death results in intestinal damage that causes fluid and electrolyte loss. CPE is now being explored for translational applications including cancer therapy/diagnosis, drug delivery, and vaccination.


Exosomes Carry microRNAs into Neighboring Cells to Promote Diffusive Infection of Newcastle Disease Virus.
Newcastle disease virus (NDV), an avian paramyxovirus, was shown to prefer to replicate in tumor cells instead of normal cells; however, this mechanism has not been fully elucidated. Exosomes play a crucial role in intercellular communication due to the bioactive substances they carry. Several studies have shown that exosomes are involved in virus infections. However, the effect that exosomes have on NDV-infected tumor cells is not known. In this study, we focus on the role of exosomes secreted by NDV-infected HeLa cells in promoting NDV replication. Three miRNA candidates (miR-1273f, miR-1184, and miR-198) embraced by exosomes were associated with enhancing NDV-induced cytopathic effects on HeLa cells. Furthermore, luciferase assays, RT-qPCR, and enzyme-linked immunosorbent assay (ELISA) all demonstrated that these miRNAs could suppress interferon (IFN)-β gene expression. Enhanced NDV replication in HeLa cells was identified by Western blot and plaque assays. Based on these results, we speculate that NDV employed exosomes entry into neighboring cells, which carry miRNAs, resulting in inhibition of the IFN pathway and promotion of viral infection. To our knowledge, this is the first report on the involvement of NDV-employed exosomes in tumor cells, and as such, it provides new insights into the development of anti-tumor therapies.


Compliance with clinical practice guidelines.
Compliance with clinical practice guidelines is a challenging topic because it depends on a variety of factors, some related to guidelines themselves, some related to users, and some to the implementation context. Among the former are guideline quality, purpose and implementation modality. Among the user-related factors are attitude to behavioural changes, authority interventions to foster adherence and eventually the type of users (general practitioners, hospital professionals, home caregivers, patients, etc.). Context is also crucial because organisational issues, such as lack of resources, can hamper guideline implementation and sometimes the original guideline intention is overridden by the guideline adaptation to a certain setting. This chapter analyses these factors and discusses their implications for the development of computerised decision support systems. Moreover, it gives examples of non-compliance detection and analysis in a specific real-world computerised guideline implementation, facing both methodological and practical issues.


Is There a Difference between Cemented and Uncemented Femoral Stem Extensions in Revision Knee Arthroplasty?
A stem is usually recommended for the femoral component in revision total knee arthroplasty (TKA) for reasons of alignment, fixation, and bone loss. However, the optimal method of fixation for the femoral component stem remains controversial. We queried the prospective revision TKA database of one surgeon and performed a clinical and radiographic evaluation of 84 knee revisions in which a femoral component stem extension was implanted. There was no established protocol for fixation of the femoral stem during this time. There were 34 knees with cemented (C) fixation and 50 with uncemented (UC) fixation. There were no significant differences in age, gender, body mass index (BMI), or Anderson's Orthopaedic Research Institute (AORI) defect between the two groups. Patients were evaluated using the classic Knee Society clinical and radiographic scores and followed for a mean of 6 years (range: 2-17 years). There was no statistically significant difference in prevalence of reoperation for loosening between cemented and uncemented stems (cemented 3.3% vs. uncemented 10%; p = 0.4). Post hoc power analysis showed that 203 knees in each group would be needed for statistical significance. With the numbers available, there was no difference in aseptic component loosening and radiographic loosening combined (one revision and two radiographic loosening, 9%, in the C group vs. five revisions and three radiographic loosening, 16%, in the UC group; p = 0.51). There was no difference between the groups in the overall rate of any reoperation. There were no differences in postoperative Knee Society pain score, change in pain score, Knee Society function score, or change in function score. Due to the numbers required, a large multicenter study will be needed to determine the optimal method of fixation of the femoral stem in revision TKA.


Hierarchically ordered oxides
Porous silica, niobia, and titania with three-dimensional structures patterned over multiple length scales were prepared by combining micromolding, polystyrene sphere templating, and cooperative assembly of inorganic sol-gel species with amphiphilic triblock copolymers. The resulting materials show hierarchical ordering over several discrete and tunable length scales ranging from 10 nanometers to several micrometers. The respective ordered structures can be independently modified by choosing different mold patterns, latex spheres, and block copolymers. The examples presented demonstrate the compositional and structural diversities that are possible with this simple approach.


Optimizing the benefit of multiple sclerosis therapy: the importance of treatment adherence.
Poor treatment adherence is problematic in many therapy areas, including multiple sclerosis (MS). Several immunomodulatory drugs are available for the treatment of MS, all of which require frequent parenteral administration. Current first-line therapies are two formulations of interferon (IFN) beta-1a, one of IFN beta-1b, and one of glatiramer acetate. Discontinuation of treatment is common, particularly in the first few months after initiation. Although the true effect of poor adherence to MS therapy is not known, it is likely to lead to a fall in treatment efficacy. Many factors influence a patient's adherence to treatment, including the patient's MS subtype and disability level, cognitive impairment resulting from MS, perceived lack of efficacy of the prescribed medication, and adverse events associated with MS therapy. This article summarizes the barriers to adherence to MS therapies, and discusses patient management strategies that can be employed to encourage adherence. Future advances in the field of MS treatment will be explored, including the development of orally administered drugs, which may enhance adherence.


Identifying a Role of Red and White Wine Extracts in Counteracting Skin Aging: Effects of Antioxidants on Fibroblast Behavior.
Dermal fibroblasts are the main actor in many proteins' secretion, including collagen, preserving skin function. Free radicals are involved in skin aging and damages involving different cellular components. The imbalance between reactive oxygen species (ROS) amount and natural antioxidant enzymes negatively affects skin homeostasis. Natural compounds have recently emerged as a potential anti-aging tool in tissue regeneration. In the present paper we evaluated the antioxidant activity of white and red wines, considering their probable use, as raw materials, for the formulation of cosmetic products with anti-aging properties. We studied a method that would allow the removal of the alcoholic fraction of wines and determined their composition by LC-MS analysis. We then tested the possible cytotoxic effects of red and white wines on fibroblasts by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay, and their antioxidant activity by the catalase activity test in stressing conditions. Finally, we evaluated their anti-aging potential through the β-galactosidase colorimetric assay. Our results showed that wine extracts exhibit a remarkable antioxidant and anti-aging activity, especially on cells exposed to a marked stressful event. These properties could suggest their possible application as cosmetical products for skin regeneration.


The Relationship Between Earlobe Creases and the Presence, Extent, and Severity of Coronary Artery Atherosclerosis: A Regional Population-Based Autopsy Study.
The association between earlobe crease(s) and coronary artery atherosclerosis has stimulated debate and controversy over the years. Most available published studies have been conducted on living patients. Although these studies offer valuable insight into such associations in patients who exhibit symptoms, no information is available from these studies on the prevalence of earlobe creases among an asymptomatic population. Postmortem studies offer the advantage of including individuals free of symptomatic cardiovascular disease, thus providing an inbuilt control group. The atherosclerotic pathological findings of 1298 individuals who underwent coronial postmortem examination at Wellington Regional Hospital, New Zealand, between 2006 and 2013 were retrospectively studied. Earlobe creases and atherosclerosis involving the coronary arteries were semiquantitatively appraised. The presence of an earlobe crease was found to be significantly associated with coronary artery atherosclerosis.


Determinants of the Financial Contribution to the NHS: The Case of the COVID-19 Emergency in Italy.
The COVID-19 pandemic has quickly become an unprecedented challenge for many countries at a global level, requiring a significant amount of financial resources to support the National Healthcare System (NHS). In Italy, most of these resources came from the general public through tax payments and monetary donations. The present work aims to investigate the antecedents of citizens' willingness to financially support the NHS in a situation of public emergency such as the one related to the COVID-19 outbreak. It also aims to distinguish between the willingness to support the system through two different forms of financial contribution, tax payment and charitable giving. An empirical study was performed in the midst of the Italian public health emergency, while the country was reaching its contagion peak. Results showed that participants were more willing to give a financial contribution when it was framed as a one-off donation rather than as a one-off tax payment. Moreover, it was found that trust in money management was the most important factor in predicting the intention to make a financial contribution to the NHS, either through a tax payment or through charitable giving. The perceived risks with regard to the pandemic, in contrast, had no impact.


Plasma histamine concentration during propranolol induced bronchoconstriction.
The mechanism of propranolol induced bronchoconstriction in asthma is uncertain, as airway beta adrenoceptors are not innervated by sympathetic nerves and circulating adrenaline concentrations are not raised. Propranolol 10 mg was infused over 27 minutes in 14 subjects with mild asthma. Peak expiratory flow (PEF) decreased by 80-235 l/min (17-51% of baseline) in nine subjects, who were called "responders," and by less than 50 l/min (12% of baseline) in five "non-responders". These two groups did not differ in baseline ventilatory function or in any clinical characteristic. In "responders" mean PEF had decreased significantly from 440 to 390 l/min after infusion of propranolol 2.1 mg, though the maximum fall in PEF occurred during or within five minutes of the end of the infusion. In nine of the subjects (six "responders" and three "non-responders") the possibility that propranolol induced bronchoconstriction is due to blockade of mast cell beta receptors leading to increased mediator release was examined by measurement of plasma histamine concentration as an index of mast cell degranulation. There was no consistent change in plasma histamine concentration in either group. No evidence of increased mast cell mediator release has been found in association with propranolol induced bronchoconstriction.


Categorical Perception of p-Values.
Traditional statistics instruction emphasizes a .05 significance level for hypothesis tests. Here, we investigate the consequences of this training for researchers' mental representations of probabilities - whether .05 becomes a boundary, that is, a discontinuity of the mental number line, and alters their reasoning about p-values. Graduate students with statistical training (n = 25) viewed pairs of p-values and judged whether they were "similar" or "different." After controlling for several covariates, participants were more likely and faster to judge p-values as "different" when they crossed the .05 boundary (e.g., .046 vs. .052) compared to when they did not (e.g., .026 vs. .032). This result suggests a categorical perception-like effect for the processing of p-values. It may be a consequence of traditional statistical instruction creating a psychologically real divide between so-called statistical "significance" and "nonsignificance." Such a distortion is undesirable given modern approaches to statistical reasoning that de-emphasize dichotomizing the p-value continuum.


Replacing alfalfa hay with amaranth hay: effects on production performance, rumen fermentation, nutrient digestibility and antioxidant ability in dairy cows.
The aim of this research was to explore the effects of dietary substitution of alfalfa hay by amaranth hay on production performance, rumen fermentation, nutrient digestibility, serum biochemical parameters and antioxidant ability in dairy cows. A total of 45 healthy Holstein cows with same parity and similar milk yield and body weight were randomly divided into 3 groups: control diet without amaranth hay (CON) or 50% and 100% alfalfa hay replaced by an equal amount of amaranth hay (dry matter basis, AH1 and AH2, respectively). All the cows were fed regularly 3 times a day at 06:30, 14:30 and 22:30 and had free access to water. The experiment lasted for 60 d. The dry matter intake of CON and AH1 groups was higher (p<0.05) than that of AH2 group. Compared with AH1 group, the milk yield of AH2 group was reduced (p<0.05). Moreover, dietary substitution of alfalfa hay by amaranth hay increased (p<0.05) milk fat, ammonia nitrogen and acetate concentrations. However, the crude protein digestibility of AH2 group was lower (p<0.05) than that of CON group, while an opposite tendency of serum urea nitrogen was found between two groups. The neutral detergent fiber digestibility of AH1 group was increased (p<0.05) when compared to AH2 group. Amaranth hay treatment increased (p<0.05) the serum concentration of glutathione peroxidase in dairy cows. Compared with CON group, the malonaldehyde activity of AH1 group was decreased (p<0.05). Dietary replacing alfalfa hay with amaranth hay (50% ratio) of dairy cows did not affect production performance but improved their antioxidant ability.


Rate-dependent shortening of action potential duration increases ventricular vulnerability in failing rabbit heart.
Congestive heart failure (CHF) predisposes to ventricular fibrillation (VF) in association with electrical remodeling of the ventricle. However, much remains unknown about the rate-dependent electrophysiological properties in a failing heart. Action potential properties in the left ventricular subepicardial muscles during dynamic pacing were examined with optical mapping in pacing-induced CHF (n=18) and control (n=17) rabbit hearts perfused in vitro. Action potential durations (APDs) in CHF were significantly longer than those observed for controls at basic cycle lengths (BCLs)>1,000 ms but significantly shorter at BCLs<400 ms. Spatial APD dispersions were significantly increased in CHF versus control (by 17-81%), and conduction velocity was significantly decreased in CHF (by 6-20%). In both groups, high-frequency stimulation (BCLs<150 ms) always caused spatial APD alternans; spatially concordant alternans and spatially discordant alternans (SDA) were induced at 60% and 40% in control, respectively, whereas 18% and 82% in CHF. SDA in CHF caused wavebreaks followed by reentrant excitations, giving rise to VF. Incidence of ventricular tachycardia/VFs elicited by high-frequency dynamic pacing (BCLs<150 ms) was significantly higher in CHF versus control (93% vs. 20%). In CHF, left ventricular subepicardial muscles show significant APD shortenings at short BCLs favoring reentry formations following wavebreaks in association with SDA. High-frequency excitation itself may increase the vulnerability to VF in CHF.


Heparin-binding sites in granulocyte-macrophage colony-stimulating factor. Localization and regulation by histidine ionization.
The biological activity of granulocyte-macrophage colony-stimulating factor (GM-CSF) is modulated by the sulfated glycosaminoglycans (GAGs) heparan sulfate and heparin. However, the molecular mechanisms involved in such interactions are still not completely understood. We have proposed previously that helix C, one of the four alpha-helices of human GM-CSF (hGM-CSF), contains a GAG-binding site in which positively charged residues are spatially positioned for interaction with the sulfate moieties of the GAGs (Wettreich, A., Sebollela, A., Carvalho, M. A., Azevedo, S. P., Borojevic, R., Ferreira, S. T., and Coelho-Sampaio, T. (1999) J. Biol. Chem. 274, 31468-31475). Protonation of two histidine residues (His83 and His87) in helix C of hGM-CSF appears to act as a pH-dependent molecular switch to control the interaction with GAGs. Based on these findings, we have now generated a triple mutant form of murine GM-CSF (mGM-CSF) in which three noncharged residues in helix C of the murine factor (Tyr83, Gln85, and Tyr87) were replaced by the corresponding basic residues present in hGM-CSF (His83, Lys85, and His87). Binding assays on heparin-Sepharose showed that, at acidic pH, the triple mutant mGM-CSF binds to immobilized heparin with significantly higher affinity than wild type (WT) mGM-CSF and that neither protein binds to the column at neutral pH. The fact that even WT mGM-CSF binds to heparin at acidic pH indicates the existence of a distinct, lower affinity heparin-binding site in the protein. Chemical modification of the single histidine residue (His15) located in helix A of WT mGM-CSF with diethyl pyrocarbonate totally abolished binding to immobilized heparin. Moreover, replacement of His15 for an alanine residue significantly reduced the affinity of mGM-CSF for heparin at pH 5.0 and completely blocked heparin binding to a synthetic peptide corresponding to helix A of GM-CSF. These results indicate a major role of histidine residues in the regulation of the binding of GM-CSF to GAGs, supporting the notion that an acidic microenvironment is required for GM-CSF-dependent regulation of target cells. In addition, our results provide insight into the molecular basis of the strict species specificity of the biological activity of GM-CSF.


A biomimetic fluorescent nanosensor based on imprinted polymers modified with carbon dots for sensitive detection of alpha-fetoprotein in clinical samples.
A biomimetic fluorescent nanosensor based on molecularly imprinted polymers modified with carbon dots (CDs@MIPs) has been prepared for rapid, selective and sensitive detection of alpha-fetoprotein (AFP) in clinical samples. The nanosensor was produced using vinyl-functionalized CDs (V-CDs) as transducer elements and support materials, AFP as the template protein, N-isopropylacrylamide (NIPAM) and 4-vinylphenylbronic acid (VPBA) as the thermo-responsive and pH-responsive monomer, respectively, and ammonium peroxodisulphate (APS) and N,N'-methylene bisacrylamide (MBA) as the initiator and cross-linker, respectively. The newly synthesized nanosensor was characterized by FT-IR, TEM, XRD and elemental analysis, which unambiguously confirmed the successful formation of the nanosensor. The fluorescence quenching degree of CDs@MIPs exhibited a good linear response to AFP in a concentration range of 10 to 100 ng mL-1, the limit of detection (LOD) of 0.474 ng mL-1, and high recoveries at three spiking levels of AFP ranging from 97.05% to 102.00%, with relative standard deviations (RSDs) below 4.2% being obtained. Moreover, the proposed CDs@MIPs were successfully exploited to detect AFP in human serum samples. This study successfully established a novel method for rapid, convenient, and highly sensitive and selective detection of AFP, which provides new ideas for the detection of tumor markers.


Extracting the ON and OFF contributions to the full-field photopic flash electroretinogram using summed growth curves.
Under cone-mediated (photopic) conditions, an "instantaneous" flash of light, including both stimulus onset and offset, will simultaneously activate both "ON" and "OFF" bipolar cells, which either depolarize (ON) or hyperpolarize (OFF) in response and, respectively, produce positive-going and negative-going deflections in the electroretinogram (ERG). The stimulus-response (SR) relationship of the photopic ON response demonstrates logistic growth, like that manifested in the rod-mediated (scotopic) b-wave, which is driven by a single class of depolarizing bipolar cell. However, the photopic b-wave SR function is importantly shaped by OFF responses, leading to a "photopic hill." Furthermore, both on and off stimuli elicit activity in both ON and OFF bipolar cells. This has made it difficult to produce meaningful parameters for ready interpretation of the photopic b-wave SR relationship. Therefore, we evaluated whether the sum of sigmoidal SR functions, as descriptors of the depolarizing and hyperpolarizing components of the photopic flash ERG, could be used to elucidate and quantitate the mechanisms that produce the photopic hill. We used a novel fitting routine to optimize a sum of simple sigmoidal curves to SR data in five groups of subjects: Healthy adult, 10-week-old infant, congenital stationary night blindness (CSNB), X-linked juvenile retinoschisis (XJR), and preterm-born, both without and with a history of retinopathy of prematurity (ROP). Differences in ON and OFF amplitude, sensitivity, and implicit time among the groups were then compared using parameters extracted from these fits. We found that our modeling procedure enabled plausible derivations of ON and OFF pathway contributions to the ERG, and that the parameters produced appeared to have physiological relevance. In adult subjects, the ON and OFF amplitudes were similar in magnitude with respectively longer and shorter implicit times. Infant, CSNB, and XJR subjects showed significant ON pathway deficits. History of preterm-birth, without or with a diagnosis of ROP, did not much affect cone responses.


Improved blood velocity measurements with a hybrid image filtering and iterative Radon transform algorithm.
Neural activity leads to hemodynamic changes which can be detected by functional magnetic resonance imaging (fMRI). The determination of blood flow changes in individual vessels is an important aspect of understanding these hemodynamic signals. Blood flow can be calculated from the measurements of vessel diameter and blood velocity. When using line-scan imaging, the movement of blood in the vessel leads to streaks in space-time images, where streak angle is a function of the blood velocity. A variety of methods have been proposed to determine blood velocity from such space-time image sequences. Of these, the Radon transform is relatively easy to implement and has fast data processing. However, the precision of the velocity measurements is dependent on the number of Radon transforms performed, which creates a trade-off between the processing speed and measurement precision. In addition, factors like image contrast, imaging depth, image acquisition speed, and movement artifacts especially in large mammals, can potentially lead to data acquisition that results in erroneous velocity measurements. Here we show that pre-processing the data with a Sobel filter and iterative application of Radon transforms address these issues and provide more accurate blood velocity measurements. Improved signal quality of the image as a result of Sobel filtering increases the accuracy and the iterative Radon transform offers both increased precision and an order of magnitude faster implementation of velocity measurements. This algorithm does not use a priori knowledge of angle information and therefore is sensitive to sudden changes in blood flow. It can be applied on any set of space-time images with red blood cell (RBC) streaks, commonly acquired through line-scan imaging or reconstructed from full-frame, time-lapse images of the vasculature.


Phasic dopamine as a prediction error of intrinsic and extrinsic reinforcements driving both action acquisition and reward maximization: a simulated robotic study.
An important issue of recent neuroscientific research is to understand the functional role of the phasic release of dopamine in the striatum, and in particular its relation to reinforcement learning. The literature is split between two alternative hypotheses: one considers phasic dopamine as a reward prediction error similar to the computational TD-error, whose function is to guide an animal to maximize future rewards; the other holds that phasic dopamine is a sensory prediction error signal that lets the animal discover and acquire novel actions. In this paper we propose an original hypothesis that integrates these two contrasting positions: according to our view phasic dopamine represents a TD-like reinforcement prediction error learning signal determined by both unexpected changes in the environment (temporary, intrinsic reinforcements) and biological rewards (permanent, extrinsic reinforcements). Accordingly, dopamine plays the functional role of driving both the discovery and acquisition of novel actions and the maximization of future rewards. To validate our hypothesis we perform a series of experiments with a simulated robotic system that has to learn different skills in order to get rewards. We compare different versions of the system in which we vary the composition of the learning signal. The results show that only the system reinforced by both extrinsic and intrinsic reinforcements is able to reach high performance in sufficiently complex conditions.


Neuroglobin correlates with cryptochrome-1 in obstructive sleep apnea with primary aldosteronism.
Neuroglobin (Ngb) is highly expressed in the suprachiasmatic nucleus, and can regulate Per1 gene expression. It is still not known whether Ngb also influences Cryptochrome (Cry). Cry is implicated in hypertension and primary aldosteronism (PA) in mice. There is a strong correlation between Obstructive Sleep Apnea (OSA) and PA. We propose to prove that Ngb and Cry play a role in OSA with PA. Subjects were recruited consecutively from residents of Jakarta, Indonesia; subjects aged 30-65 years with moderate to severe OSA and hypertension were included in the study. OSA was diagnosed using an unattended type 2 portable monitor (Alice Pdx), hypertension was diagnosed when morning blood pressure exceeded 140/90 mmHg or when taking anti-hypertensive drugs. Serum concentration of aldosterone, renin, Cry1, Cry2 and Ngb protein were determined using ELISA method. Primary aldosteronism (PA) was defined as ARR ≥20. Forty subjects were recruited, 26 male and 14 female, median age 52.5 years, BMI 27.46 kg/m2, and AHI 34.8 times/hour. We found 16 subjects with PA and 24 non PA. Cry1 and Cry2 did not correlate with ARR in PA and non PA groups. Ngb correlated positively with Cry1 (Spearman's rho = 0.455, p = 0.038) but not Cry2 in PA patients. Cry1 concentration decreased in severe hypoxia. Ngb correlates with Cry1 in OSA with PA. There is no correlation between Cry1 or Cry2 with PA.


Transient acantholytic dermatosis (Grover's disease). A skin disorder related to heat and sweating.
We report seven cases of transient acantholytic dermatosis (Grover's disease) to exemplify a causal association with heat and sweating. The excessive heat and sweating was related to the use of a hot tub, a hot water bottle, a steam bath, an electric blanket, the prolonged wearing of a polyester suit, and postoperative bed confinement.