Differences in fMRI intersubject correlation while viewing unedited and edited videos of dance performance.
Intersubject correlation (ISC) analysis of functional magnetic resonance imaging (fMRI) data provides insight into how continuous streams of sensory stimulation are processed by groups of observers. Although edited movies are frequently used as stimuli in ISC studies, there has been little direct examination of the effect of edits on the resulting ISC maps. In this study we showed 16 observers two audiovisual movie versions of the same dance. In one experimental condition there was a continuous view from a single camera (Unedited condition) and in the other condition there were views from different cameras (Edited condition) that provided close up views of the feet or face and upper body. We computed ISC maps for each condition, as well as created a map that showed the difference between the conditions. The results from the Unedited and Edited maps largely overlapped in the occipital and temporal cortices, although more voxels were found for the Edited map. The difference map revealed greater ISC for the Edited condition in the Postcentral Gyrus, Lingual Gyrus, Precentral Gyrus and Medial Frontal Gyrus, while the Unedited condition showed greater ISC in only the Superior Temporal Gyrus. These findings suggest that the visual changes associated with editing provide a source of correlation in maps obtained from edited film, and highlight the utility of using maps to evaluate the difference in ISC between conditions.


Crossover from tumbling to tank-treading-like motion in dense simulated suspensions of red blood cells.
Via computer simulations, we provide evidence that the shear rate induced red blood cell tumbling-to-tank-treading transition also occurs at quite high volume fractions, where collective effects are important. The transition takes place as the ratio of effective suspension stress to the characteristic cell membrane stress exceeds a certain value and does not explicitly depend on volume fraction or cell deformability. This value coincides with that for a transition from an orientationally less ordered to a highly ordered phase. The average cell deformation does not show any signature of transition, but rather follows a simple scaling law independent of volume fraction.


The number needed to treat for adalimumab, etanercept, and infliximab based on ACR50 response in three randomized controlled trials on established rheumatoid arthritis: a systematic literature review.
To compare the efficacy of adalimumab, etanercept, and infliximab in patients with established rheumatoid arthritis (RA) taking concomitant methotrexate (MTX) by calculating the number needed to treat (NNT) using three different methods. A systematic literature search of the Cochrane Library, MEDLINE, and EMBASE was conducted from inception to 30 June 2006. Two pairs of investigators, a Danish and a Swedish pair, independently conducted a structured literature review. The reviewers selected any published randomized, double-blind, MTX controlled study of adalimumab, etanercept, and infliximab, presenting the American College of Rheumatology 50% response (ACR50) after 12 months in RA patients with a mean disease duration of at least 5 years. The two review groups independently extracted the estimates necessary to calculate the NNT. The reviewers consistently selected the same three randomized, controlled trials (RCTs), one for each of the drugs, and extracted equal data for the number of patients completing the 12-month intervention, and the corresponding number of ACR50 responding patients after therapy. Some baseline differences were noted: patients in the etanercept trial had a shorter disease duration and did not receive MTX prior to inclusion; patients in the adalimumab study had lower Health Assessment Questionnaire (HAQ) scores. The calculated NNTs varied slightly depending on the method used. The fully adjusted NNTs (95% confidence intervals) for adalimumab, etanercept, infliximab standard dosage and infliximab double dosage were 4 (3-6), 4 (3-6), 8 (4-66), and 4 (3-11) patients, respectively. This study indicates equal efficacy of the three anti-tumour necrosis factor (TNF) therapies.


Is parvovirus B19 the cause for autoimmunity against the angiotensin II type receptor?
Initial studies have demonstrated the significance of the agonistic angiotensin II receptor AT1 autoantibody (AT1-AA) in preeclampsia, although it is unclear what factors induce its generation. Since the epitope recognized by AT1-AA shares high homology with parvovirus B19 (PVB19) capsid proteins, we have investigated the relationship between the presence of AT1-AA in maternal circulation and PVB19 sero-prevalence in normal and abnormal pregnancy. We determined the parvovirus IgG sero-prevalence in normal pregnancies in the second trimester and those with abnormal uterine perfusion that are at risk for preeclampsia. Secondly, pregnancies at delivery with preeclampsia or intrauterine growth restriction were included. All women with normal perfusion were AT1-AA-negative and 80% were parvovirus-IgG-positive. Sixty-three percent of pregnancies with abnormal uterine perfusion were AT1-AA-positive and 71% IgG-positive. Fifty-two percent of the IgG-positive pregnancies in this subgroup were also AT1-AA-positive, and 9 of the 10 parvovirus IgG-negative women were AT1-AA-positive. In the third trimester, 87% of pregnancies with manifest disease were AT1-AA-positive and 58% IgG-positive. While 79% of the PVB19 IgG-positive pregnancies were also AT1-AA-positive, all parvovirus IgG-negative women were AT1-AA-positive. In all groups, AT1-AA activity did not differ between parvovirus IgG-negative and positive women. We find parvovirus IgG-positive pregnant women in all subgroups without relation to AT1-AA presence. This favors AT1-AA generation to be independent of epitope mimicry between parvovirus B19 capsid proteins and the AT1 receptor.


A comparison of New York City playground hazards in high- and low-income areas.
To compare playground hazards in high- and low-income neighborhoods. Forty-five playgrounds were randomly selected from the 9 New York City community districts that met our study criteria and were divided into high-and low-income groups based on comparison to the median of the median incomes ($24452 per year) of the 9 districts. Playgrounds are maintained by the City of New York Parks and Recreation Department and were assessed by one of us (S.A.S.) using a standardized on-site survey based on the US Consumer Product Safety Commission's guidelines for public playground safety. Total hazards per play area were subdivided into 3 categories: park design hazards, equipment maintenance hazards, and equipment hazards relating to fall injuries. A play area was defined as an individual set of equipment. Twenty-five (56%) of the parks were located in low-median-income districts and contained 98 (53%) of the total play areas. High- and low-income playgrounds did not differ significantly in the amount or type of equipment, mean fall injury hazards per play area, or mean park design hazards per play area. Low-income districts had a significantly higher mean total hazards per play area (6.1 vs. 4.2; P = .02) and mean equipment maintenance hazards per play area (2.1 vs. 1.0; P = .02). Significantly more hazards per play area were identified in the low-income group compared with the high-income group.


Quantitative Glycoproteomic Analysis Identifies Platelet-Induced Increase of Monocyte Adhesion via the Up-Regulation of Very Late Antigen 5.
Physiological stimuli, such as thrombin, or pathological stimuli, such as lysophosphatidic acid (LPA), activate platelets circulating in blood. Once activated, platelets bind to monocytes via P-selectin-PSGL-1 interactions but also release the stored contents of their granules. These platelet releasates, in addition to direct platelet binding, activate monocytes and facilitate their recruitment to atherosclerotic sites. Consequently, understanding the changes platelet releasates induce in monocyte membrane proteins is critical. We studied the glyco-proteome changes of THP-1 monocytic cells affected by LPA- or thrombin-induced platelet releasates. We employed lectin affinity chromatography combined with filter aided sample preparation to achieve high glyco- and membrane protein and protein sequence coverage. Using stable isotope labeling by amino acids in cell culture, we quantified 1715 proteins, including 852 membrane and 500 glycoproteins, identifying the up-regulation of multiple proteins involved in monocyte extracellular matrix binding and transendothelial migration. Flow cytometry indicated expression changes of integrin α5, integrin β1, PECAM-1, and PSGL-1. The observed increase in monocyte adhesion to fibronectin was determined to be mediated by the up-regulation of very late antigen 5 via a P-selectin-PSGL-1 independent mechanism. This novel aspect could be validated on CD14+ human primary monocytes, highlighting the benefits of the improved enrichment method regarding high membrane protein coverage and reliable quantification.


Prevalence of Hepatitis Delta Virus Infection among Hepatitis B Virus-Infected and Exposed Patients.
Hepatitis delta virus (HDV) infection is a cause of coinfection and superinfection among hepatitis B virus (HBV)-infected patients. The global prevalence of HDV may vary drastically depending on the geographical location. In India, serological techniques form the basis for the determination of HDV prevalence in majority of the studies with very limited literature based on molecular techniques. In addition, sparse data on HDV infection among HBV-exposed group, i.e., patients with total antibodies to core antigen (anti-hepatitis B core [HBc]) positive and negative hepatitis B surface antigen (HBsAg), are available. This study was aimed to determine the prevalence of HDV in both HBV-infected and HBV-exposed groups, utilizing both serological and molecular methods. This was a retrospective cross-sectional study conducted from January till June 2018 where samples of 142 patients were retrieved and were categorized into two groups: Group A included patients with both HBsAg and anti-HBc positivity (n = 120/142 [85%]), i.e., confirmed HBV infection, and Group B included patients with anti-HBc positivity and HBsAg negativity (n = 22/142 [15%]), i.e., exposed to HBV. All the specimens were retrieved from -80°C and were tested for anti-HDV immunoglobulin (Ig) M (IgM), anti-HDV IgG, and HDV RNA. HDV infection was observed in only one patient in Group A and none in Group B, making an overall prevalence of 0.78% (95% confidence interval = 0.02%-3.9%). The infected patient was reactive for both IgM and IgG with a viral load of 2log10IU/ml. The present study provides evidence that HDV infection is very low(0.78%) in this part of India. However further prospective studies with larger sample size are warranted.


Genes Suggest Ancestral Colour Polymorphisms Are Shared across Morphologically Cryptic Species in Arctic Bumblebees.
Our grasp of biodiversity is fine-tuned through the process of revisionary taxonomy. If species do exist in nature and can be discovered with available techniques, then we expect these revisions to converge on broadly shared interpretations of species. But for the primarily arctic bumblebees of the subgenus Alpinobombus of the genus Bombus, revisions by some of the most experienced specialists are unusual for bumblebees in that they have all reached different conclusions on the number of species present. Recent revisions based on skeletal morphology have concluded that there are from four to six species, while variation in colour pattern of the hair raised questions as to whether at least seven species might be present. Even more species are supported if we accept the recent move away from viewing species as morphotypes to viewing them instead as evolutionarily independent lineages (EILs) using data from genes. EILs are recognised here in practice from the gene coalescents that provide direct evidence for their evolutionary independence. We show from fitting both general mixed Yule/coalescent (GMYC) models and Poisson-tree-process (PTP) models to data for the mitochondrial COI gene that there is support for nine species in the subgenus Alpinobombus. Examination of the more slowly evolving nuclear PEPCK gene shows further support for a previously unrecognised taxon as a new species in northwestern North America. The three pairs of the most morphologically similar sister species are separated allopatrically and prevented from interbreeding by oceans. We also find that most of the species show multiple shared colour patterns, giving the appearance of mimicry among parts of the different species. However, reconstructing ancestral colour-pattern states shows that speciation is likely to have cut across widespread ancestral polymorphisms, without or largely without convergence. In the particular case of Alpinobombus, morphological, colour-pattern, and genetic groups show little agreement, which may help to explain the lack of agreement among previous taxonomic revisions.


Neuropharmacology and neurochemistry of canine narcolepsy.
It is believed that narcolepsy involves abnormalities of rapid eye movement (REM) sleep, especially of REM sleep atonia. Compelling evidence suggests that the regulation of REM sleep and REM sleep atonia involves a reciprocal interaction of cholinergic and monoaminergic systems. Using our canine model of narcolepsy and a pharmacological approach, we have previously demonstrated a similar interaction in the regulation of cataplexy. Global activation of cholinergic or monoaminergic transmission aggravates or suppresses canine cataplexy, respectively. We have also identified the subtypes of monoaminergic and cholinergic receptors specifically involved in this interaction. Cataplexy is aggravated by activation of the cholinergic system via M2 stimulation, as well as deactivation of the catecholaminergic systems by either blockade of postsynaptic alpha-1b receptors or stimulation of alpha-2 or D2 inhibitory autoreceptors. These pharmacological results correspond to previously identified neurochemical abnormalities in canine narcolepsy, such as significant increases in M2 receptors in the pons, alpha-1 receptors in the amygdala, alpha-2 receptors in the locus coeruleus and D2 receptors in the amygdala and nucleus accumbens, when compared to control animals. Using local perfusion of active compounds, we have further demonstrated that cholinoceptive sites in the pontine reticular formation, as well as in the basal forebrain, are involved in the regulation of cataplexy. Although the specific sites of action of the monoaminergic compounds remain unknown, the results of our pharmacological and neurochemical studies to date suggest that a widespread hyperactivity of cholinergic systems within the central nervous system together with a hypoactivity of catecholaminergic systems underlie the pathophysiology of narcolepsy.


Experience of islet isolation without neutral protease supplementation.
We have reported improved islet isolation outcomes using a new digestion protocol where the pancreas is perfused only with collagenase, and neutral protease (NP) is administered during the digestion phase. Since the inception of this protocol, we have had some cases where administration of NP was not required. Our new protocol was utilized in 94 islet isolations. The timing of adding NP was dependent on the progression of digestion but in 10 cases the progression was rapid and most islets in the assessment samples were free from the exocrine tissue. As a result NP was not added at all for these isolations (no-NP group). In the remaining 84 isolations, NP was added during digestion phase (control group). Pancreata in the each group were digested with a similar collagenase dose. Digestion time was shorter in the no-NP (15.0±1.8 vs 19.5±0.6 min, P=0.004). At post-digestion, the no-NP had fewer trapped islets (10.9±2.8 vs 28.1±2.4%, P=0.009). Post-purification islet yield was similar (355±45 x10 ( 3) vs 318±17 x10 ( 3) IE, P=0.29). Five preparations in the no-NP were used for clinical transplantation, leading to a 64.3±15.2% reduction in insulin usage. Interestingly, cold ischemia time was longer in the no-NP (10.3±0.9 vs 7.9±0.4 h, P=0.04). One particular collagenase lot having the highest NP activity contamination was used in 7 isolations in the no-NP. Our experience indicates that supplementation of collagenase with NP is not always necessary for effective isolation. Cold ischemia time and NP contamination should be evaluated for optimal NP dosage.


Improvement in Fatigue during Natalizumab Treatment is Linked to Improvement in Depression and Day-Time Sleepiness.
Fatigue is a frequent symptom in multiple sclerosis (MS) and often interrelated with depression and sleep disorders making symptomatic treatment decisions difficult. In the single-arm, observational phase IV TYNERGY study, relapsing-remitting MS patients showed a clinically meaningful decrease in fatigue over 1 year of treatment with natalizumab. To evaluate whether fatigue improvement might be directly linked to improved depression and day-time sleepiness. Patients were assessed regarding fatigue, depression, and day-time sleepiness. The relation between changes of the two latter symptoms and changes in fatigue was analyzed. After 1 year of natalizumab treatment, the majority of patients (>92%) remained stable or improved in total, motor, and cognitive fatigue. Proportion of patients without depression increased by 17% while proportions of mildly depressed patients or patients with potential major depression decreased by 5 and 12%, respectively. Proportion of patients classified as not being sleepy increased by 13% while proportions of sleepy and very sleepy patients decreased by 11 and 2%, respectively. Most importantly, improved depression and sleepiness were significantly related to improved fatigue. Our findings highlight the importance of patient-reported outcomes in identifying potential benefits of drug treatment beyond its well-established effects on disease activity and disability progression.


Health social work in Canada: Five trends worth noting.
Highlighting a strong human rights and social justice orientation underlying health social work in Canada, this paper describes recent contributions of Canadian health social work practitioners and scholars to five areas identified by Auslander (2001) in a delphi study of health social work in its first century. Five current 'trends' are discussed which correspond with Auslander's themes of professional legitimacy and scope, social causation, dissemination of knowledge, interventions, and cultural appropriateness. These trends are: 1) defining the scope of health social work practice; 2) addressing the social determinants of health; 3) promoting evidence-based practice in health social work; 4) delivering client and family-centered care; and 5) implementing cultural safety and trauma-informed practice. Suggestions are made to further strengthen the position of health social work in Canada.


A new hormonal therapy for estrogen receptor-negative breast cancer.
We postulate that the androgen dehydroepiandrosterone sulfate (DHEAS) may represent an innovative hormonal treatment for estrogen (ER), progesterone (PR) receptor-negative, but androgen receptor (AR)-positive breast cancers by inhibiting breast cancer cell growth through AR stimulation. Three ER,PR-negative breast cancer cell lines (HCC 1137, 1954, and 38), were treated with DHEAS. DHEAS-induced growth was measured by a methylthiotetrazole (MTT) proliferation assay and apoptosis by TUNEL fluorescence. Androgen receptor gene expression levels were determined using quantitative real-time polymerase chain reaction (q-RT-PCR). HCC cell lines 1954 and 1937 were positive for AR expression; HCC 38 was weakly positive. MTT analysis showed DHEAS-induced decreases in cell proliferation of 47% in HCC 1937, 27% in HCC 1954, and 0.4% in HCC 38. Ten days of culturing HCC 1954 cells after the removal of DHEAS resulted in a 3.5-fold increase in growth. Continuous treatment for the same duration induced a 2.8-fold decrease in growth. Parallel experiments showed no significant changes in HCC 38 cultures. TUNEL assays showed DHEAS-induced apoptosis fold increases of 2.8 in HCC 1937, 1.9 in HCC 1954, and no significant difference in HCC 38 cultures. Q-RT-PCR of HCC 1954 cells showed a 6-fold DHEAS-induced decrease in AR gene expression at 4 h. Co-treatment with Casodex nullified this effect. DHEAS inhibited growth of ER,PR-negative, AR-positive breast cancer cells. DHEAS was cytotoxic to these breast cancer cells via the apoptosis pathway. DHEAS may be an effective treatment for a population previously excluded from hormone therapy.


Sixty years of anthropogenic pressure: a spatio-temporal genetic analysis of brown trout populations subject to stocking and population declines.
Analyses of historical samples can provide invaluable information on changes to the genetic composition of natural populations resulting from human activities. Here, we analyse 21 microsatellite loci in historical (archived scales from 1927 to 1956) and contemporary samples of brown trout (Salmo trutta) from six neighbouring rivers in Denmark, to compare the genetic structure of wild populations before and after population declines and stocking with nonlocal strains of hatchery trout. We show that all populations have been strongly affected by stocking, with admixture proportions ranging from 14 to 64%. Historical population genetic structure was characterized by isolation by distance and by positive correlations between historical effective population sizes and habitat area within river systems. Contemporary population genetic structure still showed isolation by distance, but also reflected differences among populations in hatchery trout admixture proportions. Despite significant changes to the genetic composition within populations over time, dispersal rates among populations were roughly similar before and after stocking. We also assessed whether population declines or introgression by hatchery strain trout should be the most significant conservation concern in this system. Based on theoretical considerations, we argue that population declines have had limited negative effects for the persistence of adaptive variation, but admixture with hatchery trout may have resulted in reduced local adaptation. Collectively, our study demonstrates the usefulness of analysing historical samples for identifying the most important consequences of human activities on the genetic structure of wild populations.


Ecology of zoonoses: natural and unnatural histories.
More than 60% of human infectious diseases are caused by pathogens shared with wild or domestic animals. Zoonotic disease organisms include those that are endemic in human populations or enzootic in animal populations with frequent cross-species transmission to people. Some of these diseases have only emerged recently. Together, these organisms are responsible for a substantial burden of disease, with endemic and enzootic zoonoses causing about a billion cases of illness in people and millions of deaths every year. Emerging zoonoses are a growing threat to global health and have caused hundreds of billions of US dollars of economic damage in the past 20 years. We aimed to review how zoonotic diseases result from natural pathogen ecology, and how other circumstances, such as animal production, extraction of natural resources, and antimicrobial application change the dynamics of disease exposure to human beings. In view of present anthropogenic trends, a more effective approach to zoonotic disease prevention and control will require a broad view of medicine that emphasises evidence-based decision making and integrates ecological and evolutionary principles of animal, human, and environmental factors. This broad view is essential for the successful development of policies and practices that reduce probability of future zoonotic emergence, targeted surveillance and strategic prevention, and engagement of partners outside the medical community to help improve health outcomes and reduce disease threats.


Fast recursive filters for simulating nonlinear dynamic systems.
A fast and accurate computational scheme for simulating nonlinear dynamic systems is presented. The scheme assumes that the system can be represented by a combination of components of only two different types: first-order low-pass filters and static nonlinearities. The parameters of these filters and nonlinearities may depend on system variables, and the topology of the system may be complex, including feedback. Several examples taken from neuroscience are given: phototransduction, photopigment bleaching, and spike generation according to the Hodgkin-Huxley equations. The scheme uses two slightly different forms of autoregressive filters, with an implicit delay of zero for feedforward control and an implicit delay of half a sample distance for feedback control. On a fairly complex model of the macaque retinal horizontal cell, it computes, for a given level of accuracy, one to two orders of magnitude faster than the fourth-order Runge-Kutta. The computational scheme has minimal memory requirements and is also suited for computation on a stream processor, such as a graphical processing unit.


Naturally split inteins assemble through a "capture and collapse" mechanism.
Split inteins are a class of naturally occurring proteins that carry out protein splicing in trans. The chemical mechanism of protein trans-splicing is well-understood and has been exploited to develop several powerful protein engineering technologies. Split intein chemistry is preceded by efficient molecular recognition between two protomers that become intertwined in their bound state. It is currently unclear how this unique topology is achieved upon fragment association. Using biophysical techniques in conjunction with protein engineering methods, including segmental isotopic labeling, we show that one split intein fragment is partly folded, while the other is completely disordered. These polypeptides capture each other through their disordered regions and form an ordered intermediate with native-like structure at their interface. This intermediate then collapses into the canonical intein fold. This mechanism provides insight into the evolutionary constraints on split intein assembly and should enhance the development of split intein-based technologies.


Pressure-driven collective growth mechanism of planar cell colonies.
The growth of cell colonies is determined by the migration and proliferation of the individual cells. This is often modeled with the Fisher-Kolmogorov (FK) equation, which assumes that cells diffuse independently from each other, but stop to proliferate when their density reaches a critial limit. However, when using measured, cell-line specific parameters, we find that the FK equation drastically underestimates the experimentally observed increase of colony radius with time. Moreover, cells in real colonies migrate radially outward with superdiffusive trajectories, in contrast to the assumption of random diffusion. We demonstrate that both dicrepancies can be resolved by assuming that cells in dense colonies are driven apart by repulsive, pressure-like forces. Using this model of proliferating repelling particles (PRP), we find that colony growth exhibits different dynamical regimes, depending on the ratio between a pressure-related equilibrium cell density and the critial density of proliferation arrest.


Polymorphism of endothelial nitric oxide synthase gene in patients with erectile dysfunction.
Endothelial-derived nitric oxide (NO), which is produced by endothelial nitric oxide synthase (eNOS) in response to increased blood flow, maintains the tumescence phase of erection. The eNOS gene is located on the seventh somatic chromosome and the polymorphism of this gene has been reported to cause changes in the structure of enzyme system, resulting in disturbance of its activity. The aim of this prospective study is to evaluate the relationship between polymorphism of eNOS gene and erectile dysfunction (ED). Thirty patients with ED (mean age: 58.7 +/- 9.97, range: 39-74 years) and 25 voluntary controls (mean age: 56.44 +/- 7.58, range: 47-72 years) were enrolled to the study. Patients with ED were evaluated with International Index of Erectile Function (IIEF) questionnaire, routine blood tests for systemic vascular risk factors, and color Doppler ultrasonography while potency of the control group were only assessed with IIEF questionnaire. The presence of polymorphism of eNOS gene was determined in both groups by polymerase chain reaction in the fourth intron of the seventh somatic chromosome that encodes eNOS gene. The incidences of diabetes mellitus and coronary artery disease were statistically higher in the ED group (P = 0.023 and 0.029, respectively) while mean IIEF score was significantly lower (P = 0.001). Evaluation with color Doppler ultrasonography revealed penile arterial insufficiency in six cases, cavernosal insufficiency in 19 cases, and mixed vascular insufficiency in five cases. The distributions of three eNOS genotypes (eNOS4b/b, eNOS4a/b, and eNOS4a/a) among ED patients and controls were similar (P > 0.05). However, eNOS4a/b genotype was statistically higher in diabetics (P = 0.042). Also, 80% of the patients with severe ED and 54.5% of the diabetic patients with ED had eNOS4a/b genotype. In our study, no correlation was detected between the polymorphism of eNOS gene and ED. However, 80% of the patients with severe ED and 54.5% of the diabetic patients with ED had eNOS4a/b genotype. Based on our data, it seems that diabetic patients with ED tend to have more eNOS4a/b genotype.


Geographic disparities in mammography capacity in the South: a longitudinal assessment of supply and demand.
Studies have shown that there is sufficient availability of mammography; however, little is known about geographic variation in capacity. The purpose of this study was to determine the locations and extent of over/undersupply of mammography in 14 southern states from 2002 to 2008. Mammography facility data were collected from the U.S. Food and Drug Administration (FDA). Population estimates, used to estimate the potential demand for mammography, were obtained from GeoLytics Inc. Using the two-step floating catchment area method, we calculated spatial accessibility at the block group level and categorized the resulting index to represent the extent of under/oversupply relative to the potential demand. Results show decreasing availability of mammography over time. The extent of over/undersupply varied significantly across the South. Reductions in capacity occurred primarily in areas with an oversupply of machines, resulting in a 68 percent decrease in the percent of women living in excess capacity areas from 2002 to 2008. The percent of women living in poor capacity areas rose by 10 percent from 2002 to 2008. Our study found decreasing mammography availability and capacity over time, with substantial variation across states. This information can assist providers and policy makers in their business planning and resource allocation decisions.


Keratitis, ichthyosis, and deafness (KID) syndrome. Vertical transmission and death from multiple squamous cell carcinomas.
A father and daughter had typical clinical features of the keratitis, ichthyosis, and deafness (KID) syndrome, as described by Skinner et al in 1981. To our knowledge, ours is the first observation of a vertical transmission of this syndrome. The mechanism of inheritance is uncertain. These two patients as well as the 26 previously described exhibited a typical hyperkeratotic eruption, which should not be confused with ichthyosis. The characteristic features are diffuse hyperkeratosis, keratotic plaques, reticulated hyperkeratosis on the face, peribuccal grooves, and heavy-grain leatherlike keratoderma. The occurrence of multiple squamous cell carcinomas underlines the seriousness of this congenital ectodermal defect. Etretinate can relieve the lesions without actually improving the chances of survival.


Image-guided Stereotactic Body Radiotherapy in Metastatic Prostate Cancer.
In the last years, the use of Image Guided Stereotactic Radiotherapy (IG-SBRT) in patients with metastatic prostate cancer has increased. In this study, we aimed to assess the role of IG-SBRT in terms of local control and safety in patients with metastatic prostate cancer. Primary and secondary endpoints of this prospective observational study were local control and safety related to IG-SBRT. All lesions were treated with 24 Gy as a single fraction or 27 Gy in 3 fractions. After SBRT, Systemic therapies were administered only after the occurrence of more than three synchronous active lesions in oligometastatic patients (patients with less than 4 active synchronous lesions) or new lesions occurrence in patients with more than 3 synchronous lesions. From April 2011 to June 2017, 78 metastatic lesions (32 bone and 46 node) from 51 patients with prostate cancer were treated. After a median follow-up of 18.5 months (range=3-103 months), only 2 lesions (4%) relapsed inside the radiation field. All local recurrences were located on the bone. Estimated 12 and 24 months local control ratios were 98.7 and 97.4%, respectively. Except for one case, toxicity greater than G2 was not recorded. IG-SBRT is safe and can be considered as a valid therapy in patients with metastatic prostate cancer requiring a long-lasting metastases control.


Validation of an easy questionnaire on the assessment of salt habit: the MINISAL-SIIA Study Program.
The aim of the present study was to validate a short questionnaire on habitual dietary salt intake, to quickly and easily identify individuals whose salt consumption exceeds recommended levels. A total of 1131 hypertensive subjects participating in the MINISAL-SIIA study were included in the analysis. Anthropometric indexes, blood pressure, and 24-h urinary sodium excretion (NaU) were measured. A fixed-sequence questionnaire on dietary salt intake was administered. NaU was significantly associated with scores, with a linear association across categories (p for trend <0.0001). In addition, participants who achieved a total score above the median value (eight points) had significantly higher NaU than those whose score was below median (p < 0.0001). In the total sample, the prevalence of "high NaU" (NaU > 85 mmol/day) and "very high NaU" (NaU > 170 mmol/day) was 86 and 35%, respectively. The score of the questionnaire had a significant ability to detect both "high NaU"-with a specificity of 95% at the score of 10 points-and "very high NaU"-with a specificity of 99.6% at score of 13 points. The main results of the study indicates that a higher score of this short questionnaire is distinctive of habitual high salt consumption in hypertensive patients.


Amphotericin B loaded sulfonated chitosan nanoparticles for targeting macrophages to treat intracellular Candida glabrata infections.
The current study assesses the potential of functionalised chitosan nanoparticles (CNPs) for proficient macrophage delivery of amphotericin B (AmpB) for the management of Candida glabrata fungemia. Chitosan was functionalised by the method of sulfation by using chlorosulfonic acid and the developed compound was confirmed by FTIR, 1H NMR and degree of sulfation and CHNS analysis. Amphotericin B encapsulated sulfated chitosan (AmpB-SCNPs), when characterized showed a hydrodynamic diameter of 310 ± 14 nm and zeta potential of 41.5 ± 2 mV. The safety of AmpB-SCNPs was established by the alamar cytotoxicity assay in nanoparticle treated macrophages following 24 h incubation. The AmpB-SCNPs showed a significant increase in the reduction of C. glabrata in comparison with the bare AmpB and AmpB-CNPs (55.2 and 42.7 vs 11.12 cfu/ml) indicating that AmpB-SCNPs could be a promising carrier for specific delivery of AmpB to macrophages for effective treatment of Candida glabrata fungemia.


Continuous versus intermittent infusion of oxacillin for treatment of infective endocarditis caused by methicillin-susceptible Staphylococcus aureus.
Infective endocarditis (IE) is the fourth leading cause of life-threatening infection in the United States and imposes significant morbidity and mortality. The American Heart Association guidelines for the diagnosis and treatment of IE do not address continuous-infusion (CI) oxacillin. This retrospective study compares outcomes between CI oxacillin and intermittent-infusion (II) oxacillin in the treatment of IE caused by methicillin-susceptible Staphylococcus aureus (MSSA). A total of 709 medical records were reviewed for inpatients with definitive IE treated between 1 January 2000 and 31 December 2007. Continuous data were analyzed by Student's t test or the Wilcoxon rank sum test. The chi-square test or Fisher's exact test was used to compare nominal data. A multivariate logistic model was constructed. One hundred seven patients met eligibility criteria for inclusion into the study. Seventy-eight patients received CI oxacillin, whereas 28 received II oxacillin. CI and II groups were similar with respect to 30-day mortality (8% versus 10%, P = 0.7) and length of stay (20 versus 25 days, P = 0.4) but differed in 30-day microbiological cure (94% versus 79%, P = 0.03). Sixty-three patients received synergistic gentamicin, whereas 44 did not. The gentamicin and no-gentamicin groups were similar with respect to 30-day mortality (11% versus 4%, P = 0.2) and 30-day microbiological cure (90% versus 89%, P = 0.8); however, times to defervescence (4 versus 2 days, P = 0.02) were significantly different. CI oxacillin is an effective alternative to II oxacillin for the treatment of IE caused by MSSA and may improve microbiological cure. This convenient and pharmacodynamically optimized dosing regimen for oxacillin deserves consideration for patients with IE caused by MSSA.


A novel approach of fMRI-guided tractography analysis within a group: construction of an fMRI-guided tractographic atlas.
Diffusion Tensor Imaging (DTI) tractography and functional Magnetic Resonance Imaging (fMRI) investigate two complementary aspects of brain networks: white matter (WM) anatomical connectivity and gray matter (GM) function. However, integration standards have yet to be defined; namely, individual fMRI-driven tractography is usually applied and only few studies address group analysis. This work proposes an efficient method of fMRI-driven tractography at group level through the creation of a tractographic atlas starting from the GM areas activated by a verbal fluency task in 11 healthy subjects. The individual tracts were registered to the MNI space. Selection ROIs derived by GM masking and dilation of group activated areas were applied to obtain the fMRI-driven subsets within tracts. An atlas of the tracts recruited among the population was obtained by selecting for each subject the fMRI-guided tracts passing through the high probability voxels (the voxels recruited by the 90% of the subjects) and merging them together. The reliability of this approach was assessed by comparing it with the probabilistic atlas previously introduced in literature. The introduced method allowed to successfully reconstruct activated tracts, which comprehended corpus callosum, left cingulum and arcuate, a small portion of the right arcuate, both cortico-spinal tracts and inferior fronto-occipital fasciculi. Moreover, it proved to give results concordant with the previously introduced probabilistic approach, allowing in addition to reconstruct 3D trajectories of the activated fibers, which appear particularly helpful in the detection of WM connections.


Renal handling of pepsinogens A and C in man.
1. Fractional excretions of pepsinogens A and C in the urine were investigated in 21 healthy subjects and in 38 patients with chronic renal insufficiency. In eight of the healthy subjects fractional excretions were measured again after oral administration of omeprazole for 9 days. 2. The mean fractional excretion of pepsinogen A was 27.6% (range 4.4-73.9%) in healthy subjects and remained unchanged after omeprazole administration. In patients with renal failure the mean fractional excretion of pepsinogen A was 37.9% (range 7.0-81.9%). The mean fractional excretion of pepsinogen C was 1.0% (range 0.04-6.8%) in healthy subjects and decreased after omeprazole. In patients with chronic renal diseases a sharp rise in fractional excretion of pepsinogen C was observed once glomerular filtration rate was less than 40 ml/min. 3. Fractional excretion of pepsinogen A was unexpectedly high for a negatively charged protein with a molecule mass of 40,000 daltons. This might be explained by the presence of the positively charged activation peptide. Furthermore, pepsinogen C seemed to be almost entirely reabsorbed from the glomerular filtrate and a tubular reabsorption maximum appeared to be present. Pepsinogen C may, therefore, be a new marker of tubular function. The cause of the remarkable difference in tubular handling of two quite similar low-molecular-mass proteins remains to be elucidated.


TRIENNIAL LACTATION SYMPOSIUM: Nutrigenomics in livestock: Systems biology meets nutrition.
The advent of high-throughput technologies to study an animal's genome, proteome, and metabolome (i.e., "omics" tools) constituted a setback to the use of reductionism in livestock research. More recent development of "next-generation sequencing" tools was instrumental in allowing in-depth studies of the microbiome in the rumen and other sections of the gastrointestinal tract. Omics, along with bioinformatics, constitutes the foundation of modern systems biology, a field of study widely used in model organisms (e.g., rodents, yeast, humans) to enhance understanding of the complex biological interactions occurring within cells and tissues at the gene, protein, and metabolite level. Application of systems biology concepts is ideal for the study of interactions between nutrition and physiological state with tissue and cell metabolism and function during key life stages of livestock species, including the transition from pregnancy to lactation, in utero development, or postnatal growth. Modern bioinformatic tools capable of discerning functional outcomes and biologically meaningful networks complement the ever-increasing ability to generate large molecular, microbial, and metabolite data sets. Simultaneous visualization of the complex intertissue adaptations to physiological state and nutrition can now be discerned. Studies to understand the linkages between the microbiome and the absorptive epithelium using the integrative approach are emerging. We present examples of new knowledge generated through the application of functional analyses of transcriptomic, proteomic, and metabolomic data sets encompassing nutritional management of dairy cows, pigs, and poultry. Published work to date underscores that the integrative approach across and within tissues may prove useful for fine-tuning nutritional management of livestock. An important goal during this process is to uncover key molecular players involved in the organismal adaptations to nutrition.


Point-of-care detection and real-time monitoring of intravenously delivered drugs via tubing with an integrated SERS sensor.
We demonstrate an approach for detection, identification, and kinetic monitoring of drugs flowing within tubing, through the use of a plasmonic nanodome array (PNA) surface. The PNA structures are fabricated using a low-cost nanoreplica molding process upon a flexible plastic substrate that is subsequently integrated with a flow cell that connects in series with ordinary intravenous (IV) drug delivery tubing. To investigate the potential clinical applications for point-of-care detection and real-time monitoring, we perform SERS detection of ten pharmaceutical compounds (hydrocodone, levorphanol, morphine, oxycodone, methadone, phenobarbital, dopamine, diltiazem, promethazine, and mitoxantrone). We demonstrate dose-dependent SERS signal magnitude, resulting in detection limits (ng ml(-1)) well below typical administered dosages (mg ml(-1)). Further, we show that the detected drugs are not permanently attached to the PNA surface, and thus our approach is capable of performing continuous monitoring of drug delivery as materials flow through IV tubing that is connected in series with the sensor. Finally, we demonstrate the potential co-detection of multiple drugs when they are mixed together, and show excellent reproducibility and stability of SERS measurements for periods extending at least five days. The capabilities reported here demonstrate the potential to use PNA SERS surfaces for enhancing the safety of IV drug delivery.


6-year follow-up of 84 patients with cartilage defects in the knee. Knee scores improved but recovery was incomplete.
The natural history of focal cartilage injury is largely unknown. In this study we investigated 6-year outcomes in patients with arthroscopically verified, focal, full-thickness cartilage injuries of the knee. In a previous report (baseline study) of 993 knee arthroscopies, 98 patients were less than 50 years old at baseline and showed grade 3–4 focal cartilage injury, as assessed with the International Cartilage Repair Society (ICRS) scale. In the present study, 84 of the 98 patients completed follow-ups at median 6.1 (5.3–7.8) years after baseline assessments. At baseline, the patients had undergone different types of cartilage repair (n = 34) or had no treatment or only debridement (n = 64) for their cartilage injury. The follow-up included evaluations with the ICRS knee evaluation form, the Lysholm score, and other knee evaluation tests. 68 patients underwent radiographic assessments with weight bearing. Improvements compared to baseline were noted in the average ICRS functional score, visual analog scale (VAS) pain score, and the patients' rating of the function in the affected knee compared to the contra-lateral knee. However, the average ICRS activity level had decreased from baseline. The average Lysholm score was 76 (SD 21). 19 patients had Kellgren-Lawrence grades 2–3 in the affected knee and 6 patients had grades 2–3 in the contralateral knee. There was a statistically significant difference between affected and contralateral knees. Patients with arthroscopically diagnosed ICRS grade 3–4 cartilage injuries in the knee may show improvement in knee function over the following 5–8 years, with or without cartilage repair. However, knee function remains substantially affected. Further studies are needed to determine whether cartilage surgery can yield better functional outcomes than non-surgical or less invasive surgical treatments.


Therapeutic potential of bacteriophages for staphylococcal infections and selected methods for in vitro susceptibility testing of staphylococci.
Staphylococcus aureus strains are the cause of frightening hospital and community infections, especially when they are resistant to antimicrobials, have important pathogenicity factors, or have biofilm production ability. Looking for novel therapeutic options which would be effective against such strains is one of the highest priorities of medicine and medical research. The study aim was to describe the occurrence of S. aureus strains and proportion of methicillin resistant strains (MRSA) detected in laboratories of the Microbiological Institute, Faculty of Medicine, Masaryk University (FM MU) and St. Anne's University Hospital, Brno in 2011-2018. Selected strains of S. aureus were tested for biofilm production ability and susceptibility to antimicrobials and Stafal®, a phage therapeutic agent. A prerequisite was to develop a simple routine method suitable for phage susceptibility testing of bacteria. Altogether 867 clinical isolates of S. aureus and 132 strains of other species of the genus Staphylococcus (isolated in 2011-2017) were tested for susceptibility to the phage therapy preparation Stafal® using the double-layer agar method. All strains of S. aureus were tested for biofilm production ability by the modified Christensen method with the use of titration microplates and for susceptibility to antistaphylococcal antibiotics by the disk diffusion test. For 95 S. aureus strains, the outcome of the double-layer agar method (DAM) was compared with that of our newly designed method (ODM) based on optical density decrease of the bacterial suspension. During the study period, the laboratories of the Faculty of Medicine, Masaryk University (FM MU) and St. Anne's University Hospital, Brno detected 2900 strains of S. aureus per year on average. The proportion of MRSA among S. aureus isolates from blood culture and venous catheters ranged between 8.8-15.2 %. S. aureus strains recovered from venous catheters and blood culture were confirmed as stronger biofilm producers than those from other clinical specimens. MRSA strains showed higher biofilm production than methicillin susceptible strains (MSSA). As many as 90.4 % of S. aureus strains tested susceptible to the Stafal® preparation. Even a higher proportion, i.e. 99.0 %, of MRSA strains were Stafal® susceptible. No relationship was found between Stafal® susceptibility and biofilm production ability. Although Stafal® targets primarily S. aureus, some susceptibility (26.5 %) was also found for other staphylococcal species. A novel simple method designed for routine testing of susceptibility to phage therapy preparations based on optical density decrease was comparably sensitive and reliable as the commonly used double-layer agar method (DAM) and, in addition to being easy and rapid to perform, after prolonged suspension culture and at higher measurement frequency, it has an extra advantage of providing the possibility for monitoring also phage action dynamics. The proportion of MRSA strains detected in this study is comparable to that reported for the whole Czech Republic, and the biofilm production data are consistent with scientific evidence. The host range of the Stafal® preparation is relatively wide and covers most strains of S. aureus and some coagulase negative staphylococci. The highest efficiency of Stafal® (99.4 %) was observed against MRSA strains with multiple types of antibiotic resistance. In vitro testing of 867 strains of S. aureus and 132 other staphylococcal species has shown the phage therapy preparation Stafal® to be a suitable candidate therapeutic option for the treatment of staphylococcal infections, especially in case of failure of conventional antibiotic therapy. Moreover, a simple method for routine phage susceptibility testing of clinical bacterial isolates has been designed, which is an essential tool to be used in phage therapy.


Study of human precorneal tear film thickness and structure using laser interferometry.
The authors previously found that measurements of precorneal tear film thickness in animals, using laser interferometry and confocal microscopy, were larger than earlier estimates. They proposed that this occurred because optical methods did not disturb film structure and measured full thickness, including mucus. In the present study, tear film thickness was measured in humans. Coherent light was reflected from eyes and formed interference patterns. Thickness was determined from spacing of fringes. Mean thickness in six subjects was 34-45 microns, more than four times larger than earlier values. Validity and accuracy of measurements by interferometry were examined in our earlier study using confocal microscopy. Here it provided supportive evidence. Tear film thickness was estimated from optical sections through the corneas of three subjects to be 41-46 microns. Mucus content of the film also was examined. Interferometry was used to measure thinning after application of a mucolytic agent. There was no change in thickness after 5 min exposure to 0.1% (weight/volume) acetylcysteine. Solutions of 20% caused thinning to 11 microns, and thickness slowly increased to reach its original value over 40 min. Thus, the film seemed to be composed substantially of mucus, not aqueous fluid. The results also provided evidence that measurements by interferometry did not include underlying epithelium. Earlier nonoptical methods probably did not include the portion of the film that contained mucus. They seem to have greatly underestimated human tear film thickness.


Gamma-aminobutyric acid increases the water accessibility of M3 membrane-spanning segment residues in gamma-aminobutyric acid type A receptors.
Gamma-aminobutyric acid type A (GABA(A)) receptors are members of the ligand-gated ion channel gene superfamily. Using the substituted cysteine accessibility method, we investigated whether residues in the alpha(1)M3 membrane-spanning segment are water-accessible. Cysteine was substituted, one at a time, for each M3 residue from alpha(1)Ala(291) to alpha(1)Val(307). The ability of these mutants to react with the water-soluble, sulfhydryl-specific reagent pCMBS(-) was assayed electrophysiologically. Cysteines substituted for alpha(1)Ala(291) and alpha(1)Tyr(294) reacted with pCMBS(-) applied both in the presence and in the absence of GABA. Cysteines substituted for alpha(1)Phe(298), alpha(1)Ala(300), alpha(1)Leu(301), and alpha(1)Glu(303) only reacted with pCMBS(-) applied in the presence of GABA. We infer that the pCMBS(-) reactive residues are on the water-accessible surface of the protein and that GABA induces a conformational change that increases the water accessibility of the four M3 residues, possibly by inducing the formation of water-filled crevices that extend into the interior of the protein. Others have shown that mutations of alpha(1)Ala(291), a water-accessible residue, alter volatile anesthetic and ethanol potentiation of GABA-induced currents. Water-filled crevices penetrating into the interior of the membrane-spanning domain may allow anesthetics and alcohol to reach their binding sites and thus may have implications for the mechanisms of action of these agents.


Influence of retroactive disability payments on recipients' compliance with substance abuse treatment.
This study examined whether substance abusers who received large retroactive payments from Social Security disability programs were more likely to terminate residential treatment precipitously than those who did not receive payments. The records of 43 patients of a long-term residential treatment facility who received disability payments at some point during their treatment stay were blindly examined. Twenty-six of these patients received a large one-time retroactive payment representing money that accumulated during processing of the claims. To test the hypothesis that receipt of such a payment would lead to precipitous discharge, a survival regression model was used. A control group of nonrecipient patients was sampled at a comparable point in treatment. Subjects in the recipient group were significantly more likely to have unplanned discharges than those in the comparison group. These preliminary data suggest that large cash infusions can be disruptive to the course of treatment for substance abusers.


Native chemical ligation at methionine bioisostere norleucine allows for N-terminal chemical protein ligation.
The development of γ-thionorleucine (ThioNle) as a handle for native chemical ligation-desulfurization is reported here. ThioNle is a new addition to the expanding thiolated amino acid toolbox and serves as a methionine substitute in NCL with the advantage that it lacks the undesirable oxidation-prone thioether moiety. Its usefulness for N-terminal ubiquitination is demonstrated by efficient preparation of fully synthetic linear diubiquitin with preserved protein folding compared to the expressed material. Interestingly, gel-based deubiquitinating assays revealed that the methionine to norleucine substitution did affect diubiquitin cleavage, which may indicate a more profound role for methionine in the interaction between ubiquitin and the deubiquitinating enzymes than has been known so far.


Understanding age-related reductions in visual working memory capacity: examining the stages of change detection.
Visual working memory (VWM) capacity is reduced in older adults. Research has shown age-related impairments to VWM encoding, but aging is likely to affect multiple stages of VWM. In the present study, we recorded the event-related potentials (ERPs) of younger and older adults during VWM maintenance and retrieval. We measured encoding-stage processing with the P1 component, maintenance-stage processing with the contralateral delay activity (CDA), and retrieval-stage processing by comparing the activity for old and new items (old-new effect). Older adults showed lower behavioral capacity estimates (K) than did younger adults, but surprisingly, their P1 components and CDAs were comparable to those of younger adults. This remarkable dissociation between neural activity and behavior in the older adults indicated that the P1 and CDA did not accurately assess their VWM capacity. However, the neural activity evoked during VWM retrieval yielded results that helped clarify the age-related differences. During retrieval, younger adults showed early old-new effects in frontal and occipital areas and a late central-parietal old-new effect, whereas older adults showed a late right-lateralized parietal old-new effect. The younger adults' early old-new effects strongly resembled an index of perceptual fluency, suggesting that perceptual implicit memory was activated. The activation of implicit memory could have facilitated the younger adults' behavior, and the lack of these early effects in older adults may suggest that they have much lower-resolution memory than do younger adults. From these data, we speculated that younger and older adults store the same number of items in VWM, but that younger adults store a higher-resolution representation than do older adults.


Long-term effects of neonatal MK-801 treatment on prepulse inhibition in young adult rats.
Blockade of N-methyl-D-asparate (NMDA) receptors has been shown to produce some of the abnormal behaviors related to symptoms of schizophrenia in rodents and human. Neonatal treatment of rats with non-competitive NMDA antagonists has been shown to induce behavioral abnormality in a later period. The aim of this study was to determine whether brief disruption of NMDA receptor function during a critical stage of development is sufficient to produce sensorimotor-gating deficits in the late adolescence or early adulthood in the rat. Male pups received the NMDA receptor blocker MK-801 (0.13 or 0.20 mg/kg), or an equal volume of saline on postnatal day (PD) 7 through 10. The animals were tested twice for prepulse inhibition (PPI) and locomotor activity in pre- (PD 35-38) and post- (PD 56-59) puberty. Neonatal exposure to both doses MK-801 disrupted PPI in the adolescence and early adulthood. Low-dose MK-801 elicited long-term effects on startle amplitudes, whereas high-dose MK-801 did not. Neither dose of MK-801 showed a significant effect on spontaneous locomotor activity, whereas the high dose attenuated rearing. The results of this study suggest neonatal exposure to MK-801 disrupted sensorimotor gating in the adolescence and early adulthood stages. These findings indicate that rats transiently exposed to NMDA blockers in neonatal periods are useful for the study of the pathophysiology and treatment of schizophrenia.


Efficacy of commercial weight-loss programs: an updated systematic review.
Commercial and proprietary weight-loss programs are popular obesity treatment options, but their efficacy is unclear. To compare weight loss, adherence, and harms of commercial or proprietary weight-loss programs versus control/education (no intervention, printed materials only, health education curriculum, or <3 sessions with a provider) or behavioral counseling among overweight and obese adults. MEDLINE and the Cochrane Database of Systematic Reviews from inception to November 2014; references identified by program staff. Randomized, controlled trials (RCTs) of at least 12 weeks' duration; prospective case series of at least 12 months' duration (harms only). Two reviewers extracted information on study design, population characteristics, interventions, and mean percentage of weight change and assessed risk of bias. We included 45 studies, 39 of which were RCTs. At 12 months, Weight Watchers participants achieved at least 2.6% greater weight loss than those assigned to control/education. Jenny Craig resulted in at least 4.9% greater weight loss at 12 months than control/education and counseling. Nutrisystem resulted in at least 3.8% greater weight loss at 3 months than control/education and counseling. Very-low-calorie programs (Health Management Resources, Medifast, and OPTIFAST) resulted in at least 4.0% greater short-term weight loss than counseling, but some attenuation of effect occurred beyond 6 months when reported. Atkins resulted in 0.1% to 2.9% greater weight loss at 12 months than counseling. Results for SlimFast were mixed. We found limited evidence to evaluate adherence or harms for all programs and weight outcomes for other commercial programs. Many trials were short (<12 months), had high attrition, and lacked blinding. Clinicians could consider referring overweight or obese patients to Weight Watchers or Jenny Craig. Other popular programs, such as Nutrisystem, show promising weight-loss results; however, additional studies evaluating long-term outcomes are needed. None. ( CRD4201-4007155).


Arthroscopic Articular Cartilage Scores of the Canine Stifle Joint with Naturally Occurring Cranial Cruciate Ligament Disease.
This study aimed to evaluate frequency, location and severity of cartilage pathology in dogs with naturally occurring cranial cruciate ligament (CCL) disease. Stifle arthroscopic video recordings (n = 120) were reviewed. A modified Outerbridge classification system (MOCS) (0-4) was used to score cartilage at 10 locations in the femorotibial (medial and lateral femoral condyles and tibial plateaus) and patellofemoral compartments (proximal, middle and distal locations of the patella and femoral trochlear groove) of the stifle joint. Synovial pathology was scored and the presence of a medial meniscal tear was recorded. A Kruskal-Wallis test was used to evaluate association of location and synovitis with cartilage score; and presence of meniscal tear with cartilage and synovitis scores. Bonferroni correction was utilized and p < 0.05 was considered significant. Cartilage pathology and synovitis were identified in all joints. Overall cartilage severity scores were low (median MOCS 1). The median MOCS of the proximal trochlear groove (2) was significantly higher than all other locations evaluated. Higher synovitis scores were significantly associated with higher cartilage severity scores and a medial meniscal tear had no association with cartilage severity scores or synovitis. Arthroscopic articular cartilage lesions are common in dogs with CCL disease at the time of surgical intervention, although the severity of cartilage damage is mild. The proximal trochlear groove of the femur had the most severe cartilage score in the stifle joint.


Catheter ablation of idiopathic premature ventricular contractions and ventricular tachycardias originating from the vicinity of endocardial and epicardial mitral annulus.
Several previous reports have revealed that idiopathic ventricular arrhythmias (VAs), including premature ventricular contractions (PVCs) and ventricular tachycardias (IVTs), can originate from endocardial mitral annulus (ENDO MA). However, these data are limited to ENDO MA VAs, and little is known about the electrocardiographic (ECG) characteristics and the efficacy of radiofrequency catheter ablation (RFCA) via the coronary venous system for the VAs arising from the epicardial MA (EPI MA). Characteristics of body surface electrocardiogram and electrophysiologic recordings were analyzed in 21 patients with symptomatic PVCs/IVTs originating from the vicinity of MA. Among 597 patients with PVCs/IVTs, the incidence of VAs originating from the ENDO and EPI MA was 3.52% (21 cases). Eleven (52%) from the ENDO MA, and 10 (48%) from the EPI MA. There were different characteristics of ECG of PVCs/VT originating from the ENDO and EPI MA. The prolonged pseudodelta wave time and intrinsicoid deflection time in lead V2 and the precordial maximum deflection index reliably differentiated EPI MA VAs from ENDO MA VAs with high sensitivity and specificity. Successful RFCA in 18 patients could be achieved (85.7% acute procedural success). ECG characteristics of PVCs/VTs originating from the different portions of the MA are different, and can help regionalize the origin of these arrhythmias. RFCA within the coronary venous system was relatively effective and safe for the PVCs/IVTs and should be seen as an alternative approach, when the MA PVCs/IVTs could not be eliminated by RFCA from the endocardium.


A hypothesis regarding the pathogenesis and epileptogenesis of pediatric cortical dysplasia and hemimegalencephaly based on MRI cerebral volumes and NeuN cortical cell densities.
This study compared MRI cerebral volumes and Neuronal-Nuclei (NeuN) cell densities in pediatric epilepsy surgery patients with cortical dysplasia (CD; n = 25) and hemimegalencephaly (HME; n = 14). Our purpose was to deduce possible mechanisms of pathogenesis and epileptogenesis based on an understanding of normal developmental corticoneurogenesis. We used MRI to measured cerebral hemisphere volumes, and NeuN staining to determine grey and white matter cell densities and cell sizes in the molecular layer, grey, and white matter. CD and HME surgical cases were compared with autopsy or non-CD cases (n = 20). Total MRI brain volumes were similar between non-CD, CD, and HME cases. However, in HME patients, the affected cerebral hemisphere was larger and the nonaffected side smaller than non-CD cases. Compared with autopsy cases, NeuN cell densities and cell sizes in CD and HME patients were increased in the molecular layer, upper grey matter, and white matter. In CD and HME cases, total cerebral hemisphere volumes were normal in size and there were more cortical neurons in upper layers than expected. The increase in cortical neuronal densities is consistent with the hypothesis that CD and HME pathogenesis involves increased neurogenesis in the late (not early) phases of cortical formation. In addition, more neurons in the molecular layer and white matter supports the concept that CD and HME pathogenesis also involves incomplete programmed cell death in the remnant cells occupying the preplate and subplate regions. Based on our anatomical and previous electrophysiological findings, we propose that in CD and HME seizure generation is the consequence of incomplete cerebral development with abnormal interactions between immature and mature cells and cellular networks.


Estimation of maternal and child mortality one year after user-fee elimination: an impact evaluation and modelling study in Burkina Faso.
To estimate the impact on maternal and child mortality after eliminating user fees for pregnant women and for children less than five years of age in Burkina Faso. Two health districts in the Sahel region eliminated user fees for facility deliveries and curative consultations for children in September 2008. To compare health-care coverage before and after this change, we used interrupted time series, propensity scores and three independent data sources. Coverage changes were assessed for four variables: women giving birth at a health facility, and children aged 1 to 59 months receiving oral rehydration salts for diarrhoea, antibiotics for pneumonia and artemesinin for malaria. We modelled the mortality impact of coverage changes in the Lives Saved Tool using several scenarios. Coverage increased for all variables, however, the increase was not statistically significant for antibiotics for pneumonia. For estimated mortality impact, the intervention saved approximately 593 (estimate range 168-1060) children's lives in both districts during the first year. This lowered the estimated under-five mortality rate from 235 deaths per 1000 live births in 2008 to 210 (estimate range 189-228) in 2009. If a similar intervention were to be introduced nationwide, 14,000 to 19,000 (estimate range 4000-28,000) children's lives could be saved annually. Maternal mortality showed a modest decrease in all scenarios. In this setting, eliminating user fees increased use of health services and may have contributed to reduced child mortality.


Method for azimuthal alignment in fixed-angle ellipsometry.
Our objective is to develop a method for azimuthal alignment of the polarizer-analyzer in fixed-angle ellipsometry systems in which measurement of the light intensity in the straight-through mode is not possible. An analytical technique has been developed that allows the determination of the reference positions of the polarizer and analyzer through the use of reflection measurements from a dielectric sample at a single angle of incidence. The method was verified by using both a high-temperature unit and a room-temperature reflectometer system. In these cases the real part of the refractive index of the test sample was inferred with accuracy to within 0.5% and 1.7%, respectively. In addition the sensitivity of the technique to the polarizer-analyzer setting was assessed.


Surface Behavior of Boronic Acid-Terminated Silicones.
Silicone polymers, with their high flexibility, lie in a monolayer at the air-water interface as they are compressed until a critical pressure is reached, at which point multilayers are formed. Surface pressure measurements demonstrate that, in contrast, silicones that are end-modified with polar groups take up lower surface areas under compression because the polar groups submerge into the water phase. Boronic acids have the ability to undergo coordination with Lewis bases. As part of a program to examine the surface properties of boronic acids, we have prepared boronic acid-modified silicones (SiBAs) and examined them at the air-water interface to better understand if they behave like other end-functional silicones. Monolayers of silicones, aminopropylsilicones, and SiBAs were characterized at the air-water interface as a function of end functionalization and silicone chain length. Brewster angle and atomic force microscopies confirm domain formation and similar film morphologies for both functionalized and non-functionalized silicone chains. There is a critical surface pressure (10 mN m(-1)) independent of chain length that corresponds to a first-order phase transition. Below this transition, the film appears to be a homogeneous monolayer, whose thickness is independent of the chain length. Ellipsometry at the air-water interface indicates that the boronic acid functionality leads to a significant increase of film thickness at low molecular areas that is not seen for non-functionalized silicone chains. What differentiates the boronic acids from simple silicones or other end-functionalized silicones, in particular, is the larger area occupied by the headgroup when under compression compared to other or non-end-functionalized silicones, which suggests an in-plane rather than submerged orientation that may be driven by boronic acid self-complexation.


Processes of consent in research for adults with impaired mental capacity nearing the end of life: systematic review and transparent expert consultation (MORECare_Capacity statement).
Involving adults lacking capacity (ALC) in research on end of life care (EoLC) or serious illness is important, but often omitted. We aimed to develop evidence-based guidance on how best to include individuals with impaired capacity nearing the end of life in research, by identifying the challenges and solutions for processes of consent across the capacity spectrum. Methods Of Researching End of Life Care_Capacity (MORECare_C) furthers the MORECare statement on research evaluating EoLC. We used simultaneous methods of systematic review and transparent expert consultation (TEC). The systematic review involved four electronic databases searches. The eligibility criteria identified studies involving adults with serious illness and impaired capacity, and methods for recruitment in research, implementing the research methods, and exploring public attitudes. The TEC involved stakeholder consultation to discuss and generate recommendations, and a Delphi survey and an expert 'think-tank' to explore consensus. We narratively synthesised the literature mapping processes of consent with recruitment outcomes, solutions, and challenges. We explored recommendation consensus using descriptive statistics. Synthesis of all the findings informed the guidance statement. Of the 5539 articles identified, 91 met eligibility. The studies encompassed people with dementia (27%) and in palliative care (18%). Seventy-five percent used observational designs. Studies on research methods (37 studies) focused on processes of proxy decision-making, advance consent, and deferred consent. Studies implementing research methods (30 studies) demonstrated the role of family members as both proxy decision-makers and supporting decision-making for the person with impaired capacity. The TEC involved 43 participants who generated 29 recommendations, with consensus that indicated. Key areas were the timeliness of the consent process and maximising an individual's decisional capacity. The think-tank (n = 19) refined equivocal recommendations including supporting proxy decision-makers, training practitioners, and incorporating legislative frameworks. The MORECare_C statement details 20 solutions to recruit ALC nearing the EoL in research. The statement provides much needed guidance to enrol individuals with serious illness in research. Key is involving family members early and designing study procedures to accommodate variable and changeable levels of capacity. The statement demonstrates the ethical imperative and processes of recruiting adults across the capacity spectrum in varying populations and settings.


Pharmacological validation of the folkloric uses of Cyperus rotundus L. in different ailments: An in vivo and in vitro research.
In vivo and in vitro research study was conducted on Cyperus rotundus to evaluate the sound mechanistic background in the treatment of gastrointestinal, bronchial and vascular disorders as well as in pain, emesis, pyrexia and bacterial infections. Results showed that crude extract of Cyperus rotundus (Cr.Cr) exhibited the dose-dependent spasmolytic effect in rabbit jejunum by inhibiting the spontaneous and K+ (80 mM)-induced contractions. Pretreatment of tissue with Cr. Cr caused the rightward shift of calcium concentration response curves, similar to verapamil. Cr. Cr also caused the relaxation of K+(80 mM)- and carbachol (1 µM)-induced contractions of trachea preparations, similar to that of verapamil. Moreover, Cr. Cr also relaxed the contraction induced by the K+ (80 mM) and phenylephrine (1 µM) of aorta preparations. Data show that C. rotundus possess the spasmolytic, bronchodilator and vasodilator activities possibly through calcium channels blockade; validating its folkloric use in diarrhea, dyspepsia, bronchitis, asthma and hypertension in addition to antibacterial, antiemetic, antipyretic and analgesic activities.


Evaluating a DVD promoting breast cancer awareness among black women aged 25-50 years in East London.
The mean age of presentation for breast cancer among black women is substantially earlier than their white counterparts. Black women also present with adverse prognostic factors that have major clinical implications, including lower survival. To pilot the use of a 6 min DVD on breast cancer in young (under 50 years) black women, to raise awareness and examine the impact of the DVD on increased consultation and referral rates among these women. Two general practices (intervention practices) in the Hackney area were randomised to have the DVD mailed to all black women aged 25-50 years registered with the practices, and two practices to no intervention (control practices). EMIS data was used to compare consultation rates preintervention and postintervention, in the intervention as well as control practices. Interviews with practice staff and focus groups with patients in participating practices provided qualitative data on the study context and DVD effectiveness. A trend of declining consultations for breast symptoms was observed (-22% and -31% among non-black women in the control and intervention practices, and -23% among black women in the control practice) except among the target population of black women aged 25-50 years for the DVD in the intervention practices, which saw an increase of 28% in consultations. The qualitative data indicated that the DVD was well received in the target population, and suggested further ways of disseminating awareness messages and overcoming barriers to help-seeking. Pilot results suggest that the strategy of distributing the DVD may increase consultations for breast problems.


Inhibition of human lung cancer cell proliferation and survival by wine.
Compounds of plant origin and food components have attracted scientific attention for use as agents for cancer prevention and treatment. Wine contains polyphenols that were shown to have anti-cancer and other health benefits. The survival pathways of Akt and extracellular signal-regulated kinase (Erk), and the tumor suppressor p53 are key modulators of cancer cell growth and survival. In this study, we examined the effects of wine on proliferation and survival of human Non-small cell lung cancer (NSCLC) cells and its effects on signaling events. Human NSCLC adenocarcinoma A549 and H1299 cells were used. Cell proliferation was assessed by thymidine incorporation. Clonogenic assays were used to assess cell survival. Immunoblotting was used to examine total and phosphorylated levels of Akt, Erk and p53. In A549 cells red wine inhibited cell proliferation and reduced clonogenic survival at doses as low as 0.02%. Red wine significantly reduced basal and EGF-stimulated Akt and Erk phosphorylation while it increased the levels of total and phosphorylated p53 (Ser15). Control experiments indicated that the anti-proliferative effects of wine were not mediated by the associated contents of ethanol or the polyphenol resveratrol and were independent of glucose transport into cancer cells. White wine also inhibited clonogenic survival, albeit at a higher doses (0.5-2%), and reduced Akt phosphorylation. The effects of both red and white wine on Akt phosphorylation were also verified in H1299 cells. Red wine inhibits proliferation of lung cancer cells and blocks clonogenic survival at low concentrations. This is associated with inhibition of basal and EGF-stimulated Akt and Erk signals and enhancement of total and phosphorylated levels of p53. White wine mediates similar effects albeit at higher concentrations. Our data suggest that wine may have considerable anti-tumour and chemoprevention properties in lung cancer and deserves further systematic investigation in animal models of lung cancer.


Visual and metabolic stimuli cause adrenocortical suppression in fasted chickens during refeeding.
Concentrations of corticosterone were determined in the plasma of fasted domestic fowl before and at intervals after refeeding. The deprivation of food markedly increased (p less than 0.001) the level of plasma corticosterone. When refed ad libitum the corticosterone concentration declined (by 70%) within 45 min to the level in fed birds and remained at this concentration thereafter. A similar depression in the corticosterone concentration was observed when fasted birds were merely given the sight of the same diet, although the concentration returned to the fasting level within 60 min of food presentation. Refeeding diets with different metabolic energy contents demonstrated that the duration of the feeding-induced adrenocortical suppression was energy related. In fasted birds the presentation of an inert cellulose diet caused a temporary decline in the corticosterone level. In the absence of visual stimuli the administration (by force feeding) of the inert diet had no effect on the corticosterone concentration, whereas force feeding of metabolizable diets still induced adrenocortical suppression. These results demonstrate that adrenocortical suppression occurs in fasted refed birds and both visual and metabolic stimuli are involved in this response.


Why do people participate in epidemiological research?
Many assumptions are made about public willingness to participate in epidemiological research, yet few empirical studies have been conducted to ascertain whether such assumptions are correct. Our qualitative study of the public and of expert stakeholders leads us to suggest that people are generally prepared to participate in epidemiological research, particularly if it is conducted by a trusted public institution such as a government health department, charity, or university. However, there is widespread community distrust of research conducted or sponsored by pharmaceutical companies. Individuals are prompted to take part if the study concerns an illness they or a family member or friend have personally experienced or if they believe the research will confer a widespread public benefit. Preferences vary about the mode of contact for the research to be conducted. Willingness to participate in telephone surveys has decreased in recent years, and this may be a consequence of an increase in calls to homes by telemarketers and market researchers. Participants also stressed the importance of knowing where their names and contact details were sourced and suggested that this information be available to prospective study participants as a matter of course in the first approach or letter. We provide valuable information to epidemiologists in designing studies.


Successful Pregnancies in Two Orthotopic Liver Transplant (OLT) Recipients in Iran; Two Case Reports.
Pregnancy and parenting have been part of human life throughout history and liver transplant recipients are not any exception. This paper reports successful pregnancies in two liver transplant recipients in Iran. The first case was a 34-year old woman who had undergone orthotopic liver transplantation (OLT) at Shiraz Namazi Educational Hospital in 2002. She decided to get pregnant seven years after the operation. During pregnancy, immunosuppressive therapy continued, except Mycophenolate Mofetil which has an absolute contra-indication in pregnancy. The patient was followed up during pregnancy by the transplant team as well as a gynecologist. She faced no significant complications and the liver function was stable during pregnancy. She later underwent a Cesarean section in the 38(th) week of gestation and the newborn was a healthy girl weighing 2480g with an Apgar score of 8 at the time of birth. There were no evidences of prematurity or structural abnormalities in the newborn. The second case was a 31-year old primipara who had received an orthotopic liver transplant (OLT) in Shiraz in 2002. She had a smooth pregnancy without any complications and the newborn was a boy weighing 3100g with Apgar scores of 8 and 10 at the time of birth and 5 minutes thereafter, respectively. As the number of transplant recipients is growing along with the number of recipients who are in their fertility years, it is vital to ensure a proper medical care by a coordinated multidisciplinary team during pregnancy.


Performance of generalist and specialist herbivores and their endoparasitoids differs on cultivated and wild Brassica populations.
Through artificial selection, domesticated plants often contain modified levels of primary and secondary metabolites compared to their wild progenitors. It is hypothesized that the changed chemistry of cultivated plants will affect the performance of insects associated with these plants. In this paper, the development of several specialist and generalist herbivores and their endoparasitoids were compared when reared on a wild and cultivated population of cabbage, Brassica oleracea, and a recently established feral Brassica species. Irrespective of insect species or the degree of dietary specialization, herbivores and parasitoids developed most poorly on the wild population. For the specialists, plant population influenced only development time and adult body mass, whereas for the generalists, plant populations also affected egg-to-adult survival. Two parasitoid species, a generalist (Diadegma fenestrale) and a specialist (D. semiclausum), were reared from the same host (Plutella xylostella). Performance of D. semiclausum was closely linked to that of its host, whereas the correlation between survival of D. fenestrale and host performance was less clear. Plants in the Brassicaceae characteristically produce defense-related glucosinolates (GS). Levels of GS in leaves of undamaged plants were significantly higher in plants from the wild population than from the domesticated populations. Moreover, total GS concentrations increased significantly in wild plants after herbivory, but not in domesticated or feral plants. The results of this study reveal that a cabbage cultivar and plants from a wild cabbage population exhibit significant differences in quality in terms of their effects on the growth and development of insect herbivores and their natural enemies. Although cultivated plants have proved to be model systems in agroecology, we argue that some caution should be applied to evolutionary explanations derived from studies on domesticated plants, unless some knowledge exists on the history of the system under investigation.


A stochastic model for predicting the mortality of breast cancer.
Consider a cohort of women, identified by year of birth, some of whom will eventually be diagnosed with breast cancer. A stochastic model is developed for predicting the U.S. breast cancer mortality that depends on advances in therapy and dissemination of mammographic screening. The predicted mortality can be compared with the same cohort having usual care with no screening program and absence of modern therapy, or a cohort in which only a proportion participate in a screening program and have modern therapy. The model envisions that a woman may be in four health states: i.e., 1) no disease or breast cancer that cannot be diagnosed (S0), 2) preclinical state (Sp), 3) clinical state (Sc), and 4) disease-specific death (Sd). The preclinical disease refers to breast cancer that is asymptomatic but that may be diagnosed with a special exam. The clinical state refers to symptomatic disease diagnosed under usual care. One of the basic assumptions of the model is that the disease is progressive; i.e., the transitions for the first three states are S0-->Sp-->Sc. The other basic assumption is that any reduction in mortality associated with earlier diagnosis is due to a stage shift in diagnosis; i.e., early diagnosis results in a larger proportion of earlier stage patients. The model is used to predict changes in female breast cancer mortality in the U.S. women for 1975-2000. The model is general and may predict mortality for other chronic diseases that satisfy the two basic assumptions.


Quantifying dimensions in autism: a factor-analytic study.
The objective of this study was to determine whether the phenotypic variation in autism and the related pervasive developmental disorders (PDDs) is a unitary construct or whether it is composed of distinct dimensions of autistic symptoms and measures of level of functioning. One hundred twenty-nine children with autism and other forms of PDD from two samples with different inclusion criteria were assessed with the Vineland Adaptive Behavior Scales to measure level of functioning and the Autism Diagnostic Interview to measure severity of autistic behaviors. A factor analysis with varimax rotation was performed on each sample, separately and combined. Two factors emerged; one representing autistic symptoms and another representing level of functioning. The factor structure was remarkably similar and robust to variations in ascertainment and inclusion criteria between the samples. The validity of the distinction was supported by differences between males and females on the symptom factor, but not on the level of functioning factor. IQ was modestly correlated with level of functioning, but not with symptoms. The phenotypic variation seen in autism/PDD is composed of at least two different dimensions of autistic symptoms and level of functioning. The implications of this dimensional heterogeneity for research, classification, and clinical practice are discussed.


Chromatic polydiacetylene with novel sensitivity.
Conjugated polymers have been investigated for a number of applications in optoelectronics and sensing due to their important electronic and optical properties. For instance, polydiacetylene (PDA) may change color in response to external stimuli and has been extensively explored as a material for chromatic sensors. However, the practical applications of PDA materials have been largely hampered by their irreversible chromatic transitions under limited stimuli such as temperature, pH, and chemical. As a result, much effort has been paid to improve the chromatic reversibility and increase the scope of external stimuli for PDA. In this tutorial review, the recent development of PDA materials which show reversible chromatic transition and respond to new stimuli including light and electrical current has been described.


Cell cycle molecules and mechanisms of the budding and fission yeasts.
The cell cycles of the budding yeast Saccharomyces cerevisiae and the fission yeast, Schizosaccharomyces pombe are currently the best understood of all eukaryotes. Studies in these two evolutionarily divergent organisms have identified common control mechanisms, which have provided paradigms for our understanding of the eukaryotic cell cycle. This chapter provides an overview of our current knowledge of the molecules and mechanisms that regulate the mitotic cell cycle in these two yeasts.


The hair follicle as an estrogen target and source.
For many decades, androgens have dominated endocrine research in hair growth control. Androgen metabolism and the androgen receptor currently are the key targets for systemic, pharmacological hair growth control in clinical medicine. However, it has long been known that estrogens also profoundly alter hair follicle growth and cycling by binding to locally expressed high-affinity estrogen receptors (ERs). Besides altering the transcription of genes with estrogen-responsive elements, 17beta-estradiol (E2) also modifies androgen metabolism within distinct subunits of the pilosebaceous unit (i.e., hair follicle and sebaceous gland). The latter displays prominent aromatase activity, the key enzyme for androgen conversion to E2, and is both an estrogen source and target. Here, we chart the recent renaissance of estrogen research in hair research; explain why the hair follicle offers an ideal, clinically relevant test system for studying the role of sex steroids, their receptors, and interactions in neuroectodermal-mesodermal interaction systems in general; and illustrate how it can be exploited to identify novel functions and signaling cross talks of ER-mediated signaling. Emphasizing the long-underestimated complexity and species-, gender-, and site-dependence of E2-induced biological effects on the hair follicle, we explore targets for pharmacological intervention in clinically relevant hair cycle manipulation, ranging from androgenetic alopecia and hirsutism via telogen effluvium to chemotherapy-induced alopecia. While defining major open questions, unsolved clinical challenges, and particularly promising research avenues in this area, we argue that the time has come to pay estrogen-mediated signaling the full attention it deserves in future endocrinological therapy of common hair growth disorders.


Association between analytic strategy and estimates of treatment outcomes in meta-analyses.
A persistent dilemma when performing meta-analyses is whether all available trials should be included in the meta-analysis. To compare treatment outcomes estimated by meta-analysis of all trials and several alternative analytic strategies: single most precise trial (ie, trial with the narrowest confidence interval), meta-analysis restricted to the 25% largest trials, limit meta-analysis (a meta-analysis model adjusted for small-study effect), and meta-analysis restricted to trials at low overall risk of bias. One hundred sixty-three meta-analyses published between 2008 and 2010 in high-impact-factor journals and between 2011 and 2013 in the Cochrane Database of Systematic Reviews: 92 (705 randomized clinical trials [RCTs]) with subjective outcomes and 71 (535 RCTs) with objective outcomes. For each meta-analysis, the difference in treatment outcomes between meta-analysis of all trials and each alternative strategy, expressed as a ratio of odds ratios (ROR), was assessed considering the dependency between strategies. A difference greater than 30% was considered substantial. RORs were combined by random-effects meta-analysis models to obtain an average difference across the sample. An ROR greater than 1 indicates larger treatment outcomes with meta-analysis of all trials. Subjective and objective outcomes were analyzed separately. Treatment outcomes were larger in the meta-analysis of all trials than in the single most precise trial (combined ROR, 1.13 [95% CI, 1.07-1.19]) for subjective outcomes and 1.03 (95% CI, 1.01-1.05) for objective outcomes). The difference in treatment outcomes between these strategies was substantial in 47 of 92 (51%) meta-analyses of subjective outcomes (meta-analysis of all trials showing larger outcomes in 40/47) and in 28 of 71 (39%) meta-analyses of objective outcomes (meta-analysis of all trials showing larger outcomes in 21/28). The combined ROR for subjective and objective outcomes was, respectively, 1.08 (95% CI, 1.04-1.13) and 1.03 (95% CI, 1.00-1.06) when comparing meta-analysis of all trials and meta-analysis of the 25% largest trials, 1.17 (95% CI, 1.11-1.22) and 1.13 (95% CI, 0.82-1.55) when comparing meta-analysis of all trials and limit meta-analysis, and 0.94 (95% CI, 0.86-1.04) and 1.03 (95% CI, 1.00-1.06) when comparing meta-analysis of all trials and meta-analysis restricted to trials at low risk of bias. Estimation of treatment outcomes in meta-analyses differs depending on the strategy used. This instability in findings can result in major alterations in the conclusions derived from the analysis and underlines the need for systematic sensitivity analyses.


A Dual Electrochemical Sensor Based on a Test-strip Assay for the Quantitative Determination of Albumin and Creatinine.
A dual-electrochemical sensor based on a test-strip assay with immunochemistry and enzyme reactions has been developed for the determination of albumin and creatinine. Each nitrocellulose membrane with an immobilization area of an anti-albumin antibody or three enzymes was prepared in the device with three working electrodes for measuring albumin, creatinine, and ascorbic acid, as well as an Ag/AgCl electrode used as a counter/pseudo-reference electrode. The reactions of three enzymes were initiated by flowing a solution containing creatinine to detect an oxidation current of hydrogen peroxide. A sandwich-type immunocomplex was formed by albumin and antibody labeled with glucose oxidase (GOx). Captured GOx catalyzed the reduction of Fe(CN)6(3-) to Fe(CN)6(4-), which was oxidized electrochemically to determine the captured albumin. The responses for creatinine and albumin increased with the concentrations in millimolar order and over the range 18.75 - 150 μg mL(-1), respectively. The present sensor would be a distinct demonstration for producing quantitative dual-assays for various biomolecules used for clinical diagnoses.


Titanium and Other Metal Hypersensitivity Diagnosed by MELISA® Test: Follow-Up Study.
This study is aimed at proving the clinical benefit of the MELISA® test in the minimization or complete elimination of health problems in patients with confirmed hypersensitivity to metals used for tissue replacements. A group of 305 patients aged 20-75 years with previously proven metal hypersensitivity (initial MELISA® test), mainly to titanium and then to another fifteen metals, was chosen from the database at the Institute of Dental Medicine. From these patients, a final group of 42 patients agreed to participate in the study, 35 of which were female and 7 were male. The patients completed a special questionnaire aimed at information regarding change of health status from their last visit and determining whether the results of the initial MELISA® test and recommendations based on it were beneficial for patients or not. They were clinically examined, and peripheral blood samples were taken to perform follow-up MELISA® tests. Questionnaire data was processed, and the follow-up MELISA® test results were compared with the results of the initial MELISA® tests. For statistical analysis, the Fisher's exact test and paired T-test were used. Thirty-two patients reported that they followed the recommendations based on the results of the initial MELISA® tests, and of these, 30 patients (94%) confirmed significant health improvement. Six patients did not follow the recommendation, and from these, only one patient reported an improvement in his health problems. By comparison of the initial and follow-up MELISA® test results, it can be stated that the hypersensitivity to the given metal decreased or disappeared after the therapeutic interventions performed based on the initial MELISA® test results. The evaluation of the data obtained from patients in this study confirmed a significant clinical benefit of MELISA® test.