Failure of a feeding jejunostomy.
A healthy 16-year-old female pedestrian was hit by a motor vehicle. She sustained multiple injuries including severe head injury. She was admitted to hospital unconscious. There was no recovery of neurological function. After a short period of time, a jejunostomy was performed for feeding purposes. The major clinical problem continued to be a feeding difficulty, with profuse diarrhoea occurring. At no stage was it possible to adequately nourish her. Hyperperistalsis was noted whilst in hospital. She died just over three months after admission. Autopsy revealed an emaciated body weighing only 25kg. An upper jejunostomy was still present containing a No. 20 French catheter. The bulb had threaded down the small bowel so that it was situated 25cm proximal to the ileocaecal valve. The small bowel was empty. The cause of death was given as malnutrition due to failure of function of a feeding jejunostomy due to small bowel hyperperistalsis in an individual with diffuse brain trauma. This complication of feeding jejunostomy causing death from malnutrition has not previously been described in the English literature.


Fragile X syndrome detection in newborns-pilot study.
Fragile X syndrome is the most common form of hereditary intellectual disability. Detection of the fragile X phenotype in the prepubertal period is very difficult, and early detection might assist in early developmental intervention and reproductive counseling. A pilot study was conducted to establish the feasibility of newborn screening for fragile X syndrome. A prospective study was done contacting mothers postdelivery in two hospitals in upstate South Carolina from 2005 to 2006. With their permission, blood samples were obtained from the male infants via heelstick and analyzed. A total of 1,459 newborns were tested, and 5 abnormal results were obtained. The results included one sex chromosome aneuploidy (47, XXY), two premutations, and two full mutations. Our study establishes the potential feasibility of such a screening process. However, more complete studies assessing a larger population and risk-benefit analyses are necessary before any universal application of this test. Our detection rate for fragile X syndrome (1:730) was inexplicably greater than anticipated but likely represents a chance occurrence among the small number of infants tested.


Angiotensinogen gene is expressed and differentially regulated in multiple tissues of the rat.
To define the role of local synthesis of angiotensinogen in tissue angiotensin production, we have quantitated angiotensinogen messenger RNA (mRNA) levels in 17 different tissues of four groups of rats: control rats, nephrectomized rats, rats given dexamethasone, ethynylestradiol, and triiodothyronine, and nephrectomized rats given dexamethasone, ethynylestradiol, and triiodothyronine. Angiotensinogen mRNA was identified in 12 tissues: liver, kidney, brain, spinal cord, aorta, mesentery, atria, lung, adrenal, large intestine, stomach, and spleen. Angiotensinogen mRNA was not identified in pituitary, ventricle, testis, small intestine, or pancreas. When expressed per gram tissue wet weight, angiotensinogen mRNA levels of extrahepatic tissues were less than 4% of hepatic levels. However, when expressed per milligram total RNA, angiotensinogen mRNA levels of brain, spinal cord, aorta, and mesentery were 26-42% of hepatic levels. Regulation of angiotensinogen mRNA levels was tissue specific. This demonstration of a widespread tissue distribution of angiotensinogen mRNA may indicate a similarly widespread distribution of local angiotensin systems that are independent of the circulating renin-angiotensin system.


Utility of lytic bacteriophage in the treatment of multidrug-resistant Pseudomonas aeruginosa septicemia in mice.
Drug resistance is the major cause of increase in morbidity and mortality in neonates. One thousand six hundred forty-seven suspected septicemic neonates were subjected for microbiological analysis over a period of 5 years. Forty-two P. aeruginosa were isolated and the antibiogram revealed that 28 P. aeruginosa were resistant to almost all the common drugs used (multidrug-resistant). The emergence of antibiotic-resistant bacterial strains is one of the most critical problems of modern medicine. As a result, a novel and most effective approaches for treating infection caused by multidrug-resistant bacteria are urgently required. In this context, one intriguing approach is to use bacteriophages (viruses that kill bacteria) in the treatment of infection caused by drug-resistant bacteria. In the present study, the utility of lytic bacteriophages to rescue septicemic mice with multidrug-resistant (MDR) P. aeruginosa infection was evaluated. MDR P. aeruginosa was used to induce septicemia in mice by intraperitoneal (i.p.) injection of 10(7) CFU. The resulting bacteremia was fatal within 48 hrs. The phage strain used in this study had lytic activity against a wide range of clinical isolates of MDR P. aeruginosa. A single i.p. injection of 3 x 10(9) PFU of the phage strain, administered 45 min after the bacterial challenge, was sufficient to rescue 100% of the animals. Even when treatment was delayed to the point where all animals were moribund, approximately 50% of them were rescued by a single injection of this phage preparation. The ability of this phage to rescue septicemic mice was demonstrated to be due to the functional capabilities of the phage and not to a nonspecific immune effect. The rescue of septicemic mice could be affected only by phage strains able to grow in vitro on the bacterial host used to infect the animals and when such strains are heat-inactivated, they lose their ability to rescue the infected mice. Multidrug-resistant bacteria have opened a second window for phage therapy. It would seem timely to begin to look afresh at this approach. A scientific methodology can make phage therapy as a stand-alone therapy for infections that are fully resistant to antibiotics.


Tissue expression and immunolocalization of tumor necrosis factor-alpha in postinfarction dysfunctional myocardium.
Tumor necrosis factor-alpha (TNF-alpha) is markedly elevated in advanced heart failure. It is not known whether tissue TNF-alpha is elevated in the common setting of myocardial infarction leading to heart failure and what the source of TNF-alpha is. To determine this, we studied the expression and protein localization of TNF-alpha and its 2 main receptors (TNF-R1/R2) in a rat model of large infarction. Male rats were randomized to proximal left anterior descending ligation. The animals were killed on days 1, 3, 10, and 35 after ligation to examine gene expression and protein production of TNF-alpha and TNF-R1/R2 from the infarct, peri-infarct, and contralateral zones of infarcted heart. There was increased TNF-alpha mRNA production throughout the myocardium at day 1, and detectable expression persisted to day 35 after myocardial infarction. The expression of this cytokine is not confined strictly to the infarct or peri-infarct zones but is expressed by cardiac myocytes within the myocardium in the contralateral normal zone. Changes in gene expression are mirrored initially by augmented protein production within the myocytes. Levels of TNF-alpha protein in the infarct and peri-infarct zones rose early to 8- to 10-fold above normal levels and rose to 4- to 5-fold in the contralateral zone. Finally, expression of the TNF-R1 mRNA transcripts was upregulated at days 3 and 10 after ligation in the infarct and peri-infarct zones, suggesting that the signal transduction pathways necessary for TNF-alpha in the heart remain intact as TNF-alpha biosynthesis increases. TNF-alpha is present early in a model of large myocardial infarction and is sustained into the later stage within the myocardium. Expression of this cytokine is not only confined strictly to the infarct or peri-infarct zone but is expressed by cardiac myocytes within the myocardium contralateral to the infarct. Therefore TNF-alpha production forms a part of an important intrinsic myocardial stress response system to injury.


Chemical characterization of surface snow in Istanbul (NW Turkey) and their association with atmospheric circulations.
The understanding of the impurities in natural snow is important in realizing its atmospheric quality, soil characteristics, and the pollution caused to the environment. Knowledge of the occurrence of major ions and trace metals in the snow in the megacity of Istanbul is very limited. This manuscript attempts to understand the origin of major soluble ions (fluoride, acetate, formate, chlorite, chloride, nitrite, chlorate, bromide, nitrate, sulfate, phosphate, and perchlorate) and some trace metals (Fe, Mn, Cd, Co, Ni, Pb, Zn, Cu) in winter surface snow, collected in Istanbul, Turkey. The sampling of the surface snow was conducted after each precipitation during the winter of 2015-2016 at three sites in the city. Besides the statistical evaluation of the major ions, and some trace metal concentrations, the chemical variations along with atmospheric circulations, which are important modification mechanisms that influence the concentrations, were investigated in the study. At examined locations and times, 12 major anions were investigated and in these anions fluoride, chlorite, chlorate, bromide, and perchlorate in the snow samples were below the detection limit; only SO42-, NO3-, and CI- were found to be in the range of 1.11-17.90, 0.75-4.52, and 0.19-3.01 mg/L. Also, according to the trace element determination, the concentration was found to be 29.2-53.7, 2.0-16.1, 1.0-2.2, 50.1-71.1, 24.2-35.2, ND-7.9, 43.2-106.6, and 3.0-17.7 μg/L for Fe, Mn, Cd, Co, Ni, Pb, Zn, and Cu, respectively. The major anions and investigated trace elements here originated mainly from anthropogenic and atmospheric circulation and mainly influenced by northerly and southerly circulation patterns. While the main limitations in the present study may be the low number of samples that may not be entirely representative, accurately reflect identification, or support other previously observed local measurements, we believe that the type of data presented in this study has the potential to be used in the field of environmental risk assessment and, as result, for human health.


Dissolved trace element biogeochemistry of a tropical river, Southwestern India.
River Swarna, a small tropical river originating in Western Ghats (at an altitude of 1,160 m above mean sea level) and flowing in the southwest coast of India discharges an average of 54 m(3)s(-1) of water into the Arabian Sea, of which significant part is being discharged during the monsoon. No studies have been made yet on the water chemistry of the Swarna River basin, even as half a million people of Udupi district use it for domestic and irrigational purposes. As large community in this region depends on the freshwater of Swarna River, there is an urgent need to study the trace element geochemistry of this west flowing river for better water management and sustainable development. The paper presents the results on the biogeochemistry of dissolved trace elements in the Swarna River for a period of 1 year. The results obtained on the trace elements show seasonal effect on the concentrations as well as behavior and thus forming two groups, discharge driven (Li, Be, Al, V, Cr, Ni, Zr, In, Pb, Bi and U) and base flow driven (groundwater input; Mn, Fe, Co, Cu, Ga, Zn, As, Se, Rb, Sr, Ag, Cd, Cs, Ba and Tl) trace elements in Swarna River. The biogeochemical processes explained through Hierarchical Cluster Analysis show complexation of Fe, Ga and Ba with dissolved organic carbon, redox control over Mn and Tl and biological control over V and Ni. Also, the water quality of Swarna River remains within the permissible limits of drinking water standards.


Perlecan: an important component of the cartilage pericellular matrix.
Perlecan (Pln) is a large proteoglycan that can bear HS (heparan sulfate) and chondroitin sulfate glycosaminoglycans. Previous studies have demonstrated that Pln can interact with growth factors and cell surfaces either via its constituent glycosaminoglycan chains or core protein. Herein, we summarize studies demonstrating spatially and temporally regulated expression of Pln mRNA and protein in developing and mature cartilage. Mutations either in the Pln gene or in genes involved in glycosaminoglycan assembly result in severe cartilage phenotypes seen in both human syndromes and mouse model systems. In vitro studies demonstrate that Pln can trigger chondrogenic differentiation of multipotential mouse CH310T1/2 stem cells as well as maintain the phenotype of adult human chondrocytes. Structural mapping indicates that these activities lie entirely within domain I, a region unique to Pln, and that they require glycosaminoglycans. We also discuss data indicating that Pln cooperates with the key chondrogenic growth factor, BMP-2, to promote expression of hypertrophic chondrocyte markers. Collectively, these studies indicate that Pln is an important component of human cartilage and may have useful applications in tissue engineering and cartilage-directed therapeutics.


Evaluation of Pacing Parameters to Induce Contractions in the Small Intestine.
Postoperative ileus and chronic intestinal pseudo-obstruction are intestinal motility disorders that can compromise bowel function resulting in a significant reduction in quality of life and prolonged hospital stays. While medication and nutritional support provides relief for some patients, a significant patient population remains untreated. Therefore, alternative treatment options are required. A novel framework that enables small intestine pacing and video mapping of the contractile response was developed. Pacing pulse parameters (pulse-period: 2.7, 10 s, pulse-width: 100, 400 ms, and pulse-amplitude: 4, 6, 8 mA) were systematically varied to investigate the effect of pacing on the small intestine contractility. The contractile response was quantified by computing the strain of the intestinal diameter at the pacing site. The framework was applied in vivo on porcine jejunal loops (n=4) where segmental contractions were induced in response to pacing pulses. Strain increased with increasing pulse-amplitude and pulse-width, while pacing at a period of 2.7 s elicited higher contractile strains compared to pacing at a period of 10 s at all settings (e.g., -0.18 ± 0.06 vs 0.12 ± 0.06 at 8 mA, 400 ms). For a pulse-width of 100 ms, the contractile strain continued to increase with increasing pulse-amplitude, while the induced strain was comparable for all pulse-amplitudes when paced with high pulse-width (400 ms). Therefore, pacing is an effective tool in modulating the intensity of segmental contractions.Clinical Relevance- Different pacing parameters can define contraction intensity and frequency in the small intestine. This is of therapeutic potential for treating motility disorders such as post-operative ileus and chronic intestinal pseudo-obstruction.


The creation and validation of predictive models to assess the risk of unfavorable outcomes following hybrid total arch repair for Stanford type A aortic dissection.
The objective of this study was to develop and validate a nomogram for the individualized prediction of adverse events in patients with Stanford type A aortic dissection (TAAD) undergoing hybrid total aortic arch repair. From April 2019 to April 2022, we conducted a comprehensive review of the medical records of Stanford type A aortic dissection patients who underwent hybrid total aortic arch repair surgery at our hospital. Patients were separated into two groups based on whether or not a composite adverse event occurred following surgery. Using univariate and multivariate analyses of logistic regression, the prediction model was created. Construct risk prediction models utilizing nomograms and evaluate their precision, discrimination, and clinical utility. Age, platelets, serum blood urea nitrogen, and ascending aortic diameter were the variables included in the nomogram by univariate and multivariate analysis. The risk model performed well in internal validation, with an area under the curve (AUC) of 0.829. The calibration curve demonstrated good agreement between predicted and actual probabilities (Hosmer-Lemeshow test, P = 0.22). Clinical decision analysis curves demonstrate predictive nomograms' clinical utility. This study created and validated a nomogram for predicting the risk of composite endpoint events in TAAD patients undergoing hybrid total aortic arch repair. The nomogram can help determine the severity of a patient's condition and provide a more personalized diagnosis and treatment.


Estimating cross-population genetic correlations of causal effect sizes.
Recent studies have examined the genetic correlations of single-nucleotide polymorphism (SNP) effect sizes across pairs of populations to better understand the genetic architectures of complex traits. These studies have estimated ρ g , the cross-population correlation of joint-fit effect sizes at genotyped SNPs. However, the value of ρ g depends both on the cross-population correlation of true causal effect sizes ( ρ b ) and on the similarity in linkage disequilibrium (LD) patterns in the two populations, which drive tagging effects. Here, we derive the value of the ratio ρ g / ρ b as a function of LD in each population. By applying existing methods to obtain estimates of ρ g , we can use this ratio to estimate ρ b . Our estimates of ρ b were equal to 0.55 ( SE = 0.14) between Europeans and East Asians averaged across nine traits in the Genetic Epidemiology Research on Adult Health and Aging data set, 0.54 ( SE = 0.18) between Europeans and South Asians averaged across 13 traits in the UK Biobank data set, and 0.48 ( SE = 0.06) and 0.65 ( SE = 0.09) between Europeans and East Asians in summary statistic data sets for type 2 diabetes and rheumatoid arthritis, respectively. These results implicate substantially different causal genetic architectures across continental populations.


Association of the kinesin superfamily motor protein KIF1Balpha with postsynaptic density-95 (PSD-95), synapse-associated protein-97, and synaptic scaffolding molecule PSD-95/discs large/zona occludens-1 proteins.
Mutation in KIF1B, a kinesin superfamily motor protein, causes a peripheral neuropathy known as Charcot-Marie-Tooth disease type 2A (CMT2A). Little is known, however, about how a defective KIF1B gene leads to CMT2A. Here we report that KIF1Balpha, one of the two splice variants of KIF1B, directly interacts through its C-terminal postsynaptic density-95 (PSD-95)/discs large/zona occludens (PDZ) domain-binding motif with PDZ proteins including PSD-95/synapse-associated protein-90 (SAP90), SAP97, and synaptic scaffolding molecule (S-SCAM)-90 (SAP90). KIF1Balpha selectively interacts with PSD-95, SAP97, and S-SCAM in yeast two-hybrid, pull-down, and in vivo coimmunoprecipitation experiments. KIF1Balpha, SAP97, and S-SCAM are widely distributed to both dendrites and axons of cultured neurons and are enriched in the small membrane fraction of the brain. In the flotation assay, KIF1Balpha cofractionates and coimmunoprecipitates with PSD-95, SAP97, and S-SCAM. These results suggest that the PSD-95 family proteins and S-SCAM have a novel function as KIF1Balpha receptors, linking KIF1Balpha to its specific cargos, and are involved in peripheral neuropathies.


Highly diverse and seasonally dynamic protist community in a pristine peat bog.
Culture-independent molecular methods based on the amplification, cloning and sequencing of small-subunit ribosomal RNA genes (SSU rDNAs) are powerful tools to study the diversity of microorganisms. Despite so, the eukaryotic microbial diversity of many ecosystems, including peatlands has not yet received much attention. We analysed the eukaryotic diversity by molecular surveys in water from the centre of a pristineSphagnum-dominated peatland in the Jura Mountains of Switzerland during a complete seasonal cycle. The clone libraries constructed from five different temporal samplings revealed a high diversity of protists with representatives of all major eukaryotic phyla. In addition, four sequence types could not be assigned to any known high-level eukaryotic taxon but branched together with a rather good statistic support, raising the possibility of a novel, deep branching eukaryotic clade. The analysis of seasonal patterns of phylotypes showed a clear change in the eukaryotic communities between the warm period (late spring and summer) and the cold period (autumn and winter). Chrysophytes dominated the samples in the cold period while testate amoebae (Arcellinida and Euglyphida) and a few other groups peaked in summer. A few phylotypes (such as a cryptomonad and a perkinsid) were abundant at given sampling times and then almost disappeared, suggesting bloom-like dynamics.


The interface between obesity and periodontitis with emphasis on oxidative stress and inflammatory response.
Obesity is characterized by the abnormal or excessive deposition of fat in the adipose tissue. Its consequences go far beyond adverse metabolic effects on health, causing an increase in oxidative stress that leads not only to endothelial dysfunction but also to negative effects in relation to periodontitis, because of the increase in proinflammatory cytokines. Thus, obesity appears to participate in the multifactorial phenomenon of causality of periodontitis through the increased production of reactive oxygen species. Within this context, this paper aims to highlight, by analysis and description of previous studies, the interface between obesity and periodontitis, with emphasis on oxidative stress and the inflammatory response.


Periprosthetic fractures around loose femoral components.
The development of periprosthetic fractures around loose femoral components can be a devastating event for patients who have undergone total hip arthroplasty (THA). As indications for THA expand in an aging population and to use in younger patients, these fractures are increasing in incidence. This review covers the epidemiology, risk factors, prevention, and clinical management of periprosthetic femoral fractures. Treatment principles and reconstructive options are discussed, along with outcomes and complications. Femoral revision with a long-stem prosthesis or a modular tapered stem is the mainstay of treatment and has demonstrated good outcomes in the literature. Other reconstruction options are available, depending on bone quality. Surgeons must have a sound understanding of the diagnosis and treatment of periprosthetic femoral fractures.


Biochemical markers in Alzheimer's disease clinical trials.
This article summarizes how biochemical markers may aid in the development of novel treatments that interfere with fundamental pathogenic processes in Alzheimer's disease. Details are given on the potential use of biomarkers in Alzheimer's disease clinical trials as additional inclusion criteria to enrich study populations with participants who really suffer from the disease, as a means to stratify study participants into meaningful subgroups that may benefit differently from the treatment, and as tools to detect desired biochemical effects and undesired side effects of the drug.


Olfactory training in normosmic individuals: a randomised controlled trial.
Even if olfactory training (OT) is a well-established treatment for individuals with olfactory dysfunction, the effect on individuals with normosmia remains uncertain. In this randomised controlled trial, we explore how OT with different exposure lengths affect olfactory function in individuals with normosmia. Two hundred normosmic individuals were randomly assigned to one of two intervention groups performing OT with different exposure lengths or to a control group. The OT groups did OT twice daily for three months, sniffing four different odours (eucalyptus, lavender, mint, and lemon) for 10 seconds per bottle during either a total of 40 seconds (standard OT) or 4 minutes (extended OT), while the control group did not perform any OT. Olfactory function was assessed using a 48-item Sniffin Sticks test at baseline, after the intervention, and after one year. We found no significant effect of OT in either of the intervention groups on any aspect of olfaction after intervention or at follow-up. There was no association between sex, age, allergic rhinitis, education or olfactory scores at baseline, and changes in olfactory function after OT. The extended OT group performed significantly fewer training sessions compared to those in the standard OT group. OT had a limited effect on olfactory function in individuals with normosmia. Further, the superiority of a more extended OT is not supported by this study, and shorter training sessions seem to improve compliance with OT.


Playground Safety is Associated With Playground, Park, and Neighborhood Characteristics.
More than 200,000 children each year are treated at emergency departments for injuries occurring on playgrounds. Empirically derived data are needed to elucidate factors associated with playground safety and reduce injury rates. Determine if neighborhood, park and playground characteristics are significantly associated with playground safety. A 24-item report card developed by the National Program for Playground Safety was used to assess playground safety at 41 public parks in a small to midsized, Midwestern city. Trained assessors evaluated the parks and playgrounds in June/July and used a standardized method to count the numbers of users. Data from the 2010 U.S. Census were used to describe the neighborhoods surrounding the parks. The average safety score for all playgrounds was 77.4% which denotes acceptable safety levels. However, 17.1% of the playgrounds were potentially hazardous and in need of corrective measures. Playgrounds were safer in neighborhoods with more youth (< 18 years of age) and educated adults and in parks with better quality features. Playgrounds with fewer amenities were relatively less safe. Park safety levels need to be improved to reduce the risk of physical injuries. Future studies examining cause-effect associations between environmental features and playground safety are warranted.


Fog catchment sand trenches constructed by tenebrionid beetles, lepidochora, from the namib desert.
Three species of coastal Namib Desert tenebrionid beetles (Lepidochora) build trenches on desert sand dunes. Trenches are constructed perpendicular to fog winds and concentrate moisture during fogs. The beetles return along the ridges of the trenches extracting water from them. The water content of a population of these beetles increased by 13.9 percent during one fog.


Multiple-input single-output closed-loop isometric force control using asynchronous intrafascicular multi-electrode stimulation.
Although asynchronous intrafascicular multi-electrode stimulation (IFMS) can evoke fatigue-resistant muscle force, a priori determination of the necessary stimulation parameters for precise force production is not possible. This paper presents a proportionally-modulated, multiple-input single-output (MISO) controller that was designed and experimentally validated for real-time, closed-loop force-feedback control of asynchronous IFMS. Experiments were conducted on anesthetized felines with a Utah Slanted Electrode Array implanted in the sciatic nerve, either acutely or chronically ( n = 1 for each). Isometric forces were evoked in plantar-flexor muscles, and target forces consisted of up to 7 min of step, sinusoidal, and more complex time-varying trajectories. The controller was successful in evoking steps in force with time-to-peak of less than 0.45 s, steady-state ripple of less than 7% of the mean steady-state force, and near-zero steady-state error even in the presence of muscle fatigue, but with transient overshoot of near 20%. The controller was also successful in evoking target sinusoidal and complex time-varying force trajectories with amplitude error of less than 0.5 N and time delay of approximately 300 ms. This MISO control strategy can potentially be used to develop closed-loop asynchronous IFMS controllers for a wide variety of multi-electrode stimulation applications to restore lost motor function.


A thrombin-sensitive protein of human platelet membranes.
The action of thrombin on intact human platelets has been studied with the aid of polyacrylamide gel electrophoresis in sodium dodecylsulfate. A single major membrane protein band with a molecular weight of 190,000 disappears after thrombin treatment, while a new membrane protein with a molecular weight of 107,000 appears. This may represent hydrolysis of the thrombin-sensitive protein. When platelets are disrupted or when the thrombin-sensitive protein is solubilized from membranes prior to thrombin treatment, no hydrolysis occurs. The effect of thrombin on the platelet membrane protein is complete within 2 min which suggests that hydrolysis of this membrane protein may trigger the physiological effects of thrombin on platelets.


High performance micro-flow cytometer based on optical fibres.
Flow cytometry is currently the gold standard for analysis of cells in the medical laboratory and biomedical research. Fuelled by the need of point-of-care diagnosis, a significant effort has been made to miniaturize and reduce cost of flow cytometers. However, despite recent advances, current microsystems remain less versatile and much slower than their large-scale counterparts. In this work, an all-silica fibre microflow cytometer is presented that measures fluorescence and scattering from particles and cells. It integrates cell transport in circular capillaries and light delivery by optical fibres. Single-stream cell focusing is performed by Elasto-inertial microfluidics to guarantee accurate and sensitive detection. The capability of this technique is extended to high flow rates (up to 800 µl/min), enabling a throughput of 2500 particles/s. The robust, portable and low-cost system described here could be the basis for a point-of-care flow cytometer with a performance comparable to commercial systems.


Does Male Circumcision Protect against Sexually Transmitted Infections? Arguments and Meta-Analyses to the Contrary Fail to Withstand Scrutiny.
We critically evaluate a recent article by Van Howe involving 12 meta-analyses that concludes, contrary to current evidence, that male circumcision increases the risk of various common sexually transmitted infections (STIs). Our detailed scrutiny reveals that these meta-analyses (1) failed to include results of all relevant studies, especially data from randomized controlled trials, (2) introduced bias through use of inappropriate control groups, (3) altered original data, in the case of human papillomavirus (HPV), by questionable adjustments for "sampling bias," (4) failed to control for confounders through use of crude odds ratios, and (5) used unnecessarily complicated methods without adequate explanation, so impeding replication by others. Interventions that can reduce the prevalence of STIs are important to international health. Of major concern is the global epidemic of oncogenic types of HPV that contribute to the burden of genital cancers. Meta-analyses, when well conducted, can better inform public health policy and medical practice, but when seriously flawed can have detrimental consequences. Our critical evaluation leads us to reject the findings and conclusions of Van Howe on multiple grounds. Our timely analysis thus reaffirms the medical evidence supporting male circumcision as a desirable intervention for STI prevention.


Granulomatous syringotropic mycosis fungoides with two lesions having reactive B-cell proliferation.
Mycosis fungoides (MF) represents the most common type of cutaneous lymphoma. The diagnosis of MF may occasionally be challenging, particularly for variants of MF such as folliculotropic MF, syringotropic MF and granulomatous MF. Herein, we describe a case of MF in which syringotropism and a prominent granulomatous reaction were noted around the affected eccrine gland. This case represents a rare example of MF with multiple unusual histopathological features, including syringotropism, a granulomatous reaction and a reactive B-cell proliferation.


6DMAP inhibition of early cell cycle events and induction of mitotic abnormalities.
N-6 dimethylaminopurine (6DMAP) has been shown to induce aberrant mitosis in different cell types including Chinese hamster fibroblasts (CHEF/18). The mechanism of action and the cellular targets, however, are still not clear. We showed previously that in CHEF/18 cells this compound inhibits DNA synthesis with a kinetic of inhibition suggestive of an effect on early events of the cell cycle. In this paper we investigated which cellular targets were affected by 6DMAP and found that: (i) the compound inhibits phosphorylation of ribosomal protein S6 and activation of the 70 kDa S6 kinase (p70S6k) known to be activated by epidermal growth factor (EGF) in keeping with the notion that it is a protein kinase inhibitor; however the inhibition in vivo appears to be specific as MAP kinase phosphorylation is not inhibited; (ii) 6DMAP drastically affects cytoskeletal components leading to a rapid morphological change in most cells. These data, together with the findings that the dose range and the treatment time effective in inducing the micronuclei containing chromosomes were the same as for DNA synthesis inhibition, suggest that a disturbance in G1 of signal transduction pathways may contribute to abnormal mitosis.


Reducing the Global Burden of Myopia by Delaying the Onset of Myopia and Reducing Myopic Progression in Children: The Academy's Task Force on Myopia.
In 2019, the American Academy of Ophthalmology (AAO) created the Task Force on Myopia in recognition of the substantial global increases in myopia prevalence and its associated complications. The Task Force, led by Richard L. Abbott, MD, and Donald Tan, MD, comprised recognized experts in myopia prevention and treatment, public health experts from around the world, and organization representatives from the American Academy of Family Physicians, American Academy of Optometry, and American Academy of Pediatrics. The Academy's Board of Trustees believes that myopia is a high-priority cause of visual impairment, warranting a timely evaluation and synthesis of the scientific literature and formulation of an action plan to address the issue from different perspectives. This includes education of physicians and other health care providers, patients and their families, schools, and local and national public health agencies; defining health policies to ameliorate patients' access to appropriate therapy and to promote effective public health interventions; and fostering promising avenues of research.


3-[(dodecylthiocarbonyl)methyl]-glutarimide attenuates graft arterial disease by suppressing alloimmune responses and vascular smooth muscle cell proliferation.
Graft arterial disease (GAD) is a major cause of late graft loss after organ transplantation. Alloimmune responses and vascular remodeling eventually cause the transplant organ to develop GAD. In this study, we aimed to limit the development of GAD by inhibiting alloimmune responses and vascular smooth muscle cell (VSMC) proliferation with a new compound, 3-[(dodecylthiocarbonyl)methyl]-glutarimide ([DTCM]-glutarimide), in a murine cardiac model of GAD. The hearts from B6.CH-2 mice were transplanted into C57BL/6 mouse recipients to examine the extent of GAD. The recipients were treated with either vehicle or DTCM-glutarimide intraperitoneally (40 mg/kg per day) for 4 weeks. The administration of DTCM-glutarimide attenuated GAD formation (luminal occlusion: 37.9 ± 5.9% vs 14.8 ± 5.4%, P < 0.05) by inhibiting the number of graft-infiltrating cells and decreasing alloreactive interferon (IFN)-γ production compared with control mice, as measured by the Enzyme-linked ImmunoSpot assay. In vitro, VSMCs proliferated on stimulation with either basic fibroblast growth factor or IFN-γ and splenocytes after transplantation, but the addition of DTCM-glutarimide resulted in the inhibition of VSMC proliferation. Moreover, DTCM-glutarimide suppressed cyclin D1 expression and inhibited cell cycle progression from G1 to S in VSMCs. The compound DTCM-glutarimide suppressed GAD development by inhibiting not only alloimmune responses but also VSMC proliferation in the graft.


Pediatric mild head trauma: is outpatient follow-up imaging necessary or beneficial?
Pediatric traumatic brain injury (TBI) is the leading cause of death among children and is a significant cause of morbidity. However, the majority of injuries are mild (Glasgow Coma Scale score 13-15) without any need for neurosurgical intervention, and clinically significant neurological decline rarely occurs. Although the question of repeat imaging within the first 24 hours has been discussed in the past, the yield of short-term follow-up imaging has never been thoroughly described. In this paper, the authors focus on the yield of routine repeat imaging for pediatric mild TBI (mTBI) at the first clinic visit following hospital discharge. The authors conducted a retrospective review of patients with pediatric brain trauma who had been admitted to Johns Hopkins All Children's Hospital (JHACH). Patients with mTBI were identified, and their presentation, hospital course, and imaging results were reviewed. Those pediatric patients with mTBI who had undergone no procedure during their initial admission (only conservative treatment) were eligible for inclusion in the study. Two distinct groups were identified: patients who underwent repeated imaging at their follow-up clinic visit and those who underwent only clinical evaluation. Each case was assessed on whether the follow-up imaging had changed the follow-up course. Between 2010 and 2015, 725 patients with TBI were admitted to JHACH. Of those, 548 patients qualified for analysis (i.e., those with mTBI who received conservative treatment without any procedure and were seen in the clinic for follow-up evaluation within 8 weeks after the trauma). A total of 392 patients had only clinic follow-up, without any diagnostic imaging study conducted as part of their clinic visit, whereas the other 156 patients underwent repeat MRI. Only 1 patient had a symptomatic change and was admitted after undergoing imaging. For 30 patients (19.2%), it was decided after imaging to continue the neurosurgical follow-up, which is a change from the institutional paradigm after mTBI. None of these patients had a change in neurological status, and all had a good functional status. All of these patients had one more follow-up in the clinic with new MRI, and none of them required further follow-up. Children with mTBI are commonly followed up in the ambulatory clinic setting. The authors believe that for children with mTBI, normal clinical examination, and no new symptoms, there is no need for routine ambulatory imaging since the clinical yield of such is relatively low.


Variability of nutritional practices in peritransplant period after allogeneic hematopoietic stem cell transplantation: a survey by the Complications and Quality of Life Working Party of the EBMT.
Recommendations on screening and nutritional support for patients undergoing hematopoietic stem cell transplantation (HSCT) have been presented by international nutritional societies, but nutritional practices remain poorly standardized. Following the general policy of the European Society for Blood and Marrow Transplantation (EBMT) to standardize transplantation procedures, the Complications and Quality of Life Working Party and Nursing Research Group carried out a survey among all EBMT centers about their current nutritional practices. The aim of this study was to better understand current practices, differences from available guidelines, and possible barriers for recommended nutritional therapy. Responses from 90 centers (19%) from 23 countries were received. We observed a marked variability in nutritional care between EBMT centers and a substantial lack of standardized operating procedures in screening patients for malnutrition and management of gastrointestinal GVHD. Furthermore, our study confirmed neutropenic diet as standard of care in most centers as well a preference for parenteral nutritional support over enteral. On the basis of these findings, future EBMT efforts will focus on better implementation of international nutritional guidelines into clinical practice.


Targeting human glioblastoma cells: comparison of nine viruses with oncolytic potential.
Brain tumors classified as glioblastomas have proven refractory to treatment and generally result in death within a year of diagnosis. We used seven in vitro tests and one in vivo trial to compare the efficacy of nine different viruses for targeting human glioblastoma. Green fluorescent protein (GFP)-expressing vesicular stomatitis (VSV), Sindbis virus, pseudorabies virus (PRV), adeno-associated virus (AAV), and minute virus of mice i-strain (MVMi) and MVMp all infected glioblastoma cells. Mouse and human cytomegalovirus, and simian virus 40 showed only low levels of infection or GFP expression. VSV and Sindbis virus showed strong cytolytic actions and high rates of replication and spread, leading to an elimination of glioblastoma. PRV and both MVM strains generated more modest lytic effects and replication capacity. VSV showed a similar oncolytic profile on U-87 MG and M059J glioblastoma. In contrast, Sindbis virus showed strong preference for U-87 MG, whereas MVMi and MVMp preferred M059J. Sindbis virus and both MVM strains showed highly tumor-selective actions in glioblastoma plus fibroblast coculture. VSV and Sindbis virus were serially passaged on glioblastoma cells; we isolated a variant, VSV-rp30, that had increased selectivity and lytic capacity in glioblastoma cells. VSV and Sindbis virus were very effective at replicating, spreading within, and selectively killing human glioblastoma in an in vivo mouse model, whereas PRV and AAV remained at the injection site with minimal spread. Together, these data suggest that four (VSV, Sindbis virus, MVMi, and MVMp) of the nine viruses studied merit further analysis for potential therapeutic actions on glioblastoma.


Spatial attention improves the quality of population codes in human visual cortex.
Selective attention enables sensory input from behaviorally relevant stimuli to be processed in greater detail, so that these stimuli can more accurately influence thoughts, actions, and future goals. Attention has been shown to modulate the spiking activity of single feature-selective neurons that encode basic stimulus properties (color, orientation, etc.). However, the combined output from many such neurons is required to form stable representations of relevant objects and little empirical work has formally investigated the relationship between attentional modulations on population responses and improvements in encoding precision. Here, we used functional MRI and voxel-based feature tuning functions to show that spatial attention induces a multiplicative scaling in orientation-selective population response profiles in early visual cortex. In turn, this multiplicative scaling correlates with an improvement in encoding precision, as evidenced by a concurrent increase in the mutual information between population responses and the orientation of attended stimuli. These data therefore demonstrate how multiplicative scaling of neural responses provides at least one mechanism by which spatial attention may improve the encoding precision of population codes. Increased encoding precision in early visual areas may then enhance the speed and accuracy of perceptual decisions computed by higher-order neural mechanisms.


Real time self-rating of decision certainty by clinicians: a systematic review.
BackgroundWe sought to establish to what extent decision certainty has been measured in real time and whether high or low levels of certainty correlate with clinical outcomes.MethodsOur pre-specified study protocol is published on PROSPERO, CRD42019128112. We identified prospective studies from Medline, Embase and PsycINFO up to February 2019 that measured real time self-rating of the certainty of a medical decision by a clinician.FindingsNine studies were included and all were generally at high risk of bias. Only one study assessed long-term clinical outcomes: patients rated with high diagnostic uncertainty for heart failure had longer length of stay, increased mortality and higher readmission rates at 1 year than those rated with diagnostic certainty. One other study demonstrated the danger of extreme diagnostic confidence - 7% of cases (24/341) labelled as having either 0% or 100% diagnostic likelihood of heart failure were made in error.ConclusionsThe literature on real time self-rated certainty of clinician decisions is sparse and only relates to diagnostic decisions. Further prospective research with a view to generating hypotheses for testable interventions that can better calibrate clinician certainty with accuracy of decision making could be valuable in reducing diagnostic error and improving outcomes.


GRANULOMATOUS FILARIAL ENCEPHALOMYELITIS CAUSED BY CHANDLERELLA QUISCALI IN A NORTHERN CRESTED CARACARA (CARACARA CHERIWAY).
A northern crested caracara (Caracara cheriway) was presented after being found nonambulatory in a field. On physical examination, the bird had severe hind-limb paresis. The bird did not improve after 10 days of hospitalization and was euthanized. Histologic examination of the cerebrum and spinal cord revealed multiple adult filarial nematodes surrounded by granulomatous inflammation with several multinucleated giant cells. These parasites were confirmed to be Chandlerella quiscali with polymerase chain reaction. This is the first report of C. quiscali in a bird of prey.


Recovery from welding-fume-exposure-induced MRI T1 signal intensities after cessation of welding-fume exposure in brains of cynomolgus monkeys.
The shortening of the MRI T1 relaxation time, indicative of a high signal intensity in a T1-weighted MRI, is known as a useful biomarker for Mn exposure after short-term welding-fume exposure. A previous monkey experimental study found that the T1 relaxation times decreased time-dependently after exposure, and a visually detectable high signal intensity appeared after 150 days of exposure. The nadir for the shortening of the T1 relaxation time was also previously found to correspond well with the blood Mn concentration in welders, suggesting a correlation between a prolonged high blood Mn concentration and shortened T1 relaxation time. Accordingly, to clarify the clearance of the brain Mn concentration after the cessation of welding-fume exposure, cynomolgus monkeys were assigned to 3 groups-unexposed, low dose (31 mg/m(3) total suspended particulate (TSP), 0.9 mg Mn/m(3)), and high dose (62 mg/m(3) TSP, 1.95 mg Mn/m(3))-and exposed to manual metal-arc stainless steel (MMA-SS) welding fumes for 2 h per day for 8 mo in an inhalation chamber system equipped with an automatic fume generator. After reaching the peak MRI T1 signal intensity (shortest T1 relaxation time), the monkeys were allowed to recover by ceasing the welding-fume exposure. Within 2 mo, the MRI T1 signal intensities for the exposed monkeys returned to nearly the same level as those for the unexposed monkeys, indicating the potential for recovery from a high MRI T1 signal intensity induced by welding-fume exposure, even after prolonged exposure. Clearance of the Mn tissue concentration was also demonstrated in the globus pallidus, plus other tissues from the brain, liver, spleen, and blood. In contrast, there was no clearance of the lung concentrations of Mn, indicating that a soluble form of Mn was transported to the blood and brain. Therefore, the solubility of Mn in welding fumes would appear to be an important determinant as regards the retention of blood Mn levels and brain tissue Mn concentrations in welders.


Selection for a large genetic duplication in Salmonella typhimurium.
Salmonella typhimurium strains containing a duplication of nearly a third of the genome have been isolated by a simple procedure involving selection for improved utilization of L-malate as sole carbon source. The duplication occurs at a very high spontaneous frequency. Strains containing the duplication can be isolated selectively on malate medium, or by a non-selective procedure involving Hfr conjugation. When strains containing the duplication are maintained on non-selective medium, the duplication is readily lost. Genetic evidence suggests that the duplication is chromosomal and tandem. The fact that the recA gene is included in the duplication has been used to obtain evidence that the recA1 marker is recessive to its wild-type allele. Unlike tandem duplications previously described in I. coli, the duplication described in this report appears to have unique endpoints.


The role of hemocytes in Anopheles gambiae antiplasmodial immunity.
Hemocytes synthesize key components of the mosquito complement-like system, but their role in the activation of antiplasmodial responses has not been established. The effect of activating Toll signaling in hemocytes on Plasmodium survival was investigated by transferring hemocytes or cell-free hemolymph from donor mosquitoes in which the suppressor cactus was silenced. These transfers greatly enhanced antiplasmodial immunity, indicating that hemocytes are active players in the activation of the complement-like system, through an effector/effectors regulated by the Toll pathway. A comparative analysis of hemocyte populations between susceptible G3 and the refractory L3-5 Anopheles gambiae mosquito strains did not reveal significant differences under basal conditions or in response to Plasmodium berghei infection. The response of susceptible mosquitoes to different Plasmodium species revealed similar kinetics following infection with P. berghei,P. yoelii or P. falciparum, but the strength of the priming response was stronger in less compatible mosquito-parasite pairs. The Toll, Imd,STAT or JNK signaling cascades were not essential for the production of the hemocyte differentiation factor (HDF) in response to P. berghei infection, but disruption of Toll, STAT or JNK abolished hemocyte differentiation in response to HDF. We conclude that hemocytes are key mediators of A. gambiae antiplasmodial responses.


Amine-functionalized carbon-fiber microelectrodes for enhanced ATP detection with fast-scan cyclic voltammetry.
Here, we provide evidence that functionalizing the carbon-fiber surface with amines significantly improves direct electrochemical adenosine triphosphate (ATP) detection with fast-scan cyclic voltammetry (FSCV). ATP is an important extracellular signaling molecule throughout the body and can function as a neurotransmitter in the brain. Several methods have been developed over the years to monitor and quantitate ATP signaling in cells and tissues; however, many of them are limited in temporal resolution or are not capable of measuring ATP directly. FSCV at carbon-fiber microelectrodes is a widely used technique to measure neurotransmitters in real-time. Many electrode treatments have been developed to study the interaction of cationic compounds like dopamine at the carbon surface yet studies investigating how to improve anionic compounds, like ATP, at the carbon fiber surface are lacking. In this work, carbon-fibers were treated with N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide (EDC) which reacts with carboxylic acid groups on the carbon surface followed by reaction with ethylenediamine (EDA) to produce NH2-functionalized carbon surfaces. Overall, we a 5.2 ± 2.5-fold increase in ATP current with an approximately 9-fold increase in amine functionality, as analyzed by X-ray Photoelectron Spectroscopy, on the carbon surface was observed after modification with EDC-EDA. This provides evidence that amine-rich surfaces improve interactions with ATP on the surface. This study provides a detailed analysis of ATP interaction at carbon surfaces and ultimately a method to improve direct and rapid neurological ATP detection in the future.


Sleep Disorders in Aboriginal and Torres Strait Islander People and Residents of Regional and Remote Australia.
To compare the use of sleep diagnostic tests, the risks, and cofactors, and outcomes of the care of Indigenous and non-indigenous Australian adults in regional and remote Australia in whom sleep related breathing disorders have been diagnosed. A retrospective cohort study of 200 adults; 100 Aboriginal and Torres Strait Islander and 100 non-indigenous adults with a confirmed sleep related breathing disorder diagnosed prior to September 2011 at Alice Springs Hospital and Cairns Hospital, Australia. Results showed overall Indigenous Australians were 1.8 times more likely to have a positive diagnostic sleep study performed compared with non-indigenous patients, 1.6 times less likely in central Australia and 3.4 times more likely in far north Queensland. All regional and remote residents accessed diagnostic sleep studies at a rate less than Australia overall (31/100,000/y (95% confidence interval, 21-44) compared with 575/100,000/y). The barriers to diagnosis and ongoing care are likely to relate to remote residence, lower health self-efficacy, the complex nature of the treatment tool, and environmental factors such as electricity and sleeping area. Indigeneity, remote residence, environmental factors, and low awareness of sleep health are likely to affect service accessibility and rate of use and capacity to enhance patient and family education and support following a diagnosis. A greater understanding of enablers and barriers to care and evaluation of interventions to address these are required. A commentary on this article appears in this issue on page 1255.


Epigenetic Metabolite Acetate Inhibits Class I/II Histone Deacetylases, Promotes Histone Acetylation, and Increases HIV-1 Integration in CD4+ T Cells.
In this study, we investigated the effect of acetate, the most concentrated short-chain fatty acid (SCFA) in the gut and bloodstream, on the susceptibility of primary human CD4+ T cells to HIV-1 infection. We report that HIV-1 replication is increased in CD3/CD28-costimulated CD4+ T cells upon acetate treatment. This enhancing effect correlates with increased expression of the early activation marker CD69 and impaired class I/II histone deacetylase (HDAC) activity. In addition, acetate enhances acetylation of histones H3 and H4 and augments HIV-1 integration into the genome of CD4+ T cells. Thus, we propose that upon antigen presentation, acetate influences class I/II HDAC activity that transforms condensed chromatin into a more relaxed structure. This event leads to a higher level of viral integration and enhanced HIV-1 production. In line with previous studies showing reactivation of latent HIV-1 by SCFAs, we provide evidence that acetate can also increase the susceptibility of primary human CD4+ T cells to productive HIV-1 infection.IMPORTANCE Alterations in the fecal microbiota and intestinal epithelial damage involved in the gastrointestinal disorder associated with HIV-1 infection result in microbial translocation that leads to disease progression and virus-related comorbidities. Indeed, notably via production of short-chain fatty acids, bacteria migrating from the lumen to the intestinal mucosa could influence HIV-1 replication by epigenetic regulatory mechanisms, such as histone acetylation. We demonstrate that acetate enhances virus production in primary human CD4+ T cells. Moreover, we report that acetate impairs class I/II histone deacetylase activity and increases integration of HIV-1 DNA into the host genome. Therefore, it can be postulated that bacterial metabolites such as acetate modulate HIV-1-mediated disease progression.


Increasing ecological inference from high throughput sequencing of fungi in the environment through a tagging approach.
High throughput sequencing methods are widely used in analyses of microbial diversity, but are generally applied to small numbers of samples, which precludes characterization of patterns of microbial diversity across space and time. We have designed a primer-tagging approach that allows pooling and subsequent sorting of numerous samples, which is directed to amplification of a region spanning the nuclear ribosomal internal transcribed spacers and partial large subunit from fungi in environmental samples. To test the method for phylogenetic biases, we constructed a controlled mixture of four taxa representing the Chytridiomycota, Zygomycota, Ascomycota and Basidiomycota. Following cloning and colony restriction fragment length polymorphism analysis, we found no significant difference in representation in 19 of the 23 tested primers. We also generated a clone library from two soil DNA extracts using two primers for each extract and compared 456 clone sequences. Community diversity statistics and contingency table tests applied to counts of operational taxonomic units revealed that the two DNA extracts differed significantly, while the pairs of tagged primers from each extract were indistinguishable. Similar results were obtained using UniFrac phylogenetic comparisons. Together, these results suggest that the pig-tagged primers can be used to increase ecological inference in high throughput sequencing projects on fungi.


Effect of the baseline Y93H resistance-associated substitution in HCV genotype 3 for direct-acting antiviral treatment: real-life experience from a multicenter study in Sweden and Norway.
Background: The NS5A resistance-associated substitution (RAS) Y93H is found quite frequently (5-10%) at baseline in direct-acting antiviral agents (DAA) treatment-naïve genotype (GT) 3a patients when studied by the population-sequencing method (cut-off 20%). This RAS may impair HCV DAA treatment response, since it possesses a high fold in vitro resistance to daclatasvir (DCV) and velpatasvir (VEL) in GT 3. We investigated the effect of baseline Y93H in patients with GT 3a infection on treatment outcome, with or without resistance-based DAA-treatment during 2014-2017. Patients/Methods: Treatment in the intervention group (n = 130) was tailored to baseline resistance-findings by population-sequencing method. Detection of baseline Y93H above 20% prompted a prolonged treatment duration of NS5A-inhibitor and sofosbuvir (SOF) and/or addition of ribavirin (RBV). Patients without baseline Y93H in the intervention group and all patients in the control group (n = 78) received recommended standard DAA-treatment. Results: A higher sustained virologic response rate (SVR) in the intervention group was shown compared to the control group at 95.4% (124/130) and 88.5% (69/78), respectively (p = .06). All five patients with baseline Y93H in the intervention group achieved SVR with personalised treatment based on results from resistance testing; either with the addition of RBV or prolonged treatment duration (24w). In the control group, 2/4 patients with Y93H at baseline treated with ledipasvir/SOF/RBV or DCV/SOF without RBV, failed treatment. Conclusion: The results from this real-life study are in accordance with the findings of the randomised controlled trials in 2015 and the EASL-guidelines of 2016, thus, baseline Y93H impacts on DCV and VEL treatment outcome.


Efficacy of 3-Dimensional Endorectal Ultrasound for Staging Early Extraperitoneal Rectal Neoplasms.
Adequate oncologic staging of rectal neoplasia is important for treatment and prognostic evaluation of the disease. Diagnostic methods such as endorectal ultrasound can assess rectal wall invasion and lymph node involvement. The purpose of this study was to correlate findings of 3-dimensional endorectal ultrasound and pathologic diagnosis of extraperitoneal rectal tumors with regard to depth of rectal wall invasion, lymph node involvement, percentage of rectal circumference involvement, and tumor extension. Consecutive patients with extraperitoneal rectal tumors were prospectively assessed by 3-dimensional endorectal ultrasound blind to other staging methods and pathologic diagnosis. Patients who underwent endorectal ultrasound followed by surgery were included in the study. The study was conducted at a single academic institution. Sensitivity, specificity, positive and negative predictive values, area under curve, and κ coefficient between 3-dimensional endorectal ultrasound and pathologic diagnosis were determined. Intraclass correlation coefficient was calculated for tumor extension and percentage of rectal wall involvement. Forty-four patients (27 women; mean age = 63.5 years) were evaluated between September 2010 and June 2014. Most lesions were malignant (72.7%). For depth of submucosal invasion, 3-dimensional endorectal ultrasound showed sensitivity of 77.3%, specificity of 86.4%, positive predictive value of 85.0%, a negative predictive value of 79.2%, and an area under curve of 0.82. The weighted κ coefficient for depth of rectal wall invasion staging was 0.67, and there was no agreement between 3-dimensional endorectal ultrasound and pathologic diagnosis for lymph node involvement (κ = -0.164). Intraclass correlation coefficient for lesion extension and percentage of rectal circumference involvement were 0.45 and 0.66. A better correlation between 3-dimensional endorectal ultrasound and pathologic diagnosis was observed in tumors <5 cm and with <50% of rectal wall involvement. The relatively small sample size of patients with early rectal lesions referred directly for surgery could represent a potential selection bias. Three-dimensional endorectal ultrasound was effective for determining rectal wall invasion and lesion extension in tumors <5 cm and with <50% of rectal wall invasion but was limited for detecting lymph node involvement in early rectal lesions.


High-risk human papillomavirus reactivation in human immunodeficiency virus-infected women: risk factors for cervical viral shedding.
To evaluate the presence of and estimate risk factors for reactivation of latent high-risk human papillomavirus (HPV) cervical infection in human immunodeficiency virus (HIV)-infected and HIV-uninfected women. Data from 898 women in the HIV Epidemiology Research Study (HERS) were used to evaluate cervical HPV latency and reactivation. Prior exposure to HPV types (16, 18, 31, 35, and 45) was determined by serologic testing at enrollment, and cervical shedding of HPV was detected by polymerase chain reaction at 6-month intervals. Human papillomavirus cervical shedding and sexual history were used to estimate rates of reactivation and recurrence. Repeated measures survival analysis was used to estimate hazard ratios and 95% confidence intervals for reactivation and recurrence. Rates of total HPV shedding (recurrence and reactivation) during follow-up were assessed by HIV status and rate ratios were calculated. Reactivation of latent HPV infections was observed in HIV-infected women, but few reactivation events were identified in HIV-uninfected women. Factors consistently associated with reactivation in HIV-infected women included CD4 count less than 200/mm and age younger than 35 years. Women infected with HIV had 1.8 to 8.2 times higher rates of viral shedding (reactivation plus recurrence) compared with HIV-uninfected women. Women with a history of cervical HPV infection may be at risk of reactivation of latent viral infection even in the absence of sexual activity, and this risk is higher in women with HIV infection. II.


Ball-Contact Injuries in 11 National Collegiate Athletic Association Sports: The Injury Surveillance Program, 2009-2010 Through 2014-2015.
Surveillance data regarding injuries caused by ball contact in collegiate athletes have not been well examined and are mostly limited to discussions of concussions and catastrophic injuries. To describe the epidemiology of ball-contact injuries in 11 National Collegiate Athletic Association (NCAA) sports during the 2009-2010 through 2014-2015 academic years. Descriptive epidemiology study. Convenience sample of NCAA programs in 11 sports (men's football, women's field hockey, women's volleyball, men's baseball, women's softball, men's and women's basketball, men's and women's lacrosse, and men's and women's soccer) during the 2009-2010 through 2014-2015 academic years. Collegiate student-athletes participating in 11 sports. Ball-contact-injury rates, proportions, rate ratios, and proportion ratios with 95% confidence intervals were based on data from the NCAA Injury Surveillance Program during the 2009-2010 through 2014-2015 academic years. During the 2009-2010 through 2014-2015 academic years, 1123 ball-contact injuries were reported, for an overall rate of 3.54/10 000 AEs. The sports with the highest rates were women's softball (8.82/10 000 AEs), women's field hockey (7.71/10 000 AEs), and men's baseball (7.20/10 000 AEs). Most ball-contact injuries were to the hand/wrist (32.7%) and head/face (27.0%) and were diagnosed as contusions (30.5%), sprains (23.1%), and concussions (16.1%). Among sex-comparable sports (ie, baseball/softball, basketball, and soccer), women had a larger proportion of ball-contact injuries diagnosed as concussions than men (injury proportion ratio = 2.33; 95% confidence interval = 1.63, 3.33). More than half (51.0%) of ball-contact injuries were non-time loss (ie, participation-restriction time <24 hours), and 6.6% were severe (ie, participation-restriction time ≥21 days). The most common severe ball-contact injuries were concussions (n = 18) and finger fractures (n = 10). Ball-contact-injury rates were the highest in women's softball, women's field hockey, and men's baseball. Although more than half were non-time-loss injuries, severe injuries such as concussions and fractures were reported.


The Greater Involvement of People Living with AIDS principle: theory versus practice in Ontario's HIV/AIDS community-based research sector.
Drawing on the Greater Involvement of People with HIV/AIDS (GIPA) principle, the HIV/AIDS movement began to "democratize" research in Canada in the mid-1990s. To date, there is little evidence about the success of the community-based research (CBR) movement in relation to the implementation of GIPA. We draw on findings from a larger study examining barriers and facilitating factors in relation to HIV-related CBR in Ontario, Canada. An online survey was completed by 39 senior managers in Ontario AIDS service organizations (ASOs). Twenty-five in-depth, semi-structured interviews were then conducted to further explore the survey findings. Survey respondents reported that, compared to researchers and frontline service providers, people living with HIV/AIDS (PLWHA) tended to be the least involved in all stages (input, process and outcome) of CBR projects. AIDS service organizations with a mandate that included serving rural and urban communities reported even lower levels of PLWHA involvement in CBR. Qualitative data reveal complex barriers that make meaningful PLWHA engagement in CBR difficult, including: HIV-related stigma; health-related challenges; "credentialism"; lack of capacity to engage in research; other issues taking priority; and mistrust of researchers. Facilitating factors included valuing lived experience; training and mentoring opportunities; financial compensation; trust building; and accommodating PLWHA's needs. While there is strong support for the GIPA principles in theory, practice lags far behind.


A nonsense variation p.Arg325X in the vascular endothelial growth factor-A gene may be associated with congenital tricuspid aortic valve stenosis.
In our recent study, we first reported that mutation in vascular endothelial growth factor-A is associated with bicuspid aortic valve stenosis. However, to date no groups have explored the role of vascular endothelial growth factor-A variations in the aetiology of congenital tricuspid aortic valve stenosis. We sequenced all eight coding exons and exon-intron boundaries of the vascular endothelial growth factor-A gene in deoxyribonucleic acid samples of a cohort of 32 sporadic patients with tricuspid aortic valve stenosis, 300 normal controls, and 103 disease controls - conotruncal defects - in order to identify sequence variants. We identified a c.973C > T heterozygous nonsense variation in exon 6 of the vascular endothelial growth factor-A gene in a patient with an isolated tricuspid aortic valve stenosis. The c.973C > T variation, which was absent in all controls, changes a highly conserved arginine at amino acid position 325 to a stop codon (p.Arg325X) and is predicted to produce a truncated protein of 324 amino acid residues. The proband's parents had a normal cardiac phenotype; however, his father was a carrier of the p.Arg325X variation, which indicates that the p.Arg325X variation is inherited and incompletely penetrant. We report for the first time that the p.Arg325X nonsense variation in the vascular endothelial growth factor-A gene may be associated with congenital tricuspid aortic valve stenosis.


Advanced Practice Registered Nurses and Long-Acting Reversible Contraception.
Advanced practice registered nurses (APRNs) are in an excellent position to address the high rates of unintended pregnancy in the United States by providing long-acting reversible contraceptives (LARCs). These methods are significant in their effectiveness in preventing pregnancy in individual women and in having population-level effects on unintended pregnancy. The aim of this study was to learn more about APRN practices around long-acting reversible contraception and influences on those practices. A cross-sectional survey of APRNs who provide women's health services was conducted during the summer of 2015 using an existing adapted instrument with items on personal and patient characteristics, opinions, practices, and training around LARC methods. Zero-inflated Poisson regression models were conducted to study the factors that influenced the number of LARC insertions in the past year. While 84% of the 390 respondents were inserting intrauterine devices (IUDs) and 77% single-rod implants, only 16% of these were inserting more devices than 5 years earlier. The most significant predictor of placement of these contraceptives was the clinical practice of requiring only one visit for completion. National guidelines and recommendations have been in place for several years stating that women should be able to receive the contraceptive method of their choice in just one clinic visit. Women's access to LARCs from APRNs may be less than optimal. Additional research is needed to understand if the limitations in accessibility of this important reproductive health service are a function of clinician practices or clinic policies.


Dexamethasone-Induced Effects on B-50/GAP-43 Expression and Neurite Outgrowth in PC 12 Cells.
Undifferentiated PC 12 cells contain detectable levels of the nervous-specific protein B-50/GAP-43. Upon treatment with NGF or change of culture medium, B-50/ GAP-43 levels remained unchanged during the first 12 hours while neuritogenesis starts. Both, B-50/GAP-43 levels and neurite outgrowth peak at 24 hours. These results suggest that in PC 12 cells the amount of B-50 already present is sufficient to support the start of NGF-induced neuritogenesis, presumably by translocation from cytosolic compartments to the membrane. Addition of DEX reversed the rise in B-50/GAP-43 levels induced by either the change of medium or by NGF. In contrast, neurite outgrowth was inhibited to a lesser extent, although after 36 hours of pretreatment with DEX neurite length was lower than control. NGF was capable of enhancing B-50/GAP-43 levels both in the presence and absence of DEX. This corroborates data from others, who concluded that DEX and NGF exert their effects through different mechanisms, e.g., transcription versus mRNA stabilization, respectively. The inhibitory effect of DEX under various conditions on both B-50 expression and neurite outgrowth in the normal PC 12 cell line demonstrates the tight coupling of these parameters that might be indicative of a threshold effect of B-50 levels on neurite outgrowth.


Isoform-selective activation of protein kinase C by nitric oxide in the heart of conscious rabbits: a signaling mechanism for both nitric oxide-induced and ischemia-induced preconditioning.
Although isoform-selective translocation of protein kinase C (PKC) epsilon appears to play an important role in the late phase of ischemic preconditioning (PC), the mechanism(s) responsible for such translocation remains unclear. Furthermore, the signaling pathway that leads to the development of late PC after exogenous administration of NO in the absence of ischemia (NO donor-induced late PC) is unknown. In the present study we tested the hypothesis that NO activates PKC and that this is the mechanism for the development of both ischemia-induced and NO donor-induced late PC. A total of 95 chronically instrumented, conscious rabbits were used. In rabbits subjected to ischemic PC (six 4-minute occlusion/4-minute reperfusion cycles), administration of the NO synthase inhibitor Nomega-nitro-L-arginine (group III), at doses previously shown to block the development of late PC, completely blocked the ischemic PC-induced translocation of PKCepsilon but not of PKCeta, indicating that increased formation of NO is an essential mechanism whereby brief ischemia activates the epsilon isoform of PKC. Conversely, a translocation of PKCepsilon and -eta quantitatively similar to that induced by ischemic PC could be reproduced pharmacologically with the administration of 2 structurally unrelated NO donors, diethylenetriamine/NO (DETA/NO) and S-nitroso-N-acetylpenicillamine (SNAP), at doses previously shown to elicit a late PC effect. The particulate fraction of PKCepsilon increased from 35+/-2% of total in the control group (group I) to 60+/-1% after ischemic PC (group II) (P<0.05), to 54+/-2% after SNAP (group IV) (P<0.05) and to 52+/-2% after DETA/NO (group V) (P<0.05). The particulate fraction of PKCeta rose from 66+/-5% in the control group to 86+/-3% after ischemic PC (P<0.05), to 88+/-2% after SNAP (P<0.05) and to 85+/-1% after DETA/NO (P<0.05). Neither ischemic PC nor NO donors had any appreciable effect on the subcellular distribution of PKCalpha, -beta1, -beta2, -gamma, -delta, - micro, or -iota/lambda; on total PKC activity; or on the subcellular distribution of total PKC activity. Thus, the effects of SNAP and DETA/NO on PKC closely resembled those of ischemic PC. The DETA/NO-induced translocation of PKCepsilon (but not that of PKCeta) was completely prevented by the administration of the PKC inhibitor chelerythrine at a dose of 5 mg/kg (group VI) (particulate fraction of PKCepsilon, 38+/-4% of total, P<0.05 versus group V; particulate fraction of PKCeta, 79+/-2% of total). The same dose of chelerythrine completely prevented the DETA/NO-induced late PC effect against both myocardial stunning (groups VII through X) and myocardial infarction (groups XI through XV), indicating that NO donors induce late PC by activating PKC and that among the 10 isozymes of PKC expressed in the rabbit heart, the epsilon isotype is specifically involved in the development of this form of pharmacological PC. In all groups examined (groups I through VI), the changes in the subcellular distribution of PKCepsilon protein were associated with parallel changes in PKCepsilon isoform-selective activity, whereas total PKC activity was not significantly altered. Taken together, the results provide direct evidence that isoform-selective activation of PKCepsilon is a critical step in the signaling pathway whereby NO initiates the development of a late PC effect both after an ischemic stimulus (endogenous NO) and after treatment with NO-releasing agents (exogenous NO). To our knowledge, this is also the first report that NO can activate PKC in the heart. The finding that NO can promote isoform-specific activation of PKC identifies a new biological function of this radical and a new mechanism in the signaling cascade of ischemic PC and may also have important implications for other pathophysiological conditions in which NO is involved and for nitrate therapy.


Processes of Belonging for Citizen-Children of Undocumented Mexican Immigrants.
In this article, we focus on the developmental contexts of middle childhood and early adolescence to explore the lives of citizen-children living with undocumented Mexican parents. We draw on the concept of belonging to highlight the distinct situation of citizen-children and the ways in which they come to understand their place in a world. To capture the experiences of citizen-children born to undocumented Mexican immigrant parents and their sense of belonging to place and community, we conducted in-depth interviews with 83 citizen-children in late childhood and early adolescence in three groups. One group of citizen-children lived in Mexico after their parents' deportation. Another group remained in the U.S. after parents were detained or deported. The third group did not have a parent in deportation proceedings. Qualitative analyses of children's recorded interviews revealed their experiences of discovery of parents' undocumented status; political, social and material exclusion; and rupture of family ties. Children were keenly aware that birthright citizenship afforded them numerous privileges unavailable to their parents, but that it did not extend to the very privilege, they valued most: an intact family. The loss of parents through detention or deportation forced some children to consider existential questions about who they were and where they belonged, sometimes pitting family members against one another. Our findings suggest that belonging is intimately tied to broader forces of legal persecution that go beyond individualized notions of illegality and have deep, possibly lasting psychological effects.


Human skeletal muscle fibroblasts stimulate in vitro myogenesis and in vivo muscle regeneration.
Accumulation of skeletal muscle extracellular matrix is an unfavourable characteristic of many muscle diseases, muscle injury and sarcopenia. The extent of cross-talk between fibroblasts, as the source of matrix protein, and satellite cells in humans is unknown. We studied this in human muscle biopsies and cell-culture studies. We observed a strong stimulation of myogenesis by human fibroblasts in cell culture. In biopsies collected 30 days after a muscle injury protocol, fibroblast number increased to four times control levels, where fibroblasts were found to be preferentially located immediately surrounding regenerating muscle fibres. These novel findings indicate an important role for fibroblasts in supporting the regeneration of muscle fibres, potentially through direct stimulation of satellite cell differentiation and fusion, and contribute to understanding of cell-cell cross-talk during physiological and pathological muscle remodelling. Accumulation of skeletal muscle extracellular matrix is an unfavourable characteristic of many muscle diseases, muscle injury and sarcopenia. In addition to the indispensable role satellite cells play in muscle regeneration, there is emerging evidence in rodents for a regulatory influence on fibroblast activity. However, the influence of fibroblasts on satellite cells and muscle regeneration in humans is unknown. The purpose of this study was to investigate this in vitro and during in vivo regeneration in humans. Following a muscle injury protocol in young healthy men (n = 7), the number of fibroblasts (TCF7L2+), satellite cells (Pax7+), differentiating myogenic cells (myogenin+) and regenerating fibres (neonatal/embryonic myosin+) was determined from biopsy cross-sections. Fibroblasts and myogenic precursor cells (MPCs) were also isolated from human skeletal muscle (n = 4) and co-cultured using different cell ratios, with the two cell populations either in direct contact with each other or separated by a permeable membrane. MPC proliferation, differentiation and fusion were assessed from cells stained for BrdU, desmin and myogenin. On biopsy cross-sections, fibroblast number was seen to increase, along with myogenic cell number, by d7 and increase further by d30, where fibroblasts were observed to be preferentially located immediately surrounding regenerating muscle fibres. In vitro, the presence of fibroblasts in direct contact with MPCs was found to moderately stimulate MPC proliferation and strongly stimulate both MPC differentiation and MPC fusion. It thus appears, in humans, that fibroblasts exert a strong positive regulatory influence on MPC activity, in line with observations during in vivo skeletal muscle regeneration.


Structure of blue phase III of cholesteric liquid crystals.
We report large scale simulations of the blue phases of cholesteric liquid crystals. Our results suggest a structure for blue phase III, the blue fog, which has been the subject of a long debate in liquid crystal physics. We propose that blue phase III is an amorphous network of disclination lines, which is thermodynamically and kinetically stabilized over crystalline blue phases at intermediate chiralities. This amorphous network becomes ordered under an applied electric field, as seen in experiments.


From Transcriptome to Noncoding RNAs: Implications in ALS Mechanism.
In the last years, numerous studies have focused on understanding the metabolism of RNA and its implication in disease processes but abnormal RNA metabolism is still unknown. RNA plays a central role in translating genetic information into proteins and in many other catalytic and regulatory tasks. Recent advances in the study of RNA metabolism revealed complex pathways for the generation and maintenance of functional RNA in amyotrophic lateral sclerosis (ALS). Interestingly, perturbations in RNA processing have been described in ALS at various levels such as gene transcription, mRNA stabilization, transport, and translational regulations. In this paper, we will discuss the alteration of RNA profile in ALS disease, starting from transcription, the first step leading to gene expression, through the posttranscriptional regulation, including RNA/DNA binding proteins and aberrant exon splicing to protein noncoding RNAs, as lncRNA and microRNA.


Peripheral ameloblastoma with neoplastic osseous invasion versus peripheral intraosseous ameloblastoma: A challenging diagnosis.
Peripheral ameloblastoma, a soft-tissue analogue of intraosseous ameloblastoma, is a rare odontogenic tumor with histologic characteristics of ameloblastoma. In contrast to conventional ameloblastoma, peripheral ameloblastomas are considered as innocuous lesions which usually do not show invasion of the underlying structures. Rarely, intraosseous ameloblastoma which penetrates the alveolar bone can fuse with the overlying oral epithelium and eventually manifest as an exophytic peripheral lesion. Such lesions which mimic peripheral ameloblastoma both clinically and microscopically are termed as peripheral intraosseous ameloblastoma. As per the existing criteria, soft-tissue ameloblastomas showing bone invasion are strictly excluded from the category of peripheral ameloblastoma and are considered as peripheral intraosseous ameloblastoma. We report a rare case of extraosseous ameloblastoma with clear origin from the superficial epithelium showing the presence of a few odontogenic islands in the underlying bone suggestive of a neoplastic osseous invasion. This paper discusses the diagnostic challenges associated with peripherally occurring ameloblastomas and stresses the need for accurate diagnosis in deciding the treatment modalities.


LjaFGD: Lonicera japonica functional genomics database.
Lonicera japonica Thunb., a traditional Chinese herb, has been used for treating human diseases for thousands of years. Recently, the genome of L. japonica has been decoded, providing valuable information for research into gene function. However, no comprehensive database for gene functional analysis and mining is available for L. japonica. We therefore constructed LjaFGD (www.gzybioinformatics.cn/LjaFGD and bioinformatics.cau.edu.cn/LjaFGD), a database for analyzing and comparing gene function in L. japonica. We constructed a gene co-expression network based on 77 RNA-seq samples, and then annotated genes of L. japonica by alignment against protein sequences from public databases. We also introduced several tools for gene functional analysis, including Blast, motif analysis, gene set enrichment analysis, heatmap analysis, and JBrowse. Our co-expression network revealed that MYB and WRKY transcription factor family genes were co-expressed with genes encoding key enzymes in the biosynthesis of chlorogenic acid and luteolin in L. japonica. We used flavonol synthase 1 (LjFLS1) as an example to show the reliability and applicability of our database. LjaFGD and its various associated tools will provide researchers with an accessible platform for retrieving functional information on L. japonica genes to further biological discovery.


Tartrate-resistant acid phosphatase 5b: a novel serum marker of bone resorption.
Human serum contains two forms of tartrate-resistant acid phosphatase (TRAP), 5a and 5b. Of these, 5a contains sialic acid and 5b does not. We show here that antigenic properties and pH optimum of TRAP purified from human osteoclasts are identical to those of serum TRAP 5b and completely different from those of serum TRAP 5a, suggesting that 5b would be derived from osteoclasts and 5a from some other source. We developed a novel immunoassay specific for 5b using a monoclonal antibody O1A as capture antibody. O1A did not bind acid phosphatase derived from platelets and erythrocytes. Western analysis showed that O1A was specific for TRAP in both human bone and serum. We measured bound TRAP activity at pH 6.1, where 5b is highly active and 5a almost completely inactive. The immunoassay detected more than 90% of the initial TRAP 5b activity after 8-h incubation of serum samples at 25 degrees C and after 3 days incubation at 4 degrees C. Serum TRAP 5b activity decreased significantly after 6 months of hormone replacement therapy (HRT) of postmenopausal women compared with the change observed in postmenopausal women receiving placebo (p < 0.0001). Instead, no significant differences were observed between the changes in the placebo and HRT groups in total serum TRAP amount. These results show that serum TRAP 5b is a specific and sensitive marker for monitoring antiresorptive treatment. Instead, total serum TRAP cannot be used for that purpose. These findings may turn out to be a significant improvement in using serum TRAP as a resorption marker.


[Epidemiological and immunological criteria of the effectiveness of immunization with adsorbed DPT vaccine by the old and new schedules].
The study revealed that the immunization of children with adsorbed DPT vaccine from the age of 3-4 months, as compared with the immunization of children from the age of 5-6 months, did not lead to an essential increase in the coverage of children with immunization at the period under study (1970-1983) and did not affect the total level of pertussis morbidity, as well as the proportion of children aged up to 1 year in the total number of pertussis cases. Children immunized at an early age produced antibodies in titers, equivalent to the titers in older children, but their immunity against pertussis, in contrast to their immunity against diphtheria and tetanus, was retained for a shorter period. The injection of adsorbed DPT vaccine at the age of 3-4 months was accompanied by a poorly pronounced increase in the content of IgG, the predominant synthesis of IgM and the suppression of the synthesis of IgA. The shift of the start of vaccination to the age of 3-4 months has probably some immunological grounds for diphtheria and tetanus, but it is premature with respect to pertussis.


Differential target cell sensitivity to CTL-activated death pathways in hepatitis B virus transgenic mice.
The current study was designed to explore the relative contribution of Fas ligand (FasL), perforin, IFN-gamma, and TNF-alpha-induced death pathways in the pathogenesis of CTL-induced liver disease. Hepatitis B virus-specific CTL that are genetically unable to produce either FasL, perforin, or IFN-gamma were injected into Fas-competent and Fas-deficient hepatitis B virus transgenic mice that are either sensitive or resistant to the cytopathic effects of IFN-gamma based on the extent to which their hepatocytes retain hepatitis B surface Ag (HBsAg). The results of these experiments indicate that FasL- and perforin-dependent signals are primarily responsible for the induction of liver disease in the absence of HBsAg retention, but both signaling pathways must be activated simultaneously by the CTL in order to kill the hepatocyte in vivo. In contrast, neither FasL nor perforin are required to kill hepatocytes that retain HBsAg as long as the CTL secrete IFN-gamma on antigen recognition. Finally the results indicate that, irrespective of their HBsAg content, hepatocytes are much less sensitive to destruction by TNF-alpha than by the other death pathways. While all of these death pathways appear to be operative during a normal CTL response, the current experiments suggest that the target cell determines which pathway is dominant and selects its mode of execution.


Worldwide Prevalence of Brugada Syndrome: A Systematic Review and Meta-Analysis.
Brugada syndrome (BrS) is considered to be an inherited arrhythmic disease associated with fatal complications and premature sudden unexpected death. The prevalence of the Brugada electrocardiogram pattern (BrP) has been reported in several countries. Nonetheless, the specific worldwide prevalence of BrS has not been reported. We estimated the worldwide prevalence of BrS and Type-2/3 BrP in general adult populations using a systematic review and meta-analysis of the existing literature. We thoroughly searched MEDLINE and SCOPUS databases up to March 2017. Included studies were population-based electrocardiogram studies in which prevalence was presented or could be calculated from available data. Pooled prevalence by country/region and/or ethnicity was estimated using a random-effect model. Twenty-eight articles with atotal population of 369,068 were included in this study. The worldwide pooled prevalence of BrS was 0.5 per 1,000 [95% confidence interval (CI): 0.3-0.7]. The highest prevalence was reported in Southeast Asia (1.8 per 1,000, 95% CI: 0.5-6.6); the lowest was found in North Africa (0 per 1,000). BrS in Asians was nine times more common than in Caucasians and 36 times more common than in Hispanics. The worldwide pooled prevalence of Type-2/3 BrP was 6.1 per 1,000 (95% CI: 5.0-7.1). The highest prevalence was also reported in Southeast Asia (35.5 per 1,000, 95% CI: 17.1-53.9). This study revealed a significant difference in the worldwide prevalence of BrS and Type-2/3 BrP. Brugada electrocardiogram patterns are highly prevalent in Southeast Asia.


Imaging myocardial fiber architecture in vivo with magnetic resonance.
Methods are presented to image the fiber architecture of the human myocardium in vitro and in vivo. NMR images are obtained of the diffusion anisotropy tensor, indicative of local myofiber orientation. Studies of cardiac necropsy specimens demonstrate classic features of ventricular myoarchitecture including the continuous endocardial to epicardial variation of fiber helix angles (angles to the ventricular circumferential direction) of approximately +1.3 to -1.3 radians. Cross-fiber anisotropy is also observed. In the beating heart, NMR diffusion data must be corrected for the effects of myocardial deformation during the cardiac cycle. This correction can be performed using an independent MRI method to map the strain-rate tensor field of the myocardium through time. Combining fiber orientation with local myocardial strain rate, local rates of myocardial fiber shortening may be computed.


Sensitivity of the xerophytic moss Syntrichia caninervis to prolonged simulated nitrogen deposition.
Biological soil crusts, comprising assemblages of cyanobacteria, fungi, lichens and mosses, are common in dryland areas and are important elements in these ecosystems. Increasing N deposition has led to great changes in community structure and function in desert ecosystems worldwide. However, it is unclear how moss crusts respond to increased atmospheric N deposition, especially in terms of growth and physiological parameters. The aim of this study was to understand how Syntrichia caninervis, a dominant species in moss crusts in many northern hemisphere desert ecosystems, responds to added N. The population and shoot growth, and physiological responses of S. caninervis to six different doses of simulated N deposition (0, 0·3, 0·5, 1·0, 1·5 and 3·0 g N m(-2) year(-1)) were studied over a 3 year period. Low amounts of added N increased shoot length and leaf size, whereas high doses reduced almost all growth parameters. Moss shoot density increased, but population biomass decreased with high N. Low N augmented chlorophyll b, total chlorophyll content and soluble protein concentrations, but not chlorophyll a or chlorophyll fluorescence. High N was detrimental to all these indices. Soluble sugar concentration declined with increased N, but proline concentration was not affected significantly. Antioxidant enzyme activities generally decreased with low N additions and increased with high doses of simulated N deposition. Low amounts of added N (0-0·5 g N m(-2) year(-1)) may enhance moss growth and vitality, while higher amounts have detrimental effects.


Synthesis and spectroscopic analysis of chromophoric lipids inducing pH-dependent liposome fusion.
We design novel chromophoric amphiphiles 6a-c, which lead to pH-dependent membrane fusion of egg phosphatidylcholine (eggPC) liposome containing them. Lipids 6a-c comprise double alkyl chains, a single chain with a 2-nitrophenol group as a pH trigger, and dipeptide (Asp-Asp) between them. The pKa values of 2-nitrophenol groups of 6a-c in liposome are larger than that of hydrophilic compound 9 in an aqueous solution. Absorption spectra indicate that the fields around 2-nitrophenol of 6a-c situated in liposome membranes are more hydrophobic than that of 9 in an aqueous solution, whereas the environments around deprotonated 2-nitrophenolate of 6b and 6c are not so hydrophobic as that of 6a. This means that protonated 2-nitrophenol groups of 6a-c are embedded in bilayer membranes. Deprotonated 2-nitrophenol groups of 6b and 6c must be located in less hydrophobic circumstances, while that of 6a is still embedded in bilayer membranes because of its larger hydrophobicity. Absorption spectra and (1)H NMR spectra respectively suggest that protonated 2-nitrophenol groups of 6a and those of 6c might take face-to-face associations in bilayer membranes.


The polypeptide composition of isolated surface projections of avian infectious bronchitis virus.
Disruption of avian infectious bronchitis virus (IBV) particles with 4% Triton X-100 and 1.0 M-KCl and centrifugation through a sucrose gradient containing 0.1% Triton X-100 and 1.0 M-KCl enabled separation of the petal-shaped surface projections. By negative-contrast electron microscopy the separated projections appeared mainly as rosettes containing 3 to 12 projections radiating from a central core, although single projections and rosettes containing up to 16 projections were seen. SDS-PAGE of these preparations revealed two polypeptides of 86,000 and 66,000 mol. wt. The larger polypeptide was glycosylated.


[Leocaine--a new generation of local anesthetics].
Leocaine is a new crystal beta-modification of beta-dimethylaminoethyl ether of n-butylaminobenzoic acid hydrochloride. Its chemical formula is the same as for dicaine, but it has a number of advantages over this drug. The anesthetic activity of leocaine is 2.5 times higher than that of dicaine. By the duration and depth of anesthesia 0.3% leocaine solution corresponds to 1% dicaine. Leocaine exerts no toxic effect on the corneal epithelium and its instillation into the conjunctival cavity does not result in the reactive dilatation of corneal or episcleral vessels. Leocaine solution is stable for 2 years. Clinical trials of leocaine carried out on more than 2500 patients showed virtually complete absence of side effects. Commercial manufacture of leocaine is launched at present. One of the commercial preparations represents a 0.3% solution of the active substance in isotonic NaCl solution. Another drug contains, besides leocaine, methylcellulose. Eye drops with leocaine are recommended for practical ophthalmology instead of dicaine for local anesthesia. The drugs are permitted for medical use and commercial manufacture by the Ministry of Health and Medical Industry of Russia.


Place matters: consensual features and regional variation in American well-being and self.
Consensual and regionally distinct features of well-being and self were examined in a nationally representative survey of midlife Americans (ages 25-75). Consistent with key American ideology, Study 1 found that a majority of Americans believe they have high levels of mastery, purpose, life satisfaction, overall health, family and work obligation, and partner and family support. Study 2 found distinct regional well-being profiles (e.g., New England reflected concern with not being constrained by others; Mountain showed concern with environmental mastery; West South Central with personal growth and feeling cheerful and happy; West North Central with feeling calm, peaceful, and satisfied; and East South Central with contributing to others' well-being). Study 3 found regional self profiles consistent with the well-being profiles.