Mammal disparity decreases during the Cretaceous angiosperm radiation.
Fossil discoveries over the past 30 years have radically transformed traditional views of Mesozoic mammal evolution. In addition, recent research provides a more detailed account of the Cretaceous diversification of flowering plants. Here, we examine patterns of morphological disparity and functional morphology associated with diet in early mammals. Two analyses were performed: (i) an examination of diversity based on functional dental type rather than higher-level taxonomy, and (ii) a morphometric analysis of jaws, which made use of modern analogues, to assess changes in mammalian morphological and dietary disparity. Results demonstrate a decline in diversity of molar types during the mid-Cretaceous as abundances of triconodonts, symmetrodonts, docodonts and eupantotherians diminished. Multituberculates experience a turnover in functional molar types during the mid-Cretaceous and a shift towards plant-dominated diets during the late Late Cretaceous. Although therians undergo a taxonomic expansion coinciding with the angiosperm radiation, they display small body sizes and a low level of morphological disparity, suggesting an evolutionary shift favouring small insectivores. It is concluded that during the mid-Cretaceous, the period of rapid angiosperm radiation, mammals experienced both a decrease in morphological disparity and a functional shift in dietary morphology that were probably related to changing ecosystems.


The developmental profile: validation of a theory-driven instrument for personality assessment.
The Developmental Profile is an instrument for personality assessment. It covers both maladaptive and adaptive characteristics. The current study examined its internal consistency and construct validity in a Dutch sample of 763 participants from various clinical and nonclinical settings. The internal consistency reliability estimates were good for the clusters of levels (adaptive, neurotic, and primitive), although not for all separate levels. Confirmatory factor analysis showed an overall good fit, with the exception of the level of primary narcissism. Furthermore, empirical evidence was found for the interpretation of a patient's Developmental Profile according to increasing levels of aggregation, with as a highest level a single maladaptivity-adaptivity scale score. This scale significantly distinguished among different patient groups.


Endogenous TRPM4-like channel in Chinese hamster ovary (CHO) cells.
Chinese hamster ovary (CHO) cells used in many transfection studies have been found to endogenously express channels permeable to monovalent cations, but not to divalent cations. In the presence of intracellular Ca(2+), 23-pS channel with a linear current-voltage (I-V) relationship could be frequently observed in inside-out patches but not in cell-attached patches. The open probability was voltage-dependent, which is higher at positive potentials. The channel was dose-dependently activated by relatively high level of Ca(2+) (EC(50)=1.04+/-0.08 mM), and sensitively inhibited by 100 microM ATP, ADP, AMP, and 1mM spermine. However, ruthenium red (2 microM) had no effect. Reverse transcript polymerase chain reaction (RT-PCR) supported the presence of mRNA encoding TRPM4b channel protein. Western blot assay finally confirmed the presence of this channel protein in membrane fraction of CHO cells. These results provide evidence that CHO cells express an endogenous TRPM4b-like channel, and thereby can be used as a tool to study de novo regulation/modulation of TRPM4 channel.


Identification of Sleep Patterns via Clustering of Hypnodensities.
Sleep patterns vary widely between individuals. We explore methods for identifying populations exhibiting similar sleep patterns in an automated fashion using polysomnography data. Our novel approach applies unsupervised machine learning algorithms to hypnodensities graphs generated by a pre-trained neural network. In a population of 100 subjects we identify two stable clusters whose characteristics we visualize graphically and through estimates of total sleep time. We also find that the hypnodensity representation of the sleep stages produces more robust clustering results than the same methods applied to traditional hypnograms.


Epidemiology of the 2020 Pandemic of COVID-19 in the State of Texas: The First Month of Community Spread.
The pandemic of novel Coronavirus (SARS-CoV-2) is currently spreading rapidly across the United States. We provide a comprehensive overview of COVID-19 epidemiology across the state of Texas, which includes vast rural & vulnerable communities that may be disproportionately impacted by the spread of this new disease. All 254 Texas counties were included in this study. We examined the geographic variation of COVID-19 from March 1 through April 8, 2020 by extracting data on incidence and case fatality from various national and state datasets. We contrasted incidence and case fatality rates by county-level demographic and healthcare resource factors. Counties which are part of metropolitan regions, such as Harris and Dallas, experienced the highest total number of confirmed cases. However, the highest incidence rates per 100,000 population were in found in counties of Donley (353.5), Castro (136.4), Matagorda (114.4) and Galveston (93.4). Among counties with greater than 10 cases, the highest CFR were observed in counties of Comal (10.3%), Hockley (10%), Hood (10%), and Castro (9.1%). Counties with the highest CFR (> 10%) had a higher proportion of non-Hispanic Black residents, adults aged 65 and older, and adults smoking, but lower number of ICU beds per 100,000 population, and number of primary care physicians per 1000 population. Although the urban areas of Texas account for the majority of COVID-19 cases, the higher case-fatality rates and low health care capacity in rural areas need attention.


Provocative mesenteric angiography for lower gastrointestinal hemorrhage: results from a single-institution study.
To determine the diagnostic capability, complication rate, and potential predictors of success for provocative mesenteric angiography in patients with obscure and recurrent lower gastrointestinal (GI) hemorrhage. Thirty-four patients (age, 7-92 years; 22 men) underwent 36 provocative mesenteric angiograms between January 2002 and December 2008. Provocative mesenteric angiography consisted of systemic anticoagulation with heparin followed by selective transcatheter injection of vasodilator and tissue plasminogen activator into the arterial distribution of highest suspicion. Medications were administered incrementally until active extravasation was visualized or until the operator deemed the outcome negative. The pertinent clinical, radiologic, surgical, laboratory, and pathologic notes were retrospectively reviewed. Among 36 provocative mesenteric angiograms, 11 resulted in angiographically visible extravasation (31%) and an additional procedure resulted in angiographic visualization of an undiagnosed hypervascular mass, resulting in the identification of a source of a hemorrhage in 33% overall. In 10 of the 11 cases with visualized extravasation, transcatheter embolization successfully controlled recurrent hemorrhage, while the hypervascular mass without extravasation was successfully resected. Therefore, a total of 11 of 36 studies (31%) resulted in successful definitive treatment of recurrent hemorrhage. One embolization-related complication occurred, resulting in surgical resection of perforated ischemic bowel. No hemorrhagic complications were identified. Patients with melena and patients admitted for reasons other than acute lower GI hemorrhage were significantly less likely to benefit from provocative mesenteric angiography. In this series, provocative mesenteric angiography was safe and effective for eliciting the source of occult lower GI hemorrhage, leading to definitive therapy in about one third of patients.


Low potassium dextran is superior to University of Wisconsin solution in high-risk lung transplant recipients.
The ideal solution for recovery of donor lungs remains unknown. Low potassium dextran (LPD) solution is most common, but University of Wisconsin (UW) solution is also used. The United Network for Organ Sharing (UNOS) database allows assessment of preservation solutions in a large cohort of lung transplant (LTx) patients. We retrospectively reviewed the UNOS data set for adult primary LTx patients (2005-2008) whose donor lungs were recovered with UW or LPD solution. Patients were stratified by UW vs LPD, and secondarily grouped by quartiles of the lung allocation score (LAS) to examine high-risk recipients. Kaplan-Meier (KM) short-term mortality (30 days, 90 days, 1 year) and rejection in the first year were examined for intervals with adequate follow-up. Cox proportional hazard regression using 11 variables examined all cause 1-year mortality. Of 4,455 patients, 4,161 (93.4%) received LPD lungs and 294 (6.6%) received UW lungs, and 1,105 patients (24.8%) died during the study. There was no mortality difference based on flush solution with all patients examined together. However, patients in the upper 2 LAS quartiles (Q3: 37.8-45.4, Q4: > 45.4) receiving LPD lungs had greater 1-year survival of 81.5% vs 73.5% (p = 0.02). On multivariable analysis, flush with UW solution resulted in an increased risk of 1-year mortality (hazard ratio, 1.77. 95% confidence interval, 1.21-2.58; p = 0.003) vs LPD. Preservation solution did not affect rejection rates in the year after LTx. KM modeling demonstrated the effect of flush solution on survival (p = 0.02). This study is the largest modern cohort to evaluate the effect of donor lung flush solutions on survival in adult LTx. UW solution increases the risk of 1-year mortality in high-risk LTx recipients.


Magnesium and hearing.
The last several decades have revealed clinical and experimental data regarding the importance of magnesium (Mg) in hearing. Increased susceptibility to noise damage, ototoxicity, and auditory hyperexcitability are linked to states of Mg deficiency. Evidence for these processes has come slowly and direct effects have remained elusive because plasma Mg levels do not always correlate with its deficiency. Despite the major progress in the understanding of cochlear mechanical and auditory nerve function, the neurochemical and pharmacologic role of Mg is not clear. The putative mechanism suggests that Mg deficiency may contribute to a metabolic cellular cascade of events. Mg deficiency leads to an increased permeability of the calcium channel in the hair cells with a consequent over influx of calcium, an increased release of glutamate via exocytosis, and over stimulation of NMDA receptors on the auditory nerve. This paper provides a current overview of relevant Mg metabolism and deficiency and its influence on hearing.


Incidence of oral cavity and pharynx cancer in Kentucky.
Oral cavity and pharyngeal (OCOP) cancer is strongly associated with tobacco use and alcohol consumption. Kentucky consistently has one of the highest rates of tobacco use in the United States. The purpose of this study was to examine the differences in incidence rates in Kentucky as compared to nationwide data as well as regional differences within the state. Oral and pharyngeal cancer incidence data for the years 1995-2004 in Kentucky were obtained from Kentucky Cancer Registry (KCR). Data for the same time period for the United States were approximated using SEER*Stat 6.3.5 provided by the Surveillance, Epidemiology, and End Results (SEER) Program. Age-adjusted incidence rates and smoothed incidence rates by county were examined. The overall incidence of oral cavity and pharyngeal cancer in Kentucky was 12.1/100,000. This was significantly higher than the rate seen in the SEER data of 11.3/100,000 population (p < 0.05). This difference was more pronounced for males in Kentucky, where a 20% higher rate (19.2 vs 16.3/100,000 SEER) was observed. The vast majority of cases (62.1%) had a documented smoking history, and this number was higher in advanced stage disease (73%). Rates were lower in Appalachian regions (11.4/100,000) compared to non-Appalachian regions (12.4/10/ 100,000), p < 0.01, with additional geographic variations observed. Kentucky has a higher incidence rate for oral cavity and pharyngeal cancer than the national average. The high prevalence of tobacco use in the state is likely a strong contributing factor. The etiology of regional patterns of incidence rates statewide requires further study.


Vulnerability to ventricular arrhythmia: assessment by mapping of body surface potential.
It is now well established that the vulnerability of the ventricular myocardium to repetitive dysrhythm increases in the presence of greater than normal disparity local recovery times. Local recovery is reflected in the electrocardiographic waveform as an area of the ventricular deflection (QRST time integral), and thus disparate ventricular recovery may be manifested in the body surface distribution of this quality. To assess this possibility, we obtained simultaneous 120-lead electrocardiograms from both the anterior and posterior torso in 140 subjects (ages 8 to 75) grouped as follows: group A, 97 normal subjects; group B, 16 patients resuscitated from ventricular fibrillation or sustained ventricular tachycardia; and group C, 27 patients 6 to 12 months after myocardial infarction but without clinically significant arrhythmia. In each subject, the QRST integral was evaluated for each lead and isointegral contour maps were plotted. A score was assigned to each map, based on the number of extrema; each maximum or minimum scored one point, with the exception of simultaneously occurring anterior and posterior minima on the right shoulder (frequently occurring in normal subjects), which scored together only one point. All but one group A subject had dipolar QRST integral maps (mean +/- SD score 2.11 +/- 0.2). Conversely, 10 of 16 (62.5%) group B patients had scores of 3 or more (mean 3.16 +/- 1.08; p less than .01 vs group A). Group C patients had intermediate values, with eight of 27 (29.6%) scoring 3 or more (mean 2.46 +/- 83); this was less than in group B (p less than .01), but more (p less than .05) than in group A.(ABSTRACT TRUNCATED AT 250 WORDS)


'Total pain', disciplinary power and the body in the work of Cicely Saunders, 1958-1967.
Pain first emerged as an area of clinical specialisation in the 1950s, but more recently has attracted wider interest from social scientists and clinicians who seek to expand its understanding to incorporate ideas about meaning, embodiment and culture. So far there have been few empirical studies which focus on how ideas and practices about pain are changing in modern healthcare. This paper addresses these issues through a specific case study of the early writings of Cicely Saunders in the period 1958-1967. A professional training in the three disciplines of nursing, social work and medicine, coupled with a strong personal religious faith, provided the biographical context for the development of Cicely Saunders' concern with pain. Through these influences we find in her work with dying patients an emphasis on pain as a key which unlocks other problems and as something which requires multiple interventions for its resolution. From here the concept of 'total pain' is formulated, to include physical, psychological, social, emotional and spiritual elements. This concept, which proved so important to the development of hospice clinical practice, is shown to have paradoxical and conflicting implications. Adopting current ideas about the social theory of the body, 'total pain' may be formulated either as a nomenclature of inscription, or as a nomenclature of facilitation. It is suggested that both of these may be at work in the discourse of 'total pain' and that an appreciation of each enhances our understanding of the concept.


The pro-apoptotic substance thapsigargin selectively stimulates re-growth of brain capillaries.
Thapsigargin is a pro-apoptotic chemical, which has been shown to be useful to study cell death of cholinergic or dopaminergic neurons, or cells, which degenerate in Alzheimer's disease or Parkinson's disease, respectively. The aim of the present work was to study the effects of thapsigargin in the well established organotypic brain co-slice model composed of the basal nucleus of Meynert (nBM), ventral mesencephalon (vMes), dorsal striatum (dStr) and parietal cortex (Ctx). Cholinergic acetyltransferase-positive neurons in the nBM and dStr and dopaminergic tyrosine hydroxylase-positive neurons in the vMes survived, when cultured for 4 weeks with nerve growth factor and glial cell line-derived neurotrophic factor. Nerve fibers of cholinergic nBM neurons grew into the cortex and dopaminergic nerve fibers sprouted into dopamine D2 receptor-positive dStr. The whole co-slice contained a dense laminin-positive capillary network. Treatment of co-cultures with 3 microM thapsigargin for 24 hr significantly decreased the number of cholinergic neurons and dopaminergic neurons. This cell death displayed apoptotic DAPI-positive malformed nuclei and enhanced TUNEL-positive cells. Thapsigargin selectively stimulated the laminin-positive capillary growth between the nBM and Ctx. In conclusion, the induced cell death of cholinergic and dopaminergic neurons may be accompanied by enhanced angiogenic activity.


Early effects of dexamethasone and anti-VEGF therapy in an inflammatory corneal neovascularization model.
Inflammatory angiogenesis is the pathogenic mechanism of various sight-threatening eye diseases, among them corneal neovascularization. Current treatment options include steroids which have undesirable side effects, or anti-VEGF which has only limited efficacy. In an inflammatory environment, however, angiogenesis can be stimulated by numerous factors not directly targeted by anti-VEGF therapy. The aim of this study was to induce corneal inflammation leading to angiogenesis, and investigate the early, differential effects of steroid and anti-VEGF therapy at the cellular, tissue, and gene expression levels. Fifty-two Wistar rats received a single intrastromal corneal suture to induce a controlled inflammatory angiogenic response. Rats were subsequently treated with dexamethasone, rat specific anti-VEGF, or goat IgG (control), topically 4 times daily for 7 days. In vivo confocal microscopy of the cornea was performed longitudinally from 5 h up to 7 d to investigate morphology at the cellular and tissue-level. In vivo photographic vessel analysis and immunohistochemistry were also performed. RT-PCR for VEGF-A, FGF-2, IL-6, TNF-α, CXCL2, CCL2, CCL3 and DLL4 was performed at 24 h, and for VEGF-A, IL-6, TNF-α, FGF-2, CXCL2, CCL2, and CCL3 at 7 days. Early infiltration of CD11b + myeloid cells into the cornea at 5 h post-suture was delayed by both treatments relative to controls; however neither treatment was able to suppress accumulation of myeloid cells at day 2 or 7. Limbal vessel dilation was inhibited at 5 h by both treatments, but only dexamethasone showed sustained effect until day 2. Early macrophage recruitment was also suppressed by dexamethasone (but not by anti-VEGF) until day 2. Dexamethasone furthermore suppressed corneal neovascularization at day 7 by over 90%, whereas suppression by anti-VEGF was 14%. Despite differential suppression of vessel dilation, macrophage recruitment, and vascular invasion, anti-VEGF and dexamethasone both down-regulated VEGF-A and IL-6 expression at 24 h with sustained effect to 7 d. They also both down regulated FGF-2 and TNF-α at 24 h and CCL2 at 7 d. In conclusion, anti-angiogenic treatments influence early, pre-angiogenic tissue activity such as limbal vessel dilation, inflammatory cell infiltration of the stroma, and macrophage recruitment. Importantly, the differential effects of steroids and anti-VEGF treatment in suppressing neovascular growth could not be attributed to differential inhibition of several major angiogenic and inflammatory factors in the early pre-sprouting phase, including IL-6, VEGF-A, FGF-2, TNF-α, CCL2, CCL3, CXCL2, or DLL4.


Nano-selenium alleviates cadmium-induced cerebellar injury by activating metal regulatory transcription factor 1 mediated metal response.
This study aims to investigate the role of metal regulatory transcription factor 1 (MTF1)-mediated metal response in cadmium (Cd)-induced cerebellar injury, and to evaluate the antagonistic effects of nano-selenium (Nano-Se) against Cd toxicity. A total of 80 chicks (1 d old, male, Hy-Line Variety White) were randomly allocated to 4 treatment groups for 3 months: the control group (fed with a basic diet, n = 20), the Nano-Se group (basic diet with 1 mg/kg nano-Se 1 mg/kg Nano-Se in basic diet, n = 20), the Nano-Se + Cd group (basic diet with 1 mg/kg Nano-Se and 140 mg/kg CdCl2, n = 20) and the Cd group (basic diet with 140 mg/kg CdCl2 , n = 20). The results of the experiment showed that the Purkinje cells were significantly decreased with their degradation and indistinct nucleoli after Cd exposure. Moreover, exposure to Cd caused a significant accumulation of Cd and cupper. However, the contents of Se, iron, and zinc were decreased, thereby disturbing the metal homeostasis in the cerebellum. The Cd exposure also resulted in high levels of malondialdehyde (MDA) and down regulation of selenoprotein transcriptome. Furthermore, the expressions of MTF1, metallothionein 1 (MT1), MT2, zinc transporter 3 (ZNT3), ZNT5, ZNT10, zrt, irt-like protein 8 (ZIP8), ZIP10, transferrin (TF), ferroportin 1 (FPN1), ATPase copper transporting beta (ATP7B), and copper uptake protein 1 (CTR1) were inhibited by Cd exposure. However, all these changes were significantly alleviated by the supplementation of Nano-Se. This study proved that Cd could disorder metal homeostasis and induce oxidative stress, whereas Nano-Se could relieve all these negative effects caused by Cd via activating the MTF1-mediated metal response in the cerebellum of chicken.


IL-4 inhibits IL-2 synthesis and IL-2-induced up-regulation of IL-2R alpha but not IL-2R beta chain in CD4+ human T cells.
There is growing evidence to suggest a regulatory role of IL-4 in the immune system affecting both proliferation and lymphokine production. In the present work we have analyzed the effect of IL-4 on IL-2 and IFN-gamma synthesis by stimulating CD4+ human T cells (+10% accessory cells) with Con A in the presence of several doses (1 to 100 U/ml) of human rIL-4. The results showed an impaired IL-2 and IFN-gamma synthesis in the presence of IL-4. This inhibition was dose dependent and was evident only when IL-4 was added in the first 2 h of culture. Moreover, the external addition of IL-2 did not revert the inhibitory effect of IL-4 on IL-2 and IFN-gamma synthesis induced by Con A. We have also analyzed the effect of IL-4 on the expression of both alpha- and beta-chains of the IL-2R. Although the expression of IL-2R alpha mRNA was not modified after 6 h in culture in the presence of IL-4, a decrease was observed at 24 and 48 h. The addition of rIL-2 showed that the inhibition in IL-2R alpha expression could be explained by an impairment in the up-regulatory signal transmitted through the IL-2R. In addition to this, IL-4 did not modify the IL-2R beta mRNA expression at 6 and 24 h although a decreased expression was observed at 48 h which could be explained by the defective IL-2 production. The differential effect of IL-4 on the up-regulatory effect of IL-2 in the expression of IL-2R alpha and IL-2R beta suggest the existence of different regulatory mechanisms acting on the expression of both chains.


Purification and immunological characterization of recombinant antigens expressed in the form of insoluble aggregates (inclusion bodies).
In the field of clinical diagnosis the determination of specific antibodies against distinct structural or functional antigenic proteins of a given pathogen is the most commonly used diagnostic tool for the detection of infections. Although most of the established test systems still use natural antigen from different sources, the advent of nucleic acid engineering opens up the possibility of producing proteins of limited natural availability as well as designing novel proteins using in vitro mutagenesis techniques. Recombinant technology has already proven to be an excellent alternative for the production of specific antigens, that are able to improve sensitivity as well as specifity. In general, the production of recombinant antigens for diagnostic purposes is inexpensive compared to the use of purified natural antigens. The major problems associated with the setup of recombinant test systems are, of course, the identification of those antigens or antigenic determinants that guarantee a safe serological diagnosis (see Chapter 1 and Chapter 2 ) and the expression of these fragments with high efficiency.


Development of a Reference Model for Keratoconus Progression Prediction Based on Characterization of the Course of Nonsurgically Treated Cases.
To evaluate and characterize long-term clinical changes in keratoconus cases not requiring surgical treatment because of the absence of clinically significant visual degradation and to design a predictive model for the progression rate. This retrospective longitudinal study enrolled 68 nonsurgically treated keratoconic eyes of 46 patients (age range, 18-66 years), with a follow-up period of 6 years ± 12 months. Visual, refractive, topographic, and aberrometric changes were evaluated, detecting the abnormal levels of longitudinal changes in each clinical variable analyzed (percentiles 10% or 90%). Subsequently, the eyes were stratified into progression and no-progression groups based on the different variables evaluated, analyzing baseline differences between them. A progression index (PI%) was defined, and its relationship with baseline data was modeled using multiple linear regression analysis. Significant differences were detected in more quantity of baseline parameters between progression and no-progression groups for changes in sphere, spherical-like and coma-like root mean square, central mean keratometry (KM3mm), corneal asphericity (Q80mm), and central astigmatism (Ast3mm). The progression index (PI%) was defined using these variables, obtaining a mean value of 24.39 ± 51.09% and a median of 1.85%. This parameter was significantly related to the baseline sphere, K23 mm (steepest central keratometry), and Q80 mm (P < 0.001, R = 0.429). More pronounced progression seems to be present in myopic eyes with central localized steepening but normal mid-periphery flattening. A new index has been defined to characterize and predict the level of progression in nonsurgically treated keratoconus in a medium-long term.


The neuroprotective effect of Sulindac after ischemia-reperfusion injury in rats.
To investigate the neuroprotective effects of Sulindac on the hippocampal complex after global cerebral ischemia/reperfusion (I/R) injury in rats. Thirty one Sprague-Dawley rats were used, distributed into group I (sham) n:7 were used as control. For group II (n:8), III (n:8) and IV (n:8) rats, cerebral ischemia was performed via the occlusion of bilateral internal carotid artery for 45 minutes and continued with reperfusion process. 0.3 mL/kg/h 0.9 % sodium chloride was infused intraperitoneally to the Group II rats before ischemia, 5μg/kg/h/0.3 ml sulindac was infused intraperitoneally to the Group III rats before ischemia and 5μg/kg/h/0.3 ml sulindac was infused intraperitoneally to the Group IV rats after ischemia and before reperfusion process. The levels of MDA, GSH and MPO activity were measured in the left hippocampus tissue. The hippocampal tissue of all group members were taken for histopathological study. The MDA and MPO levels increased from group I (control) to group II (I/R) (P<0.05) and decreased from group II (I/R) to group III (presulindac + I/R) and IV (postsulindac + I/R) (P<0.05). Beside these, the GSH levels decreased from group I (control) to group II (I/R) (P<0.05) and increased from group II (I/R) to group III (presulindac + I/R) and IV (postsulindac + I/R) (P<0.05).The number of apoptotic neurons increased from group I (control) to group II (I/R) (P<0.05) and decreased from group II (I/R) to group III (presulindac + I/R) and IV (postsulindac + I/R) (P<0.05). The Sulindac may have neuroprotective effects on ischemic neural tissue to prevent the reperfusion injury after ischemia.


Current results of surgical therapy for chronic mesenteric ischemia.
Although recognition of chronic mesenteric ischemia has increased in recent years, this disorder has continued to present diagnostic and therapeutic challenges. To examine the modern results of surgical revascularization for chronic mesenteric ischemia. Retrospective review. University medical center. The management of 24 consecutive patients (mean +/- SEM age, 58 +/- 3 years; 5 men, 19 women) who were undergoing surgical treatment of chronic mesenteric ischemia between 1986 and 1996 was reviewed. Surgical mesenteric revascularization. Postoperative course, long-term graft patency rate, and long-term symptom-free survival rate. The most frequent presenting symptoms were postprandial abdominal pain (18 patients [75%]) and weight loss (14 patients [58%]). Less specific complaints included nausea and vomiting (8 patients [33%]), diarrhea (7 patients [29%]), and constipation (4 patients [17%]). Atherosclerotic risk factors were common, including tobacco use (20 patients [83%]), coronary artery disease (10 patients [42%]), and hypertension (10 patients [42%]). The cause was identified as atherosclerosis in 21 patients, median arcuate ligament compression in 2 patients who were monozygotic twins, and Takayasu arteritis in 1 patient. Lesions were localized to all 3 major visceral vessels (celiac artery, superior mesenteric artery [SMA], and inferior mesenteric artery) in 8 patients, celiac artery and SMA in 13, SMA alone in 2, and SMA and inferior mesenteric artery in 1. Seventeen patients underwent antegrade reconstructions from the supraceliac aorta to the SMA and/or celiac artery; 7 patients underwent revascularization by use of a retrograde bypass that originated from the infrarenal aorta or a prosthetic graft. There were no perioperative deaths although 1 patient died in the hospital 6 weeks after early graft failure and sepsis (overall in-hospital mortality, 4%). Follow-up ranged from 3 months to 10 years (median, 2.4 years). The mean +/- SEM 5-year primary graft patency rate, as objectively documented by use of contrast angiography or duplex scanning in 19 of 24 patients, was 78% +/- 11%. Primary failure was documented in 3 patients (at 3 weeks, 5 months, and 7 months). Two patients required a thrombectomy; 1 of these patients subsequently died of an intestinal infarction. The mean +/- SEM 5-year survival rate by use of life-table analysis was 71% +/- 11%. No patient with a patent graft experienced a symptomatic recurrence. Chronic mesenteric ischemia is usually a manifestation of advanced systemic atherosclerosis. Symptoms almost always reflect midgut ischemia in the distribution of the SMA. An antegrade bypass from the supraceliac aorta can be performed with acceptable operative morbidity and is currently the preferred reconstructive technique. Surgical revascularization affords long-term symptom-free survival in a majority of patients with chronic mesenteric ischemia.


The differential expression of mgl mRNA by Porphyromonas gingivalis affects the production of methyl mercaptan.
A large number of individuals have halitosis. The total amount of volatile sulfur compounds, which are the main cause of halitosis, has been correlated with periodontitis following bacterial infection. In this study, Porphyromonas gingivalis (Pg), a major periodontopathogenic bacterium, was isolated from patients with halitosis by the amplification of 16S rRNA, and the ability of isolated Pg to produce methyl mercaptan (CH3 SH) was determined to clarify the relationship between halitosis and Pg infection. CH3 SH concentrations were measured in patients using Oral Chroma. The production of CH3 SH by Pg standard and clinical strains was also measured in vitro. Real-time PCR was performed to compare the expression of mgl mRNA (which encoded l-methionine-a-deamino-g-mercaptomethane-lyase) among the Pg strains. The production of CH3 SH and the expression of mgl mRNA were also determined to assess the effects of oriental medicine. The production of CH3 SH and the expression of mgl mRNA strongly correlated with each other in the presence of l-methionine. The expression of mgl mRNA by Pg W83 was strongly inhibited by magnoliaceae. The production of CH3 SH was correlated with the expression of mgl. Furthermore, the oriental medicine, magnoliaceae, may represent a potential treatment for halitosis.


Developing patient reference groups within general practice: a mixed-methods study.
Clinical commissioning groups (CCGs) are required to demonstrate meaningful patient and public engagement and involvement (PPEI). Recent health service reforms have included financial incentives for general practices to develop patient reference groups (PRGs). To explore the impact of the patient participation direct enhanced service (DES) on development of PRGs, the influence of PRGs on decision making within general practice, and their interface with CCGs. A mixed-methods approach within three case study sites in England. Three case study sites were tracked for 18 months as part of an evaluation of PPEI in commissioning. A sub-study focused on PRGs utilising documentary and web-based analysis; results were mapped against findings of the main study. Evidence highlighted variations in the establishment of PRGs, with the number of active PRGs via practice websites ranging from 27% to 93%. Such groups were given a number of descriptions such as patient reference groups, patient participation groups, and patient forums. Data analysis highlighted that the mode of operation varied between virtual and tangible groups and whether they were GP- or patient-led, such analysis enabled the construction of a typology of PRGs. Evidence reviewed suggested that groups functioned within parameters of the DES with activities limited to practice level. Data analysis highlighted a lack of strategic vision in relation to such groups, particularly their role within an overall patient and PPEI framework). Findings identified diversity in the operationalisation of PRGs. Their development does not appear linked to a strategic vision or overall PPEI framework. Although local pragmatic issues are important to patients, GPs must ensure that PRGs develop strategic direction if health reforms are to be addressed.


Optimal median-type filtering under structural constraints.
This paper presents a method for the design of median-type filters that achieve the maximum noise attenuation under structural constraints imposed by the requirement of preserving certain signal or image features. As compared with the design of optimal weighted median (WM) filters that calls for solving a set of linear inequalities, this method is extremely simple yet general enough. The filter is obtained by modifying directly the Boolean function of a median filter, and an analytic, closed-form representation of its Boolean function can be obtained. Furthermore, it is proven theoretically that under the same set of structural constraints, the filter designed in this way will never do worse in removing i.i.d. noise with any distribution than the optimal WM filter-improvements as high as 41, 46, and 52% have been achieved in simulations in a 2-D case for the uniform, Gaussian, and double-exponential distributions, respectively. Also, the improvement in the impulsive noise environment is very significant, as is demonstrated by an image enhancement application.


Perception of disease severity in adult patients with cystic fibrosis.
To evaluate the perception of disease severity in patients with cystic fibrosis (CF), investigating its relationship with clinical score, radiographic score, respiratory function tests, adherence to treatment and perception of self-care practices. Prospective, cross-sectional study involving CF patients treated in a program for adults with CF. The perception of disease severity, adherence to treatment and reported self-care practices were evaluated by means of questionnaires. Clinical data, Shwachman-Kulczycki clinical score, Brasfield radiographic score and spirometry were obtained for all of the patients. Of the 38 patients studied, 3 (7.9%) patients rated their perception of health status as well below average; 5 (13.2%), as below average; 15 (39.5%), as average; 10 (26.3%), as above average; and 5 (13.2%), as well above average. The perception of disease severity correlated significantly with clinical score (r = 0.43, p = 0.007), FVC (r = 0.34, p = 0.034), FEV1 (r = 0.38, p = 0.019) and self-care practices (r = 0.33, p = 0.044), but not with degree of adherence (r = -0.03, p = 0.842) and radiographic score (r = 0.33, p = 0.51). The perception of disease severity correlated with objective measurements of disease severity (clinical score and respiratory function tests) and with reported self-care practices, but not with adherence to treatment.


Postnatal renal adaptation in preterm and term lambs.
The present experiments determined if increases in renal reabsorptive capacity during the transition from fetal to neonatal life are gestation dependent. Renal function was studied in chronically-catheterized fetal lambs (133 +/- 1 days; term, 145-150 days). Additionally, renal function was studied in anaesthetized, ventilated, caesarean-delivered preterm lambs (109-139 days gestation) and term lambs (148 days gestation), and in 2-day-old spontaneously-delivered term lambs. Newborns < or = 120 days old received surfactant to facilitate ventilation and maintenance of physiologic blood gases. Two hours after caesarian delivery, urine osmolality, urine flow, glomerular filtration rate (GFR), and fractional sodium excretion (FENa) values were similar for all gestations. Relative to fetal values, caesarean-delivered newborn renal values included lower urine flow rates (0.20 +/- 0.03 v. 0.05 +/- 0.01 mL min-1 kg-1), higher urine osmolalities (118 +/- 15 v. 422 +/- 16 mOsmol kg-1 H2O), and no differences in GFR or FENa. Relative to caesarean-delivered newborns, 2-day newborn renal function included higher values for GFR (0.7 +/- 0.1 v. 3.0 +/- 0.1 mL min-1 kg-1) and urine osmolality (724 +/- 32 mosmol kg-1 H2O), and lower FENa (7.0 +/- 1.5 v. 0.2 +/- 0.02%), and urine flow (0.005 +/- 0.003 mL min-1 kg-1). The 132- and 139-day animals were ventilated for 5 h and 10 h respectively; the only functional change at 10 h was a decrease in FENa (7.0 +/- 1.5 v. 2.8 +/- 0.1%). It is concluded that: (1) relative to fetal animals, renal adaptive responses in anaesthetized, ventilated newborns begin within 2 h following caesarian delivery; (2) initial adaptive responses are not gestation dependent after 109 days; and (3) the combined effects of ventilation and/or anaesthesia delay postnatal renal adaptations for at least 10 h after birth.


Caffeine Uptake into the Vitreous after Peroral Coffee Consumption.
Caffeine and its metabolites have antioxidant activity, scavenging reactive oxygen species. The aim of our study was to measure caffeine concentrations in vitreous samples after peroral caffeine intake. This prospective study included patients scheduled for 23-G pars plana vitrectomy with membrane peeling due to epiretinal membranes. The study was performed in two parts: in the first part, patients were recruited into three different groups: group A consisted of habitual coffee drinkers who agreed to drink coffee containing 180 mg caffeine 1 h before surgery (n = 10), group B consisted of habitual coffee drinkers who were not offered coffee before surgery (n = 5), and group C consisted of non-habitual coffee drinkers, forming the control group (n = 5). In the second part (group D) patients (habitual coffee drinkers) agreed to give additional blood serum samples for measurement of caffeine concentration. Harvested samples of vitreous (groups A-D), epiretinal membranes (groups A-C), and blood serum samples (group D) were examined for concentrations of caffeine with gas chromatography-mass spectrometry. Samples of 40 eyes of 40 patients were harvested. The concentrations of caffeine in the vitreous samples were 1,998 ± 967 ng/mL in group A and 1,108 ± 874 ng/mL in group B. In group C, caffeine concentrations were below 176 ng/mL in all vitreous samples. Both groups A and B had significantly higher concentrations of caffeine in the vitreous samples than group C (p < 0.002, p < 0.01, Mann-Whitney U test). Caffeine concentrations in epiretinal membranes were below the limits of detection. Correlation of caffeine concentrations between blood serum samples and vitreous samples in group D was high, with significantly higher caffeine concentrations in the blood serum. Coffee consumption leads to significant caffeine levels in the vitreous compared to patients in the control group, and caffeine concentrations in the vitreous showed a high correlation to blood serum concentrations of caffeine after peroral coffee consumption.


PACAP neuropeptide promotes Hepatocellular Protection via CREB-KLF4 dependent autophagy in mouse liver Ischemia Reperfusion Injury.
Organ ischemia reperfusion injury (IRI), associated with acute hepatocyte death, remains an unresolved problem in clinical orthotopic liver transplantation (OLT). Autophagy, an intracellular self-digesting progress, is responsible for cell reprograming required to regain post-stress homeostasis. Methods: Here, we analyzed the cytoprotective mechanism of pituitary adenylate cyclase-activating polypeptide (PACAP)-promoted hepatocellular autophagy in a clinically relevant mouse model of extended hepatic cold storage (4 °C UW solution for 20 h) followed by syngeneic OLT. Results: In contrast to 41.7% of liver graft failure by day 7 post-transplant in control group, PACAP treatment significantly improved graft survival (91.7% by day 14), and promoted autophagy-associated regeneration programs in OLT. In parallel in vitro studies, PACAP-enhanced autophagy ameliorated cellular damage (LDH/ALT levels), and diminished necrosis in H2O2-stressed primary hepatocytes. Interestingly, PACAP not only induced nuclear cAMP response element-binding protein (CREB), but also triggered reprogramming factor Kruppel-like factor 4 (KLF4) expression in IR-stressed OLT. Indeed, CREB inhibition attenuated hepatic autophagy and recreated hepatocellular injury in otherwise PACAP-protected livers. Furthermore, CREB inhibition suppressed PACAP-induced KLF4 expression, whereas KLF4 blockade abolished PACAP-promoted autophagy and neutralized PACAP-mediated hepatoprotection both in vivo and in vitro. Conclusion: Current study documents the essential neural regulation of PACAP-promoted autophagy in hepatocellular homeostasis in OLT, which provides the emerging therapeutic principle to combat hepatic IRI in OLT.


The epidemiology of schistosomiasis in Egypt: Qalyubia Governorate.
The primary objectives of this study, carried out in Qalyubia Governorate in Egypt (south-central Nile Delta), were to continue tracking historical trends of infection prevalence of Schistosoma mansoni and S. haematobium, determine whether satellites (ezbas) of mother villages differed significantly with respect to schistosomiasis transmission, and to asses schistosomiasis-induced morbidity on a population basis using ultrasonography. Our study revealed that S. haematobium has virtually disappeared from Qalyubia governorate, and that S. mansoni prevalence continues to decline slowly (17% in 1991 compared with 19% in 1990). The prevalence of intestinal schistosomiasis was actually higher in the mother villages than in the ezbas of the same villages, indicating that prevalence based on surveys of villages alone did not (at least for Qalyubia) cause underestimates of true prevalence. (A mother village is the large village in an area that includes hamlets or ezbas. In many areas, the infection rate in ezbas is significantly higher than in the larger central village.) Ultrasonographic studies revealed that less than 3% of the population had stage 2 or stage 3 periportal fibrosis, commonly associated with chronic schistosomiasis mansoni. This low level of morbidity was consistent with earlier data from Qalyubia, which also showed a low level of S. mansoni-induced morbidity in this governorate.


Prevalence and aetiology of cataract in Punjab.
Three districts in the Punjab plains were surveyed in 1976-7 for senile cataract and potential risk factors. The prevalence of senile cataract was 15.3% among 1269 persons examined who were aged 30 ang older, and 4.3% for all ages. These figures confirmed previous reports of high prevalence. The prevalence was 1% for ages 30-49 and increased markedly in the sixth and seventh decades to 67% for ages 70 and older. Univariate age-adjusted analyses of selected socioeconomic, demographic, dietary, and other variables suggested that a higher prevalence was associated with being widowed, low education, use of rock salt in cooking, infrequent consumption of various protein foods (beans and lentils, milk, eggs, and curd), short height, and low weight. Multivariate analysis further suggested low total protein consumption as a risk factor that may account for as much as 40% of the excess prevalence of Punjab cataract over that in a US population study.


Death of a sibling: five sisters, five stories.
The sudden, unexpected death of a child is likely to have profound and enduring implications for surviving siblings. In this article, stories from five sisters are presented to demonstrate how children's experiences of and responses to the death of a sibling can vary greatly, even within the same family. Each child creates his or her own reality, and this "unique" definition of reality influences the child's behavior. Giving children a chance to "tell their stories" may help nurses and other professionals to understand the meanings and values that are guiding how children respond following the unexpected death of a sibling.


The "mini-perc" technique: a less invasive alternative to percutaneous nephrolithotomy.
The disadvantages of standard percutaneous nephrolithotomy (PCNL) as compared with ureteroscopy or extracorporeal shock-wave lithotripsy include increased blood loss, greater pain, and longer hospital stay. A 13-Fr "mini-perc" technique using a ureteroscopy sheath for PCNL was developed in an attempt to address these drawbacks. Nine "mini-percs" have been performed in patients aged 40-73 years with stone burdens of < or = 2 cm2. On average, patients had 1.4 stones with a cross-sectional area of 1.5 cm2. The mean total procedure time, estimated blood loss, and hematocrit decrease were 176 min, 83 ml, and 6.6%, respectively. On average, patients used 14 mg of parenteral morphine and stayed 1.7 days in the hospital. There was no procedure-related complication or transfusion. Eight of nine kidneys (89%) were stone-free on early follow-up at a mean of 3.8 weeks. As compared with standard PCNL, the "mini-perc" technique has similar early success rates in selected patients and may offer advantages with respect to hemorrhage, postoperative pain, and shortened hospital stays.


Reversal of learned helplessness by morphine in rats: involvement of a dopamine mediation.
The aim of this study was to examine the role of dopamine neurotransmission in the effects of morphine in the learned helplessness paradigm in rats, a generally recognized model of depression. In this model, rats first exposed to inescapable shocks (stressed rats) exhibited an escape deficit in a subsequent shuttle-box test performed 48 h later for 3 consecutive days. The numbers of escape failures and intertrial crossings (motor activity during each intertrial interval) were recorded. Morphine was injected twice daily for 5 days (6 mg/kg/day, s.c.), and haloperidol, a preferential D2-dopamine receptor antagonist, was injected i.p. 15 min before each shuttle-box session. At the highest dose tested (150 microg/kg) haloperidol mimicked the behavioral deficit produced by inescapable shocks. A 37.5 microg/kg dose of haloperidol, which was ineffective by itself, reversed the morphine-induced improvement of escape behavior in previously stressed rats and the morphine-induced increase in intertrial activity in both stressed and nonstressed animals. These results support roles (a) for a dysregulation of dopaminergic neuronal activity in the expression of escape deficit subsequent to an inescapable aversive situation, and (b) for a dopaminergic mediation in the effects of morphine in the learned helplessness paradigm.


Backbone Engineered γ-Peptide Amphitropic Gels for Immobilization of Semiconductor Quantum Dots and 2D Cell Culture.
We are reporting a spontaneous supramolecular assembly of backbone engineered γ-peptide scaffold and its utility in the immobilization of semiconductor quantum dots and in cell culture. The stimulating feature of this γ-peptide scaffold is that it efficiently gelates both aqueous phosphate buffers and aromatic organic solvents. A comparative and systematic investigation reveals that the greater spontaneous self-aggregation property of γ-peptide over the α- and β-peptide analogues is mainly due to the backbone flexibility, increased hydrophobicity, and π-π stacking of γ-phenylalanine residues. The hydrogels and organogels obtained from the γ-peptide scaffold have been characterized through field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), FT-IR, circular dichroism (CD), wide-angle X-ray diffraction, and rheometric study. Additionally, the peptide hydrogel has displayed a stimuli-responsive and thixotropic signature, which leads to the injectable hydrogels. 2D cell culture studies using normal and cancer cell lines reveal the biocompatibility of γ-peptide hydrogels. Further, the immobilization of semiconductor core-shell quantum dots in the transparent γ-peptide organogels showed ordered arrangement of quantum dots along the peptide fibrillar network with retaining photophysical property. Overall, γ-peptide scaffolds may serve as potential templates for the design of new functional biomaterials.


Particle-mediated gene transfer of opioid growth factor receptor cDNA regulates cell proliferation of the corneal epithelium.
This study was designed to determine at the molecular level whether interactions between the opioid growth factor (OGF) and OGF receptor (OGFr) play a role in regulating DNA synthesis in the homeostasis of the corneal epithelium. The plasmid pcDNA3.1+OGFr-HA, carrying the rat OGFr cDNA epitope-tagged with a C-terminal hemagglutinin (HA), or the empty-vector (pcDNA3.1+), was delivered twice by the Helios Gene Gun System at 300 psi to the cornea of anesthetized rats. The contralateral (untreated) cornea served as the naive specimen. BrdU was used to determine whether the recombinant OGFr was effective in regulating DNA synthesis in the rat peripheral corneal epithelium. Within 18 hours of transfection, positive HA staining was apparent in both the basal and suprabasal layers (efficiency > 90% of the cells) throughout the central and peripheral cornea. Quantitative immunohistochemistry with rhodamine-conjugated anti-OGFr antibodies revealed twofold more OGFr expression in the central and peripheral epithelium of transfected corneas relative to naive corneas. The number of BrdU-positive basal cells in the peripheral epithelium of the transfected cornea was one-third of that in the naive cornea. These data demonstrate the direct role of the OGF-OGFr system in determining cellular renewal in the mammalian corneal epithelium. Moreover, the successful establishment of a novel delivery system of cDNAs to the ocular surface suggests a therapeutic role for gene therapy in the eye.


[Effect of water immersion on indices of central hemodynamics in subjects older than 45 years].
The effect of 7-day dry immersion on central hemodynamics of four test subjects, aged 46, with boundary arterial hypertension was investigated. The controls were two healthy men, aged 24. Central hemodynamics was examined by integrated rheography. Variations in blood pressure, central venous pressure, stroke and cardiac indexes, heart rate and total peripheral resistance were measured. The control subjects showed a decrease of blood pressure during exposure (P less than 0.01). Two of the test subjects with a short history of boundary arterial hypertension displayed similar variations (P less than 0.01), whereas two others showed an increase of blood pressure during the immersion period (P less than 0.01). The test and control subjects did not exhibit significant differences in the stroke and cardiac indexes, heart rate, central venous pressure or total peripheral resistance: stroke and cardiac indexes decreased while central venous pressure and total peripheral resistance increased, and heart rate remained unchanged.


Impact on perioperative outcomes of concomitant hiatal hernia repair with laparoscopic gastric bypass.
The role of laparoscopic hiatal hernia repair (LHHR) at the time of laparoscopic Roux-en-y gastric bypass (LRYGB) is still debatable. This study aims to assess the safety of concomitant LHHR with LRYGB. This study is a multi-center, retrospective analysis of a large administrative database. The University Health System Consortium (UHC) is a group of 112 academic medical centers and 256 of their affiliated hospitals. The UHC database was queried using International Classification of Diseases-9 codes and main outcome measures were analyzed. From October 2006 to January 2010, we found 33,717 patients who underwent LRYGB and did not have a hiatal hernia. In this same time period, 644 patients underwent concomitant LRYGB and LHHR, while 1,589 patients underwent LRYGB without repair of their hiatal hernias. On comparison of patients undergoing LRYGB with simultaneous LHHR with those who underwent LRYGB without a diagnosis of HH, there was no significant difference in mortality, morbidity, length of stay (LOS), 30-day readmission, or cost shown. On comparison of patients with HH who underwent LRYGB and simultaneous LHHR with those who had LRYGB without LHHR, no significant difference with regards to all the outcome measures was also shown. In conclusion, concomitant hiatal hernia repair with LRYGB appears to be safe and feasible. These patients did not have any significant differences in morbidity, mortality, LOS, readmission rate, or cost. Randomized controlled studies should further look into the benefit of hiatal hernia repair in regards to reflux symptoms and weight loss for LRYGB patients.


Biocompatible copper formate-based nanoparticles with strong antibacterial properties for wound healing.
Copper-based antibacterial materials have emerged as a potential alternative for combating bacterial infections, which continue to pose significant health risks. Nevertheless, the use of copper-based nanoparticles as antibacterial agents has faced challenges due to their toxicity towards cells and tissues. To overcome this obstacle, we propose a new approach using a contact-active copper-based nanoparticles called polydopamine (PDA)-coated copper-amine (Cuf-TMB@PDA). The positively charged surface of Cuf-TMB@PDA enables efficient targeting of negatively charged bacteria, allowing controlled release of Cu(II) into the bacterial cell membrane. Moreover, Cuf-TMB@PDA exhibits similar ·OH signals as Cuf-TMB suspensions in previous work. In cytotoxicity assays conducted over 72 h, Cuf-TMB@PDA demonstrated an efficacy of 98.56%, while releasing lower levels of Cu(II) that were less harmful to cells, resulting in enhanced antimicrobial effects. These antimicrobial properties are attributed to the synergistic effects of charge-contact activity of PDA, controlled release of Cu(II), and free radicals. Subsequent in vivo experiments confirmed the strong antimicrobial potency of Cuf-TMB@PDA and its ability to promote wound healing.


Neonatal sepsis in low-income countries: epidemiology, diagnosis and prevention.
Introduction: Sepsis accounts for up to one-third of neonatal deaths in the world each year. The World Health Organization acknowledges neonatal sepsis as a major global health concern, and that the highest burden occurs in low- and middle-income countries (LMICs). Despite major research and clinical progress in this area, we still lack accurate diagnostic tools for neonatal sepsis, complicating the management of this condition.Areas covered: The purpose here is to review the latest data on the incidence, diagnosis, prevention, and management of neonatal sepsis in LMIC. We discuss the limitations of current diagnostic tests - including their lack of availability - and how this may influence global estimates of cases. We review the benefits of antenatal, intrapartum, and post-natal preventive measures. We briefly discuss the management, highlighting the emergence of antimicrobial resistance. Finally, we expose some high priority areas.Expert opinion: Neonatal sepsis is a challenging condition requiring a multifaceted approach to address the major diagnostic issues, but also the underlying socio-economic causes that nourish epidemic cases in LMIC. Focusing on antibiotics as a main pillar of intervention is likely to engender antimicrobial resistance, eventually hindering the appreciable gains LMICs have achieved in neonatal health outcomes.


[A thromboelastographic method of determining the antiaggregation activity of the vascular wall].
Thromboelastography was used for the assessment of the vascular wall antiaggregation function; this function was determined as the activity of prostacyclin, synthesized and released by the vascular wall after local ischemia of the limb vessels, antiaggregatory towards the blood platelets. This method permits a rapid and easy objective assessment of the vascular wall antiaggregation function and gives information on the role of the blood ingredients, the prostacyclin activity contributing to their effect.


Black Ginseng and Ginsenoside Rb1 Promote Browning by Inducing UCP1 Expression in 3T3-L1 and Primary White Adipocytes.
In this study, we investigated the effects of black ginseng (BG) and ginsenoside Rb1, which induced browning effects in 3T3-L1 and primary white adipocytes (PWATs) isolated from C57BL/6 mice. BG and Rb1 suppressed the expressions of CCAAT/enhancer-binding protein alpha (C/EBPα) and sterol regulatory element-binding transcription factor-1c (SREBP-1c), whereas the expression level of peroxisome proliferator-activated receptor gamma (PPARγ) was increased. Furthermore, BG and Rb1 enhanced the protein expressions of the brown-adipocyte-specific markers PR domain containing 16 (PRDM16), peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α), and uncoupling protein 1 (UCP1). These results were further supported by immunofluorescence images of mitochondrial biogenesis. In addition, BG and Rb1 induced expressions of brown-adipocyte-specific marker proteins by AMP-activated protein kinase (AMPK) activation. BG and Rb1 exert antiobesity effects by inducing browning in 3T3-L1 cells and PWATs through AMPK-mediated pathway activation. We suggest that BG and Rb1 act as potential functional antiobesity food agents.


Effects of massage therapy of asthmatic children on the anxiety level of mothers.
Asthma is the most common chronic disease of childhood and its prevalence is increasing all over the world. Asthma influences on many aspects of family daily life. Health care of children with chronic asthma can have deep impact on health and welfare of the family members. Studies showed a relation between the life quality of children suffering from asthma and the anxiety level of parents. These parents are looking for ways to confront with their stress, to reduce their anxiety in encountering with their asthmatic children, and to improve their performance. This research was accomplished with the aim of determining the influence of massage therapy on anxiety level of mothers with asthmatic children. This was a quasi-experimental study with two groups and a pretest and posttest design. The samples of research were 60 mothers of 5-14 year-old asthmatic children who were under treatment in medical centers of Isfahan. They were randomly divided into two groups of control and massage therapy by convenience sampling method. The data were collected by standard Spielberger questionnaire. Mothers of massage group were trained to massage head, neck, face, shoulder, hand, leg, and back of their children every night before bedtime for one month while there was no intervention for the control group during this month except the standard treatment. In both groups, the Spielberger standard questionnaire was filled by mothers. The data were analyzed by descriptive analysis, independent t-test, paired-t test, and chi-square test. The results showed no significant difference in mean anxiety level between the two groups before the intervention but there was a significant difference between them after intervention (p < 0.03). Also, there was a significant difference in mean level of anxiety score of mothers before and after the intervention in massage group (p < 0.001). The anxiety level of mothers can be reduced by effective utilization of daily child massage therapy and giving an active role to the mothers in caring and treating the child. Daily massage helped mothers to have more sense of participation in caring their children and as a non-pharmacological method can be accompanied with pharmacological methods.


Effort, reward and self-reported mental health: a simulation study on negative affectivity bias.
In the present article, we propose an alternative method for dealing with negative affectivity (NA) biases in research, while investigating the association between a deleterious psychosocial environment at work and poor mental health. First, we investigated how strong NA must be to cause an observed correlation between the independent and dependent variables. Second, we subjectively assessed whether NA can have a large enough impact on a large enough number of subjects to invalidate the observed correlations between dependent and independent variables. We simulated 10,000 populations of 300 subjects each, using the marginal distribution of workers in an actual population that had answered the Siegrist's questionnaire on effort and reward imbalance (ERI) and the General Health Questionnaire (GHQ). The results of the present study suggested that simulated NA has a minimal effect on the mean scores for effort and reward. However, the correlations between the effort and reward imbalance (ERI) ratio and the GHQ score might be important, even in simulated populations with a limited NA. When investigating the relationship between the ERI ratio and the GHQ score, we suggest the following rules for the interpretation of the results: correlations with an explained variance of 5% and below should be considered with caution; correlations with an explained variance between 5% and 10% may result from NA, although this effect does not seem likely; and correlations with an explained variance of 10% and above are not likely to be the result of NA biases.


Cytotoxicity of citral against melanoma cells: The involvement of oxidative stress generation and cell growth protein reduction.
Citral is a natural compound that has shown cytotoxic and antiproliferative effects on breast and hematopoietic cancer cells; however, there are few studies on melanoma cells. Oxidative stress is known to be involved in all stages of melanoma development and is able to modulate intracellular pathways related to cellular proliferation and death. In this study, we hypothesize that citral exerts its cytotoxic effect on melanoma cells by the modulation of cellular oxidative status and/or intracellular signaling. To test this hypothesis, we investigated the antiproliferative and cytotoxic effects of citral on B16F10 murine melanoma cells evaluating its effects on cellular oxidative stress, DNA damage, cell death, and important signaling pathways, as these pathways, namely, extracellular signal-regulated kinases 1/2 (ERK1/2), AKT, and phosphatidylinositol-3 kinase, are involved in cell proliferation and differentiation. The p53 and nuclear factor kappa B were also investigated due to their ability to respond to intracellular stress. We observed that citral exerted antiproliferative and cytotoxic effects in B16F10; induced oxidative stress, DNA lesions, and p53 nuclear translocation; and reduced nitric oxide levels and nuclear factor kappa B, ERK1/2, and AKT. To investigate citral specificity, we used non-neoplastic human and murine cells, HaCaT (human skin keratinocytes) and NIH-3T3 cells (murine fibroblasts), and observed that although citral effects were not specific for cancer cells, non-neoplastic cells were more resistant to citral than B16F10. These findings highlight the potential clinical utility of citral in melanoma, with a mechanism of action involving the oxidative stress generation, nitric oxide depletion, and interference in signaling pathways related to cell proliferation.


Management of macular edema secondary to branch retinal vein occlusion: an evidence-based update.
Retinal vein occlusions are common retinal vascular disorders with the potential for significant vision-related morbidity. Retinal vein occlusions are classified as either branch retinal vein occlusion (BRVO), central retinal vein occlusion (CRVO), or hemiretinal vein occlusion (HRVO) based on the specific occlusion site. The most common cause of decreased vision in patients afflicted with BRVO is the accumulation of fluid within the macula (macular edema). The Branch Vein Occlusion Study (BVOS) demonstrated the efficacy of grid laser photocoagulation in the treatment of BRVO-related macular edema. After publication of that report, grid laser became the standard of care for decreased vision due to BRVO-associated macular edema in patients similar to those enrolled in the BVOS. However, several recent major randomized, controlled clinical trials have investigated new therapeutic modalities for the treatment of decreased vision due to macular edema secondary to BRVO. This article aims to provide insight into current evidence-based approaches to management of macular edema secondary to BRVO. A companion article reviews approaches for management of macular edema secondary to CRVO.


[Current Status and Prospects of Complement-Targeting Therapy for Neuromyelitis Optica].
Neuromyelitis optica (NMO) is clinically characterized by severe optic neuritis and long myelitis; and is associated with aquaporin-4 immunoglobulin-G (AQP4-IgG), an autoantibody directed against aquaporin-4 (AQP4), which is an astrocytic water channel protein. Until recent years, the treatment of NMO has mainly focused on the suppression of lymphocytes and depletion of autoantibodies. However, several studies on the pathogehesis of the disease in human pathology, cultured cells, and animal models have revealed that astrocyte injury in NMO is mainly caused by the complement-dependent cytotoxicity following AQP4-IgG binding to AQP4. Moreover, complement-targeting therapy has recently been translated into practical applications in several hematological disorders. and similary, also in the cases of NMO. In this article, we review the relevance of the complement system in the pathogenesis of NMO. Additionally, we review the current status and prospects of the complement-targeting therapy for NMO, including the clinical trials of eculizumab and C1 inhibitor for NMO, and the experimental studies on C1 inhibition by monoclonal antibodies.


The validity and heritability of self-report osteoarthritis in an Australian older twin sample.
In order to investigate the genetic and environmental antecedents of osteoarthritis (OA), self-report measures of joint pain, stiffness and swelling were obtained from a population-based sample of 1242 twin pairs over 50 years of age. In order to provide validation for these self-report measures, a subsample of 118 twin pairs were examined according to the American College of Rheumatology clinical and radiographic criteria for the classification of osteoarthritis. A variety of statistical methods were employed to identify the model derived from self-report variables which would provide optimal prediction of these standardised assessments, and structural equation modelling was used to determine the relative influences of genetic and environmental influences on the development of osteoarthritis. Significant genetic effects were found to contribute to osteoarthritis of the hands, hips and knees in women, with heritability estimates ranging from 30-46% depending on the site. In addition, the additive genetic effects contributing to osteoarthritis in various parts of the body were confirmed to be the same. Statistically significant familial aggregation of osteoarthritis in men was also observed, but it was not possible to determine whether this was due to genetic or shared environmental effects.


Patient-reported outcomes in KEYNOTE-006, a randomised study of pembrolizumab versus ipilimumab in patients with advanced melanoma.
Report results of patient-reported health-related quality of life (HRQoL) and symptoms from phase III KEYNOTE-006 study of pembrolizumab versus ipilimumab in patients with ipilimumab-naive advanced melanoma. Patients received pembrolizumab 10 mg/kg every 2 (Q2W) or every 3 weeks (Q3W) for up to 2 years, or four cycles of ipilimumab 3 mg/kg Q3W. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) was administered at baseline and throughout the study. Patient-reported outcome (PRO) analyses were pre-specified exploratory endpoints; the primary PRO assessment was the score change from baseline to week 12 in EORTC QLQ-C30 global health status (GHS)/HRQoL score between the arms using constrained longitudinal data analysis. The PRO analysis population included 776 patients: pembrolizumab Q2W (n = 270); pembrolizumab Q3W (n = 266); ipilimumab (n = 240). Baseline GHS was similar across arms. QLQ-C30 compliance rates at week 12 were 87% (n = 214), 97% (n = 226), and 96% (n = 178), for the pembrolizumab Q2W, pembrolizumab Q3W, and ipilimumab arms, respectively. From baseline to week 12, GHS/HRQoL scores were better maintained with pembrolizumab than with ipilimumab (decrease of -1.9 and -2.5 for pembrolizumab versus -10.0 for ipilimumab; p < 0.001 for each pembrolizumab arm versus ipilimumab). Fewer patients treated with pembrolizumab experienced deterioration in GHS at week 12 (31% for pembrolizumab Q2W; 29% for Q3W and 44% for ipilimumab), with similar trends observed for individual functioning and symptoms scales. HRQoL was better maintained with pembrolizumab than with ipilimumab in patients with ipilimumab-naive advanced melanoma. CLINICALTRIALS. NCT01866319.


Solution structure and backbone dynamics of the N-terminal region of the calcium regulatory domain from soybean calcium-dependent protein kinase alpha.
Ca(2+)-dependent protein kinases (CDPKs) are vital Ca(2+)-signaling proteins in plants and protists which have both a kinase domain and a self-contained calcium regulatory calmodulin-like domain (CLD). Despite being very similar to CaM (>40% identity) and sharing the same fold, recent biochemical and structural evidence suggests that the behavior of CLD is distinct from its namesake, calmodulin. In this study, NMR spectroscopy is employed to examine the structure and backbone dynamics of a 168 amino acid Ca(2+)-saturated construct of the CLD (NtH-CLD) in which almost the entire C-terminal domain is exchange broadened and not visible in the NMR spectra. Structural characterization of the N-terminal domain indicates that the first Ca(2+)-binding loop is significantly more open than in a recently reported structure of the CLD complexed with a putative intramolecular binding region (JD) in the CDPK. Backbone dynamics suggest that parts of the third helix exhibit unusually high mobility, and significant exchange, consistent with previous findings that this helix interacts with the C-terminal domain. Dynamics data also show that the "tether" region, consisting of the first 11 amino acids of CLD, is highly mobile and these residues exhibit distinctive beta-type secondary structure, which may help to position the JD and CLD. Finally, the unusual global dynamic behavior of the protein is rationalized on the basis of possible interdomain rearrangements and the highly variable environments of the C- and N-terminal domains.


Oxygen tolerance and coupling of mitochondrial electron transport.
Oxygen is critical to aerobic metabolism, but excessive oxygen (hyperoxia) causes cell injury and death. An oxygen-tolerant strain of HeLa cells, which proliferates even under 80% O2, termed "HeLa-80," was derived from wild-type HeLa cells ("HeLa-20") by selection for resistance to stepwise increases of oxygen partial pressure. Surprisingly, antioxidant defenses and susceptibility to oxidant-mediated killing do not differ between these two strains of HeLa cells. However, under both 20 and 80% O2, intracellular reactive oxygen species (ROS) production is significantly (approximately 2-fold) less in HeLa-80 cells. In both cell lines the source of ROS is evidently mitochondrial. Although HeLa-80 cells consume oxygen at the same rate as HeLa-20 cells, they consume less glucose and produce less lactic acid. Most importantly, the oxygen-tolerant HeLa-80 cells have significantly higher cytochrome c oxidase activity (approximately 2-fold), which may act to deplete upstream electron-rich intermediates responsible for ROS generation. Indeed, preferential inhibition of cytochrome c oxidase by treatment with n-methyl protoporphyrin (which selectively diminishes synthesis of heme a in cytochrome c oxidase) enhances ROS production and abrogates the oxygen tolerance of the HeLa-80 cells. Thus, it appears that the remarkable oxygen tolerance of these cells derives from tighter coupling of the electron transport chain.


Oxytocin Acts in Nucleus Accumbens to Attenuate Methamphetamine Seeking and Demand.
Evidence indicates that oxytocin, an endogenous peptide well known for its role in social behaviors, childbirth, and lactation, is a promising addiction pharmacotherapy. We employed a within-session behavioral-economic (BE) procedure in rats to examine oxytocin as a pharmacotherapy for methamphetamine (meth) addiction. The BE paradigm was modeled after BE procedures used to assess motivation for drugs in humans with addiction. The same BE variables assessed across species have been shown to predict later relapse behavior. Thus, the translational potential of preclinical BE studies is particularly strong. We tested the effects of systemic and microinfused oxytocin on demand for self-administered intravenous meth and reinstatement of extinguished meth seeking in male and female rats using a BE paradigm. Correlations between meth demand and meth seeking were assessed. Female rats showed greater demand (i.e., motivation) for meth compared with male rats. In both male and female rats, meth demand predicted reinstatement of meth seeking, and systemic oxytocin decreased demand for meth and attenuated reinstatement to meth seeking. Oxytocin was most effective at decreasing meth demand and seeking in rats with the strongest motivation for drug. Finally, these effects of systemic oxytocin were mediated by actions in the nucleus accumbens. Oxytocin decreases meth demand and seeking in both sexes, and these effects depend on oxytocin signaling in the nucleus accumbens. Overall, these data indicate that development of oxytocin-based therapies may be a promising treatment approach for meth addiction in humans.


Saccharomyces boulardii CNCM I-745 reduces the duration of diarrhoea, length of emergency care and hospital stay in children with acute diarrhoea.
Evidence from the literature has shown that Saccharomyces boulardii provides a clinically significant benefit in the treatment of acute infectious diarrhoea in children. In this multicentre, randomised, prospective, controlled, single blind clinical trial performed in children with acute watery diarrhoea, we aimed to evaluate the impact of S. boulardii CNCM I-745 in hospitalised children, in children requiring emergency care unit (ECU) stay and in outpatient settings. The primary endpoint was the duration of diarrhoea (in hours). Secondary outcome measures were duration of hospitalisation and diarrhoea at the 3(rd) day of intervention. In the whole study group (363 children), the duration of diarrhoea was approximately 24 h shorter in the S. boulardii group (75.4±33.1 vs 99.8±32.5 h, P<0.001). The effect of S. boulardii (diarrhoea-free children) was observed starting at 48 h. After 72 h, only 27.3% of the children receiving probiotic still had watery diarrhoea, in contrast to 48.5% in the control group (P<0.001). The duration of diarrhoea was significantly reduced in the probiotic group in hospital, ECU and outpatient settings (P<0.001, P<0.01 and P<0.001, respectively). The percentage of diarrhoea-free children was significantly larger after 48 and 72 h in all settings. The mean length of hospital stay was shorter with more than 36 h difference in the S. boulardii group (4.60±1.72 vs 6.12±1.71 days, P<0.001). The mean length of ECU stay was shorter with more than 19 h difference in the probiotic group (1.20±0.4 vs 2.0±0.3 days, P<0.001). No adverse effects related to the probiotic were noted. Because treatment can shorten the duration of diarrhoea and reduce the length of ECU and hospital stay, there is likely a social and economic benefit of S. boulardii CNCM I-745 in adjunction to oral rehydration solution in acute infectious gastroenteritis in children.


Social and biological measures of hyperactivity and inattention: are they describing similar underlying constructs of child behavior?
The relationship between 27 different measures of hyperactive, impulsive, and inattentive behavior, including those considered to be more objective and those considered more influenced by social factors, is examined using a normal sample of 219 Mexican children, ages 6 to 12. Measures were based on activity monitoring by accelerometry, ethological observation of attentional and movements states in the classroom, cognitive testing using the TOVA continuous performance test (CPT), and parents' and teachers' reports on ratings scales and symptom checklists. Factor analysis was used to examine to what degree these different measures are reporting similar underlying constructs (factors) of hyperactivity and inattention. Parent and teacher ratings appear to be describing underlying constructs that are distinct from those described by the other measures, but measures based on CPT, observation, and activity monitoring did not factor together either, nor more highly correlate to each other. Analysis combining all the measures showed that parent and teacher ratings factored together based on who was reporting the behavior, rather than the behavior being reported. The findings underscore that each type of measurement of hyperactivity, impulsivity, and inattention measures a different aspect of a complex behavioral phenomenon, rather than some better measuring than others the same underlying factor.


Enrichment double-antibody sandwich indirect enzyme-linked immunosorbent assay that uses a specific monoclonal antibody for sensitive detection of Ralstonia solanacearum in asymptomatic potato tubers.
Sensitive and specific routine detection of Ralstonia solanacearum in symptomless potato tubers was achieved by efficient enrichment followed by a reliable double-antibody sandwich indirect enzyme-linked immunosorbent assay based on the specific monoclonal antibody 8B-IVIA. This monoclonal antibody reacted with 168 typical R. solanacearum strains and did not recognize 174 other pathogenic or unidentified bacteria isolated from potato. The optimized protocol included an initial enrichment step consisting of shaking the samples in modified Wilbrink broth for 72 h at 29 degrees C. This step enabled specific detection by the enzyme-linked immunosorbent assay of 1 to 10 CFU of R. solanacearum per ml of initial potato extract. Analysis of 233 commercial potato lots by this method provided results that coincided with the results of conventional methods.


Benchmarking the quality-monitoring process: a comparison of outcomes analysis by trauma and injury severity score (TRISS) methodology with the peer-review process.
One measure of optimal function within a trauma center is the ability to critically examine outcomes from the process of care within the institution, yet guidelines for evaluation of the peer-review process are lacking. This study was conducted to determine the correlation between mortality analysis performed by the peer-review process (PR) within a trauma division and outcome analysis as determined by Trauma and Injury Severity Score (TRISS) methodology. The mortality peer-review data for an entire year at our level I trauma center served as the study population. Information was obtained on probability of survival, and a determination of preventability was made using standard, preexisting criteria. Peer review involves assigning each outcome to a specific category through the process of multidisciplinary assessment. Probability of survival data was not used for this purpose. Kappa analysis was performed to determine the degree of agreement in each category and then tested for significance. One hundred four deaths in 1,868 trauma patients (5.5%) were reviewed at our multidisciplinary conference. Outcomes were judged as preventable, potentially preventable, or nonpreventable. Death directly related to exsanguination was typically categorized as potentially preventable. Kappa analysis demonstrated the greatest agreement between PR and TRISS in the nonpreventable category (kappa = 0.213) and the least agreement in the potentially preventable category (kappa = -0.197). Overall, the kappa Z statistic was nonsignificant (Z = 1.24). Multidisciplinary peer-review outcomes analysis is at least as effective as the computer-generated TRISS probability of survival data for evaluating quality of care in a trauma center and may be more effective for analysis of potentially preventable outcomes.


Motility-, autocorrelation-, and polarization-sensitive optical coherence tomography discriminates cells and gold nanorods within 3D tissue cultures.
We propose a method for differentiating classes of light scatterers based upon their temporal and polarization properties computed from time series of polarization-sensitive optical coherence tomography (PS-OCT) images. The amplitude (motility) and time scale (autocorrelation decay time) of the speckle fluctuations are combined with the cross-polarization pixel-wise to render Motility-, autocorrelation-, and polarization-sensitive (MAPS) OCT contrast images. This combination of metrics provides high specificity for discriminating diffusive gold nanorods and mammary epithelial cell spheroids within 3D tissue culture, based on their unique MAPS signature. This has implications toward highly specific contrast in molecular (nanoparticle-based) and functional (cellular activity) imaging using standard PS-OCT hardware.


Update in splinting materials and methods.
Current hand splinting methods, materials, and components are reviewed and summarized. Additional subjective and objective tests of thermoplastic materials are performed and results combined with those from other studies. Available samples of thermoplastic materials are tested for fatigue and viscoelastic properties using standard compression cycling methods. Soft splint materials are seeing increased application and appear to be the material for the future.


Evolutionarily stable strategy in a sex- and frequency-dependent selection model.
In this paper, a sex-dependent matrix game haploid model is investigated. For this model, since the phenotypes of female and male individuals are determined by alleles located at a single locus and are sex dependent, any given genotype corresponds to a strategy pair. Thus, a strategy pair is an ESS if and only if the allele corresponding to this strategy pair cannot be invaded by any mutant allele. We show that an ESS equilibrium must be locally asymptotically stable if it exists.


Development and evaluation of a field-based high-throughput phenotyping platform.
Physiological and developmental traits that vary over time are difficult to phenotype under relevant growing conditions. In this light, we developed a novel system for phenotyping dynamic traits in the field. System performance was evaluated on 25 Pima cotton (Gossypium barbadense L.) cultivars grown in 2011 at Maricopa, Arizona. Field-grown plants were irrigated under well watered and water-limited conditions, with measurements taken at different times on 3 days in July and August. The system carried four sets of sensors to measure canopy height, reflectance and temperature simultaneously on four adjacent rows, enabling the collection of phenotypic data at a rate of 0.84ha h-1. Measurements of canopy height, normalised difference vegetation index and temperature all showed large differences among cultivars and expected interactions of cultivars with water regime and time of day. Broad-sense heritabilities (H2)were highest for canopy height (H2=0.86-0.96), followed by the more environmentally sensitive normalised difference vegetation index (H2=0.28-0.90) and temperature (H2=0.01-0.90) traits. We also found a strong agreement (r2=0.35-0.82) between values obtained by the system, and values from aerial imagery and manual phenotyping approaches. Taken together, these results confirmed the ability of the phenotyping system to measure multiple traits rapidly and accurately.


Noncontact detection of homemade explosive constituents via photodissociation followed by laser-induced fluorescence.
Noncontact detection of the homemade explosive constituents urea nitrate, nitromethane and ammonium nitrate is achieved using photodissociation followed by laser-induced fluorescence (PD-LIF). Our technique utilizes a single ultraviolet laser pulse (approximately 7 ns) to vaporize and photodissociate the condensed-phase materials, and then to detect the resulting vibrationally-excited NO fragments via laser-induced fluorescence. PD-LIF excitation and emission spectra indicate the creation of NO in vibrationally-excited states with significant rotational energy, useful for low-background detection of the parent compound. The results for homemade explosives are compared to one another and 2,6-dinitrotoluene, a component present in many military explosives.


Molecular profiling, including TERT promoter mutations, of acral lentiginous melanomas.
Acral lentiginous melanoma (ALM) is the less common subtype with singular characterization. TERT (human telomerase reverse transcriptase) promoter mutations have being described as recurrent in melanomas and infrequent in ALM, but their real incidence and clinical relevance is unclear. The objectives of this study were to describe the prevalence of TERT promoter mutations in ALM, and correlate with the molecular profile of other drive genes and clinical features. Sixty-one samples from 48 patients with ALM were analyzed. After DNA isolation, the mutation profiles of the hotspot region of BRAF, NRAS, KIT, PDGFRA, and TERT genes were determined by PCR amplification followed by direct Sanger sequencing. KIT, PDGFRA, and VEGFR2 gene amplification was performed by quantitative PCR. Clinical information such as survival, clinical stage, and Breslow tumor classification were obtained from medical records. TERT promoter mutations were found in 9.3% of the cases, BRAF in 10.3%, NRAS in 7.5%, KIT in 20.7%, and PDGFRA in 14.8% of ALM. None of the cases showed KIT, PDGFRA, or VEGFR2 gene amplification. We found an association between KIT mutations and advanced Clark level (IV and V, P=0.043) and TERT promoter mutations with low mitotic index. No other significant associations were observed between mutation profile and patients' clinical features nor survival rates. Oncogenic TERT promoter mutations are present in a fraction of ALMs. No relevant associations were found between TERT mutation status and clinical/molecular features nor survival. Mutations of KIT and PDGFRA are the most common genetic alterations, and they can be therapeutic targets for these patients.


Estimation of parametric failure time distributions based on interval-censored data with irregular dependent follow-up.
Event history studies based on disease clinic data often face several complications. Specifically, patients may visit the clinic irregularly, and the intermittent observation times could depend on disease-related variables; this can cause a failure time outcome to be dependently interval-censored. We propose a weighted estimating function approach so that dependently interval-censored failure times can be analysed consistently. A so-called inverse-intensity-of-visit weight is employed to adjust for the informative inspection times. Left truncation of failure times can also be easily handled. Additionally, in observational studies, treatment assignments are typically non-randomized and may depend on disease-related variables. An inverse-probability-of-treatment weight is applied to estimating functions to further adjust for measured confounders. Simulation studies are conducted to examine the finite sample performances of the proposed estimators. Finally, the Toronto Psoriatic Arthritis Cohort Study is used for illustration. Copyright © 2017 John Wiley & Sons, Ltd.


A Consensus View of ESCRT-Mediated Human Immunodeficiency Virus Type 1 Abscission.
The strong dependence of retroviruses, such as human immunodeficiency virus type 1 (HIV-1), on host cell factors is no more apparent than when the endosomal sorting complex required for transport (ESCRT) machinery is purposely disengaged. The resulting potent inhibition of retrovirus release underscores the importance of understanding fundamental structure-function relationships at the ESCRT-HIV-1 interface. Recent studies utilizing advanced imaging technologies have helped clarify these relationships, overcoming hurdles to provide a range of potential models for ESCRT-mediated virus abscission. Here, we discuss these models in the context of prior work detailing ESCRT machinery and the HIV-1 release process. To provide a template for further refinement, we propose a new working model for ESCRT-mediated HIV-1 release that reconciles disparate and seemingly conflicting studies.


Growth of saprotrophic fungi and bacteria in soil.
Bacterial and fungal growth rate measurements are sensitive variables to detect changes in environmental conditions. However, while considerable progress has been made in methods to assess the species composition and biomass of fungi and bacteria, information about growth rates remains surprisingly rudimentary. We review the recent history of approaches to assess bacterial and fungal growth rates, leading up to current methods, especially focusing on leucine/thymidine incorporation to estimate bacterial growth and acetate incorporation into ergosterol to estimate fungal growth. We present the underlying assumptions for these methods, compare estimates of turnover times for fungi and bacteria based on them, and discuss issues, including for example elusive conversion factors. We review what the application of fungal and bacterial growth rate methods has revealed regarding the influence of the environmental factors of temperature, moisture (including drying/rewetting), pH, as well as the influence of substrate additions, the presence of plants and toxins. We highlight experiments exploring the competitive and facilitative interaction between bacteria and fungi enabled using growth rate methods. Finally, we predict that growth methods will be an important complement to molecular approaches to elucidate fungal and bacterial ecology, and we identify methodological concerns and how they should be addressed.


Epistemology and history.
The essay reviews Hans-Jörg Rheinberger's intensive engagement with French epistemology that has remained a constant throughout his career. It focuses especially on a set of recent writings by Rheinberger that all revolve around the question: how has epistemology become historical? This question is discussed in the context of Rheinberger's own move from philosophy to an embracement of history.


MiR-490-3p inhibited the proliferation and metastasis of esophageal squamous cell carcinoma by targeting HMGA2.
To identify the potential role of miR-490-3p in the development of esophageal squamous cell carcinoma (ESCC), and to explore the possible underlying mechanism. Human ESCC tissues and cancer-adjacent normal tissues were collected. The mRNA expression level of miR-490-3p was detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). On-line target gene prediction software was applied to screen high-mobility group AT-hook 2 (HMGA2). Subsequently, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide), qRT-PCR, Western blotting, transwell and scratch-wound assays were conducted to analyze the effect of miR-490-3p on the biological function of the ESCC cell line (EC-109). In our study, the mRNA expression level of miR-490-3p was remarkably reduced in ESCC tissues and cells. Molecular mechanism analysis confirmed that miR-490-3p could act on the 3'-UTR of HMGA2 and regulate its expression. Subsequent functional experiments indicated that decreased expression of HMGA2 resulting from the up-regulation of miR-490-3p could inhibit the proliferation, invasion, migration and epithelial-mesenchymal transition (EMT) of ESCC cells. We discovered the inhibitory effect of miR-490-3p on ESCC by targeting HMGA2, and revealed that miR-490-3p could be a potential therapeutic target for ESCC.


[Advances in sleep disorders].
This review aims to offer a panoramic overview of the most common sleep disorders, the methodology of the study, their clinical and physiopathological aspects and their treatment. First, we give a brief overview of the methodology of the study of sleep/wakefulness with examinations which are considered essential today. Next, and following the International Classification, we describe sleep disorders which require the knowledge of a physician specialized in sleep pathology: insomnia, hypersomnia, circadian rhythm disorders and parasomnias. We also describe conditions related to sleep or worsened during sleep (snoring, apneas, cardiovascular disorders, etc.), the study of which requires the collaboration of a large number of specialists. The study of sleep and wakefulness disorders is clearly a branch of medicine due to the high prevalence of these disorders in the general population, their morbidity and their negative consequences in social and working life, especially as a cause of road and workplace accidents.


Endocrine disrupting effects on Chinese rare minnow (Gobiocypris rarus) fed with field collected Limnodrilus sp.
The potential endocrine disrupting effects and other toxicity effects on aquatic biota resulted from food uptake was simulated by feeding the laboratory cultured rare minnow( Gobiocypris rarus) with field collected Limnodrilus sp. The results indicated that the food chain processes affected significantly the growth, slightly reduced gonadosomatic indices, and elevated hepatosomatic indices. There was an obvious vitellogenin(VTG) induction, which generally only occurred in mature female, in the serum of juvenile rare minnow and mature male when fed with Limnodrilus sp. In addition, the rare minnow feeding on Limnodrilus sp. had significantly high renal indices, it meant obvious renal hyperplasia. The present work suggested that Limnodrilus sp. from field water may contain toxic pollutants and could lead to endocrine disruption effects to the predators. It was concluded that endocrine disruptors may not only be assimilated through water, but also be bioconcentrated through food web. The results also suggested the importance of food selection in conducting the study of endocrine disruption effects using sensitive species.


[Acupoint selection rules and characteristics of insomnia in the elderly treated with acupuncture].
The published literature of insomnia in the elderly treated with acupuncture was retrieved in CNKI, Wanfang and VIP from the date of establishment to December 31, 2019. Association rule analysis and cluster analysis were used to summarize the acupoint selection rules of insomnia in the elderly treated with acupuncture. A total of 37 articles were included, involving 60 acupuncture prescriptions. The most commonly used acupoints were Sanyinjiao (SP 6), Shenmen (HT 7), Anmian (Extra), Baihui (GV 20), Sishencong (EX-HN 1), Neiguan (PC 6), Xinshu (BL 15) and Taixi (KI 3). The most commonly used acupoint combinations were Sanyinjiao (SP 6)-Anmian (Extra)-Baihui (GV 20)-Sishencong (EX-HN 1)-Shenting (GV 24)-Shenmen (HT 7)-Xinshu(BL 15), Xinshu(BL 15)-Pishu (BL 20)-Shenshu (BL 23)-Shenting (GV 24), Zhaohai (KI 6)-Shenmai (BL 62), Taichong (LR 3)-Ganshu (BL 18), Daling (PC 7)-Taixi (KI 3), Neiguan (PC 6)- Zusanli (ST 36) and Guanyuan (CV 4)-Qihai (CV 6)-Zhongwan (CV 12). On the basis of acupoint selection according to disease differentiation, the acupoint selection rules and characteristics of insomnia in the elderly treated with acupuncture are regulating and supplementing the spleen and kidney and treating according to spleen-kidney.