Higher-quality diet and non-consumption of meat are associated with less self-determined disability progression in people with multiple sclerosis: A longitudinal cohort study.
Modifiable lifestyle factors, including diet, may affect clinical outcomes in multiple sclerosis (MS). This study assessed the relationships between diet, and disability, fatigue, and depression risk in people with MS. Participants from the Health Outcomes and Lifestyle In a Sample of people with Multiple sclerosis (HOLISM) international cohort were assessed over 2.5 years. Dietary data were obtained using a modified Diet Habits Questionnaire (DHQ), disability using the calculated Patient-determined MS Severity Score (P-MSSS), fatigue using the Fatigue Severity Scale, and depression risk using the Patient Health Questionnaire-2. Participants reported whether they were experiencing symptoms due to a recent relapse. Cross-sectional and prospective relationships of diet and disease outcomes were explored, adjusted for relevant confounders. Among 1,346 participants, higher DHQ scores showed significant dose-dependent associations with lower frequencies of severe disability, fatigue, and depression risk, cross-sectionally. Prospectively, higher baseline DHQ scores were associated with a lower risk of increasing disability, those above the median having 41% and 36% lower risk of increasing disability, and 0.30 P-MSSS points less disability progression, but were not associated with fatigue or depression risk. Meat consumption was associated with 0.22 P-MSSS points higher disability cross-sectionally, while prospectively, baseline meat consumption was associated with 76% higher risk of increasing disability and 0.18 P-MSSS points higher disability progression. Dairy consumption showed mixed associations cross-sectionally and prospectively. These results show that better quality of diet, as well as not consuming meat, were associated with reduced disability progression in people with MS. Substantiation of these findings in other settings may inform opportunities to manage disability progression in people with MS using dietary modifications.


Studies on mode of antagonism between adrenergic beta-mimetics and beta-blocking agents (I). Beta-blocking action of mescaline and its derivatives.
In order to clarify whether or not trimetoquinol (TMQ) and isoproterenol (ISO) interact with the same receptor, the pA2 values of propranolol (PR) and certain trimethoxybenzene derivatives were measured, using isolated guinea pig tracheal chains. Each of PR, mescaline (MES) and its derivatives gave almost the same pA2 values for TMQ and ISO. Introduction of an alkyl group into the N atom of MES increased the affinity to the receptor in the order of methyl and isopropyl as well as the structureactivity relationship of catecholamines, while that of hydroxyl group in the beta-position of the side chain decreased pA2 values. The slopes of the regression lines for anti-TMQ action of MES derivatives as well as PR were almost one, but those for their anti-ISO action were less than 0.3. 3,4,5-Trimethoxyaniline and 3,4,5-trimethoxybenzoic acid had little activity as beta-blocking agents. These results suggest the possibility that TMQ and ISO would interact with the same receptor sites. The importance of the trimethoxybenzene and the phenethylamine moieties in the MES-derivatives for anti-TMQ action is discussed.


Impact of Comorbidities on Prostate Cancer Stage at Diagnosis in Florida.
To examine the association of major types of comorbidity with late-stage prostate cancer, a random sample of 11,083 men diagnosed with prostate cancer during 2002-2007 was taken from the Florida Cancer Data System. Individual-level covariates included demographics, primary insurance payer, and comorbidity following the Elixhauser Index. Socioeconomic variables were extracted from Census 2000 data and merged to the individual level data. Provider-to-case ratio at county level was alsocomputed. Multilevel logistic regression was used to assess associations between these factors and late-stage diagnosis of prostate cancer. Higher odds of late-stage diagnosis was significantly related to presence of comorbidities, being unmarried, current smoker, uninsured, and diagnosed in not-for-profit hospitals. The study reported that the presence of certain comorbidities, specifically 10 out of the 45, was associated with late-stage prostate cancer diagnosis. Eight out of 10 significant comorbid conditions were associated with greater risk of being diagnosed at late-stage prostate cancer. On the other hand, men who had chronic pulmonary disease, and solid tumor without metastasis, were less likely to be diagnosed with late-stage prostate cancer. Late-stage diagnosis was associated with comorbidity, which is often associated with increased health care utilization. The association of comorbidity with late-stage prostate cancer diagnosis suggests that individuals with significant comorbidity should be offered routine screening for prostate cancer rather than focusing only on managing symptomatic health problems.


Hydrolysis of inositol phosphates by plant cell extracts.
A gel-filtered soluble fraction prepared from suspension-cultured Nicotiana tabacum cells hydrolysed inositol mono-, bis- and tris-phosphates. At a concentration of 7.5 microM the rates of hydrolysis followed the sequence Ins(1,4,5)P3 greater than Ins(1,4)P2 greater than Ins(4)P congruent to Ins(1)P. The major products of Ins(1,4,5)P3 hydrolysis identified by h.p.l.c. were Ins(1,4)P2 and Ins(4,5)P2. Ins(1,4)P2 was hydrolysed exclusively to Ins(4)P. The inclusion of Ca2+ in the incubation buffer markedly stimulated the hydrolysis of all the inositol phosphate substrates. Under identical conditions, Ca2+ inhibited the hydrolysis of inositol phosphates by soluble extracts prepared from rat brain. Half-maximal stimulation of Ins(1,4)P2 hydrolysis was obtained at free [Ca2+] of 0.6 and 1.2 microM when the Mg2+ concentration in the incubations was 0.3 and 1.0 mM respectively. This effect of Ca2+ was exerted solely by increasing the Vmax. of hydrolysis without affecting the Km for Ins(1,4)P2. Again, in contrast with brain, the hydrolysis of inositol bis- or mono-phosphates was insensitive to high concentrations of Li+. We conclude that plants contain specific Li+-insensitive inositol phosphate phosphatases that are regulated by low concentrations of Ca2+ in a manner which is different from that observed in mammalian tissues.


Three Mars years: viking lander 1 imaging observations.
The Mutch Memorial Station (Viking Lander 1) on Mars acquired imaging and meteorological data over a period of 2245 martian days (3:3 martian years). This article discusses the deposition and erosion of thin deposits (ten to hundreds of micrometers) of bright red dust associated with global dust storms, and the removal of centimeter amounts of material in selected areas during a dust storm late in the third winter. Atmospheric pressure data acquired during the period of intense erosion imply that baroclinic disturbances and strong diurnal solar tidal heating combined to produce strong winds. Erosion occurred principally in areas where soil cohesion was reduced by earlier surface sampler activities. Except for redistribution of thin layers of materials, the surface appears to be remarkably stable, perhaps because of cohesion of the undisturbed surface material.


Use of alteplase in childhood arterial ischaemic stroke: a multicentre, observational, cohort study.
The safety and efficacy of thrombolysis after acute stroke in children have not been established. Our aim was to describe current practices and results of the use of alteplase for acute arterial ischaemic stroke in children enrolled in an international pediatric stroke registry and to compare current practices with those published in case reports and with guidelines for the use of alteplase for adult stroke. In this multicentre observational cohort study, we analysed the clinical features, the dosing and timing of treatment, and the short-term outcome in children treated with alteplase for acute arterial ischaemic stroke who were enrolled in the International Pediatric Stroke Study (IPSS) between January, 2003, and July, 2007. The findings from the IPSS were compared with published case reports for clinical features, adherence to adult guidelines for alteplase, and outcomes. Of 687 children with acute arterial ischaemic stroke enrolled in the IPSS, 15 (2%) received alteplase: nine received intravenous alteplase and six received intra-arterial alteplase. The median time to treatment from stroke onset was 3.3 h (range 2.0-52.0 h) for intravenous alteplase and 4.5 h (3.8-24.0 h) for intra-arterial alteplase. Two patients died (one owing to massive infarction and brain herniation, and one owing to brainstem infarction). At discharge from hospital, one patient was healthy and 12 patients had neurological deficits. Intracranial haemorrhage after alteplase occurred in four of 15 patients, although none of the bleeding events was judged to be acutely symptomatic. When compared with ten patients reported in published articles who were given intravenous alteplase, the nine patients in the IPSS cohort were mostly younger, waited longer for treatment, and had worse outcomes, which suggests there is a publication bias towards short treatment intervals from symptom onset and favourable outcomes. Children with acute stroke received alteplase infrequently and at time intervals that often deviated from adult guidelines. Although no alteplase-related deaths or symptomatic intracranial haemorrhage was reported, poor neurological outcome was common. Clinical trials to evaluate the dose and the safety and efficacy of alteplase are needed in childhood stroke.


The traditional midwife in Saudian villages.
To identify the role of the midwife in rural Saudi Arabia, a house to house survey was conducted in 10 randomly selected communities in Riyadh district. The study showed that the midwife's role in a village is particularly significant in protecting the health of the poor and less educated mother. If effective coverage of ante-natal, delivery and post-natal services is to be achieved then it is suggested that a greater emphasis should be placed upon training the midwives.


Molecular characterization of a novel short-chain dehydrogenase/reductase that reduces all-trans-retinal.
The reduction of all-trans-retinal in photoreceptor outer segments is the first step in the regeneration of bleached visual pigments. We report here the cloning of a dehydrogenase, retSDR1, that belongs to the short-chain dehydrogenase/reductase superfamily and localizes predominantly in cone photoreceptors. retSDR1 expressed in insect cells displayed substrate specificities of the photoreceptor all-trans-retinol dehydrogenase. Homology modeling of retSDR1 using the carbonyl reductase structure as a scaffold predicted a classical Rossmann fold for the nucleotide binding, and an N-terminal extension that could facilitate binding of the enzyme to the cell membranes. The presence of retSDR1 in a subset of inner retinal neurons and in other tissues suggests that the enzyme may also be involved in retinol metabolism outside of photoreceptors.


Cost-Effectiveness of Telemedicine in Remote Orthopedic Consultations: Randomized Controlled Trial.
Telemedicine consultations using real-time videoconferencing has the potential to improve access and quality of care, avoid patient travels, and reduce health care costs. The aim of this study was to examine the cost-effectiveness of an orthopedic videoconferencing service between the University Hospital of North Norway and a regional medical center in a remote community located 148 km away. An economic evaluation based on a randomized controlled trial of 389 patients (559 consultations) referred to the hospital for an orthopedic outpatient consultation was conducted. The intervention group (199 patients) was randomized to receive video-assisted remote orthopedic consultations (302 consultations), while the control group (190 patients) received standard care in outpatient consultation at the hospital (257 consultations). A societal perspective was adopted for calculating costs. Health outcomes were measured as quality-adjusted life years (QALYs) gained. Resource use and health outcomes were collected alongside the trial at baseline and at 12 months follow-up using questionnaires, patient charts, and consultation records. These were valued using externally collected data on unit costs and QALY weights. An extended sensitivity analysis was conducted to address the robustness of the results. This study showed that using videoconferencing for orthopedic consultations in the remote clinic costs less than standard outpatient consultations at the specialist hospital, as long as the total number of patient consultations exceeds 151 per year. For a total workload of 300 consultations per year, the annual cost savings amounted to €18,616. If costs were calculated from a health sector perspective, rather than a societal perspective, the number of consultations needed to break even was 183. This study showed that providing video-assisted orthopedic consultations to a remote clinic in Northern Norway, rather than having patients travel to the specialist hospital for consultations, is cost-effective from both a societal and health sector perspective. This conclusion holds as long as the activity exceeds 151 and 183 patient consultations per year, respectively. ClinicalTrials.gov NCT00616837; https://clinicaltrials.gov/ct2/show/NCT00616837 (Archived by WebCite at http://www.webcitation.org/762dZPoKX).


Safety and efficacy of atezolizumab in patients with autoimmune disease: Subgroup analysis of the SAUL study in locally advanced/metastatic urinary tract carcinoma.
Patients with pre-existing autoimmune disease (AID) are typically excluded from clinical trials of immune checkpoint inhibitors, and there are limited data on outcomes in this population. The single-arm international SAUL study of atezolizumab enrolled a broader 'real-world' patient population. We present outcomes in patients with a history of AID. Patients with locally advanced/metastatic urinary tract carcinoma received atezolizumab 1200 mg every 3 weeks until loss of clinical benefit or unacceptable toxicity. The primary end-point was safety. Overall survival (OS) was a secondary end-point. Subgroup analyses of AID patients were prespecified. Thirty-five of 997 treated patients had AID at baseline, most commonly psoriasis (n = 15). Compared with non-AID patients, AID patients experienced numerically more adverse events (AEs) of special interest (46% versus 30%; grade ≥3 14% versus 6%) and treatment-related grade 3/4 AEs (26% versus 12%), but without relevant increases in treatment-related deaths (0% versus 1%) or AEs necessitating treatment discontinuation (9% versus 6%). Pre-existing AID worsened in four patients (11%; two flares in two patients); three of the six flares resolved, one was resolving, and two were unresolved. Efficacy was similar in AID and non-AID patients (median OS, 8.2 versus 8.8 months, respectively; median progression-free survival, 4.4 versus 2.2 months; disease control rate, 51% versus 39%). In 35 atezolizumab-treated patients with pre-existing AID, incidences of special- interest and treatment-related AEs appeared acceptable. AEs were manageable, rarely requiring atezolizumab discontinuation. Treating these patients requires caution, but pre-existing AID does not preclude atezolizumab therapy. NCT02928406.


Multiple Pathways Act Together To Establish Asymmetry of the Ventral Nerve Cord in Caenorhabditis elegans.
The central nervous system of most animals is bilaterally symmetrical. Closer observation often reveals some functional or anatomical left-right asymmetries. In the nematode Caenorhabditis elegans, the most obvious asymmetry in the nervous system is found in the ventral nerve cord (VNC), where most axons are in the right axon tract. The asymmetry is established when axons entering the VNC from the brain switch from the left to the right side at the anterior end of the VNC. In genetic screens we identified several mutations compromising VNC asymmetry. This includes alleles of col-99 (encoding a transmembrane collagen), unc-52/perlecan and unc-34 (encoding the actin modulator Enabled/Vasodilator-stimulated phosphoproteins). In addition, we evaluated mutants in known axon guidance pathways for asymmetry defects and used genetic interaction studies to place the genes into genetic pathways. In total we identified four different pathways contributing to the establishment of VNC asymmetry, represented by UNC-6/netrin, SAX-3/Robo, COL-99, and EPI-1/laminin. The combined inactivation of these pathways in triple and quadruple mutants leads to highly penetrant VNC asymmetry defects, suggesting these pathways are important contributors to the establishment of VNC asymmetry in C. elegans.


Sickle cell dehydration: Pathophysiology and therapeutic applications.
Cell dehydration is a distinguishing characteristic of sickle cell disease and an important contributor to disease pathophysiology. Due to the unique dependence of Hb S polymerization on cellular Hb S concentration, cell dehydration promotes polymerization and sickling. In double heterozygosis for Hb S and C (SC disease) dehydration is the determining factor in disease pathophysiology. Three major ion transport pathways are involved in sickle cell dehydration: the K-Cl cotransport (KCC), the Gardos channel (KCNN4) and Psickle, the polymerization induced membrane permeability, most likely mediated by the mechano-sensitive ion channel PIEZO1. Each of these pathways exhibit unique characteristics in regulation by oxygen tension, intracellular and extracellular environment, and functional expression in reticulocytes and mature red cells. The unique dependence of K-Cl cotransport on intracellular Mg and the abnormal reduction of erythrocyte Mg content in SS and SC cells had led to clinical studies assessing the effect of oral Mg supplementation. Inhibition of Gardos channel by clotrimazole and senicapoc has led to Phase 1,2,3 trials in patients with sickle cell disease. While none of these studies has resulted in the approval of a novel therapy for SS disease, they have highlighted the key role played by these pathways in disease pathophysiology.


Exposure to psychosocial work factors in 31 European countries.
Although psychosocial work factors are recognized as major occupational risk factors, little information is available regarding the prevalence of exposure to these factors and the differences in exposure between countries. To explore the differences in various psychosocial work exposures between 31 European countries. The study was based on a sample of 14,881 male and 14,799 female workers from the 2005 European Working Conditions Survey. Eighteen psychosocial work factors were studied: low decision latitude (skill discretion and decision authority), high psychological demands, job strain, low social support, iso-strain, physical violence, sexual harassment, bullying, discrimination, work-family imbalance, long working hours, high effort, job insecurity, low job promotion, low reward and effort-reward imbalance. Covariates were age, number of workers in household, occupation, economic activity, self-employed/employee, public/private sector and part/full time work. Statistical analysis was performed using multilevel logistic regression analysis. Significant differences in all psychosocial work factors were observed between countries. The rank of the countries varied according to the exposure considered. However, some countries, especially Denmark, Netherlands and Norway, displayed a significantly lower prevalence of exposure to four factors or more, while some Southern and Eastern countries, especially Czech Republic, Greece, Lithuania and Turkey, had a higher prevalence. Differences in psychosocial work exposures were found between countries. This study is the first to compare a large set of psychosocial work exposures between 31 European countries. These findings may be useful to guide prevention policies at European level.


STAT3 and NFkappaB activation precedes glial reactivity in the excitotoxically injured young cortex but not in the corresponding distal thalamic nuclei.
In this study we evaluated the activation of the cytokine and growth factor responsive transcription factors signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa B (NFkappaB) after different grades of neural damage in the immature rat brain using double immunocytochemical techniques and electron microscopy. Following neocortical N-methyl-D-aspartate induced excitotoxic cell death, both these transcription factors are mainly activated in astrocytes, although microglia, endothelial cells, and neurons show transient activation at specific times and locations. Interestingly, activation of both transcription factors is only observed in cortical areas affected by severe tissue damage, neuronal degeneration, and blood-brain barrier (BBB) disruption. In contrast, the milder glial response occurring in the distal thalamus is not preceded by immunocytochemically detectable STAT3 and NFkappaB activation, although microglial response, astroglial hypertrophy, and glial fibrillary acidic protein (GFAP) overexpression do occur. In the cortex, astrocytes show STAT3 and NFkappaB activation already at 2 to 4 hours post-lesion, preceding cell hypertrophy and GFAP upregulation, and being maintained in the long-term formed glial scar. STAT3 and NFkappaB activation in microglial cells is protracted and observed at 10 to 24 hours post-lesion. The early activation of both transcription factors in astroglial cells could contribute to the changes in gene expression leading to astrogliosis and the release of signalling molecules which may contribute to the subsequent activation of these transcription factors in microglial cells.


Characterization of zebra mussel (Dreissena polymorpha) sperm morphology and their motility prior to and after spawning.
In order to understand more about the reproductive physiology of the zebra mussel (Dreissena polymorpha), we have examined the effect of spawning on the kinematics and fertilization ability of their spermatozoa. Sperm morphology was characterized using scanning electron microscopy, differences in sperm kinematics were examined using CASA following manual collection of sperm from the gonad or spawning induced by 5-hydroxytryptamine (5-HT), and the fertilization ability of spawned and manually removed spermatozoa were compared. D. polymorpha sperm have a tail 50 microns long, a midpiece consisting of four spherical mitochondria-rich regions approximately 0.6 micron in diameter, a conical nucleus 2.52 microns in length, and a cylindrical acrosome 0.72 micron in height and width. Kinematic analysis revealed that manually removed sperm exhibit significantly lower motion characteristics as compared to spawned sperm. Treatment with 5-HT had no significant effect on the sperm kinematics of either manually removed or spawned spermatozoa. These data suggest that D. polymorpha spermatozoa have a similar morphology to other bivalve sperm, spawning results in a significant enhancement in sperm kinematics, and 5-HT does not directly alter sperm motion.


The fall and rise of prostate-specific antigen. Kinetics of serum prostate-specific antigen levels after radiation therapy for prostate cancer.
The serum kinetics of prostate-specific antigen (PSA) after radiation therapy for prostate cancer are not well characterized, and the potential prognostic significance of serum half-lives and of serum doubling times is unclear. This study was designed to address those issues. One hundred fifty-four patients with at least four serial PSA determinations who received external-beam radiation therapy alone were analyzed to determine PSA kinetics and to correlate kinetic parameters with outcome. Nonlinear regression techniques were used to estimate PSA half-lives and doubling times. The PSA data fitted well to exponential models consistent with the hypothesis that PSA kinetics after radiation follow first-order (exponential) kinetics. The mean PSA half-life was 1.9 months (range, 0.5 to 9.2 months). No significant correlation existed between half-life and grade, stage, acid phosphatase level, serum testosterone level, or patient age. A weak correlation between half-life and pretreatment PSA level was observed: patients with low PSA levels tended to have longer half-lives. Half-life did not correlate with disease relapse or with the likelihood of developing a rising PSA profile. PSA doubling time in 37 patients with rising values ranged from 1.6 to 53 months (mean, 12.5 months). Doubling times were significantly longer than half-lives by an average factor of 6.5 and there was no correlation between half-life and subsequent doubling time. Doubling times were longer in low-grade tumors. Serum kinetics of PSA in particular its rate of fall after radiation provide little, if any, useful clinical information. It is possible that serum kinetics of PSA are related to tumor cell kinetics but such relationships remain speculative. Correlative cell kinetic--PSA kinetic studies are needed to elucidate the mechanisms underlying the changes in PSA level after radiation therapy.


Differential transcriptional activity of plant-pathogenic begomoviruses in their whitefly vector (Bemisia tabaci, Gennadius: Hemiptera Aleyrodidae).
Plant-pathogenic begomoviruses have a complex association with their whitefly vector and aspects concerning virus genetic activity (genome replication and gene transcription) within the insect remain highly controversial. Virus transcript abundance was assessed by quantifying selected gene transcripts of Tomato mottle virus (ToMoV, a New World bipartite begomovirus) and Tomato yellow leaf curl virus (TYLCV, an Old World monopartite begomovirus) in whiteflies (Bemisia tabaci biotype B) after feeding on virus-infected tomato plants and after subsequent transfer to cotton, a plant that is immune to the selected begomoviruses. Real-time RT-PCR was performed using specific primers for three ToMoV genes (AV1, BC1 and BV1) and three TYLCV genes (V1, V2 and C3). The ToMoV gene transcripts rapidly became undetectable in whiteflies following transfer from tomato to cotton, probably because degradation was not accompanied by new synthesis. On the other hand, TYLCV transcripts increased after transfer of whiteflies to cotton, indicating active TYLCV transcription. Interestingly, the difference observed in ToMoV and TYLCV transcripts in the vector parallel observations on the different biological effects of these viruses on whiteflies, i.e. TYLCV, but not ToMoV, reduces whitefly fitness.


Advancements in detection and removal of antibiotic resistance genes in sludge digestion: A state-of-art review.
Sludge from wastewater treatment plants can act as a repository and crucial environmental provider of antibiotic resistance genes (ARGs). Over the past few years, people's knowledge regarding the occurrence and removal of ARGs in sludge has broadened remarkably with advancements in molecular biological techniques. Anaerobic and aerobic digestion were found to effectively achieve sludge reduction and ARGs removal. This review summarized advanced detection and removal techniques of ARGs, in the last decade, in the sludge digestion field. The fate of ARGs due to different sludge digestion strategies (i.e., anaerobic and aerobic digestion under mesophilic or thermophilic conditions, and in combination with relevant pretreatment technologies (e.g., thermal hydrolysis pretreatment, microwave pretreatment and alkaline pretreatment) and additives (e.g., ferric chloride and zero-valent iron) were systematically summarized and compared in this review. To date, this is the first review that provides a comprehensive assessment of the state-of-the-art technologies and future recommendations.


Sensitivity versus accuracy in multiclass problems using memetic Pareto evolutionary neural networks.
This paper proposes a multiclassification algorithm using multilayer perceptron neural network models. It tries to boost two conflicting main objectives of multiclassifiers: a high correct classification rate level and a high classification rate for each class. This last objective is not usually optimized in classification, but is considered here given the need to obtain high precision in each class in real problems. To solve this machine learning problem, we use a Pareto-based multiobjective optimization methodology based on a memetic evolutionary algorithm. We consider a memetic Pareto evolutionary approach based on the NSGA2 evolutionary algorithm (MPENSGA2). Once the Pareto front is built, two strategies or automatic individual selection are used: the best model in accuracy and the best model in sensitivity (extremes in the Pareto front). These methodologies are applied to solve 17 classification benchmark problems obtained from the University of California at Irvine (UCI) repository and one complex real classification problem. The models obtained show high accuracy and a high classification rate for each class.


Hemoperitoneum caused by spontaneous rupture of a true splenic cyst.
A 34 year-old man presented with hemoperitoneum from a spontaneously ruptured spleen. At laparotomy, a 5-cm diameter splenic cyst was found to be ruptured. Histological examination confirmed the diagnosis of a true splenic cyst of the mesothelial type. Spontaneous rupture with hemoperitoneum is a rare but potentially lethal complication of a true splenic cyst.


Effects of the administration of thyroid hormone on the plasma levels of atrial natriuretic peptides and on atrial myoendocrine cells in the rat: an immunochemical, ultrastructural, and stereological study.
The effects of an altered thyroidal status on the levels of immunoreactive (ir-) atrial natriuretic peptide (ANP) in serum and in the right and left atria, as well as on the subcellular structures of atrial myoendocrine cells were explored in groups of male Sprague Dawley rats given the vehicle or triiodothyronine in the toxicological dose-range (50 micrograms/100 g bw/day) for 0,5, 1,2,4,7 or 14 days. Plasma levels of ir-ANP were 30% higher in T3-treated rats compared with controls at 0,5 and 1 day after hormone administration and then decreased to levels 30-40% lower than controls at days 2 and 4 to rise again above control values on day 7 and 14. Atrial ir-ANP levels decreased at first both in the right and in the left atria with different latencies (1 and 2 days, respectively) and rose back towards control levels by day 4. Changes in the numerical density of specific granules followed a parallel temporal pattern. An increased in the individual volume of the granules followed was also observed. Investigation into the circulatory effects of T3 administration showed that the heart rate was increased by hour 12 after hormone administration (simultaneously with the early rise in plasma ir-ANP levels) and that blood pressure was increased by day 2.(ABSTRACT TRUNCATED AT 250 WORDS)


Isolation of a ribonucleoprotein complex involved in mRNA localization in Drosophila oocytes.
Localization of bicoid (bcd) mRNA to the anterior and oskar (osk) mRNA to the posterior of the Drosophila oocyte is critical for embryonic patterning. Previous genetic studies implicated exuperantia (exu) in bcd mRNA localization, but its role in this process is not understood. We have biochemically isolated Exu and show that it is part of a large RNase-sensitive complex that contains at least seven other proteins. One of these proteins was identified as the cold shock domain RNA-binding protein Ypsilon Schachtel (Yps), which we show binds directly to Exu and colocalizes with Exu in both the oocyte and nurse cells of the Drosophila egg chamber. Surprisingly, the Exu-Yps complex contains osk mRNA. This biochemical result led us to reexamine the role of Exu in the localization of osk mRNA. We discovered that exu-null mutants are defective in osk mRNA localization in both nurse cells and the oocyte. Furthermore, both Exu/Yps particles and osk mRNA follow a similar temporal pattern of localization in which they transiently accumulate at the oocyte anterior and subsequently localize to the posterior pole. We propose that Exu is a core component of a large protein complex involved in localizing mRNAs both within nurse cells and the developing oocyte.


Physical therapies as an adjunct to Botulinum toxin-A injection of the upper or lower limb in adults following neurological impairment.
Spasticity of muscles is a common consequence of central nervous system impairment. Traditionally, neurological rehabilitation for spasticity has involved occupational and physical therapy; however, increasingly Botulinum toxin-A injections may be provided. Injection effects are temporary. Consequently, understanding the effect of adjunct physical therapies will help inform multimodal rehabilitation decisions. Presently, these effects are not known. This systematic review will identify and summarize evidence on physical therapies used after Botulinum toxin-A injection to improve motor function in adults with neurological impairments. Systematic searching of seven electronic databases will occur to identify relevant randomized trials. Available trial data will be extracted into a list of pre-defined primary outcomes, including range of movement, spasticity and functional limb use. Pre-defined secondary outcomes will also be reviewed where trials have these data available for reporting. Effects will be expressed as mean differences or standardized mean differences with 95% confidence intervals (CI). Where possible, comparable results will be meta-analyzed, and a summary of the available pool of evidence produced.All randomized controlled trials will be rated using the PEDro methodological quality scale. Where possible, study data will be meta-analyzed using RevMan 5 Software. The protocol was registered in PROSPERO international prosepective register of systematic reviews (PROSPERO 2011:CRD42011001491). Review results will be the most comprehensive answer available to the following question: Are physical therapies clinically effective after Botulinum toxin-A injections in adults with neurological spasticity? Results will inform healthcare providers and managers who determine who gets access to and provision of Botulinum toxin-A injection and whether this is done with or without physical therapies. Results will inform the clinicians who conduct physical therapy following injection. This protocol provides readers with the scope and depth of a search that will ultimately answer a complex and pressing treatment question. The variability of current practice and high level of expense associated with multimodal rehabilitation means review results will be more useful and less contestable if the protocol is revealed in full through advance publication.


Animal models for investigating chronic pancreatitis.
Chronic pancreatitis is defined as a continuous or recurrent inflammatory disease of the pancreas characterized by progressive and irreversible morphological changes. It typically causes pain and permanent impairment of pancreatic function. In chronic pancreatitis areas of focal necrosis are followed by perilobular and intralobular fibrosis of the parenchyma, by stone formation in the pancreatic duct, calcifications in the parenchyma as well as the formation of pseudocysts. Late in the course of the disease a progressive loss of endocrine and exocrine function occurs. Despite advances in understanding the pathogenesis no causal treatment for chronic pancreatitis is presently available. Thus, there is a need for well characterized animal models for further investigations that allow translation to the human situation. This review summarizes existing experimental models and distinguishes them according to the type of pathological stimulus used for induction of pancreatitis. There is a special focus on pancreatic duct ligation, repetitive overstimulation with caerulein and chronic alcohol feeding. Secondly, attention is drawn to genetic models that have recently been generated and which mimic features of chronic pancreatitis in man. Each technique will be supplemented with data on the pathophysiological background of the model and their limitations will be discussed.


Syntaxin 16 and syntaxin 5 are required for efficient retrograde transport of several exogenous and endogenous cargo proteins.
Retrograde transport allows proteins and lipids to leave the endocytic pathway to reach other intracellular compartments, such as trans-Golgi network (TGN)/Golgi membranes, the endoplasmic reticulum and, in some instances, the cytosol. Here, we have used RNA interference against the SNARE proteins syntaxin 5 and syntaxin 16, combined with recently developed quantitative trafficking assays, morphological approaches and cell intoxication analysis to show that these SNARE proteins are not only required for efficient retrograde transport of Shiga toxin, but also for that of an endogenous cargo protein - the mannose 6-phosphate receptor - and for the productive trafficking into cells of cholera toxin and ricin. We have found that the function of syntaxin 16 was specifically required for, and restricted to, the retrograde pathway. Strikingly, syntaxin 5 RNA interference protected cells particularly strongly against Shiga toxin. Since our trafficking analysis showed that apart from inhibiting retrograde endosome-to-TGN transport, the silencing of syntaxin 5 had no additional effect on Shiga toxin endocytosis or trafficking from TGN/Golgi membranes to the endoplasmic reticulum, we hypothesize that syntaxin 5 also has trafficking-independent functions. In summary, our data demonstrate that several cellular and exogenous cargo proteins use elements of the same SNARE machinery for efficient retrograde transport between early/recycling endosomes and TGN/Golgi membranes.


Intracellular trafficking of TREM2 is regulated by presenilin 1.
Genetic mutations in triggering receptor expressed on myeloid cells 2 (TREM2) have been linked to a variety of neurodegenerative diseases including Alzheimer's disease, amyotrophic lateral sclerosis, frontotemporal dementia and Parkinson's disease. In the brain, TREM2 is highly expressed on the cell surface of microglia, where it can transduce signals to regulate microglial functions such as phagocytosis. To date, mechanisms underlying intracellular trafficking of TREM2 remain elusive. Mutations in the presenilin 1 (PS1) catalytic subunit of the γ-secretase complex have been associated with increased generation of the amyloidogenic Aβ (amyloid-β) 42 peptide through cleavage of the Aβ precursor amyloid precursor protein. Here we found that TREM2 interacts with PS1 in a manner independent of γ-secretase activity. Mutations in TREM2 alter its subcellular localization and affects its interaction with PS1. Upregulation of PS1 reduces, whereas downregulation of PS1 increases, steady-state levels of cell surface TREM2. Furthermore, PS1 overexpression results in attenuated phagocytic uptake of Aβ by microglia, which is reversed by TREM2 overexpression. Our data indicate a novel role for PS1 in regulating TREM2 intracellular trafficking and pathophysiological function.


Magnetic alginate microspheres: system for the position controlled delivery of nerve growth factor.
The use of polymeric carriers containing dispersed magnetic nanocrystalline particles for targeted delivery of drugs in clinical practice has attracted the interest of the scientific community. In this paper a system comprised of alginate microparticles with a core of magnetite and carrying nerve growth factor (NGF) is described. The magnetic properties of these microspheres, typical of superparamagnetic materials, allow precise and controlled delivery to the intended tissue environment. Experiments carried out on PC12 cells with magnetic alginate microspheres loaded with NGF have confirmed the induction of cell differentiation which is strongly dependent on the distance from the microsphere cluster. In addition, finite element modelling (FEM) of the release profile from the microspheres in culture, indicated the possibility of creating defined and predictable NGF gradients from the loaded microspheres. These observations on the carriage and release of growth factors by the proposed microparticles open new therapeutic options for both neuronal regeneration and of the development of effective neuronal interfaces.


Adeno-associated virus-binding antibodies detected in cats living in the Northeastern United States lack neutralizing activity.
Cats are a critical pre-clinical model for studying adeno-associated virus (AAV) vector-mediated gene therapies. A recent study has described the high prevalence of anti-AAV neutralizing antibodies among domestic cats in Switzerland. However, our knowledge of pre-existing humoral immunity against various AAV serotypes in cats is still limited. Here, we show that, although antibodies binding known AAV serotypes (AAV1 to AAV11) are prevalent in cats living in the Northeastern United States, these antibodies do not necessarily neutralize AAV infectivity. We analyzed sera from 35 client-owned, 20 feral, and 30 specific pathogen-free (SPF) cats for pre-existing AAV-binding antibodies against the 11 serotypes. Antibody prevalence was 7 to 90% with an overall median of 50%. The AAV-binding antibodies showed broad reactivities with other serotypes. Of 44 selected antibodies binding AAV2, AAV6 or AAV9, none exhibited appreciable neutralizing activities. Instead, AAV6 or AAV9-binding antibodies showed a transduction-enhancing effect. AAV6-binding antibodies were highly prevalent in SPF cats (83%), but this was primarily due to cross-reactivity with preventive vaccine-induced anti-feline panleukopenia virus antibodies. These results indicate that prevalent pre-existing immunity in cats is not necessarily inhibitory to AAV and highlight a substantial difference in the nature of AAV-binding antibodies in cats living in geographically different regions.


Association between vaginal bleeding in pregnancy that resulted in delivery and risk of cancer: A Danish registry-based cohort study.
Vaginal bleeding (VB) before 20 gestational weeks of a viable pregnancy is a manifestation of a threatened miscarriage. VB is associated with increased levels of pro-inflammatory cytokines such as interferon-gamma, tumour necrosis factor-alpha and interleukin-6. Increased levels of these cytokines and oxidative stress are risk factors for cancer. The risk of cancer following a VB-affected pregnancy that ended in childbirth is unknown. To investigate the associations between VB in pregnancy that resulted in delivery and risk of incident cancer. We conducted a cohort study (1995-2018) in Denmark using administrative and healthcare registries. We included 37,082 VB-affected deliveries, 1,363,614 VB-unaffected deliveries, 324,328 pregnancies ending in terminations, and 137,104 miscarriages. We computed the absolute risk of cancer and hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age, calendar year, morbidities, and socio-economic factors using Cox proportional hazards regression. Multiple pregnancies to the same woman were accounted for in the analysis. The median (25th-75th percentile) follow-up in the study was 12.6 (6.9, 18.2) years. The prevalence of VB in the present study was 3%. At the end of the follow-up, there were 1320 cancer cases among the VB-affected delivery cohort, 40,420 among the VB-unaffected delivery cohort, 10,300 among the termination cohort and 4790 among the miscarriage cohort. HRs for any cancer among VB-affected deliveries were 1.03 (95% CI 0.97, 1.08) compared with VB-unaffected deliveries, 1.03 (95% CI 0.97, 1.09) compared with terminations and 0.90 (95% CI 0.84, 0.95) compared with miscarriages. There were no increased risks of premenopausal breast cancer, cervical cancer, ovary and fallopian tube cancer or uterine cancer following VB-affected deliveries vs. comparison cohorts. We found no evidence of an association between vaginal bleeding in pregnancy and an increased risk of cancer.


The roles of testicular nuclear receptor 4 (TR4) in male fertility-priapism and sexual behavior defects in TR4 knockout mice.
Successful reproductive efforts require the establishment of a situation favorable for reproduction that requires integration of both behavior and internal physiological events. TR4 nuclear receptor is known to be involved in male fertility via controlling spermatogenesis, yet its roles in regulating other biological events related to reproduction have not been completely revealed. Male TR4 knockout (TR4 -/-) and wild type mice were used for the sexual behavior and penile dysfunction studies. Mice were sacrificed for histological examination and corresponding genes profiles were analyzed by quantitative RT-PCR. Reporter gene assays were performed. We describe an unexpected finding of priapism in TR4 -/- mice. As a transcriptional factor, we demonstrated that TR4 transcriptionally modulates a key enzyme regulating penis erection and neuronal nitric oxide synthese NOS (nNOS). Thereby, elimination of TR4 results in nNOS reduction in both mRNA and protein levels, consequently may lead to erectile dysfunction. In addition, male TR4 -/- mice display defects in sexual and social behavior, with increased fear or anxiety, as well as reduced mounting, intromission, and ejaculation. Reduction of ER alpha, ER beta, and oxytocin in the hypothalamus may contribute to defects in sexual behavior and stress response. Together, these results provide in vivo evidence of important TR4 roles in penile physiology, as well as in male sexual behavior. In conjunction with previous finding, TR4 represents a key factor that controls male fertility via regulating behavior and internal physiological events.


Active motion of passive asymmetric dumbbells in a non-equilibrium bath.
Persistent motion of passive asymmetric bodies in non-equilibrium media has been experimentally observed in a variety of settings. However, fundamental constraints on the efficiency of such motion are not fully explored. Understanding such limits, and ways to circumvent them, is important for efficient utilization of energy stored in agitated surroundings for purposes of taxis and transport. Here, we examine such issues in the context of erratic movements of a passive asymmetric dumbbell driven by non-equilibrium noise. For uncorrelated (white) noise, we find a (non-Boltzmann) joint probability distribution for the velocity and orientation, which indicates that the dumbbell preferentially moves along its symmetry axis. The dumbbell thus behaves as an Ornstein-Uhlenbeck walker, a prototype of active matter. Exploring the efficiency of this active motion, we show that in the over-damped limit, the persistence length l of the dumbbell is bound from above by half its mean size, while the propulsion speed v∥ is proportional to its inverse size. The persistence length can be increased by exploiting inertial effects beyond the over-damped regime, but this improvement always comes at the price of smaller propulsion speeds. This limitation is explained by noting that the diffusivity of a dumbbell, related to the product v∥l, is always less than that of its components, thus severely constraining the usefulness of passive dumbbells as active particles.


Arsenic trioxide as a treatment for myelodysplastic syndrome.
Myelodysplastic syndrome (MDS) is a heterogeneous bone marrow disorder primarily affecting older adults, for whom the only curative therapy, bone marrow transplantation, is rarely an option. New therapies, or novel applications of historical therapies, are desperately needed. Arsenic trioxide (ATO), which acts through pro-apoptotic, antiproliferative, and anti-angiogenesis mechanisms, has been used successfully to treat a variety of hematologic malignancies, including MDS. As monotherapy or in combination with other agents, it can effect hematologic improvement in 22% to 26% of patients, with tolerable side effects. MDS patients whose cells express the EVI1 mutation in particular may derive benefit from this therapy.


Suppression of arthritis by an inhibitor of nitric oxide synthase.
Nitric oxide (NO), a toxic radical gas produced during the metabolism of L-arginine by NO synthase (NOS), has been implicated as a mediator of immune and inflammatory responses. A single injection of streptococcal cell wall fragments (SCW) induces the accumulation of inflammatory cells within the synovial tissue and a cell-mediated immune response that leads destructive lesions. We show here that NO production is elevated in the inflamed joints of SCW-treated rats. Administration of NG-monomethyl-L-arginine, an inhibitor of NOS, profoundly reduced the synovial inflammation and tissue damage as measured by an articular index and reflected in the histopathology. These studies implicate the NO pathway in the pathogenesis of an inflammatory arthritis and demonstrate the ability of a NOS inhibitor to modulate the disease.


[The use of melamine-formaldehyde latex in the automated analysis of immunocompetent cells].
The optimization of the loading of monodispersed melamine-formaldehyde latex with fluorochrome has permitted its use as indicator material, equally suitable both for the visual evaluation of the reaction of phagocytosis and for the automated evaluation of this reaction by means of a scanning fluorescent microscope. The study has shown the possibility of using fluorescent melamine formaldehyde latex for the evaluation of the phagocytosis of mouse peritoneal macrophages and human blood cells, as well as the analysis of the surface receptors of immunocompetent cells.


Financial Toxicity in Crohn's Disease.
A patient-reported outcome measure called Comprehensive Score for Financial Toxicity (COST) was previously developed and validated in patients with cancer. We sought to assess the financial toxicity associated with Crohn's disease (CD) by administering the COST questionnaire to patients treated at a tertiary care center. Forty-eight patients diagnosed with CD completed questionnaires, which included the COST quality of life instrument as well as questions with regard to sociodemographics and clinical characteristics. Analysis of results was performed with Minitab. Forty-eight completed questionnaires were scored. The mean age of the cohort was 37.6±13.4 years and 58% of patients were women. COST scores had a normal distribution (Anderson-Darling, P=0.31). The median COST score was 22, a result associated with mild negative impact on health-related quality of life. Patients' COST score stratum differed based on their education level (P<0.001), employment status (P=0.037), disability status (P=0.016), household income (P=0.004), and housing arrangement (P=0.006). Disease activity in the past 6 months and more frequent feelings of anxiety and depression also correlated with higher COST score. In this survey study, we found that the majority of our patients with CD experienced at least mild financial distress. Lower income and education level increased disease activity, and the presence of anxiety and depression increased the financial distress experienced by patients. Further research is needed to develop effective interventions to minimize financial toxicity in this patient population.


Prevalence of Caries among Schoolchildren in the Interior of Suriname.
The aim of this study was to determine the prevalence of caries among children living in the interior of Suriname and to investigate the influence of the reachability of their habitats and different ethnicities on the prevalence of caries. As part of children's regular dental check-ups, data on the prevalence of caries were registered for schoolchildren (n = 1,309) living in four different regions. Prevalence of caries was expressed by the number of decayed, missing, and filled teeth (DMFT index). Consequences of severe caries were recorded by counting the number of teeth with pulp involvement, ulcerations, fistulas, and abscesses. Depending on the habitat, the number of children with caries in their primary dentition varied between 68% and 100%, in the mixed dentition between 79% and 98%, and in their permanent dentition between 54% and 94%. After the World Health Organization criteria, the average scores of dmft were high in children with primary teeth (except for Brokopondo), moderate to high in children with mixed dentition and low to moderate in children with permanent teeth. Children in more remote areas had a greater prevalence of caries than children in less remote regions. Severe consequences of caries were seen in 14-75% of the children. Treatments were rarely performed. Children in the interior of Suriname are in great need of preventive and curative dental treatments.


Habits and perceptions regarding open science by researchers from Spanish institutions.
The article describes the results of the online survey on open science (OS) carried out on researchers affiliated with universities and Spanish research centres and focused on open access to scientific publications, the publication process, the management of research data and the review of open articles. The main objective was to identify the perception and habits of researchers with regard to practices closely linked to open science and the scientific value added is that offers an in-depth picture of researchers as one of the main actors to whom this transformation and implementation of open science will fall. It focuses on the different aspects of OS: open access, open data, publication process and open review in order to identify habits and perceptions. This is to make possible an implementation of the OS movement. The survey was carried out among researchers who had published in the years 2020-2021, according to data obtained from WoS. It was emailed to a total of 8,188 researchers and obtained a total of 666 responses, of which 554 were complete, the rest being forms with some questions unanswered. The main results showed that open access still requires the diffusion of practices and services provided by the institution, as well as training (library or equivalent service) and institutional support from the competent authorities (vice rectors or equivalent) in specific aspects such as data management. In the case of data, around 50% of respondents stated they had stored data in a repository, and of all the options, the most frequently given was that of an institutional repository, followed by a discipline repository. Among the main reasons for doing this, we found transparency, visibility of data and the ability to validate results. For those who stated they had never stored data, the most frequent reasons for not having done so were privacy and confidentiality, the lack of a mandated data policy or a lack of knowledge of how to do it. In terms of open peer review, participants mentioned a certain reticence to the opening of evaluations due to potential conflicts of interest that may arise or because lower-quality content might be accepted in order to avoid conflicts. In addition, the hierarchical structure of senior researcher versus junior researcher might affect reviews. The main conclusions indicate a need for persuasion of OA to take place; APCs are an economic barrier rather than the main criterion for journal selection; OPR practices may seem innovative and emerging; scientific and evaluation policies seem to have a clear effect on the behaviour of researchers; researchers state that they share research data more for reasons of persuasion than out of obligation. Researchers do question the pathways or difficulties that may arise on a day-to-day basis and seem aware that we are undergoing change, where academic evaluation or policies related to open science, its implementation and habits among researchers may change. In this sense, more and better support is needed on the part of institutions and faculty support services.


The role of Gemtuzumab Ozogamicin in the treatment of acute myeloid leukemia patients.
Gemtuzumab Ozogamicin (GO) is an antibody-targeted chemotherapy agent consisting of the humanized murine CD33 antibody (clone P67.6) to which the calicheamicin-g1 derivative is attached via a hydrolysable bifunctional linker. GO is able to induce apoptosis in vitro in CD33-expressing cells and it has been approved in USA and in Europe as monotherapy for the treatment of elderly patients (older than 60 years) with relapsed acute myeloid leukemia (AML). GO administered as a single agent has resulted in overall response rates of about 30% in previously relapsed adults AML patients (including also with incomplete platelet recovery). Preliminary data indicate a potential role for GO also as a component of induction or consolidation regimens in adults and children. As for adverse events, veno-occlusive syndrome characterizes its tolerability profile, but GO is comparatively well tolerated by most patients.


[Economic aspects of prevention: an international perspective].
This article provides an overview of selected economic aspects of primary prevention, from an international perspective. It starts by qualifying two widely held myths about the economics of prevention. It then discusses two core components of the economic argument for (or against) prevention: first, this involves providing a very basic, efficiency-based rationale for a role of government in prevention; second, we review the existing evidence on the cost-effectiveness of primary prevention. While a fair amount of encouraging evidence exists, there has definitely been far more cost-effectiveness research on clinical than on non-clinical primary prevention (e. g., health promotion). The article seeks to explain this comparative shortage, which carries over to pure effectiveness research on prevention. It concludes by arguing the economic case for a role of government not only in prevention but also, and even more so, in research on non-clinical prevention.


Induction of glutathione S-transferase genes of Nicotiana benthamiana following infection by Colletotrichum destructivum and C. orbiculare and involvement of one in resistance.
Four glutathione S-transferase (GST) genes, NbGSTU1, NbGSTU2, NbGSTU3, and NbGSTF1, were amplified from cDNA of Nicotiana benthamiana leaves infected with Colletotrichum destructivum using primers based on conserved regions of N. tabacum GST sequences. Expression of NbGSTU1 and NbGSTU3 increased progressively during infection by either C. destructivum or Colletotrichum orbiculare, except for a slight decrease by NbGSTU1 late in the infection, whereas NbGSTU2 and NbGSTF1 expression remained relatively constant. Each of the four genes was cloned into a PVX vector for virus-induced gene silencing, and reduced expression of the four genes was detected by RT-PCR. A statistically significant increase in susceptibility of N. benthamiana to infection following gene silencing was found only for NbGSTU1-silenced plants, which had 130% more lesions and 67% more colonization by C. orbiculare compared with control plants. These results demonstrate that the different GST genes respond in different ways to fungal infection, and at least one plant GST gene has an important role in disease development.


AGTR1 gene variation: association with depression and frontotemporal morphology.
The renin-angiotensin system (RAS) is implicated in the response to physiological and psychosocial stressors, but its role in stress-related psychiatric disorders is poorly understood. We examined if variation in AGTR1, the gene coding for the type 1 angiotensin II receptor (AT(1)R), is associated with a diagnosis of depression and differences in white matter hyperintensities and frontotemporal brain volumes. Participants comprised 257 depressed and 116 nondepressed elderly Caucasian subjects who completed clinical assessments and provided blood samples for genotyping. We used a haplotype-tagging single nucleotide polymorphism (htSNP) analysis to test for variation in AGTR1. For measurement of hyperintense lesions, 1.5 Tesla magnetic resonance imaging (MRI) data were available on 33 subjects. For measurements of the hippocampus and dorsolateral prefrontal cortex (dlPFC), 3 Tesla MRI data were available on 70 subjects. Two htSNPs exhibited statistically significant frequency differences between diagnostic cohorts: rs10935724 and rs12721331. Although hyperintense lesion volume did not significantly differ by any htSNP, dlPFC and hippocampus volume differed significantly for several htSNPs. Intriguingly, for those htSNPs differing significantly for both dlPFC and hippocampus volume, the variant associated with smaller dlPFC volume was associated with larger hippocampal volume. This supports the idea that genetic variation in AGTR1 is associated with depression and differences in frontotemporal morphology.


Acute Care Utilization and Costs Up to 4 Years After Index Sleeve Gastrectomy or Roux-en-Y Gastric Bypass: A National Claims-based Study.
To compare acute care utilization and costs following sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB). Comparing postbariatric emergency department (ED) and inpatient care use patterns could assist with procedure choice and provide insights about complication risk. We used a national insurance claims database to identify adults undergoing SG and RYGB between 2008 and 2016. Patients were matched on age, sex, calendar-time, diabetes, and baseline acute care use. We used adjusted Cox proportional hazards to compare acute care utilization and 2-part logistic regression models to compare annual associated costs (odds of any cost, and odds of high costs, defined as ≥80th percentile), between SG and RYGB, overall and within several clinical categories. The matched cohort included 4263 SG and 4520 RYGB patients. Up to 4 years after surgery, SG patients had slightly lower risk of ED visits [adjusted hazard ratio (aHR): 0.90; 95% confidence interval (CI): 0.85,0.96] and inpatient stays (aHR: 0.80; 95% CI: 0.73,0.88), especially for events associated with digestive-system diagnoses (ED aHR: 0.68; 95% CI: 0.62,0.75; inpatient aHR: 0.61; 95% CI: 0.53,0.72). SG patients also had lower odds of high ED and high total acute costs (eg, year-1 acute costs adjusted odds ratio (aOR) 0.77; 95% CI: 0.66,0.90) in early follow-up. However, observed cost differences decreased by years 3 and 4 (eg, year-4 acute care costs aOR 1.10; 95% CI: 0.92,1.31). SG may have fewer complications requiring emergency care and hospitalization, especially as related to digestive system disease. However, any acute care cost advantages of SG may wane over time.


Cost-effectiveness of continuous subcutaneous insulin infusion (CSII) in children: illusion or delusion?
Cost-effectiveness of continuous subcutaneous insulin infusion (CSII) in children is reviewed in the context of possible improvement of percentage of hemoglobin A1c (HbA1c) and of other clinical benefits over multiple daily injections (MDI). Cost-effectiveness depends on clinical efficacy but reported clinical efficacy parameters may overlook definite benefits perceived by children and parents using CSII. There are few detailed reports on cost comparisons between CSII and MDI in adults, even less in children or adolescents. Review of direct extra costs for CSII over conventional treatment, including MDI, suggest that these may double, 5000-6000 EUR vs. 3000 EUR per patient year. An example is given of how to calculate direct cost differences, showing local differences. Randomized comparisons between CSII and MDI in childhood and adolescence show few marked clinical effects, but non-randomized comparisons favor CSII. Quality of life parameters fall short in any such comparison in children and adolescents alike. The reasons for the apparent discrepancy between non-randomized childhood studies and the randomized prospective ones are given. There is a dire need for better parameters to assess the well-being of diabetic children treated by CSII or MDI. Only then is it warranted to estimate the cost-effectiveness of CSII vs. MDI in childhood and adolescence.


Efficacy of gamma radiation and aqueous chlorine on Escherichia coli O157:H7 in hydroponically grown lettuce plants.
Interaction of Escherichia coli O157:H7/pGFP with hydroponically grown lettuce plants was evaluated in this study. Lettuce seedlings were planted in contaminated Hoagland's nutrient solution and thereafter subjected to gamma radiation at 0.25, 0.5, and 0.75 kGy, and aqueous chlorine at 200 ppm. There was no trace of E. coli O157:H7/pGFP in lettuce leaves harvested from noncontaminated nutrient solution (control); however, for plants grown in contaminated nutrient solution, the pathogen was recovered from the leaves disinfected with 80% ethanol and 0.1% mercuric chloride. Most of the lettuce seedlings grown in contaminated nutrient solution tested negative for E. coli O157:H7/pGFP under controlled conditions. Gamma radiation at 0.25 and 0.5 kGy, and aqueous chlorine at 200 ppm failed to eliminate E. coli O157:H7/pGFP in lettuce tissue completely; however, the bacteria were not detected in 0.75-kGy treated plants. The presence of E. coli O157:H7/pGFP in lettuce leaves is an indication that the pathogen migrated from the contaminated hydroponic system through the roots to the internal locations of lettuce tissue. Due to inaccessibility and limited penetrating power, aqueous chlorine could not eliminate the bacteria localized in the internal tissue. Findings from this study suggest that gamma irradiation was more efficacious than was aqueous chlorine to control internal contamination in hydroponically grown lettuce. Gamma irradiation is a process that processors can use to inactivate E. coli O157:H7 and therefore, consumers benefit from a safer food product [corrected]


Oxidative Stress and Inflammatory Biomarkers in People with Methamphetamine Use Disorder.
This study aimed to investigate the blood serum levels of biomarkers specifying oxidative stress status and systemic inflammation between people using methamphetamine (METH) and the control group (CG). Serum thiol/disulfide balance and ischemia-modified albumin levels were studied to determine oxidative stress, and serum interleukin-6 (IL-6) levels and complete blood count (CBC) were to assess inflammation. Fifty patients with METH use disorder (MUD) and 36 CG participants were included in the study. Two tubes of venous blood samples were taken to measure oxidative stress, serum thiol/disulfide balance, ischemia-modified albumin, and IL-6 levels between groups. The correlation of parameters measuring oxidative stress and inflammation between groups with sociodemographic data was investigated. In this study, serum total thiol, free thiol levels, disulfide/native thiol percentage ratios, and serum ischemia- modified albumin levels of the patients were statistically significantly higher than the healthy controls. No difference was observed between the groups in serum disulfide levels and serum IL-6 levels. Considering the regression analysis, only the duration of substance use was a statistically significant factor in explaining serum IL-6 levels. The parameters showing inflammation in the CBC were significantly higher in the patients than in the CG. CBC can be used to evaluate systemic inflammation in patients with MUD. Parameters measuring thiol/disulfide homeostasis and ischemia-modified albumin can be, also, used to assess oxidative stress.


Comparison of Myeloid Cells in Circulation and in the Tumor Microenvironment of Patients with Colorectal and Breast Cancers.
We have previously reported levels of myeloid cells in the periphery and in the tumor microenvironment (TME) of patients with primary breast cancer (PBC) and colorectal cancer (CRC). We found that both PBC and CRC patients have significantly higher levels of granulocytic and immature myeloid cells in the TME. Additionally, we reported an expansion of circulating granulocytic myeloid cells in CRC patients, but not in PBC patients. In this report, we compared levels of myeloid cells between these two common cancers and have added data from more cancer patients. We also investigated associations between clinical stage/histological grade of tumors and levels of myeloid cells in cancer patients. We found that although granulocytic myeloid cells were expanded in the TME of both PBC and CRC patients, the levels of these cells were significantly higher in the TME of CRC patients. Moreover, our results indicate that increased levels of circulating granulocytic myeloid cells are associated with poorly differentiated tumors in CRC patients. Taken together, this work suggests that CRC patients may benefit more from the development of therapeutic agents to promote myeloid cell differentiation or inhibition for the reversal of immune suppression.


Is determination of creatine kinase-2 after electrophoretic separation accurate?
Since 1991, the Ontario Laboratory Proficiency Testing Program has assessed the analytical performance of creatine kinase (CK; EC 18.104.22.168) isoenzyme-2, using fresh human serum supplemented with purified human CK isoenzymes. In Ontario, the 142 laboratories licensed to analyze CK-2 use a variety of methods: electrophoresis-based, immunoinhibition, and mass assays. During a 1992 survey, duplicate CK-2 samples with different total CK activities showed poorer precision when analyzed after electrophoretic separation than by any other method. A 1993 survey designed to validate these observations conclusively showed that electrophoresis-based assays are subject to a bias proportional to the total CK activity. These survey results were confirmed by studies with selected patients' specimens. We therefore conclude that electrophoresis-based assays may not warrant their reputation as the gold standard for CK isoenzyme measurement.


Project ECHO: linking university specialists with rural and prison-based clinicians to improve care for people with chronic hepatitis C in New Mexico.
Project Extension for Community Healthcare Outcomes (Project ECHO) is a telemedicine and distance-learning program designed to improve access to quality health care for New Mexicans with hepatitis C. Project ECHO links health-care providers from rural clinics, the Indian Health Service, and prisons with specialists at the University of New Mexico. At weekly clinics, partners present and discuss patients with hepatitis C with specialists. Partners can receive continuing education credits for participating. Since June 2003, 173 hepatitis C clinics have been conducted with 1,843 case presentations. Partners have received 390 hours of training and 2,997 hours of continuing education credits. And in 2006, the State Legislature approved $1.5 million in annual funding for the project. Project ECHO has increased access to state-of-the art hepatitis C virus care for patients living in rural areas or prisons. Because of its success with hepatitis C, this project is being expanded to other chronic medical conditions.


Peritoneal dialysis immediately after kidney transplantation.
Approximately 10% - 20% of adult kidney transplant recipients and as many as 40% of pediatric recipients receive peritoneal dialysis (PD) before kidney transplantation. An important aspect of perioperative kidney transplant care is management of the PD catheter. Peritoneal dialysis can be performed immediately after transplantation for delayed graft function (DGF), which can occur with as many as 20% of deceased-donor kidney grafts, especially when expanded criteria or organs from donation after cardiac death are used. However, leaving the PD catheter in place has been associated with an increased risk for infections such as peritonitis and exit-site infection, even when the catheter is not used. Although no consensus has been reached about the management of PD catheters after kidney transplantation, transplant centers should have a low threshold for PD catheter removal at the time of surgery, especially in recipients with a low risk for DGF. In individuals with high risk for DGF the PD catheter can be left in place, but it must be removed in a timely manner once it is no longer needed.


An Extragenital Colonic Salpingiosis.
Endosalpingiosis is a rare condition characterized by the presence of benign fallopian tubal-like glandular epithelium derived from Mullerian ducts, usually affecting the serosal surfaces of the pelvis and peritoneum. It is histologically differentiated from endometriosis as endosalpingiosis lacks endometrial stroma. Endosalpingiosis tends to affect older women and has been associated with ovarian serous tumors of low malignant potential. The extragenital endosalpingosis is typically without symptoms, reported only once as chronic pelvic pain. It rarely affects the appendix but can be mistaken for acute appendicitis or appendiceal tumors. No reports of endoscopic findings have been never described. Its treatment is challenging and provides a multidisciplinary approach with gynecologist, surgeon and gastrointestinal endoscopist. Our case reports for the first time an endoscopic finding of colonic salpingiosis and it is challenging both for the diagnosis and for the treatment.


Optimization and validation of a two-step method for the determination of polybrominated diphenyl ethers in Croatian house dust samples.
Microwave-assisted extraction was applied as a method for extraction of seven polybrominated diphenyl ether (PBDE) congeners (28, 47, 99, 100, 153, 154, and 183) from house dust samples. Optimization of MAE experimental conditions was achieved using a multivariate design approach, and the results indicated that only the choice of extraction solvent had a statistically significant influence on extraction efficiency. The extract purification step was also investigated in detail with a goal to achieve effective cleaning, with minor solvent consumption. As the final operating conditions, 20 min MAE extraction from 1 g of dust with 20 mL of n-hexane : acetone (1 : 1, v/v) at 80 °C and extract purification on an in-lab prepared column containing 2 g of neutral silica and 4 g of acidified silica, whereby the PBDEs were eluted from the column with 15 mL of n-hexane : dichloromethane (4 : 1, v/v), were selected. The extracts were analyzed on a dual GC-μECD system, and GC-MS/MS was used as a confirmatory method. The performance of the optimized method was validated by analyzing spiked dust samples and a standard reference material (NIST 2585 "Organic Contaminants in House Dust"). Congener specific PBDE recovery ranged from 76% to 90% for the spiked samples (with very good repeatability; RSD < 7%) and the measured mass concentrations of selected PBDEs were in excellent agreement with certified values for a standard reference material. The proposed method was successfully applied to the analysis of targeted PBDEs in house dust samples.


Ginger, a Possible Candidate for the Treatment of Dementias?
As the human life expectancy increases, age-linked diseases have become more and more frequent. The worldwide increment of dementia cases demands medical solutions, but the current available drugs do not meet all the expectations. Recently the attention of the scientific community was attracted by natural compounds, used in ancient medicine, known for their beneficial effects and high tolerability. This review is focused on Ginger (Zingiber officinale) and explore its properties against Alzheimer's Disease and Vascular Dementia, two of the most common and devastating forms of dementia. This work resumes the beneficial effects of Ginger compounds, tested in computational in vitro and in vivo models of Alzheimer's Disease and Vascular Dementia, along with some human tests. All these evidences suggest a potential role of the compounds of ginger not only in the treatment of the disease, but also in its prevention.


PCR-Based Analysis of ColE1 Plasmids in Clinical Isolates and Metagenomic Samples Reveals Their Importance as Gene Capture Platforms.
ColE1 plasmids are important vehicles for the spread of antibiotic resistance in the Enterobacteriaceae and Pasteurellaceae families of bacteria. Their monitoring is essential, as they harbor important resistant determinants in humans, animals and the environment. In this work, we have analyzed ColE1 replicons using bioinformatic and experimental approaches. First, we carried out a computational study examining the structure of different ColE1 plasmids deposited in databases. Bioinformatic analysis of these ColE1 replicons revealed a mosaic genetic structure consisting of a host-adapted conserved region responsible for the housekeeping functions of the plasmid, and a variable region encoding a wide variety of genes, including multiple antibiotic resistance determinants. From this exhaustive computational analysis we developed a new PCR-based technique, targeting a specific sequence in the conserved region, for the screening, capture and sequencing of these small plasmids, either specific for Enterobacteriaceae or specific for Pasteurellaceae. To validate this PCR-based system, we tested various collections of isolates from both bacterial families, finding that ColE1 replicons were not only highly prevalent in antibiotic-resistant isolates, but also present in susceptible bacteria. In Pasteurellaceae, ColE1 plasmids carried almost exclusively antibiotic resistance genes. In Enterobacteriaceae, these plasmids encoded a large range of traits, including not only antibiotic resistance determinants, but also a wide variety of genes, showing the huge genetic plasticity of these small replicons. Finally, we also used a metagenomic approach in order to validate this technique, performing this PCR system using total DNA extractions from fecal samples from poultry, turkeys, pigs and humans. Using Illumina sequencing of the PCR products we identified a great diversity of genes encoded by ColE1 replicons, including different antibiotic resistance determinants, supporting the previous results achieved with the collections of bacterial isolates. In addition, we detected cryptic ColE1 plasmids in both families with no known genes in their variable region, which we have named sentinel plasmids. In conclusion, in this work we present a useful genetic tool for the detection and analysis of ColE1 plasmids, and confirm their important role in the dissemination of antibiotic resistance, especially in the Pasteurellaceae family of bacteria.


A catastrophic death assemblage and paleoclimatic implications of pliocene seabirds of Florida.
A deposit of fossil seabirds from the late Pliocene of Florida includes more than 130 skeletons of an extinct cormorant that is related phylogenetically to Recent species currently restricted to the eastern north Pacific. Evidence suggests the birds died in a single catastrophic event, perhaps a red tide. The fossil cormorant, along with other extinct seabirds and marine mammals, supports molluscan evidence for cold-water upwelling along the Florida Gulf Coast during the Pliocene. A decline in species richness of marine vertebrates throughout the Pliocene of Florida coincides with cessation of upwelling after emergences of the Panamanian Land Bridge.


Transmission of HIV-1 drug-resistant variants: prevalence and effect on treatment outcome.
Human immunodeficiency virus type 1 (HIV-1) drug resistance is an important threat to the overall success of antiretroviral therapy (ART). Because of the limited sensitivity of commercial assays, transmitted drug resistance (TDR) may be underestimated; thus, the effect that TDR has on treatment outcome needs to be investigated. The objective of this study was to investigate the prevalence of TDR in HIV-infected patients and to evaluate the significance of TDR with respect to treatment outcome by analyzing plasma viral RNA and peripheral blood mononuclear cell proviral DNA for the presence of drug resistance mutations. In a prospective study, we investigated the level of TDR in 61 patients by comparing the results of a sensitive multiplex-primer-extension approach (termed HIV-SNaPshot) that is capable of screening for 9 common nucleoside reverse-transcriptase inhibitor and nonnucleotide reverse-transcriptase inhibitor mutations with those of a commercial genotyping kit, ViroSeq (Abbott). Twenty-two patients were found to carry mutations. More patients with TDR were identified by the HIV-SNaPshot assay than by ViroSeq analysis (33% vs 13%; [P=.015). There was no significant difference in the time from initiation of ART to virological suppression between susceptible patients and those carrying low- or high-level resistance mutations (mean +/- standard deviation, 128 +/- 59.1 vs 164.9 +/- 120.4; P=.147). Furthermore, analyses of CD4 cell counts showed no significant difference between these 2 groups 1 year after the initiation of ART (mean, 184 vs 219 cells/microL; P=.267). We found the prevalence of TDR in recently infected ART-naive patients to be higher than that estimated by ViroSeq genotyping alone. Follow-up of patients after treatment initiation showed a trend toward there being more clinical complications for patients carrying TDR, although a significant effect on treatment outcome could not be demonstrated. Therefore, the clinical relevance of low-abundance resistant quasispecies in early infection is still in question.


Pediatric solid tumors and associated cancer predisposition syndromes: Workup, management, and surveillance. A summary from the APSA Cancer Committee.
Cancer predisposition syndromes (CPS) are a heterogeneous group of inherited disorders that greatly increase the risk of developing malignancies. CPS are particularly relevant to pediatric surgeons since nearly 10% of cancer diagnoses are due to inherited genetic traits, and CPS often contribute to cancer development during childhood. The English language literature was searched for manuscripts, practice guidelines, and society statements on "cancer predisposition syndromes in children". Following review of these manuscripts and cross-referencing of their bibliographies, tables were created to summarize findings of the most common CPS associated with surgically treated pediatric solid malignancies. Pediatric surgeons should be aware of CPS as the identification of one of these syndromes can completely change the management of certain tumors, such as WT. The most common CPS associated with pediatric solid malignancies are outlined, with an emphasis on those most often encountered by pediatric surgeons: neuroblastoma, Wilms' tumor, hepatoblastoma, and medullary thyroid cancer. Frequently associated non-tumor manifestations of these CPS are also included as a guide to increase surgeon awareness. Screening and management guidelines are outlined, and published genetic testing and counseling guidelines are included where available. Pediatric surgeons play an important role as surgical oncologists and are often the first point of contact for children with solid tumors. In their role of delivering a diagnosis and developing a follow-up and treatment plan as part of a multidisciplinary team, familiarity with common CPS will ensure evidence-based practices are followed, including important principles such as organ preservation and intensified surveillance plans. This review defines and summarizes the CPS associated with common childhood solid tumors encountered by the pediatric surgeon, as well as common non-cancerous disease stigmata that may help guide diagnosis. Summary paper. 5.


Lithium antagonism of ethanol-induced intoxication: relationship to intracellular lithium levels.
Seventeen detoxified chronic alcoholics participated in a double-blind trial comparing placebo and lithium (Li+) effects on acute ethanol (1 g/kg) intoxication. In a repeated measures, split-half crossover design, subjects were maintained for 7 days on Li+ or placebo before the ethanol challenge. Plasma Li+ levels on day 7 averaged 1.3 +/- 0.3 mM. Li+ was not more effective than placebo in attenuating ethanol effects across the subjective dimensions of intoxication, desire to drink, and control of drinking and across the cognitive dimensions measured by Trail Making A, Speed of Closure, and the Minnesota Clerical Test. Li+ was not significantly more effective than placebo in preventing the ethanol-induced rise in plasma prolactin. Subjects were divided according to high and low red blood cell (RBC) Li+ intracellular/extracellular Li+ ratios. In a comparison of the Li+ to placebo arms of the trial, the high ratio subjects (n = 9) showed a significant 44% decrease in ethanol-induced intoxication, while the low ratio subjects (n = 8) showed a 15% increase. Furthermore, the high ratio subjects performed better than the low ratio subjects, independent of the ethanol effect, on all tests of cognitive performance. These preliminary data suggest that the Li+ ratio may be a useful tool in defining unique subgroups of alcoholic patients.


ST-segment monitoring: putting standards into practice.
ST-segment monitoring is one key reason that continuous electrocardiographic monitoring is performed in hospitals, and can help with early detection of myocardial ischemia for at-risk patients. Although ST-segment monitoring research, guidelines, and expert consensus statements have been published, ST-segment monitoring has not been implemented in all appropriate clinical areas. The purpose of this article is to present relevant research, review the latest practice standards, and discuss issues important to nurses wishing to implement ST-segment monitoring.


Predictors of Passive and Active Suicidal Ideation and Suicide Attempt Among Older People: A Study in Tertiary Care Settings in Thailand.
This study compared predictors of passive suicidal ideation (SI), active SI, and suicide attempt (SA) among elderly Thai patients in tertiary care settings. Psychiatric diagnoses and suicidality of 803 older people were assessed using the Mini-International Neuropsychiatric Interview and the Structured Clinical Interview for DSM-IV-TR. All participants completed the Montreal Cognitive Assessment, multidimensional scale of perceived social support (MSPSS), 15-item Thai geriatric depression scale (TGDS-15), 10-item perceived social scale and the Core Symptoms Index. The chi-square test, t-test and ANOVA were used for bivariate analysis of predictors of specific suicidality types. Multiple logistic regression was used to determine the predictors for each type of suicidality. The patients' mean age was 69.24 ± 6.90 years, and the majority were female (69.74%). Passive SI, active SI and SA were found among 20.42%, 3.74% and 2.37%, respectively, of the patients. Major depressive disorder (MDD) was a predictor of both passive and active SI (OR = 2.06 and 3.74, respectively). Other predictors of passive SI included hypomania (OR = 8.27) and positive score on the TGDS-15 (OR = 1.29). Predictors of active SI included agoraphobia (OR = 6.84) and hypomania (OR = 7.10). Predictors of SA included a family history of alcohol dependence (OR = 14.16), a history of depression (OR = 4.78) and agoraphobia (OR = 19.89). Surprisingly, hypertension and self-reported anxiety symptoms were protective factors for passive SI (OR = 0.51 and 0.85, respectively). Likewise, MSPSS was a protective factor for SA (OR = 0.90). Predictors of each type of suicidality differed. MDD was the main predictor for SI; however, agoraphobia and poor perceived social support were more pronounced among individuals with SA. Further investigation, especially in longitudinal fashion, should be warranted.


Calcitriol Suppression of Parathyroid Hormone Fails to Improve Skeletal Properties in an Animal Model of Chronic Kidney Disease.
Chronic kidney disease (CKD) leads to complex metabolic changes and an increased risk of fracture. Currently, calcitriol is the standard of care as it effectively suppresses parathyroid hormone (PTH) levels in CKD patients. While calcitriol and its analogs improve BMD and reduce fractures in the general population, the extension of these benefits to patients with advanced kidney disease is unclear. Here, the impact of calcitriol on the skeleton was examined in the setting of reduction in PTH. Male Cy/+ rats, a PKD-like CKD model, were treated with either vehicle or calcitriol for 5 weeks. Their normal littermates served as controls. Animals were assessed for changes in mineral metabolism and skeletal parameters (microCT, histology, whole bone mechanics and bone quality). PTH levels were significantly higher (12-fold) in animals with CKD compared to normal controls. CKD animals also exhibited negative changes in bone structural and mechanical properties. Calcitriol treatment resulted in a 60% suppression of PTH levels in animals with CKD. Despite these changes, it had no impact on bone volume (cortical or cancellous), bone turnover, osteoclast number or whole bone mechanical properties. These data indicate that while calcitriol effectively lowered PTH in rats with CKD, it did little to prevent the negative effects of secondary hyperparathyroidism on the skeleton.


Mushroom Consumption and Cardiovascular Health: A Systematic Review.
Edible mushrooms have a great nutritional value including high protein, essential amino acids, fiber, vitamins (B1, B2, B12, C, and D), minerals (calcium [Ca], potassium [K], magnesium [Mg], sodium [Na], phosphorus [P], copper [Cu], iron [Fe], manganese [Mn], and selenium [Se]), low fatty foods, and sodium. The objective of this systematic review was to determine the relationship between edible mushroom consumption and overall cardiovascular risk. We systematically searched Ovid MEDLINE, Embase, Ovid Cochrane Database of Systematic Reviews, Scopus, and Web of Science from database inception from 1966 through August 2020 for observational studies that reported the association between edible mushroom consumption and cardiovascular risk. Two investigators independently reviewed data. Conflicts were resolved through consensus discussion. Of 1479 studies, we identified 7 prospective studies. Edible mushroom consumption may have favorable effects on lipid profiles by changing some metabolic markers such as low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, total cholesterol, and triglycerides. Moreover, edible mushroom consumption is probably associated with reduced mean blood pressure. The beneficial overall cardiovascular risk, stroke risk, and coronary artery disease of edible mushroom consumption are not consistent. Edible mushroom consumption has not been shown to conclusively affect cardiovascular risk factors to date. However, potential health benefits may exist, including a favorable alteration of lipid profiles and blood pressure reduction.


An Incidental Case of Morgagni Hernia With Beaver Tail Liver in an Adult.
Morgagni hernia is a rare congenital defect of the diaphragm, especially seen in children but rarely observed in adults. It occurs due to a congenital defect during the development of the diaphragm. Bochdalek hernia is a common congenital form of diaphragmatic hernia. Morgagni hernia is usually rare with a prevalence of approximately 2-3%. Beaver tail liver, which is also called sliver of liver, is a rare variant of liver morphology. Sometimes elongated left lobe of the liver can extend laterally across the midline to contact and often surround the spleen. A 46-year-old female from Karnataka complained of fever with chills and lower back aches for seven days with no history of chest pain, vomiting, or diarrhea. There have been no similar complaints in the past. She had no other comorbidities. She was a non-smoker and non-alcoholic. Biomass gas exposure for 20 years was noted as she cooked food with firewood. She was a housewife by occupation with no history of trauma or surgeries in the past. The general physical exam was unremarkable. The respiratory system was normal. Auscultation showed decreased breath sounds in the mammary area of the right side of the chest with normal vesicular breath sounds in all other areas. Per abdominal exam showed a flat abdomen. Umbilicus was central in position. There was tenderness in the right hypochondriac and epigastric regions with no guarding or rigidity. On examining the cardiovascular system, apical impulses could not be palpated and normal heart sounds were heard with no cardiac murmurs. Other systems examination was normal. Routine blood investigations were done, revealing hemoglobin of 11.6%, total WBC of 6270 cells, and hematocrit of 33.1%. The renal function test was within normal limits (creatinine = 0.7 mg/dl). A chest X-ray revealed a right lower zone, para cardiac well-circumscribed structure suggestive of a cyst with an air-fluid level inside. Chest CT was suggestive of a hernia in the anterior aspect of the diaphragm measuring 3.5 x 3.3 cm at the level of D9 vertebral body with transverse colon and omentum as its contents, ascending upwards into anterior and superior mediastinum for a length of 13 cm causing shift of cardia posteriorly and to the left (anterior midline diaphragmatic hernia - Morgagni hernia). A hyperdense lesion (Hounsfield unit = 64) measuring 1.3 x 1.8 cm was noted in segment seven of the right lobe of the liver, suggestive of a complex cyst. Beaver tail was noted in the liver. Morgagni hernia usually presents in younger age groups with respiratory symptoms. Its incidental detection in adults is very rare. In this case, the patient was having lower backache and no other gastrointestinal symptoms. The respiratory and cardiothoracic systems get affected because the intestinal contents herniating through the diaphragm shift the position of the cardia and the lower lobes of the lungs, which may have implications such as repeated cough and infections. Symptomatic hernias are usually detected in an early age group. It can present with symptoms of gastrointestinal obstruction or acute chest symptoms or can even be asymptomatic. Treatment is primarily surgical repair of the hernia. This can be done either transthoracically or transabdominally. It is usually advised that surgical repair should be done even in asymptomatic cases as in this case, to avoid obstruction of the intestine or worsening of the hernia that is pulling the abdominal contents into the thorax.


Level of macroautophagy drives senescent keratinocytes into cell death or neoplastic evasion.
Senescence is a non-proliferative state reached by normal cells in response to various stresses, including telomere uncapping, oxidative stress or oncogene activation. In previous reports, we have highlighted that senescent human epidermal keratinocytes have two opposite outcomes: either they die by autophagic programmed cell death or they evade in the form of neoplastic postsenescence emergent (PSNE) cells. Herein, we show that partially reducing macroautophagy in senescent keratinocytes using 3-methyl adenine or anti-Atg5 siRNAs increases the PSNE frequency, suggesting that senescent keratinocytes have to escape autophagic cell death to generate PSNE cells. However, totally inhibiting macroautophagy impairs PSNE and leads to a huge accumulation of oxidative damages, indicating that senescent keratinocytes need to achieve quality-control macroautophagy for PSNE to occur. In accordance, we demonstrate that the progenitors of PSNE cells display a level of macroautophagy slightly lower than that of the average senescent population, which is directly dictated by their level of reactive oxygen species, their level of upregulation of MnSOD, their level of activation of NF-κB transcription factors and their level of dysfunctional mitochondria. Macroautophagy thus has antagonistic roles during senescence, inducing cell death or promoting neoplastic transformation, depending on its level of activation. Taken together, these data suggest that levels of oxidative damages and ensuing macroautophagic activity could be two main determinants of the very initial phases of neoplastic transformation by senescence evasion.


Risk indicators for aggressive periodontitis in an untreated isolated young population from Brazil.
This study aimed to assess the prevalence of aggressive periodontitis (AgP), and to investigate the association between demographic, socioeconomic and behavioral risk indicators with AgP in an untreated and isolated young population in Southeastern Brazil. For this cross-sectional survey, 134 subjects aged 12-29 years were selected by a census. Of those eligible, 101 subjects received a full-mouth clinical examination, and were interviewed using a structured written questionnaire. Cases were defined as individuals with 4 or more teeth with attachment loss > 4 mm or > 5 mm in the age groups 12-19 and 20-29, respectively. Overall, 9.9% of the subjects presented AgP (10.3% of the 12-19-year-olds and 9.7% of the 20-29-year-olds). The only risk indicator significantly associated with AgP in this isolated population was a high proportion of sites (> 30%) presenting supragingival calculus [OR = 23.2]. Having experienced an urgency dental treatment was a protective factor for AgP [OR = 0.1]. The authors concluded that this isolated and untreated population from Brazil presented a high prevalence of AgP. Local plaque-retaining factors played a major role in the prevalence of AgP in this isolated population, and should be included in further studies evaluating this destructive periodontal disease form.


Chemically accurate simulation of a prototypical surface reaction: H2 dissociation on Cu(111).
Methods for accurately computing the interaction of molecules with metal surfaces are critical to understanding and thereby improving heterogeneous catalysis. We introduce an implementation of the specific reaction parameter (SRP) approach to density functional theory (DFT) that carries the method forward from a semiquantitative to a quantitative description of the molecule-surface interaction. Dynamics calculations on reactive scattering of hydrogen from the copper (111) surface using an SRP-DFT potential energy surface reproduce data on the dissociative adsorption probability as a function of incidence energy and reactant state and data on rotationally inelastic scattering with chemical accuracy (within approximately 4.2 kilojoules per mole).


Plant parasitic nematodes associated with leatherleaf fern.
Seven species of plant parasitic nematodes were found to be associated with leatherleaf fern (Rumohra adiantiformis) in central Florida. Of these, Pratylenchus penetrans, Tylenchorhynchus claytoni, and Criconemoides curvatum were commonly encountered. Nematode communities generally included two or three species of plant parasitic nematodes, with greatest diversity in nematode species occurring in ferneries shaded by oak trees. Species diversity was not correlated with fernery age. Leatherleaf fern was tolerant of P. penetrans and T. claytoni in microplot tests.