Expression of sulfated carbohydrate chain and core peptides of mucin detected by monoclonal antibodies in Barrett's esophagus and esophageal adenocarcinoma.
Columnar epithelium-lined esophagus (Barrett's esophagus) is an acquired disorder associated with a high incidence of adenocarcinoma of the lower esophagus. Columnar epithelium resembling intestinal metaplasia (IM) is especially important, since it is considered to be a premalignant condition. The aim of this study was to define the sulfated carbohydrate chain of mucin and its core peptide profile in Barrett's esophagus (BE) and to compare it with the profile in Barrett's adenocarcinoma and lower esophageal adenocarcinoma. The sulfated carbohydrate chain was not expressed in 16 specimens of normal esophageal epithelium, but in BE, it was expressed in 50% (8/16) of the specimens. This chain was detected in 100% (7/7) of esophageal adenocarcinoma specimens, including four cases of Barrett's adenocarcinoma. These data suggest that the sulfated carbohydrate chain may be associated with malignant phenotype of the esophagus. MUC1 core peptide was positive in 87% (13/15) of BE specimens and in 29% (2/7) of the esophageal adenocarcinoma specimens. MUC2 core peptide was present in 57% (8/14) and 43% (3/7) of these specimens, respectively. These data suggest that Barrett's epithelium, which is similar to IM, but not normal esophageal epithelium, expresses the sulfated sugar chain which is known to be present in gastric IM and colonic mucosa. However, there was no significant correlation between the expression of the sulfated sugar chain and the expression of either mucin core peptide MUC1 or MUC2. Thus, this carbohydrate chain may be expressed on as yet unidentified core proteins, other than MUC1 or MUC2 core peptide, in BE and esophageal adenocarcinoma. Identification of these proteins may be very important in helping to detect premalignant status in BE.


Genomic and metabolic features of the Lactobacillus sakei JD10 revealed potential probiotic traits.
Lactic acid bacteria that inhabit in the lung play important roles in maintaining the microbiome balance by interacting with the host immune system. Numerous metabolites (e.g., short chain fatty acids, bacteriocins, and hydrogen peroxide) produced by Lactobacillus sakei possess a special inhibitory spectrum against invading pathogens. In this research, the whole genome of L. sakei JD10 strain isolated from the porcine lung was sequenced and investigated. The whole size of the L. sakei JD10 chromosome was 1,989,921 bp, which encoded a total of 1951 predicted genes. Genome analyses revealed that many genes encoded carbohydrate-active enzymes (CAZymes) were predicted, which were responsible for the carbohydrate degradation and short chain fatty acids production. The metabolic profiles of short chain fatty acids in the L. sakei JD10 culture medium were measured by GC/TOFMS, and their regulatory effects on bacterial phagocytosis of RAW264.7 cells were also determined. The bacteriocin-producing genes of the L. sakei JD10 genome were also predicted, and a bacteriocin gene encoding carnocin was characterized and its molecular structure was analyzed. Two CRISPR-Cas system related genes were identified from the L. sakei JD10 genome, revealed that precise and efficient genome editing technologies could be applied for genetic engineering-manipulation. In all, investigation on the genomic features and metabolic features of L. sakei JD10 showed the potential probiotic traits to fight against pathogenic infection and regulate the host immune function.


Identification of non-specific hybridization using an empirical equation fitted to non-equilibrium dissociation curves.
Non-equilibrium dissociation curves (NEDCs) have the potential to identify non-specific hybridizations on high throughput, diagnostic microarrays. We report a simple method for the identification of non-specific signals by using a new parameter that does not rely on comparison of perfect match and mismatch dissociations. The parameter is the ratio of specific dissociation temperature (T(d-w)) to theoretical melting temperature (T(m)) and can be obtained by automated fitting of a four-parameter, sigmoid, empirical equation to the thousands of curves generated in a typical experiment. The curves fit perfect match NEDCs from an initial experiment with an R(2) of 0.998±0.006 and root mean square of 108±91 fluorescent units. Receiver operating characteristic curve analysis showed low temperature hybridization signals (20-48°C) to be as effective as area under the curve as primary data filters. Evaluation of three datasets that target 16S rRNA and functional genes with varying degrees of target sequence similarity showed that filtering out hybridizations with T(d-w)/T(m)<0.78 greatly reduced false positive results. In conclusion, T(d-w)/T(m) successfully screened many non-specific hybridizations that could not be identified using single temperature signal intensities alone, while the empirical modeling allowed a simplified approach to the high throughput analysis of thousands of NEDCs.


Positive indium-111 leukocyte imaging in post myocardial infarction syndrome.
The diagnosis of post myocardial infarction syndrome (PMIS) is sometimes difficult because of the absence of a specific test. We report a 68-year-old man with PMIS who had a persistent accumulation of indium-111 oxine labeled leukocytes in the infarcted myocardium for 1 month. The uptake of leukocytes preceded the appearance of the main symptoms and disappeared with the clinical improvement after the therapy with steroids. Leukocyte imaging has a potential as a useful tool for early diagnosis, evaluation of therapy and assessing the mechanism of PMIS.


Disruption of N terminus long range non covalent interactions shifted temp.opt 25°C to cold: Evolution of point mutant Bacillus lipase by error prone PCR.
Cold adapted enzymes have applications in detergent, textile, food, bioremediation and biotechnology processes. Bacillus lipases are 'generally recognized as safe' (GRAS) and hence are industrially attractive. Bacillus lipase of 1.4 subfamily are of lowest molecular weight and are reversibly unfolded due to absence of disulphide bonds. Therefore these are largely used to study energetic of protein stability that represents unfolding of native protein to fully unfolded state. In present study, metagenomically isolated Bacillus LipJ was laboratory evolved for cold adaptation by error Prone PCR. Library of variants were screened for high relative activity at low temperature of 10°C compared to native protein LipJ. Point mutant sequenced as Phe19→Leu was determined to be active at cold and was selected for extensive biochemical, biophysical characterization. Variant F19L showed its maximum activity at 10°C where parent protein LipJ had 20% relative activity. Psychrophilic nature of F19L was established with about 50% relative active at 5°C where native protein was frozen to act. Variant F19L showed no activity at temperature 40°C and above, establishing its thermolabile nature. Thermostability studies determined mutant to be unstable above 20°C and three fold decrease in its half life at 30°C compared to native protein. Far UV-CD and intrinsic fluorescence study demonstrated unstable tertiary structure of point variant F19L leading to its unfolding at low temperature of 20°C. Cold adaptation of mutant F19L is accompanied with increased specific activity. Mutant was catalytically more efficient with 1.3 fold increase in kcat. Homologue structure modelling predicted disruption of intersecondary hydrophobic core formed by aromatic ring of Phe19 with non polar residues placed at β3, β4, β5, β6, αF. Increased local flexibility of variant F19L explains molecular basis of its psychrophilic nature.


Association between human papillomavirus vaccine status and sexually transmitted infection outcomes among females aged 18-35 with a history of sexual activity in the United States: A population survey-based cross-sectional analysis.
Current human papillomavirus (HPV) vaccine coverage in the United States (in 2019, 66-70%), remains below the Healthy People 2020 coverage goal of 80%. HPV vaccine misinformation, including parental concerns of sexual risk-compensation influence vaccine uptake. We examined the association between HPV vaccination and sexually transmitted infection (STI) outcomes. Of the 20,146 participants from 2013 to 2014 and 2015-2016 cycles of the National Health and Nutrition Examination Survey, 1050 females aged 18-35 with a history of sexual activity had complete case data. Roa-Scott Chi-squared and F-tests assessed survey-weighted socio-demographic differences between vaccinated and unvaccinated participants. Weighted logistic regression assessed crude and adjusted associations between self-reported HPV vaccination (none vs. ≥ 1dose) and lab-confirmed STIs (trichomonas and chlamydia) and vaccine-type HPV (6/11/16/18). As a sensitivity analysis, we conducted weighted-propensity score (PS) models and inverse probability weighting by vaccination status. PS and logistic regression were estimated through survey-weighted logistic regression on variables including race, education, income, marital status, US citizenship, cycle year and age. Overall, 325 (31.8%) females with a history of sexual activity were HPV vaccinated, of which 22 (6.1%) received the vaccine at the routine-recommended ages of 11-12, 65.7% were vaccinated after their self-reported sexual debut, 3.8% had a lab-confirmed STI and 3.5% had vaccine-type HPV. There was no association between HPV vaccination and any STIs (adjusted odds ratio [aOR] 0.67, 95%CI:0.38-1.20), and vaccinated participants had 61% reduced odds of vaccine-type HPV (vs. unvaccinated; aOR 0.39, 95%CI:0.19-0.83). Results from the PS sensitivity analysis were similar to the main findings. Among females who reported a history of sexual activity, HPV vaccination status was protective against vaccine-type HPV and not associated with lab-based STI outcomes. Although findings may be susceptible to reporting bias, results indicating low vaccine uptake at routine-recommended ages requires additional efforts promoting HPV vaccination before sexual-debut.


The General Factor of Personality: A General Critique.
Recently, it has been proposed that all non-cognitive measures of personality share a general factor of personality. A problem with many of these studies is a lack of clarity in defining a general factor. In this paper we address the multiple ways in which a general factor has been identified and argue that many of these approaches find factors that are not in fact general. Through the use of artificial examples, we show that a general factor is not: The first factor or component of a correlation or covariance matrix.The first factor resulting from a bifactor rotation or biquartimin transformationNecessarily the result of a confirmatory factor analysis forcing a bifactor solution We consider how the definition of what constitutes a general factor can lead to confusion, and we will demonstrate alternative ways of estimating the general factor saturation that are more appropriate.


Epidermal nuclear immunofluorescence: serological correlations supporting an in vivo reaction.
Epidermal nuclear deposits of immunoglobulins (Ig) were studied by direct immunofluorescence in three groups of patients: ten scleroderma (SD, systemic sclerosis), seven dermatomyositis (DM) and seven systemic lupus erythematosus (SLE). Each patient had skin biopsies taken from three different sites (nailfold, forearm, buttock) on the same day that a serum sample was also obtained. Epidermal nuclear deposits were observed in nine of twenty-four patients (five SD, two DM, two SLE). A high serum ANA titre correlated significantly with the presence of epidermal nuclear Ig deposits. The nucleolar epidermal nuclear pattern was limited to the SD group, four of ten patients showing this pattern. Two of nine patients with positive results in the nailfold and forearm had negative findings in the buttock, supporting the view that deposition of Ig in the epidermal nuclei occurs in vivo.


Activation of phenotypically distinct neuronal subpopulations in the anterior subdivision of the rat basolateral amygdala following acute and repeated stress.
The effects of acute and repeated stress on expression of the early immediate gene c-fos in the basolateral amygdala have previously been reported; however, characterization of which neuronal subpopulations are activated by these stimuli has not been investigated. This question is of considerable relevance, insofar as the basolateral amygdala houses a heterogeneous population of neurons, including those of gamma-aminobutyric acid (GABA)-ergic and glutamatergic phenotypes that may be subcategorized based on their expression of various calcium-binding proteins, including parvalbumin, calbindin, calretinin, and the calcium-sensitive enzyme calcium/calmodulin-dependent kinase II. Characterization of these subpopulations has revealed unique differences in their physiology, synaptology, and morphology, suggesting that each distinct phenotype may have profound effects on the local circuitry of the amygdala. Therefore, we examined the effects of acute and repeated restraint stress on expression of the immediate early gene c-fos in neurons containing parvalbumin, calbindin, calretinin, or calcium/calmodulin-dependent kinase II in the basolateral amygdala. Double-label immunohistochemistry revealed that acute restraint stress activated a proportion of parvalbumin-, calbindin-, or calcium/calmodulin-dependent kinase II-positive neurons. Prior exposure to repeated restraint stress markedly attenuated acute-stress mediated activation of these neuronal populations, although not equally. Expression of c-Fos protein was not detected in calretinin-positive neurons in any experimental group. These results demonstrate that distinct neuronal phenotypes in the basolateral amygdala are activated by acute restraint stress and that prior repeated restraint stress differentially affects this response.


Improving the quality of depression and pain care in multiple sclerosis using collaborative care: The MS-care trial protocol.
Evidence-based pharmacological and behavioral interventions are often underutilized or inaccessible to persons with multiple sclerosis (MS) who have chronic pain and/or depression. Collaborative care is an evidence-based patient-centered, integrated, system-level approach to improving the quality and outcomes of depression care. We describe the development of and randomized controlled trial testing a novel intervention, MS Care, which uses a collaborative care model to improve the care of depression and chronic pain in a MS specialty care setting. We describe a 16-week randomized controlled trial comparing the MS Care collaborative care intervention to usual care in an outpatient MS specialty center. Eligible participants with chronic pain of at least moderate intensity (≥3/10) and/or major depressive disorder are randomly assigned to MS Care or usual care. MS Care utilizes a care manager to implement and coordinate guideline-based medical and behavioral treatments with the patient, clinic providers, and pain/depression treatment experts. We will compare outcomes at post-treatment and 6-month follow up. We hypothesize that participants randomly assigned to MS Care will demonstrate significantly greater control of both pain and depression at post-treatment (primary endpoint) relative to those assigned to usual care. Secondary analyses will examine quality of care, patient satisfaction, adherence to MS care, and quality of life. Study findings will aid patients, clinicians, healthcare system leaders, and policy makers in making decisions about effective care for pain and depression in MS healthcare systems. (PCORI- IH-1304-6379; clinicaltrials.gov: NCT02137044). This trial is registered at ClinicalTrials.gov, protocol NCT02137044.


The human medulloblastoma cell line TE671 expresses a muscle-like acetylcholine receptor. Cloning of the alpha-subunit cDNA.
Nicotinic acetylcholine receptors (AChRs) from muscle bind alpha-bungarotoxin (alpha Bgt) and are composed of four kinds of subunits, whereas AChRs from mammalian brains do not bind alpha Bgt and are composed of two kinds of subunits. alpha Bgt-binding proteins whose function is unknown are also found in brain. All these proteins belong to the same gene family. The human medulloblastoma cell line TE671 expresses a functional AChR which binds alpha Bgt. Surprisingly, the AChR of this neuron-derived cell line has electrophysiological, immunological and biochemical properties different from neuronal AChRs and very similar to muscle AChRs. The TE671 AChR binds alpha Bgt, but is different from alpha Bgt-binding proteins in brain. Here we show that TE671 expresses the alpha-subunit mRNA coding for the muscle AChR, thereby proving that TE671 expresses a muscle-type AChR that is not expressed in adult brain. The isolated cDNA clones should prove useful for expression of large amounts of human muscle-type AChR alpha-subunit protein for studies of the autoimmune response to muscle AChRs in human myasthenia gravis.


Amyloid-beta(25-35)-induced memory impairments correlate with cell loss in rat hippocampus.
Amyloid beta-peptide (Abeta) plays an important role in the pathophysiology of Alzheimer's disease. The relationship between amnesia induced by central administration of aggregated Abeta(25-35) and neurodegeneration in the hippocampus was investigated. One month after a single intracerebroventricular injection of Abeta(25-35) (15 nmol), male Wistar rats were tested in an eight-arm radial maze. A quantitative evaluation of cell number in hippocampal regions was carried out on H&E-stained brain sections of rats used in the behavioral study. Indices of free radical-mediated processes in the hippocampus were evaluated in additional groups of animals 1, 3, 5, and 30 days after surgery. Abeta(25-35) induced impairments of working and reference memory (RM) as well as neurodegeneration in the CA1 but not in the CA3 field of the hippocampus. A significant correlation between both reference and working memory (WM) impairments and the neuronal cell loss in the hippocampal CA1 region was demonstrated. A gradually developing oxidative stress was evident in the hippocampus of rats treated with Abeta(25-35) as indicated by the increase in 2-thiobarbituric acid (TBARS) reactive substances and superoxide generation. These data suggest the involvement of oxidative stress in Abeta(25-35)-induced neurodegeneration and a relation between memory impairment and neurodegeneration in the CA1 subfield of the hippocampus.


Effect of allopurinol or superoxide dismutase plus catalase on cardiovascular function after burn injury in the anaesthetized rat.
A scald burn injury was applied to 22-23 per cent of the body surface area of anaesthetized rats. The cardiac output was 38-60 per cent lower in the burn injury group than in the control group; heart rate and mean arterial blood pressure were only slightly affected, but burn injury caused a significant increase in total peripheral resistance. The involvement of oxygen-free radicals in this immediate fall in cardiac output was investigated. Pretreatment with a blocker of free radical production, allopurinol or the infusion of the free radical scavengers superoxide dismutase plus catalase caused no cardiovascular improvement, suggesting that oxygen free radicals are not involved in the fall in cardiac output after burn injury. Allopurinol treatment, however, prevented the rise in total peripheral resistance seen after burn injury.


Antibiotic Use Prior to COVID-19 Vaccine Is Associated with Higher Risk of COVID-19 and Adverse Outcomes: A Propensity-Scored Matched Territory-Wide Cohort.
Background: Antibiotics may increase the risk of COVID-19 among non-vaccinated subjects via probable gut dysbiosis. We aimed to investigate whether antibiotics also affect the clinical outcomes of COVID-19 vaccine recipients. Methods: This was a territory-wide cohort study of 3,821,302 COVID-19 vaccine recipients (aged ≥ 18 years) with ≥2 doses of either BNT162b2 or CoronaVac. Exclusion criteria included prior COVID-19, prior gastrointestinal surgery, and immunocompromised status. The primary outcome was COVID-19 infection and secondary outcomes included COVID-19-related hospitalization and severe infection (composite of intensive care unit admission, ventilatory support, and/or death). Exposure was pre-vaccination antibiotic use (within 180 days of first vaccine dose). Covariates included age, sex, Charlson Comorbidity Index, and concomitant medication use. Subjects were followed from the index date (first dose vaccination) until outcome occurrence, death, an additional dose of vaccination, or 15 November 2022. Propensity score (PS) matching and a Poisson regression model were used to estimate the adjusted incidence rate ratio (aIRR) of outcomes with antibiotic use. Results: Among 342,338 PS matched three-dose vaccine recipients (mean age: 57.4 years; male: 45.1%) with a median follow-up of 13.6 months (IQR: 9.2-16.3), antibiotics were associated with a higher risk of COVID-19 infection (aIRR: 1.16;95% CI: 1.14-1.19), hospitalization (aIRR: 1.75;95% CI: 1.65-1.86), and severe infection (aIRR: 1.60; 95% CI: 1.21-2.11). Notably, antibiotic use was associated with a higher risk of severe infection and death among CoronaVac recipients (aIRR: 1.62 95% CI: 1.18-2.22 and aIRR: 2.70, 95% CI: 1.54-4.73 for the two secondary outcomes, respectively), but not BNT162b2 recipients. Conclusions: Pre-vaccination use of antibiotics was associated with a higher risk of COVID-19 infection, hospitalization, and severe disease outcomes.


Prevalence study of intermittent hormonal therapy of Prostate Cancer patients in Spain.
Background: Although intermittent androgen deprivation therapy was introduced many years ago to improve patients' quality of life with the same carcinologic efficiency as continuous hormonal therapy, recent data suggest that those patients could be overtreated. This study aims to estimate the prevalence of prostate cancer patients receiving intermittent androgen deprivation therapy in Spain. Methods: A retrospective, longitudinal study was conducted using electronic drug dispensation data from four Spanish autonomous communities, which encompass 17.23 million inhabitants (36.22% of the total population in Spain). We estimated intermittent androgen therapy use (%IAD) and the prevalence of patients under intermittent androgen therapy (P IAD) overall and stratified by region. Other outcome variables included the pharmaceutical forms dispensed and the total direct annual expenditure on androgen deprivation therapy-associated medications. Results: A total of 863,005 dispensations corresponding to a total of 65,752 men were identified, treated with either luteinizing hormone-releasing hormone (LHRH) analogues (353,162) administered alone or in combination with anti-androgens (509,843). Overall, the mean (±SD) age of the patients was 76.9 (±10.4) years. Results revealed that the mean annual P IAD along the study was 6.6% in the total population studied, and the overall %IAD during the five-year study period was 5.6%. The mean cost of hormonal therapy per year was 25 million euros for LHRH analogues and 6.3 million euros for anti-androgens. Conclusions: An important proportion of prostate cancer patients in Spain could benefit from intermittent androgen therapy during the study period while avoiding overtreatment harms associated with continuous hormonal therapy.


Formation of 4-hydroxynonenal and further aldehydic mediators of inflammation during bromotrichlorornethane treatment of rat liver cells.
Bromotrichloromethane (CBrCl(3)) treatment is a model for studies on molecular mechanisms of haloalkane toxicity with some advantages compared with CCl(4) treatment. The formation of 4-hydroxynonenal and similar aldehydic products of lipid peroxidation, which play a role as mediators of inflammatory processes, was clearly demonstrated in rat hepatocytes treated with CBrCl(3). It may be assumed that haloalkane toxicity is connected with the biological effects of those inflammation mediatory aldehydic compounds.


A mutation in the intron splice acceptor site of a GA3ox gene confers dwarf architecture in watermelon (Citrullus lanatus L.).
Dwarf architecture is an important trait associated with plant yield, lodging resistance and labor cost. Here, we aimed to identify a gene causing dwarfism in watermelon. The 'w106' (dwarf) and 'Charleston Gray' (vine) were used as parents to construct F1 and F2 progeny. Dwarf architecture of 'w106' was mainly caused by longitudinal cell length reduction and was controlled by a single recessive gene. Whole-genome sequencing of two parents and two bulk DNAs of F2 population localized this gene to a 2.63-Mb region on chromosome 9; this was further narrowed to a 541-kb region. Within this region, Cla015407, encoding a gibberellin 3β-hydroxylase (GA3ox), was the candidate gene. Cla015407 had a SNP mutation (G → A) in the splice acceptor site of the intron, leading to altered splicing event and generating two splicing isoforms in dwarf plants. One splicing isoform retained the intron sequences, while the other had a 13-bp deletion in the second exon of GA3ox transcript, both resulting in truncated proteins and loss of the functional Fe2OG dioxygenase domain in dwarf plants. RNA-Seq analysis indicated that expression of Cla015407 and other GA biosynthetic and metabolic genes were mostly up-regulated in the shoots of dwarf plants compared with vine plants in F2 population. Measurement of endogenous GA levels indicated that bioactive GA4 was significantly decreased in the shoots of dwarf plants. Moreover, the dwarf phenotype can be rescued by exogenous applications of GA3 or GA4+7, with the latter having a more distinct effect than the former. Subcellular localization analyses of GA3ox proteins from two parents revealed their subcellular targeting in nucleus and cytosol. Here, a GA3ox gene controlling dwarf architecture was identified, and loss function of GA3ox leads to GA4 reduction and dwarfism phenotype in watermelon.


Marine mollusc extracts-Potential source of SARS-CoV-2 antivirals.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel human coronavirus and the causative agent of coronavirus disease 2019 (Covid-19). There is an urgent need for effective antivirals to treat current Covid-19 cases and protect those unable to be vaccinated against SARS-CoV-2. Marine molluscs live in an environment containing high virus densities (>107 virus particles per ml), and there are an estimated 100,000 species in the phylum Mollusca, demonstrating the success of their innate immune system. Mollusc-derived antivirals are yet to be used clinically despite the activity of many extracts, including against human viruses, being demonstrated in vitro. Hemolymph of the Pacific oyster (Crassostrea gigas) has in vitro antiviral activity against herpes simplex virus and human adenovirus, while antiviral action against SARS-CoV-2 has been proposed by in silico studies. Such evidence suggests that molluscs, and in particular C. gigas hemolymph, may represent a source of antivirals for human coronaviruses.


Cloning and mapping of Np95 gene which encodes a novel nuclear protein associated with cell proliferation.
We previously obtained a monoclonal antibody (Th-10a mAb) that recognizes a single 95-kDa mouse nuclear protein (NP95). Immunostaining analyses revealed that the NP95 was specifically stained in the S phase of normal mouse thymocytes. In contrast, mouse T cell lymphoma cells exhibited a constantly high level of NP95 accumulation irrespective of cell stages during the cell cycle. In the present study, we isolated the cDNA encoding the NP95 from a lambdagt-11 cDNA expression library, using the Th-10a mAb. Sequencing of the whole 3.5-kb cDNA revealed that NP95 is a novel nuclear protein with an open reading frame (ORF) consisting of 782 amino acids. The ORF contains a zinc finger motif, a potential ATP/GTP binding site, a putative cyclin A/E-cdk2 phosphorylation site, and the retinoblastoma protein (RB)-binding motif "IXCXE". The chromosomal location of Np95 gene was determined by fluorescence in situ hybridization. Np95 gene locates on mouse Chromosome (Chr) 17DE1.1. and rat Chr 9q11.2-q12.1. Np95 was strongly expressed in the testis, spleen, thymus, and lung tissues, but not in the brain, liver, or skeletal muscles. These results collectively implicate this novel nuclear protein in cell cycle progression and/or DNA replication.


A 970 Hounsfield units (HU) threshold of kidney stone density on non-contrast computed tomography (NCCT) improves patients' selection for extracorporeal shockwave lithotripsy (ESWL): evidence from a prospective study.
What's known on the subject? and What does the study add? Stone density on non-contrast computed tomography (NCCT) is reported to be a prognosis factor for extracorporeal shockwave lithotripsy (ESWL). In this prospective study, we determined that a 970 HU threshold of stone density is a very specific and sensitive threshold beyond which the likelihood to be rendered stone free is poor. Thus, NCCT evaluation of stone density before ESWL may useful to identify which patients should be offered alternative treatment to optimise their outcome. • To evaluate the usefulness of measuring urinary calculi attenuation values by non-contrast computed tomography (NCCT) for predicting the outcome of treatment by extracorporeal shockwave lithotripsy (ESWL). • We prospectively evaluated 50 patients with urinary calculi of 5-22 mm undergoing ESWL. • All patients had NCCT at 120 kV and 100 mA on a spiral CT scanner. Patient age, sex, body mass index, stone laterality, stone size, stone attenuation values (Hounsfield units [HU]), stone location, and presence of JJ stent were studied as potential predictors. • The outcome was evaluated 4 weeks after the ESWL session by NCCT. • ESWL success was defined as patients being stone-free (SF) or with remaining stone fragments of <4 mm, which were considered as clinically insignificant residual fragments (CIRF). • Our survey concluded that 26 patients (52%) were SF, 12 (24%) had CIRF and 12 (24%) had residual fragment on NCCT after a one ESWL treatment. • Stones of patients who became SF or had CIRF had a lower density compared with stones in patients with residual fragments [mean (sd) 715 (260) vs 1196 (171) HU, P < 0.001]. • The Youden Index showed that a stone density of 970 HU represented the most sensitive (100%) and specific (81%) point on the receiver-operating characteristic curve. • The stone-free rate for stones of <970 HU was 96% vs 38% for stones of ≥ 970 HU (P < 0.001). A linear relationship between the calculus density and the success rate of ESWL was identified. • The use of NCCT to determine the attenuation values of urinary calculi before ESWL helps to predict treatment outcome, and, consequently, could be helpful in planning alternative treatment for patients with a likelihood of a poor outcome from ESWL.


Incorporating active-learning techniques and competency assessment into a critical care elective course.
To design, implement, and measure the effectiveness of a critical care elective course for second-year students in a 3-year accelerated doctor of pharmacy (PharmD) program. A critical care elective course was developed that used active-learning techniques, including cooperative learning and group presentations, to deliver content on critical care topics. Group presentations had to include a disease state overview, practice guidelines, and clinical recommendations, and were evaluated by course faculty members and peers. Students' mean scores on a 20-question critical-care competency assessment administered before and after the course improved by 11% (p < 0.05). Course evaluations and comments were positive. A critical care elective course resulted in significantly improved competency in critical care and was well-received by students.


Expression of N-methyl-d-aspartate receptor 1 and its phosphorylated state in basal ganglia of a neonatal piglet hypoxic-ischemic brain injury model: a controlled study of (1)H MRS.
Excitatory amino acids (EAAs) and excitotoxicity medicated by receptors of these amino acids play an important role in hypoxic-ischemic brain injury (HIBI), but most studies were ex vivo experiments, the mechanism in vivo is not well understood. We sought to study the expression of N-methyl-d-aspartate receptor 1 (NR1) and phosphorylated N-methyl-d-aspartate receptor 1 (P-NR1) in basal ganglia in a piglet model of HIBI and to investigate the correlation between Glx(Glu/Gln) value measured by magnetic resonance spectroscopy (MRS) and NR1/P-NR1 expression. Multi-voxel (1)H MRS was applied to detect change in Glx in basal ganglia of the newborn piglets in vivo. Automatic amino acid analyzer was applied to accurately quantify the Glu concentration. Immunohistochemical method was used to examine the expression of NR1 and P-NR1. The NR1 receptors in basal ganglia of the newborn piglets were significantly activated after HIBI. P-NR1 expression in the basal ganglia was consistent with the change in brain Glu content, so the activation status of NMDA receptor in the brain could be indirectly reflected by β-, γ-Glx/NAA measured by (1)H MRS.


Heart rate variability in obsessive compulsive disorder in comparison to healthy controls and as predictor of treatment response.
Obsessive compulsive disorder (OCD) has a large impact on the quality of life of patients. It often takes years to get the right diagnosis and to receive treatment. Therefore, biomarkers that could inform the diagnostic process and provide information on response or non-response for first line treatment approaches are urgently needed. The aim of this study was to analyze whether (1) heart rate (HR) and heart rate variability (HRV) markers of the autonomous nervous system could distinguish between healthy controls (HC) and patients suffering from OCD and (2) HRV parameters additionally yield useful information to separate therapy-responders from non-responders. A fifteen-minute resting state ECG (electrocardiogram) was recorded from 51 unmedicated OCD patients before treatment and 28 HC. The function of the autonomic nervous system was assessed by using parameters of the HRV. Clinical Global Impression (CGI) scores served as baseline and outcome parameters following three to six months of therapy (cognitive behavioral therapy n = 18, selective-serotonin-reuptake-inhibitor n = 11 or combination n = 22). Differences between patients and HC and responders and non-responders were identified using analysis of covariance (ANCOVAs). Predictive values were calculated following binary regression modelling and receiver operating characteristics (ROC). OCD patients revealed a significantly higher HR in comparison to HC. Although patients were thus characterized by increased sympathetic and decreased parasympathetic tone, treatment responders exhibited a larger High Frequency Power as a marker for increased parasympathetic activity at baseline. ROC-curves for OCD vs HC and R vs NR showed clinically relevant areas under curve (83%, 88% respectively). These results are in line with findings of increased sympathetic and decreased parasympathetic activity in OCD in comparison to healthy subjects. The findings further provide clinically useful information on treatment response in OCD. Results may facilitate the clinical use of electrophysiological markers in OCD.


Protein kinase C signalling involved in prothoracicotropic hormone-stimulated prothoracic glands in the silkworm, Bombyx mori.
In the present study, the participation of protein kinase C (PKC) signalling in prothoracicotropic hormone (PTTH)-stimulated ecdysteroidogenesis in Bombyx prothoracic glands (PGs) is demonstrated and characterized. PTTH stimulated phosphorylation of a 37-kDa protein in Bombyx PGs both in vitro and in vivo, as recognized by a PKC substrate antibody. Treatment with either A23187 or thapsigargin also stimulated this 37-kDa protein phosphorylation. PTTH-stimulated phosphorylation of the 37-kDa protein was markedly attenuated in the absence of Ca2+ . The phospholipase C (PLC) inhibitor, U73122, greatly inhibited PTTH-stimulated phosphorylation of this protein, indicating the involvement of Ca2+ and PLC. A mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitor (U0126), a phosphoinositide 3-kinase (PI3K) inhibitor (LY294002) and a chemical activator of adenosine 5'-monophosphate-activated protein kinase (AMPK) (5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside) did not affect PTTH-stimulated phosphorylation of the 37-kDa protein, implying that ERK and PI3K/AMPK are not the upstream signalling pathways for PKC-dependent protein phosphorylation. The mitochondrial oxidative phosphorylation inhibitors (the uncoupler carbonyl cyanide p-trifluoromethoxyphenylhydrazone and diphenylene iodonium) inhibited PTTH-stimulated phosphorylation of the 37-kDa protein, indicating its redox regulation. Treatment with PKC inhibitors (either calphostin C, chelerythrine C or rottlerin) reduced PTTH-stimulated phosphorylation of the 37-kDa protein. PTTH-stimulated ecdysteroidogenesis was also inhibited by treatment with rottlerin, thus further confirming participation of PKC-dependent phosphorylation in PTTH signalling. From these results, we demonstrated that redox-regulated PTTH-stimulated PKC signalling is involved in ecdysteroid secretion in Bombyx PGs.


Frozen embryo transfer outcomes decline with increasing female body mass index with female but not male factor infertility: analysis of 56,564 euploid blastocyst transfers.
To evaluate the association of body mass index (BMI) with cycle outcomes after euploid frozen blastocyst transfer. Retrospective cohort study. Not applicable. A total of 56,564 first single autologous euploid frozen embryo transfers (FET) from the 2016-2019 Society for Assisted Reproductive Technology database were analyzed by BMI and by World Health Organization BMI cohorts. Sub-analyses were performed on cycles among patients with a sole diagnosis of polycystic ovary syndrome (PCOS) (n = 4,626) and among patients with only male factor (n = 10,854). None. Clinical pregnancy, pregnancy loss, and live birth. (s): Success rates and adjusted odds ratios (aORs) with 95% confidence intervals (CIs) for all outcomes were most favorable among those with normal BMI and progressively worsened with increasing BMI. These trends persisted among patients with PCOS for clinical pregnancy (aOR 0.99, 95% CI 0.98-0.997, p 0.003), pregnancy loss (aOR 1.02, 95% CI 1.01-1.04, p 0.01), and live birth (aOR 0.98, 95% CI 0.97-0.99, p <0.001), but not among patients with male factor only for clinical pregnancy (aOR 1.00, 95% CI 0.99-1.01, p 0.425), pregnancy loss (aOR 1.01, 95% CI 0.99-1.03, p 0.07), or live birth (aOR 0.99, 95% CI 0.98-1.00, p 0.08). (s): In the largest cohort to date, increasing BMI was associated with decreased pregnancy and live birth and increased pregnancy loss following euploid FET among the entire cohort and among patients with a sole diagnosis of PCOS; however, these results were attenuated among patients with a sole diagnosis of male factor infertility, suggesting that associated female infertility diagnoses and not BMI alone may underly this trend.


Practical considerations in the testing of VO2max in runners.
Maximal oxygen intake (VO2max) may be the most physiologically significant and, therefore, the most commonly measured parameter in the physiological assessment of well trained runners. To insure valid and reliable VO2max values, there are a number of practical concerns that must be addressed. An exercise modality must be selected that activates the specific muscle mass and duplicates the motion utilised in the runners' training programme. Motorized treadmill running has been shown to allow the most efficient, valid and reproducible VO2max values in a controlled testing environment. A testing protocol must be used that is easily administered, comfortable for the runner, allows test completion within 10 minutes, uses grade increments at a constant speed, and is reproducible. Speeds should be selected that approximate the runner's training pace. The criterion for the attainment of VO2max include the levelling off of VO2 with an increase in work stage, the onset of extreme exhaustion, the respiratory exchange ratio exceeding 1.1, blood lactate levels approaching or exceeding 10 mmol/L, and ratings of perceived exertion of 19 or 20. Quality control in terms of standardisation of procedures and calibration and maintenance of equipment is essential for the minimisation of technological error. Measurement equipment must be affordable, dependable, easily calibrated, yield reproducible data, and be within the technical skill levels of the operating personnel.


The specificity of cathepsin B. Hydrolysis of glucagon at the C-terminus by a peptidyldipeptidase mechanism.
The manner in which human liver cathepsin B (EC 18.104.22.168) digests glucagon was determined. After reaction of the proteinase with the substrate for 24h, more than 15 products were formed. During the first 7 h of reaction, eight products were formed; seven of these were dipeptides that originated from the C-terminal portion of the glucagon molecule, whereas the eighth peptide was the remaining large fragment of the hormone, consisting of residues 1-19. Measurement of the rate of formation of the products showed that cathepsin B degraded glucagon by a sequential cleavage of dipeptides from the C-terminal end of the molecule. Cathepsin B from both rat liver and bovine spleen was shown to hydrolyse glucagon by the same mechanism.


Human small-intestinal epithelium contains functional natural killer lymphocytes.
CD3(-) non-T lymphocytes constitute the second most abundant lymphoid subset in the human small-bowel epithelium, and these CD3(-) intraepithelial lymphocytes are virtually absent in active celiac disease. Phenotypically, they resemble natural killer cells and have been termed natural killer-like intraepithelial lymphocytes. Because of the limited availability of appropriate human samples, functional studies have not yet been reported, and it is not yet clear whether these are true natural killer cells. We used magnetic bead-based purification and flow cytometry to study several aspects of normal human small-bowel natural killer-like intraepithelial lymphocytes: intracellular cytokine content (basally and after activation); ability to lyse natural killer-sensitive K562 target cells; and expression of perforins, Fas ligand, and other functional markers. CD3(-) intraepithelial lymphocytes cultured in interleukin-2 showed a higher lymphokine-activated killer activity than CD3(+) intraepithelial lymphocytes (48%-83% lysis exerted by CD3(-) intraepithelial lymphocytes at an effector-target cell ratio of 2:1 vs. 8%-18% by CD3(+) intraepithelial lymphocytes). Perforin content correlated with this lytic potential (75% +/- 4% in CD3(-) vs. 5% +/- 4% in CD3(+) intraepithelial lymphocytes). Both CD3(-) and CD3(+) cells displayed a type I cytokine profile (interferon-gamma > tumor necrosis factor-alpha > interleukin-2; undetectable interleukin-4 and interleukin-10). In addition to their activated phenotype, subsets of natural killer-like intraepithelial lymphocytes expressed CD8alphaalpha and intracellular CD3epsilon chain, showing the existence of heterogeneity within this cell lineage. This is the first demonstration of functional natural killer cells within the human gut epithelium. These cells might play an important role in innate mucosal immunity (host defense and tumor surveillance) and tolerance.


Infinitely Variable Tiling Patterns: From Truchet to Sol LeWitt Revisited.
Repeating patterns in architecture are utilized in elements at a variety of scales, from a façade to perforated ceilings and wall reliefs to carpeting and tile stonework. The Truchet tiling concept is one means to develop a modular non-repeating pattern. This paper explores some of the basic concepts of Truchet tilings, variations developed, and some current examples of using these methods with digital generation and fabrication methods.


A new method to reveal the genotoxic effects of N-nitrosodimethylamine in pregnant mice.
DNA damage and repair in kidney and liver of mouse fetuses exposed to selected doses of N-nitrosodimethylamine (NDMA) (CAS No. 62.75.9) were studied using the alkaline elution technique. CD1 female mice (15 days pregnant) were treated i.p. with 2 and 10 mg/kg b.w. of NDMA; a slight increase in DNA damage was observed in their fetuses compared to untreated controls. A 2-fold higher extent of DNA damage was induced when mice were treated by intrafetal injections of a rat S9 activating fraction (S9) immediately before exposure to the same dose of NDMA by transplacental means. The DNA-strand breaks disappeared as a function of time in animals treated with NDMA alone. In contrast, a significant persistence of DNA damage was detected in the liver and lung of fetuses which were treated with S9 and NDMA in sequence. These experiments demonstrate the metabolic immaturity of unborn mice as far as the carcinogenic activation of NDMA is concerned and show the high susceptibility of fetal tissues to DNA-damaging agents. The alkaline elution applied in vivo by the transplacental route combined with the intrafetal injection of an exogenous activating microsomal fraction allow to extend our knowledge on the interaction of metabolism-dependent chemicals with fetal tissues.


Linking measures of adolescent nicotine dependence to a common latent continuum.
Using the theoretical model of nicotine dependence (ND) operationalized within the Diagnostic and Statistical Manual of Mental Disorder, fourth Edition (DSM-IV: American Psychiatric [American Psychiatric Association, 1994. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. American Psychiatric Association, Washington, DC]) as a frame of reference, we used methods based in item response theory to link alternative instruments assessing adolescent nicotine dependence severity to a common latent continuum. A multi-ethnic cohort of 6th-10th graders selected from the Chicago Public Schools (CPS) completed five household interviews over 2 years. Youth who reported at least some cigarette use in the last 30 days prior to the interviews at waves W3-W5 completed measures of DSM-IV ND, the Modified Fagertrom Tolerance Questionnaire (mFTQ: Prokhorov et al., 1998) and the Nicotine Dependence Syndrome Scale (NDSS: Shiffman et al., 2004), yielding samples of 253, 241, and 296 respondents at W3-W5, respectively. Confirmatory factor analysis supported a primary dimension of ND. Each instrument's items had complementary and stable relationships to ND across multiple waves of assessment. By aligning symptoms along a common latent ND continuum, we evaluated the consistency of symptoms from different instruments that target similar content. Further, these methods allowed for the examination of the DSM-IV as a continuous index of ND, evaluation of the degree of heterogeneity in levels of ND within groups above and below diagnostic thresholds, and the utility of using the pattern or particular DSM-IV symptoms that led to each score in further differentiating levels of ND. Finally, we examined concurrent validity of the ND continuum and levels of current of smoking at each wave of assessment.


Distinctive activation patterns in constitutively active and gefitinib-sensitive EGFR mutants.
Mutations in the kinase domain of epidermal growth factor receptor (EGFR) are associated with clinical responsiveness to gefitinib in patients with non-small-cell lung cancers (NSCLC). Recently, we have identified many novel EGFR mutations in NSCLC tissues. In this study, we found that gefitinib could suppress the tyrosine phosphorylation of most EGFR mutants better than the wild-type receptor. However, gefitinib had quite variable growth-suppressive effects on different EGFR mutant-expressing cells. All tested EGFR mutants have high basal phosphorylation at multiple tyrosine residues. Upon EGF stimulation, the mutated EGFRs did not have apparently stronger phosphorylation at tyrosines 845, 992, 1,068, and 1,173 than the wild-type receptor. However, stronger phosphorylation at tyrosine 1,045 was observed in the S768I, L861Q, E709G, and G719S mutants. The E746-A750 deletion mutant was less responsive to EGF than the wild-type and other mutant receptors. The S768I, L861Q, E709G, and G719S mutants were refractory to EGF-induced ubiquitination and had more sustained tyrosine phosphorylation. E709G and G719S also lacked EGF-induced receptor downregulation. Our results indicate that, in addition to sensitivity to gefitinib, EGFR mutations also caused various changes in EGFR's regulatory mechanisms, which may contribute to the constitutive activation of EGFR mutants and oncogenesis in NSCLC.


Inhalant and Additional Mucosal-Related Environmental Risks for Rheumatoid Arthritis.
Rheumatoid arthritis (RA) occurs as the result of a complex interplay of environmental factors in a genetically susceptible individual. There is considerable evidence that the lungs may serve as an initial site of tolerance loss in the generation of RA-related autoimmunity, and several environmental inhalant exposures and lung diseases have been associated with RA risk. There is additional evidence that immune and microbial dysregulation of other mucosal sites, including the oral and gastrointestinal mucosa, may contribute to the development of RA. Epidemiologic evidence linking mucosal exposures to various environmental insults as risk determinants in RA will be reviewed.


Complexity of human gait pattern at different ages assessed using multiscale entropy: From development to decline.
Multiscale entropy (MSE) has been applied in biomechanics to evaluate gait stability during human gait and was found to be a promising method for evaluating fall risk in elderly and/or pathologic subjects. The hypothesis of this work is that gait complexity is a relevant parameter of gait development during life, decreasing from immature to mature gait and then increasing again during old age. In order to verify this hypothesis, MSE was applied on trunk acceleration data collected during gait of subjects of different ages: toddlers at the onset of walking, pre-scholar and scholar children, adolescents, young adults, adults and elderlies. MSE was estimated by calculating sample entropy (SEN) on raw unfiltered data of L5 acceleration along the three axes, using values of τ ranging from 1 to 6. In addition, other performance parameters (cadence, stride time variability and harmonic ratio) were evaluated. The results followed the hypothesized trend when MSE was applied on the vertical and/or anteroposterior axis of trunk acceleration: an age effect was found and adult SEN values were significantly different from children ones. From young adults to elderlies a slight increase in SEN values was shown although not statistically significant. While performance gait parameters showed adolescent gait similar to the one of adults, SEN highlighted that their gait maturation is not complete yet. In conclusion, present results suggest that the complexity of gait, evaluated on the sagittal plane, can be used as a characterizing parameter of the maturation of gait control.


Synthesis and application of ion-imprinted polymer for extraction and pre-concentration of iron ions in environmental water and food samples.
In this work, a novel Fe(III) ion imprinted polymer as a sorbent for extraction of iron ions from different samples was synthesized. Precipitation of thermal copolymerization was used for preparation of polymeric sorbent. In this technique, methacrylic acid, ethylene glycoldimethacrylate, 2,2'-azobisisobutyronitrile and (DHBPT)2 {(DHBPT)2=3,6-bis (3,5-dimethyl-1-H-pyrzol-1-yl)-1,2-dihydro-1,2,4,5-tetrazine)} were used as monomer, cross-linker, initiator and ligand, respectively, in the presence of Fe(III) ions and ethanol as a porogenic solvent. Moreover, control polymer (NIP) particles were similarly prepared without the Fe(III) ions. XRD, FT-IR, SEM and nitrogen adsorption-desorption techniques have been used to characterization of these prepared polymeric samples. Iron ion imprinted polymer particles, abbreviated as Fe(III)-IIP, were leached with 50 mL of HCl (50% (v/v)). Absorption capacity for ion imprinted polymer was calculated about 40.41 mg·g(-1). Per-concentration of iron ion was investigated as a function of pH, weight of IIP, adsorption and desorption times, and volumes of sample. FAAS technique was used to determination of Fe(III) ion in the foods and waters samples.


The missing link: Unlocking the power of cardiac rhythm monitoring device based QT interval detection.
The QT interval is of high clinical value as QT prolongation can lead to Torsades de Pointes (TdP) and sudden cardiac death. Insertable cardiac monitors (ICMs) have the capability of detecting both absolute and relative changes in QT interval. In order to determine feasibility for long-term ICM based QT detection, we developed and validated an algorithm for continuous long-term QT monitoring in patients with ICM. The QT detection algorithm, intended for use in ICMs, is designed to detect T-waves and determine the beat-to-beat QT and QTc intervals. The algorithm was developed and validated using real-world ICM data. The performance of the algorithm was evaluated by comparing the algorithm detected QT interval with the manually annotated QT interval using Pearson's correlation coefficient and Bland Altman plot. The QT detection algorithm was developed using 144 ICM ECG episodes from 46 patients and obtained a Pearson's coefficient of 0.89. The validation data set consisted of 136 ICM recorded ECG segments from 76 patients with unexplained syncope and 104 ICM recorded nightly ECG segments from 10 patients with diabetes and Long QT syndrome. The QT estimated by the algorithm was highly correlated with the truth data with a Pearson's coefficient of 0.93 (p < .001), with the mean difference between annotated and algorithm computed QT intervals of -7 ms. Long-term monitoring of QT intervals using ICM is feasible. Proof of concept development and validation of an ICM QT algorithm reveals a high degree of accuracy between algorithm and manually derived QT intervals.


Quantitative HBcrAg and HBcAb versus HBsAg and HBV DNA in predicting liver fibrosis levels of chronic hepatitis B patients.
To evaluate the performance of the quantitative markers of hepatitis B core-related antigen (HBcrAg) and anti-hepatitis B core antigen antibodies HbcAb versus hepatitis B surface antigen (HBsAg) and hepatitis B virus DNA (HBV DNA) in predicting liver fibrosis levels in chronic hepatitis B patients. Two hundred and fifty hepatitis B e antigen (HBeAg)-positive and 245 HBeAg-negative patients were enrolled. With reference to the Scheuer standard, stage 2 or higher and stage 4 liver disease were defined as significant fibrosis and cirrhosis, respectively. A receiver operating characteristic (ROC) curve was used to evaluate the performance of the HBV markers investigated. The areas under the ROC curves (AUCs) of HBcrAg in predicting significant fibrosis and cirrhosis in HBeAg-positive patients (0.577 and 0.700) were both close to those of HBsAg (0.617 and 0.762) (both P> 0.05). In HBeAg-negative patients (0.797 and 0.837), they were both significantly greater than those of HBV DNA (0.723 and 0.738) (P=0.0090 and P=0.0079). The AUCs of HBcAb in predicting significant fibrosis and cirrhosis in HBeAg-positive patients (0.640 and 0.665) were both close to those of HBsAg. In HBeAg-negative patients (0.570 and 0.621), they were both significantly less than those of HBcrAg (P <0.0001 and P=0.0001). Specificity in predicting significant fibrosis and sensitivity in predicting cirrhosis in HBeAg-positive patients, using a single cut-off of HBsAg ≤5,000 IU/ml, were 76.5% and 72.7%, respectively. In HBeAg-negative patients, using a single cut-off of HBcrAg>80kU/ml, they were 85.9% and 81.3%, respectively. HBsAg has good performance in predicting liver fibrosis levels in HBeAg-positive and HBeAg-negative patients, and HBcrAg has very good performance in predicting liver fibrosis levels in HBeAg-negative patients.


Enzymatic deconjugation of catecholamines in human and rat plasma and red blood cell lysate.
We have developed a method for enzymatic hydrolysis of both sulfated and glucuronidated catecholamines in plasma and red blood cell lysate. Hydrolysis occurs in the course of the radioenzymatic assay for catecholamines. In human plasma, catecholamines are conjugated almost entirely with sulfate while, in rat plasma, glucuronides are the main conjugates of epinephrine and dopamine but not norepinephrine. Rat plasma contains less percent conjugated catecholamine than human plasma. Human red blood cell lysate contains less conjugated catecholamine than plasma, whereas free E in lysate exceeds that of plasma and free NE has same level both in sulfated + glucuronidated) catecholamines and the nature of conjugated catecholamines.


Characterisation of Malian and Belgian solid waste composts with respect to fertility and suitability for land application.
Two composts, a Malian (C1) and a Belgian (C2), and a peat substrate (C3) were analyzed for their suitability for land application. The results revealed that the materials can be used in agriculture but only the application of the peat substrate may create N immobilization. Composts had higher P, Ca, and Mg contents and lower C and K contents and C/N ratio than the peat substrate. The available P extracted from the three materials ranged from 15% (for C2) to 48% (for C3) and available K from 36% (in the composts) to 48% (for C3) of the total elements respectively. The fractionation of Mn, Fe, Zn and Cu in operationally defined fractions (water soluble, exchangeable, complexed, organically bound and residual) allows an estimation of the availability of metals for uptake. For example, 16% of the total Mn in the composts (C1 and C2) and 22% in the peat substrate would be plant available. Available Fe in the three materials was less than 2%. Available Zn varied between 10 and 25%. The fractionation allowed an estimation of the potential for contamination of groundwater following the applications of composts to agricultural lands.


Intussusception of sigmoid colon in an adult. Spontaneous expulsion of sequestered bowel and restoration of bowel continuity.
A 67-year-old white man presented with bloody diarrhea and passed a 22-cm long segment of full-thickness sigmoid colon following a barium enema. He had advanced peripheral and cerebral vascular disease and had undergone pelvic irradiation for a bladder cancer five years previously. He recovered uneventfully from the bowel sloughage. This was apparently due to an intussusception of the sigmoid colon followed by the formation of adhesions between the edges of the adjacent viable bowel.


[Prognostic value of treadmill exercise echocardiography].
Exercise echocardiography (EE) is useful for diagnosing coronary disease, but little is known about its value for risk stratification. We aimed to determine: a) whether data from EE supplemented clinical data and data from exercise testing and resting echocardiography in predicting cardiac events; and b)whether the number and location of abnormal regions and their responses to exercise influenced risk stratification. The 2,436 patients referred for EE were followed up for 2.1+/-1.5 years. Some 120 serious cardiovascular events (i.e., non-fatal myocardial infarction or cardiovascular death) occurred before revascularization. In 1203 patients (49%), EE gave abnormal results. There were 89 events in patients with an abnormal result (7.3%) and 31 in those with a normal result (2.5%; P<.0001). Multivariate analysis of clinical data, and data from exercise testing, resting echocardiography, and EE showed that male sex (RR=1.7; 95% CI, 1.1-2.8; P=.02), metabolic equivalents or METs (RR=0.9; 95% CI, 0.86-0.98; P=.01), peak heart rate x blood pressure (RR= 0.9;95% CI, 0.9; P=.002), resting wall motion score index (RR=2.5; 95% CI, 1.5-4.1; P<.0001), and number of abnormal regions at peak exercise (RR=1.4; 95% CI, 1.2-1.7; P<.0001) were independently associated with the risk of a serious event (final model chi2, 170; incremental P<.0001). The same variables, excluding sex, were independently associated with cardiovascular death (final model chi2, 169; incremental P=.01). Exercise echocardiography supplements clinical data and data from exercise testing and resting echocardiography in patients with known or suspected coronary artery disease.


Pharmacological studies of water extract of the Zizyphus seed and the Zizyphus seed containing drug.
1. The pharmacological properties of a water extract of the Zizyphus seed (HO2) and that of the Zizyphus seed containing drug (HO1) were studied. 2. After oral or intraduodenal administration of 3 g/kg of HO1 or HO2, the hypnotic effects induced by hexobarbital-Na (38 mg/kg, i.p.) and diazepam-induced sleep in mice were potentiated. 3. After oral or intraduodenal administration of 3 g/kg of HO1 or HO2, gastric juice secretion and ulcers induced by water immersion stress, histamine and reserpine in rats were inhibited.


Estrogen target cells in the pituitary of platyfish, Xiphophorus maculatus.
The distribution of estradiol-concentrating cells in the pituitary of the platyfish, Xiphophorus maculatus, is studied after the injection of 3H estradiol-17 beta by thaw-mount autoradiography. Autoradiograms prepared 2-8 h after the injection show nuclear concentration of radioactivity in certain cells of the rostral pars distalis, pars intermedia and pars nervosa. Radioactively labeled cells are identified as gonadotropes by a combined technique of thaw-mount autoradiography and immunoperoxidase staining with antiserum to ovine LH. Approximately 80% of the immunoreactive LH cells show a concentration of radioactivity in their nuclei. These observations indicate that in teleosts, as in mammals, estradiol has a direct effect on pituitary gonadotropes.


Extending and refining the fearful ape hypothesis.
The fearful ape hypothesis (FAH) presents an evolutionary-developmental framework stipulating that in the context of cooperative caregiving, unique to human great ape group life, heightened fearfulness was adaptive. This is because from early in human ontogeny fearfulness expressed and perceived enhanced care-based responding and cooperation with mothers and others. This response extends and refines the FAH by incorporating the commentaries' suggestions and additional lines of empirical work, providing a more comprehensive and nuanced version of the FAH. Specifically, it encourages and hopes to inspire cross-species and cross-cultural, longitudinal work elucidating evolutionary and developmental functions of fear in context. Beyond fear, it can be seen as a call for an evolutionary-developmental approach to affective science.


Concentrations of polybrominated diphenyl ethers, organochlorine compounds and nitro musks in mother's milk from Germany (Bavaria).
The aim of this study was to determine a new spectrum of substances that will be selected for future breast milk monitoring in Bavaria, Germany. Up to now, the analysis of breast milk in Bavaria was limited to selected organochlorine pesticides (OCP) and polychlorinated biphenyls (PCB). Information on background levels of toxicologically interesting substances, such as dioxins and dioxin-like polychlorinated biphenyls (dl-PCB) or on flame retardants, such as polybrominated diphenyl ethers (PBDE) are very limited or not available for Bavaria. We present here levels on OCP, some nitro musks, indicator PCB, polychlorinated dibenzo-p-dioxins (PCDD), polychlorinated dibenzofurans (PCDF) and dl-PCB concentrations in breast milk collected at 12 weeks post-partum of 43 primiparous mothers living in Bavaria. The average concentrations of PCDD, PCDF and dl-PCB were 4.98, 4.93 and 9.92 pg WHO-TEQ g(-1) lipid, respectively. The mean contribution of PCDD, PCDF, non-ortho and mono-ortho PCB to the total WHO-TEQ is consistently about 25% each. Furthermore the concentration on PBDE in breast milk at two sampling points, 12 weeks and 16 weeks after delivery, were determined. Overall, 19 PBDE congeners were analysed, however the level of 12 PBDE congeners were below the limit of detection. BDE-153 and BDE-47 were the predominant congeners accounting for about 66% of the total PBDE. The means of the total concentrations of PBDE (five congeners) at the first and second sampling point were 1.90 and 2.03 ng g(-1) lipid, respectively. Based on our results the overall concentrations of the analysed substances in milk samples from Bavaria are consistent with the levels of breast milk samples of other European countries reflecting the low background body burden of these compounds.


Drivers' judgments of the effect of headlight glare on their ability to see pedestrians at night.
Several studies have concluded that pedestrians typically overestimate their own conspicuity to approaching drivers at night. The present experiments extended this research by exploring the accuracy of drivers' judgments of pedestrian conspicuity while facing varying degrees of headlight glare. In Experiment 1, participants on an open road estimated their ability to see a roadside pedestrian in each of two clothing configurations and with each of three different glare intensities present. In Experiment 2, participants responded to a roadside pedestrian under the same open road conditions; the participants were naïve with regard to both the position of the pedestrian and to the clothing and glare manipulations. Consistent with earlier research, estimates of response distance were, on the average, over three times greater than actual recognition distance. The extent to which participants overestimated conspicuity was greater when the pedestrian wore a retroreflective vest, and participants incorrectly judged that headlight glare would not degrade drivers' ability to see a pedestrian wearing a retroreflective vest. These results confirm that road users' understanding of issues involving drivers' night vision is limited. These misunderstandings may result in road users behaving in ways that increase the risk of nighttime collisions with pedestrians.


Fortum stability in different disposable infusion devices by pyridine assay.
The stability of ceftazidime in 5% dextrose injection and 0.9% sodium chloride injection when stored in a different disposable infusion device was determined. Solutions of ceftazidime 40 mg/ml were used to fill the drug administration devices. Stability was determined for both 5% dextrose injection and 0.9% sodium chloride injection solutions at 37 degrees C in four disposable infusion devices. Ceftazidime and its mean degradation product, pyridine, were simultaneously assayed in triplicate by a stability-indicating high-performance liquid chromatographic (HPLC) method. This method was simple, sensitive (limit of quantitation (LOQ), 2 ng injected for both compounds), rapid (run time was 7 min) and precise (mean recovery was 100.5+/-2.9 and 103.6+/-1.9% for pyridine and ceftazidime, respectively). The ceftazidime stability in the 5% dextrose solution was lower than in the 0.9% sodium chloride solution. When stored at 37 degrees C in a disposable infusion device, the stability of the ceftazidime is included in large hourly range, depending strongly on the manufacturer. The stability of ceftazidime exceed 19 h in none studied cases. The pyridine formed in 24 h was in the range of 100-400 mg depending on devices and infusions.


Targeting Stat3 suppresses growth of U251 cell-derived tumours in nude mice.
Malignant gliomas are highly invasive tumours associated with high levels of mortality, and the treatment of gliomas remains a major neurosurgical challenge. Stat3, a member of the signal transducer and activator of transcription family, has a critical role in a variety of cancer cells. We have previously shown that downregulation of Stat3 decreases invasiveness and induces apoptosis in U251 human glioma cells in vitro, but to date it has been unclear whether this treatment would be beneficial in vivo. In the present study, we found that downregulation of Stat3 via RNAi suppressed tumour growth in a xenograft mouse model by inducing apoptosis of U251 tumour cells and inhibiting tumour neo-angiogenesis. We also found that Stat3 RNAi suppresses the expression of Bcl-2 in vivo to induce apoptosis. These results indicate that Stat3 is a critical factor in the survival of patients with glioma, and that targeting Stat3 may offer a potential therapeutic approach.


Investigating pyrolysis and combustion characteristics of torrefied bamboo, torrefied wood and their blends.
Bamboo and masson pine was torrefied with 300°C of temperature for 2.0h of residence time using GSL 1600X tube furnace in the argon atmosphere. Torrefied bamboo and masson pine particles were uniform mixed with different weight ratios. Pyrolysis and combustion characteristics were investigated through thermogravimetry (TGA). The results showed that pyrolysis and combustion process of all samples included three steps even though their characteristics were different. Torrefied biomass had a higher pyrolysis and combustion temperature, due to moisture and volatile removal and thermal decomposition of hemicelluloses, cellulose and lignin during torrefaction process. Torrefaction also increased high heating value, ash content and C/H and C/O ratio of biomass. The synergy of torrefied bamboo and torrefied mason pine was not found during pyrolysis and combustion process of blends. The results from this research will be very important and helpful to develop and utilize the wastes of masson pine and bamboo for energy products.


The link between endometrial stromal cell senescence and decidualization in female fertility: the art of balance.
Cell senescence seems to be an ambivalent biological phenomenon in many aspects. At the cellular level it is considered as an irreversible cell-cycle arrest commonly caused by the DNA damage. Senescent cells harbor a lot of impairments in various intracellular systems. Presence of senescent cells within tissues should ultimately lead to their malfunctioning. However, the interlink between cellular senescence and tissue/organismal functioning is far from always being unidirectional. The entangled and complex relationship between senescence and tissue-specific decidual differentiation of endometrial stromal cells (ESCs) is the excellent example reflecting dualism of cellular senescence. ESCs decidualization conditions endometrium responsiveness to embryonic signals and plays a critical role in embryo biosensoring, selection and implantation. Based on the analysis of the existing literary data, here we will try (1) to puzzle out how cellular senescence simultaneously may be an integral part of normal decidualization and may be involved in the progression of repeated implantation failures and recurrent pregnancy losses; (2) to suppose the sequence of cellular events reflecting the role of ESCs' senescence during normal and impaired decidualization. Together, the deep scan of the interlink between ESCs' senescence and decidualization will allow to suggest the preferable application scheme for senolytics targeting senescent cells as a possible approach to restore impaired endometrial receptivity and thus to increase the effectiveness of in vitro fertilization cycles.


Implementing a community-based participatory intervention to improve essential newborn care in rural Nepal.
The persistence of high perinatal and neonatal mortality rates in many developing countries make efforts to improve perinatal care in the home and at local health facilities important public health concerns. We describe a study which aims to evaluate a community-level participatory intervention in rural Nepal. The effectiveness of community-based action research interventions with mothers and other key members of the community in improving perinatal health outcomes is being examined using a cluster randomized, controlled trial covering a population of 28,000 married women of reproductive age. The unit of randomization was the village development committee (VDC): 12 VDCs receive the intervention while 12 serve as controls. The key elements of the intervention are the activities of female facilitators, each of whom works in one VDC facilitating the activities of women's groups in addressing problems in pregnancy, childbirth and the newborn period. Each group moves through a participatory planning cycle of assessment, sharing experiences, planning, action and reassessment, with the aim of improving essential maternal and newborn care. Outcomes assessed are neonatal and perinatal mortality rates, changes in patterns of home care, health care seeking and referral. The study also aims to generate programmatic information on the process of implementation in communities.


Budding and fission of vesicles.
We report on budding and fission of protein-free vesicles swollen from a natural lipid mixture of bovine brain sphingomyelins. Budding was induced by increasing the area-to-volume ratio through heating. Morphological changes were monitored by phase contrast microscopy and correlated with the thermal behavior of the bilayer by differential scanning calorimetry. Freeze fracture electron microscopy revealed that budding and fission are not restricted to giant vesicles but also occur on length scales relevant for cellular processes. We also observed osmotically induced budding and fission in mixtures of dimyristoyl phosphatidylcholine with cholesterol. We find that these shape transitions are driven by liquid/gel domain formation and/or coupling of the spontaneous curvature of the membrane to the local lipid composition. Our results provide evidence that coat proteins are not necessary for budding and fission of vesicles. The physics of the lipid bilayer is rich enough to explain the observed behavior.


Long-chain triglycerides reduce the efficacy of enteral feeds in patients with active Crohn's disease.
Elemental diets are effective treatments for active Crohn's disease. To determine which dietary constituents are of therapeutic importance, the effectiveness of four separate feeds was related to their compositions, and the findings substantiated by meta-analysis of previous dietary studies. 76 patients with active Crohn's disease were recruited. 17 were randomised to an amino acid-based elemental diet (E028), 22 to E028 with added long-chain triglyceride (E028 LCT), 18 to a semi-elemental, peptide based diet (Pepdite 2+) and 19 received E028 with added medium-chain triglyceride (E028 MCT). Disease activity fell in all groups and remission rate was negatively correlated with the amount of energy derived from LCT (r = -0.97, p = 0.016). Inflammatory indices fell in the groups (E028 + E028 MCT) containing least LCT. No other dietary constituents correlated with remission rate. A meta-analysis of published studies confirmed a negative correlation between remission rate and LCT (r = -0.63, p = 0.006) but not other constituents. The association between dietary LCT and remission rate may have pathogenic significance and allow the development of more effective enteral feeds.


Does calcium cause the different effects of Gelofusine and Haemaccel on coagulation?
Gelofusine (which does not contain calcium) has a greater effect on coagulation than Haemaccel (which contains 6.25 mmol/l of calcium). This in vitro study was performed to assess whether calcium might be the cause of the different effects on coagulation. Three solutions were compared; (a) Gelofusine, (b) Gelofusine with calcium added to 6.25 mmol/l, and (c) Haemaccel. Thromboelastography (Sonoclot) was used to examine whole blood coagulation, with time to peak clot weight as the primary outcome measure. There was no significant difference between the Gelofusine containing solutions. Both Gelofusine solutions gave a greater impairment of coagulation than the Haemaccel solution. The different effect of Gelofusine on coagulation compared with Haemaccel does not seem to be related to the different calcium contents of the solutions.


Modeling oxygen transport in human placental terminal villi.
Oxygen transport from maternal blood to fetal blood is a primary function of the placenta. Quantifying the effectiveness of this exchange remains key in identifying healthy placentas because of the great variability in capillary number, caliber and position within the villus-even in placentas deemed clinically "normal". By considering villous membrane to capillary membrane transport, stationary oxygen diffusion can be numerically solved in terminal villi represented by digital photomicrographs. We aim to provide a method to determine whether and if so to what extent diffusional screening may operate in placental villi. Segmented digital photomicrographs of terminal villi from the Pregnancy, Infection and Nutrition study in North Carolina 2002 are used as a geometric basis for solving the stationary diffusion equation. Constant maternal villous oxygen concentration and perfect fetal capillary membrane absorption are assumed. System efficiency is defined as the ratio of oxygen flux into a villus and the sum of the capillary areas contained within. Diffusion screening is quantified by comparing numerical and theoretical maximum oxygen fluxes. A strong link between various measures of villous oxygen transport efficiency and the number of capillaries within a villus is established. The strength of diffusional screening is also related to the number of capillaries within a villus. Our measures of diffusional efficiency are shown to decrease as a function of the number of capillaries per villus. This low efficiency, high capillary number relationship supports our hypothesis that diffusional screening is present in this system. Oxygen transport per capillary is reduced when multiple capillaries compete for diffusing oxygen. A complete picture of oxygen fluxes, capillary and villus areas is obtainable and presents an opportunity for future work.


Anti-diarrhoeal Activity.
Diarrhoea is characterized by an increase in the frequency of bowel movements, wet stool and abdominal pains. It is the world's third highest killer disease, contributing substantially to paediatric morbidity and mortality, especially in the malnourished. Antibiotics used as anti-diarrhoeal drugs sometimes provoke adverse effects and microorganisms tend to develop resistance towards them. Therefore, the search for safe and more effective agents from plant origin using standard protocols of charcoal meal-induced diarrhoea has been defined in this chapter.


Occipital extra- and intracranial lipoencephalocele associated with tectocerebellar dysraphia.
Tectocerebellar dysraphism was first described by Padget and Lindenberg, together with occipital encephaloceles, cerebellar midline defects, tectal beaking, posterior kinked and displaced brainstem, and inverted cerebellum. We present a unique case of lipoencephalocele associated with tectocerebellar dysraphia and discuss the etiologies of both pathologies. The importance of the developmental comprehension of posterior fossa malformations is stressed. A 9-month-old girl in good health was referred for a huge occipital mass. On local examination, the patient had a rounded mass about 10 x 12 cm in size, covered by alopecic skin, with a small eccentric dimple without any discharge. Magnetic resonance imaging revealed a lipoencephalocele with an intra- and an extracranial part, associated with tectocerebellar dysraphia with no aspect of inverted cerebellum as originally described in the tectocerebellar dysraphia. Resection of the extracranial part of the lipoma was performed for esthetic reasons. The intracranial part remained in situ. The association of lipoencephalocele and tectocerebellar dysraphia is extremely rare. The functional prognosis seems to be less severe for this combination than for the isolated tectocerebellar dysraphia. This association favors the dysraphic theory for the embryogenesis of the lipoma. It seems safe to restrict the surgery of this bizarre malformation to its external part.


Failure of biceps tenodesis with interference screw fixation.
Tenodesis is a common surgical procedure used to treat pain caused by inflammation or instability of the long head of the biceps tendon. Many studies have evaluated different forms of fixation and their biomechanical characteristics, but few have discussed clinical complications or failures as a result of these techniques. The purpose of this article is to report a case series of 3 patients with failures after undergoing arthroscopic biceps tenodesis with an interference screw.


Publisher Correction: Artificial intelligence aims to improve cancer screenings in Kenya.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


[Effect of entomopathogenic fungus inoculum on the control of Corythycha ciliata Say adults, wintering on plane-trees of city groves].
Within a three years research program, infection tests were carried on adults of Corythucha ciliata wintering on the plane-trees of same city avenues, inoculating entomopathogenic deuteromycetes Beauveria bassiana, Verticillium lecanii, Paecilomyces farinsus, microorganisms which are known to be naturally present in such an environment. Inoculated fungi were able to settle only where the trees were free from any kind of disturbance, while this failed to occur in the areas of intense car traffic. Number of treatments efficiently affected pathogens diffusion in the trees. The persistency of the parasites on the insects, even one year after the treatment, seems to indicate the possibility of their use for the limitation of C. ciliata.


Environmental impact of particles emitted from Windscale Piles, 1954-7.
During 1954-7 particles of irradiated uranium oxide were emitted from the Windscale Piles. The particles were large compared with most ambient aerosols, 85% by weight being between 10 and 100 micron diameter, and they mostly fell within a few kilometers of the works. From measurements of activity in soil in 1958 onwards, it is estimated that about 12 kg of uranium, 20 Ci of 137Cs, 18 Ci of 90Sr and 0.3 Ci of 239+240Pu were emitted. To estimate the concentrations of 90Sr and 137Cs in milk during the emissions, comparison is made with the fallout of fission products from bomb tests, which also began in 1954, but continued longer. It is calculated that the average level of 90Sr in milk at Seascale, 1954-7, was 36 pCi per g Ca, with higher concentrations, 100-200 pCi (g Ca)-1, in milk from farms immediately surrounding the Windscale plant. For comparison, in 1963/5 the average level of 90Sr in milk in the UK was 20-30 pCi (g Ca)-1, with 90-170 pCi (g Ca)-1 in milk from certain hill farms. Since the oxide particles were larger than those derived from bomb tests, and the conditions of deposition different, an extended review is given (Appendix 1) of the factors determining the entry of radioactive or stable contaminants from fallout into food chains. It is concluded that the oxide particles would have been less efficient in this respect than bomb fallout, mainly because their relatively large size and high density would have given impact velocities sufficient to cause them to bounce off leaves, leaving little activity on the edible herbage. For this reason, the calculations are on the safe side.


Identification of high-risk factors associated with mortality at 1-, 3-, and 5-year intervals in gastric cancer patients undergoing radical surgery and immunotherapy: an 8-year multicenter retrospective analysis.
Combining immunotherapy with surgical intervention is a prevailing and radical therapeutic strategy for individuals afflicted with gastric carcinoma; nonetheless, certain patients exhibit unfavorable prognoses even subsequent to this treatment regimen. This research endeavors to devise a machine learning algorithm to recognize risk factors with a high probability of inducing mortality among patients diagnosed with gastric cancer, both prior to and during their course of treatment. Within the purview of this investigation, a cohort of 1015 individuals with gastric cancer were incorporated, and 39 variables encompassing diverse features were recorded. To construct the models, we employed three distinct machine learning algorithms, specifically extreme gradient boosting (XGBoost), random forest (RF), and k-nearest neighbor algorithm (KNN). The models were subjected to internal validation through employment of the k-fold cross-validation technique, and subsequently, an external dataset was utilized to externally validate the models. In comparison to other machine learning algorithms employed, the XGBoost algorithm demonstrated superior predictive capacity regarding the risk factors that affect mortality after combination therapy in gastric cancer patients for a duration of one year, three years, and five years posttreatment. The common risk factors that significantly impacted patient survival during the aforementioned time intervals were identified as advanced age, tumor invasion, tumor lymph node metastasis, tumor peripheral nerve invasion (PNI), multiple tumors, tumor size, carcinoembryonic antigen (CEA) level, carbohydrate antigen 125 (CA125) level, carbohydrate antigen 72-4 (CA72-4) level, and H. pylori infection. The XGBoost algorithm can assist clinicians in identifying pivotal prognostic factors that are of clinical significance and can contribute toward individualized patient monitoring and management.


Feeding Strategies to Mitigate Enteric Methane Emission from Ruminants in Grassland Systems.
Ruminants produce approximately 30% of total anthropogenic methane emissions globally. The objective of this manuscript was to review nutritional enteric methane abatement practices for ruminants that are applicable under grazing conditions. A total of 1548 peer-reviewed research articles related to the abatement of enteric methane emissions were retrieved and classified into four categories: non-experimental, in vitro, in vivo confined, and in vivo grazing. The methane abatement strategies for grazing systems were arranged into grazing management and supplementation practices. Only 9% of the retrieved papers have been conducted under grazing conditions. Eight grazing management practices have been evaluated to reduce methane emissions. Decreasing the pre-grazing herbage mass reduced the methane emission per unit of product. Other grazing management practices such as increased stocking rate, decreased forage maturity, rotational stocking, and incorporating tannin-containing or non-tannin-containing feeds showed contradictory results. Nitrogen fertilization or silvopastoral systems did not modify methane emissions. Conversely, supplementation practices in grazing conditions showed contradictory responses on methane emissions. Lipid supplementation showed promising results and suggests applicability under grazing conditions. Identifying and implementing grazing strategies and supplementation practices under grazing conditions is required to increase efficiency and reduce the environmental impact of these systems.


Androgen receptor and Kennedy disease/spinal bulbar muscular atrophy.
Kennedy Disease/Spinal Bulbar Muscular Atrophy (KD/SBMA) is a progressive neurodegenerative disease caused by genetic polyglutamine expansion of the androgen receptor. We have recently found that overexpression of wildtype androgen receptor in skeletal muscle of transgenic mice results in a KD/SBMA phenotype. This surprising result challenges the orthodox view that KD/SBMA requires expression of polyglutamine expanded androgen receptor within motoneurons. Theories relating to the etiology of this disease drawn from studies of human patients, cellular and mouse models are considered with a special emphasis on potential myogenic contributions to as well as the molecular etiology of KD/SBMA.


Bioenergy from forestry and changes in atmospheric CO2: reconciling single stand and landscape level approaches.
Analyses of global warming impacts from forest bioenergy systems are usually conducted either at a single stand level or at a landscape level, yielding findings that are sometimes interpreted as contrasting. In this paper, we investigate and reconcile the scales at which environmental impact analyses of forest bioenergy systems are undertaken. Focusing on the changes caused in atmospheric CO2 concentration of forest bioenergy systems characterized by different initial states of the forest, we show the features of the analyses at different scales and depict the connections between them. Impacts on atmospheric CO2 concentration at a single stand level are computed through impulse response functions (IRF). Results at a landscape level are elaborated through direct application of IRFs to the emission profile, so to account for the fluxes from all the stands across time and space. Impacts from fossil CO2 emissions are used as a benchmark. At a landscape level, forest bioenergy causes an increase in atmospheric CO2 concentration for the first decades that is similar to the impact from fossil CO2, but then the dynamics clearly diverge because while the impact from fossil CO2 continues to rise that from bioenergy stabilizes at a certain level. These results perfectly align with those obtained at a single stand for which characterization factors have been developed. In the hypothetical case of a sudden cessation of emissions, the change caused in atmospheric CO2 concentration from biogenic CO2 emissions reverses within a couple of decades, while that caused by fossil CO2 emissions remains considerably higher for centuries. When counterfactual aspects like the additional sequestration that would have occurred in the forest if not harvested and the theoretical displacement of fossil CO2 are included in the analysis, results can widely differ, as the CO2 debt at a landscape level ranges from a few years to several centuries (depending on the underlying assumptions considered).


Outcome of hematopoietic stem cell transplantation for pediatric patients with therapy-related acute myeloid leukemia or myelodysplastic syndrome.
Therapy-related myelodysplastic syndrome (t-MDS) and acute myeloid leukemia (t-AML) carry a poor prognosis. We analyzed the results of allogeneic HSCT in 38 children to determine which factors, if any, affected outcome. The effects of demographic, donor, and disease-related factors were analyzed to determine their effects on overall and disease-free survival (OS, DFS), relapse, and non-relapse mortality (NRM). OS and DFS for t-AML and t-MDS were similar. Three-year OS and EFS were the same (15.4 +/- 5.8%) and the 3-year NRM was 59.6 +/- 8.4%. The 1-year cumulative risk of grade III-IV acute graft-versus-host disease (GVHD) and relapse were 23.7 +/- 7.0% and 18.7 +/- 6.5%, respectively. The percentage of pre-transplant bone marrow (BM) blasts was positively associated with relapse (P = 0.05), while the percentage of BM blasts at diagnosis of therapy-related disease tended to associate with NRM (P = 0.07). Alternative donor and matched sibling donor grafts had similar outcomes. NRM was higher among patients who did not develop acute GVHD as compared to those with grade 1-2 acute GVHD (69.2 +/- 14.2% vs. +/- 12.7%, respectively), while NRM was 100% in patients with grade III-IV acute GVHD (P = 0.007). The percentage of BM blasts is associated with relapse in these disorders. High rates of NRM negatively impact the outcome of allogeneic HSCT for children with t-AML and t-MDS. Future studies should focus on reducing NRM.


Adenoid cystic carcinoma of the salivary glands. A study of ninety-three cases.
The present study reviews ninety-three cases of adenoid cystic carcinoma of the major (80 cases) and minor (13 cases) salivary glands occuring in ninety-one patients. This tumor is insidious in its presentation and subsequent clinical course with early perineural lymphatic invasion and late metastases. Many patients remain alive but with recurrent disease. The high incidence of recurrent disease (parotid gland 20 of 47, submaxillary gland 20 of 33, and minor salivary glands 7 of 11) suggests inadequate initial surgery at all anatomic sites. Misdiagnosis (16 cases) on frozen or permanent section has led to less than optimum primary treatment. The frequency of perineural lymphatic involvement with recurrence (11 of 19 cases) suggests that the tumor may be extending along the nerve roots in an anatomic area with extensive nerve distribution (the head and neck). Radical neck dissection, in our studies, has contributed to improved survival rates when the primary site has been the submaxillary gland. The treatment of recurrent disease has been primarily surgical (3 operations per patient), and palliation with prolonged survival has been achieved with radical excision of recurrence. The fifteen year determinate cure rate of 19 per cent in comparable to that reported in the world literature. Radiation therapy has been helpful in palliation but has not been curative. Radiation treatment was used for recurrence in twenty-seven patients, and the average time from radiation treatment to death was 3.8 years.


Nationwide trends in incidence, healthcare utilization, and mortality in hospitalized heart failure patients in Taiwan.
The objective of this study was to estimate the nationwide annual incidence, healthcare utilization, and mortality among hospitalized heart failure (HF) patients in Taiwan. People aged 20 years or older and having been newly admitted for HF between 2010 and 2015 were identified from Taiwan's National Health Insurance Research Database. For 124 816 patients with incident HF hospitalizations between 2010 and 2012, we further analysed their treatment patterns, healthcare utilizations, and mortality during index hospitalization and within 3 years following discharge from the index hospitalization. The age-stratified incidences were declined by 10-20% in people aged 55 years or older, but increased by ~4% among people younger than 44 years old between 2010 and 2015. For all incident hospitalized HF patients, the percentages of patients visiting the emergency room, were rehospitalized, and treated with guideline-directed medical therapy were highest in the first year. Approximately two-thirds of subsequent hospitalizations were due to non-HF and non-cardiovascular causes. The all-cause mortality rate during index hospitalization was 8.5%, whereas the mortality rates at 30 days, 90 days, 180 days, 1 year, 2 years, and 3 years following discharge were 3.5%, 8.9%, 14.4%, 22.5%, 33.9%, and 42.8%, respectively, for those surviving index HF hospitalization. Non-cardiovascular disease-related deaths accounted for nearly 60% of all deaths. Our study reveals that, in contemporary Taiwan, the >10% annual mortality following the first year of hospitalization, 30% deaths occurring outside the hospital, and 60% non-cardiovascular-related deaths, along with the decreasing use of guideline-directed medical therapy, highlight sectors requiring more attention.


Inhibition of autophagy enhances apoptosis induced by Ce6-photodynamic therapy in human colon cancer cells.
To evaluate the therapeutic effect of Chlorin e6 photodynamic therapy (Ce6-PDT) in human colorectal cancer cells and investigate the role of autophagy in Ce6-PDT. SW480 cells underwent Ce6-PDT with and without pretreatment with the autophagy inhibitor 3-methyladenine (3MA). Cell viability was assessed using 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was evaluated using an Annexin V assay, using a rhodamine 123 (RH123) assay to evaluate mitochondrial membrane potential (MMP), and by measuring Caspase-3 and Bcl-2 protein expression using western blotting. Autophagy was evaluated by directly visualizing acridine orange-stained acidic vesicular organelles (AVOs) using fluorescent microscopy and by measuring LC3Ⅰ/Ⅱand Atg5 expression using western blotting. Ce6-PDT decreased SW480 viability in a dose-dependent manner. Ce6-PDT induced apoptosis in SW480 cells via the mitochondrial apoptosis pathway as indicated by decreased mitochondrial membrane potential, increased Annexin V staining, and increased Caspase-3 expression. Ce6-PDT was also shown to induce autophagy as demonstrated by increased acridine-orange stained AVOs as well as increased expression of the autophagy-associated proteins Atg5. Inhibition of autophagy with 3MA potentiated SW480 cell response to Ce6-PDT and increased the rate of apoptosis in the treated cells. Ce6-PDT induces autophagy and apoptosis of SW480 cells in a dose-dependent manner. Inhibition of autophagy increases the apoptosis induced by Ce6-PDT. Modulation of autophagy may be a potential therapeutic target for colon cancer cells treated with Ce6-PDT.


Efficacy and acceptability of varenicline for alcoholism: A systematic review and meta-analysis of randomized-controlled trials.
Current pharmacological treatment for alcoholism remains unsatisfactory. While there have been several clinical trials investigating the efficacy and safety of the therapeutic use of varenicline in alcoholism, no definitive review of this topic has been carried out. This systematic review aimed to determine the efficacy and acceptability of the use of varenicline in treating alcoholism. This systematic review included double-blinded, randomized, placebo-controlled trials reporting heavy drinking days, amount of alcohol consumption, overall dropouts, or dropouts due to adverse events. We searched PubMed, Scopus, Web of Science, ClinicalTrials.gov, and the Cochrane Library in January 2019. We independently selected the trials and assessed the quality of included studies. We calculated standardized mean differences on heavy drinking days and the amount of alcohol consumption. We calculated the relative risks for dropout rate. All data were pooled using random-effects models. This systematic review included nine double-blind, randomized, placebo-controlled trials (N = 585). The study duration ranged from 4 to 13 weeks. Varenicline therapy was not superior to placebo in decreasing heavy drinking days but significantly superior to placebo in decreasing alcohol consumption. There were no statistically significant differences between groups on dropout rates due to any reason or due to adverse events. Varenicline therapy is effective in decreasing alcohol consumption over a period of time. It may be an option for decreasing heavy drinking days in patients with alcoholism. It is a well-accepted medication for alcoholism. More studies are needed to determine if varenicline is effective in decreasing heavy drinking.