[Comparative Analysis of Behavior in The Open-field Test in Wild Grey Rats (Rattus norvegicus) and in Grey Rats Subjected to Prolonged Selection for Tame And Aggressive Behavior].
The aim of this work is analysis of the open-field behavior in grey rats selected for the tame and aggressive behavior in comparison with the wild grey rats. Significant influences of the rat group factor on the 13 of 19 behavioral features studied in the open-field were found. This effect, in general, depends on existence of great differences between behaviors of the wild rats from the one hand and behaviors of the tame and aggressive rats from the other. The behaviors of the rats from the last two groups are practically identical. Multidimensional analysis confirms the distinct separation in coordinates of the two main components of the wild rat behavior from the behavior of both the tame and selectively bred aggressive rats. The first main component dimension corresponds to the grade of fear, which was significantly enhanced in the wild rats. So, in spite of the equality of behavioral aggressiveness of the wild rats and the rats selected for aggression with the glove test, the behavior of selected aggressive rats in the open-field is analogous to behavior of the rats selected for tameness. Comparison of behavioral features with the hormonal stress responsiveness allowed us to conclude that the aggressive behavior of the wild and se lected for aggression rats based on different motivational and neuroendocrine processes.


Arthrobacter silvisoli sp. nov., isolated from forest soil.
A novel Gram-stain-positive, strictly aerobic strain, NEAU-SA1T, which showed a rod-coccus growth life cycle, was isolated from forest soil from Zhangjiajie, Hunan Province, China. The isolate grew at 10-40 °C (optimum 28 °C), at pH 5.0-10.0 (optimum pH 7.0) and in the presence of up to 5 % (w/v) NaCl, although NaCl was not required for growth. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain NEAU-SA1T belonged to the genus Arthrobacter and was closely related to Arthrobacter cupressi DSM 24664T (98.1 % similarity). Average nucleotide identity values between NEAU-SA1T and A. cupressi DSM 24664T were 88.91 and 87.41 % by ANIm and ANIb analysis, respectively. The in silico DNA-DNA hybridization value between strain NEAU-SA1T and A. cupressi DSM 24664T was 34.20 %, again indicating they belong to different taxa. The genomic DNA G+C content was 66.74 mol%. The major cellular fatty acids (>10 %) were anteiso-C15 : 0, anteiso-C17 : 0 and iso-C16 : 0. The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol and two unidentified glycolipids. The predominant menaquinone was MK-9(H2). The peptidoglycan type was A3α with an interpeptide bridge comprising l-Lys and l-Ala. Glucose, ribose and galactose were the whole-cell sugars. On the basis of morphological, physiological, biochemical and chemotaxonomic analysis, strain NEAU-SA1T was classified as representing a novel species in the genus Arthrobacter, for which the name Arthrobacter silvisoli sp. nov. is proposed. The type strain is NEAU-SA1T (=DSM 106716T=CCTCC AB 2017271T).


Evaluation of fasting metabolism of growing water buffalo (Bubalus, Bubalis).
The objectives of the present study were to evaluate fasting metabolism (FM) of water buffalo (Bubalus, Bubalis) at three stages of growth (12, 18 and 24 months) in Guangxi, China. Five female water buffalo were used for each age group and their live weight was on average 254, 326 and 338 kg, respectively. All animals were of average body condition, healthy and de-wormed before start of the study. Prior to a 6-day fasting period, buffalo were offered a mixed diet of forage and concentrates (70% and 30%, dry matter basis) on a restricted nutritional level (419 kJ/kg(0.75) of metabolizable energy, ME) for 15 days. Gas exchanges for each animal were determined for 3 days from day 4 of starvation, using open-circuit respiratory head hoods. Fasting body weight was 0.918 of live weight (P < 0.001, r(2) = 0.99). Both fasting heat production (FHP) and FM (MJ/day) increased significantly with increased age of animals (P < 0.05). Linear regression analysis indicated a positive relationship between fasting body weight (kg(0.75)) and FHP (MJ/day, P < 0.01, r(2) = 0.49) or FM (MJ/day P < 0.01, r(2) = 0.52) when using individual animal data across three groups. However, when expressed as kJ/kg(0.75) of fasting body weight, the differences in FHP or FM between three groups of animals were not significant. The present average FHP and FM (322 and 347 kJ/kg(0.75) of fasting body weight) were compatible to those published in the literature for water buffalo, beef and dairy cattle. The present FM data were also used to estimate net energy (NE(m)) and ME (ME(m)) requirements for maintenance for water buffalo. The results for these two parameters were similar to those for FHP and FM. There was no significant difference between three groups of buffalo in NE(m) or ME(m) when expressed as kJ/kg(0.75) of live weight. The present average NE(m) and ME(m) values (347 and 506 kJ/kg(0.75) of live weight) are close to those proposed by the Agricultural and Food Research Council adopted in UK for beef and dairy cattle. The results indicate that the present FM data can be used as a basis for rationing water buffalo in China.


Quorum sensing signal molecules produced by Pseudomonas aeruginosa cause inflammation and escape host factors in murine model of urinary tract infection.
Quorum sensing (QS) is well established for its role in pathogenesis of various infections of Pseudomonas aeruginosa. However, its role in local tissue damage during urinary tract infection (UTI) is not yet fully established. To have insight in this, the present study was planned. UTI was established in mice using standard strain PAO1 and its isogenic QS mutant JP2. One group was challenged only with QS signals. Damage was assessed in terms of histopathology and pathology markers, malondialdehyde (MDA) and reactive nitrogen intermediates (RNI). Effect on pathogen motility, uroepithelial adhesion, and host serum sensitivity was also ascertained. PAO1-infected mice showed severe inflammation and tissue destruction, while mice infected with JP2 showed no significant destruction. JP2 was also unable to mount any tissue pathology markers, MDA and RNI, whereas PAO1 showed significantly higher levels of these two. Presence of only QS signals also showed considerable renal pathology. Strain JP2 also showed less motility, reduced uroepithelial cell adhesion, and increased serum sensitivity. Result highlights that QS signals induce local tissue pathology along with interference of host protective mechanisms during UTI.


Regional patterns of gray matter volume, hypometabolism, and beta-amyloid in groups at risk of Alzheimer's disease.
Alzheimer's disease (AD) is characterized by the presence of β-amyloid (Aβ) deposition and neurodegeneration. To seek for signs of such pathologies, we compared regional biomarker degrees and patterns of Aβ deposition, glucose hypometabolism, and gray matter volume (GMV) reduction in 3 groups at risk of AD. In elderly carriers of the apolipoprotein E ε4 (APOE4, n = 17), patients with subjective cognitive decline (n = 16), and patients with mild cognitive impairment (n = 30), head-to-head intermodality comparisons were performed on cross-sectional structural magnetic resonance images as well as 18F-fluorodeoxyglucose and 18F-florbetapir positron emission tomography scans. In mild cognitive impairment patients, 3 distinct biomarker patterns were recovered, similarly seen in AD patients: (1) in medial temporal regions, local GMV reduction exceeded hypometabolism, (2) in temporoparietal regions, hypometabolism predominated over GMV reduction, and (3) in frontal regions, Aβ deposition exceeded GMV reduction and hypometabolism. In subjective cognitive decline patients, only pattern 1 was detected, while APOE4 carriers demonstrated only pattern 3. Our findings highlight that regional AD-like biomarker patterns may vary across different at-risk populations, potentially reflecting differential mediators of these risks.


Beneficial Metabolic Effects of TREM2 in Obesity Are Uncoupled From Its Expression on Macrophages.
Obesity-induced white adipose tissue (WAT) hypertrophy is associated with elevated adipose tissue macrophage (ATM) content. Overexpression of the triggering receptor expressed on myeloid cells 2 (TREM2) reportedly increases adiposity, worsening health. Paradoxically, using insulin resistance, elevated fat mass, and hypercholesterolemia as hallmarks of unhealthy obesity, a recent report demonstrated that ATM-expressed TREM2 promoted health. Here, we identified that in mice, TREM2 deficiency aggravated diet-induced insulin resistance and hepatic steatosis independently of fat and cholesterol levels. Metabolomics linked TREM2 deficiency with elevated obesity-instigated serum ceramides that correlated with impaired insulin sensitivity. Remarkably, while inhibiting ceramide synthesis exerted no influences on TREM2-dependent ATM remodeling, inflammation, or lipid load, it restored insulin tolerance, reversing adipose hypertrophy and secondary hepatic steatosis of TREM2-deficient animals. Bone marrow transplantation experiments revealed unremarkable influences of immune cell-expressed TREM2 on health, instead demonstrating that WAT-intrinsic mechanisms impinging on sphingolipid metabolism dominate in the systemic protective effects of TREM2 on metabolic health.


Almanac 2014: congenital heart disease.
This Almanac summarises important congenital heart disease articles published between 2012 and 2014 in Heart and other major cardiac journals. It highlights what the authors perceive to be highly relevant articles in the field. While the aim was to provide a comprehensive overview of the area, a focus on certain areas of interest was required. The selection is, therefore, by necessity a subjective one.


Investigating Correlates of Self-Regulation in Early Childhood with a Representative Sample of English-Speaking American Families.
Children who possess less self-regulatory skill are at a disadvantage when compared to children who demonstrate greater skill at regulating their emotions, cognitions and behavior. Children with these regulatory deficits have difficulty connecting with peers, generating relationships with teachers, negotiating their social world, and succeeding academically. By understanding the correlates of self-regulatory abilities, interventions can be developed to ensure that children at-risk for poor self-regulation receive the support necessary to enhance their regulatory skills. Using data from a nationally representative survey of English-speaking American parents with children between the ages of two and eight (n = 1,141), we evaluated a host of demographic and parenting variables to isolate the correlates of self-regulation. Older children were found to have fewer regulatory problems than younger children while children from low-income homes and male children were found to have greater problems with self-regulation. Minority status, household composition (single vs multi-parent), and parental education were not significant correlates of self-regulation. Findings also illustrate the powerful relationship between parenting style and self-regulation. Parents who rely on nurturing parenting practices that reinforce the child's sense of autonomy while still maintaining a consistent parenting presence (i.e., authoritative parenting) have children who demonstrate stronger self-regulatory skills. Parents who exert an excess of parental control (i.e., authoritarian parents) have children with weaker self-regulatory skills. And lastly, parents who have notable absence of control (i.e., permissive parents) are more likely to have children with considerable regulatory deficits. Results offer implications for both practitioners and scholars.


Circulating odd-chain saturated fatty acids were associated with arteriosclerosis among patients with diabetes, dyslipidemia, or hypertension in Sri Lanka but not Japan.
The differences in the morbidity and mortality of cardiovascular diseases between Sri Lankan and Japanese populations might be explained by the differences in their diet, especially fat. To test the hypothesis that the fatty acid (FA) compositions differ between Sri Lankan and Japanese populations and that high concentrations of n-3 polyunsaturated FAs and linoleic acid are associated with a low level of arteriosclerosis, the authors compared the circulating FA compositions between Sri Lankan and Japanese populations and examined the association of the circulating FA composition with arterial stiffness in each population. The study participants were patients with diabetes, dyslipidemia, or hypertension in Sri Lanka (n = 100) or Japan (n = 236). Serum FA compositions were measured by gas chromatography. Arterial stiffness was measured using the cardio-ankle vascular index (CAVI). Analysis of covariance was used to compare the FA compositions between the populations. Multiple regression was used to assess the association between each FA and CAVI levels. The concentrations of myristic, γ-linolenic, dihomo-γ-linolenic, and arachidonic acids were higher in the Sri Lankan patients than in the Japanese patients. In contrast, the concentrations of linoleic, α-linolenic, and eicosapentaenoic acids were higher in the Japanese patients than in the Sri Lankan patients. Although no associations of n-3 polyunsaturated FAs and linoleic acid with CAVI were observed in both patient populations, odd-chain saturated FAs (pentadecanoic and heptadecanoic acids) were significantly inversely associated with CAVI levels in the Sri Lankan (P for trend = .03) but not the Japanese patients. The odd-chain saturated FAs might be inversely associated with atherosclerosis in this Sri Lankan population.


Intra-amygdala infusion of the NPY Y1 receptor antagonist BIBP 3226 attenuates operant ethanol self-administration.
Neuropeptide Y (NPY) is the most abundant and widely distributed peptide in the mammalian central nervous system. Evidence suggests that NPY transmission at Y1 receptors may regulate alcohol self-administration in rodent models. The purpose of the present study was to test the involvement of NPY Y1 receptors in the amygdala in the reinforcing effects of alcohol. Long-Evans rats were trained to self-administer ethanol (10% v/v) vs. water on a concurrent FR-1 schedule of reinforcement using a sucrose fading procedure. After a 1 month baseline period, bilateral injector cannulae were surgically implanted to terminate 1 mm dorsal to the central nucleus of the amygdala. Daily (Monday through Friday) operant self-administration sessions were conducted for 6 months after surgery. Then, the effects of intra-amygdala infusion of the high-affinity nonpeptide NPY Y1 receptor antagonist BIBP 3226 (1, 10, or 20 microMg) were determined on parameters of operant alcohol self-administration. Intra-amygdala administration of 10 microM or 20 microM BIBP 3226 decreased total alcohol-reinforced responding and dose of self-administered ethanol (g/kg) without significantly altering total water responses or intake compared with vehicle control. Response onset was unaffected. Analysis of the temporal pattern of ethanol- and water-reinforced responding showed that BIBP 3226 decreased cumulative ethanol-reinforced responding during the 30 to 60 min period of the sessions. Water-reinforced responses were increased by the low dose of BIBP 3226 (1 microM) during the 50 to 60 min period. Results from this study indicate that alcohol-reinforced responding is reduced by acute blockade of NPY Y1 receptors in the amygdala of rats with a long-term history of alcohol self-administration. These data are consistent with the hypothesis that alcohol self-administration is maintained by NPY neurotransmission at Y1 receptors in the central nucleus of the amygdala.


Expression of inducible nitric oxide synthase in the epithelial linings of odontogenic keratocyst, dentigerous cyst and radicular cyst: a pathological insight.
The present study is aimed at analyzing the expression of inducible nitric oxide synthase (iNOS) in the epithelial lining of odontogenic keratocyst (OKC), dentigerous cyst (DC), radicular cyst (RC) in order to understand the possible role of iNOS with special reference to its neoplastic nature and local aggressive of cysts. The primary aim of the following study is to analyze the immunohistochemical expression of iNOS and secondary aim is to compare the iNOS expression, pattern and intensity of staining among the epithelial linings of OKC, DC and RC. iNOS in the epithelial lining cells were analyzing in 10 OKC's, 10 DC's and 10 RC's using immunohistochemistry. The percentage of positive cells was assessed and presented as mean ± standard deviation. The correlation with respect to the intensity and percentage of staining within the epithelial linings of OKCs, DCs and RCs was carried out using (analysis of variance and Student's t-test) Chi-square test. Staining intensity of iNOS portion was seen in the entire thickness of the epithelial linings of OKC, whereas in DC's only one case had entire thickness of the epithelial lining staining and in RC's none of the cases showed entire thickness of staining. On comparing the staining intensity of iNOS between OKC, DC and RC groups, using Chi-square test, there was a statistically significant difference between these groups (P < 0.01). On analyzing the immuno-reactivity of iNOS in OKC, DC and RC there was a positive variable expression iNOS between the cysts. iNOS was over expressed in OKCs when compared with DC and RC suggesting that iNOS may contribute to the aggressive behavior of OKC. This is yet another evidence to support that OKC is the neoplasm.


Novel individualized power training protocol preserves physical function in adult and older mice.
Sarcopenia, the age-related loss of muscle mass and strength, contributes to frailty, functional decline, and reduced quality of life in older adults. Exercise is a recognized therapy for sarcopenia and muscle dysfunction, though not a cure. Muscle power declines at an increased rate compared to force, and force output declines earlier than mass. Thus, there is a need for research of exercise focusing on improving power output and functionality in older adults. Our primary purpose was proof-of-concept that a novel individualized power exercise modality would induce positive adaptations in adult mice, before the exercise program was applied to an aged cohort. We hypothesized that after following our protocol, both adult and older mice would show improved function, though there would be evidence of anabolic resistance in the older mice. Male C57BL/6 mice (12 months of age at study conclusion) were randomized into control (n = 9) and exercise (n = 6) groups. The trained group used progressive resistance (with a weighted harness) and intensity (~ 4-10 rpm) on a custom motorized running wheel. The mice trained similarly to a human workout regimen (4-5 sets/session, 3 sessions/week, for 12 weeks). We determined significant (p < 0.05) positive adaptations post-intervention, including: neuromuscular function (rotarod), strength/endurance (inverted cling grip test), training physiology (force/power output per session), muscle size (soleus mass), and power/velocity of contraction (in vitro physiology). Secondly, we trained a cohort of older male mice (28 months old at conclusion): control (n = 12) and exercised (n = 8). While the older exercised mice did preserve function and gain benefits, they also demonstrated evidence of anabolic resistance.


An economic evaluation of laparoscopic cholecystectomy for public hospitals in Trinidad and Tobago.
Laparoscopic Cholecystectomy (LC) is compared to the Open and Minilap approaches in a Cost Minimization Analysis for public hospitals in Trinidad and Tobago. The analysis shows that despite the high initial equipment cost required to perform LC, substantial savings can be achieved at the hospital level by converting from a minilap or open regime to a laparoscopic regime for cholecystectomy. Because of the reduced recovery period for the patient, LC represents further savings to other sectors of the economy as patients return to work much earlier after LC than after the other two approaches.


[Syndromic approach to MR diagnosis of gouty arthritis].
The objective of the study was to improve radiodiagnosis of gouty arthritis. Thirty-six gout patients aged 39 to 58 years were examined. All the patients underwent X-ray of affected joints and magnetic resonance imaging (MRI). X-ray and MRI revealed tophus formation. The latter also showed articular syndrome and extraarticular manifestations of gout. Analysis of the findings indicated that MRI could enhance the informative value of clinicoradiographic examination of gout patients.


Dietary Supplementation with Lysine and Threonine Modulates the Performance and Plasma Metabolites of Broiler Chicken.
Here, we investigated whether the optimal threonine (Thr) to lysine (Lys) ratio in high Lys diet improves the growth performance of modern broiler chickens at finisher period and determined the possible mechanism underlying improvement in the growth performance of chickens fed with high Lys or Lys + Thr diet using metabolome analyses. Eighteen 21-day-old chickens housed in individual cages were randomly divided into three groups of six chickens fed with different diets as follows: control diet, high Lys diet (150% Lys content of National Research Council requirement), and high Lys + Thr diet (0.68 of Thr/Lys in high Lys diet). Body weight gain (BWG) increased in chickens receiving high Lys diet as compared with those fed with the control diet (P<0.05); no significant difference was observed in BWG of chickens from high Lys + Thr and high Lys groups. Feed conversion ratio (FCR) was lower in chickens fed with high Lys or high Lys + Thr diet than in those on the control diet. Serotonin concentration increased in the plasma of chickens fed with high Lys diet as compared to those fed with other diets. A negative correlation was observed between plasma serotonin concentration and FCR. These results provide the first evidence on the use of high Lys in broiler diets to reduce FCR during finisher period, which may be associated with change in plasma serotonin concentration. These findings suggest that high Lys content in finisher diet, but not high Thr + Lys diet, may affect the peripheral serotonergic metabolism and improve FCR. Thus, plasma serotonin may serve as a biomarker of FCR in broilers.


Development of molecular driven screening for desulfurizing microorganisms targeting the dszB desulfinase gene.
COnsensus DEgenerate Hybrid Oligonucleotide Primers (CODEHOP) were developed for the detection of the dszB desulfinase gene (2'-hydroxybiphenyl-2-sulfinate desulfinase; EC 184.108.40.206) by polymerase chain reaction (PCR), which allow to reveal larger diversity than traditional primers. The new developed primers were used as molecular monitoring tool to drive a procedure for the isolation of desulfurizing microorganisms. The primers revealed a large dszB gene diversity in environmental samples, particularly in diesel-contaminated soil that served as inoculum for enrichment cultures. The isolation procedure using the dibenzothiophene sulfone (DBTO2) as sole sulfur source reduced drastically the dszB gene diversity. A dszB gene closely related to that carried by Gordonia species was selected. The desulfurization activity was confirmed by the production of desulfurized 2-hydroxybiphenyl (2-HBP). Metagenomic 16S rRNA gene sequencing showed that the Gordonia genus was represented at low abundance in the initial bacterial community. Such observation highlighted that the culture medium and conditions represent the bottleneck for isolating novel desulfurizing microorganisms. The new developed primers constitute useful tool for the development of appropriate cultural-dependent procedures, including medium and culture conditions, to access novel desulfurizing microorganisms useful for the petroleum industry.


Nutritional omega-3 modulates neuronal morphology in the prefrontal cortex along with depression-related behaviour through corticosterone secretion.
Understanding how malnutrition contributes to depression is building momentum. In the present study we unravel molecular and cellular mechanisms by which nutritional disturbances lead to impaired emotional behaviour in mice. Here we report that nutritional n-3 polyunsaturated fatty acids (PUFA) deficiency induces a chronic stress state reflected by disrupted glucocorticoid receptor (GR)-mediated signalling pathway along with hypothalamic-pituitary-adrenal (HPA) axis hyperactivity. This hyperactivity in turn resulted in neuronal atrophy in the dorsolateral (dl)- and dorsomedial (dm)- prefrontal cortex (PFC) and subsequent mood-related behaviour alterations, similarly to chronic social defeat stress. Supplementation of n-3 PUFA prevented detrimental chronic social defeat stress-induced emotional and neuronal impairments by impeding HPA axis hyperactivity. These results indicate a role for dietary n-3 PUFA in the prevention of HPA axis dysfunction associated with the development of some neuropsychiatric disorders including depression.


Status of antituberculosis drug resistance in Saudi Arabia 1979-98.
All published material on the prevalence of drug-resistant tuberculosis within Saudi Arabia over the period 1979-98 was reviewed. The prevalence of single-drug-resistant tuberculosis ranged from 3.4% to 41% for isoniazid, 0% to 23.4% for rifampicin, 0.7% to 22.7% for streptomycin and 0% to 6.9% for ethambutol. The prevalence of multidrug-resistant tuberculosis (defined by WHO as resistance to two or more first-line antituberculosis drugs) ranged from 1.5% to 44% in different regions. No strong conclusions could be drawn owing to variations in the populations studied, geographical origins, site of Mycobacterium tuberculosis isolation (pulmonary or extrapulmonary) and drug sensitivity testing. However, the need to develop a standardized national policy for surveillance of drug-resistant tuberculosis in Saudi Arabia is clear.


The hydrocortisone-responsive urinary metabolome of premature infants.
Extremely premature infants are at risk for circulatory collapse or respiratory failure that are often treated with hydrocortisone (HC); however, there is no information on the metabolic consequences of this therapy. Longitudinal urine samples from infants <28 weeks gestation in the Trial of Late Surfactant were analyzed by untargeted UHPLC:MS/MS. Fourteen infants who received a tapering course of HC beginning at 3 mg/kg/day for ≥9 days were compared to 14 matched control infants. A secondary cross-sectional analysis by logistic regression used urines from 314 infants. Of 1145 urinary metabolites detected, abundance of 219, representing all the major biochemical pathways, changed at p < 0.05 in the HC-treated group with 90% decreasing; 3 cortisol derivatives increased ~2-fold with HC therapy. Only 11% of regulated metabolites remained responsive at the lowest HC dose. Regulated metabolites included two steroids and thiamin that are associated with lung inflammation in infants. HC responsiveness was confirmed in 57% of metabolites by cross-sectional analysis. HC treatment of premature infants influenced in a dose-dependent manner abundance of 19% of identified urinary metabolites of diverse biochemical systems, primarily reducing concentrations. These findings indicate that exposure to HC reversibly impacts the nutritional status of premature infants. Hydrocortisone treatment of premature infants with respiratory failure or circulatory collapse alters levels of a subset of urinary metabolites representing all major biochemical pathways. This is the first description of the scope, magnitude, timing and reversibility of metabolomic changes in infants in response to hydrocortisone, and it confirms corticosteroid regulation of three biochemicals that are associated with lung inflammatory status. The findings indicate a dose-dependency of hydrocortisone for metabolomic and anti-inflammatory effects, that prolonged therapy may lower the supply of many nutrients, and that monitoring concentrations of cortisol and inflammation markers may be a useful clinical approach during corticosteroid therapy.


Excitation of GABAergic Neurons in the Bed Nucleus of the Stria Terminalis Triggers Immediate Transition from Non-Rapid Eye Movement Sleep to Wakefulness in Mice.
Emotionally salient situations usually trigger arousal along with autonomic and neuroendocrine reactions. To determine whether the extended amygdala plays a role in sleep-wakefulness regulation, we examined the effects of optogenetic and pharmacogenetic excitation of GABAergic neurons in the bed nucleus of the stria terminalis (GABABNST neurons). Acute optogenetic excitation of these cells during nonrapid eye movement (NREM) sleep resulted in an immediate state transition to wakefulness, whereas stimulation during REM sleep showed no effect on sleep-wakefulness states in male mice. An anterograde tracing study suggested GABABNST neurons send axonal projections to several brain regions implicated in arousal, including the preoptic area, lateral hypothalamus, periaqueductal gray, deep mesencephalic nucleus, and parabrachial nucleus. A dual orexin receptor antagonist, DORA-22, did not affect the optogenetic transition from NREM sleep to wakefulness. Chemogenetic excitation of GABABNST neurons evoked a sustained wakefulness state, but this arousal effect was markedly attenuated by DORA-22. These observations suggest that GABABNST neurons play an important role in transition from NREM sleep to wakefulness without the function of orexin neurons, but prolonged excitation of these cells mobilizes the orexin system to sustain wakefulness.SIGNIFICANCE STATEMENT We examined the role of the bed nucleus of the stria terminalis (BNST) in the regulation of wakefulness. Optogenetic excitation of GABAergic neurons in the BNST (GABABNST neurons) during nonrapid eye movement (NREM) sleep in mice resulted in immediate transition to a wakefulness state without function of orexins. Prolonged excitation of GABABNST neurons by a chemogenetic method evoked a longer-lasting, sustained wakefulness state, which was abolished by preadministration of a dual orexin receptor antagonist, DORA-22. This study revealed a role of the BNST GABAergic system in sleep-wakefulness control, especially in shifting animals' behavioral states from NREM sleep to wakefulness, and provides an important insight into the pathophysiology of insomnia and the role of orexin in arousal regulation.


Gastroesophageal reflux disease and asthma.
Asthma and gastroesophageal reflux disease (GERD) are both common diseases, and hence they often coexist. However, the coexistence of asthma and GERD is far more frequent than chance association. There remains debate regarding the mechanism of this relationship and whether treatment of GERD improves asthma outcomes. Recent data have confirmed the high prevalence of GERD among patients with asthma. Many asthmatic patients with GERD documented by pH probe do not have classic symptoms of GERD and are considered to have 'silent GERD'. On the basis of smaller trials with somewhat conflicting results regarding improved asthma control with treatment of GERD, consensus guidelines recommend a trial of GERD treatment for symptomatic asthmatic patients even without symptoms of GERD. Recently, a large multicenter trial demonstrated that the treatment of asymptomatic GERD with proton pump inhibitors did not improve asthma control in terms of pulmonary function, rate of asthma exacerbations, asthma-related quality of life, or asthma symptom frequency. Asthmatic patients have more GERD than the general population. There is not a clear understanding of why this is true. Current guidelines recommend that physicians consider treating patients who have poorly controlled asthma for GERD, even without GERD symptoms. Recent data suggest that this is not a useful practice for mild-to-moderate asthmatic patients.


Correlative intravital imaging of cGMP signals and vasodilation in mice.
Cyclic guanosine monophosphate (cGMP) is an important signaling molecule and drug target in the cardiovascular system. It is well known that stimulation of the vascular nitric oxide (NO)-cGMP pathway results in vasodilation. However, the spatiotemporal dynamics of cGMP signals themselves and the cGMP concentrations within specific cardiovascular cell types in health, disease, and during pharmacotherapy with cGMP-elevating drugs are largely unknown. To facilitate the analysis of cGMP signaling in vivo, we have generated transgenic mice that express fluorescence resonance energy transfer (FRET)-based cGMP sensor proteins. Here, we describe two models of intravital FRET/cGMP imaging in the vasculature of cGMP sensor mice: (1) epifluorescence-based ratio imaging in resistance-type vessels of the cremaster muscle and (2) ratio imaging by multiphoton microscopy within the walls of subcutaneous blood vessels accessed through a dorsal skinfold chamber. Both methods allow simultaneous monitoring of NO-induced cGMP transients and vasodilation in living mice. Detailed protocols of all steps necessary to perform and evaluate intravital imaging experiments of the vasculature of anesthetized mice including surgery, imaging, and data evaluation are provided. An image segmentation approach is described to estimate FRET/cGMP changes within moving structures such as the vessel wall during vasodilation. The methods presented herein should be useful to visualize cGMP or other biochemical signals that are detectable with FRET-based biosensors, such as cyclic adenosine monophosphate or Ca(2+), and to correlate them with respective vascular responses. With further refinement and combination of transgenic mouse models and intravital imaging technologies, we envision an exciting future, in which we are able to "watch" biochemistry, (patho-)physiology, and pharmacotherapy in the context of a living mammalian organism.


[Serum insulin and androgen concentrations in women with histories of gestational diabetes].
There is a certain degree of peripheral cell resistance to insulin in the physiopathology of gestational diabetes. These disturbances may persist following pregnancy giving place to secondary hyperinsulinism. Insulin exerts a trophic action on the ovary and favors the production of androgens. The aim of this study was to verify whether the patients diagnosed of gestational diabetes present androgenic alterations following pregnancy. The existence of a correlation between the values of insulin and androgens was analyzed. Fifty-one patients were studied. The study group (n = 297) was composed of patients diagnosed of gestational diabetes during their last week of pregnancy. The control group (n = 24) included patients with normal carbohydrate tolerance. The basal values of insulin, glucose, androstenedione, testosterone and SHBG were determined in a postmenstrual phase. Insulin was found to be higher in the study group (78.1 +/- 32.9 pmol/1 vs 63.0 +/- 27.6 pmol/1) although the differences were not significant. The insulin/glucose ratio was significantly higher in the study group (18.1 +/- 8.0 vs 13.9 +/- 7.7; p less than 0.05). Basal insulin and the insulin/glucose ratio were comparable among the obese and non obese patients of both groups. The remaining parameters studied dit not present any significant differences. No significant associations were observed between the values of insulin and insulin/glucose with the androgenic hormonal parameters. No elevated androgenic profile was observed in the women with previous gestational diabetes. The use of insulin and insulin/glucose values as indicators of insulin resistance did not demonstrate any correlation with the androgenic parameters.


Effects of fish meal in beef cattle diets on growth performance, carcass characteristics, and fatty acid composition of longissimus muscle.
We investigated the effects of fish meal (FM) in beef cattle diets on growth performance, carcass characteristics, and fatty acid (FA) composition of longissimus muscle in 63 yearling steers (335 +/- 23 kg). High-moisture corn and alfalfa silage diets were supplemented with either a corn gluten/blood meal mixture or FM at 10% of the diet. Fish meal contained (as-is basis) 5.87 g/kg eicosapentaenoic acid (EPA) and 9.84 g/kg docosahexaenoic acid (DHA). Seven strategies were developed to feed either a control diet (no FM) or diets containing 5 or 10% FM with FM fed for either 56, 112, or 168 d before slaughter. Average daily gain and feed efficiency were not affected (P > .10) by FM feeding but DMI decreased. Within FM diets, cattle fed 5% FM consumed more (P < .01) DM and gained more (P < .02) than cattle fed 10% FM. Carcass traits were not affected (P > .05) by feeding strategy except for fatter (P < .05) and lower (P < .06) yielding carcasses in cattle fed 5 vs 10% FM diets. Fish meal feeding increased (P < .01) concentrations of (n-3) FA, including EPA and DHA, and decreased (P < .05) concentrations of arachidonic acid. Increasing the amount of dietary FM further increased (P < .01) concentrations of EPA and DHA and decreased (P < .05) concentrations of (n-6) FA. We estimate that a 114-g steak from cattle fed 10% FM would supply 35 to 90% of the current average daily intake of EPA and DHA in North America. The results indicate that FM may have a role in niche marketing of beef provided that eating quality is not compromised.


Cytokine activation leads to acidification and increases maturation of Mycobacterium avium-containing phagosomes in murine macrophages.
Mycobacterium avium (MAC) organisms multiply in phagosomes that have restricted fusigenicity with lysosomes, do not acidify due to a paucity of vacuolar proton-ATPases, yet remain accessible to recycling endosomes. During the course of mycobacterial infections, IFN-gamma-mediated activation of host and bystander macrophages is a key mechanism in the regulation of bacterial growth. Here we demonstrate that in keeping with earlier studies, cytokine activation of host macrophages leads to a decrease in MAC viability, demonstrable by bacterial esterase staining with fluorescein diacetate as well as colony-forming unit counts from infected cells. Analysis of the pH of MAC phagosomes demonstrated that the vacuoles in activated macrophages equilibrate to pH 5.2, in contrast to pH 6.3 in resting phagocytes. Biochemical analysis of MAC phagosomes from both resting and activated macrophages confirmed that the lower intraphagosomal pH correlated with an increased accumulation of proton-ATPases. Furthermore, the lower pH is reflected in the transition of MAC phagosomes to a point no longer accessible to transferrin, a marker of the recycling endosomal system. These alterations parallel the coalescence of bacterial vacuoles from individual bacilli in single vacuoles to communal vacuoles with multiple bacilli. These data demonstrate that bacteriostatic and bactericidal activities of activated macrophages are concomitant with alterations in the physiology of the mycobacterial phagosome.


[Free radical oxidation of DNA and its biomarker oxidized guanosine(8-oxodG)].
Endogenous free radicals, in particular, reactive species of oxygen, nitrogen, chlorine cause DNA oxidation which is potentiated by exogenous prooxidant factors. The free radicals cause various DNA damages. This review highlights one of them, oxidative modification of guanosine, and also modern methods of the estimation of oxidized guanosine (8-oxodG) content. The numerous data on an induction of 8-oxodG in DNA by exogenous genotoxicants in vitro and in vivo are presented. 8-oxodG is used as a biomarker of DNA oxidation, accompanying some human diseases.


ChoRe: A device for trans-catheter chordae tendineae repair.
This work focuses on the design of a new device (called ChoRe) to place artificial chords in the mitral valve structure during a trans-catheter procedure. The aim of the device is to restore the correct functionality of the valve and solve mitral valve regurgitation, that is, a common consequence of chordae tendineae rupture. An analysis of the requirements was carried out and used to design and develop a first functional prototype. The resulting device was able to connect artificial chords at the posterior leaflet of the mitral valve and at the apex of the left ventricle, also allowing the control of the artificial chord length. The ChoRe was tested ex-vivo in bovine hearts. The qualitative assessment of the ChoRe focused on the performance of the device and preliminary evaluation of the procedure time. Results demonstrated that the device is able to create a top and bottom fixation in an average time of 3.45 ± 1.44 min. Future improvements will focus on enhancing the connection at the leaflet, as well as the overall functionality, in order to guarantee better control of the artificial chord length. This work shows future potentials for more patient-specific treatments in trans-catheter scenarios for mitral valve repair.


Association of ghrelin receptor promoter polymorphisms with weight loss following Roux-en-Y gastric bypass surgery.
Ghrelin plays a role in appetite and has been hypothesized to play a role in the mechanism of Roux-en-Y gastric bypass (RYGB) surgery. Single nucleotide polymorphisms (SNPs) in the promoter region of its receptor gene (growth hormone secretagogue receptor type 1a--GHSR) have also been associated with weight loss outcomes following long-term dietary intervention in adults with impaired glucose tolerance. Our objectives were to evaluate changes in serum ghrelin levels and determine the effect of GHSR promoter polymorphisms on post-RYGB surgery weight loss. Preoperative and 6-month postoperative serum ghrelin levels were measured in 37 patients with extreme obesity undergoing RYGB surgery. Total ghrelin was also measured in liver tissue collected intraoperatively. Association analysis between genotypes for SNPs rs9819506 and rs490683 in the promoter region of the GHSR gene and weight loss outcomes in the 30 months following surgery was performed in over 650 RYGB patients. Serum ghrelin levels increased after RYGB surgery. Weight loss trajectories were significantly different using an additive model for both ghrelin SNPs, with patients homozygous for the rs490683 CC genotype exhibiting the most weight loss. Weight loss trajectories were also different using a dominant model. The rs490683 risk allele demonstrated decreased promoter activity in vitro. The role of increased ghrelin levels in weight loss outcomes following RYGB surgery may be influenced by variation in the GHSR gene.


The primacy of the public: in support of bioethics commissions as deliberative forums.
In a 2004 article, we argued that bioethics commissions should be assessed in terms of their usefulness as public forums. A 2006 article by Summer Johnson argued that our perspective was not supported by the existing literature on presidential commissions, which had not previously identified commissions as public forums and that we did not properly account for the political functions of commissions as instruments of presidential power. Johnson also argued that there was nothing sufficiently unique about bioethics commissions to make the public forum perspective particularly applicable. We respond by arguing that analysis of commissions' work as public forums fits well within the literature on commissions, especially on their agenda-setting functions, and that the political functions of commissions are often compatible with their functioning as public forums. We also demonstrate how the origins and concerns of bioethics make public forum analysis particularly applicable to bioethics commissions.


Anilides related to substituted benzamides. Potential antipsychotic activity of N-(4-amino-5-chloro-2-methoxyphenyl)-1-(phenylmethyl)-4-piperidinecarboxamide.
The substituted benzamides are used clinically both as antipsychotics and as stimulants of gastric motility. The antipsychotic effects are considered to be a consequence of their central dopamine antagonist properties, but there is evidence that the gastric stimulatory effects may be mediated by other mechanisms. Clebopride (3) is a substituted benzamide that although marketed for its stimulatory effects on gastric motility, is also a potent central dopamine antagonist. The corresponding anilide, BRL 20596 (4a), where the amide bond has been reversed, has been synthesized and found to lack gastric stimulatory activity. However, the potent central dopamine antagonist activity is retained, suggesting that benzamides and anilides have similar affinities for central dopamine receptors. The implications of the conformations adopted by benzamides and anilides at such receptors are discussed. Evidence is also presented that there is a further lipophilic binding site on such receptors for which the N-benzyl group is an optimal fit.


Second - harmonic generation of ultra-high intensity femtosecond pulses with a KDP crystal.
We investigated second harmonic generation with ultrahigh intensity femtosecond laser pulses from a terawatt Ti: sapphire laser system. Energy conversion efficiency of about 80 % for a type I potassium dideuterium phosphate crystal was obtained with 130 fs laser pulses at an intensity as high as 192 GW/cm 2.


Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance.
Protease inhibitors have the highest potency among antiviral therapies against HIV-1 infections, yet the virus can evolve resistance. Darunavir (DRV), currently the most potent Food and Drug Administration-approved protease inhibitor, retains potency against single-site mutations. However, complex combinations of mutations can confer resistance to DRV. While the interdependence between mutations within HIV-1 protease is key for inhibitor potency, the molecular mechanisms that underlie this control remain largely unknown. In this study, we investigated the interdependence between the L89V and L90M mutations and their effects on DRV binding. These two mutations have been reported to be positively correlated with one another in HIV-1 patient-derived protease isolates, with the presence of one mutation making the probability of the occurrence of the second mutation more likely. The focus of our investigation is a patient-derived isolate, with 24 mutations that we call "KY"; this variant includes the L89V and L90M mutations. Three additional KY variants with back-mutations, KY(V89L), KY(M90L), and the KY(V89L/M90L) double mutation, were used to experimentally assess the individual and combined effects of these mutations on DRV inhibition and substrate processing. The enzymatic assays revealed that the KY(V89L) variant, with methionine at residue 90, is highly resistant, but its catalytic function is compromised. When a leucine to valine mutation at residue 89 is present simultaneously with the L90M mutation, a rescue of catalytic efficiency is observed. Molecular dynamics simulations of these DRV-bound protease variants reveal how the L90M mutation induces structural changes throughout the enzyme that undermine the binding interactions.


Lack of detection of human papillomavirus (HPV) in transformed laryngeal keratoses by in situ hybridization (ISH) technique.
Laryngeal keratosis (LK) is a precancerous mucosal change with a variable possibility of malignant transformation. Recent studies evidencing HPV-DNA genomes in a large series of non-malignant and malignant laryngeal lesions suggest a role of HPV in the transformation of laryngeal lesions possibly in synergistic interaction with other carcinogens. In this study, we analyzed 115 biopsy specimens from benign laryngeal lesions to evaluate the risk of malignant transformation and its relationship to degree of dysplasia and to histological features of virus cell infection. The rate of transformation of LK was 8% (9/115). Our results indicate that the risk of transformation in laryngeal keratoses without dysplasia (LKWOD) is lower than that in laryngeal keratoses with dysplasia (2.2% vs 25%, respectively) (p < 0.05). An increased risk of malignant evolution in laryngeal keratoses with dysplasia (LKWD) was also related to the degree of dysplasia (rate of transformation of 12.5, 22.2 and 36% in mild, moderate and severe dysplasia, respectively). Histological features suggesting HPV infection (koilocytic-like atypia and epithelial papillary hyperplasia) were found in 6 LK only, no case subsequently developing cancer. In both benign and transformed LK, analyzed by ISH, we failed to detect HPV genomes, suggesting a major role of others carcinogens, such as tobacco and/or alcohol, in the transformation of LK.


Fast Mass-Production of Medical Safety Shields under COVID-19 Quarantine: Optimizing the Use of University Fabrication Facilities and Volunteer Labor.
COVID-19 pandemic provoked a number of restrictive measures, such as the closure or severe restriction of border transit for international trading traffic, quarantines and self-isolation. This caused a series of interrelated consequences that not only prevent or slow down the spread of disease, but also impact the medical systems' capability to treat the patients and help their recovery. In particular, steeply growing demand for medical safety goods cannot be satisfied by regular suppliers due to the shortage of raw materials originating from other countries or remotely located national sources, under conditions of quarantined manpower. The current context inevitably brings back memories (and records!) of the situation 80 years ago, when WWII necessitated major effort directed at the rapid build-up of low-cost mass production to satisfy all aspects of war-time need. In the present short report we document a successful case of fast mass-production of light transparent medical safety face shields (thousands per day) realized in Skolkovo Institute of Science and Technology (Skoltech) at Fablab and Machine Shop Shared Facility (Skoltech FabLab). The demand for safety face shields by tens of hospitals in Moscow and other cities rapidly ramped up due to the need to protect medical staff during patient collection and transportation to hospitals, and within both the infected ("red") and uninfected ("green") zones. Materials selection for sterilizable transparent materials was conducted based on the analysis of merit indices, namely, minimal weight at given stiffness and minimal cost at given stiffness. Due to the need for permanent wear, design was motivated by low weight and comfortable head fixation, along with high production efficiency. The selection of minimal tooling in University fabrication workshops and the use of distributed volunteer labor are discussed.


Embryo deadenylation element-dependent deadenylation is enhanced by a cis element containing AUU repeats.
The deadenylation of maternal mRNAs in the Xenopus embryo is a sequence-specific process. One cis element that targets maternal mRNAs for deadenylation after fertilization is the embryo deadenylation element (EDEN). This element, composed of U/R repeats, is specifically bound by a protein, EDEN-BP. In the present study we show that the rate at which an RNA containing an EDEN is deadenylated can be increased by the presence of an additional cis element composed of three AUU repeats. This effect was observed for a natural EDEN (c-mos) and two synthetic EDENs. Hence, the enhancement of EDEN-dependent deadenylation conferred by the (AUU)3 motif is not due to an interaction with a particular EDEN sequence. Mutation of the (AUU)3 motif abrogated the enhancement of EDEN-dependent deadenylation. These data indicate that the rate at which a specific maternal mRNA is deadenylated in Xenopus embryos is probably defined by a cross talk between multiple cis elements.


Modulation of polymorphonuclear neutrophil functions by astrocytes.
Neuroinflammation is a complex process involving cells from the immune system and the central nerve system (CNS). Polymorphonuclear neutrophils (PMN) are the most abundant class of white blood cells, and typically the first type of leukocyte recruited to sites of inflammation. In the CNS, astrocytes are the most abundant glial cell population and participate in the local innate immune response triggered by a variety of insults. In the present study, we investigated the impacts of astrocytes on PMN function. Primary astrocyte cultures were derived from postnatal C57BL/6 mice and primary neutrophils were isolated from 8 to 12 weeks old C57BL/6 mice. PMNs respiratory burst was analyzed by H2DCFDA assay. For phagocytosis assay, neutrophils were incubated with FITC-labeled E. coli and the phagocytosis of E coli was determined by flow cytometer. PMNs degranulation was determined by myeloperoxidase assay. Cytokine expression was determined by real-time PCR. To determine the involvement of different signaling pathway, protein lysates were prepared and western blots were conducted to assess the activation of Akt, Erk1/2, and p38. Using ex vivo neutrophils and primary astrocyte cultures, our study demonstrated that astrocytes differentially regulate neutrophil functions, depending upon whether the interactions between the two cell types are direct or indirect. Upon direct cell-cell contact, astrocytes attenuate neutrophil apoptosis, respiratory bust, and degranulation, while enhancing neutrophil phagocytic capability and pro-inflammatory cytokine expression. Through indirect interaction with neutrophils, astrocytes attenuate apoptosis and enhance necrosis in neutrophils, augment neutrophil phagocytosis and respiratory burst, and inhibit neutrophil degranulation. In addition, astrocytes could augment Akt, Erk1/2, and p38 activation in neutrophils. Astrocytes differentially regulate neutrophil functions through direct or indirect interactions between the two cell types. The diversified actions of astrocytes on neutrophils might provide protection against potential microbial infections given compromised blood-brain barrier integrity under certain neuropathological conditions. The complex actions of astrocytes on neutrophils could provide further insight to harness the inflammatory response to promote CNS repair.


Lung Fluid Volume during Cardiopulmonary Exercise Testing.
Background and Objectives: Cardiopulmonary exercise testing can be used to quantify exercise capacity in patients with heart failure with reduced ejection fraction (HfrEF). Lung fluid levels as measured non-invasively by remote dielectric sensing (ReDSTM), often correlate with intracardiac filling pressures. The change in lung fluid levels in patients with HfrEF during cardiopulmonary exercise testing is unknown. Materials and Methods: Patients with chronic HfrEF who underwent cardiopulmonary exercise testing between October 2021 and March 2022 were prospectively included in this proof-of-concept study, with ReDS values measured before and after testing. Results: Thirteen patients (median age 41 (37, 52) years, 69% men, plasma B-type natriuretic peptide 141 (57, 368) pg/mL) were included. Median peak oxygen consumption was 11.4 (10.7, 14.0) mL/kg/min. During the test, ReDS values increased from 25% to 32% only in one patient on inotropic support, whereas ReDS values remained unchanged in the other 12 patients. The former patient remained hospitalized, whereas the other patients were dischargeable without any new incidence of clinical events during the observational period (median duration 69 (33, 112] days). Conclusions: The ReDS system may be a feasible complementary tool to noninvasively assess the changes in lung fluid levels during cardiopulmonary exercise testing. The clinical implications of ReDS values during exercise needs further investigation.


Green Biologics: Harnessing the Power of Plants to Produce Pharmaceuticals.
Plants are increasingly used for the production of high-quality biological molecules for use as pharmaceuticals and biomaterials in industry. Plants have proved that they can produce life-saving therapeutic proteins (Elelyso™-Gaucher's disease treatment, ZMapp™-anti-Ebola monoclonal antibodies, seasonal flu vaccine, Covifenz™-SARS-CoV-2 virus-like particle vaccine); however, some of these therapeutic proteins are difficult to bring to market, which leads to serious difficulties for the manufacturing companies. The closure of one of the leading companies in the sector (the Canadian biotech company Medicago Inc., producer of Covifenz) as a result of the withdrawal of investments from the parent company has led to the serious question: What is hindering the exploitation of plant-made biologics to improve health outcomes? Exploring the vast potential of plants as biological factories, this review provides an updated perspective on plant-derived biologics (PDB). A key focus is placed on the advancements in plant-based expression systems and highlighting cutting-edge technologies that streamline the production of complex protein-based biologics. The versatility of plant-derived biologics across diverse fields, such as human and animal health, industry, and agriculture, is emphasized. This review also meticulously examines regulatory considerations specific to plant-derived biologics, shedding light on the disparities faced compared to biologics produced in other systems.


Serum antibodies to Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis in juvenile periodontitis and adult periodontitis (part I).
Recent microbiological studies support the concept that specific gram negative bacteria play a major role in the etiology and pathogenesis of human chronic inflammatory periodontal disease. Actinobacillus actinomycetemcomitans has been isolated frequently from juvenile periodontitis and Porphyromonas gingivalis has been shown to be a prominent species in adult periodontitis in humans. The purpose of this study was to determine levels of the specific antibodies to A.actinomycetemcomitans and P.gingivalis in 17 patients with juvenile and 15 patients with adult periodontitis and 24 healthy subjects. IgG and IgM antibody titers against these antigens were determined by enzyme-linked immunosorbent assay (ELISA). The levels of antibodies against A.actinomycetemcomitans were significantly higher in the juvenile periodontitis compared to the adult periodontitis patients and controls. Anti-P.gingivalis antibodies were elevated in adult periodontitis compared to juvenile periodontitis patients and controls.


Emerging role of exosomes in allorecognition and allograft rejection.
This article reviews recent literature on the nature of extracellular vesicles released by allogeneic transplants and examine their role in T-cell alloimmunity involved in rejection and tolerance of these grafts. Donor cells release extracellular vesicles, including exosomes, after transplantation of allogeneic organs and tissues. Consequently, recipient APCs take up these exosomes and present donor MHC antigens on their surface (allo-MHC cross-dressing) thus, activating some alloreactive T cells via a mechanism called semi-direct pathway of allorecognition. In addition, one study shows that exosomes carrying noninherited maternal antigens are associated with maternal microchimerism and tolerance in offspring. Finally, a few studies describe potential utilization of exosomes as modulators of alloimmunity and biomarkers of rejection in allotransplantation. Extracellular vesicles, including exosomes, released by allografts contribute to recognition of donor antigens by T cells after allotransplantation. This occurs through cross-dressing of recipient APCs with donor MHC antigens and subsequent activation of T cells, a process called semi-direct alloreactivity. The relevance of this phenomenon in rejection and tolerance of allografts and the potential utilization of exosomes as biomarkers in transplantation are discussed.


Viral loads in throat and anal swabs in children infected with SARS-CoV-2.
Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay on anal swabs was recently reported to be persistently positive even after throat testing was negative during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, data about the consistent performance of RT-PCR assay on throat and anal swabs remain limited in paediatric patients. Here, we retrospectively reviewed RT-PCR-testing results of 212 paediatric patients with suspected SARS-CoV-2 infection at Wuhan Children's Hospital. The diagnostic potential of these two types of specimens showed significant difference (positive rate: 78.2% on throat swabs vs. 52.6% on anal swabs, McNemar Test P = 0.0091) and exhibited a weak positive consistency (Kappa value was 0.311, P < 0.0001) in paediatric patients. Furthermore, viral loads detected on both throat and anal swabs also showed no significant difference (P = 0.9511) and correlation (Pearson r = 0.0434, P = 0.8406), and exhibited an inconsistent kinetic change through the course of SARS-CoV-2 infection. Besides, viral loads in the throat and anal swabs were correlated with different types of immune states, immune-reactive phase, and the resolution phase/immunologic tolerance, respectively. These findings revealed that RT-PCR-testing on throat and anal swabs showed significant difference for monitoring SARS-CoV-2 infection and correlated with different immune state in paediatric patients.


What People "Like": Analysis of Social Media Strategies Used by Food Industry Brands, Lifestyle Brands, and Health Promotion Organizations on Facebook and Instagram.
Health campaigns have struggled to gain traction with young adults using social media, even though more than 80% of young adults are using social media at least once per day. Many food industry and lifestyle brands have been successful in achieving high levels of user engagement and promoting their messages; therefore, there may be lessons to be learned by examining the successful strategies commercial brands employ. This study aims to identify and quantify social media strategies used by the food industry and lifestyle brands, and health promotion organizations across the social networking sites Facebook and Instagram. The six most engaging posts from the 10 most popular food industry and lifestyle brands and six health promotion organizations were included in this study. A coding framework was developed to categorize social media strategies, and engagement metrics were collected. Exploratory linear regression models were used to examine associations between strategies used and interactions on Facebook and Instagram. Posts from Facebook (143/227, 63.0%) and Instagram (84/227, 37.0%) were included. Photos (64%) and videos (34%) were used to enhance most posts. Different strategies were most effective for Facebook and Instagram. Strategies associated with higher Facebook interactions included links to purchasable items (beta=0.81, 95% CI 0.50 to 1.13, P<.001) featuring body image messages compared with food content (beta=1.96, 95% CI 1.29 to 2.64, P<.001), and where the content induced positive emotions (beta=0.31, 95% CI 0.04 to 0.57, P=.02). Facebook interactions were negatively associated with using pop culture (beta=-0.67, 95% CI -0.99 to -0.34, P<.001), storytelling (beta=-0.86, 95% CI -1.29 to -0.43, P<.001) or visually appealing graphics (beta=-0.53, 95% CI -0.78 to -0.28, P<.001) in their posts compared with other strategies. Posting relatable content was negatively associated with interactions on Facebook (beta=-0.29, 95% CI -0.53 to -0.06, P=.01), but positively associated on Instagram (beta=0.50, 95% CI 0.05 to 0.95, P=.03). Instagram interactions were negatively associated with weight loss (beta=-1.45, 95% CI -2.69 to -0.21, P=.02) and other content (beta=-0.81, 95% CI -1.57 to -.06, P=.04) compared with food content. Health promotion professionals and organizations can improve engagement using positive messaging and tailoring posts appropriate for different social media channels.


Catechin and proanthocyanidin B4 from grape seeds prevent doxorubicin-induced toxicity in cardiomyocytes.
The clinical use of doxorubicin, a highly active anticancer drug, is limited by its severe cardiotoxic side effects. Grape seed extract has been reported to exert protective effects on doxorubicin-induced cardiotoxicity. The cardiovascular protective effects of grape seed extract are believed to be ascribed to its antioxidative properties. A series of studies have has demonstrated that polyphenols are instrumental for the antioxidative properties of grape seed extract. This study was designed to investigate whether two major polyphenols isolated from grape seed extract, catechin and proanthocyanidin B4 (Pc B(4)), had protective effects against doxorubicin-induced toxicity in cardiomyocytes and their underlying mechanisms. The results showed that grape seed polyphenols catechin and Pc B(4) pretreatment would protect cardiomyocytes against doxorubicin-induced toxicity by decreasing reactive oxygen species generation as well as the number of apoptotic cells, preventing DNA fragmentation, regulating the expression levels of the pro-apoptotic protein Bax-alpha and the anti-apoptotic protein Bcl-2, and inhibiting apoptotic signaling pathways.


Induced smoothing for rank-based regression with recurrent gap time data.
Various semiparametric regression models have recently been proposed for the analysis of gap times between consecutive recurrent events. Among them, the semiparametric accelerated failure time (AFT) model is especially appealing owing to its direct interpretation of covariate effects on the gap times. In general, estimation of the semiparametric AFT model is challenging because the rank-based estimating function is a nonsmooth step function. As a result, solutions to the estimating equations do not necessarily exist. Moreover, the popular resampling-based variance estimation for the AFT model requires solving rank-based estimating equations repeatedly and hence can be computationally cumbersome and unstable. In this paper, we extend the induced smoothing approach to the AFT model for recurrent gap time data. Our proposed smooth estimating function permits the application of standard numerical methods for both the regression coefficients estimation and the standard error estimation. Large-sample properties and an asymptotic variance estimator are provided for the proposed method. Simulation studies show that the proposed method outperforms the existing nonsmooth rank-based estimating function methods in both point estimation and variance estimation. The proposed method is applied to the data analysis of repeated hospitalizations for patients in the Danish Psychiatric Center Register.


Cyclic Ether Triggers for Polymeric Frustrated Lewis Pair Gels.
Sterically hindered Lewis acid and base centers are unable to form Lewis adducts, instead forming frustrated Lewis pairs (FLPs), where latent reactivity can be utilized for the activation of small molecules. Applying FLP chemistry into polymeric frameworks transforms this chemistry into responsive and functional materials. Here, we report a versatile synthesis strategy for the preparation of macromolecular FLPs and explore its potential with the ring-opening reactions of cyclic ethers. Addition of the cyclic substrates triggered polymer network formation, where the extent of cross-linking, strength of network, and reactivity are tuned by the steric and electronic properties of the ethers. The resultant networks behave like covalently cross-linked polymers, demonstrating the versatility of FLPs to simultaneously tune both small-molecule capture and mechanical properties of materials.


Two new species of the genus Longicheles Valle, 1953 from the Kelkit Valley, Turkey, with redescription Longicheles lagrecai (Valle, 1963) (Acari: Macrochelidae).
The Kelkit Valley is geographically a transitional zone between the Middle Black Sea and Inner Anatolia regions in Turkey. Two new species of Macrochelidae are described from this area--Longicheles ozkani sp. nov. and Longicheles ayyildizi sp. nov. Longicheles lagrecai (Valle, 1963) is recorded for the Turkish fauna and redescribed on the basis of specimens collected from the Valley. A world-wide key to species of Longicheles Valle is provided.


Halofuginone down-regulates Smad3 expression and inhibits the TGFbeta-induced expression of fibrotic markers in human corneal fibroblasts.
Due to its ability to disrupt transforming growth factor beta (TGF-β) signaling, halofuginone has been successfully used to treat various fibrotic disorders. Here we investigated the antifibrotic potential of halofuginone in human corneal fibroblasts. Human corneal fibroblasts were isolated from human donor corneas for in vitro experiments. TGF-β was used to stimulate pro-fibrotic responses from corneal fibroblasts under halofuginone treatment. The expression of alpha smooth muscle actin (α-SMA) and fibronectin was analyzed by western blots. Phalloidin toxin was used to stain cultures for stress fiber assemblies. Quantitative reverse transcription PCR (qRT-PCR) and immunostaining were used to analyze the expression of type I collagen mRNA and protein, respectively. The expression of Smad2, Smad3, phospho-Smad2, and phospho-Smad3 was determined by western blots. Halofuginone was well tolerated by human corneal fibroblasts up to 10 ng/ml as demonstrated by a cell viability assay. At this concentration, TGF-β-induced expression of the fibrotic markers α-SMA, fibronectin, and type I collagen was significantly reduced. Interestingly, under our experimental conditions, halofuginone treatment led to reduced protein expression of Smad3, which was both dose- and time-dependent. Our results suggest that halofuginone may exert its antifibrotic effects in the cornea via a novel molecular mechanism and may be used as an antifibrotic agent for corneal fibrosis treatment.


Influence of obesity on drug disposition.
Physiologic changes associated with obesity and their effects on the distribution, protein binding, metabolism, and renal excretion of drugs are described. Changes in the volume of distribution correlate with drug lipophilicity. Drugs that have a high affinity for adipose tissue have an increased volume of distribution, whereas the distribution of drugs that have low partition coefficients is not altered substantially. Albumin and total protein concentrations are comparable in lean and obese subjects, but concentrations of alpha 1-acid glycoprotein are increased. Consequently, protein binding of acidic drugs is unchanged, but the free fraction of basic drugs may be decreased. Changes in hepatic drug clearance are complex. Phase 1 reactions and acetylation, a Phase 2 reaction, appear to be unaffected by obesity, but activity of Phase 2 glucuronidation and sulfation pathways is enhanced. Available physiologic and pharmacokinetic data on the effect of obesity on systemic clearance of highly extracted drugs are conflicting. Both glomerular filtration and tubular secretion appear to be increased in obese individuals, and tubular secretion may be disproportionately increased compared with filtration. Clearance of drugs that depend on glomerular filtration for elimination is consistently higher in obese subjects. Differences among patient populations, other conditions associated with obesity, and the small study populations described to date may account for some discrepancies in reported results. Awareness of the physiologic effects of obesity is essential for ensuring appropriate drug therapy in obese patients.


[Penetrating wounds of the thorax].
From January 1989 to December 1993 at the Institute of Clinical Surgery of the University of Perugia, 5 patients were under observation for penetrating chest injuries. Two of them had show-wounds, one a slash, one a stabbing and slash and one a cutting blow. One of the patients with shot-wounds died on the operating table from a haemorrhage while the other was saved by surgery. One patient successfully underwent surgery for loss of tissue in the thorax walls. Another had a mini-thoracotomy plus lung suture which were successful. Finally, in the patient with a slash in the front region of the thorax and a slight pneumothorax, we inserted a chest thorax tube and so obtained a complete re-expansion of the lung. Total mortality was 20%. Surgical exploration of the thorax we believe is necessary wherever there is a risk of haemorrhage or possible lung damage requiring only surgery. According to many authors, video-thoracoscopy has the advantage of a reliable diagnosis and above all, enable us to repair lung wounds without opening the thorax. In one of our patients we could have avoided the mini-thoracotomy and used thoracoscopy to repair the lung damage.


[Transplantation of fetal tissues in otorhinolaryngology: current status and prospects for the future].
Insufficient efficacy of treatment of neurosensory hypoacusis makes investigators search for new methods. Transplantation of fetal tissue taken from healthy embryos of gestation stage II tried in various fields of medicine, such as neurology, endocrinology, surgery, etc., was also tested in management of various forms of neurosensory hypoacusis. Endonasal, endaural, endolumbal and intracochlear methods of the transplantation are detailed. Results of combined dynamic audiological control of these patients including tonal threshold audiometry in extended frequency range are presented. A 1-year follow-up provided evidence in favour of endolumbal and intracochlear transplantation. Further investigations are needed.


The optimal number of major histocompatibility complex molecules in an individual.
A straightforward argument is presented to calculate the number of different major histocompatibility complex (MHC) molecules in an individual that maximizes the probability of mounting immune responses against a large number of foreign peptides. It is assumed that increasing the number of MHC molecules per individual, n, has three different effects: (i) it increases the number of foreign peptides that can be presented; (ii) it increases the number of different T-cell receptors (TCRs) positively selected in the thymus; but (iii) it reduces the number of TCRs by negative selection. The mathematical analysis shows that n = 1/f maximizes the number of different TCRs that pass through positive and negative selection and that n = 2/f maximizes the probability to mount immune responses against a large fraction of foreign peptides. Here f is the fraction of TCRs deleted by one MHC molecule. Both results depend on approximations that are discussed in the paper. The model presented has implications for our understanding of the evolutionary forces acting on the MHC.


Adolescent Neighborhood Environments and Latino Intraethnic Disparities in Trajectories of Serious Violent Behaviors.
The purpose of this study was to describe the longitudinal trajectories of risk for serious violent behaviors among Latinos of different ancestry in the United States and to examine the impact of neighborhood perceptions, socioeconomic status (SES), and racial/ethnic and immigrant concentration during adolescence in long-term risk. Guided by sociological theories and life-course frameworks, we utilized data from Mexican (n = 755), Cuban (n = 182), Puerto Rican (n = 219), and other Latino (n = 289) respondents who participated in all waves of the National Longitudinal Study of Adolescent to Adult Health. Stratified, weighted, multilevel growth curve models were conducted in Stata 14 MP to determine unadjusted and adjusted trajectories between 13 and 32 years of age for each ancestry group by sex. Violent behaviors decreased over time, and were lower among females of all groups. Puerto Ricans and Cubans had higher risk than Mexicans or other Latinos. Neighborhood factors did not have consistent effects across groups. Neighborhood satisfaction reduced risk among most groups, while social cohesion increased violent behaviors among Mexicans. Neighborhood economic well-being (SES) and proportion of non-Latino Whites had no impact among any group. Living in predominantly Black neighborhoods during adolescence reduced the risk into adulthood among Puerto Ricans, but increased it among other Latinos. Higher neighborhood immigrant concentration was related to higher risk among other Latinos. Initial and long-term risk for violent behaviors differed across Latino ancestry, with slower decreases among Puerto Ricans and Cubans. The impact of neighborhood perceptions, SES, and racial/ethnic and immigrant composition was inconsistent.


Granular cell myoblastoma: a cause of biliary obstruction.
An 11-year-old boy was seen with gradual onset of jaundice. Dilated bile ducts were demonstrated by ultrasound and computerized axial tomography. The obstruction was caused by an unusual benign tumor, a granular cell myoblastoma. Cure was effected by resection and choledochojejunostomy.


Blockade of Stromal Gas6 Alters Cancer Cell Plasticity, Activates NK Cells, and Inhibits Pancreatic Cancer Metastasis.
Pancreatic ductal adenocarcinoma (PDA) is one of the deadliest cancers due to its aggressive and metastatic nature. PDA is characterized by a rich tumor stroma with abundant macrophages, fibroblasts, and collagen deposition that can represent up to 90% of the tumor mass. Activation of the tyrosine kinase receptor AXL and expression of its ligand growth arrest-specific protein 6 (Gas6) correlate with a poor prognosis and increased metastasis in pancreatic cancer patients. Gas6 is a multifunctional protein that can be secreted by several cell types and regulates multiple processes, including cancer cell plasticity, angiogenesis, and immune cell functions. However, the role of Gas6 in pancreatic cancer metastasis has not been fully investigated. In these studies we find that, in pancreatic tumors, Gas6 is mainly produced by tumor associated macrophages (TAMs) and cancer associated fibroblasts (CAFs) and that pharmacological blockade of Gas6 signaling partially reverses epithelial-to-mesenchymal transition (EMT) of tumor cells and supports NK cell activation, thereby inhibiting pancreatic cancer metastasis. Our data suggest that Gas6 simultaneously acts on both the tumor cells and the NK cells to support pancreatic cancer metastasis. This study supports the rationale for targeting Gas6 in pancreatic cancer and use of NK cells as a potential biomarker for response to anti-Gas6 therapy.


Association of single-nucleotide polymorphisms in the IL27 gene with autoimmune thyroid diseases.
Background Accumulating data have shown that interleukin-27 (IL27) polymorphisms are linked to the susceptibility of some autoimmune diseases. We assessed whether there was an association between three single-nucleotide polymorphisms (SNPs) of IL27 gene and autoimmune thyroid diseases (AITDs). Methods Three SNPs (rs153109, rs17855750 and rs181206) of IL27 gene were genotyped by Hi-SNP high-throughput genotyping in 843 patients with AITDs (516 Graves' disease (GD) and 327 Hashimoto's thyroiditis (HT)) and 677 healthy controls in Chinese Han population. Results Compared with controls, rs153109 displayed significant associations with GD in allele and genotype frequencies (P = 0.002 and P = 0.008, respectively) and rs17855750 displayed significant associations with HT in allele frequencies (P = 0.02), whereas no differences in genotype or allele frequencies were found between AITD patients and controls at rs181206. Conclusion Our study, for the first time, showed the significant association of the IL27 gene SNPs with AITD.


THE KINETICS OF TRYPSIN DIGESTION : IV. THE COURSE OF THE REACTION WHEN BOTH SUBSTRATE AND ENZYME CONCENTRATIONS ARE DECREASING.
The rate of hydrolysis of edestin by trypsin at 40 degrees and in the presence of 1 M NaCl has been studied. Under these conditions the enzyme is rapidly inactivated and the equation for the reaction may be written See PDF for Equation in which E(t) is the concentration of enzyme during the interval (T(1)-T(2)). This equation has been tested by determining the enzyme concentration at various times during the reaction and substituting these values in the above equation. The experimental results agree with this formula when the initial enzyme or edestin concentrations are varied. No anomalous results of varying substrate concentrations are apparent. It can further be assumed as a first approximation that the enzyme is decomposing monomolecularly and the equation can then be written See PDF for Equation This equation is also satisfactory provided high enzyme concentrations and low edestin concentrations are used. With high concentrations of edestin and low trypsin the effects of the products of the reaction on the enzyme become too large to be neglected and the formula no longer holds.


Newborn Infant With Mothball Toxicity Due to Maternal Ingestion.
Naphthalene poisoning due to exposure to mothballs is a common cause of toxicity in children worldwide. Naphthalene toxicity is known to cause hemolytic anemia, methemoglobinemia, and hepatic and renal injury. Neonates are more susceptible to the effects of oxidative stress from naphthalene because of their low glutathione stores and immaturity of hepatic enzymes. However, there are no reported cases of chronic fetal exposure to naphthalene during pregnancy. We report a novel case of chronic fetal exposure to naphthalene-containing mothballs that occurred from the second trimester through the third trimester of pregnancy. Our patient presented with hyperbilirubinemia, requiring exchange transfusion, severe hemolytic anemia, pulmonary hypertension, respiratory failure, and renal failure and progressed to develop "bronze baby" syndrome. Pregnant mothers should be diligently screened for such exposures and if found should receive psychiatric evaluation and counseling to prevent such devastating effects in neonates.


Echinococcus antigens.
Much of the work on immunology of hydatidosis has so far been devoted to the development of suitable methods for serological diagnosis. The precise nature of hydatid antigens and their chemical characterization has still not been worked out, largely because of the complex life-history of the parasite and the difficulties of in vitro cultivation. The most widely used antigen for routine serological testing in hydatidosis caused by Echinococcus granulosus is fluid taken from the cyst. This fluid is, however, a complex mixture of substances and contains several protein and carbohydrate fractions as well as end-products of carbohydrate and protein metabolism. The cyst fluid from different sources is variable in its antigenic properties, and the fluid from sterile cysts is especially lacking in antigenic activity. Antigens from tissue extracts of hydatid cysts appear to have greater specificity. Cyst extracts of E. multilocularis, the cysts of which contain relatively little fluid, have also been used but are poor antigens, and contain measurable amounts of host protein. Antigens prepared from other cestodes and metabolic antigens are also reviewed.Biochemical analysis of Echinococcus antigens covering polysaccharides, proteins, lipids, and blood-group substances is considered, together with the characterization of antigens by electrophoresis, column chromatography and gel-diffusion methods. The problems associated with the standardization of antigens are discussed. Recent data on the character and reactivity of antigens employed in Echinococcus studies are summarized.


Radiographic analysis of the angle in the lateromedial projection of the metacarpophalangeal joint and the distal interphalangeal joint in metacarpophalangeal flexural deformities in calves.
The bone alignment of the metacarpophalangeal joint (MPJ) of the distal interphalangeal joint (DIPJ) in metacarpophalangeal flexural deformity (MPFD) in calves was evaluated by radiography. This study was designed by retrospective study of radiographs. Lateral to medial radiographs of distal forelimbs were taken from 19 MPFD affected calves (35 forelimbs) and 21 normal calves (42 forelimbs). Based on the radiographs, the lateral angles of MPJ were measured from the metacarpal bone axis and proximal phalanx axis, and lateral angles of DIPJ were measured from the middle phalanx axis and distal phalanx axis. Mean lateral angle of MPJ in the normal limbs was 175.9 (95% CI 174.5 to 177.4). Mean lateral angles of MPJ in MPFD were as follows: mild: 167.1 (158.9-175.2), moderate: 165.1 (158.5-171.7) and severe: 150.6 (146-155.1). MPJ angle in MPFD limbs was narrower than that in the normal limbs (mild, moderate and severe: P=0.017, P=0.003 and P<0.001, respectively). Mean lateral angle of DIPJ in the normal limbs was 211.9 (210.7-213.2). Mean lateral angles of DIPJ in moderate: 200.6 (195.2-206.1) and severe: 204.9 (203.3-206.5) MPFD were narrower than that in the normal limbs (both P<0.001). There was no significant difference between the normal limbs and mild: 210.3 (206.9-213.7) MPFD limbs (P=0.7). The clinical severity of MPFD corresponded well with the lateral angle of MPJ. The flexion of DIPJ in moderate and severe MPFD was similar to the flexion of MPJ in MPFD. This suggested that the lateral to medial radiographs accurately reflected the MPJ flexion and the DIPJ in MPFD in calves, providing useful information for the treatment of MPFD.


NF-kappaB and AP-1 activation by nitric oxide attenuated apoptotic cell death in RAW 264.7 macrophages.
A toxic dose of the nitric oxide (NO) donor S-nitrosoglutathione (GSNO; 1 mM) promoted apoptotic cell death of RAW 264.7 macrophages, which was attenuated by cellular preactivation with a nontoxic dose of GSNO (200 microM) or with lipopolysaccharide, interferon-gamma, and NG-monomethyl-L-arginine (LPS/IFN-gamma/NMMA) for 15 h. Protection from apoptosis was achieved by expression of cyclooxygenase-2 (Cox-2). Here we investigated the underlying mechanisms leading to Cox-2 expression. LPS/IFN-gamma/NMMA prestimulation activated nuclear factor (NF)-kappaB and promoted Cox-2 expression. Cox-2 induction by low-dose GSNO demanded activation of both NF-kappaB and activator protein-1 (AP-1). NF-kappaB supershift analysis implied an active p50/p65 heterodimer, and a luciferase reporter construct, containing four copies of the NF-kappaB site derived from the murine Cox-2 promoter, confirmed NF-kappaB activation after NO addition. An NF-kappaB decoy approach abrogated not only Cox-2 expression after low-dose NO or after LPS/IFN-gamma/NMMA but also inducible protection. The importance of AP-1 for Cox-2 expression and cell protection by low-level NO was substantiated by using the extracellular signal-regulated kinase inhibitor PD98059, blocking NO-elicited Cox-2 expression, but leaving the cytokine signal unaltered. Transient transfection of a dominant-negative c-Jun mutant further attenuated Cox-2 expression by low-level NO. Whereas cytokine-mediated Cox-2 induction relies on NF-kappaB activation, a low-level NO-elicited Cox-2 response required activation of both NF-kappaB and AP-1.


Radioprotective effects of hawthorn fruit extract against gamma irradiation in mouse bone marrow cells.
The radioprotective effect of hawthorn (Crataegus microphylla) fruit extract against genotoxicity induced by gamma irradiation has been investigated in mouse bone marrow cells. A single intraperitoneal (ip) administration of hawthorn extract at doses of 25, 50, 100 and 200 mg/kg 1h prior to gamma irradiation (2 Gy) reduced the frequencies of micronucleated polychromatic erythrocytes (MnPCEs). All four doses of hawthorn extract significantly reduced the frequencies of MnPCEs and increased the PCE/PCE+NCE ratio (polychromatic erythrocyte/ polychromatic erythrocyte + normochromatic erythrocyte) in mice bone marrow compared with the non drug-treated irradiated control (p < 0.02-0.00001). The maximum reduction in MnPCEs was observed in mice treated with extract at a dose of 200 mg/kg. Administration of amifostine at dose 100 mg/kg and hawthorn at dose 200 mg/kg reduced the frequency of MnPCE almost 4.8 and 5.7 fold; respectively, after being exposed to 2 Gy of gamma rays, compare with the irradiated control group. Crataegus extract exhibited concentration-dependent activity on 1,1-diphenyl 2-picrylhydrazyl free radical showing that Crataegus contained high amounts of phenolic compounds and the HPLC analysis determined that it contained chlorogenic acid, epicatechin and hyperoside. It appeared that hawthorn extract with antioxidant activity reduced the genotoxicity induced by gamma irradiation in bone marrow cells.


Acculturation, diet, and psychological health among Asian students.
Objective: The study examined the association between acculturation level, dietary nutrient intake, and psychological health of Asian students at the University of Delaware. Participants: A total of 172 students completed the study. Methods: Data were collected, using questionnaires, through Qualtrics®. Linear regression models were used to examine the association between normally distributed diet and acculturation and demographic data. Results: As length of residence in the United States increased, acculturation level and maintenance of original culture both increased. There was no significant association between acculturation and nutrient intake. Chinese students were more likely than other Asian students to have nonspecific psychological distress. Conclusion: There was no significant association between diet and acculturation level. A larger sample population with longer US residence is needed to further investigate this association. In an effort to improve psychological health of Asian students, challenges specific to this population, such as the language barrier, should be addressed.


[Multilocular cystic renal carcinoma: pathologic study of 14 cases].
The article focuses on the multilocular cystic renal carcinoma, the most frequent of the renal cystic carcinomas. The importance of performing a separate analysis of these cystic tumors comes from their better prognosis some authors have suggested. Moreover, they are frequently difficult to differentiate from multilocular benign cysts and other benign lesions by radiological studies, cytology or even during surgery. Pathologic study is essential for a definitive diagnosis of the lesion. We reviewed 14 cases of multilocular cystic renal carcinoma obtained from the series of 191 renal cell carcinomas diagnosed in our hospital in the period 1995-2002. Inclusion criteria were existence of a multicystic complex mass, in which clear cells partially or completely covered the cystic walls and accumulate within the septa. The lack of well-documented cases of multilocular cystic renal carcinoma with metastases supports the fact that they are tumors with a very good prognosis. In conclusion, data from both literature and our series support that multilocular cystic renal carcinoma should be considered a low-grade neoplasia, and its treatment should be conservative.


Enhancement of bistability in spinal motoneurons in vivo by the noradrenergic alpha1 agonist methoxamine.
Enhancement of bistability in spinal motoneurons in vivo by the noradrenergic alpha1 agonist methoxamine. Like many types of motoneurons, spinal motoneurons in the adult mammal can exhibit bistable behavior. This means that short periods of excitatory input can initiate long periods of self-sustained firing and that equally short periods of inhibition can return the cell to the quiescent state. Usually, the presence of one of the monoamines (either serotonin or norepinephrine) is required for spinal motoneurons to express bistable behaviors. Because the decerebrate cat preparation has tonic activity in monoaminergic fibers that originate in the brain stem and project to spinal motoneurons, these cells sometimes exhibit bistable behavior. However, exogenous application of the noradrenergic alpha1 agonist methoxamine greatly enhances bistable behavior in the decerebrate. The goal of this study was to identify the mechanisms of this action of methoxamine. The total persistent inward current (IPIC) in spinal motoneurons in the decerebrate cat was measured from I-V functions generated by triangular voltage commands applied using discontinuous single electrode voltage clamp. The effect of methoxamine on IPIC was assessed by comparing its properties in a control cell sample without methoxamine to its properties in a sample of cells obtained after application of methoxamine. In most experiments, at least one cell was obtained from each sample. Our results showed that methoxamine approximately doubled the amplitude of IPIC without changing its onset voltage, its offset voltage, or its persistence. The reduced amplitude was a consistent finding within experiments and so was unlikely to be caused by interanimal variability. In addition, methoxamine depolarized motoneurons without altering their input conductances, so that a smaller amount of current was required to reach the onset voltage of IPIC. These effects of methoxamine were approximately equal in all cells. As a result of these changes, methoxamine greatly enhanced the tendency for motoneurons to become bistable. It is proposed that the methoxamine-induced increase in the amplitude of IPIC is effective in enhancing the duration of bistable firing because this increase makes IPIC more resistant to the deactivating effects of the afterhyperpolarizations between spikes.


[Primary malignant nephrosclerosis (author's transl)].
Primary malignant nephrosclerosis shows a haemolytic-uraemic symptomatology and can be differentiated from secondary malignant nephrosclerosis on clinical and histological grounds. The disease was observed in 4 patients: a 25-year-old man and 3 women aged 19, 28 and 49 years. The disease is characterized by a fulminating course, malignant hypertension with progressive retinopathy, and development of progressive renal failure with subsequent irreversible anuria. In addition haemolytic anaemia or posthaemolytic states as well as consumption coagulopathy occur. In 2 cases schizozytes and in particular helmet-shaped forms could be demonstrated. On histology an obliterating necrotizing vascular change is seen which is limited to the kidneys as was demonstrated in one case by angiography. Therapeutic attempts included antibiotics, steroids, heparin, streptokinase, antihypertensive drugs, and haemodialysis. The 3 female patients died, the man survived after bilateral nephrectomy.


Ocular signs in four dogs with hypertension.
Four dogs suddenly developed visual problems associated with retinal detachment and haemorrhage. They all had a high arterial blood pressure measured with a Doppler ultrasonic blood pressure monitor. Two of the dogs showed evidence of cardiac hypertrophy and one had hypercholesterolaemia; in three of them there was no conclusive evidence of underlying systemic disease. The condition was treated and assessed over a period of 12 months. In the absence of any findings suggesting the presence of underlying systemic disease, it is possible that the ocular changes were the result of primary hypertension, although not every possible cause of secondary hypertension could be excluded.


Recently increased prevalence of the human median artery of the forearm: A microevolutionary change.
The median artery has been considered as an embryonic structure, which normally regresses around the 8th week of gestation. However, various prevalences have been reported in adults since the 18th century. Furthermore, in a study by Henneberg and George (1995; Am J Phys Anthropol 96, 329-334), has suggested that increasing prevalence of the median artery during the 20th century was a 'possible secular trend'. The present study, conducted nearly a quarter of a century later, is a continuation of that study. A total of 26 median arteries were found in 78 upper limbs obtained from Australians aged 51 to 101 years, who died in the period 2015-2016, a prevalence rate of 33.3%. Analysis of the literature showed that the presence of the median artery has been significantly increasing (p = .001) over time, from approximately 10% in people born in the mid-1880s to approximately 30% by the end of the 20th century. The significance of the prevalence increased to a p value <.0001, when the results of the present study and other studies conducted by our research team were combined. After removal of the studies that were possibly biased, because of their specific focus on the evolutionary aspects of the median artery, the significance remained at p = .018. The present study provides an example of microevolutionary changes in the internal anatomy of the human body. Second-order polynomial regression of the median artery's prevalence on dates of birth shows that it is now present in 35% of people and predicts that people born 80 years from now will all carry a median artery if the trend continues. When the median artery prevalence reaches 50% or more, it should not be considered as a variant, but as a 'normal' human structure.


Effect of modified Sanhuang Xiexin Tang plus additional herbs combined with.
To determine the effectiveness of modified Sanhuang Xiexin Tang (SHXXT) plus additional herbs (MSAH) combined with ""standard triple therapy"" for eradication of Helicobacter pylori (H.pylori) and amelioration of related symptoms in comparison with standard triple and standard quadruple therapies. From October 2015 to May 2016, we recruited patients with dyspepsia symptoms confirmed to have H.pylori infection by the 13C urea breath test in our outpatient clinic. Patients were randomly divided into three treatment groups: Nexium? standard triple therapy (group A; EAC); Nexium® standard quadruple therapy (group B; EBAC); or Nexium? standard triple therapy combined with MSAH (group C; EAC+MSAH). Comparisons of Hpylori eradication and symptom amelioration rates were made among the three groups at 2 or 6 weeks after group assignment. There was no difference in H. pylori eradication rates between groups B (EBAC) and C (EAC+MSAH) (P = 0.486), and eradication rates in groups B and C were significantly higher than that in group A (EAC) (P A vs B = 0.001; P A vs C = 0.003). There was no difference in the total symptom score among the groups before treatment. In all groups, the total symptom scores after treatment (2 or 6 weeks after group assignment) were significantly lower than those before treatment (P<65308; 0.001 for all). However, group C (EAC + MSAH) demonstrated superior total symptom scores and symptom amelioration rates than groups A (EAC) and B (EBAC). Group B also demonstrated better scores and rates than group A. There was no difference in symptom amelioration rates at 2 and 6 weeks within each group. There is no difference between MSAH combined with standard triple therapy and standard quadruple therapy containing bismuth with regard to H.pylori eradication rate. However, MSAH combined with standard triple therapy has a higher symptom amelioration rate and therefore appears to be an ideal treatment scheme for H.pylori eradication.